Head and Neck Diseases by Alexandros G.Sfakianakis: Ιουλίου 2017

Δευτέρα 31 Ιουλίου 2017

Acquired capillary haemangioma of the eyelid in a 10-year-old boy

A 10-year-old boy presented with painless, gradually increasing mass in right upper lid without preceding trauma for the past 2 months. On examination, the mass was bluish red, soft to firm in consistency which bleeds on touch. Contrast-enhanced CT showed a well-defined heterogeneously enhancing mass lesion without any continuity with the underlying bone or the orbital cavity. Complete excision of the mass was performed under general anaesthesia, subsequent histopathological examination showed findings consistent with an acquired variant of capillary haemangioma. At the end of 1 year, patient is cosmetically fine without any recurrence/morbidity.

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Carotid dissection presenting as a prolonged cluster-like headache in a patient with episodic cluster headache

We present a patient with known episodic cluster headache, who presented with cluster-like headache in the course of internal carotid artery dissection (ICAD) and discuss possible pathophysiological links between the two diseases. It is well known that cluster-like headache could be the presenting symptom of ICAD. However, ICAD occurring in a patient with a known episodic cluster headache was only once previously described. In the end of the manuscript, we propose red flags to help clinicians differentiate between primary cluster headache and cluster-like attacks masking underlying ICAD. Finally, we raise the question whether at least some proportion of those patients with cluster headache and Horner syndrome previously classified as a primary headache disorder might have been secondary cases to ICAD.

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The non-resolving lung cavity: a case of pulmonary cystic echinococcosis

The authors report a case of a 20-year-old woman who was diagnosed with pulmonary cystic echinococcosis. She was admitted to hospital with a 1-week history of unresolving cough, coloured sputum with occasional haemoptysis and fever despite oral antibiotics. Radiology revealed a cavitating right lower lobe lung abscess. After 4 weeks of treatment, follow-up radiology showed incomplete resolution. Bronchoscopy revealed a white, avascular cystic lesion in the right lower lobe and serology testing for Echinococcus granulosus was positive. Repeat imaging eventually confirmed the cystic lesion with the 'air bubble'sign. A thorough travel history, a high index of clinical suspicion and close follow-up are essential in making a diagnosis of pulmonary cystic echinococcosis.

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Incidental finding of persistent left superior vena cava after 'bubble study verification of central venous catheter

We report a case of a patient with septic shock who underwent central venous catheter placement in the left internal jugular vein, and a bedside ultrasound 'bubble study' revealed venous cannulation. A chest X-ray postprocedure revealed concern for arterial system catheterisation. However, the possibility of a persistent left superior vena cava was discussed and confirmed with a formal transthoracic echocardiogram and CT. This case demonstrates the importance of ultrasound-guided visualisation of anatomical structures in real time during central venous catheterisation. Other similar cases from the literature are briefly described.

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Turbulent tackle: a novel surgical approach to a rugby-related jejunal perforation

Viscus perforation in the context of blunt-force abdominal trauma is a rarity. Within a sporting context, it is especially rare. However, the increasing physicality observed in rugby union, both in the amateur and professional setting, has resulted in a higher rate of serious injury. We report a novel laparoscopic surgical approach to the management of a traumatic jejunal perforation sustained on the playing field in a previously fit and healthy 28-year-old.

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Huge cardiac myxoma in pregnancy

A 28-year-old pregnant woman presented at 28 weeks of gestation. She was diagnosed to have a left atrial myxoma 2 years earlier, but was lost to follow-up. During this pregnancy, the transthoracic echocardiography showed a 9 cm mass in the left atrium obstructing mitral valve inflow, interfering with mitral valve closure, causing severe mitral regurgitation and severe pulmonary hypertension. However, there were no clinical signs of pulmonary and systemic congestion or obstruction. Based on the clinical symptoms of the patient, the echocardiographic findings and the term of her pregnancy, the patient decided to schedule for a vaginal delivery with surgical correction after delivery. She gave birth at 32 weeks of gestation. During labour, pulmonary oedema developed but was detected early and it responded to therapy. Two weeks after delivery, a right anterior thoracotomy was performed to facilitate the removal of the left atrial myxoma and repair of the mitral valve.

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Peripheral hepatojejunostomy: a last resort palliative solution in Greece during the economic crisis

The geographical distribution of Greece and the growing proportion of uninsured patients make imperative the need for effective and efficient palliative solutions regarding obstructive jaundice due to hepatic malignancy, while repeated endoscopic interventions and all associated materials are either not accessible to the whole population or not even available on a daily basis due to the economic crisis and the difficulties on the hospital supply. On this basis, palliative hepatojejunostomy, introduced more than 50 years ago, could be revisited in the Greek reality in very selected cases and under these special circumstances. We report on two patients with locally advanced hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma, respectively, who were treated with a combination of double hepaticojejunostomy with peripheral hepatojejunostomy or peripheral hepatoejunostomy alone, respectively. Both patients experienced an adequate decompression of the biliary tract over more than a year. Palliative hepatojejunostomy could be an ultimate solution for selected patients and circumstances in Greece during the economic crisis.

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Embryonal carcinoma presenting as a calcified solitary testicular mass on ultrasound

A 24-year-old man presented with a 2-week history of a painless right testicular mass; ultrasound demonstrated a dense, solitary calcified mass. The patient elected observation after further workup showed no evidence of metastasis.

A repeat ultrasound 3 months later showed interval growth and the patient underwent right radical orchiectomy. Pathology was consistent with pure embryonal carcinoma of the testis. Calcified testicular masses are typically benign but do carry a differential of spermatic granuloma, large-cell calcifying Sertoli cell tumour, trauma, tuberculosis, filariasis, calcified Leydig cell tumour and burned-out testicular tumour.

To our knowledge, this is the first case report of pure embryonal carcinoma presenting as a solitary calcified testicular mass.

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Wernickea{euro}™s encephalopathy associated with liver abscess

Wernicke's encephalopathy is a rare neurological disorder caused by thiamine deficiency, characterised by ocular motor dysfunction, ataxia and impairment in consciousness. It predominantly affects brain regions with a high metabolic rate such as mammillary bodies, medial thalamic nuclei, the tectal region and the cerebellum. Although chronic alcoholism is the most common cause of Wernicke's encephalopathy, various other conditions not related to alcohol consumption such as bariatric surgery, acute pancreatitis, hyperemesis gravidarum, prolonged fasting and gastrointestinal surgery have been implicated in its aetiology. We report the case of a patient who underwent surgery for liver abscess and subsequently developed Wernicke's encephalopathy; he showed a positive response to thiamine supplementation. This is the first report describing liver abscess as the cause of Wernicke's encephalopathy.

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Pseudo retinitis pigmentosa in a case of missed intraocular foreign body

A 35-year-old man presented with history of painless, progressive loss of vision in the left eye for the past 7 years. There was history of trauma to the same eye with an iron object 7 years prior. Fundus examination revealed pigmentary retinopathy (unilateral advanced retinitis pigmentosa (RP)-like picture). X-ray orbits were suspicious of retained intraocular foreign body (IOFB). CT orbits confirmed the presence of IOFB. Electroretinogram revealed depressed responses. Right eye examination was within normal limits. A diagnosis of siderosis bulbi with unilateral pseudo RP-like fundus was made. No surgical intervention was planned for IOFB in view of poor visual prognosis.

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Triggering of the abductor pollicis longus in association with deQuervain's tenosynovitis

DeQuervain's tenosynovitis is a common cause of radial-sided wrist pain. Symptoms result from a narrow first dorsal compartment and associated tendinosis of the enclosed extensor pollicis brevis and/or abductor pollicis longus (APL). Surgical intervention, offered when conservative measures fail to adequately relieve symptoms, requires a detailed understanding of potentially aberrant anatomy in order to avoid persistence or recurrence of symptoms. We describe a case whereby the patient presented with complaints of thumb triggering in extension and associated disabling first dorsal compartment tendinosis. Intraoperatively, after supernumerary tendons were identified and addressed, the APL was at risk for subluxation over a prominent fibroosseous ridge. Routine first dorsal compartment release alone may have failed to address all of this patient's pathology.

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Tuberculosis presenting as broncho-oesophageal fistula in a young healthy man

A 21-year-old Saudi man presented with a history of dysphagia and choking. CT scan of the chest showed clear evidence of chronic recurrent aspiration pneumonia in the left lung. It also showed a fistula connecting the left main bronchus to the oesophagus. Endoscopy showed clear opening on the oesophageal side. Bronchoscopy also confirmed the presence of a broncho-oesophageal fistula on the left bronchial side with the presence of secretions on swallowing. Bronchoalveolar lavage (BAL) was done and sent for mycobacterial tuberculosis culture. The fistula was closed with clips under endoscopic guidance, which alleviated his symptoms of dysphagia and choking. The BAL culture grew mycobacterial tubercle bacilli. The patient showed marked improvement after starting antitubercular therapy and was discharged to be followed up in the clinic.

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Anticuerpos antitiroideos: el daño en las células tiroideas

El organismo produce anticuerpos habitualmente. Este mecanismo es parte de la respuesta inmune natural ante la presencia de "invasores" en el organismo, como pueden ser los virus y las bacterias.

En determinadas circunstancias, algunas proteínas del organismo pueden ser atacadas por las células defensivas (anticuerpos). Cuando esto sucede, es posible que células del organismo sean dañadas o destruidas por error, ya que pueden provocar inflamación crónica, que conlleva daño en los tejido y alteración de su funcionamiento. Este fenómeno puede tener lugar en la tiroides, con lo cual la enfermedad recibe el "apellido" 'autoimnune'.

Los análisis para detectar anticuerpos que afectan a la tiroides suelen llevarse a cabo principalmente para diagnosticar una enfermedad tiroidea de origen autoinmune y para distinguirla de otras dolencias que se manifiestan en esta glándula.

Cuándo se solicita el análisis

En presencia de bocio (aumento del tamaño de la tiroides)
Cuando otras pruebas de la función tiroidea están alteradas
- T3 total
- T3 libre
- T4 libre
- TSH
- Tiroglobulina

Como método de control de la función tiroidea (revisiones) en personas sanas o en pacientes con enfermedad tiroidea autoinmune
En mujeres embarazadas que padecen alguna otra forma de enfermedad autoinmune

Los anticuerpos más frecuentes son:

Anti-TPO (Anticuerpos Antitiroideosanti-TPO, que bloquean la peroxidasa) y también se conocen como:
- Anticuerpos antimicrosómicos de la tiroides
- Anticuerpos microsómicos
- Anticuerpos contra peroxidasa de la tiroides
- TPOAb

Anticuerpos antitiroglobulina (TG Ab)
Anticuerpos anti-TSI (inmunoglobulina estimulante deltiroides)

Los TPOAb están elevados en los pacientes que tienen enfermedad de Hashimoto, o tiroiditis autoimmune. En esta condición, las células de la glándula tiroides sufren el ataque del sistema inmune y van siendo destruidas poco a poco. Los pacientes pueden presentarse en la consulta bien con enfermedad de Hashimoto o están en fase de desarrollar la enfermedad, con la consiguiente reducción de la función de la glándula tiroides. Se detectan niveles altos en prácticamente todos los casos de enfermedad de Hashimoto. También se ha observado una presencia elevada de TPOAb en más de la mitad -65%- de las personas con enfermedad de Graves.

Los TG Ab son anticuerpos que se encuentran típicamente elevados también en la enfermedad de Hashimoto, aunque no una proporción tan elevada de los casos.

El tercer grupo de anticuerpos, los anti-TSI, tienen como objetivo los receptores de la TSH (hormona estimulante de la tiroides) en la glándula tiroides, y los activan de una forma disfuncional. Esto estimula la producción excesiva de hormonas tiroideas. Constituyen la causa principal de enfermedad de Graves.

Es posible que tanto los anticuerpos que actúan contra la inmunoglobulina estimulante de la tiroides como los que interfieren en la actividad de la peroxidasa estén elevados en el hipotiroidismo (enfermedad de Hashimoto) y el hipertiroidismo (enfermedad de Graves).

Fase preclínica (sin síntomas)

Se han documentado casos en los que hay sujetos con niveles elevados de los tres tipos de anticuerpos sin que se haya manifestado síntoma alguno. Es posible que esto sea así antes de que el daño a la función tiroidea sea suficientemente significativo. No obstante, son personas en situación de riesgo de desarrollar enfermedades de la tiroides en el futuro, y se recomienda que en estos casos el médico efectúe revisiones periódicas de la función de la glándula.

La precaución indica que cualquier nivel, por leve que sea, de elevación de los anticuerpos sea considerado indicio de posible enfermedad en el futuro.

La entrada Anticuerpos antitiroideos: el daño en las células tiroideas se publicó primero en Cuida tu tiroides.

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The lymphocyte cytokinesis block micronucleus test in human populations occupationally exposed to vinyl chloride: a systematic review and meta-analysis

Publication date: Available online 31 July 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Claudia Bolognesi, Marco Bruzzone, Marcello Ceppi, Micheline Kirsch-Volders
Vinyl chloride (VC) is widely used in industry in the production of polyvinyl chloride (PVC), which is used to manufacture a large variety of materials. VC was classified as a known (Group 1) human carcinogen by IARC on the basis of increased risk for liver angiosarcoma and hepatocellular cancer, and the carcinogenicity of VC was shown to be mediated by a genotoxic mechanism. Following inhalation, the compound is rapidly absorbed and metabolized in the liver to the electrophilic metabolites chloroethylene-oxide and chloroacetaldehyde, which form DNA adducts that can be processed into point mutations in cancer-related genes detected in humans and rats exposed to VC. A number of genotoxicity biomarkers were applied in workers exposed to VC to detect early biological responses associated with the carcinogenesis process. The present systematic review analyzed the published studies in which the cytokinesis-block micronucleus assay in peripheral lymphocytes (L-CBMN) was applied in VC-exposed subjects. Thirteen out of fifteen retrieved studies performed in China showed increased MN frequencies (FR 1.92-3.98) associated with increased cumulative exposure or employment time. Twofold and more than threefold increases were detected in PVC-exposed workers exposed to a mean of 50ppm of VC in the former Yugoslavia and in South India, respectively. The meta-analysis of MN frequency from six eligible studies confirmed this tendency (pooled MR 2.32 − 95% CI 1.64-3.27). The benchmark dose lower limit for 10% excess risk (BMDL 10) calculated from three studies resulted in an estimated exposure limit of 0.03-0.07mg/m³. Overall the results of this review showed the need for further studies, especially because PVC products from China may contain high levels of uncoupled VCM that could represent a source of exposure to workers and consumers. Moreover, the results underline the importance of re-evaluating the recommended exposure limits using new biomonitoring methods in addition to MN.

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Atopic Dermatitis: Early Treatment in Children

Opinion Statement

Therapeutic regimens for the treatment and long-term management of Atopic Dermatitis (AD) have a twofold objective of decreasing skin inflammation and repairing the defective skin barrier. Essential treatments for AD in children should include topical moisturizers for skin hydration and prevention of flares, topical anti-inflammatory medications (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitor), allergen/irritant avoidance, and treatment of skin infections. Treatment regimens should be severity-based and implemented in a stepwise approach tailored to the individual patient. This stepwise approach includes initial use of emollients, gentle skin care, and escalating to more potent anti-inflammatory treatments as the disease severity increases. Currently available systemic medications should be reserved for the presence of recalcitrance to topical therapies due to associated toxicities.

We believe that early treatment of AD is not only essential in treating the skin disease but also in preventing the development of additional atopic diseases, such as food allergy, asthma, and allergic rhinitis. The defective skin barrier of AD permits a route of entry for food and environmental allergens, and upon exposure, keratinocytes secrete thymic stromal lymphopoietin, which activates Type 2 immune responses. This Type 2 immune response initiates the atopic march and the subsequent diseases that are seen. This review highlights treatment options and strategies in pediatric AD therapy with an emphasis on early therapy. Supporting evidence on the efficacy and safety of each intervention will be discussed.

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Phylogenetic diversity and functional characterization of the Manila clam microbiota: a culture-based approach

Abstract

According to the hologenome theory, the microbiota contributes to the fitness of the holobiont having an important role in its adaptation, survival, development, health, and evolution. Environmental stress also affects the microbiota and its capability to assist the holobiont in coping with stress factors. Here, we analyzed the diversity of cultivable bacteria associated with Manila clam tissues (mantle, gills, hemolymph) in two non-contaminated sites (Portugal and France) and one metal-contaminated site (Portugal). A total of 240 isolates were obtained. Representative isolates (n = 198) of the overall diversity were identified by 16S rDNA sequencing and subjected to functional characterization. Isolates affiliated with Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. Proteobacteria (mostly Pseudoalteromonadaceae and Vibrionaceae) were dominant in non-contaminated sites while Actinobacteria (mostly Microbacteriaceae) dominated in the metal-contaminated site. The main factor affecting the microbiota composition was contamination. No significant differences were observed between clam tissues and geographic regions. Several isolates tested positive for antibacterial activity, biofilm formation, protease, and siderophore production. The results show that the Manila clam harbors a diverse microbiota that may contribute to clam protection and overall fitness, as well as to its adaptation to stressful environments. In addition, the Manila clam microbiota is revealed as a promising source of novel probiotics with potential application in aquaculture.

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Outcome of patients with lung adenocarcinoma with transformation to small-cell lung cancer following tyrosine kinase inhibitors treatment: A Systematic Review and Pooled Analysis

Publication date: Available online 31 July 2017
Source:Cancer Treatment Reviews
Author(s): Elisa Roca, Cristina Gurizzan, Vito Amoroso, William Vermi, Vittorio Ferrari, Alfredo Berruti
BackgroundLung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported.MethodsWe performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases.ResultsTwenty-five eligible publications were identified, contributing to 39 patients. The median time from initial diagnosis of lung adenocarcinoma to the transformation to SCLC (ttSCLC) was 19 months (range 1-61 months). The median survival after SCLC diagnosis was 6 months. Female gender was significantly associated with longer ttSCLC at the multivariable analysis. Smoking status seemed to be associated with worse prognosis after the diagnosis of SCLC.ConclusionIn this series of published cases, the transformation to a SCLC phenotype after an initial diagnosis of lung adenocarcinoma following TKI therapy appeared to be a late phenomenon. The prognosis after SCLC diagnosis is poor and current treatment strategies derived from primary SCLC seem to be largely inefficacious. New therapies are needed in the management of transformed SCLC.

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Immunotherapy in ovarian, endometrial and cervical cancer: state of the art and future perspectives

Publication date: Available online 31 July 2017
Source:Cancer Treatment Reviews
Author(s): Jole Ventriglia, Immacolata Paciolla, Carmela Pisano, Sabrina Chiara Cecere, Marilena Di Napoli, Rosa Tambaro, Daniela Califano, Simona Losito, Giosuè Scognamiglio, Sergio Venanzio Setola, Laura Arenare, Sandro Pignata, Chiara Della Pepa
The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy. Immunotherapy, including a number of approaches, checkpoint inhibitors, adoptive cellular transfer, vaccines, has experienced a remarkable growth in the last few years and it is already an available option in melanoma, lung and renal malignancies. We reviewed the main findings about the immune microenvironment in ovarian, endometrial and cervical cancer with a special focus on the clinical data, the therapeutic implications and the most promising novel agents.

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Re: Comparison of different hypotensive anaesthesia techniques in orthognathic surgery with regard to intraoperative blood loss, quality of the surgical field, and postoperative nausea and vomiting

In regard to our low incidence of postoperative nausea and vomiting (PONV) after bimaxillary osteotomies, minimizing the use of inhalational agents and narcotic pain medication are the two main focuses in our clinical practice, as inhalational agents and narcotics are associated with an increased incidence of PONV.

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Characterizing the skull base in craniofacial microsomia using principal component analysis

The aim of this study was to compare the anatomical differences in the skull base between the affected and non-affected side in patients with craniofacial microsomia (CFM), and to compare the affected and non-affected sides with measurements from a normal population. Three-dimensional computed tomography scans of 13 patients with unilateral CFM and 19 normal patients (age range 7–12 years) were marked manually with reliable homologous landmarks. Principal component analysis (PCA), as part of a point distribution model (PDM), was used to analyse the variability within the normal and preoperative CFM patient groups.

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Hypotensive anaesthesia techniques in orthognathic surgery

We read with interest the article by Lin et al., "Comparison of different hypotensive anaesthesia techniques in orthognathic surgery with regard to intraoperative blood loss, quality of the surgical field, and postoperative nausea and vomiting".1 It provoked a lot of discussion and an audit of our practice. The low incidence of postoperative nausea and vomiting (PONV) was particularly notable. In a group of similar cases of similar age and sex ratio, the incidence of PONV requiring intervention in the post anaesthesia care unit (PACU) was 35%, comparable to the sevoflurane group in the study.

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Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol cream or 0.025% tretinoin cream in subjects with mild to severe photoaging

Summary

Background

Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating.

Objective

Evaluate the effectiveness and tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA-Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin.

Methods

A 12-week, split-face, randomized trial was conducted in 48 female subjects, aged 30-65 years with mild to severe photodamage. AHA-Ret was applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to the other side (PM). Expert blinded evaluation of images and Nova measurements occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study.

Results

Forty-seven subjects completed the study. AHA-Ret demonstrated significant reductions in average severity from baseline: Fine Lines/Wrinkles (P<.001; all time points); Erythema (P=.004, P<.0001; 8 and 12 weeks, respectively); Dyschromia (P<.0001; all time points); Skin Tone (P<.0001; all time points), and Pore Size (P=.035, P<.0001; 8 and 12 weeks, respectively). AHA-Ret induced less Erythema vs retinol at 8 (P=.008) and 12 (P<.02) weeks. AHA-Ret was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks. Improvements in Hydration occurred at every time point with AHA-Ret only (P<.04, P<.03, P<.01). Less irritation was reported with AHA-Ret vs retinol or tretinoin.

Conclusions

Treatment with a double-conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA-Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.

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Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol cream or 0.025% tretinoin cream in subjects with mild to severe photoaging

Summary

Background

Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating.

Objective

Evaluate the effectiveness and tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA-Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin.

Methods

Results

Conclusions

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Conceptualisation, development and validation of T-QoL© (Teenagers’ Quality of Life): a patient-focused measure to assess quality of life of adolescents with skin diseases

Abstract

Aim

To develop and validate a dermatology-specific quality of life (QoL) instrument for adolescents with skin diseases.

Methods

Qualitative semi-structured interviews were conducted with adolescents with skin disease to gain in-depth understanding of how skin diseases affect their QoL. A prototype instrument based on the themes identified from content analysis of interviews was tested in several stages, using Classical Test Theory (CTT) and Item Response Theory (IRT) models to develop this new tool and conduct its psychometric evaluation.

Results

Thirty-three QoL issues were identified from semi-structured interviews with 50 adolescents. A questionnaire based on items derived from content analysis of interviews was subjected to Rasch analysis: factor analysis identified three domains, therefore not supporting the validity of T-QoL as a unidimensional measure. Psychometric evaluation of the final 18-item questionnaire was carried out in a cohort of 203 adolescents. Convergent validity was demonstrated by significant correlation with Skindex-Teen and CDLQI or DLQI. The T-QoL showed excellent internal consistency reliability: Cronbach's α=0.89 for total scale score and 0.85, 0.60, and 0.74 respectively for domains 1, 2 and 3. Test-retest reliability was high in stable subjects. T-QoL showed sensitivity to change in two sub-groups of patients who indicated change in their self-assessed disease severity.

Conclusion

Built on rich qualitative data from patients, the T-QoL is a simple and valid tool to quantify the impact of skin disease on adolescents' QoL; it could be used as an outcome measure in both clinical practice and clinical research.

http://ift.tt/2vdwNcJ

Conceptualisation, development and validation of T-QoL© (Teenagers’ Quality of Life): a patient-focused measure to assess quality of life of adolescents with skin diseases

Abstract

Aim

To develop and validate a dermatology-specific quality of life (QoL) instrument for adolescents with skin diseases.

Methods

Results

Conclusion

http://ift.tt/2vdwNcJ

Association Between Handgrip Muscle Strength and Cardiometabolic z-Score in Children 6 to 19 Years of Age: Results from the Canadian Health Measures Survey

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.

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The protective effect of platelet released growth factors and bone augmentation (Bio-Oss®) on ethanol impaired osteoblasts

Publication date: Available online 31 July 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Tolga Taha Sönmez, Andreas Bayer, Tillman Cremer, Jennifer Vanessa Phi Hock, Bernd Lethaus, Nisreen Kweider, Christoph Jan Wruck, Wolf Drescher, Holger Jahr, Sebastian Lippross, Thomas Pufe, Mersedeh Tohidnezhad
BackgroundChronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss^® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss^® in ethanol (EtOH) treated osteoblasts.MethodsThe SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss^® were assessed.ResultsThe application of PRGF and Bio-Oss^® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss^® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss^® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells.ConclusionsThese results indicate that the simultaneous application of PRGF and Bio-Oss^® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration.

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Expression of C-X-C motif chemokine receptors 4 and 7 in salivary gland neoplasms

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Ekarat Phattarataratip, Kittipong Dhanuthai
ObjectivesChemokine receptors have been shown to overexpress in several cancer types. Binding of chemokines to their cognate chemokine receptors on tumor cells can promote tumor growth, angiogenesis and metastasis. The purposes of this study was to examine the expression of chemokine receptors, CXCR4 and CXCR7, in salivary gland neoplasms and its association with pathologic characteristics.DesignSixty-two cases of salivary gland neoplasms, including 25 mucoepidermoid carcinomas (MEC), 18 adenoid cystic carcinomas (ACC), 14 pleomorphic adenomas (PA) and 5 polymorphous low-grade adenocarcinoma (PLGA) were investigated for CXCR4 and CXCR7 expression immunohistochemically. The immunoreactivity was categorized as low expression or high expression group, based on whether the positive staining was below or higher than 50% of the neoplastic cells, respectively.ResultsThe majority of MECs, ACCs and PLGAs showed high CXCR4 and CXCR7 expression, whereas most PAs showed high CXCR4 but low CXCR7 expression. The levels of CXCR4 and CXCR7 expression were significantly correlated. In MECs, the expression of both chemokine receptors was localized to squamous cells, intermediate cells and glandular epithelial cells, whereas mucous cells and clear cells were negative. In ACCs and PAs, their immunoreactivity was more intense in ductal cells than myoepithelial cells. Most neoplastic myoepithelial cells in PAs did not express CXCR7, while those in ACCs showed strong CXCR7 expression. The increased CXCR4 expression was significantly associated with advanced pathologic grade of MECs (P=0.03).ConclusionOverexpression of CXCR4 and CXCR7 is common in the 4 salivary gland neoplasms investigated. CXCR4 may play a role in the progression of MECs.

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Imaging children suffering from lymphoma: an evaluation of different 18 F-FDG PET/MRI protocols compared to whole-body DW-MRI

Abstract

Objectives

The objectives of this study were to evaluate and compare the diagnostic potential of different PET/MRI reading protocols, entailing non-enhanced / contrast-enhanced and diffusion-weighted ¹⁸F–FDG PET/MR imaging and whole-body diffusion-weighted MRI for lesion detection and determination of the tumor stage in pediatric lymphoma patients.

Methods

A total of 28 ¹⁸F–FDG PET/MRI datasets were included for analysis of four different reading protocols: (1) PET/MRI utilizing sole unenhanced T2w and T1w imaging, (2) PET/MRI utilizing additional contrast enhanced sequences, (3) PET/MR imaging utilizing unenhanced, contrast enhanced and DW imaging or (4) WB-DW-MRI. Statistical analyses were performed on a per-patient and a per-lesion basis. Follow-up and prior examinations as well as histopathology served as reference standards.

Results

PET/MRI correctly identified all 17 examinations with active lymphoma disease, while WB-DW-MRI correctly identified 15/17 examinations. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 96%, 96.5%, 97%, 95%, and 96% for PET/MRI₁; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI₂; 97%, 96.5%, 97%, 96.5%, and 97% for PET/MRI₃ and 77%, 96%, 96%, 78.5% and 86% for MRI-DWI.

Conclusion

¹⁸F–FDG PET/MRI is superior to WB-DW-MRI in staging pediatric lymphoma patients. Neither application of contrast media nor DWI leads to a noticeable improvement of the diagnostic accuracy of PET/MRI. Thus, unenhanced PET/MRI may play a crucial role for the diagnostic work-up of pediatric lymphoma patients in the future.

http://ift.tt/2hiEuZp

Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions

Abstract

Methods

After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha<0.61]. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation.

Results

Between-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K's alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K's alpha: 0.64). K's alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written.

Conclusion

We hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.

http://ift.tt/2f3hInq

Reply to: Predicting the outcome of peptide receptor radionuclide therapy in neuroendocrine tumors: the importance of dual-tracer imaging

http://ift.tt/2hj7qk2

Patterns of failure after radical prostatectomy in prostate cancer – implications for radiation therapy planning after 68 Ga-PSMA-PET imaging

Abstract

Background

Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). ⁶⁸Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases.

Objective

In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not.

Methods and materials

Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from ⁶⁸Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, ⁶⁸Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE.

Results

Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by ⁶⁸Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of ⁶⁸Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of ⁶⁸Ga-PSMA-PET imaging.

Conclusion

Compared to conventional CT or MRI staging, ⁶⁸Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

http://ift.tt/2f3qEcx

Monitoring early response to chemoradiotherapy with 18 F-FMISO dynamic PET in head and neck cancer

Abstract

Purpose

There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of ¹⁸F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC.

Experimental design

Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0–30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy. Voxelwise pharmacokinetic modeling was conducted using an irreversible one-plasma two-tissue compartment model to calculate surrogate biomarkers of tumor hypoxia (k ₃ and Tumor-to-Blood Ratio (TBR)), perfusion (K ₁ ) and FMISO distribution volume (DV). Additionally, Tumor-to-Muscle Ratios (TMR) were derived by visual inspection by an experienced nuclear medicine physician, with TMR > 1.2 defining hypoxia.

Results

One hundred and thirty-five lesions in total were analyzed. TBR, k ₃ and DV decreased on early response scans, while no significant change was observed for K ₁ . The k ₃ -TBR correlation decreased substantially from baseline scans (Pearson's r = 0.72 and 0.76 for mean intratumor and pooled voxelwise values, respectively) to early response scans (Pearson's r = 0.39 and 0.40, respectively). Both concordant and discordant examples of changes in intratumor k ₃ and TBR were identified; the latter partially mediated by the change in DV. In 13 normoxic patients according to visual analysis (all having lesions with TMR = 1.2), subvolumes were identified where k ₃ indicated the presence of hypoxia.

Conclusion

Pharmacokinetic modeling of FMISO dynamic PET reveals a more detailed characterization of the tumor microenvironment and assessment of response to chemoradiotherapy in HNC patients than a single static image does. In a clinical trial where absence of hypoxia in primary tumor and lymph nodes would lead to de-escalation of therapy, the observed disagreement between visual analysis and pharmacokinetic modeling results would have affected patient management in <20% cases. While simple static PET imaging is easily implemented for clinical trials, the clinical applicability of pharmacokinetic modeling remains to be investigated.

http://ift.tt/2hiEbhd

Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer

Abstract

Purpose

Radium Ra 223 dichloride (radium-223, Xofigo®) is the first targeted alpha therapy for patients with castration-resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision.

Methods

An independent research consultancy agency observed radium-223 procedures and conducted interviews with all key staff members involved in radium-223 treatment delivery in 11 nuclear medicine centres across six countries (Germany, Italy, the Netherlands, Spain, Switzerland and the UK) experienced in administering radium-223. The findings were collated and discussed at a meeting of experts from these centres, during which key consensus recommendations were defined.

Results

The recommendations cover centre organization and preparation; patient referral; radium-223 ordering, preparation and disposal; radium-223 treatment delivery/administration; and patient experience. Guidance includes structured coordination and communication within centres and multidisciplinary teams, focusing on sharing best practice to provide high-quality, patient-centred care throughout the treatment pathway.

Conclusions

These expert recommendations are intended to complement existing management guidelines. Sharing best practice and experience will help nuclear medicine centres to optimize radium-223 service provision and improve patient care.

http://ift.tt/2f3b4h2

SPECT/CT and PET/CT molecular imaging in medullary thyroid carcinoma. Are we running in the right direction?

http://ift.tt/2hiSXVb

The role of 18 F-FDG PET/CT in the detection of osteosarcoma recurrence

Abstract

Aim

The aim of this study was to investigate the diagnostic accuracy of ¹⁸F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy.

Methods

Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) ¹⁸F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of ¹⁸F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). ¹⁸F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated.

Results

¹⁸F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis ¹⁸F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after ¹⁸F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively.

Conclusion

¹⁸F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.

http://ift.tt/2f31nzd

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence

Abstract

Purpose

PET/CT using ⁶⁸Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that ⁶⁸Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on ⁶⁸Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i..

Methods

203 consecutive PC patients with biochemical failure referred to ⁶⁸Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243–491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUV_max) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans.

Results

26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUV_max: 10.8; range: 4.7–40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUV_max: 5.9; range: 2.9–17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUV_max of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281–491 vs. 243–311 s p.i.; p < 0.001). Median SUV_max value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUV_max: 5.9 vs. 1.9, 4.0 and 2.4, respectively).

Conclusions

Performance of early imaging in ⁶⁸Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

http://ift.tt/2hi9sk5

Players of ‘hypoxia orchestra’ – what is the role of FMISO?

http://ift.tt/2f3hBIw

PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies

Abstract

We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [¹¹C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging.

http://ift.tt/2f3b3cY

A new perspective for nuclear medicine: expanding the indications for PSMA targeted imaging and therapy

http://ift.tt/2hj7osq

Selective removal of carious lesion with Er:YAG laser followed by dentin biomodification with chitosan

Abstract

The aim of this study was to evaluate the effect of Er:YAG laser for selective removal of carious lesion, followed by biomodification with chitosan gel where the subsurface microhardness, chemical composition, and morphological changes of the residual caries-affected dentin were examined. Artificial dentinal lesions were created by pH-cycling method (14 days) in 104 bovine specimens (5 × 5 mm). Specimens were randomly divided according to the carious removal method: bur (low-speed handpiece) or Er:YAG laser (250 mJ/4 Hz). Specimens were treated with 35% phosphoric acid and were subdivided into two groups according to dentin biomodification: without chitosan (control) and 2.5% chitosan. Forty specimens were restored with an adhesive system and composite resin. Subsurface microhardness tests were performed in sound dentin, caries-affected dentin, residual caries-affected dentin, and after the restoration. The other 64 specimens were subjected to SEM-EDS atomic analysis. Data were statistically analyzed (p < 0.05). After the Er:YAG laser excavation, the microhardness value of residual caries-affected dentin was higher (p < 0.05) than bur-treated dentin. A significant decrease in the amount of Ca, P, and Ca/P ratio was found after the removal of carious lesions with Er:YAG laser (p < 0.05). The biomodification with chitosan did not influence the microhardness and atomic percentage of Ca, P, and Ca/P ratio of residual caries-affected dentin (p > 0.05). SEM analysis showed morphological changes on residual caries-affected dentin (p > 0.05). The selective removal of carious dentin with Er:YAG laser increased microhardness of residual caries-affected dentin, changing its surface morphology and chemical composition. The biomodification with chitosan did not influence the structural and chemical composition of residual caries-affected dentin.

http://ift.tt/2vc54sY

Factor Structure of the Intolerance of Uncertainty Scale for Children

Publication date: Available online 31 July 2017
Source:Journal of Anxiety Disorders
Author(s): Danielle Cornacchio, Amanda L. Sanchez, Stefany Coxe, Amy Roy, Donna B. Pincus, Kendra L. Read, Robert M. Holaway, Philip C. Kendall, Jonathan S. Comer
Intolerance of uncertainty (IU), a dispositional negative orientation toward uncertainty and its consequences, has been studied in adults, but research has only recently examined IU in youth. Despite some advances, little is known about the factor structure of measures of IU in youth. The present study used confirmatory factor analysis to examine the structure of IU as measured by the Intolerance of Uncertainty Scale for Children (IUSC; Comer et al., 2009) in a sample of youth (N=368) 9-18 years of age (Mage=12.47) with and without anxiety disorders and their mothers. Findings demonstrated multiple acceptable factor structures: a correlated factors 2-factor structure and a bifactor model where a general factor underlies all items. While the bifactor model provides better fit and reliability to the data, multivariate analyses indicated that the 2-factor structure distinguishes apprehensive anxiety regarding future events (prospective IU) from present-focused inhibition of behavior due to uncertainty and negative reactions to the presence of uncertainty (inhibitory IU); a total IU score predicted all anxiety domains for self- and parent-reports except for parent-report harm avoidance. Findings are discussed in terms of consistency of IU across adult and youth samples, and how results can inform treatment efforts and etiologic models of IU and anxiety.

http://ift.tt/2vdptxw

Functional regulatory evolution outside of the minimal even-skipped stripe 2 enhancer [RESEARCH ARTICLE]

Justin Crocker and David L. Stern

Transcriptional enhancers are regions of DNA that drive precise patterns of gene expression. While many studies have elucidated how individual enhancers can evolve, most of this work has focused on what are called "minimal" enhancers, the smallest DNA regions that drive expression that approximates an aspect of native gene expression. Here we explore how the Drosophila erecta even-skipped (eve) locus has evolved by testing its activity in the divergent D. melanogaster genome. We found, as has been reported previously, that the D. erecta eve stripe 2 enhancer (eveS2) fails to drive appreciable expression in D. melanogaster (1). However, we found that a large transgene carrying the entire D. erecta eve locus drives normal eve expression, including in stripe 2. We performed a functional dissection of the region upstream of the D. erecta eveS2 region and found multiple Zelda motifs that are required for normal expression. Our results illustrate how sequences outside of minimal enhancer regions can evolve functionally through mechanisms other than changes in transcription factor binding sites that drive patterning.

http://ift.tt/2f3pP3l

Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation [RESEARCH ARTICLE]

Jeannine M. Basta, Lynn Robbins, Darcy R. Denner, Grant R. Kolar, and Michael Rauchman

The formation of the proper number of nephrons requires a tightly regulated balance between renal progenitor cell self-renewal and differentiation. The molecular pathways that regulate the transition from renal progenitor to renal vesicle are not well understood. Here we show that Sall1interacts with the Nucleosome Remodeling and Deacetylase Complex (NuRD) to inhibit premature differentiation of nephron progenitor cells. Disruption of Sall1-NuRD in vivo in knock-in mice (SRM) resulted in accelerated differentiation of nephron progenitors and bilateral renal hypoplasia. Transcriptional profiling of mutant kidneys revealed a striking pattern in which genes of the glomerular and proximal tubule lineages were either unchanged or upregulated, and those in the loop of Henle and distal tubule lineages were downregulated. These global changes in gene expression were accompanied by a significant decrease in THP, NKCC2, AQP-1 positive loop of Henle nephron segments in mutant SRM kidneys. These findings highlight an important function of Sall1-NuRD interaction in the regulation of Six2 positive multipotent renal progenitor cells and formation of the loop of Henle.

http://ift.tt/2hig8in

The extracellular metalloprotease AdamTS-A anchors neural lineages in place within and preserves the architecture of the central nervous system [RESEARCH ARTICLE]

James B. Skeath, Beth A. Wilson, Selena E. Romero, Mark J. Snee, Yi Zhu, and Haluk Lacin

The extracellular matrix (ECM) regulates cell migration and sculpts organ shape. AdamTS proteins are extracellular metalloproteases known to modify ECM proteins and promote cell migration, but demonstrated roles for AdamTS proteins in regulating CNS structure and ensuring cell lineages remain fixed in place have not been uncovered. Using forward genetic approaches in Drosophila, we find that reduction of AdamTS-A function induces both the mass exodus of neural lineages out of the CNS and drastic perturbations to CNS structure. Expressed and active in surface glia, AdamTS-A acts in parallel to perlecan and in opposition to viking/collagen IV and βPS-integrin to keep CNS lineages rooted in place and to preserve the structural integrity of the CNS. viking/collagen IV and βPS-integrin are known to promote tissue stiffness and oppose the function of perlecan, which reduces tissue stiffness. Our work supports a model in which AdamTS-A anchors cells in place and preserves CNS architecture by reducing tissue stiffness.

http://ift.tt/2f3pKwz

Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells [RESEARCH ARTICLE]

Anastasiia Nemashkalo, Albert Ruzo, Idse Heemskerk, and Aryeh Warmflash

Paracrine signals maintain developmental states and create cell-fate patterns in vivo, and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro. Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ("μColonies") to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in μColonies and standard culture conditions and find that in μColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions, BMP4 acts as morphogen, but this effect requires secondary signals and particular cell densities. We further find that a "community effect" enforces a common fate within μColonies both in the state of pluripotency and when cells are differentiated, and that this effect allows more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation.

http://ift.tt/2hi3Ia1

Patterning of the Drosophila L2 vein is driven by regulatory interactions between region-specific transcription factors expressed in response to Dpp signalling [RESEARCH ARTICLE]

Mercedes Martin, Cristina M. Ostale, and Jose F. de Celis

Pattern formation relies on the generation of transcriptional landscapes regulated by signalling pathways. A paradigm of epithelial patterning is the distribution of vein territories in the Drosophila wing disc. In this tissue, Decapentaplegic signalling regulates its target genes at different distances from the source of the ligand. The transformation of signalling into coherent territories of gene expression requires regulatory cross-interactions between these target genes. Here we analyse the mechanisms generating the domain of knirps expression in the presumptive L2 vein of the wing imaginal disc. We find that knirps is regulated by four Decapentaplegic target genes encoding transcription factors: aristaless, spalt mayor, spalt related and optix. The expression of optix is activated by Dpp and repressed by the Spalt proteins, becoming restricted to the most anterior region of the wing blade. In turn, the expression of knirps is activated by Aristaless and repressed by Optix and the Spalt proteins. In this manner, the expression of Knirps became restricted to those cells where Spalt levels are sufficient to repress optix, but not sufficient to repress knirps.

http://ift.tt/2f3miSB

Genome-wide identification of Grainy head targets in Drosophila reveals regulatory interactions with the POU-domain transcription factor, Vvl [RESEARCH ARTICLE]

Liqun Yao, Shenqiu Wang, Jakub Orzechowski-Westholm, Qi Dai, Ryo Matsuda, Chie Hosono, Sarah Bray, Eric C. Lai, and Christos Samakovlis

Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions, we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU-domain TF, Vvl, (ventral veins lacking) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation.

http://ift.tt/2hiN0rj

Effect of mechanical loading on the metabolic activity of cells in the temporomandibular joint: a systematic review

Abstract

Objectives

The purpose of this systematic review was to elucidate how different modalities and intensities of mechanical loading affect the metabolic activity of cells within the fibro-cartilage of the temporomandibular joint (TMJ).

Materials and methods

A systematic review was conducted according to PRISMA guidelines using PubMed, Embase, and Web of Science databases. The articles were selected following a priori formulated inclusion criteria (viz., in vivo and in vitro studies, mechanical loading experiments on TMJ, and the response of the TMJ).

A total of 254 records were identified. After removal of duplicates, 234 records were screened by assessing eligibility criteria for inclusion. Forty-nine articles were selected for full-text assessment. Of those, 23 were excluded because they presented high risk of bias or were reviews. Twenty-six experimental studies were included in this systematic review: 15 in vivo studies and 11 in vitro ones.

Conclusion

The studies showed that dynamic mechanical loading is an important stimulus for mandibular growth and for the homeostasis of TMJ cartilage. When this loading is applied at a low intensity, it prevents breakdown of inflamed cartilage. Yet, frequent overloading at excessive levels induces accelerated cell death and an increased cartilage degradation.

Clinical Significance

Knowledge about the way temporomandibular joint (TMJ) fibrocartilage responds to different types and intensities of mechanical loading is important to improve existing treatment protocols of degenerative joint disease of the TMJ, and also to better understand the regenerative pathway of this particular type of cartilage.

http://ift.tt/2tYEFyQ

MAIT cells in infectious diseases

Marion Salou | Katarzyna Franciszkiewicz | Olivier Lantz

http://ift.tt/2f35gUM

Vaccines targeting helper T cells for cancer immunotherapy

Marit Melssen | Craig L Slingluff

http://ift.tt/2hiKgu1

Towards an evidence based approach for the development of adjuvanted vaccines

Derek T O'Hagan | Leonard R Friedland | Emmanuel Hanon | Arnaud M Didierlaurent

http://ift.tt/2f39Vpy

TNF-receptor superfamily agonists as molecular adjuvants for cancer vaccines

Timothy NJ Bullock

http://ift.tt/2f39Ou8

Four pathways of CD1 antigen presentation to T cells

D Branch Moody | Rachel N Cotton

http://ift.tt/2hivPGo

Dural metastasis of nasopharyngeal carcinoma: A case report

Publication date: Available online 16 June 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Mohd Irman Shah Ibrahim, Aishah Harizah Abdullah Alwi, Amran Mohamad, Norhafiza Mat Lazim
Nasopharyngeal carcinoma (NPC) with dural metastasis is extremely rare, mostly asymptomatic, leaving it to be highly at risk of being overlooked. We report a case of a woman with dural metastasis of NPC almost 1year post concurrent chemoradiotherapy (CCRT) that was detected following a trivial trauma to her head. Owing to its rare occurence, it presents a great challenge for clinicians to make a prompt diagnosis because delayed in the treatment may lead to a fatal outcome.

http://ift.tt/2hiVE9k

Effect of glycerol test on audiovestibular tests in patients with Meniere’s disease

Publication date: Available online 9 May 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Enass S. Mohamed, Eman A. Said, Nashwa A. Mahmoud
This stud to explore the effect of glycerol on audiovestibular tests in patients with Meniere's disease (MD) and to reflect different pathologic states of endolymphatic hydrops (EH) in the inner ear and compare the results of glycerol on these results.SubjectsThirty patients and 15 normal volunteers.MethodsEach subject of this study underwent pure tone audiometry testing, evoked vestibular evoked myogenic potential (VEMP) and Vidionystagmography (VNG) before G1 and 2h after glycerol G2 administration (1.3g/kg).ResultsAffected ears were 32 and unaffected ears were 28. The affected ears had higher hearing and SRT thresholds when compared to the unaffected ears and control group. VEMPs of the affected ears were normal in six ears (18.75%), absent in four ears (12.5%) and augmented amplitude in 22 (68.75%), their VNG results showed peripheral vestibular disorder. After oral administration of glycerol, the previous test battery was repeated and it's result on PTA showed that 53.13% (17/32) of affected ears had positive glycerol test mainly in stage II and III. Ten of the 32 affected ears (31.26%) showed improvement of VEMPs after glycerol administration. Also, two (7.8%) of the unaffected ears showed positive glycerol. Latency of the VEMP had no significant changes after glycerol administration and there was no statistical correlation between the results of G-PTA and G-VEMP. There was statistical significant improvement of the slow peak velocity of caloric test in patient's affected ears and insignificant improvement in control group and in unaffected ears after glycerol administration.

http://ift.tt/2f2xe37

Editorial Board

Publication date: March 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences, Volume 18, Issue 1

http://ift.tt/2hiVAq6

Comparative study between selective nerve blocks and the intravenous opioids in mastoid surgery

Publication date: Available online 17 June 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Santosh Kumar Swain, Chandrasekhar Pradhan, Sidharth Mohanty, Mahesh Chandra Sahu
ObjectiveThis double-blind randomized trial was conducted to compare the efficacy of selective nerve blocks over intravenous use of morphine during mastoid surgery.Materials and methodsA total of 50 patients between the ages 25 to 45years were divided into two groups as per the anaesthetic techniques used; nerve block group (N) and intravenous morphine group (M). After induction of general anaesthesia and before surgical incision: Group N patients (nerve block group) were given Great Auricular Nerve (GAN) and Auriculo-Temporal Nerve (ATN) block with 0.25% bupivacaine. Group M patients (morphine group) received 0.1mg/kg morphine. In the post anaesthesia care unit (PACU), Visual Analogue Scale (VAS) was used to assess post operative pain, Ramsay Sedation Scale (RSS) for sedation and post operative nausea and vomiting (PONV) impact scale score.ResultsVAS scores and requirement of rescue analgesics in the PACU was significantly less in the N Group for first 3h. The group N patients had a less frequent incidence of vomiting requiring intervention and were ready to be discharged from hospital after 3h of surgery.ConclusionCombination of GAN and ATN block with general anaesthesia is an uncomplicated, effective and well tolerated method for the safe conduct of mastoid surgery.

http://ift.tt/2f2wFq1

Dural metastasis of nasopharyngeal carcinoma: A case report

Effect of glycerol test on audiovestibular tests in patients with Meniere’s disease

Editorial Board

Publication date: March 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences, Volume 18, Issue 1

http://ift.tt/2hiVAq6

Comparative study between selective nerve blocks and the intravenous opioids in mastoid surgery

Bio-inspired hybrid scaffold of zinc oxide-functionalized multi-wall carbon nanotubes reinforced polyurethane nanofibers for bone tissue engineering

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): Bishnu Kumar Shrestha, Sita Shrestha, Arjun Prasad Tiwari, Jeong-In Kim, Sung Won Ko, Han-Joo Kim, Chan Hee Park, Cheol Sang Kim
In this study, we prepared nanotopographical polyurethane (PU)-based bioactive scaffolds that incorporated uniformly dispersed functionalized multi-wall carbon nanotubes (fMWCNTs) and zinc oxide (ZnO) nanoparticles (NPs) using an electrospinning technique. We found that well dispersed fMWCNTs along with ZnO NPs reinforced PU fibers demonstrated significant improvement in mechanical strength, hydrophilicity, thermal stability, electrical conductivity, degradability, biomineralization, and biocompatibility. Inspired by the exciting nature of biopolymeric composite (PU/ZnO-fMWCNTs) membranes, these hybrid scaffolds offer extensive interest to tissue engineering as a potential biomedical application. The specific bioactive properties and cell-biomaterial interaction of electrospun scaffold containing 0.2wt% ZnO with 0.4wt% fMWCNTs were found to demonstrate anti-bacterial activity and cytocompatibility. Furthermore, the highly charged density, large surface-to-volume ratio, and more functional groups in fMWCNTs integrated on the scaffolds promote osteogenic differentiation of pre-osteoblast (MC3T3-E1) cells. Therefore, the novel as-prepared multifunctional electrospun fibrous scaffold could suggest new avenues for exploration as promising osteoproductive and osteoinductive biomaterials that offer great benefit to bone tissue engineering.

Graphical abstract

http://ift.tt/2tSZzLF

Tailoring modulus and hardness of in-situ formed β-Ti in bulk metallic glass composites by precipitation of isothermal ω-Ti

Publication date: 5 November 2017
Source:Materials & Design, Volume 133
Author(s): L. Zhang, S. Chen, H.M. Fu, H. Li, Z.W. Zhu, H.W. Zhang, Z.K. Li, A.M. Wang, H.F. Zhang
It is challenging to tailor the mechanical properties of in-situ formed β phases in Ti/Zr-based bulk metallic glass composites (β-type BMGCs) without changing the morphologies of the β phases. Recently, BMGCs containing metastable β-Ti/Zr phases (metastable β-type BMGCs) exhibit an exothermic reaction below the glass transition temperature (sub-Tg) of the glassy matrices during heating, however, the corresponding structural origin remains unclear. In this work, the precipitation of ω phase inside β phase was revealed to account for the sub-Tg exothermic event of the metastable Ti45.7Zr33Cu5.8Co3Be12.5 BMGC. The sub-Tg annealing of metastable β-type BMGCs causes the precipitation of nanometer-sized isothermal ω phase, which leads to a large increase in the modulus and hardness of the crystalline phase. This finding provides a novel route to tailor the modulus and hardness of the crystalline phases in BMGCs without changing their morphologies, including volume fractions, sizes, and distributions. On this basis, the influence of the modulus and hardness of the crystalline phase on mechanical properties of BMGCs was exclusively investigated. Our experimental results together with finite-element simulations proved that lower modulus and hardness of the crystalline phase benefit a larger plasticity of BMGCs.

Graphical abstract

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The Impact of the Cosurgeon Model on Bilateral Autologous Breast Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0037-1604106

Background Microsurgical breast reconstructions (MBRs) are time and labor intensive procedures. To circumvent these barriers, plastic surgeons have started working together as cosurgeons (CSs). This study aims to evaluate the impact of the CS model (CSM) specifically on bilateral MBR. The hypothesis is that CS procedures reduce operative time and surgical complications. Study Design This was a single institutional retrospective cohort study, which included all consecutive patients who underwent bilateral MBR from 2014 to 2016. Patients were grouped into single surgeon (SS) or CSs based on the number of the attending plastic surgeons present. Demographic and clinical characteristics including age, body mass index, smoking, American Society of Anesthesiologist class, radiation, and the timing of the reconstruction were assessed. Univariate and multivariate analyses were performed for outcomes including operative time and postoperative complications. Results Of the 136 patients included in the study, 41% had breast reconstruction performed by CSs, whereas 59% had a SS. Sociodemographic features were evenly distributed with the exception of a greater number of delayed reconstructions in the SS group (33 vs. 13%; p <0.01). Pedicle TRAMS (transverse rectus abdominis musculocutaneous flaps) were performed in 5 versus 0% of SS versus CS cases, respectively. Rates of major (4 vs. 16%) and minor (11 vs. 24%) complications were significantly lower in CS procedures. Multivariate analyses demonstrated CS operations required significantly shorter operative time by 73 minutes (p <0.001), and trended toward a reduced postoperative complication rate (p = 0.07). Conclusion The CSM is associated with improved operative efficiency for bilateral MBR. Further evaluation of the CSM may prove useful in other surgical disciplines with time and labor intense procedures.
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Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents | Abstract | Full text

http://ift.tt/2uPBqsm

Stable Coronary Syndromes: The Case for Consolidating the Nomenclature of Stable Ischemic Heart Disease.

Author: Berry, Colin MD, PhD

Page: 437-439

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Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial).

Author: Soliman, Elsayed Z. MD, MSc, MS; Ambrosius, Walter T. PhD; Cushman, William C. MD; Zhang, Zhu-ming MD, MPH; Bates, Jeffrey T. MD; Neyra, Javier A. MD, MSCS; Carson, Thaddeus Y. MD; Tamariz, Leonardo MD, MPH; Ghazi, Lama MD; Cho, Monique E. MD; Shapiro, Brian P. MD; He, Jiang MD, PhD; Fine, Lawrence J. MD, DrPH; Lewis, Cora E. MD, MSPH; For the SPRINT Research Study Group

Page: 440-450

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Intensive Blood Pressure Lowering and Regression of Left Ventricular Hypertrophy.

Author: Verdecchia, Paolo MD; Angeli, Fabio MD; Reboldi, Gianpaolo MD, PhD, MSc

Page: 451-453

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Associations Between Adding a Radial Artery Graft to Single and Bilateral Internal Thoracic Artery Grafts and Outcomes: Insights From the Arterial Revascularization Trial.

Author: Taggart, David P. MD, PhD; Altman, Douglas G. DSc; Flather, Marcus MD; Gerry, Stephen MSc; Gray, Alastair PhD; Lees, Belinda BSc, PhD; Benedetto, Umberto MD, PhD; On Behalf of the ART (Arterial Revascularization Trial) Investigators

Page: 454-463

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Human Plasma Thioredoxin-80 Increases With Age and in ApoE-/- Mice Induces Inflammation, Angiogenesis, and Atherosclerosis.

Author: Couchie, Dominique PhD; Vaisman, Boris PhD; Abderrazak, Amna PhD; Mahmood, Dler Faieeq Darweesh PhD; Hamza, Magda M. PhD; Canesi, Fanny; Diderot, Vimala; El Hadri, Khadija PhD; Negre-Salvayre, Anne PhD; Le Page, Aurelie PhD; Fulop, Tamas MD, PhD; Remaley, Alan T. MD, PhD; Rouis, Mustapha PhD

Page: 464-475

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Functional Characterization of the GUCY1A3 Coronary Artery Disease Risk Locus.

Author: Kessler, Thorsten MD *; Wobst, Jana MS *; Wolf, Bernhard MD; Eckhold, Juliane BS; Vilne, Baiba PhD; Hollstein, Ronja MS; von Ameln, Simon PhD; Dang, Tan An MS; Sager, Hendrik B. MD; Moritz Rumpf, Philipp MD; Aherrahrou, Redouane PhD; Kastrati, Adnan MD; Bjorkegren, Johan L.M. MD, PhD; Erdmann, Jeanette PhD; Lusis, Aldons J. PhD; Civelek, Mete PhD; Kaiser, Frank J. PhD; Schunkert, Heribert MD

Page: 476-489

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Should We Perform Catheter Ablation for Asymptomatic Atrial Fibrillation?.

Author: Kalman, Jonathan M. MBBS, PhD; Sanders, Prashanthan MBBS, PhD; Rosso, Raphael MD; Calkins, Hugh MD

Page: 490-499

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Soda Taxes Take Off Across the Country.

Author: Kuehn, Bridget M.

Page: 500-501

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Chest Pain in an 18-Year-Old Man.

Author: Abdelghany, Mahmoud MD; Chaudhary, Arbind MD; Liu, Kan MD, PhD

Page: 502-504

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Letter by Shi et al Regarding Article, "Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis".

Author: Shi, Yu MD; Yu, Hai MD; Yang, Xiao-Yun MD

Page: 505-506

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Letter by Banack et al Regarding Article, "Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis".

Author: Banack, Hailey R. PhD; Stovitz, Steven D. MD, MS; Kaufman, Jay S. PhD

Page: 507-508

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Letter by Butcher et al Regarding Article, "Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis".

Author: Butcher, Anna BMed, MBBS, PhD; Klein, Andrew MBBS; Richards, Toby MBBS, MD

Page: 509

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Response by Mariscalco and Murphy to Letters Regarding Article, "Body Mass Index and Mortality Among Adults Undergoing Cardiac Surgery: A Nationwide Study With a Systematic Review and Meta-Analysis".

Author: Mariscalco, Giovanni MD, PhD; Murphy, Gavin J. MD

Page: 510-511

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2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

Author: Shen, Win-Kuang MD, FACC, FAHA, FHRS, Chair +; Sheldon, Robert S. MD, PhD, FHRS, Vice Chair; Benditt, David G. MD, FACC, FHRS *++; Cohen, Mitchell I. MD, FACC, FHRS ++; Forman, Daniel E. MD, FACC, FAHA ++; Goldberger, Zachary D. MD, MS, FACC, FAHA, FHRS ++; Grubb, Blair P. MD, FACC [S]; Hamdan, Mohamed H. MD, MBA, FACC, FHRS *++; Krahn, Andrew D. MD, FHRS *[S]; Link, Mark S. MD, FACC ++; Olshansky, Brian MD, FACC, FAHA, FHRS *++; Raj, Satish R. MD, MSc, FACC, FHRS *[S]; Sandhu, Roopinder Kaur MD, MPH ++; Sorajja, Dan MD ++; Sun, Benjamin C. MD, MPP, FACEP %7c%7c; Yancy, Clyde W. MD, MSc, FACC, FAHA ++,[P]

Page: e25-e59

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2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

Page: e60-e122

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Pacing as a Treatment for Reflex-Mediated (Vasovagal, Situational, or Carotid Sinus Hypersensitivity) Syncope: A Systematic Review for the 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

Author: Varosy, Paul D. MD, FACC, FAHA, FHRS, Chair; Chen, Lin Y. MD, MS, FACC, FAHA, FHRS *; Miller, Amy L. MD, PhD *; Noseworthy, Peter A. MD *; Slotwiner, David J. MD, FACC, FHRS *; Thiruganasambandamoorthy, Venkatesh MBBS *

Page: e123-e135

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Correction to: Effect of Intensive Blood Pressure Lowering on Left Ventricular Hypertrophy in Patients With Hypertension: SPRINT (Systolic Blood Pressure Intervention Trial).

Author:

Page: e136

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A comparative intracellular proteomic profiling of Pseudomonas aeruginosa strain ASP-53 grown on pyrene or glucose as sole source of carbon and identification of some key enzymes of pyrene biodegradation pathway

Publication date: Available online 31 July 2017
Source:Journal of Proteomics
Author(s): Ashis K. Mukherjee, Pabitra Bhagowati, Bhim Bahadur Biswa, Abhishek Chanda, Bhargab Kalita
Pseudomonas aeruginosa strain ASP-53, isolated from a petroleum oil-contaminated soil sample, was found to be an efficient degrader of pyrene. PCR amplification of selected hydrocarbon catabolic genes (alkB gene, which encodes for monooxygenase, and the C12O, C23O, and PAH-RHDα genes encoding for the dioxygenase enzyme) from the genomic DNA of P. aeruginosa strain ASP-53 suggested its hydrocarbon degradation potential. The GC–MS analysis demonstrated 30.1% pyrene degradation by P. aeruginosa strain ASP-53 after 144h of incubation at pH6.5, 37°C. Expressions of 115 and 196 intracellular proteins were unambiguously identified and quantitated by shotgun proteomics analysis when the isolate was grown in medium containing pyrene and glucose, respectively. The pyrene-induced uniquely expressed and up-regulated proteins in P. aeruginosa strain ASP-53 in addition to substrate (pyrene) metabolism are also likely to be associated with different cellular functions for example-related to protein folding (molecular chaperone), stress response, metabolism of carbohydrate, proteins and amino acids, and fatty acids; transport of metabolites, energy generation such as ATP synthesis, electron transport and nitrate assimilation, and other oxidation-reduction reactions. Proteomic analyses identified some important enzymes involved in pyrene degradation by P. aeruginosa ASP-53 which shows that this bacterium follows the salicylate pathway of pyrene degradation.SignificanceThis study is the first report on proteomic analysis of pyrene biodegradation pathway by Pseudomonas aeruginosa, isolated from a petroleum-oil contaminated soil sample. The pathway displays partial similarity with deduced pyrene degradation mechanisms of Mycobacterium vanbaalenii PYR-1. The GC–MS analysis as well as PCR amplification of hydrocarbon catabolic genes substantiated the potency of the bacterium under study to effectively degrade high molecular weight, toxic PAH such as pyrene for its filed scale bioremediation experiments. The proteomics approach (LC-MS/MS analysis) identified the differentially regulated intracellular proteins of the isolate P. aeruginosa ASP-53 when grown in pyrene medium. This study identified some important pyrene biodegradation enzymes in Pseudomonas aeruginosa ASP-53 and highlights that the bacterium follows salicylate pathway for pyrene degradation.

Graphical abstract

http://ift.tt/2tYDHTq

Synovial sarcoma showing loss of a green signal in SS18 fluorescence in situ hybridization: a clinicopathological and molecular study of 12 cases

Abstract

The phenomenon of losing a green signal in synovial sarcoma (SS) using the SS18 break-apart probe by fluorescence in situ hybridization (FISH) has been poorly described. In this study, 12 SS with missing a green signal were identified. This series included 7 males and 5 females, aged 17 to 69 years (median, 38.5 years). The tumors involved the extremities (50%), mediastinum (16.7%), hypopharynx (8.3%), neck (8.3%), thyroid (8.3%), and retroperitoneum (8.3%). The tumors were classified as monophasic SS (58.3%) and poorly differentiated SS (41.7%). An anaplastic SS showing features of pleomorphic sarcoma was observed. Immunostaining for TLE1, BCL2, CD99, epithelial membrane antigen, cytokeratin (AE1/AE3), cytokeratin 7, S-100 protein, and CD34 was consistent with typical SS. In FISH, all the tumors showed the pattern of 1 to 3 fused signal(s) with 1 to 3 red signal(s), without corresponding a green signal. The fusion transcripts included SS18-SSX1 (8/10, 80%) and SS18-SSX2 (2/10, 20%) fusions. Median and 5-year overall survival were 19.1 months and 43.6%, respectively. In conclusion, we reported a series of SS losing a green signal in the SS18 FISH assay. We propose that this variant FISH pattern should be interpreted as a peculiar unbalanced rearrangement of the SS18 gene and subsequent SS18-SSX fusion test should be recommended. The cases in this study seem to show some unusual clinicopathological features, including unusual locations, higher proportions of poorly differentiated SS, and aggressive clinical course. However, whether this variant FISH pattern is associated with peculiar clinicopathologic features awaits larger series.

http://ift.tt/2wfqTo9

Early hominin landscape use in the Lower Omo Valley, Ethiopia: Insights from the taphonomical analysis of Oldowan occurrences in the Shungura Formation (Member F)

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Tiphaine Maurin, Pascal Bertran, Anne Delagnes, Jean-Renaud Boisserie
The Oldowan archeological record of the Shungura Formation, Member F (Lower Omo valley, Ethiopia) comprises more than one hundred occurrences distributed within archeological complexes, where multiple small spots were found in association with one or two larger occurrences. Such spatial patterning could reflect hominin spatial behavior, repeated occupations within a single sedimentary unit, or taphonomic and/or collection biases. Here we test these hypotheses by way of a geoarcheological and taphonomical analysis using four criteria to assess the preservation of the lithic assemblages: (1) size composition, (2) artifact abrasion, (3) bone abrasion, and (4) orientations of lithic artifacts and bones (i.e., fabrics). We propose a new model of taphonomically induced spatial patterning where the multiple, small, well circumscribed occurrences result primarily from post-depositional processes and therefore do not reflect any underlying behavioral patterns. The large number of archeological occurrences documented in Member F, therefore, corresponds to a limited number of primary occupations (<10). The archeological occupation is mainly restricted to the lower part of Member F and may reflect a single or a small number of occupation episodes, which were located on previous levees of the paleo-Omo River, in nearby floodplain areas, or on the riverbank. This strongly suggests that most of the knapping activities originally took place close to the river. This preference of the Omo toolmakers for riverine environments could explain the scarcity of archeological material in the upper part of Member F that comprises primarily distal floodplain sedimentary facies.

http://ift.tt/2wfjyEZ

Evidence of Neanderthals in the Balkans: The infant radius from Kozarnika Cave (Bulgaria)

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Anne-marie Tillier, Nikolay Sirakov, Aleta Guadelli, Philippe Fernandez, Svoboda Sirakova, Irena Dimitrova, Catherine Ferrier, Guillaume Guérin, Maryam Heidari, Ivailo Krumov, Jean-Claude Leblanc, Viviana Miteva, Vasil Popov, Stanimira Taneva, Jean-Luc Guadelli
Excavations conducted by a Bulgarian-French team at Kozarnika Cave (Balkans, Bulgaria) during several seasons yielded a long Paleolithic archaeological sequence and led to the discovery of important faunal, lithic, and human samples. This paper aims to describe the unpublished radius shaft of an infant who died approximately before the sixth month postnatal that was recovered from layer 10b, which contained East Balkan Levallois Mousterian with bifacial leaf points. The layer was dated between 130 and 200 ka (large mammals biochronology) and between 128 ± 13 ka and 183 ± 14 ka (OSL), i.e. OIS6. Here we show that, given the scarcity of Middle Pleistocene infant remains in general, and Middle Paleolithic human remains from this part of Eastern Europe in particular, the study of the Kozarnika specimen is of special interest. We discuss its place in the Middle Pleistocene European hominine record and substantiate the hypothesis of early Neanderthal presence in the eastern Balkans.

http://ift.tt/2vmMgHM

Paleolithic subsistence strategies and changes in site use at Klissoura Cave 1 (Peloponnese, Greece)

Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Britt M. Starkovich
Klissoura Cave 1 in southern Greece preserves a long archaeological sequence that spans roughly 90,000 years and includes Middle Paleolithic, Uluzzian, Upper Paleolithic, and Mesolithic deposits. The site provides a unique opportunity to examine diachronic change and shifts in the intensity of site use across the Late Pleistocene. There is an overall picture of the intensified use of faunal resources at the site, evidenced by a shift from large to small game, and to small fast-moving taxa in particular. This trend is independent of climatic change and fluctuations in site use, and most likely reflects a broader, regional growth of hominin populations. At the same time, multiple lines of evidence (e.g., input of artifacts and features, sedimentation mechanisms, and intensification of faunal resources) indicate that the intensity of site use changed, with a sharp increase from the Middle Paleolithic to Aurignacian. This allows us to address a fundamental issue in the study of human evolution: differences in population size and site use between Neandertals and modern humans. At Klissoura Cave 1, the increase in occupation intensity might be related to population growth or larger group size, but it might also be due to changes in season of site use, more favorable environmental conditions at the beginning of the Upper Paleolithic, and/or changes in the composition of people occupying the site. These explanations are not necessarily mutually exclusive, and indeed the data support a combination of factors. Ascribing the increase in occupation intensity to larger Upper Paleolithic populations more broadly is difficult, particularly because there is little consensus on this topic elsewhere in Eurasia. The data are complicated and vary greatly between sites and regions. This makes Klissoura Cave 1, as the only currently available case study in southeastern Europe, a critical example in understanding the range of variation in demography and site use across the Middle to Upper Paleolithic transition.

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Αρχειοθήκη ιστολογίου

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Η λίστα ιστολογίων μου

Δευτέρα 31 Ιουλίου 2017

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