Head and Neck Diseases by Alexandros G.Sfakianakis: 06/15/18

Παρασκευή 15 Ιουνίου 2018

Cosmetics, Vol. 5, Pages 38: Screening-Level Safety Assessment of Personal Care Product Constituents Using Publicly Available Data

Cosmetics, Vol. 5, Pages 38: Screening-Level Safety Assessment of Personal Care Product Constituents Using Publicly Available Data

Cosmetics doi: 10.3390/cosmetics5020038

Authors: Ernest S. Fung Derek A. Drechsel Kevin M. Towle Melinda T. Hoang Rachel M. Novick Cayla Poteete Dennis J. Paustenbach Andrew D. Monnot

Organizations recommend evaluating individual ingredients when assessing the safety of personal care or cosmetic products. The goal of this study was to present a screening-level safety assessment methodology to evaluate the safety of a product by identifying individual ingredients, determining their frequency of use in on-market products, and examining published safe-level-of-use information for each ingredient. As a case study, we evaluated WEN by Chaz Dean (WCD) cleansing conditioners since there have been claims of adverse health effects associated with product use. We evaluated 30 ingredients in three on-market WCD cleansing conditioners. We then analyzed the National Library of Medicine’s Household Products Database and the Environmental Working Group’s (EWG) Skin Deep Cosmetic Database, two of the largest publicly available databases, for other on-market personal care and cosmetic products that contained these ingredients. Safe-level-of-use information for each ingredient was obtained by reviewing peer-reviewed literature, the Food and Drug Administration’s (FDA) generally recognized as safe (GRAS) database, available Cosmetic Ingredient Review (CIR) publications, and available product safety publications. The results of this analysis showed that more than 20,000 personal care and cosmetic products contained one or more of the evaluated ingredients used in WCD cleaning conditioners. Published safety information was available for 21 of the 30 evaluated ingredients: seven identified ingredients were designated as GRAS by the FDA and 16 ingredients had safe-level-of-use information available from the CIR. This study presents a screening-level safety assessment methodology that can serve as an initial screening tool to evaluate the safety of an ingredient intended for use in personal care and cosmetic products before a product is launched onto the market. This study provides evidence that the evaluated WCD cleansing conditioner ingredients are commonly used in other personal care and cosmetic products, and ingredients with available safety information are generally considered safe for the intended use. The scope of this analysis is limited to frequency of use information and available toxicological data. Additional testing including in silico, in vitro, and clinical studies may be needed to evaluate the potential toxicity of an ingredient.

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Atypical chest pain in a patient with hydatid cyst of the interventricular septum

We report a 57-year-old man presenting with symptoms of sharp pricking, exertional retrosternal chest pain multiple times, each episode lasting for a few seconds. On evaluation, the ECG of the patient showed normal sinus rhythm with T wave inversions in leads V1–V3. Troponin T test was negative. Transthoracic echocardiography showed a globular mass in the interventricular septum. Cardiac MRI was suspicious of the lesion to be a hydatid cyst. Surgical excision of the lesion followed by histopathology was confirmatory of hydatid cyst.

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Dengue fever with encephalitis: a rare phenomenon

The clinical profile and presentation of patients with dengue fever may differ from asymptomatic infection to the dreadful complications like dengue shock syndrome. However, neurological complications are very rare. Dengue encephalitis occurs by a direct involvement of central nervous system by the dengue virus which is an extremely rare complication. A 33-year-old man presented with fever, vomiting and severe headache. He had one episode of generalised tonic-clonic seizure followed by an altered sensorium on the day of admission to the hospital. The diagnosis of dengue fever was confirmed by dengue serology (IgM) and (NS1) antigen assay. MRI brain was suggestive of encephalitis. Thus, the patient was treated symptomatically and discharged in stable condition with minimal neurological deficit.

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Rotator cuff tear following long-standing axillary neuropathy in a female motocross racer

A 'terrible triad' of anterior shoulder dislocation, axillary nerve damage and rotator cuff tear has been previously described. However, we are unaware of any report of anterior shoulder dislocation, humeral fracture, axillary neuropathy and subsequent rotator cuff tear requiring surgery when the axillary neuropathy was deemed permanent. We report the case of a 20-year-old woman who fell in a motocross accident and had an anterior shoulder dislocation, humeral fracture and axillary neuropathy. The fracture was treated surgically with open reduction and internal fixation. The axillary nerve injury was ultimately permanent. Thirteen months after the motocross accident, the patient sustained a rotator cuff tear from seemingly minor trauma. However, several months of aggressive physical therapy preceded the rotator cuff tear. The tear was repaired and the patient was followed for 5 years after the initial injury. She returned to competing in motocross, even though the axillary neuropathy remained complete and permanent.

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Thiazide diuretics-associated skin rash

Description

A 50-year-old man with a history of hypertension and dyslipidaemia, both controlled with oral medications, was admitted to the emergency department due to a sudden onset of pruritus 2 days before, which would not improve with the application of topic antihistamines prescribed by his family doctor. A maculopapular, symmetric rash with plaques located on sun-exposed areas (hands, forearms, face and upper torso, sparing the abdomen, lower limbs and arm flexures) had appeared a few hours before coming to the emergency department (figures 1 and 2). The patient denied any sort of respiratory distress, as well as prolonged exposure to sunlight, history of drug allergies or having seen anyone in his family with the same problem before. The only recent change had been to his hypertension medication in the last 13 days, when hydrochlorothiazide was combined with his usual medication (losartan), which he had been taking for the...

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Transdermal rotigotine patch in Parkinsons disease with a history of intestinal operation

A 42-year-old Japanese man with a history of small intestine resection and familial Mediterranean fever was referred to our hospital for a second opinion on parkinsonism. At the age of 35, the patient attended a hospital due to impaired left-hand movement and resting tremor. He was previously diagnosed with multiple system atrophy based on the lack of effectiveness of levodopa treatment. With suspicion of malabsorption due to his history of ileostomy, a levodopa challenge test with levodopa intravenous infusion was conducted, and revealed a 65% improvement in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale part III. Therefore, diagnosis of Parkinson's disease was made and a transdermal rotigotine patch was selected as a treatment. This treatment dose-dependently improved the patient's symptoms. The transdermal drug delivery should be considered when patients show dose failure due to malabsorption.

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Delayed presentation of iatrogenic splenic injury 21 days after laparoscopic donor left nephrectomy

We report the case of a 46-year-old woman who had presented with left-sided abdominal pain 21 days after undergoing a left-sided laparoscopic nephrectomy for donation. Initial haemoglobin and haematocrit levels were within normal range, and vital signs on admission were unremarkable. Significant intra-abdominal pathology was not suspected; however, inpatient CT scan of the abdomen showed a posterolateral subcapsular splenic haematoma with free abdominal fluid. Initial trial of conservative management was not successful as the patient became hypotensive on the third day of admission with a sudden decrease in haemoglobin and haematocrit. The patient was immediately taken to theatre for laparotomy and splenectomy. Recovery was uneventful and was discharged home on the fifth postoperative day. In this article, we aim to discuss several important clinical lessons involving iatrogenic injury of the spleen, its management, and diagnosis of acute and severe haemorrhage.

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Paraneoplastic cerebellar degeneration in a patient with anaplastic non-Hodgkins lymphoma

A 31-year-old man presented with a subacute cerebellar syndrome of unknown aetiology. Investigations including a paraneoplastic antibody screen were negative and a working diagnosis of possible vasculitis was concluded. After 1 month, he re-presented with worsening of his symptoms and a neck lump. He was diagnosed with anaplastic lymphoma kinase, negative non-Hodgkin's lymphoma and paraneoplastic cerebellar syndrome. A more extensive paraneoplastic antibody screen found patient to be Tr (delta/notch-like epidermal growth factor-related receptor) antibody positive. After a period of chemotherapy and steroid treatments, his symptoms are now stable in terms of cerebellar function. This case report summarises a very rare diagnosis of paraneoplastic cerebellar degeneration with a positive onconeuronal antibody associated with anaplastic non-Hodgkin's lymphoma.

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Ectopic varices: a potential cause of gastrointestinal bleeding in patients with portal hypertension

A newly diagnosed 53-year-old woman with cirrhosis has repeated gastrointestinal bleeding with resulting symptomatic anaemia. She underwent routine diagnostic endoscopic evaluation without localisation of the aetiology of her bleed. Ultimately, she was found to have ectopic varices in the small bowel as a result of underlying high portal pressures. She underwent transjugular intrahepatic portosystemic shunt for portal system decompression with resolution in her bleeding.

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Lymphedema secondary to limited cutaneous systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterised by vascular abnormalities, immune system activation and fibrosis. Lymphatic involvement in SSc was described more recently and starts in early stages. This report describes a 46-year-old patient who developed over the last 2 years asymmetric lymphedema in lower extremities. Compromise in lymphatic drainage was confirmed by lymphoscintigraphy. She also presented Raynaud's phenomenon, a scleroderma pattern in nailfold capillaroscopy, cutaneous thickening and anticentromere antibodies, which together resulted in a new diagnosis of limited cutaneous SSc. Treatment with methotrexate, prednisolone and lymphatic drainage resulted in lymphedema improvement. To our knowledge, this is the first case of grade 2 lymphedema in the setting of anticentromere-positive limited cutaneous SSc. We highlight the importance of considering rheumatic diseases in the differential diagnosis of lymphedema.

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Graves disease presenting as severe postpartum pruritus

A 39-year-old multigravida woman presented 3 weeks postpartum with worsening generalised pruritus without primary rash. Workup was significant for cholestasis and undiagnosed Graves' disease. She began to have symptomatic relief after starting methimazole, and liver function tests normalised as she became euthyroid.

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Closed-loop small bowel obstruction from lateral trocar site hernia following robotic sigmoid resection

Description

A 67-year-old man with medical history significant for hypertension and hyperlipidaemia was found on screening colonoscopy to have a large, polypoid adenomatous polyp of the distal descending colon not amenable to colonoscopic resection. He underwent a robotic sigmoid colon resection with primary anastomosis. Postoperatively the patient developed persistent abdominal distention, nausea and had no passage of flatus or bowel movements after 7 days which was initially attributed to ileus. Cross-sectional CT revealed a closed-loop small bowel obstruction secondary to an incarcerated hernia at the right lateral 8 mm robotic trocar site with surrounding subcutaneous emphysema (figure 1). On physical examination, there was no palpable bulge or overlying erythema along the previous incision. The patient was brought back to the operating room and underwent a diagnostic laparoscopy utilising the prior robotic incisions. On exploration, the incarcerated small bowel loop was easily reduced with gentle traction and appeared...

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Common femoral artery aneurysm repair using bifurcated graft

Common femoral artery aneurysms are rare, and surgical repair is indicated if they are significantly large, or if they are symptomatic (thrombosis causing limb ischaemia and compression of surrounding structures). Synthetic grafts are preferred, especially in cases involving large aneurysms, or the bifurcation of the common femoral artery. We present a case of bilateral common femoral artery aneurysms extending into the bifurcation repaired using a synthetic graft which is traditionally used for an axillobifemoral bypass. This technique was employed due to the specific anatomical relationship between the profunda femoris and the superficial femoral artery in our patient. We will also review the current literature on the operative approaches to repair of common femoral artery aneurysms.

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Prenatal omega-3 LCPUFA and symptoms of allergic disease and sensitization throughout early childhood – a longitudinal analysis of long-term follow-up of a randomized controlled trial

Randomized controlled trials of prenatal omega (ω-3) long chain polyunsaturated fatty acid (LCPUFA) supplementation are suggestive of some protective effects on allergic sensitization and symptoms of allergic ...

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Debates in Allergy Medicine: Does oral immunotherapy shorten the duration of milk and egg allergy? The pro argument

The development of oral tolerance or food allergy is an active process, related to dynamic interactions between host immune cells, microbiome, dietary factors, and food allergens. Oral tolerance is the default...

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Debates in Allergy Medicine: Oral immunotherapy shortens the duration of milk and egg allergy - the con argument

Oral immunotherapy (OIT) has been shown to be effective for inducing desensitization in children with cow's milk and egg allergy. In contrast, there is limited evidence that OIT can induce tolerance or sustain...

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Early functional improvement after stroke correlates with cardiovascular fitness

Publication date: Available online 15 June 2018
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Chun-Kai Chen, Mao-Hsiung Huang, Wen-Lung Liang, Ruey-Tay Lin, Suh-Hang H. Juo
Cardiovascular fitness exerts directly beneficial effects on functional and cognitive outcomes in patients of chronic stroke. However, the effect of early rehabilitation on cardiovascular function has not yet been thoroughly examined. We tested whether complementary rehabilitation program could influence cardiovascular fitness in an early stage of stroke patients. The associations for post-acute stroke functional recovery with cardiovascular fitness were explored. Thirty-seven patients with mean poststroke interval of 8.6 ± 3.8 days underwent inpatient rehabilitation of 22.8 ± 3.8 days. Functional outcomes of 15.3 points (17.2%) in functional independence measure improved after rehabilitation program. The therapeutic cardiovascular fitness was determined in ramp exercise test on a cycling ergometer. Peak oxygen uptake (V˙O2peak) significantly increased by 24.8% after early stroke rehabilitation. Multivariate regression analysis was performed to assess for associations of functional improvement with respect to change in V˙O2peak and extremities motor impairment. V˙O2peak gain accounted for more functional recovery than extremities motor improvement (R² = 0.42). In conclusion, these results suggest that cardiovascular fitness appears to increase after complementary program in early stroke rehabilitation, and better cardiovascular fitness may be associated with greater functional improvement.

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Effects of anti-allergic drugs on T cell-mediated nasal hyperresponsiveness in a murine model of allergic rhinitis

Publication date: Available online 15 June 2018
Source:Allergology International
Author(s): Tomoe Nishimura, Osamu Kaminuma, Mayumi Saeki, Noriko Kitamura, Minoru Gotoh, Akio Mori, Takachika Hiroi
BackgroundWe have recently demonstrated that T cell-mediated nasal hyperresponsiveness (NHR) is a representative pathophysiological feature of allergic rhinitis (AR). Although several anti-allergic drugs are used for the treatment of AR, the efficacy of these drugs on T cell-mediated NHR have not been elucidated. In these studies we investigated the effects of dexamethasone (Dex), montelukast (Mk), and chlorpheniramine (Chl) on NHR in antigen-immunized and antigen-specific Th2 cell-transferred mice.MethodsOVA-immunized BALB/c mice were treated with Dex, Mk, or Chl and challenged intranasally with OVA. We then assessed NHR, the number of inflammatory cells in the nasal lavage fluid (NALF), mRNA expression of Th2 cytokines in the nasal tissue, the population of CD3⁺CD4⁺ cells in the nasal lymphoid tissue (NALT), and antigen-specific serum IgE and IgG levels. Antigen-induced NHR and changes in antigen-specific T cells in the NALT were investigated in OVA-specific Th2 cell-transferred mice.ResultsDex significantly suppressed antigen-induced NHR, inflammatory cell infiltration, and IL-4, IL-5, IL-6, and IL-13 expression in immunized mice. Chl was completely ineffective, and only IL-13 expression was suppressed by Mk. None of these drugs affected IgE and IgG production. Antigen-induced NHR and the increase in antigen-specific T cells in the NALT of Th2 cell-transferred mice were inhibited by Dex, but not by Mk or Chl.ConclusionsSteroids are effective for the reduction of NHR in AR by suppressing the accumulation of inflammatory cells, especially antigen-specific T cells.

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Monthly dynamics of atmospheric wet nitrogen deposition on different spatial scales in China

Abstract

China is one of three global hotspots for nitrogen (N) deposition, which has concerned scientists and the public. While previous studies on N deposition in China have focused on its composition, spatial pattern, and interannual dynamics, its monthly dynamics in different regions remain unclear, hindering our ability to evaluate its ecological effects. Therefore, we obtained monthly wet N deposition data from196 sites after continuous network observations and published data in China and analyzed the monthly dynamics of NH₄⁺–N, NO₃⁻–N, and dissolved inorganic N (DIN=NH₄⁺−N+NO₃⁻–N) deposition fluxes on site, regional, and national scales. We observed that the deposition fluxes of NH₄⁺–N, NO₃⁻–N, and DIN in China showed clear monthly patterns and regional differences. In Northern China, wet N deposition predominantly showed a unimodal trend, whereas in Southern China, it revealed a bimodal trend or irregular fluctuations. During 2000–2016, NH₄⁺–N, NO₃⁻–N, and DIN deposition fluxes were estimated as 9.09, 6.12, and 15.21 kg N ha⁻¹ year.⁻¹, respectively. Our findings enhance our understanding of atmospheric wet N deposition, and can serve as a reference for N deposition simulation experiments in different regions, and for generating long-term N deposition data for model optimization. Regional differences in the monthly dynamics of wet N deposition should be emphasized to accurately evaluate its ecological effects on terrestrial ecosystems in different regions.

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Characterization of Mg-based bimetal treatment of insensitive munition 2,4-dinitroanisole

Abstract

The manufacturing of insensitive munition 2,4-dinitroanisole (DNAN) generates waste streams that require treatment. DNAN has been treated previously with zero-valent iron (ZVI) and Fe-based bimetals. Use of Mg-based bimetals offers certain advantages including potential higher reactivity and relative insensitivity to pH conditions. This work reports preliminary findings of DNAN degradation by three Mg-based bimetals: Mg/Cu, Mg/Ni, and Mg/Zn. Treatment of DNAN by all three bimetals is highly effective in aqueous solutions (> 89% removal) and wastewater (> 91% removal) in comparison with treatment solely with zero-valent magnesium (ZVMg; 35% removal). Investigation of reaction byproducts supports a partial degradation pathway involving reduction of the ortho or para nitro to amino group, leading to 2-amino-4-nitroanisole (2-ANAN) and 4-amino-2-nitroanisole (4-ANAN). Further reduction of the second nitro group leads to 2,4-diaminoanisole (DAAN). These byproducts are detected in small quantities in the aqueous phase. Carbon mass balance analysis suggests near-complete closure (91%) with 12.4 and 78.4% of the total organic carbon (TOC) distributed in the aqueous and mineral bimetal phases, respectively. Post-treatment surface mineral phase analysis indicates Mg(OH)₂ as the main oxidized species; oxide formation does not appear to impair treatment.

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The relationship between anticipated response and subsequent experience of cancer treatment-related side effects: A meta-analysis comparing effects before and after treatment exposure

Publication date: Available online 15 June 2018
Source:Cancer Treatment Reviews
Author(s): Chloe Fletcher, Carlene Wilson, Amanda D. Hutchinson, Elizabeth Alice Grunfeld
ObjectiveTo review the evidence for a systematic relationship between cancer patients' pre-treatment expectations (anticipated side effects) and subsequent experience of treatment-related side effects, and to compare this relationship in patients with no prior treatment experience (cognitive expectations) and with some prior treatment experience (conditioned response).MethodsA total of 12,952 citations were identified through a comprehensive search of the literature published on or before November 2016 and screened against inclusion criteria. Studies were eligible if they included participants undergoing curative treatment for cancer, measured a treatment side effect, examined the relationship between anticipation and experience of side effects, and reported quantitative data.ResultsThirty-one studies were included in the review and meta-analysis (total N = 5,069). The side effects examined were nausea (anticipatory and post-treatment), vomiting, fatigue, pain, problems with concentration, and skin reactions. Meta-analyses indicated significant and positive associations between anticipation and subsequent experience for all included side effects in patients with no prior treatment exposure (r = 0.153 – 0.431). Stronger associations were found for all included conditioned side effects in patients with previous treatment experience (r = 0.211 – 0.476). No significant differences were found when overall effect sizes for patients with and without prior treatment exposure were compared for each side effect, except for anticipatory nausea (p = 0.012).ConclusionThese results may have implications for future interventions that target patients' expectations of cancer treatment-related side effects. Future research could explore patient reports of messages received about likely treatment effects both before and during treatment.

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A questionnaire using vocal symptoms in quality control of phonosurgery: vocal surgical questionnaire

Quality control after phonosurgery is important and may be time consuming. Often questionnaires focusing on quality of life are applied. We aimed at investigating the use of organ specific symptoms, such as ho...

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Oncogenic drivers in 11q13 associated with prognosis and response to therapy in advanced oropharyngeal carcinomas

Publication date: August 2018
Source:Oral Oncology, Volume 83
Author(s): M.C. Barros-Filho, L.A. Reis-Rosa, M. Hatakeyama, F.A. Marchi, T. Chulam, C. Scapulatempo-Neto, U.R. Nicolau, A.L. Carvalho, C.A.L. Pinto, S.A. Drigo, L.P. Kowalski, S.R. Rogatto
ObjectivesTo identify potential molecular drivers associated with prognosis and response to treatment in advanced oropharyngeal squamous cell carcinomas (OPSCC).Materials and methodsThirty-three OPSCC biopsies from untreated Brazilian patients were evaluated for human papilloma virus genotyping, genome wide copy number alterations and gene expression profiling. Data were integrated using CONEXIC algorithm. Validation with TCGA dataset and confirmation by RT-qPCR of candidate genes were performed.ResultsHigh-risk HPV positive cases, detected in 55% of advanced OPSCC, were associated with better outcome. Losses of 8p11.23-p11.22, 14q11.1-q11.2 and 15q11.2, and gains of 11q13.2 and 11q13.2-q13.3 were detected as recurrent alterations. Gains of 3q26.31 and 11q13.2 and losses of 9p21.3 were exclusively detected in HPV-negative tumors. Two clusters of expression profiles were observed, being one composed mostly by HPV positive cases (83%). HPV-positive enriched cluster showed predominantly immune response-related pathways. Integrative analysis identified 10 modulators mapped in 11q13, which were frequently cancer-related. These 10 genes showed copy number gains, overexpression and an association with worse survival, further validated by TCGA database analyses. Overexpression of four genes (ORAOV1, CPT1A, SHANK2 and PPFIA1) evaluated by RT-qPCR confirmed their association with poor survival. Multivariate analysis showed that PPFIA1 overexpression and HPV status are independent prognostic markers. Moreover, SHANK2 overexpression was significantly associated with incomplete response to treatment.ConclusionThe integrative genomic and transcriptomic data revealed potential driver genes mapped in 11q13 associated with worse prognosis and response to treatment, giving fundamentals for the identification of novel therapeutic targets in OPSCC.

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Association Between Thyroid Dysfunction and Lipid Profiles Differs According to Age and Sex: Results from the Korean National Health and Nutrition Examination Survey

Thyroid, Ahead of Print.

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Editorial Board

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Comments for Mertens et al. (2018), Glyphosate, a chelating agent—relevant for ecological risk assessment?

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Multimode ultrasound viscoelastography for three-dimensional interrogation of microscale mechanical properties in heterogeneous biomaterials

Publication date: September 2018
Source:Biomaterials, Volume 178
Author(s): Xiaowei Hong, Ramkumar T. Annamalai, Tyler S. Kemerer, Cheri X. Deng, Jan P. Stegemann
Both static and time-dependent mechanical factors can have a profound impact on cell and tissue function, but it is challenging to measure the mechanical properties of soft materials at the scale which cells sense. Multimode ultrasound viscoelastography (MUVE) uses focused ultrasound pulses to both generate and image deformations within soft hydrogels non-invasively, at sub-millimeter resolution, and in 3D. The deformation and strain over time data are used to extract quantitative parameters that describe both the elastic and viscoelastic properties of the material. MUVE was used in creep mode to characterize the viscoelastic properties of 3D agarose, collagen, and fibrin hydrogels. Quantitative comparisons were made by extracting characteristic viscoelastic parameters using Burger's lumped parameter constitutive model. Spatial resolution of the MUVE technique was found to be approximately 200 μm, while detection sensitivity, defined as the capability to differentiate between materials based on mechanical property differences, was approximately 0.2 kPa using agarose hydrogels. MUVE was superior to nanoindentation and shear rheometry in generating consistent microscale measurements of viscoelastic behavior in soft materials. These results demonstrate that MUVE is a rapid, quantitative, and accurate method to measure the viscoelastic mechanical properties of soft 3D hydrogels at the microscale, and is a promising technique to study the development of native and engineered tissues over time.

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Integrin α6 and EGFR signaling converge at mechanosensitive calpain 2

Publication date: September 2018
Source:Biomaterials, Volume 178
Author(s): A.D. Schwartz, C.L. Hall, L.E. Barney, C.C. Babbitt, S.R. Peyton
Cells sense and respond to mechanical cues from the extracellular matrix (ECM) via integrins. ECM stiffness is known to enhance integrin clustering and response to epidermal growth factor (EGF), but we lack information on when or if these mechanosensitive growth factor receptors and integrins converge intracellularly. Towards closing this knowledge gap, we combined a biomaterial platform with transcriptomics, molecular biology, and functional assays to link integrin-mediated mechanosensing and epidermal growth factor receptor (EGFR) signaling. We found that high integrin α6 expression controlled breast cancer cell adhesion and motility on soft, laminin-coated substrates, and this mimicked the response of cells to EGF stimulation. The mechanisms that drove both mechanosensitive cell adhesion and motility converged on calpain 2, an intracellular protease important for talin cleavage and focal adhesion turnover. EGF stimulation enhanced adhesion and motility on soft substrates, but required integrin α6 and calpain 2 signaling. In sum, we identified a new role for integrin α6 mechanosensing in breast cancer, wherein cell adhesion to laminin on soft substrates mimicked EGF stimulation. We identified calpain 2, downstream of both integrin α6 engagement and EGFR phosphorylation, as a common intracellular signaling node, and implicate integrin α6 and calpain 2 as potential targets to inhibit the migration of cancer cells in stiff tumor environments.

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Nitroxide radical-containing nanoparticles attenuate tumorigenic potential of triple negative breast cancer

Publication date: September 2018
Source:Biomaterials, Volume 178
Author(s): Babita Shashni, Yukio Nagasaki
The critical importance of reactive oxygen species (ROS) as oncogene activators and essential secondary messengers in cancer cell survival have been widely reported. Since oxidative stress has been implicated as being pivotal in various cancers, antioxidant therapy seems an apt strategy to abrogate ROS-mediated cellular processes to attenuate cancers. We therefore synthesized ROS scavenging nitroxide radical-containing nanoparticles (RNPs); pH insensitive RNP^O and pH sensitive RNP^N, to impede the proliferative and metastatic characteristics of the triple negative breast cancer cell line, MDA-MB-231, both in vitro and in vivo. RNPs significantly curtailed the proliferative and clonogenic potential of MDA-MB-231 and MCF-7 cell lines. Inhibition of ROS-mediated migratory and invasive characteristics of MDA-MB-231, via down regulation of NF-κB and MMP-2, was also confirmed. Furthermore, a significant anti-tumor and anti-metastatic potential of RNPs was observed in an MDA-MB-231 mouse xenograft model. Such tumoricidal effects of RNPs were attained with negligible adverse effects, compared to conventional low molecular weight antioxidants, TEMPOL. Thus, the tumoricidal effects of RNPs are suggestive of insights on precedence of nanoparticle-based therapeutics over current low molecular weight antioxidants to curtail ROS-induced tumorigenesis of various cancers.

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Biomimetic O2-Evolving metal-organic framework nanoplatform for highly efficient photodynamic therapy against hypoxic tumor

Publication date: September 2018
Source:Biomaterials, Volume 178
Author(s): Shutao Gao, Pengli Zheng, Zhenhua Li, Xiaochen Feng, Weixiao Yan, Shizhu Chen, Weisheng Guo, Dandan Liu, Xinjian Yang, Shuxiang Wang, Xing-Jie Liang, Jinchao Zhang
Improving the supply of O2 and the circulation lifetime of photosensitizers for photodynamic therapy (PDT) in vivo would be a promising approach to eliminate hypoxic tumors. Herein, by taking advantage of the significant gas-adsorption capability of metal-organic frameworks (MOFs), a biomimetic O2-evolving photodynamic therapy (PDT) nanoplatform with long circulating properties was fabricated. Zirconium (IV)-based MOF (UiO-66) was used as a vehicle for O2 storing, then conjugated with indocyanine green (ICG) by coordination reaction, and further coated with red blood cell (RBC) membranes. Upon 808 nm laser irradiation, the initial singlet oxygen (¹O2) generated by ICG would decompose RBC membranes. At the same time, The photothermal property of ICG could facilitate the burst release of O2 from UiO-66. Subsequently, the generated O2 could significantly improve the PDT effects on hypoxic tumor. Owing to the advantages of long circulation and O2 self-sufficient, the designed nanotherapeutic agent can improve the efficiency of treatment against hypoxia tumor via PDT. Hence, this study presents a new paradigm for co-delivery of O2 and photosensitizers, and provides a new avenue to eliminate hypoxic tumors.

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Transcutaneously refillable, 3D-printed biopolymeric encapsulation system for the transplantation of endocrine cells

Publication date: September 2018
Source:Biomaterials, Volume 177
Author(s): Marco Farina, Corrine Ying Xuan Chua, Andrea Ballerini, Usha Thekkedath, Jenolyn F. Alexander, Jessica R. Rhudy, Gianluca Torchio, Daniel Fraga, Ravi R. Pathak, Mariana Villanueva, Crystal S. Shin, Jean A. Niles, Raffaella Sesana, Danilo Demarchi, Andrew G. Sikora, Ghanashyam S. Acharya, A. Osama Gaber, Joan E. Nichols, Alessandro Grattoni
Autologous cell transplantation holds enormous promise to restore organ and tissue functions in the treatment of various pathologies including endocrine, cardiovascular, and neurological diseases among others. Even though immune rejection is circumvented with autologous transplantation, clinical adoption remains limited due to poor cell retention and survival. Cell transplant success requires homing to vascularized environment, cell engraftment and importantly, maintenance of inherent cell function. To address this need, we developed a three dimensional (3D) printed cell encapsulation device created with polylactic acid (PLA), termed neovascularized implantable cell homing and encapsulation (NICHE).In this paper, we present the development and systematic evaluation of the NICHE in vitro, and the in vivo validation with encapsulated testosterone-secreting Leydig cells in Rag1−/− castrated mice. Enhanced subcutaneous vascularization of NICHE via platelet-rich plasma (PRP) hydrogel coating and filling was demonstrated in vivo via a chorioallantoic membrane (CAM) assay as well as in mice. After establishment of a pre-vascularized bed within the NICHE, transcutaneously transplanted Leydig cells, maintained viability and robust testosterone secretion for the duration of the study. Immunohistochemical analysis revealed extensive Leydig cell colonization in the NICHE. Furthermore, transplanted cells achieved physiologic testosterone levels in castrated mice. The promising results provide a proof of concept for the NICHE as a viable platform technology for autologous cell transplantation for the treatment of a variety of diseases.

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Identification of complement inhibitory activities of two chemotherapeutic agents using a high-throughput cell imaging-based screening assay

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Lingjun Zhang, Yuriy Fedorov, Drew Adams, Feng Lin
Excessive complement activation contributes significantly to the pathogeneses of various diseases. Currently, significant developmental research efforts aim to identify complement inhibitors with therapeutic uses have led to the approval of one inhibitor for clinical use. However, most existing complement inhibitors are based on monoclonal antibodies, which have many drawbacks such as high costs and limited administration options. With this report, we establish an inexpensive, cell imaging-based high-throughput assay for the large-scale screening of potential small molecule complement inhibitors. Using this assay, we screened a library containing 3115 bioactive chemical compounds and identified cisplatin and pyridostatin as two new complement inhibitors in addition to nafamostat mesylate, a compound with known complement inhibitory activity. We further demonstrated that cisplatin and pyridostatin inhibit C5 convertases in the classical pathway of complement activation but have no effects on the alternative pathway of complement activation. In summary, this work has established a simple, large-scale, high-throughput assay for screening novel complement inhibitors and discovered previously unknown complement activation inhibitory activities for cisplatin and pyridostatin.

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Regulatory T cell subsets are differentially dependent on CD28 for their proliferation

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Ei Wakamatsu, Hiroki Omori, Shizuka Ohtsuka, Shuhei Ogawa, Jonathan M. Green, Ryo Abe
It is thought that CD28 plays a crucial role in the maintenance of regulatory T cell (Treg) pool size through promoting the development and proliferation of these cells. However, recently we found that the dependency on CD28 co-stimulation for their development is different between Treg subsets, thymus-derived Tregs (tTregs, CD28-dependent) and peripherally-derived Tregs (pTregs, CD28-independent), suggesting that CD28 may also have differential influences on the homeostasis of each Treg subset. Here, we demonstrated that both Treg subsets were reduced in secondary lymphoid organs of CD28 deficient mice, and that this reduction was due to impaired proliferation in both Treg subsets by the intrinsic CD28 defect. However, we found that the massive proliferation of both Treg subsets under lymphopenic condition was regulated by CD28, whereas the proliferative activity of tTregs but not pTregs in the steady state was dependent on CD28. Also, experiments using mutant CD28 knock-in mice revealed that proliferation of pTregs under lymphopenic condition required only the Lck-NFκB pathway of CD28, whereas tTregs required an additional unknown pathway. These findings indicate that the dependency on CD28 for proliferation in each Treg subset differs depending on the environment.

https://ift.tt/2MubWHL

Orexin A prevents degradation of the articular matrixes in human primary chondrocyte culture

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Dong Wang, Hui Ren, Chunlong Li, Fanghe Liu, Guangzhi Wang, Fengjun Shi, Yuanxin Sun
Excessive production of pro-inflammatory cytokines such as interleukin-1β (IL-1β) plays a key role in the pathophysiological development of osteoarthritis (OA). Orexin A is an important peptide of hypothalamic origin, which has displayed its multiple biological functions in several chronic diseases via activation of its specific G-protein coupled receptors, orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R). In this study, we aimed to characterize the protective effects of orexin A against IL-1β-induced degradation of articular cartilage matrixes in human chondrocytes. Our results indicate that OX1R but not OX2R was expressed in human chondrocytes. We also found that the expression of OX1R was significantly lower in chondrocytes from OA patients, and that treatment with IL-1β decreased the expression of OX1R in a dose-dependent manner. The presence of orexin A ameliorated IL-1β-induced degradation of type II collagen and aggrecan, the two major components of articular cartilage matrixes. Our results also show that orexin A prevented IL-1β-induced expression of catabolic enzymes such as MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5. Mechanistically, orexin A treatment abolished activation of the transcriptional factor NF-κB via inhibition of KKα/IκB-α phosphorylation and IκB-α degradation. These findings suggest that orexin A might act as an effective therapeutic agent for the treatment of OA.

https://ift.tt/2tegTLQ

Identification of complement inhibitory activities of two chemotherapeutic agents using a high-throughput cell imaging-based screening assay

Regulatory T cell subsets are differentially dependent on CD28 for their proliferation

Orexin A prevents degradation of the articular matrixes in human primary chondrocyte culture

The Challenges of Preventing Food Allergy: lessons learned from LEAP and EAT

Publication date: Available online 15 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Helen Fisher, George Du Toit, Henry T. Bahnson, Gideon Lack

https://ift.tt/2JFNwgx

Hymenoptera Venom Immunotherapy: Past, Present, and Future

Publication date: Available online 15 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): John Oppenheimer MD, David BK Golden MD

https://ift.tt/2yeUDr9

Vitamin D insufficiency, TH2 cytokines, and allergy markers in Puerto Rican children with asthma

Publication date: Available online 15 June 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Yueh-Ying Han, Erick Forno, Nadia Boutaoui, Glorisa Canino, Juan C. Celedón

https://ift.tt/2MstjIV

Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study

Publication date: August 2018
Source:European Journal of Cancer, Volume 99
Author(s): Gertraud Stocker, Ulrich T. Hacker, Frédéric Fiteni, Jestinah John Mahachie, Arnaud D. Roth, Eric Van Cutsem, Marc Peeters, Florian Lordick, Murielle Mauer
BackgroundDose reduction in obese cancer patients has been replaced by fully weight-based dosing recommendations. No data, however, are available on the effects of dose reduction in obese stage III colon cancer patients undergoing adjuvant chemotherapy.MethodsSurvival outcomes and toxicity data of obese (body mass index [BMI] ≥30 kg/m²), stage III colon cancer patients treated within the phase III PETACC 3 trial comparing leucovorin, 5-FU (LV5FU2) with LV5FU2 plus irinotecan were analysed retrospectively according to chemotherapy dosing at first infusion (i.e. fully weight-based dosed - versus dose-reduced group). Multivariate analyses on relapse free survival (RFS) and overall survival (OS) were conducted to adjust for baseline prognostic factors using Cox regression model.Results13.4% (280 of 2094 patients) had a BMI ≥ 30 kg/m², and 5.3% had both a BMI ≥ 30 kg/m² and a body surface area (BSA) ≥2 m². Dose reductions occurred in 16.1% of patients with a BMI ≥ 30 kg/m² and 32.4% with BMI ≥ 30 kg/m² and BSA ≥ 2 m², respectively. In patients with BMI ≥ 30 kg/m², multivariate analysis demonstrated a trend towards better RFS in the fully dosed compared to the dose-reduced group (Hazard ratio (HR): 0.69, 95% CI: 0.43–1.09; p = 0.11); however, there was no statistically significant difference in OS. In patients with BMI ≥ 30 kg/m² and BSA ≥ 2 m², multivariate analysis demonstrated better RFS in fully dosed compared with dose-reduced patients (HR: 0.48, 95% CI: 0.27–0.85; p = 0.01) and a strong trend towards better OS (HR: 0.53, 95% CI: 0.28–1.01; p = 0.052). This group comprised predominantly of men.ConclusionsData support the recommendation of using fully dosed chemotherapy for the adjuvant treatment in obese patients with colon cancer.

https://ift.tt/2JNTxDT

Applications and limitations of using patient-specific 3D printed molds in autologous breast reconstruction

Abstract

Background

Over the last years, several techniques have been proposed to improve the outcome of autologous breast reconstruction procedures. One of these innovations describes patient-specific, three-dimensional (3D) printed breast molds for intraoperative use based on 3D stereophotogrammetry. In this article, we want to share our preliminary experiences with producing such templates, its clinical possibilities and limitations in practice.

Methods

Patient-specific templates were designed based on 3D stereophotogrammetry images. The 3D template was fabricated using a 3D printer. During breast reconstruction, the autologous flap was placed inside the printed template to aid the surgeon in determining the shape and volume of the autologous flap creating the desired breast dimensions. Patients were 3D-photographed 6 to 9 months post-operatively.

Results

Three patients with unilateral breast reconstructions showed a width difference of 0.5 cm and mean volume difference of 211 ml between the reconstructed and contralateral breasts. In the three bilateral reconstructed patients, a mean difference in breast width and volume of respectively 0.5 cm and 16 ml was found.

Conclusions

Patient-specific breast templates are inexpensive and relatively easy to design, while being practical and convenient to obtain insight in the dimensions of the desired breast during reconstruction, according to the operating surgeons. Patient selection is however critical, as patients must have sufficient donor volume and/or satisfying breast shape to be able to use the template to its full potential.

Level of evidence: Level IV, therapeutic study.

https://ift.tt/2JUU1LX

Variation in Out of Pocket Health Care Costs for Individuals with Anxiety Disorders by Type of Insurance Coverage

Publication date: Available online 15 June 2018
Source:Journal of Anxiety Disorders
Author(s): Klariz Tucker, Tyra Dark, Jeffrey S. Harman
PurposeGiven that out-of-pocket (OOP) costs impact adherence to treatment and recent and proposed changes to the health insurance system that impact OOP costs, it is imperative to understand the OOP cost burden faced by individuals with anxiety disorders depending upon type of insurance coverage. The objective of this study was to determine the annual OOP cost burden faced by individuals with anxiety disorders and the variation of these costs by type of insurance coverage.MethodsUsing weighted nationally representative data from the 2011–2014 Medical Expenditure Panel Surveys, total OOP health care costs were assessed for all respondents who indicated that they had an anxiety disorder (N = 9,985). Total OOP health care costs were also calculated separately by type of insurance.ResultsAverage annual OOP costs among individuals with anxiety was $1,152. The highest OOP cost were incurred by individuals with private fee-for-service (FFS) insurance ($1,356/year, 4.1% of annual income), while individuals enrolled in HMOs with dual Medicare/Medicaid had the lowest OOP cost ($129/year, 6.8% of annual income). Individuals without insurance had high OOP cost burden ($1,309/year, 12.5% of annual income).ConclusionIndividuals with anxiety disorders have a wide range of OOP cost depending upon their insurance coverage. Those with anxiety should carefully consider their choice of insurance coverage if interested in minimizing OOP costs.

https://ift.tt/2tcWcQG

Editorial Board

Publication date: June 2018
Source:Journal of Anxiety Disorders, Volume 57

https://ift.tt/2lb6Fsf

Predictors of treatment outcome for the unified protocol for transdiagnostic treatment of emotional disorders in children (UP-C)

1-s2.0-S0887618518X00048-cov150h.gif

Publication date: June 2018
Source:Journal of Anxiety Disorders, Volume 57
Author(s): Sarah M. Kennedy, Niza A. Tonarely, Jamie A. Sherman, Jill Ehrenreich-May
Various efficacious treatment packages exist for youth anxiety, and cognitive behavior therapy (CBT) is now considered to be a well-established treatment for child anxiety disorders (Higa-McMillan, Francis, Rith-Najarian, & Chorpita, 2016). Improving outcomes for the significant proportion of anxious youth who demonstrate inadequate response to CBT is imperative, but our understanding of who does and does not benefit is incomplete. Further, there are no known empirical studies of predictors of treatment response for youth who receive a transdiagnostic intervention for anxiety or depression, and it is therefore unclear whether predictors of response to a transdiagnostic treatment for children are similar to those found in previous studies of anxiety-specific treatments. This study investigated potential predictors of outcome following administration of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children (UP-C; Ehrenreich-May et al., 2018). Participants were 60 children ages 6–13 (M = 9.47, SD = 1.68) with a primary anxiety diagnosis (with or without comorbid depression) who received a 15-week UP-C group treatment. Consistent with prior literature on CBT for anxiety, social anxiety emerged as a consistent predictor of poorer response to the UP-C. Inconsistent with prior literature, depression, symptom severity, parent psychopathology, and child age were not significant predictors of poor outcome. Results indicate some differences between predictors for transdiagnostic versus anxiety-focused treatments, but point to a need for both types of interventions to better target social anxiety in children.

https://ift.tt/2tcVYci

Comparison of Hand-Sewn versus Coupled Venous Anastomoses in Traumatic Lower Extremity Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0038-1660831

Background Microvascular reconstruction of the lower extremity has the highest reported complication and flap failure rates of any anatomical region. Despite widespread adoption of the mechanical anastomotic venous coupler and encouraging results in other anatomical regions, there are limited reports examining its use in the lower extremity. This study compares outcomes between coupled and hand-sewn venous anastomoses in traumatic lower extremity reconstruction. Methods Retrospective review of our institutional flap registry from 1979 to 2016 identified soft tissue free flaps performed for the reconstruction of Gustilo type IIIB/IIIC open tibial fractures. Patient demographics, flap characteristics, use of a venous anastomotic coupler, and perioperative outcomes were examined. Analysis was performed using chi-square and Student's t-tests. Results A total of 361 patients received a microvascular free flap for coverage of a Gustilo type IIIB or IIIC tibial fracture following traumatic injury. After excluding cases that lacked adequate information on coupler use, 358 free flaps were included in the study. There were 72 (20%) free flaps performed using a venous coupler and 286 (80%) performed with hand-sewn venous anastomoses. There were comparable rates of major complications (22.2 vs. 26.1%; p = 0.522), total flap failure (6.5%, vs. 10.2%; p = 0.362), and partial flap failure (9.7 vs. 12.2%; p = 0.579) between venous coupler and hand-sewn anastomoses, respectively. Furthermore, use of the venous coupler was not associated with increased rates of operative take backs (22.8 vs. 23.0%; p = 0.974). However, reconstructions performed using a venous coupler were significantly more likely to have a second venous anastomosis performed (37.5 vs. 21.3%; p = 0.004). Conclusion Complication and flap failure rates were similar between reconstructions performed with a venous coupler and those performed with hand-sewn venous anastomoses. These findings suggest that use of the venous anastomotic coupler is safe and effective in lower extremity reconstruction, with comparable outcomes to conventional sutured anastomoses.
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Article in Thieme eJournals:
Table of contents | Abstract | Full text

https://ift.tt/2t2hxwP

“Rejuvenation” Reclaimed!

Rejuvenation Research, Volume 21, Issue 3, Page 191-192, June 2018.

https://ift.tt/2taG2r5

Meetings Calendar

Rejuvenation Research, Volume 21, Issue 3, Page 283-289, June 2018.

https://ift.tt/2lb1yZ1

Finally, a Regimen to Extend Human Life Expectancy

Rejuvenation Research, Volume 21, Issue 3, Page 278-282, June 2018.

https://ift.tt/2t6IY7Y

Treatment of giant cervico-mediastinal lymphatic malformations: a case series

Lymphatic malformations are histologically benign vascular structures that vary in anatomic lesion and size. Extensive head and neck lymphatic malformations may be life-threatening. In the present study, we de...

https://ift.tt/2JVCGlT

Editorial Board

Publication date: May 2018
Source:Biological Psychology, Volume 135

https://ift.tt/2JNqTml

A pilot study to investigate the therapeutic effect of Valsalva maneuver on otitis media with effusion in adults

This pilot study was performed to investigate the therapeutic effect of Valsalva maneuver on otitis media in adults and to evaluate the prognostic factors for the good response.

https://ift.tt/2taZYKo

Ultrasonography for classifying lymphatic sclerosis types and deciding optimal sites of lymphatic-venous anastomosis in lymphoedema patients

We have previously categorised the degree of degeneration of the collecting lymphatic vessels into four types: normal, ectasis, contraction and sclerosis type (NECST classification). Here, we evaluated the collective lymphatic vessels in lymphoedema-affected limbs using ultrasonography. In step 1, we investigated 110 lymphatic vessels from 25 patients with lymphoedema, who underwent lymphatic-venous anastomosis (LVA) following preoperative ultrasonography. We classified the lymphatic vessels using the NECST classification via intraoperative microscopic observation.

https://ift.tt/2JQPA1B

Hydrochlorothiazide use and risk of Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study

Hydrochlorothiazide use has been associated with markedly increased risk of squamous cell carcinoma. No previous studies have investigated the association between hydrochlorothiazide use and the risk of Merkel cell carcinoma (MCC) and malignant adnexal skin tumors (MAST).

https://ift.tt/2JNtgFR

Fibroproliferative Genes are Preferentially Expressed in Central Centrifugal Cicatricial Alopecia

CCCA and FPDs both commonly affect patients of African descent.Critical genes implicated in FPDs are upregulated in CCCA affected scalp tissue.Anti-fibrotic therapies may play a role in the treatment of CCCA.

https://ift.tt/2sZI4ec

Motorized 0.8 mm micro-punch grafting for refractory vitiligo: A retrospective study of 230 cases

Punch grafting for vitiligo has been time-consuming and may result in cobblestone-like appearances. We devised a motorized 0.8 mm micro-punch grafting procedure to overcome these limitations.

https://ift.tt/2tcxArn

Lipofibromas are not related to diabetes mellitus or obesity

https://ift.tt/2t0URx4

Reply to “Wound Management Strategies in Stevens-Johnson syndrome/Toxic Epidermal Necrolysis: An unmet need”

https://ift.tt/2t9CgOB

Wound Management Strategies in Stevens-Johnson syndrome/Toxic Epidermal Necrolysis: An unmet need

https://ift.tt/2Mviar4

Philadelphia chromosome-positive lymphoblastic lymphoma—Is it rare or underdiagnosed?

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Ahmad Alshomar, Riad El Fakih
Lymphoblastic lymphomas (LBLs) are neoplasms of precursor B and T cells; they are considered in the same spectrum as precursor B and T cell acute lymphoblastic leukemia (ALL). The World Health Organization classification classifies both LBL and ALL as one disease entity. While chromosome abnormalities are well defined with all of their therapeutic and prognostic implications in ALL, these are not well studied in LBL. Here, we describe a case of Philadelphia chromosome-positive LBL and review the available literature regarding this entity.

https://ift.tt/2t0UliC

Rosai-Dorfman disease masquerading as Uveal Melanoma: Case report and review of literature

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Yacoub A. Yousef, Maysa Al-Hussaini, Rashed Nazzal, Ghadeer Abdeen, Ibrahim Alnawaiseh, Khaleel Alrawashdeh
Objective/BackgroundIntra ocular Rosai-Dorfman disease (RDD) is an extremely rare disease. We are reporting the first case of RDD presenting as ciliary body mass mimicking ciliary body melanoma, and we are reviewing the English literature reporting on cases of RDD presented with intraocular disease.MethodsAn 18-year-old lady presented with loss of vision in the right eye, and was found to have intraocular mass lesion. She was diagnosed clinically and radiologically as a case of ciliary body melanoma associated with total retinal detachment.ResultsHistopathological sections and stains proved to be intraocular RDD. Review of the literature revealed three cases of intraocular RDD; two of them had choroid thickening associated with serous retinal detachment, and one presented with intraocular mass mimicking choroid melanoma. Two of the three cases were enucleated. Our case is the first case in English literature of intraocular ciliary body RDD, mimicking ciliary body melanoma.ConclusionRDD can present as an intraocular mass that mimics ciliary body melanoma. This case emphasizes the importance of diagnostic biopsy before considering the final therapy in unclear cases, mainly when associated with unusual systemic features like lymphadenopathy.

https://ift.tt/2LVTCGx

Granulocytic sarcoma and mediastinal germ cell tumor: A common cell of origin?

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sarbajit Mukherjee, Sami Ibrahimi, Teresa Scordino, Mohamad Cherry

https://ift.tt/2t74iez

Parvovırus-induced thrombocytopenıa

Publication date: Available online 15 June 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Burak Furkan Demir, Aysenur Karahan Meteris, Gokhan Yirgin, Mustafa Comoglu, Bilal Katipoglu, Nisbet Yılmaz, Ihsan Ates

https://ift.tt/2LQuT6n

Regional Anesthesia: What We Need to Know in the Era of Enhanced Recovery After Surgery Protocols and the Opioid Epidemic

Publication date: Available online 15 June 2018
Source:Anesthesiology Clinics
Author(s): Lee A. Fleisher

https://ift.tt/2lekK8k

Regional Anesthesia: What We Need to Know in the Era of Enhanced Recovery After Surgery Protocols and the Opioid Epidemic

Publication date: Available online 15 June 2018
Source:Anesthesiology Clinics
Author(s): Lee A. Fleisher

https://ift.tt/2lekK8k

Toward A variable RBE for proton beam therapy

Publication date: Available online 14 June 2018
Source:Radiotherapy and Oncology
Author(s): Henning Willers, Antino Allen, David Grosshans, Stephen J. McMahon, Cläre von Neubeck, Claudia Wiese, Bhadrasain Vikram
In the clinic, proton beam therapy (PBT) is based on the use of a generic relative biological effectiveness (RBE) of 1.1 compared to photons in human cancers and normal tissues. However, the experimental basis for this RBE lacks any significant number of representative tumor models and clinically relevant endpoints for dose-limiting organs at risk. It is now increasingly appreciated that much of the variations of treatment responses in cancers are due to inter-tumoral genomic heterogeneity. Indeed, recently it has been shown that defects in certain DNA repair pathways, which are found in subsets of many cancers, are associated with a RBE increase in vitro. However, there currently exist little in vivo or clinical data that confirm the existence of similarly increased RBE values in human cancers. Furthermore, evidence for variable RBE values for normal tissue toxicity has been sparse and conflicting to date. If we could predict variable RBE values in patients, we would be able to optimally use and personalize PBT. For example, predictive tumor biomarkers may facilitate selection of patients with proton-sensitive cancers previously ineligible for PBT. Dose de-escalation may be possible to reduce normal tissue toxicity, especially in pediatric patients. Knowledge of increased tumor RBE may allow us to develop biologically optimized therapies to enhance local control while RBE biomarkers for normal tissues could lead to a better understanding and prevention of unusual PBT-associated toxicity. Here, we will review experimental data on the repair of proton damage to DNA that impact both RBE values and biophysical modeling to predict RBE variations. Experimental approaches for studying proton sensitivity in vitro and in vivo will be reviewed as well and recent clinical findings discussed. Ultimately, therapeutically exploiting the understudied biological advantages of protons and developing approaches to limit treatment toxicity should fundamentally impact the clinical use of PBT.

https://ift.tt/2tgkHwu

Impact of the addition of new vaccines in the early childhood schedule on vaccine coverage by 24 months of age from 2006 to 2016 in Quebec, Canada

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Marilou Kiely, Nicole Boulianne, Denis Talbot, Manale Ouakki, Maryse Guay, Monique Landry, Joseline Zafack, Chantal Sauvageau, Gaston De Serres
ContextBetween 2004 and 2016, in the province of Quebec (Canada), 4 new antigens were added in the early childhood vaccine schedule from birth to 18 months, increasing the number of injections or doses needed from 7 to 12. These additions may have decreased the proportion of children who had received all recommended vaccines.ObjectivesTo assess the impact of the introduction of new vaccines to the childhood schedule on the 24-month vaccine coverage from 2006 to 2016 and identify factors associated with incomplete vaccination status by 24 months of age.MethodsWe used the data from six cross-sectional vaccine coverage surveys conducted every two years which included a total of 3515 children aged 2 years old and randomly selected from the Quebec public health insurance database. Factors associated with an incomplete vaccine status by 24 months were identified with multivariable logistic regression.ResultsDespite the addition of 4 new vaccine antigens since 2004, the vaccine coverage remained high from 2006 (82.4%) through 2016 (88.3%) for vaccines present in the schedule since 2006. In 2016, vaccine coverage was 78.2% for all vaccines included in the schedule. The vaccine coverage of new vaccines increases rapidly within 2 years of their introduction. For both new and older vaccines, incomplete vaccine status by 24 months of age is associated with a delay of 30 days or more in receiving the vaccines scheduled at 2 and 12 months of age.ConclusionsIncreasing to 12 the number of doses in the recommended schedule has slightly reduced the vaccine coverage by 24 months of age and the vaccine coverage of vaccines already in the schedule remained stable over the years. Future additions to the vaccine schedule may not be similarly accepted by the population and this will require continuing the monitoring of vaccine coverage.

https://ift.tt/2tclG0C

Immunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Marina R. Pulido, Meritxell García-Quintanilla, Jerónimo Pachón, Michael J. McConnell
Outer membrane complex (OMC) vaccines, which contain antigens from the bacterial outer membrane, have been developed for multiple Gram-negative bacteria. However, OMC vaccines demonstrate high endotoxin activity due to the presence of lipopolysaccharide in the bacterial outer membrane, thus precluding their use in humans. We isolated OMCs from an LPS-deficient strain of A. baumannii (IB010) which completely lacks LPS due to a mutation in the lpxD gene. OMCs from IB010 demonstrated a more than 10,000-fold reduction in endotoxin activity compared to OMCs from wild type A. baumannii. Vaccination with IB010 OMCs produced similar levels of antigen-specific IgG and IgM after two administrations compared to wild type OMCs, and resulted in a similar reduction in post-infection spleen bacterial loads and serum pro-inflammatory cytokine levels. Vaccination with IB010 OMCs provided significant protection against infection compared to control mice, indicating the LPS-free OMCs could contribute to vaccine strategies for preventing infection by A. baumannii.

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Pertussis vaccination in a cohort of older Australian adults following a cocooning vaccination program

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): A. Dyda, P. McIntyre, S. Karki, C.R. MacIntyre, A.T. Newall, E. Banks, J. Kaldor, B. Liu
BackgroundWhile recommendations to vaccinate adults against pertussis exist, information on uptake for adult tetanus-diphtheria-pertussis vaccine (Tdap) among older adults is limited.MethodsWe used data from the 45 and Up Study, a prospective cohort of adults aged ≥45 years who completed a questionnaire between 2012 and 2014 asking about pertussis vaccination. We evaluated Tdap uptake following a program providing free vaccine for adults in contact with young children between 2009 and 2012.ResultsAmong 91,432 adults (mean age = 66.3 years, SD = 9.6), 3.1% (n = 2823) reported receiving Tdap prior to the program. This increased seven-fold to 21.8% (n = 19898) after the program finished. Tdap coverage was almost twice as high in women compared to men and among adults more likely to be grandparents than those not.ConclusionThese findings suggest that funding for a targeted program can help to substantially increase vaccination coverage as well as decrease disparities in the uptake of Tdap in different sub-groups.

https://ift.tt/2JOCWQs

Intranasal inoculate of influenza virus vaccine against lethal virus challenge

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Xueting Fan, Qiudong Su, Feng Qiu, Yao Yi, Liping Shen, Zhiyuan Jia, Pu Liang, Yening Zou, Shengli Bi
Vaccine adjuvants are essential for enhancing immune responses during vaccination. However, only a limited number of safe and effective adjuvants, especially mucosal adjuvants, are available for use in vaccines. The development of a practically applicable mucosal adjuvant is therefore urgently needed. Here, we showed that the non-toxic CTA1-DD adjuvant, which combined the full enzymatic activity of the A1 subunit of cholera toxin (CT) with two immunoglobulin-binding domains of Staphylococcus aureus protein A (SpA), promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal administration with H1N1 split vaccine in mice. We demonstrated that CTA1-DD-adjuvant vaccine provided 100% protection against mortality and greatly reduced morbidity in a mouse model. We also showed that addition of CTA1-DD to the vaccine elicited significantly higher hemagglutination inhibition titers and IgG antibodies in sera than alum adjuvant. Furthermore, CTA1-DD significantly promoted the production of mucosal secretory IgA in lung lavages and vaginal lavages. We also showed that CTA1-DD could be used as a mucosal adjuvant to enhance T cell responses. Our results clearly indicated that CTA1-DD contributed to the elicitation of a protective cell-mediated immune response required for efficacious vaccination against influenza virus, which suggested that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for respiratory diseases and other mucosal diseases.

https://ift.tt/2MtFHIQ

Caregiver recall in childhood vaccination surveys: Systematic review of recall quality and use in low- and middle-income settings

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Rakesh N. Modi, Carina King, Naor Bar-Zeev, Tim Colbourn
IntroductionHigh population coverage is key to the impact of vaccines. However, vaccine coverage estimates in low- and middle-income countries (LMICs) have repeatedly been shown to be of poor quality. LMICs often rely on 'caregiver recall' of vaccination, the validity and collection method of which remains uncertain. We aimed to critique the quality of caregiver recall and make recommendations for its collection and use.MethodsWe performed a systematic review for methods assessing childhood vaccination coverage in LMICs. We searched Medline using variations of the key terms: (child) AND (vaccinat^∗) AND (survey OR recall OR coverage) AND (reliab^∗ OR valid^∗). We selected articles assessing the quality of recall in LMICs and extracted reported validity, reliability and completeness. We synthesised recommendations on collecting, analysing and presenting caregiver recall for varying resource availabilities.ResultsOf 1268 articles, 134 full texts were screened and eight were included for review. There was heterogeneity in study designs, ways of incorporating recall data and outcomes measured. Sensitivity of recall was 41–98%; specificity was 12–80%. There was a dearth of reliability measures and no consistent method for dealing with data incompleteness.ConclusionThere are quality concerns with caregiver recall and difficulty in assessing it given the lack of a 'gold standard' for vaccine status. To improve coverage estimates and the impact of vaccines, caregiver recall should be used. Other recommendations include: recall is included for those presenting vaccine records; missing data is imputed; recall and record quality are assessed in a sub-sample; and sensitivity analyses are performed.

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Tumor lysate-loaded Bacterial Ghosts as a tool for optimized production of therapeutic dendritic cell-based cancer vaccines

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): N. Dobrovolskienė, V. Pašukonienė, A. Darinskas, J.A. Kraśko, K. Žilionytė, A. Mlynska, Ž. Gudlevičienė, E. Mišeikytė-Kaubrienė, V. Schijns, W. Lubitz, P. Kudela, M. Strioga
Cancer immunotherapy with dendritic cell (DC)-based vaccines has been used to treat various malignancies for more than two decades, however generally showed a limited clinical success. Among various factors responsible for their modest clinical activity is the lack of universally applied, standardized protocols for the generation of clinical-grade DC vaccines, capable of inducing effective anti-tumor immune responses. We investigated Bacterial Ghosts (BGs) – empty envelopes of Gram-negative bacteria – as a tool for optimized production of DC vaccines. BGs possess various intact cell surface structures, exhibiting strong adjuvant properties required for the induction of DC maturation, whereas their empty internal space can be easily filled with a source tumor antigens, e.g. tumor lysate. Hence BGs emerge as an excellent platform for both the induction of immunogenic DC maturation and loading with tumor antigens in a single-step procedure. We compared the phenotype, cytokine secretion profile, functional activity and ability to induce immunogenic T-cell responses in vitro of human monocyte-derived DCs generated using BG platform and DCs matured with widely used lipopolysaccharide (LPS) plus interferon-γ cocktail and loaded with tumor lysate. Both approaches induced DC maturation, however BG-based protocol was superior to LPS-based protocol in terms of the ability to induce DCs with a lower tolerogenic potential, resulting in a more robust CD8⁺ T cell activation and their functional activity as well as significantly lower induction of regulatory T cells. These superior parameters are attributed, at least in part, to the ability of BG-matured DCs to resist potential immunosuppressive and pro-tolerogenic activity of various tumor cell lysates, including melanoma, renal carcinoma and glioblastoma.

https://ift.tt/2t1dAZv

Protection against transplacental transmission of moderately virulent classical swine fever virus using live marker vaccine “CP7_E2alf”

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Julia Henke, Jolene Carlson, Laura Zani, Simone Leidenberger, Theresa Schwaiger, Kore Schlottau, Jens P. Teifke, Charlotte Schröder, Martin Beer, Sandra Blome
Classical swine fever (CSF) remains as one of the most important infectious diseases of swine. While prophylactic vaccination is usually prohibited in free countries with industrialized pig production, emergency vaccination is still foreseen. In this context, marker vaccines are preferred as they can reduce the impact on trade.The live-attenuated Suvaxyn® CSF Marker vaccine by Zoetis (based on pestivirus chimera "CP7_E2alf"), was recently licensed by the European Medicines Agency. Its efficacy for the individual animal had been shown in prior studies, but questions remained regarding protection against transplacental transmission. To answer this question, a trial with eight pregnant sows and their offspring was performed as prescribed by the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Six of the sows were intramuscularly vaccinated on day 44 of gestation, while the other two remained as unvaccinated controls. All sows were challenged with the moderately virulent CSFV strain "Roesrath" and euthanized shortly before the calculated farrowing date. Sows and piglets were grossly examined and necropsied. Organs (spleen, tonsil, lymph node, and kidney), EDTA-blood and serum were collected from all animals. All samples were tested for antibodies against CSFV glycoproteins E2 and E^rns as well as CSFV (virus, antigen and genome). It could be demonstrated that the vaccine complies with all requirements, i.e. no virus was found in the blood of vaccinated sows and their fetuses, and no antibodies were found in the serum of the fetuses from the vaccinated sows. All controls were valid.Thus, it was demonstrated that a single dose vaccination in the sows efficiently protected the offspring against transplacental infection with a moderately virulent CSFV strain.

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Editorial Board/Aims and Scope

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29

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Flagellin is a Th1 polarizing factor for human CD4+ T cells and induces protection in a murine neonatal vaccination model of rotavirus infection

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Rosario Guadalupe Labastida-Conde, Oscar Ramírez-Pliego, Mercedes Peleteiro-Olmedo, Delia Vanessa Lopez-Guerrero, Oscar Daniel Badillo-Godinez, María de Lourdes Gutiérrez-Xicoténcatl, Gabriela Rosas-Salgado, África González-Fernández, Fernando R. Esquivel-Guadarrama, M. Angélica Santana
Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4⁺ T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates. Among them, flagellin, the TLR5 ligand, is effective at very low doses; prior immunity to flagellin does not impair its adjuvant activity. Human CD4⁺ and CD8⁺ T cells express TLR5. We found that flagellin induces the expression of IFN-γ, IL-1β and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4⁺ T cells were activated in the presence of flagellin, there was high level of expression of IFN-γ in both neonates and adults. Furthermore, flagellin induced IFN-γ production in Th1 cells obtained from adult donors; in the Th2 population, it inhibited IL-4 cytokine production. Flagellin also promoted expression of the IFN-γ receptor in naive CD4⁺ T cells from neonates and adults. To test the adjuvant capacity of flagellin in vivo, we used a murine neonate vaccination model for infection with rotavirus, a pathogen responsible for severe diarrhea in young infants. Using the conserved VP6 antigen, we observed an 80% protection against rotavirus infection in the presence of flagellin, but only in those mice previously primed in the neonatal period. Our data suggest that flagellin could be an attractive adjuvant for achieving a Th1 response.

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Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2012–2016

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): William L. Walker, Susan L. Hills, Elaine R. Miller, Marc Fischer, Ingrid B. Rabe
BackgroundIn March 2009, the U.S. Food and Drug Administration licensed an inactivated Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [IXIARO®]) for use in persons aged ≥17 years. In 2013, licensure was extended to include children aged ≥2 months. A previous analysis reviewed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from May 2009 through April 2012.MethodsWe reviewed adverse events reported to VAERS following JE-VC administered from May 1, 2012 through April 30, 2016. Adverse event reporting rates were calculated using 802,229 doses distributed.ResultsDuring the 4-year period, 119 adverse event reports were received for a reporting rate of 14.8 per 100,000 doses distributed. Nine (8%) adverse events were classified as serious for a reporting rate of 1.1 per 100,000 distributed. The most commonly reported event was hypersensitivity (n = 24; 20%) for a rate of 3.0 per 100,000 doses distributed; 1 anaphylaxis event was reported. Ten (8%) neurologic events were reported for a rate of 1.2 per 100,000 doses distributed; 2 events were classified as seizures. Sixty-three (53%) adverse events occurred after a first dose of JE-VC. Eighty (67%) adverse events occurred after administration of JE-VC with other vaccines. Eleven (9%) adverse events were reported in children; 1 was considered serious.ConclusionsThese data continue to support the generally favorable safety profile of JE-VC. Reporting rates of adverse events were similar to those of the previous analysis. Although reporting rates of adverse events in children could not be calculated, there were low numbers of reported events in this age group. Post-licensure adverse event surveillance for this relatively new vaccine continues to be important to monitor adverse event reporting rates and identify possible rare serious events.

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Protection by universal influenza vaccine is mediated by memory CD4 T cells

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Sophie A. Valkenburg, Olive T.W. Li, Athena Li, Maireid Bull, Thomas A. Waldmann, Liyanage P. Perera, Malik Peiris, Leo L.M. Poon
There is a diverse array of influenza viruses which circulate between different species, reassort and drift over time. Current seasonal influenza vaccines are ineffective in controlling these viruses. We have developed a novel universal vaccine which elicits robust T cell responses and protection against diverse influenza viruses in mouse and human models. Vaccine mediated protection was dependent on influenza-specific CD4⁺ T cells, whereby depletion of CD4⁺ T cells at either vaccination or challenge time points significantly reduced survival in mice. Vaccine memory CD4⁺ T cells were needed for early antibody production and CD8⁺ T cell recall responses. Furthermore, influenza-specific CD4⁺ T cells from vaccination manifested primarily Tfh and Th1 profiles with anti-viral cytokine production. The vaccine boosted H5-specific T cells from human PBMCs, specifically CD4⁺ and CD8⁺ T effector memory type, ensuring the vaccine was truly universal for its future application. These findings have implications for the development and optimization of T cell activating vaccines for universal immunity against influenza.

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A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among older adults

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Marc Baay, Kaatje Bollaerts, Thomas Verstraeten
IntroductionNew adjuvants have been developed to improve the efficacy of vaccines and for dose-sparing capacity and may overcome immuno senescence in the elderly. We reviewed the safety of newly-adjuvanted vaccines in older adults.MethodsWe searched Medline for clinical trials (CTs) including new adjuvant systems (AS01, AS02, AS03, or MF59), used in older adults, published between 01/1995 and 09/2017. Safety outcomes were: serious adverse events (SAEs); solicited local and general AEs (reactogenicity); unsolicited AEs; and potentially immune-mediated diseases (pIMDs). Standard random effects meta-analyses were conducted by type of safety event and adjuvant type, reporting Relative Risks (RR) with 95% confidence intervals (95% CI).ResultsWe identified 1040 publications, from which we selected 7, 7, and 12 CTs on AS01/AS02, AS03 and MF59, respectively. 47,602 study participants received newly-adjuvanted vaccine and 44,521 control vaccine, or placebo. Rates of SAEs (RR = 0.99, 95% CI = 0.96–1.02), deaths (RR = 0.99, 95% CI = 0.92–1.06) and pIMDs (RR = 0.94, 95% CI = 0.79–1.1) were comparable in newly-adjuvanted and control groups. Vaccine-related SAEs occurred in <1% of the subjects in both groups. The reactogenicity of AS01/AS02 and AS03 adjuvanted vaccines was higher compared to control vaccines, whereas MF59-adjuvanted vaccines resulted only in more pain. Grade 3 reactogenicity was reported infrequently, with fatigue (RR = 2.48, 95% CI = 1.69–3.64), headache (RR = 2.94, 95% CI = 1.24–6.95), and myalgia (RR = 2.68, 95% CI = 1.86–3.80) occurring more frequently in newly-adjuvanted groups. Unsolicited AEs occurred slightly more frequently in newly-adjuvanted groups (RR = 1.04, 95% CI = 1.00–1.08).ConclusionsOur review suggests that, within the clinical trial setting, the use of new adjuvants in older adults has not led to any safety concerns, with no increase in SAEs or fatalities. Higher rates for solicited AEs were observed, especially for AS01/AS02 and AS03 adjuvanted vaccines, but AEs were mostly mild and transient. Further evidence will need to come from the use of new adjuvants in the real-world setting, where larger numbers can be studied to potentially detect rare reactions.

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Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Vivek Vaidya, Rajeev Dhere, Snehal Agnihotri, Ravindra Muley, Sanjay Patil, Amit Pawar
Foetal Bovine Serum (FBS) and porcine trypsin are one of the essential raw materials used in the manufacturing of cell culture based viral vaccines. Being from animal origin, these raw materials can potentially contaminate the final product by known or unknown adventitious agents. The issue is more serious in case of live attenuated viral vaccines, where there is no inactivation step which can take care of such adventitious agents. It is essential to design production processes which can offer maximum viral clearance potential for animal origin products. Ultraviolet-C irradiation is known to inactivate various adventitious viral agents; however there are limited studies on ultraviolet inactivation of viruses in liquid media. We obtained a recently developed UVivatec ultraviolet-C (UV-C) irradiation based viral clearance system for evaluating its efficacy to inactivate selected model viruses. This system has a unique design with spiral path of liquid allowing maximum exposure to UV-C light of a short wavelength of 254 nm. Five live attenuated vaccine viruses and four other model viruses were spiked in tissue culture media and exposed to UV-C irradiation. The pre and post UV-C irradiation samples were analyzed for virus content to find out the extent of inactivation of various viruses. These experiments showed substantial log reduction for the majority of the viruses with few exceptions based on the characteristics of these viruses. Having known the effect of UV irradiation on protein structure, we also evaluated the post irradiation samples of culture media for growth promoting properties using one of the most fastidious human diploid cells (MRC-5). UV-C exposure did not show any notable impact on the nutritional properties of culture media. The use of an UV-C irradiation based system is considered to be promising approach to mitigate the risk of adventitious agents in cell culture media arising through animal derived products.

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Meningococcal C conjugate vaccine effectiveness before and during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C/cc11, Tuscany, Italy

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Patrizio Pezzotti, Alessandro Miglietta, Arianna Neri, Cecilia Fazio, Paola Vacca, Fabio Voller, Giovanni Rezza, Paola Stefanelli
IntroductionIn Tuscany, Italy, where a universal immunization program with monovalent meningococcal C conjugate vaccine (MCC) was introduced in 2005, an outbreak of invasive meningococcal disease (IMD) due to the hypervirulent strain of Neisseria meningitidis C/cc11 occurred in 2015–2016, leading to an immunization reactive campaign using either the tetravalent (ACWY) meningococcal conjugate or the MCC vaccine. During the outbreak, IMD serogroup C (MenC) cases were also reported among vaccinated individuals. This study aimed to characterize meningococcal C conjugate vaccines (MenC-vaccines) failures and to estimate their effectiveness since the introduction (2005–2016) and during the outbreak (2015–2016).MethodsMenC cases and related vaccine-failures were drawn from the National Surveillance System of Invasive Bacterial Disease (IBD) for the period 2006–2016. A retrospective cohort-study, including the Tuscany' population of the birth-cohorts 1994–2014, was carried out. Based on annual reports of vaccination, person-years of MenC-vaccines exposed and unexposed individuals were calculated by calendar-year, birth-cohort, and local health unit. Adjusted (by birth-cohort, local health unit, and calendar-year) risk-ratios (ARR) of MenC invasive disease for vaccinated vs unvaccinated were estimated by the Poisson model. Vaccine-effectiveness (VE) was estimated as: VE = 1-ARR.ResultsIn the period 2006–2016, 85 MenC-invasive disease cases were reported; 61 (71.8%) from 2015 to 2016. Twelve vaccine failures occurred, all of them during the outbreak. The time-interval from immunization to IMD onset was 20 days in one case, from 9 months to 3 years in six cases, and ≥7 years in five cases. VE was, 100% (95%CI not estimable, p = 0.03) before the outbreak (2006–2014) and 77% (95%CI 36–92, p < 0.01) during the outbreak; VE was 80% (95%CI 54–92, p < 0.01) during the overall period.ConclusionsIn Tuscany, MenC-vaccine failures occurred exclusively during the 2015–2016 outbreak. Most of them occurred several years after vaccination. VE during the outbreak-period was rather high supporting an effective protection induced by MenC-vaccines.

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A flagellin-adjuvanted PED subunit vaccine improved protective efficiency against PEDV variant challenge in pigs

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Qianniu Li, Zhichao Xu, Tingting Wu, Ouyang Peng, Licheng Huang, Yun Zhang, Chunyi Xue, Zhifen Wen, Qingfeng Zhou, Yongchang Cao
PEDV variants, causing severe diarrhea in neonatal suckling piglets with a mortality rate up to 100%, have being epidemic since late 2010 in china. To meet the pressing need of safe and cost-efficient PED maternal vaccines against PEDV variant, we vaccinated growing piglets with a flagellin-adjuvanted PED vaccine rSF-COE-3D by injection at Houhai acupoint. The vaccination not only enhanced the antibody responses of serum IgG/IgA, mucosal IgA and serum neutralizing antibody, but also improved the production of IFN-γ and IL-4. Moreover, rSF-COE-3D could provide a better protection against the challenge of a high pathogenic PEDV variant, with less diarrhea pigs, less pigs with detectable PEDV shed, lower rank values of feces and less apparent lesions and inflammation in duodenum of the PEDV infected pigs. The improved protective efficiency of rSF-COE-3D compared with COE was mostly benefited from the enhanced production of serum IgA, mucosal IgA in feces and serum neutralizing antibody titers. Taken together, our data suggest that rSF-COE-3D would be a novel efficient PED vaccine.

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Childhood vaccines in Uganda and Zambia: Determinants and barriers to vaccine coverage

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): David E. Phillips, Joseph L. Dieleman, Jessica C. Shearer, Stephen S. Lim
BackgroundImproving childhood vaccine coverage is a priority for global health, but challenging in low and middle-income countries. Although previous research has sought to measure determinants of vaccination, most has limitations. We measure determinants using a clearly-defined hypothetical model, multi-faceted data, and modeling strategy that makes full use of the hypothesis and data.MethodsWe use linked, cross-sectional survey data from households, health facilities, patients and health offices in Uganda and Zambia, and Bayesian Structural Equation Modeling to quantify the proportion of variance in childhood vaccination that is explained by key determinants, controlling for known confounding.ResultsWe find evidence that the leading determinant of vaccination is different for different outcomes. For three doses of pentavalent vaccine, intent to vaccinate (on the part of the mother) is the leading driver, but for one dose of the vaccine, community access is a larger factor. For pneumococcal conjugate vaccine, health facility readiness is the leading driver. Considering specifically-modifiable determinants, improvements in cost, facility catchment populations and staffing would be expected to lead to the largest increase in coverage according to the model.ConclusionsThis analysis measures vaccination determinants using improved methods over most existing research. It provides evidence that determinants should be approached in the context of relevant outcomes, and evidence of specific determinants that could have the greatest impact in these two countries, if targeted. Future studies should seek to improve our analytic framework, apply it in different settings, and utilize stronger study designs. Programs that focus on a particular determinant should use these results to select an outcome that is appropriate to measure their effectiveness. Vaccination programs in these countries should use our findings to better target interventions and continue progress against vaccine preventable diseases.

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Multi-clade H5N1 virus-like particles: Immunogenicity and protection against H5N1 virus and effects of beta-propiolactone

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Peter Pushko, Irina Tretyakova, Rachmat Hidajat, Xiangjie Sun, Jessica A. Belser, Terrence M. Tumpey
During the past decade, H5N1 highly pathogenic avian influenza (HPAI) viruses have diversified genetically and antigenically, suggesting the need for multiple H5N1 vaccines. However, preparation of multiple vaccines from live H5N1 HPAI viruses is difficult and economically not feasible representing a challenge for pandemic preparedness. Here we evaluated a novel multi-clade recombinant H5N1 virus-like particle (VLP) design, in which H5 hemagglutinins (HA) and N1 neuraminidase (NA) derived from four distinct clades of H5N1 virus were co-localized within the VLP structure. The multi-clade H5N1 VLPs were prepared by using a recombinant baculovirus expression system and evaluated for functional hemagglutination and neuraminidase enzyme activities, particle size and morphology, as well as for the presence of baculovirus in the purified VLP preparations. To remove residual baculovirus, VLP preparations were treated with beta-propiolactone (BPL). Immunogenicity and efficacy of multi-clade H5N1 VLPs were determined in an experimental ferret H5N1 HPAI challenge model, to ascertain the effect of BPL on immunogenicity and protective efficacy against lethal challenge. Although treatment with BPL reduced immunogenicity of VLPs, all vaccinated ferrets were protected from lethal challenge with influenza A/VietNam/1203/2004 (H5N1) HPAI virus, indicating that multi-clade VLP preparations treated with BPL represent a potential approach for pandemic preparedness vaccines.

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Rapid development and evaluation of a live-attenuated QX-like infectious bronchitis virus vaccine

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Yun Zhang, Songjian Huang, Yuyao Zeng, Chunyi Xue, Yongchang Cao
Infectious bronchitis (IB) is an acute, highly contagious disease, which causes economic losses to the poultry industry worldwide. To control the disease, biosecurity and vaccination are required. In the current research, we rapidly attenuated a QX-like IBV field strain ZYY-2014 using passage in embryos at limiting dilution and tested the safety and efficacy of the attenuated Chinese QX-like IBV strain ZYYR-2014 in 1-day-old specific-pathogen-free (SPF) chickens through spray route. Our result revealed that the attenuated strain presented a decreased pathogenicity in 1-day-old chickens. The strain ZYY-2014 inoculated birds presented typical IBV clinical signs with a mortality of 43%, while the attenuated strain ZYYR-2014 inoculated birds remained healthy. The strain ZYYR-2014 also presented stronger antibody responses and lower viral loads in tracheas, lungs and kidneys. When vaccinated through spray route into 1-day-old SPF chickens, our data suggest a potential of the attenuated ZYYR-2014 strain as a vaccine candidate applied in hatchery, which can contribute in preventing the QX-like IBV infections. Furthermore, attenuation by passage at limiting dilution could be applied for rapid vaccine development against emerging strains.

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Cost-effectiveness of nonavalent HPV vaccination among males aged 22 through 26 years in the United States

Publication date: 5 July 2018
Source:Vaccine, Volume 36, Issue 29
Author(s): Harrell W. Chesson, Elissa Meites, Donatus U. Ekwueme, Mona Saraiya, Lauri E. Markowitz
IntroductionIn the United States, routine human papillomavirus (HPV) vaccination is recommended for females and males at age 11 or 12 years; the series can be started at age 9 years. Vaccination is also recommended for females through age 26 years and males through age 21 years. The objective of this study was to assess the health impact and cost-effectiveness of harmonizing female and male vaccination recommendations by increasing the upper recommended catch-up age of HPV vaccination for males from age 21 to age 26 years.MethodsWe updated a published model of the health impact and cost-effectiveness of 9-valent human papillomavirus vaccine (9vHPV). We examined the cost-effectiveness of (1) 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years, and (2) an expanded program including males through age 26 years.ResultsCompared to no vaccination, providing 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years cost an estimated $16,600 (in 2016 U.S. dollars) per quality-adjusted life year (QALY) gained. The estimated cost per QALY gained by expanding male vaccination through age 26 years was $228,800 and ranged from $137,900 to $367,300 in multi-way sensitivity analyses.ConclusionsThe cost-effectiveness ratios we estimated are not so favorable as to make a strong economic case for recommending expanding male vaccination, yet are not so unfavorable as to preclude consideration of expanding male vaccination. The wide range of plausible results we obtained may underestimate the true degree of uncertainty, due to model limitations. For example, the cost per QALY might be less than our lower bound estimate of $137,900 had our model allowed for vaccine protection against re-infection. Models that specifically incorporate men who have sex with men (MSM) are needed to provide a more comprehensive assessment of male HPV vaccination strategies.

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Η λίστα ιστολογίων μου

Παρασκευή 15 Ιουνίου 2018

Abstract

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