Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Η λίστα ιστολογίων μου

Τετάρτη 11 Οκτωβρίου 2017

Microphthalmia with linear skin defects (MLS) syndrome: familial presentation



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Linear IgA bullous dermatosis associated with amyotrophic lateral sclerosis



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Milia: a useful clinical marker of CYLD mutation carrier status



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Microphthalmia with linear skin defects (MLS) syndrome: familial presentation



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Linear IgA bullous dermatosis associated with amyotrophic lateral sclerosis



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Milia: a useful clinical marker of CYLD mutation carrier status



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Scorpion bite-induced ischaemic stroke

We report a 54-year-old woman with scorpion bite. After 3 hours of admission, the patient developed sudden onset tachycardia with hypotension. Cardiac evaluation showed raised creatine kinase MB isoenzyme was elevated; ECG and two-dimensional echocardiography findings were suggestive of myocarditis. Subsequently, she developed transient ventricular tachycardia before developing abrupt onset, right hemiplegia, global aphasia and progressive worsening of sensorium 12 hours after the bite. MRI of brain revealed massive left middle cerebral artery (MCA) territory infarct. The magnetic resonance angiography showed non-visualisation of left internal carotid artery (ICA) and MCA. Coagulation parameters were normal. Sudden complete occlusion of left ICA was probably secondary to cardioembolic phenomenon leading to massive infarct. Despite aggressive medical and supportive measures, she clinically worsened rapidly to Glasgow Coma Scale of 3/15 over next 6 hours and succumbed to her illness the next day.



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Oesophageal ischaemia: an uncommon cause of chest pain

A 79-year-old woman with a history of ischaemic heart disease and atrial fibrillation presented to hospital with severe chest pain. Blood tests showed an elevated D-dimer and a rise in troponin I. ECG showed right bundle branch block pattern and T wave inversion in leads V1 to V3, although these changes were present in old ECGs. A chest X-ray was done which was normal. Due to the nature and severity of her pain a CT aortic angiogram was done. This did not show any evidence of aortic dissection or a pulmonary embolism. The patient then had several episodes of haematemesis. An urgent oesophagogastroduodenoscopy was done which showed a circumferential, well demarcated area of blackened oesophageal mucosa. The patient was diagnosed with ischaemic damage to her oesophagus.



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Posterior fossa progressive multifocal leukoencephalopathy: first presentation of an unknown autoimmune disease

We present a case of a 57-year-old man who presented with progressive cerebellar dysarthria and cerebellar ataxia. Additional investigations confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML) in the posterior fossa. This is a demyelinating disease of the central nervous system, caused by an opportunistic infection with John Cunningham virus. PML has previously been considered a lethal condition, but because of careful monitoring of patients with HIV and of patients using immunosuppressive drugs it is discovered in earlier stages and prognosis can be improved. Our patient had no known immune-compromising state, but further work-up revealed that the PML was most likely the first presentation of a previous untreated autoimmune disorder: sarcoidosis.



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Subclinical meningoventriculitis as a cause of obstructive hydrocephalus

Communicating hydrocephalus may complicate infantile bacterial meningitis, typically presenting with systemic features of infection. We report a rare case of 'subclinical meningoventriculitis' causing obstructive hydrocephalus and its challenging management. A healthy 10-week-old immunocompetent male patient presented with failure to thrive and vomiting, secondary to presumed gastro-oesophageal reflux. The child was neurologically alert, afebrile with normal inflammatory markers. Progressive macrocephaly prompted an MRI confirming triventricular hydrocephalus secondary to aqueductal stenosis. An endoscopic third ventriculostomy was performed however abandoned intraoperatively due to the unexpected finding of intraventricular purulent cerebrospinal fluid. A 6-week course of intravenous ceftriaxone was commenced for Escherichia coli meningoventriculitis. However, the child was readmitted 18 days postoperatively with acute hydrocephalus requiring a ventricular washout and staged ventriculoperitoneal shunt insertion at 4 weeks. Serial head circumference measurements are paramount in the assessment of a paediatric patient. In an immunocompetent child, a subclinical fibropurulent meningoventriculitis can result in several management challenges.



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A unique case of nephrogenic systemic fibrosis from gadolinium exposure in a patient with normal eGFR

A 57-year-old woman presented with swelling and thickening of the skin of the lower extremities. Three months prior to presentation, patient had MRI with gadolinium as part of an evaluation for suspected pancreatic malignancy. Creatinine levels at the time of gadolinium exposure were 0.9–1.2 mg/dL, with a corresponding estimated glomerular filtration rate of 64 mL/min/1.73m2 by modification of diet in renal disease equation. Twenty-four-hour urine creatinine clearance was performed as an outpatient following development of symptoms. This revealed a creatinine clearance of 23 mL/min, suggestive of advanced chronic kidney disease despite an estimated glomerular filtration rate of 64 mL/min/1.73m2. Skin biopsy was positive for sclerosing dermopathy. These findings, in addition to the temporal association with gadolinium exposure, led to the diagnosis of nephrogenic systemic fibrosis.



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Allergic bronchopulmonary mycosis presenting as a new lung mass

Description

A 69-year-old man with invasive pancreatic ductal adenocarcinoma underwent pancreaticoduodenectomy and adjuvant chemotherapy. Three years later, a right upper lobe (RUL) lung mass was noted on surveillance imaging, suspicious for disease recurrence. He was treated for bronchitis and remained asymptomatic 4 months later with an unremarkable physical exam. Chest imaging (figure 1A,B) showed an RUL central mass with an infiltrative pattern of growth and right paratracheal adenopathy that is negative for malignancy on endobronchial ultrasound-guided needle aspiration. Bronchoalveolar lavage and brushing grew branching septate hyphae identified as Bipolaris species. The presence of cylindrical bronchiectasis with bronchial wall thickening, mucus plugging, peripheral eosinophilia (810 cells/µL), elevated total serum immunoglobulin E (422.6 IU/mL) and negative aspergillus antibodies suggested allergic bronchopulmonary mycosis (ABPM) caused by Bipolaris species. After 3 months of therapy with prednisone and posaconazole, the mass-like consolidation was completely resolved (figure 1C,D).

Figure 1

Chest CT...



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Unusual case of prosthetic joint infection caused by Francisella Tularensis

Tularaemia is a zoonotic infection caused by Francisella tularensis.Ulceroglandular, glandular, oculoglandular, pharyngeal, typhoidal and pneumonic types are the different types of the disease. Infection of prosthetic joints occurs at an exceedingly uncommon rate. We report a case of prosthetic joint infection involving the hip with F. tularensis, which to the best of our knowledge after a thorough literature review is the second of its kind.



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Cryptococcus neoformans osteomyelitis and intramuscular abscess in a liver transplant patient

Cryptococcus neoformans is an important pathogen that can cause severe illness and mortality in immunocompromised patients. We highlight here the case of a 53-year-old man presenting to hospital 4 years postliver transplant with fever, acute renal failure and a medial thigh lesion. Initially treated as bacterial sepsis, the patient failed to improve on broad-spectrum antibiotics. Further investigations revealed disseminated cryptococcemia complicated by patellar osteomyelitis and an intramuscular abscess. Unfortunately, although the patient initially showed signs of clinical improvement after starting standard antifungal agents, he deteriorated and died secondary to acute renal failure. Osteomyelitis is a rare manifestation of cryptococcal infection for which there is often a significant delay to diagnosis and treatment. This is the fourth reported case of cryptococcal osteomyelitis in a liver transplant patient and underlines the importance of considering fungal infections in the differential diagnosis of osseous lesions in solid organ transplant and other immunocompromised patients.



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Olfactory bulb agenesis with normal sexual hormones

An 18-year-old Caucasian man presented with a lack of sense of surrounding smell. The problem was first noticed when a family member discussed the smell of the food, which he had no idea what it was. The patient had normal development and sexual function, no history of trauma, surgery, chemical exposure or infection. Physical examination revealed no significant abnormalities. Smell threshold test using phenyl-ethyl-alcohol revealed bilateral anosmia. MRI showed bilateral aplastic olfactory bulbs and tracts associated with absent cortical growth of the olfactory sulci and asymmetrical gyrus rectus. Circulating hormones including cortisol, growth hormone, insulin-like growth factor 1, adrenocorticotropic hormone, thyroid hormones, follicle-stimulating hormone, luteinizing hormone, prolactin and testosterone were within normal ranges. Doppler ultrasound showed normal testis with bilateral supratesticular varicoceles. Given the loss of warning smell sensation, counselling for daily living precautions especially those related to gas, fire and rotten food was given.



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Hydatid cyst of the thigh: a challenging diagnosis

Description

Hydatid disease is a common infection in Mediterranean countries. It is caused by a parasite 'Echinococcus granulosus', which may affect several organs. Liver and lungs are frequent locations. Primary hydatid cyst located in the musculoskeletal system is uncommon.1

These images illustrate the case of a 27-year-old man without past medical history who presented with a swelling of the right thigh that appeared 6 months ago. Physical examination showed a tender mass of the upper third of the right thigh. There was no history of trauma or fever. Inflammatory blood markers were normal. Ultrasonography was first performed revealing a huge multilocular intramuscular cystic mass of the thigh without tissue components or calcifications. The aspect was suspicious of a cystic lymphangioma. An MRI of the thigh was performed to evaluate accurately the size of the mass and its location. It revealed a voluminous mass of 10x6 cm developed in the...



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Syncope from radiation-induced baroreceptor failure

Orthostatic hypotension has a vast differential that has been previously described throughout the literature. However, baroreceptor failure as a sequela of head and neck radiation is not often recognised as an important cause of dramatic haemodynamic variability. As a result, individuals suffering from baroreceptor failure likely have been undertreated. Herein, we report a case of a patient with a history of radiation to the neck for squamous cell carcinoma of the tongue and resultant baroreceptor failure resulting in syncope.



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Live 'Baby dance among the red blood cells

Description

A 35-year-old woman presented to outpatients with a 1-week history of high-grade fever and generalised malaise. General and systemic examination was unremarkable. On evaluation, her complete haemogram was within normal limits; however peripheral smear revealed the presence of thread-like larval forms of filaria, belonging to the species Wuchereria bancrofti. A wet mount preparation of the centrifuged whole blood sample was done, which demonstrated 'dancing' microfilaria, recorded in real time (see online ).

Dancing adult worms can be visualised within the dilated lymphatic channels on high-resolution ultrasound by their characteristic wriggling type movements, known as the 'filarial dance sign'.1 A wet mount of blood from a patient with microfilaraemia can demonstrate 'dance sign' of the baby worms under a microscope, identical to the parental wriggling movements. Microfilariae are larval forms, released into the blood from adult female worms inhabiting the regional lymphatic vessels. Circulating microfilariae are...



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Erdheim-Chester disease: atypical presentation of a rare disease

We report the clinical case of an adult patient referred to our hospital because of trismus due to a tumour in the right infratemporal and pterygomaxillary fossa. He referred hyporexia, weight loss and right trigeminal neuralgia. On physical examination, he had trismus and diplopia. On neuroimaging, the tumour invaded the central nervous system affecting the right temporal lobe and orbit, and the sellar region. Tumour biopsy revealed foamy histiocytes and isolated giant multinuclear cells immunoreactive to CD68 and negative to CD1a and S100. A diagnosis of Erdheim-Chester disease was made. Non-evidence of large bone involvement was found in neither plain radiographs nor Technetium 99 m bone scintigraphy. BRAFV600E mutation analysis was negative. Because of raised intracranial pressure, a debulking surgery of the intracranial histiocytic process was performed. The patient improved his symptoms and remains clinically stable after 12 months of treatment with pegylated interferon-α–2a 180 µg/weekly.



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Radioactive and stable cesium isotope distributions and dynamics in Japanese cedar forests

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Publication date: Available online 11 October 2017
Source:Journal of Environmental Radioactivity
Author(s): Vasyl Yoschenko, Tsugiko Takase, Thomas G. Hinton, Kenji Nanba, Yuichi Onda, Alexei Konoplev, Azusa Goto, Aya Yokoyama, Koji Keitoku
Dynamics of the Fukushima-derived radiocesium and distribution of the natural stable isotope 133Cs in Japanese cedar (Cryptomeria japonica D. Don) forest ecosystems were studied during 2014–2016. For the experimental site in Yamakiya, Fukushima Prefecture, we present the redistribution of radiocesium among ecosystem compartments during the entire observation period, while the results obtained at another two experimental site were used to demonstrate similarity of the main trends in the Japanese forest ecosystems. Our observations at the Yamakiya site revealed significant redistribution of radiocesium between the ecosystem compartments during 2014–2016. During this same period radionuclide inventories in the aboveground tree biomass were relatively stable, however, radiocesium in forest litter decreased from 20 ± 11% of the total deposition in 2014 to 4.6 ± 2.7% in 2016. Radiocesium in the soil profile accumulated in the 5-cm topsoil layers. In 2016, more than 80% of the total radionuclide deposition in the ecosystem resided in the 5-cm topsoil layer.The radiocesium distribution between the aboveground biomass compartments at Yamakiya during 2014–2016 was gradually approaching a quasi-equilibrium distribution with stable cesium. Strong correlations of radioactive and stable cesium isotope concentrations in all compartments of the ecosystem have not been reached yet. However, in some compartments the correlation is already strong. An increase of radiocesium concentrations in young foliage in 2016, compared to 2015, and an increase in 2015–2016 of the 137Cs/133Cs concentration ratio in the biomass compartments with strong correlations indicate an increase in root uptake of radiocesium from the soil profile. Mass balance of the radionuclide inventories, and accounting for radiocesium fluxes in litterfall, throughfall and stemflow, enabled a rough estimate of the annual radiocesium root uptake flux as 2 ± 1% of the total inventory in the ecosystem.



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Cancer Immunotherapy Trials Underutilize Immune Response Monitoring

AbstractImmune‐related radiological and biomarker monitoring in cancer immunotherapy trials permits interrogation of efficacy and reasons for therapeutic failure. We report the results from a cross‐sectional analysis of response monitoring in 685 T‐cell checkpoint‐targeted cancer immunotherapy trials in solid malignancies, as registered on the U.S. National Institutes of Health trial registry by October 2016. Immune‐related radiological response criteria were registered for only 25% of clinical trials. Only 38% of trials registered an exploratory immunological biomarker, and registration of immunological biomarkers has decreased over the last 15 years. We suggest that increasing the utilization of immune‐related response monitoring across cancer immunotherapy trials will improve analysis of outcomes and facilitate translational efforts to extend the benefit of immunotherapy to a greater proportion of patients with cancer.

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A Comprehensive Review of Sequencing and Combination Strategies of Targeted Agents in Metastatic Colorectal Cancer

AbstractThe emergence of targeted therapies for the treatment of metastatic colorectal cancer (mCRC) has considerably improved survival, but has resulted in a dilemma of identifying the optimal sequence and combination of various agents in the mCRC treatment landscape. A number of cytotoxic agents, including irinotecan, oxaliplatin, 5‐fluorouracil, capecitabine, and TAS‐102, are available for treatment of mCRC. Additionally, whereas patients harboring rat sarcoma viral oncogene homolog (RAS)–wild type mCRC can be treated with the anti‐epidermal growth factor receptor antibodies cetuximab and panitumumab or antiangiogenic agents (bevacizumab, ziv‐aflibercept, and ramucirumab), patients with RAS‐mutant mCRC are limited to antiangiogenic agents as biologic options. Regorafenib, a multikinase inhibitor, can be used in both RAS subgroups. As such, the recommended sequence of therapies that should be received by each subgroup must also be considered separately. This review provides an overview of recent clinical data for approved and investigational targeted therapies that have been studied across different mCRC treatment lines and patient subgroups. It also examines emerging trends in the treatment landscape for mCRC, including treatment with immune checkpoint inhibitors and the utilization of genomic profiling.Implications for Practice.Currently, there are no established guidelines for optimal sequencing of cytotoxic or targeted agents in metastatic colorectal cancer (mCRC). This review provides a snapshot of the current mCRC treatment paradigm. We review the latest clinical data that support the utilization of several targeted agents alone or in combination with backbone chemotherapy across different lines of treatment and patient populations and highlight recommendations for their usage. Recent advances in the treatment landscape are also summarized, including genomic profiling and preliminary results with immune checkpoint inhibitors.

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Cost‐Effectiveness of Nivolumab in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma

AbstractBackground.Treatment options for patients with platinum‐refractory, recurrent, metastatic head and neck squamous cell carcinoma (r/m HNSCC) are limited and prognosis is poor. The recent CheckMate 141 clinical trial demonstrated that nivolumab, an anti‐programmed cell death protein 1 monoclonal antibody, was efficacious in extending the median overall survival (OS) in this patient population compared with standard therapies. We conducted a cost‐effectiveness analysis to determine whether nivolumab is a cost‐effective treatment in this patient population and examined various subgroups to determine for which, if any, the treatment is more cost‐effective.Materials and Methods.We implemented a state transition model for HNSCC with a patient cohort who had tumor progression 6 months after the last dose of platinum‐containing chemotherapy and compared the cost‐effectiveness of nivolumab with docetaxel. Treatment effect estimates and adverse event rates were obtained from CheckMate 141. Costs, utilities, and other model inputs were gathered from published sources. We used a Canadian perspective, a 5‐year time horizon, and a 1.5% discount rate for the analysis.Results.Nivolumab extended mean OS by 4 months compared with docetaxel and resulted in fewer treatment‐related adverse events, producing an incremental effectiveness of 0.13 quality‐adjusted life years (QALY). The incremental cost of treatment with nivolumab was $18,823. At a willingness‐to‐pay threshold of $100,000/QALY, nivolumab was not a cost‐effective treatment option for r/m HNSCC, with an incremental cost‐effectiveness ratio of $144,744/QALY. Nivolumab would be cost‐effective if its price was reduced by 20%. Our subgroup analysis seemed to indicate that nivolumab might be cost‐effective for tumors with expression of programmed death‐ligand 1 >5%.Conclusion.We conclude that although nivolumab offers clinical benefit for the treatment of r/m HNSCC over current regimens, it is not cost‐effective based on its list price. We have also established a value‐based price estimate for nivolumab to be cost‐effective in this patient population. Further study is required to draw a definitive conclusion on biomarkers for cost‐effectiveness.Implications for Practice.In health care settings in which cost considerations are a constraint on choice of therapy, patient selection should be carefully considered to maintain efficiency in the system. Until a biomarker for response to therapy is identified for nivolumab, this medication is unlikely to be cost‐effective for most patients with recurrent, metastatic head and neck squamous cell carcinoma.

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Outcomes of a Specialized Interdisciplinary Approach for Patients with Cancer with Aberrant Opioid‐Related Behavior

AbstractBackground.Data on the development and outcomes of effective interventions to address aberrant opioid‐related behavior (AB) in patients with cancer are lacking. Our outpatient supportive care clinic developed and implemented a specialized interdisciplinary team approach to manage patients with AB. The purpose of this study was to report clinical outcomes of this novel intervention.Materials and Methods.The medical records of 30 consecutive patients with evidence of AB who received the intervention and a random control group of 70 patients without evidence of AB between January 1, 2015, and August 31, 2016, were reviewed.Results.At baseline, pain intensity (p = .002) and opioid dose (p = .001) were significantly higher among patients with AB. During the course of the study, the median number of ABs per month significantly decreased from three preintervention to 0.4 postintervention (p < .0001). The median morphine equivalent daily dose decreased from 165 mg/day at the first intervention visit to 112 mg/day at the last follow‐up (p = .018), although pain intensity did not significantly change (p = .984). "Request for opioid medication refills in the clinic earlier than the expected time" was the AB with the highest frequency prior to the intervention and the greatest improvement during the study period. Younger age (p < .0001) and higher Edmonton Symptom Assessment System anxiety score (p = .005) were independent predictors of the presence of AB.Conclusion.The intervention was associated with a reduction in the frequency of AB and opioid utilization among patients with cancer receiving chronic opioid therapy. More research is needed to further characterize the clinical effectiveness of this intervention.Implications for Practice.There are currently no well‐defined and evidence‐based strategies to manage cancer patients on chronic opioid therapy who demonstrate aberrant opioid‐related behavior. The findings of this study offer a promising starting point for the creation of a standardized strategy for clinicians and provides valuable information to guide their practice regarding these patients. The study results will also help clinicians to better understand the types and frequencies of the most common aberrant behaviors observed among patients with cancer who are receiving chronic opioid therapy. This will enhance the process of timely patient identification, management, or referral to the appropriate specialist teams.

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Prof. Gian Franco Bottazzo MD FRCP FRCPath (1946–2017)



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Luciano Martini (1927–2017): a memoir



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Peritoneal pre-conditioning reduces macrophage marker expression in collagen-containing engineered vascular grafts

Publication date: Available online 5 October 2017
Source:Acta Biomaterialia
Author(s): Mozhgan Shojaee, Kristin B. Wood, Lisa K. Moore, Chris A. Bashur
Engineered vascular grafts have shown promise as arteriovenous shunts, but they have not yet progressed to clinical trials for coronary arteries <4 mm in diameter such as the coronary arteries. Control over initial biomaterial properties and remodeling are necessary to generate viable grafts. In this study, we blended collagen with a synthetic material, poly(ε-caprolactone), to modulate the post-grafting inflammatory response while avoiding aneurysmal-like dilation and failure that can occur with pure collagen grafts. We also used pre-implantation in an "in vivo bioreactor" to recruit autologous cells and improve patency after grafting. Electrospun conduits were pre-implanted within rat peritoneal cavities and then grafted autologously into abdominal aortae. Conduit collagen percentages and pre-implantation were tested for their impact on graft remodeling and patency. Burst pressures >2000 mmHg, reproducible expansion with systole/diastole, and maintenance of mechanical integrity were observed. More importantly, peritoneal pre-implantation reduced overall lipid oxidation, intimal layer thickness, and expression of an M1 macrophage marker. The condition with the most collagen, 25%, exhibited the lowest expression of macrophage markers but also resulted in a thicker intimal layer. Overall, the 10% collagen/PCL with peritoneal pre-implantation condition appeared to exhibit the best combination of responses, and may result in improved clinical graft viability.Statement of SignificanceThis manuscript describes a rodent study to systematically determine the benefits of both pre-implantation in the peritoneal cavity and specific ratios of collagen on engineered vascular graft viability. We show that pre-implantation had a significant benefit, including decreasing the expression of macrophage markers and reducing lipid oxidation after grafting. This study is the first time that the benefits of peritoneal pre-implantation have been compared to an "off the shelf," directly grafted control condition. We also demonstrated the importance of specific collagen ratio on the response after grafting. Overall, we feel that this article will be of interest to the field and it has the potential to address a significant clinical need: a graft for coronary arteries <4 mm in diameter.

Graphical abstract

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Synchronous HPV-Related Cancer of Bilateral Tonsils Detected Using Transoral Endoscopic Examination with Narrow-Band Imaging

Background. The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy. Methods and Results. We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy. Conclusion. To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.

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Synchronous HPV-Related Cancer of Bilateral Tonsils Detected Using Transoral Endoscopic Examination with Narrow-Band Imaging

Background. The incidence of human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing worldwide. HPV is reported in approximately 50% cases of OPSCC in Japan. However, there are few reports of synchronous bilateral HPV-positive tonsillar carcinoma, and, in almost all those cases, carcinoma was detected using positron emission tomography/computed tomography and/or bilateral tonsillectomy. Methods and Results. We report the case of a 63-year-old male with bilateral tonsillar carcinoma detected using transoral endoscopic examination with narrow-band imaging (NBI). A biopsy of the bilateral tonsils revealed squamous cell carcinoma, which was demonstrated to be HPV-related using in situ hybridization and p16 immunohistochemistry. The patient was diagnosed as synchronous bilateral tonsillar carcinoma: T1 (2) N2b M0. He was treated with induction chemotherapy, bilateral radical tonsillectomy with neck dissection, and radiotherapy. Conclusion. To our knowledge, this is the first report of a synchronous bilateral tonsillar carcinoma detected using transoral NBI in the outpatient setting. Early diagnosis without the inspection under general anesthesia is beneficial for the patients with lymph node metastasis from unknown primary lesion.

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Management of Patients who Receive an Organ Transplant Abroad and Return Home for Follow-up Care: Recommendations From the Declaration of Istanbul Custodian Group.

Eradicating transplant tourism depends upon complex solutions that include efforts to progress towards self-sufficiency in transplantation. Meanwhile, professionals and authorities are faced with medical, legal, and ethical problems raised by patients who return home after receiving an organ transplant abroad, particularly when the organ has been obtained through illegitimate means. In 2016, the Declaration of Istanbul Custodian Group convened an international, multidisciplinary workshop in Madrid, Spain, to address these challenges and provide recommendations for the management of these patients, which are presented in this paper. The core recommendations are grounded in the belief that principles of transparency, traceability and continuity of care applied to patients who receive an organ domestically should also apply to patients who receive an organ abroad. Governments and professionals are urged to ensure that, upon return, patients are promptly referred to a transplant center for evaluation and care; not cover the costs of transplants resulting from organ or human trafficking; register standardized information at official registries on patients who travel for transplantation; promote international exchange of data for traceability; and develop a framework for the notification of identified or suspected cases of transnational transplant-related crimes by health professionals to law enforcement agencies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Rhesus Alloimunization Occurs After Rh Incompatible Liver Transplantation in Children.

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No abstract available

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Venous Thromboembolism After Adult Lung Transplantation: A Frequent Event Associated with Lower Survival.

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Background: The incidence of venous thromboembolism (VTE) after lung transplantation (LTX) varies significantly across studies. Two studies have suggested that these thrombotic events are associated with a lower posttransplant survival. Herein, we sought to determine the incidence, predictors and impact of VTE on survival after LTX at a quaternary referral center. Methods: This was a large cohort study of LTX recipients. Key outcome parameters were time to VTE after transplant and survival. Deep vein thrombosis (DVT) diagnosis required a positive ultrasound. Pulmonary embolism diagnosis required either a positive chest computed tomography angiogram or a high-probability ventilation/perfusion scan. Results: The overall incidence of VTE among 701 LTX recipients was 43.8%, of which 97.7% were DVT episodes, of which 71.3% were in the upper extremities. Predictors of VTE were prior history of DVT (HR 2.82, 95% CI 1.49 - 5.37), days in intensive care (HR 1.01, 95% CI 1.01 - 1.02), and the use of extracorporeal membrane oxygenation (HR 2.22, 95% CI 1.43 - 3.45). Importantly, VTE predicted a lower posttransplant survival (HR 1.70, 95% CI 1.28 - 2.26), when occurring within or after the first 30 days. The location of the DVT, either upper extremity or below the knee, also predicted a poor survival. Conclusions: VTE was frequent in LTX recipients and predicted a poor survival even when located in the upper extremities or below the knee. Post LTX factors were the major predictors of VTE. These data suggest that aggressive VTE screening/treatment protocols be implemented in post LTX population. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The Optimization of the Prevascularization Procedures for Improving Subcutaneous Islet Engraftment.

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Background: Subcutaneous islet transplantation (SC Tx) is associated with minimal invasiveness, but poor vascularization. Thus, the optimization of the prevascularization procedures is crucial for improving the outcomes. Although the effectiveness of basic fibroblast growth factor (bFGF) was reported, the optimal procedures remain unclear. We sought to optimize the prevascularization procedures including the use of a novel scaffold, recombinant peptide (RCP). Methods: Devices containing various amount of bFGF with/without heparin, or RCP were implanted into the subcutaneous space of diabetic C57BL/6 mice. Syngeneic islets were transplanted into the prevascularized space. Blood glucose, intra-peritoneal glucose tolerance, and immunohistochemistry were evaluated. Results: The cure rates in all the device groups irrespective of bFGF doses were considerably higher than in the nondevice group. The cure rate in the bFGF0 group was unexpectedly higher than that in the subcutaneous islet transplant alone group (the None group) (57.1 vs. 28.6%). Glucose tolerance was ameliorated in the bFGF10(-), 10(+) and 15(-) groups. The number of vWF-positive vessels in the bFGF10(+) group was significantly higher than that in the None and bFGF0 groups (P

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Interactive effects of PAHs with different rings and As on their uptake, transportation, and localization in As hyperaccumulator

Abstract

In order to illuminate the mechanism of the interaction of polycyclic aromatic hydrocarbon (PAH) with different benzene rings and arsenic (As) in As hyperaccumulator, Pteris vittata L., the uptakes of PAHs were investigated using hydroponics simulation and localizations of PAHs in the plant were determined using two-photon laser scanning confocal microscopy (TPLSCM). The results showed that the total As concentration in different parts of P. vittata decreased in the presence of PAHs with increased numbers of benzene rings: 38.0–47.4% for benzo(a)pyrene (BaP, five rings), 20.5–35.9% for pyrene (PYR, four rings), and 13.7–16.6% for fluorine (FLU, three rings). BaP and PYR concentrations increased, while FLU concentration decreased in the presence of As. The results of TPLSCM revealed that PAHs distributed in epidermal cells of roots, xylem, and endothelial cells of rachis, epidermis, and stomatal cells of pinnae; however, the fluorescence intensity of BaP and PYR were higher than FLU significantly in plant. This study provided important basis to further research on interactive effects of PAHs and As in the P. vittata. These findings were important to understand the mechanisms of PAH and As translocation and distribution by P. vittata.



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In search of a comprehensible set of endpoints for the routine monitoring of neurotoxicity in vertebrates: sensory perception and nerve transmission in zebrafish ( Danio rerio ) embryos

Abstract

In order to develop a test battery based on a variety of neurological systems in fish, three sensory systems (vision, olfaction, and lateral line) as well as nerve transmission (acetylcholine esterase) were analyzed in zebrafish (Danio rerio) embryos with respect to their suitability as a model for the screening of neurotoxic trace substances in aquatic ecosystems. As a selection of known or putative neurotoxic compounds, amidotrizoic acid, caffeine, cypermethrin, dichlorvos, 2,4-dinitrotoluene, 2,4-dichlorophenol, 4-nonylphenol, perfluorooctanoic acid, and perfluorooctane sulfonic acid were tested in the fish embryo test (OECD test guideline 236) to determine EC10 values, which were then used as maximum test concentration in subsequent neurotoxicity tests. Whereas inhibition of acetylcholinesterase was investigated biochemically both in vivo and in vitro (ex vivo), the sensory organs were studied in vivo by means of fluorescence microscopy and histopathology in 72- or 96-h-old zebrafish embryos, which are not regarded as protected developmental stages in Europe and thus — at least de jure — represent alternative test methods. Various steps of optimization allowed this neurotoxicity battery to identify neurotoxic potentials for five out of the nine compounds: Cypermethrin and dichlorvos could be shown to specifically modulate acetylcholinesterase activity; dichlorvos, 2,4-dichlorophenol, 4-nonylphenol, and perfluorooctane sulfonic acid led to a degeneration of neuromasts, whereas both vision and olfaction proved quite resistant to concentrations ≤ EC10 of all of the model neurotoxicants tested. Comparison of neurotoxic effects on acetylcholinesterase activity following in vivo and in vitro (ex vivo) exposure to cypermethrin provided hints to a specific enzyme-modulating activity of pyrethroid compounds. Enhancement of the neuromast assay by applying a simultaneous double-staining procedure and implementing a 4-scale scoring system (Stengel et al. 2017) led to reduced variability of results and better statistical resolution and allowed to differentiate location-dependent effects in single neuromasts. Since acetylcholinesterase inhibition and neuromast degeneration can be analyzed in 72- and 96-h-old zebrafish embryos exposed to neurotoxicants according to the standard protocol of the fish embryo toxicity test (OECD TG 236), the fish embryo toxicity test can be enhanced to serve as a sensitive neurotoxicity screening test in non-protected stages of vertebrates.



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Prognostic significance of standardized uptake value on F18-FDG PET/CT in patients with extranodal nasal type NK/T cell lymphoma: A multicenter, retrospective analysis

The purpose of this study was to evaluate the value of parameters assessed with F18-flurodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting relapse free survival and overall survival in patients with extranodal nasal type NK/T cell lymphoma.

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Prognostic significance of standardized uptake value on F18-FDG PET/CT in patients with extranodal nasal type NK/T cell lymphoma: A multicenter, retrospective analysis

The purpose of this study was to evaluate the value of parameters assessed with F18-flurodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting relapse free survival and overall survival in patients with extranodal nasal type NK/T cell lymphoma.

http://ift.tt/2z0ueJd

Fluoride containing bioactive glass composite for orthodontic adhesives – ion release properties

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Publication date: Available online 10 October 2017
Source:Dental Materials
Author(s): N.A. Al-eesa, F.S.L. Wong, A. Johal, R.G. Hill
ObjectiveDental materials that release calcium, phosphate and fluoride ions could prevent demineralisation and/or enhance remineralisation of enamel. The objective was to develop a novel bioactive glass (BAG) resin and investigate pH changes and ion release in 3 immersion media.MethodsQuench melt derived BAG (35.25% SiO2, 6% Na2O, 43% CaO, 5.75% P2O5, and 10% CaF2) was incorporated into a resin (42.25% BisEMA, 55% TEGDMA, 0.25% DMAEM, 0.5% camphorquinone and 2% 4-Meta), with a filler load of 80% by weight. Ninety composite disks for each BAG loading of 80%, 60%, 50%, 40%, 20%, and 0% were made and each disk was immersed in 10ml of either tris buffer (TB), or artificial saliva at pH=7 (AS7) or pH=4 (AS4), n=30 for each solution. Three disks of each loading were taken from each of the solutions, at ten time points (6h–6months), for measurement of pH, fluoride, calcium and phosphate.ResultsThe BAG adhesive raised the pH in all the solutions, release Ca, PO4 and F ions especially in AS4. The rise in pH and the release of Ca and F are directly related to the BAG loading and the time of immersion. The pH and the ion releases were maintained and continued over 6months.SignificanceUnlike glass ionomer resins, favourable ions F, Ca and PO4 releases were maintained over a long time period especially in acidic condition for this novel BAG-resin composite. This indicates the resin has the potential to prevent formation and progression of early caries lesions.



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Structural and Ultrastructural Analyses of Bone Regeneration in Rabbit Cranial Osteotomy: Piezosurgery Versus Traditional Osteotomes

Clinical advantages of piezosurgery have been already proved. However, few investigations have focused on the dynamics of bone healing. The aim of this study was to evaluate, in adult rabbits, bone regeneration after cranial linear osteotomies with two piezoelectrical devices (Piezosurgery Medical – PM and Piezosurgery Plus – PP), comparing them with conventional rotary osteotomes (RO). PP was characterized by an output power three times higher than PM. Fifteen days after surgery, histomorphometric analyses showed that the osteotomy gap produced with PM and PP was about half the size of that produced by RO, and in a more advanced stage of recovery.

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Effect of an alkaline environment on the engineering behavior of cement-stabilized/solidified Zn-contaminated soils

Abstract

Although the stabilization/solidification method has been widely used for remediation of heavy metal-contaminated soils in recent decades, the engineering behavior and mobility of heavy metal ions under alkaline groundwater conditions are still unclear. Therefore, the unconfined compressive strength test (UCS) combined with toxicity characteristic leaching procedure (TCLP) and general acid neutralization capacity (GANC) was used to investigate the effects of alkalinity (using NaOH to simulate alkalinity in the environment) on the mechanical and leaching characteristics of cement-solidified/stabilized (S/S) Zn-contaminated soils. Moreover, the microstructure was analyzed using the scanning electron microscope (SEM) technology. The results indicated that alkaline environment could accelerate the UCS development compared with specimens without soaking in NaOH solution,, regardless of whether the specimens contained Zn2+ or not. And the UCS varied obviously attributed to the variations of both NaOH concentration and soaking time. Except for the specimens soaked for 90 days, the leached Zn2+ concentrations were higher than that of without soaking. However, the leachability of Zn2+ in all the stabilized specimens is in the regulatory level. ANC results indicated that the Zn2+ leaching behavior can be divided into three stages related to the initial leachate pH. Moreover, SEM results proved that the alkaline environment could actually facilitate the cement hydration process. The results proved in the present paper could be useful in treating the heavy metal-contaminated soils involved in the solidification/stabilization technology under alkaline environment.



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Continuous positive airway pressure treatment with nasal pillows in obstructive sleep apnea: long-term effectiveness and adherence

s: Mask-related side effects can negatively influence adherence to continuous positive airway pressure (CPAP). Nasal pillows (P) can be an alternative to the standard nasal masks (N), although there are no data about their long-term efficacy. This study aimed to assess long-term effectiveness and adherence to CPAP therapy delivered with nasal pillows in obstructive sleep apnea syndrome (OSAS) patients.

http://ift.tt/2hCyp74

The effect of sleep duration and sleep quality on hypertension in middle-aged and older Chinese: the Dongfeng-Tongji Cohort Study

To examine the independent and combined associations of sleep duration and sleep quality with hypertension in a middle-aged and older Chinese population.

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Assessment of intervention-related changes in non-rapid-eye-movement sleep depth: importance of sleep depth changes within stage 2

Depth of sleep within non-rapid-eye-movement (non-REM) stage-2 (N2-depth) varies from being nearly similar to stage-1 to nearly similar to stage-3. Differences in N2-depth are not captured by conventional indices of sleep depth (N1–N3 times, arousal/awakening index) when comparing sleep depth under different conditions. Magnitude of changes in N2-depth in the same individual under different experimental conditions, and the importance of measuring these changes are unknown.

http://ift.tt/2hCyibE

Prevalence of sleep-disordered breathing in Japanese medical students based on type-3 out-of-center sleep test

Sleep-disordered breathing (SDB), especially obstructive sleep apnea disorder (OSA), is thought to mainly affect men over the age of 40. Following findings that Asian people are more likely to experience severe OSA, regardless of obesity, we investigated the prevalence of SDB and OSA in a larger sample and in more younger age groups than those described in previous reports.

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Longitudinal associations between sleep and anxiety during pregnancy, and the moderating effect of resilience, using parallel process latent growth curve models

For many women, pregnancy-related sleep disturbances and pregnancy-related anxiety change as pregnancy progresses are both associated with lower maternal quality of life and less favorable birth outcomes. Thus, the interplay between these two problems across pregnancy is of interest. In addition, psychological resilience may explain individual differences in this association, as it may promote coping with both sleep disturbances and anxiety, and thereby reduce their mutual effects. Therefore, the aim of the current study was to examine whether sleep quality and sleep duration, and changes in sleep are associated with the level of and changes in anxiety during pregnancy.

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Analysis and experimental evaluation of shunt active power filter for power quality improvement based on predictive direct power control

Abstract

This paper discusses the use of the concept of classical and predictive direct power control for shunt active power filter function. These strategies are used to improve the active power filter performance by compensation of the reactive power and the elimination of the harmonic currents drawn by non-linear loads. A theoretical analysis followed by a simulation using MATLAB/Simulink software for the studied techniques has been established. Moreover, two test benches have been carried out using the dSPACE card 1104 for the classic and predictive DPC control to evaluate the studied methods in real time. Obtained results are presented and compared in this paper to confirm the superiority of the predictive technique. To overcome the pollution problems caused by the consumption of fossil fuels, renewable energies are the alternatives recommended to ensure green energy. In the same context, the tested predictive filter can easily be supplied by a renewable energy source that will give its impact to enhance the power quality.



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Long-term treatment with dopamine D3 receptor agonists induces a behavioral switch that can be rescued by blocking the dopamine D1 receptor

Restless legs syndrome (RLS) is commonly treated with the dopamine agonists, pramipexole and rotigotine, which target the inhibitory dopamine receptor subtype, D3R. While initially highly effective, these compounds lose their efficacy in treating RLS over time, and long-term therapy regularly leads to a worsening of the symptoms (augmentation). This dopamine agonist-induced augmentation has become a prime concern in the treatment of RLS, and while alternate therapies are being proposed, the mechanisms leading to augmentation remain opaque.

http://ift.tt/2yGgGGr

Gender differences in sleep symptoms after repeat concussions

There are notable gender differences in concussion as well as sleep. Sleep disturbance is a major symptom of post-concussive syndrome. The interplay between sleep disturbance, concussion, and gender has yet to be examined. The objective of this study was to determine whether sleep disturbance plays a role in the known gender differences associated with concussion.

http://ift.tt/2hCy5VU

Photoreduction of Cr(VI) in water using BiVO 4 -Fe 3 O 4 nano-photocatalyst under visible light irradiation

Abstract

The residuals of hexavalent chromium in the aquatic environment have raised much concern for water decontamination. In this study, BiVO4-Fe3O4 was synthesized using a solvothermal method and adopted as a photoreduction catalyst to removal of Cr(VI) in water under visible light irradiation. The physical and chemical properties of BiVO4-Fe3O4 were characterized by UV-vis-DRS, SEM, XRD, FTIR, and BET. The results demonstrated that the band gap for the obtained material is 1.74 eV with an average size of 15 nm and a specific surface area of 55.16 m2/g. A high photocatalytic performance was observed on the photoreduction of Cr(VI) and the removal efficiency was increased in the lower pH condition. The ascending catalyst dosages made the promotion effect, while the increase of Cr(VI) concentration contributed the inhibition for the reduction performance. The structural characteristics of the selected hole scavengers (ethanol, isopropanol, formic acid, citric acid, and oxalic acid) showed the various effects on the reactions due to the amounts of α-OH. For the optimal condition, 79.37% Cr(VI) was removed. Based on the excellent reusability of BiVO4-Fe3O4, this study demonstrated a potential method for the economic-friendly removal of high-valence metals with easier separation in the water.



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The role of α1- and α2-adrenoceptor subtypes in the vasopressor responses induced by dihydroergotamine in ritanserin-pretreated pithed rats

Dihydroergotamine (DHE) is an acute antimigraine agent that displays affinity for dopamine D2-like receptors, serotonin 5-HT1/2 receptors and α1/α2-adrenoceptors. Since activation of vascular α1/α2-adrenoceptors ...

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Audiological findings in a de novo mutation of ANKRD11 gene in KBG syndrome: Report of a case and review of the literature

KBG syndrome is a rare genetic disorder, due to a mutation of ANKRD11, characterized by specific craniofacial dysmorphism, short stature and macrodontia of upper central incisors, intellectual disability and skeletal anomalies. We report a de novo mutation of ANKRD11 gene in a 7-years old girl, affected by KBG syndrome with bilateral conductive hearing loss. The aim of this article was to review the audiological findings of this syndrome.

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The addition of PRP to facial lipofilling: a double-blind placebo-controlled randomized trial.

Background: Lipofilling is a treatment modality to restore tissue volume, but may also rejuvenate the aging skin. Platelet-rich plasma has been reported to augment the efficacy of lipofilling, both on graft take and rejuvenation by altering the ADSC. Authors hypothesized that PRP addition would increase the rejuvenating effect while shortening recovery time. Methods: The study conducted was a single-centre, double blinded, placebo-controlled randomized trial (2012-2015). In total, a well-defined cohort of 32 healthy females enrolled in the study, with 25 completing the follow-up. All patients underwent aesthetic facial lipofilling with either saline or PRP added. Outcome was determined by changes in skin elasticity, volumetric changes of the nasolabial fold, recovery time and patient satisfaction during follow-up (1 year). Results: PRP did not improve the outcome of facial lipofilling when looking at skin elasticity improvement, graft volume maintenance in the nasolabial fold or patient satisfaction. Patient recovery after surgery however, dropped significantly. Furthermore, no skin rejuvenation effects from lipofilling could be observed. Conclusion: This study clearly demonstrates that the addition of PRP to the lipograft significantly reduces patient's reported recovery time, but does not significantly improve skin elasticity, volume retention nor overall patient satisfaction as compared to lipofilling alone. Moreover, reported effects of 'normal' (not SVF/ADSC enriched) lipofilling on skin rejuvenation, as has been reported and suggested to be seen in clinical studies when used in combination with facelift surgery, could also not be addressed. (C)2017American Society of Plastic Surgeons

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The lateral thigh perforator (LTP) flap for autologous breast reconstruction: A prospective analysis of 138 flaps.

Background: The septocutaneous tensor fasciae latae (sc-TFL) or lateral thigh perforator (LTP) flap was previously introduced by our group as an alternative flap for autologous breast reconstruction when the abdomen is not suitable as a donor site. The aim of this study was to analyze our experience with the LTP flap and to present the surgical refinements that were introduced. Methods: A prospective study was conducted of all LTP flap breast reconstructions performed since September 2012. Patient demographics, operative details, complications and flap re-explorations were recorded. Preoperative imaging with MRA was performed in all patients. Surgical refinements that were introduced during this study included limitation of the flap width and the use of quilting sutures at the donor site. Results: A total of 138 LTP flap breast reconstructions were performed in 86 consecutive patients. Median operation times were 277 minutes (range 196-561) for unilateral and 451 minutes (range 335-710) for bilateral procedures. Median flap weight was 348 grams (range 175-814). Two total flap losses (1.4%) were recorded and eleven flaps (8.0%) required re-exploration, which resulted in viable flaps. The incidence of donor-site complications reduced significantly after the surgical refinements were introduced. Wound problems decreased from 40.0% to 6.3%, seroma from 25.0% to 9.5%, and infection from 27.5% to 9.5%, respectively. Conclusions: The LTP flap is an excellent option for autologous breast reconstruction with minimal recipient-site complications. The surgical refinements resulted in a significant reduction of donor-site complications. Therefore, the LTP flap is currently our second choice after the DIEP flap. (C)2017American Society of Plastic Surgeons

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Complications and Patient-Reported Outcomes after Abdominal-Based Breast Reconstruction: Results of the Mastectomy Reconstruction Outcomes Consortium (MROC) Study.

Background: Abdominal flap reconstruction is the most popular form of autologous breast reconstruction. The current study compared complications and patient-reported outcomes (PROs) after pedicled transverse rectus abdominis myocutaneous (PTRAM), free TRAM (FTRAM), deep inferior epigastric perforator (DIEP), and superficial inferior epigastric artery (SIEA) flaps. Methods: Patients having abdominal-based breast reconstruction at 11 centers were prospectively evaluated for abdominal donor-site and breast complications. PROs were measured by the BREAST-Q and PROMIS surveys. Mixed-effects regression models were used to assess the effects of procedure type on outcomes. Results: 720 patients had one-year follow-up and 587 had two-year follow-up. Two years after reconstruction, SIEA compared with DIEP flap was associated with a higher rate of donor-site complications (OR=2.7, p=0.001), however SIEA reported higher BREAST-Q abdominal physical well-being scores than DIEP at one year (mean difference: 4.72, p=0.053, on a scale from 0 to 100). This difference was not significant at two years. Abdominal physical well-being scores at two year post-operatively were lower in PTRAM group by 7.2 points (p=0.006) than DIEP and by 7.8 points (p = 0.03) than SIEA, and in FTRAM group lower by 4.9 points (p = 0.04) than DIEP. Bilateral reconstruction had significantly lower abdominal physical well-being scores compared with unilateral reconstruction. Conclusions: While all abdominal-based flaps are viable breast reconstruction options, DIEP and SIEA flaps are associated with a higher abdominal physical well-being than PTRAM and FTRAM flaps. Although SIEA flaps offer the advantage of not violating the fascia, higher rates of donor-site complications may diminish patient satisfaction. (C)2017American Society of Plastic Surgeons

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Outcomes After Phalloplasty: Do Transgender Patients and Multiple Urethral Procedures Carry a Higher Rate of Complication?.

Introduction: Phalloplasty is associated with improved quality-of-life in those with penile defects, and in female-to-male transgender (transmale) patients seeking gender-confirming surgery. However, aggregate complication and outcome data is sparse. This study compares phalloplasty outcomes between transmale and cismale patients and between those with primary versus staged urethroplasty. Methods: A comprehensive literature search of PubMed, MEDLINE, and Google Scholar databases was conducted for studies relating to phalloplasty. Data on techniques, complications, outcomes, and patient demographics were collected. Analysis using the random-effects model with subgroup analyses was performed. Results: A total of 50 studies (1,351 patients) were included; 19 studies (869 patients) for transmale patients and 31 studies (482 patients) for cismale patients. The urethral complication rate in the transmale group was 39.4% (95% CI: 30.6-48.9, p=0.028) compared to 24.8% (95% CI: 16.5-35.4, p

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From Classical to Unusual: Report on 5 Cases of Transient Reactive Aquagenic Pseudokeratoderma and Review of the Literature.

Transient reactive aquagenic pseudokeratoderma is characterized by transient whitish and translucent papules after water exposure in palms and soles. We report 5 additional cases and their histopathologic features. Patient 5 showed a topography that had not been reported before; this demonstrates that it is not an exclusive condition of palms and soles. Patient 2 presents very subtle clinical findings, making difficult the diagnosis. And the other 3 patients have a typical presentation. Transient reactive aquagenic pseudokeratoderma has heterogeneous clinical features; in some cases, histopathologic findings, although subtle, help to confirm the diagnosis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Tumour auto-contouring on 2d cine MRI for locally advanced lung cancer: A comparative study

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Publication date: Available online 10 October 2017
Source:Radiotherapy and Oncology
Author(s): Martin F. Fast, Björn Eiben, Martin J. Menten, Andreas Wetscherek, David J. Hawkes, Jamie R. McClelland, Uwe Oelfke
Background and purposeRadiotherapy guidance based on magnetic resonance imaging (MRI) is currently becoming a clinical reality. Fast 2d cine MRI sequences are expected to increase the precision of radiation delivery by facilitating tumour delineation during treatment. This study compares four auto-contouring algorithms for the task of delineating the primary tumour in six locally advanced (LA) lung cancer patients.Material and methodsTwenty-two cine MRI sequences were acquired using either a balanced steady-state free precession or a spoiled gradient echo imaging technique. Contours derived by the auto-contouring algorithms were compared against manual reference contours. A selection of eight image data sets was also used to assess the inter-observer delineation uncertainty.ResultsAlgorithmically derived contours agreed well with the manual reference contours (median Dice similarity index: ⩾0.91). Multi-template matching and deformable image registration performed significantly better than feature-driven registration and the pulse-coupled neural network (PCNN). Neither MRI sequence nor image orientation was a conclusive predictor for algorithmic performance. Motion significantly degraded the performance of the PCNN. The inter-observer variability was of the same order of magnitude as the algorithmic performance.ConclusionAuto-contouring of tumours on cine MRI is feasible in LA lung cancer patients. Despite large variations in implementation complexity, the different algorithms all have relatively similar performance.



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Interim 18F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal cancer patients. A systematic review

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Publication date: Available online 10 October 2017
Source:Radiotherapy and Oncology
Author(s): Marta Cremonesi, Cristina Garibaldi, Robert Timmerman, Mahila Ferrari, Sara Ronchi, Chiara Maria Grana, Laura Travaini, Laura Gilardi, Anna Starzyńska, Delia Ciardo, Roberto Orecchia, Barbara Alicja Jereczek-Fossa, Maria Cristina Leonardi
Oesophageal cancer is an aggressive disease. The possibility to early stratify patients as responsive and non-responsive with a non-invasive method is extremely appealing. The uptake of Fluorodeoxyglucose (18F-FDG) in tumours, provided by positron emission tomography (PET) images, has been proved to be useful to assess the initial staging of the disease, recurrence, and response to chemotherapy and chemo-radiotherapy (CRT). In the last years, efforts have been focused on the possibility to use ad interim 18F-FDG-PET/CT (PETint) to evaluate response during radiation therapy. However, controversial findings have been reported, although some relevant results would support its use for individual therapeutic decision.The present review assembles the comprehensive literature of the last decade to evaluate whether and in which cases PETint may offer predictive potential in oesophageal cancer. All the analysed studies (13 studies, 697 patients) denoted PETint as a challenging examination for early assessment of outcomes during CRT. In particular, 8 studies advocated the predictivity of PETint, whilst 5 did not find any correlation between the interim variation of PET parameters and the pathological complete response and/or the clinical outcome. The reasons that possibly have caused contradictions among the studies demand further research with prospective and uniform protocols and methods of analysis to assess the predictive and prognostic value of PETint in oesophageal cancer.



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Split-Overlapping Genioplasty: Surgical Technique, Morphological and Radiological Long-Term Outcomes.

Background: The overlapping bone flap genioplasty, described by Tessier, was developed to treat major retrognathia or long and retruded chins. For 15 years, we have used a modified version of this technique to avoid its drawbacks. The aim of this article is to describe our modification and evaluate the long-term morphologic and radiologic outcomes. Patients and Method: The authors included every split-overlapping genioplasty performed in our department between 2004 and 2014. Demographics, surgical data, and complications were recorded. Radiologic bone resorption was evaluated comparing preoperative, day-1 postoperative, and year-1 postoperative cephalometric x-rays. Morphologic outcomes were evaluated on standardized pre- and postoperative views using an analogic Likert scale. Surgical Technique: The main modification of the procedure consists in separating the posterior cortex of the transplant using a reciprocating saw. After overlapping the reduced transplant onto the mandible, the posterior cortex is used as an apposition graft to soften the labiomental crease. Results: Forty-seven patients were analyzed during this period. In 44 patients, the procedure was combined with mandibular and/or maxillary osteotomy. The average reduction of symphysis height was 5 mm, and the average pogonion advancement was 4.3 mm. After 1 year, we recorded 7% average bone resorption. No major complications (nerve injury, hematoma, among others) were reported. Morphologic outcomes were deemed satisfactory or very satisfactory in the vast majority of cases. Conclusion: Split-overlapping genioplasty is a safe and reliable procedure with stable, long-lasting outcomes. This versatile technique is particularly useful for the correction of a massive symphysis or high and retruded chins. (C) 2017 by Mutaz B. Habal, MD.

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A Research of Pyogenic Granuloma Genesis Factor With Immunohistochemical Analysis.

Pyogenic granuloma (PG) is a type of vascular tumor for which the growth mechanism is poorly understood. Estrogen and progesterone may influence vascular malformations by increasing neovascularization in the lesions. Pregnancy tumor is a term for PG that occurs on the gingival mucosa of pregnant women in response to local irritation or injury. The etiology and pathogenesis of this phenomenon are not fully understood. Hormonal imbalance has been hypothesized to be responsible for the development of gingival hyper-reactive inflammatory responses. Moreover, it has been shown in vitro that the female sex hormone is a potential regulator of the production of several growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and nerve growth factor, in various cell types. Epidermal growth factor receptor (EGFR) is also involved in a signaling cascade that influences proliferation and other tumor-promoting activities, as well as the responsiveness to chemotherapy. The aim of this study was to examine the relationship between PG pathogenesis and hormone imbalance in 21 patients. All specimens were analyzed by immunohistochemical staining with hematoxylin and eosin for the following hormones: estrogen receptor, progesterone receptor, VEGF, and EGFR. The analysis of the specimens showed that estrogen receptor and EGFR were not associated with PG, while VEGF was statistically related to PG. In addition, there was no significantly difference between sex, tumor location, or pregnancy. There are few studies about correlation between the pathogenesis of PG and sex hormones or growth factors demonstrated via immunohistochemical analysis. The results of this study indicate that estrogen and progesterone do not influence the pathogenesis of PG; however, VEGF may be associated with the pathogenesis of PG. (C) 2017 by Mutaz B. Habal, MD.

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Lolium perenne peptides for treatment of grass pollen allergy: A randomized, double-blind, placebo-controlled clinical trial

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Publication date: Available online 10 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Mohamed H. Shamji, Jan Ceuppens, Claus Bachert, Peter Hellings, Gaël Placier, Gaëtan Thirion, Nicolas Bovy, Stephen R. Durham, Jean Duchateau, Thierry Legon, Sabine Pirotton




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Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes c11orf30/EMSY as a genetic risk factor for food allergy

Publication date: Available online 10 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Yuka Asai, Aida Eslami, C. Dorien van Ginkel, Loubna Akhabir, Ming Wan, George Ellis, Moshe Ben-Shoshan, David Martino, Manuel A. Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W. de Jong, Roy N. Gerth van Wijk, Anthony E.J. Dubois, Rick Chin, Steven Cheuk, Joshua Hoffman, Eric Jorgensen, John S. Witte, Ronald B. Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W. (Bill) Musk, Michael Hunter, Alan L. James, Gerard H. Koppelman, Andrew J. Sandford, Ann E. Clarke, Denise Daley
BackgroundPeanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis.ObjectiveTo investigate genetic susceptibility to PA.MethodsEight hundred and fifty cases and 926 hyper-controls and >7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. Meta-analysis of two phenotypes (PA and food allergy) was conducted using 7 studies from the Canadian, American (2), Australian, German and Dutch (2) populations.ResultsA SNP near ITGA6 reached genome-wide significance with PA (p=1.80×10-8), while SNPs associated with SKAP1, MMP12/MMP13, CTNNA3, ARHGAP24, ANGPT4, c11orf30 (EMSY), and EXOC4 reached a threshold suggestive of association (p≤1.49×10-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, c11orf30 and EXOC4 were significant (p≤1.49×10-6). When a phenotype of any food allergy was used for meta-analysis, the c11orf30 locus reached genome-wide significance (p=7.50×10-11), while SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, EXOC4 and additional c11orf30 SNPs were suggestive (p≤1.49×10-6). Functional annotation indicated SKAP1 regulates expression of CBX1, which co-localizes with the EMSY protein coded by c11orf30.ConclusionThis study identifies multiple novel loci as risk factors for PA and food allergy and establishes c11orf30 as a risk locus for both peanut and food allergy. Multiple genes (c11orf30/EMSY, SKAP1 and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

Teaser

C11orf30 (EMSY) is a risk locus for food allergy, reaching genome-wide significance in meta-analysis (p=7.50×10-11). Meta-analyses showed five loci suggestive of significance with peanut allergy. These 6 novel loci suggest epigenetic mechanisms.


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A systematic review of factors affecting vaccine uptake in young children

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Louise E. Smith, Richard Amlôt, John Weinman, Jenny Yiend, G. James Rubin
BackgroundMany parents make a conscious decision not to vaccinate their child. Multiple beliefs and perceptions surround this choice. If uptake of routine child vaccination is to increase, public health communications about vaccines must be informed by evidence on the factors affecting uptake.MethodWe conducted a systematic review to investigate psychological, social and contextual factors associated with uptake of routine vaccines in young children. Studies were included if they reported analyses of the association between psychological factors and uptake or included parents' self-reported reasons for or against vaccination.ResultsOur search identified 9110 citations after deduplication. Sixty-eight citations describing sixty-four studies were included in the review. The quality of the studies was mixed. There is strong evidence for an association between vaccination uptake and: not perceiving vaccines to cause adverse effects; general positive attitudes towards vaccination; positive vaccine recommendations; and perceiving fewer practical difficulties of vaccination. While there was good evidence for an association between vaccination and perceived susceptibility to the illness, evidence for an association between perceived severity of an illness and vaccination was weak. Other factors associated with vaccination include knowledge about the vaccine, social influences and trust in the healthcare profession. Having increased information about the vaccine was associated with vaccination, but the influence of different sources of information needs more research.ConclusionUnderstanding which factors are consistently associated with the decision to vaccinate one's child is important to identify messages which should be targeted by public health communications about routine child vaccinations.



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Salmonella Enteritidis with double deletion in phoP fliC and a competitive exclusion culture elicit substantial additive protective effects against Salmonella exposure in newly hatched chicks

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): U. Methner, A. Berndt, M. Locke
A live Salmonella Enteritidis vaccine (SE147N ΔphoP fliC), able to express both a homologous intestinal colonisation-inhibition effect and a systemic invasion-inhibition effect, was tested for its potential to generate a postulated additive protective effect in case of combined application with a competitive exclusion (CE) culture against Salmonella exposure in very young chicks. Both, SE147N ΔphoP fliC and the CE culture alone were highly protective against systemic and intestinal colonisation of the challenge strain in case of moderate Salmonella exposure, consequently, additive protective effects in combined use could not be detected. However, in case of high Salmonella Enteritidis challenge with 106 cfu/bird at day 3 of life the combination of the ΔphoP fliC vaccine and the CE culture resulted in a protective effect much more pronounced than either of the single preparations and most substantial compared to untreated control birds. The term additive protective effects reflects the recognition that exclusion effects by gut flora cultures and inhibition effects by Salmonella vaccines are caused by different mechanisms.



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Personality and demographic correlates of New Zealanders’ confidence in the safety of childhood vaccinations

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Carol H.J. Lee, Isabelle M. Duck, Chris G. Sibley
Despite extensive scientific evidence on the safety of standard vaccinations, some parents express skeptical attitudes towards the safety of childhood immunisations. This paper uses data from the 2013/14 New Zealand Attitudes and Values Study (NZAVS) survey (N=16,642) to explore the distribution, and demographic and personality correlates of New Zealanders' attitudes towards the safety of childhood vaccinations. Around two thirds (68.5%) of New Zealanders strongly agreed/were confident that "it is safe to vaccinate children following the standard New Zealand immunisation schedule," 26% were skeptical and 5.5% were strongly opposed. Multiple regression analysis indicated that people lower on Conscientiousness and Agreeableness but higher on Openness to Experience expressed lower confidence about vaccine safety. Having higher subjective health satisfaction, living rurally, being Māori, single, employed and not a parent were all associated with lower confidence, while a higher income and educational attainment were associated with greater confidence. Our findings suggest that the majority of New Zealand adults trust in the safety of scheduled childhood vaccinations, but about one third do express some degree of concern. This finding highlights the importance of improving public education about the safety and necessity of vaccinations.



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Parental perceptions of childhood seasonal influenza vaccination in Singapore: A cross-sectional survey

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Mabel S.F. Low, Hweeyong Tan, Mikael Hartman, Clarence C. Tam, Cheehow Hoo, Jiaqing Lim, Simin Chiow, Simin Lee, Renzhi Thng, Mingzhe Cai, Yanru Tan, Jingzhan Lock
PurposeSeasonal influenza vaccination is recommended in children aged 6–59months, but little is known about child vaccination coverage and determinants in Asian settings. We report the results of a survey of knowledge, attitudes, practices, and determinants of child influenza vaccination in Singapore.MethodsIn December 2015-March 2016, we conducted a survey of 332 parents of children aged 6months to 5years attending pre-schools. We assessed child influenza vaccine coverage and parental knowledge, attitudes, and practices of child influenza vaccination. We used multivariable regression and structural equation models to identify factors associated with child influenza vaccination.ResultsKnowledge about influenza, perceived benefit of vaccination, and willingness to vaccinate were high. However, only 32% of children had ever received influenza vaccine, and only 15% in the past year. Factors independently associated with child influenza vaccination included: being recommended influenza vaccine by a child's doctor (prevalence ratio (PR)=2.47, 95% CI: 1.75–3.48); receiving influenza vaccine information from a private general practitioner (PR=1.47, 95% CI: 1.05–2.04); regularly receiving pre-travel influenza vaccine (PR=1.64, 95% CI: 1.19–2.25); higher willingness to vaccinate (PR=1.58, 95% CI:1.24–2.04 per unit increase in willingness score); and feeling well-informed about influenza vaccine (PR=1.44, 95% CI: 1.04–1.99). Parents who obtained influenza vaccine information from television were less likely to have vaccinated their child (PR=0.44, 95% CI: 0.23–0.85). Path analysis indicated that being recommended vaccination by a child's doctor increased willingness to vaccinate and self-efficacy (feeling well-informed about influenza vaccine). Median willingness-to-pay for a dose of influenza vaccine was SGD30 (interquartile range: SGD20-SGD50), and was higher in parents of vaccinated compared with unvaccinated children (SGD45vs SGD30, p=0.0012).ConclusionKnowledge and willingness to vaccinate was high in this parent population, but influenza vaccine uptake in children was low. Encouraging medical professionals to recommend vaccination of eligible children is key to improving uptake.



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Evaluation of T and B memory cell responses elicited by the pandemic H1N1 vaccine in HIV-infected and HIV-uninfected individuals

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Peifang Sun, Nancy F. Crum-Cianflone, Gabriel Defang, Maya Williams, Anuradha Ganesan, Brian K. Agan, Tahaniyat Lalani, Timothy Whitman, Carolyn Brandt, Timothy H. Burgess
BackgroundThis study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV+ and HIV groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine.MethodsBlood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV/LAIV, HIV/TIV and HIV+/TIV subgroups according to the trivalent live-attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG+ memory B cells (BMem) and IFNγ+ T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively.ResultsOverall BMem responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific BMem at day 28 for the HIV/LAIV, HIV/TIV and HIV+/TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of BMem between HIV/LAIV and the two TIV subgroups were significant. For the IFNγ response, the overall spot counts ranged widely between 0 and 958/106 PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV/LAIV, HIV/TIV and HIV+/TIV subgroups, respectively. The average increase of IFNγ response at day 28 vs day 0 in all three subgroups did not reach 2-fold.ConclusionParticipants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV+ and HIV subject groups in terms of BMem. The BMem response declined at 6months.



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Association of both consistency and strength of self-reported clinician recommendation for HPV vaccination and HPV vaccine uptake among 11- to 12-year-old children

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Lila J. Finney Rutten, Jennifer L. St. Sauver, Timothy J. Beebe, Patrick M. Wilson, Debra J. Jacobson, Chun Fan, Carmen Radecki Breitkopf, Susan T. Vadaparampil, Kathy L. MacLaughlin, Robert M. Jacobson
PurposeWe tested the hypotheses that consistency and strength of clinician recommendation of the human papillomavirus (HPV) vaccination would be associated with vaccine delivery rates.MethodsFrom October 2015 through January 2016, we conducted a survey of primary care clinicians (n=227) in Southeastern Minnesota to evaluate clinician behaviors regarding HPV vaccination. The survey response rate was 41.0% (51 clinical sites). We used the Rochester Epidemiology Project, a clinical data linkage infrastructure, to ascertain clinical site-level HPV vaccination rates. We examined associations of clinician self-reports of both the consistency and strength of their recommendations for HPV vaccination for patients aged 11–12years (n=14,406) with site-level vaccination rates.ResultsThe majority of clinicians reported consistently (always or usually) recommending the HPV vaccine to females (79.0%) and to males (62.2%); 71.9% of clinicians reported strongly recommending the vaccine to females while 58.6% reported strongly recommending to males. Consistency and strength of recommending the HPV vaccine was significantly higher among those practicing in pediatrics and board certified in pediatrics compared to family medicine. Higher rates of initiation (1 dose) [Incidence Rate Ratio (IRR)=1.05; 95% CI (1.01–1.09)] and completion (3 doses) [IRR=1.08; 95% CI (1.02–1.13)] were observed among clinical sites where, on average, clinicians more frequently reported always or usually recommending the vaccine for females compared to sites where, on average, clinicians reported recommending the vaccine less frequently. Similarly, higher rates of initiation [IRR=1.03; 95% CI (1.00–1.06)] and completion [IRR=1.04; CI (1.00, 1.08)] were observed among sites where clinicians reported strongly recommending the vaccine to females more frequently compared to sites where, on average, clinicians reported strongly recommending the HPV vaccine less frequently; similar associations were observed for male initiation [IRR=1.05; CI (1.02,1.08)] and completion [IRR=1.05; 95% CI (1.01, 1.09)].ConclusionsConsistency and strength of HPV vaccination recommendation was associated with higher vaccination rates.



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Investigating the candidacy of a capsular polysaccharide-based glycoconjugate as a vaccine to combat Haemophilus influenzae type a disease: A solution for an unmet public health need

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Andrew D. Cox, Dean Williams, Chantelle Cairns, Frank St. Michael, Perry Fleming, Evgeny Vinogradov, Mélanie Arbour, Luke Masson, Wei Zou
After the introduction of the glycoconjugate vaccine based upon the capsular polysaccharide ofHaemophilus influenzaetype b in the mid 1980s there was a remarkable decrease in the number of invasive cases reported for this organism. Since the 1990s several groups have observed the emergence ofHaemophilus influenzaetype a (Hia), especially in indigenous communities in the northern regions of Canada and Alaska, to a stage where a solution is warranted to prevent further unnecessary deaths due to this pathogen. A glycoconjugate vaccine solution based upon the type a capsular polysaccharide (CPS) was investigated pre-clinically in an effort to illustrate the proof of concept for this approach. In this study we describe the growth of Hia and the isolation, purification and conjugation of the CPS to several carrier proteins. The resulting glycoconjugates were immunised in mice and rabbits provoking sera that facilitated bactericidal killing against all type a strains that we tested. This study has illustrated the pre-clinical proof of concept of a glycoconjugate vaccine based on the CPS of Hia asa solution to this emerging disease.



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Cost-effectiveness of a potential group B streptococcal vaccine for pregnant women in the United States

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Sun-Young Kim, Chi Nguyen, Louise B. Russell, Sara Tomczyk, Fatimah Abdul-Hakeem, Stephanie J. Schrag, Jennifer R. Verani, Anushua Sinha
BackgroundIn the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS.MethodsUsing a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease.ResultsIn the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of ≥70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY.ConclusionsGBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine's public health impact.



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Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6months in a nonhuman primate neonate model

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Beth C. Holbrook, Ralph B. D'Agostino, S. Tyler Aycock, Matthew J. Jorgensen, Mallinath B. Hadimani, S. Bruce King, Martha A. Alexander-Miller
Generation of a potent antibody response that can be sustained over time is highly challenging in young infants. Our previous studies using a nursery-reared nonhuman primate model identified R848 conjugated to inactivated influenza virus as a highly immunogenic vaccine for neonates. Here we determined the effectiveness of this vaccine in mother-reared infants as well as its ability to promote improved responses at 6months compared to vaccination in the absence of R848. In agreement with our nursery study, R848 conjugated to influenza virus induced a higher antibody response in neonates compared to the non-adjuvanted vaccine. Further, the increase in the response relative to that induced by the non-adjuvanted vaccine was maintained at 6months suggesting the increased antibody secreting cells that resulted from inclusion of conjugated R848 production were capable of surviving long term. There was no significant difference in quality of antibody (i.e. neutralization or affinity), suggesting the beneficial effect of conjugated R848 during vaccination of neonates with inactivated influenza virus is likely manifest during the early generation of antibody secreting cells.



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Value of an in-depth analysis of unpublished data on the safety of influenza vaccines in pregnant women

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Neal A. Halsey, Tina Proveaux
BackgroundUnpublished data can sometimes provide valuable information on the safety of biologic products.MethodsWe assessed information potentially available from regulatory authorities, manufacturers, and public health agencies. We explored 4 recently established vaccine registries, reviewed package inserts from 99 influenza vaccines, and contacted vaccine manufacturers and regulatory agencies for data on influenza vaccine safety in pregnant women.ResultsThe vaccine registries did not have sufficient data to analyze and there are problems with the quality of the information. The majority of package inserts provided no product-specific safety information for pregnant women, especially in less developed countries. The majority of available data come from reports gathered from passive adverse event reporting systems in the general population and reports of women enrolled in clinical trials of influenza vaccines who became pregnant at various times before or after receiving influenza vaccine. The information was not collected in a systematic manner, there are inconsistencies in the follow up of pregnant women and the available information about pregnancy outcomes. Considerable resources would be needed to systematically identify all of the information, try to obtain missing follow up information, and conduct analyses. There would be substantial limitations to any attempt to conduct a systematic analysis.ConclusionsThe value of trying to analyze unpublished data on the safety of influenza vaccine in pregnancy is limited and would require considerable resources to thoroughly investigate. Expanding efforts to identify and review unpublished data regarding the safety of influenza vaccines in pregnancy is not likely to produce information of high scientific value or information that could not be identified from publications and other publically available data.



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Trends in pneumococcal meningitis hospitalizations following the introduction of the 13-valent pneumococcal conjugate vaccine in the United States

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Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): David M. Jacobs, Francine Yung, Emily Hart, Melanie N.H. Nguyen, Amy Shaver
BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 in the U.S. and its impact on pneumococcal meningitis (PM) is unknown. We assessed the impact of PCV13 on PM hospitalization rates 4years after the vaccine was introduced.MethodsThis was a retrospective analysis of the National Inpatient Sample from 2008–2014. Patients with an ICD-9-CM code for PM (320.1) were identified and rates calculated using US Census data as the denominator. Data weights were used to derive national estimates. We examined three time periods: 2008–2009 (late post-PCV7), 2010 (transition year), and 2011–2014 (post-PCV13).ResultsDuring the study period, there were 10,493 hospitalizations due to PM in the U.S. Overall, PM incidence decreased from 0.62 to 0.38 cases per 100,000 over this time (39% decrease; P<0.01). Among children <2years, the average annualized PM rate decreased by 45% from 2.19 to 1.20 per 100,000 (P=0.10). Annual PM rates decreased in those aged 18–39years (0.25–0.15 cases per 100,000; P=0.02) and 40–64years (0.95–0.54 cases per 100,000; P=0.03). A total of 1016 deaths were due to PM, and the case fatality rate was variable over the study period (8.3%–11.2%; P=0.96).ConclusionFollowing the introduction of PCV13, hospitalization rates for PM decreased significantly with no subsequent improvements in case-fatality rate.



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CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles

Publication date: 27 October 2017
Source:Vaccine, Volume 35, Issue 45
Author(s): Catherine Goujon, Marie-Lise Gougeon, Laura Tondeur, Béatrice Poirier, Valérie Seffer, Philippe Desprès, Paul-Henri Consigny, Muriel Vray
For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine.The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6–24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area.Subjects and methods: A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1–27days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27days between receiving the measles vaccine and yellow fever vaccine.The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample.Results: One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1.Discussion: The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27days. The absence of protective antibodies against yellow fever was observed only among infants who received both vaccines simultaneously.Conclusion: These results may support a revision of current vaccination recommendations concerning the administration of these two live attenuated vaccines either on the same day or at least 28days apart. Our findings show no statistically significant difference if the interval between both vaccines is more than 24 h, but the immune response seems to be reduced when the two vaccines are given at the same time.



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Nano-material as an excellent catalyst for reducing a series of nitroanilines and dyes: triphosphonated ionic liquid- CuFe2O4-modified boron nitride

Publication date: March 2018
Source:Applied Catalysis B: Environmental, Volume 222
Author(s): Vasanthakumar Arumugam, Pavithra Sriram, Ta-Jen Yen, Gyanasivan Govindsamy Redhi, Robert Moonsamy Gengan
In this study a nanomaterial containing a novel tri-cationic phosphonate ionic liquid (TCPIL), copper ferrite magnetic nanoparticles (CuFe2O4 NP) and partially oxidized modified boron nitride nanosheet (BNONS) was synthesized, characterized and used as an efficient catalyst to reduce a series of nitro-anilines (NAs), and dyes. Three different ionic liquids (ILs) [DABCO]+[PDOL], [APIC]+[PDOL] and [PYR]+[PDOL] were synthesized separately, characterized and used to prepare a novel TCPIL {[DABCO, PYR, APIC-PDOL]+[ATMP]}ionic liquid. Thereafter CuFe2O4 NPs and BNONS were used to synthesize the nanomaterial (TCPIL/CuFe2O4/BNONS): spectroscopic, microscopic and surface morphological studies were undertaken. The catalytic reduction of a series of NAs such as 2-nitroaniline (2-NA), 3-nitroaniline (3-NA), 4-nitroaniline (4-NA) and 4-nitro-2-phenylenediamine (4-NPDA) and dyes methylene blue (MB) and allura red (AR) in aqueous solution at ambient temperature were effective in all compounds tested: the order of reduction, based on reaction time, was 4-NPD>4-NA>3-NA>2-NA. Kinetic studies indicated either zero order or pseudofirst order. The rate constant, order of the reaction, activation energy and constant ratio were also calculated for each substrate. Furthermore kinetic studies at various temperatures showed that an increase in temperature speeded the reaction whilst by increasing the amount of catalyst the reaction occurred faster. In addition, the nanomaterial was easily recovered and re-used for more than seven times with negligible loss of its catalytic activity. Moreover, it is possible to make different nanomaterial by combining different d-block metals such Zn, Pd, Pt and Mn with BNONSs for potential applications in biomedical, sensors and catalytic fields.

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Food stories: Unraveling the mechanisms underlying healthful eating

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Publication date: 1 January 2018
Source:Appetite, Volume 120
Author(s): Emily Swan, Laura Bouwman, Noelle Aarts, Leah Rosen, Gerrit Jan Hiddink, Maria Koelen
The biomedical model of health (BMH) studies the causes and origins of disease. When applied to nutrition research, eating is studied as a behavior that supports physical health. However, the lack of attention the BMH pays to social and historical circumstances in which health behaviors are constructed has been widely addressed in literature. When people are studied without considering contextual influences, the relevance to everyday life is limited. As a result, how individuals actively deal with their context to manage healthful eating is poorly understood. This research applies a complementary model, salutogenic model of health (SMH), and uses life course research methodology to study a group of healthy eaters. The purpose of this research is to unravel how healthful eating develops in everyday life. Healthy eaters (n = 17) were identified and recruited from the NQplus research panel at Wageningen University, the Netherlands. Life course experiences were examined through narrative inquiry. Participants recalled and visually explored life experiences with food and health using timelines. Results indicate that healthful eating results from exposure to individual- and context-bounded factors during childhood and adulthood and involves specific mental and social capacities relevant to coping including amongst others, critical self-awareness; flexibility, craftiness, and fortitude. Through life-course learning moments, participants were able to develop proactive coping strategies which strengthened their sense of agency and helped them in overcoming stressors and challenges. Findings show that nutrition strategies should not only focus on strengthening food-specific factors like cooking skills and nutrition knowledge, but other factors like stress management, empowerment, and participation. Such factors support the development of adaptive skills and behaviors, enable individuals to deal with the demands of everyday life, and are building blocks for health promotion.



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EZH2 regulates dental pulp inflammation by direct effect on inflammatory factors

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Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Tianqian Hui, Peng A., Yuan Zhao, Jing Yang, Ling Ye, Chenglin Wang
ObjectivePulpitis is a multi-factorial disease that could be caused by complex interactions between genetics, epigenetics and environmental factors. We aimed to evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory response of human dental pulp cells (HDPCs) and dental pulp tissues.MethodsThe expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2 siRNA with or without rhTNF-α were examined by quantitative real-time polymerase chain reaction (q-PCR). The levels of secreted inflammatory cytokines including IL-6, IL-8, IL-15, CCL2 and CXCL12 in culture supernatants were measured by Luminex assay. In rat pulpitis model, the effects of EZH2 on dental pulp tissues were verified by histology. We invested the mechanisms of the effect of EZH2 on the inflammatory factors by ChIP assay.ResultsEZH2 down-regulation inhibited the expression of inflammatory factors, including IL-6, IL-8, IL-15, CCL2 and CXCL12 in HDPCs. EZH2 complex promoted the expression and secretion of these inflammatory factors in HDPCs, while EZH2 silencing could attenuate the promotion of inflammatory factors that were induced by rhTNF-α. In pulpitis models of rats, EZH2 down-regulation inhibited the inflammatory process of dental pulp while EZH2 complex showed no significant facilitation of pulpal inflammation. In addition, EZH2 could bind on the promoters of IL-6, IL-8 and CCL2, but not IL-15 and CXCL12, to affect the transcription of these proinflammatory cytokines.ConclusionsIn HDPCs, EZH2 could induce inflammation, while EZH2 down-regulation could attenuate the inflammatory responses. EZH2 plays an important role in this inflammatory process of dental pulp.



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A dual energy micro-CT methodology for visualization and quantification of biofilm formation and dentin demineralization

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Publication date: January 2018
Source:Archives of Oral Biology, Volume 85
Author(s): Paula Maciel Pires, Thais Pires dos Santos, Andrea Fonseca-Gonçalves, Matheus Melo Pithon, Ricardo Tadeu Lopes, Aline de Almeida Neves
ObjectiveThe aim of this study was to induce artificial caries in human sound dentin by means of a microcosm model using human saliva as source of bacteria and to apply a novel dual-energy micro-CT technique to quantify biofilm formation and evaluate its demineralization potential.DesignEight sound third molars had the occlusal enamel removed by cutting with a diamond disk and five cylindrical cavities (±2mm diameter; ±1.5mm depth) were prepared over the dentin surface in each specimen (n=40 cavities). After sterilization, each specimen received the bacterial salivary inoculum obtained from individuals without any systemic diseases presenting dentin caries lesions and were incubated in BHI added of with 5% sucrose for 96h to allow biofilm formation. After that, two consecutive micro-CT scans were acquired from each specimen (40kv and 70kv). Reconstruction of the images was performed using standardized parameters. After alignment, registration, filtering and image calculations, a final stack of images containing the biofilm volume was obtained from each prepared cavity. Dentin demineralization degree was quantified by comparison with sound dentin areas. All data were analyzed using Shapiro-Wilk test and Spearman correlation using α=5%.ResultsDual-energy micro-CT technique disclosed biofilm formation in all cavities. Biofilm volume inside each cavity varied from 0.30 to 1.57mm3. A positive correlation between cavity volume and volume of formed biofilm was obtained (0.77, p<0.01). The mineral decrease obtained in dentin was high (±90%) for all cavities and all demineralized areas showed mineral density values lower than a defined threshold for dentin caries (1.2g/cm3).ConclusionDual-energy micro-CT technique was successful in the quantification of a microcosm human bacterial biofilm formation and to quantify its demineralization potential in vitro.



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