European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications – field cancerization, photorejuvenation and inflammatory/infective dermatoses

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Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

Cervical adenocarcinoma presenting as a cardiac tamponade in a 57-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pericardial effusion as a complication of malignant gynecological disorders is rare. Few cases of endometrial cancer, squamous cell carcinoma of the cervix, ovarian cancer and uterine carcinosarcoma have been previously reported. We report the first case of cardiac tamponade secondary to a cervical adenocarcinoma.</p> <p>Case presentation</p> <p>A 54-year-old Caucasian woman, without any relevant medical history and no gynecological aftercare, was admitted to our hospital emergency room with severe dyspnea. Echocardiography revealed severe pericardial effusion with a swinging heart. An emergency pericardial drainage was performed through a pericardial window, which permitted the draining of 700 mL of bloody fluid and a pericardial biopsy. Cytological examination of the fluid revealed atypical cells, and the biopsy specimen showed tumor emboli suggestive of adenocarcinoma. Magnetic resonance imaging showed a 35 mm cervical lesion indicative of an endocervical tumor. Exploratory laparoscopy revealed diffuse peritoneal lesions and histological examination of cervical curettage showed a poorly differentiated micropapillary adenocarcinoma of the cervix.</p> <p>Conclusion</p> <p>Carcinomatous pericarditis as the first symptom of a malignant gynecological adenocarcinoma has not, to the best of our knowledge, been documented before. This case highlights the extreme severity of pericardial effusion secondary to cervical adenocarcinoma, a sign of advanced disease. Gynecological malignancies have to be considered in cases of neoplastic pericardial effusion.</p

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048

Ankles back in randomized controlled trial (ABrCt): braces versus neuromuscular exercises for the secondary prevention of ankle sprains. Design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Ankle sprains are the most common sports and physical activity related injury. There is extensive evidence that there is a twofold increased risk for injury recurrence for at least one year post injury. In up to 50% of all cases recurrences result in disability and lead to chronic pain or instability, requiring prolonged medical care. Therefore ankle sprain recurrence prevention in athletes is essential. This RCT evaluates the effect of the combined use of braces and neuromuscular training (e.g. proprioceptive training/sensorimotor training/balance training) against the individual use of either braces or neuromuscular training alone on ankle sprain recurrences, when applied to individual athletes after usual care.</p> <p>Methods/Design</p> <p>This study was designed as three way randomized controlled trial with one year follow-up. Healthy individuals between 12 and 70 years of age, who were actively participating in sports and who had sustained a lateral ankle sprain in the two months prior to inclusion, were eligible for inclusion. After subjects had finished ankle sprain treatment by means of usual care, they were randomised to any of the three study groups. Subjects in group 1 received an eight week neuromuscular training program, subjects in group 2 received a sports brace to be worn during all sports activities for the duration of one year, and group 3 received a combination of the neuromuscular training program and a sports brace to be worn during all sports activities for the duration of eight weeks. Outcomes were assessed at baseline and every month for 12 months therafter. The primary outcome measure was incidence of ankle sprain recurrences. Secondary outcome measures included the direct and indirect costs of recurrent injury, the severity of recurrent injury, and the residual complaints during and after the intervention.</p> <p>Discussion</p> <p>The ABrCt is the first randomized controlled trial to directly compare the secondary preventive effect of the combined use of braces and neuromuscular training, against the use of either braces or neuromuscular training as separate secondary preventive measures. This study expects to identify the most effective and cost-efficient secondary preventive measure for ankle sprains. The study results could lead to changes in the clinical guidelines on the prevention of ankle sprains, and they will become available in 2012.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2157">NTR2157</a></p

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù

Ingraft chimerism in lung transplantation - a study in a porcine model of obliterative bronchiolitis

<p>Abstract</p> <p>Background</p> <p>Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.</p> <p>Methods</p> <p>A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors.</p> <p>Results</p> <p>Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (<it>R </it>= 0.610 - 0.671 and <it>p </it>< 0.05) and of obliteration of the bronchial lumen (<it>R </it>= 0.698 and <it>p </it>< 0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (<it>p </it>< 0.05), or bronchial wall (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.</p

Outcome and quality of life after aorto-bifemoral bypass surgery

<p>Abstract</p> <p>Background</p> <p>Aorto-bifemoral bypass (AFB) is commonly performed to treat aorto-iliac disease and a durable long-term outcome is achieved. Most studies documenting beneficial outcomes after AFB have been limited to mortality and morbidity rates, costs and length of hospital stay (LOS). Few studies have examined the dependency of patients and how their perception of their own health changes after surgery. The aim of the present study was to evaluate outcome after AFB and to study its determinants.</p> <p>Methods</p> <p>This retrospective study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. Out of 1597 intensive care patients admitted to the PACU, 75 were submitted to infrarenal AFB and admitted to these intensive care unit (ICU) beds over 2 years. Preoperative characteristics and outcome were evaluated by comparing occlusive disease with aneurysmatic disease patients. Six months after discharge, the patients were contacted to complete a Short Form-36 questionnaire (SF-36) and to have their dependency in Activities of Daily Living (ADL) evaluated. Patient's characteristics and postoperative follow-up data were compared using Mann-Whitney U test, t test for independent groups, chi-square or Fisher's exact test. Patient preoperative characteristics were evaluated for associations with mortality using a multiple logistic regression analysis.</p> <p>Results</p> <p>The mortality rate was 12% at six months. Multivariate analysis identified congestive heart disease and APACHE II as independent determinants for mortality. Patients submitted to AFB for occlusive disease had worse SF-36 scores in role physical and general health perception. Patients submitted to AFB had worse SF-36 scores for all domains than a comparable urban population and had similar scores to other PACU patients. Sixty-six percent and 23% of patients were dependent in at least one activity in instrumental and personal ADL, respectively, but 64% reported having better general health.</p> <p>Conclusion</p> <p>This study shows that congestive heart disease and APACHE II were risk factors for mortality after AFB surgery. Survivors who have undergone AFB perceive an improved quality of life although they are more dependent in ADL tasks and have worse scores in almost all SF-36 than the population to which they belong.</p

Isotopic evidences for microbiologically mediated and direct C input to soil compounds from three different leaf litters during their decomposition

We show the potentiality of coupling together different compound-specific isotopic analyses in a laboratory experiment, where 13C-depleted leaf litter was incubated on a 13C-enriched soil. The aim of our study was to identify the soil compounds where the C derived from three different litter species is retained. Three 13C-depleted leaf litter (Liquidambar styraciflua L., Cercis canadensis L. and Pinus taeda L., δ13CvsPDB ≈ −43‰), differing in their degradability, were incubated on a C4 soil (δ13CvsPDB ≈ −18‰) under laboratory-controlled conditions for 8 months. At harvest, compound-specific isotope analyses were performed on different classes of soil compounds [i.e. phospholipids fatty acids (PLFAs), n-alkanes and soil pyrolysis products]. Linoleic acid (PLFA 18:2ω6,9) was found to be very depleted in 13C (δ13CvsPDB ≈ from −38 to −42‰) compared to all other PLFAs (δ13CvsPDB ≈ from −14 to −35‰). Because of this, fungi were identified as the first among microbes to use the litter as source of C. Among n-alkanes, long-chain (C27–C31) n-alkanes were the only to have a depleted δ13C. This is an indication that not all of the C derived from litter in the soil was transformed by microbes. The depletion in 13C was also found in different classes of pyrolysis products, suggesting that the litter-derived C is incorporated in less or more chemically stable compounds, even only after 8 months decomposition