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Resilience has been defined as the maintenance or quick recovery of mental health during and after stressor exposure. One popular operationalization of this concept is to model prototypical trajectories of mental health in response to an adverse event, where trajectories of undisturbed low or rapidly recovering symptoms both comply with the resilience definition. However, mental health responses are likely also influenced by other stressors occurring before or during the observation time window. These "background" stressors may affect a person's assignment to a trajectory class. When using these classes as dependent variables to identify resilience-predictive factors, this may lead to false estimates. A new method to build exposure-controlled trajectories based on time courses of stressor reactivity (SR), rather than pure mental health scores, is demonstrated on a data set of 707 initially healthy participants living in Germany (67.33% female; Mage = 29.20, SD = 8.27). SR scores express individual deviations from the sample's normative mental health reaction to observed real-life stressors during the observation time window, thus accounting for individual differences in exposure to background stressors. The resulting trajectory models are plausible. In analyses additionally controlling for background stressors occurring before the observation time window (past life events), low SR trajectories are predicted by the well-documented resilience factor sense of coherence, suggesting construct validity. Further, they are associated with lower odds of developing categorical mental health conditions, suggesting predictive validity. Our study provides the first proof of principle for a refined method to identify predictors of resilience to major stressor events. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Animal and human bites are a common reason for emergency consultation, especially in children. The most common complication of bite wounds is local infection. Systemic infections are much rarer. The key in reducing the risk of infection after a mammalian bite is local wound management with either primary or delayed closure. The benefit of administering prophylactic antibiotics is controversial.In this review, we provide a summary of the current evidence for the management of mammalian bites in children, including recommendations for appropriate investigations, wound management, administration of prophylactic and therapeutic antibiotics and the prevention of systemic infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Inflammatory biomarkers, as indicators of biological states, provide a valuable approach for accurate and reproducible measurements, crucial for the effective management of mild traumatic brain injury (mTBI) in pediatric patients. This study aims to assess the diagnostic utility of blood-based inflammatory markers IL6, IL8, and IL10 in children with mTBI, including those who did not undergo computed tomography (CT) scans., Methods: A prospective multicentric cohort study involving 285 pediatric mTBI patients was conducted, stratified into CT-scanned and non-CT-scanned groups within 24 h post-trauma, alongside 74 control subjects. Biomarker levels were quantitatively analyzed using ELISA. Sensitivity and specificity metrics were calculated to determine the diagnostic efficacy of each biomarker., Results: A total of 223 mTBI patients (78%) did not undergo CT scan examination but were kept in observation for symptoms monitoring at the emergency department (ED) for more than 6 h (in-hospital-observation patients). Among CT-scanned patients ( n = 62), 14 (23%) were positive (CT+). Elevated levels of IL6 and IL10 were found in mTBI children compared to controls. Within mTBI patients, IL6 was significantly increased in CT+ patients compared to both CT- and in-hospital-observation patients. No significant differences were observed for IL8 among the compared groups. IL6 yielded a specificity of 48% in identifying CT- and in-hospital-observation patients, with 100% sensitivity in excluding all CT+ cases. These performances were maintained whether IL6 was measured within 6 h or within 24 h after the trauma., Conclusion: The inflammatory marker IL6 emerges as a robust biomarker, showing promising stratification value for pediatric mTBI patients undergoing CT scans or staying in observation in a pediatric ED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chiollaz, Pouillard, Habre, Seiler, Romano, Spigariol, Ritter Schenk, Korff, Maréchal, Wyss, Gruaz, Montaner, Manzano and Sanchez.)

Background: Structured competency-based training is one of the most frequently articulated wishes of residents., Methods: A survey of 19 residents was conducted regarding their satisfaction with the resident education at a level 1 trauma center. In this article the development of a revised competency-based education concept was carried out., Results: The survey reflected uncertainty as to whether the current structures could meet the requirements of the residency regulations. The improved competency-based education concept consists of clinical mentoring, competency-based catalogs of learning objectives, regular theoretical and practical workshops as well as regular and structured staff evaluations., Conclusion: The education concept presented reflects the attempt to establish a contemporary surgical training program which will be evaluated as it progresses., (© 2024. The Author(s).)

Children are highly vulnerable to mild traumatic brain injury (mTBI). Blood biomarkers can help in their management. This study evaluated the performances of biomarkers, in discriminating between children with mTBI who had intracranial injuries (ICIs) on computed tomography (CT+) and (1) patients without ICI (CT-) or (2) both CT- and in-hospital-observation without CT patients. The aim was to rule out the need of unnecessary CT scans and decrease the length of stay in observation in the emergency department (ED). Newborns to teenagers (≤16 years old) with mTBI (Glasgow Coma Scale > 13) were included. S100b, glial fibrillary acidic protein (GFAP), and heart fatty-acid-binding protein (HFABP) performances to identify patients without ICI were evaluated through receiver operating characteristic curves, where sensitivity was set at 100%. A total of 222 mTBI children sampled within 6 h since their trauma were reported. Nineteen percent ( n = 43/222) underwent CT scan examination, whereas the others ( n = 179/222) were kept in observation at the ED. Sixteen percent ( n = 7/43) of the children who underwent a CT scan had ICI, corresponding to 3% of all mTBI-included patients. When sensibility (SE) was set at 100% to exclude all patients with ICI, GFAP yielded 39% specificity (SP), HFABP 37%, and S100b 34% to rule out the need of CT scans. These biomarkers were even more performant: 52% SP for GFAP, 41% for HFABP, and 39% for S100b, when discriminating CT+ versus both in-hospital-observation and CT- patients. These markers can significantly help in the management of patients in the ED, avoiding unnecessary CT scans, and reducing length of stay for children and their families., (© Anne-Cécile Chiollaz et al., 2024; Published by Mary Ann Liebert, Inc.)

Public health and safety measures (PHSM) made in response to the COVID-19 pandemic have been singular, rapid, and profuse compared to the content, speed, and volume of normal policy-making. Not only can they have a profound effect on the spread of the disease, but they may also have multitudinous secondary effects, in both the social and natural worlds. Unfortunately, despite the best efforts by numerous research groups, existing data on COVID-19 PHSM only partially captures their full geographical scale and policy scope for any significant duration of time. This paper introduces our effort to harmonize data from the eight largest such efforts for policies made before September 21, 2021 into the taxonomy developed by the CoronaNet Research Project in order to respond to the need for comprehensive, high quality COVID-19 data. In doing so, we present a comprehensive comparative analysis of existing data from different COVID-19 PHSM datasets, introduce our novel methodology for harmonizing COVID-19 PHSM data, and provide a clear-eyed assessment of the pros and cons of our efforts., (© 2024. The Author(s).)

Metabolic fluxes, the number of metabolites traversing each biochemical reaction in a cell per unit time, are crucial for assessing and understanding cell function. 13C Metabolic Flux Analysis (13C MFA) is considered to be the gold standard for measuring metabolic fluxes. 13C MFA typically works by leveraging extracellular exchange fluxes as well as data from 13C labeling experiments to calculate the flux profile which best fit the data for a small, central carbon, metabolic model. However, the nonlinear nature of the 13C MFA fitting procedure means that several flux profiles fit the experimental data within the experimental error, and traditional optimization methods offer only a partial or skewed picture, especially in "non-gaussian" situations where multiple very distinct flux regions fit the data equally well. Here, we present a method for flux space sampling through Bayesian inference (BayFlux), that identifies the full distribution of fluxes compatible with experimental data for a comprehensive genome-scale model. This Bayesian approach allows us to accurately quantify uncertainty in calculated fluxes. We also find that, surprisingly, the genome-scale model of metabolism produces narrower flux distributions (reduced uncertainty) than the small core metabolic models traditionally used in 13C MFA. The different results for some reactions when using genome-scale models vs core metabolic models advise caution in assuming strong inferences from 13C MFA since the results may depend significantly on the completeness of the model used. Based on BayFlux, we developed and evaluated novel methods (P-13C MOMA and P-13C ROOM) to predict the biological results of a gene knockout, that improve on the traditional MOMA and ROOM methods by quantifying prediction uncertainty., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.D.K. has financial interests in Amyris, Ansa Biotechnologies, Apertor Pharma, Berkeley Yeast, Cyklos Materials, Demetrix, Lygos, Napigen, ResVita Bio and Zero Acre Farms., (Copyright: © 2023 Backman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Assess urgent care (UC) clinician prescribing practices and factors associated with first-line antibiotic selection and recommended duration of therapy for sinusitis, acute otitis media (AOM), and pharyngitis., Design: Retrospective cohort study., Participants: All respiratory UC encounters and clinicians in the Intermountain Health (IH) network, July 1st, 2019-June 30th, 2020., Methods: Descriptive statistics were used to characterize first-line antibiotic selection rates and the duration of antibiotic prescriptions during pharyngitis, sinusitis, and AOM UC encounters. Patient and clinician characteristics were evaluated. System-specific guidelines recommended 5-10 days of penicillin, amoxicillin, or amoxicillin-clavulanate as first-line. Alternative therapies were recommended for penicillin allergy. Generalized estimating equation modeling was used to assess predictors of first-line antibiotic selection, prescription duration, and first-line antibiotic prescriptions for an appropriate duration., Results: Among encounters in which an antibiotic was prescribed, the rate of first-line antibiotic selection was 75%, the recommended duration was 70%, and the rate of first-line antibiotic selection for the recommended duration was 53%. AOM was associated with the highest rate of first-line prescriptions (83%); sinusitis the lowest (69%). Pharyngitis was associated with the highest rate of prescriptions for the recommended duration (91%); AOM the lowest (51%). Penicillin allergy was the strongest predictor of non-first-line selection (OR = 0.02, 95% CI [0.02, 0.02]) and was also associated with extended duration prescriptions (OR = 0.87 [0.80, 0.95])., Conclusions: First-line antibiotic selection and duration for respiratory UC encounters varied by diagnosis and patient characteristics. These areas can serve as a focus for ongoing stewardship efforts., (© The Author(s) 2023.)

Rhodococcus opacus is a bacterium that has a high tolerance to aromatic compounds and can produce significant amounts of triacylglycerol (TAG). Here, we present iGR1773, the first genome-scale model (GSM) of R. opacus PD630 metabolism based on its genomic sequence and associated data. The model includes 1773 genes, 3025 reactions, and 1956 metabolites, was developed in a reproducible manner using CarveMe, and was evaluated through Metabolic Model tests (MEMOTE). We combine the model with two Constraint-Based Reconstruction and Analysis (COBRA) methods that use transcriptomics data to predict growth rates and fluxes: E-Flux2 and SPOT (Simplified Pearson Correlation with Transcriptomic data). Growth rates are best predicted by E-Flux2. Flux profiles are more accurately predicted by E-Flux2 than flux balance analysis (FBA) and parsimonious FBA (pFBA), when compared to 44 central carbon fluxes measured by 13 C-Metabolic Flux Analysis ( 13 C-MFA). Under glucose-fed conditions, E-Flux2 presents an R 2 value of 0.54, while predictions based on pFBA had an inferior R 2 of 0.28. We attribute this improved performance to the extra activity information provided by the transcriptomics data. For phenol-fed metabolism, in which the substrate first enters the TCA cycle, E-Flux2's flux predictions display a high R 2 of 0.96 while pFBA showed an R 2 of 0.93. We also show that glucose metabolism and phenol metabolism function with similar relative ATP maintenance costs. These findings demonstrate that iGR1773 can help the metabolic engineering community predict aromatic substrate utilization patterns and perform computational strain design.

Introduction: Breast reduction surgery is one of the most frequently performed surgeries amongst plastic and reconstructive surgeons worldwide. Previous studies have shown decreased risk of breast cancer development in women undergoing breast reduction surgery of up to 28%. We aimed to evaluate the relative risk of breast cancer development in our patients after breast reduction surgery in relation to the general female population of Austria., Methods: A total of 637 women underwent breast reduction surgery between 2003 and 2017 at our department. From those women, 513 patients completed a follow-up assessment of breast cancer development and were included into the study sample. The age-specific incidence rate data of the general female population of Austria served as the control group and basis for the calculation of the standardized incidence ratio (SIR) and Poisson test., Results: Relative to 5.66 expected cases of breast cancer, our cohort showed 1 subject with breast cancer after breast reduction surgery (SIR = 0.1765). An exact Poisson test was carried out to determine the level of significance of the difference between the incidence rate observed in the sample compared to the expected rate based on the age-specific incidence rates of the general population ( p = 0.023, α = 0.05)., Discussion: Our study underlines the strong evidence of previous studies for significant breast cancer reduction in patients after reductive mammoplasty. In comparison to the general female population of Austria, our cohort showed a reduction in breast cancer incidence of about 82%. The authors believe that different techniques in reduction mammoplasty have different levels of safety regarding the prevention and risk reduction for breast cancer. Further investigation must be conducted to evaluate the reduction of breast cancer risk with different surgical techniques., Competing Interests: All named authors hereby declare that they have no conflicts of interest to disclose., (Copyright © 2021 by S. Karger AG, Basel.)

Background: To date, few data are available about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in young children and the role of early-life childcare arrangements in transmission of the virus. In this study, we assessed the SARS-CoV-2 seroprevalence in children less than 6 years of age in the canton of Fribourg and identified risk factors associated with seropositivity., Methods: The COVPED study is a population-based cross-sectional study in children less than 6 years of age living in the canton of Fribourg, Switzerland, who presented to a private paediatrician or the paediatric emergency department of the Fribourg Hospital during a 9-week period between 11 January and 14 March 2021. Immunoglobulin G antibodies against SARS-CoV-2 trimeric spike protein were measured in capillary blood samples using an in-house Luminex assay. A mean fluorescence intensity ratio of above 6 was considered as positive. Metadata was collected through electronic questionnaires. Logistic regression analysis was performed to assess the risk of seropositivity and associated factors., Results: A total of 871 children, with a median age of 33 months (range 6 days to 5 years 11 months) were included; 412 (47%) were female. Overall, 180 (21%, 95% confidence interval [CI] 18-24%) children were seropositive. Age as continuous variable was not associated with seropositivity risk, apart from a higher rate in children less than 3 months of age. Univariable analysis showed that female sex was associated with a lower seropositivity risk (unadjusted odds ratio [OR] 0.69, 95% CI 0.49-0.96; p = 0.03). Day-care attendance was also associated with a lower seropositivity risk (OR 0.67, 95% CI 0.47-0.95; p = 0.03), whereas all other childcare arrangements were not associated with seropositivity. No association was found between the number of children and adults present in extra-familial care and seropositivity. Multivariable analysis identified the number of household members above the age of 12 years being positive for SARS-CoV-2 as the main risk factor for seropositivity in children (adjusted odds ratio [aOR] 7.80, 95% CI 4.65-13.07; p <0.001 for one household member, aOR 22.07, 95% CI 13.49-36.11; p <0.001 for two household members and aOR 32.20, 95% CI 9.30-111.55; p <0.001 for three or more household members)., Conclusion: The number of household members tested positive for SARS-CoV-2 (PCR test) is the main exposure risk to seropositivity for children less than 6 years of age. But the family size is not associated with an increased risk of infection. In young children, extra-familial care does not increase the risk of becoming SARS-CoV-2 seropositive, neither does the number of contacts present in extra-familial care. As adults and children will be vaccinated and new virus variants will be circulating the risk of exposure for young children will likely change and needs further monitoring.

Background: Male support for partners' antenatal care (ANC) has the potential to improve women's care-seeking and maternal health outcomes. This study describes factors that are associated with men's involvement in household tasks and explores the relationship between men's help with tasks and women's ANC-seeking, diet and workload during pregnancy as well as other health behaviors., Methods: This study was conducted in five Lake Zone regions of Tanzania. Cross-sectional surveys were carried out among approximately 10,000 households that had children under the age of 2 years. Surveys were administered to mothers of children less than 2 years and where available, their male partners. Data were collected between December 2015 and May 2020, in conjunction with a large-scale campaign aimed at reducing childhood stunting by changing the behavior of mothers, caregivers, and decision makers. Data analysis included bivariate analysis and logistic regression modeling., Results: Men's engagement in household activities was significantly associated with living in an urban setting, being younger, having at least some formal schooling, early verbal interactions with their children, and male involvement in healthcare decisions. Additionally, mothers of male partners that were engaged in household activities were significantly older and more likely to have at least some secondary school education. Relative to households where men only infrequently helped out with chores or not at all, women from households where men frequently helped were significantly more likely to have taken iron tablets during pregnancy, report having eaten more than usual, lessening their household workload during their most recent pregnancy, and more likely to have played with their child in the week prior to the survey., Conclusion: Male's participation in household tasks is associated with a general improvement in mother's ANC behaviors. Implicit in these findings is that general primary education for both men and women has health benefits that transcend socioeconomic class and that future interventions aimed to engage males in household tasks may target older males with less education living in rural areas., (© 2021. The Author(s).)

Introduction: The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genetics in Latin American countries. Methods: A systematic review was completed, aimed at identifying the frequency, clinical heterogeneity, and genetics studies of FTD in Latin American populations. The search strategies used a combination of standardized terms for FTD and related disorders. In addition, at least one author per Latin American country summarized the available literature. Collaborative or regional studies were reviewed during consensus meetings. Results: The first FTD reports published in Latin America were mostly case reports. The last two decades marked a substantial increase in the number of FTD research in Latin American countries. Brazil (165), Argentina (84), Colombia (26), and Chile (23) are the countries with the larger numbers of FTD published studies. Most of the research has focused on clinical and neuropsychological features ( n = 247), including the local adaptation of neuropsychological and behavioral assessment batteries. However, there are little to no large studies on prevalence ( n = 4), biomarkers ( n = 9), or neuropathology ( n = 3) of FTD. Conclusions: Future FTD studies will be required in Latin America, albeit with a greater emphasis on clinical diagnosis, genetics, biomarkers, and neuropathological studies. Regional and country-level efforts should seek better estimations of the prevalence, incidence, and economic impact of FTD syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Llibre-Guerra, Behrens, Hosogi, Montero, Torralva, Custodio, Longoria-Ibarrola, Giraldo-Chica, Aguillón, Hardi, Maestre, Contreras, Doldan, Duque-Peñailillo, Hesse, Roman, Santana-Trinidad, Schenk, Ocampo-Barba, López-Contreras and Nitrini.)

Introduction: A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open., Methods: A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm., Results: Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression., Discussion: Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America., (© 2020 the Alzheimer's Association.)

Objective: Prostate lesions detected with multiparametric magnetic resonance imaging (mpMRI) are classified for their malignant potential according to the Prostate Imaging-Reporting And Data System (PI-RADS™2). In this study, we evaluate the diagnostic accuracy of the mpMRI with and without gadolinium, with emphasis on the added diagnostic value of the dynamic contrast enhancement (DCE)., Materials and Methods: The study was retrospective for 286 prostate lesions / 213 eligible patients, n = 116/170, and 49/59% malignant for the peripheral (Pz) and transitional zone (Tz), respectively. A stereotactic MRI-guided prostate biopsy served as the histological ground truth. All patients received a mpMRI with DCE. The influence of DCE in the prediction of malignancy was analyzed by blinded assessment of the imaging protocol without DCE and the DCE separately., Results: Significant (CSPca) and insignificant (IPca) prostate cancers were evaluated separately to enhance the potential effects of the DCE in the detection of CSPca. The Receiver Operating Characteristics Area Under Curve (ROC-AUC), sensitivity (Se) and specificity (Spe) of PIRADS-without-DCE in the Pz was 0.70/0.47/0.86 for all cancers (IPca and CSPca merged) and 0.73/0.54/0.82 for CSPca. PIRADS-with-DCE for the same patients showed ROC-AUC/Se/Spe of 0.70/0.49/0.86 for all Pz cancers and 0.69/0.54/0.81 for CSPca in the Pz, respectively, p>0.05 chi-squared test. Similar results for the Tz, AUC/Se/Spe for PIRADS-without-DCE was 0.75/0.61/0.79 all cancers and 0.67/0.54/0.71 for CSPca, not influenced by DCE (0.66/0.47/0.81 for all Tz cancers and 0.61/0.39/0.75 for CSPca in Tz). The added Se and Spe of DCE for the detection of CSPca was 88/34% and 78/33% in the Pz and Tz, respectively., Conclusion: DCE showed no significant added diagnostic value and lower specificity for the prediction of CSPca compared to the non-enhanced sequences. Our results support that gadolinium might be omitted without mitigating the diagnostic accuracy of the mpMRI for prostate cancer., Competing Interests: The authors have declared that no competing interests exist.

Background: At present, the flexible endoscopic evaluation of swallowing (FEES) is one of the most commonly used methods for the objective assessment of swallowing. This multicenter trial prospectively collected data on the safety of FEES and also assessed the impact of this procedure on clinical dysphagia management., Methods: Patients were recruited in 23 hospitals in Germany and Switzerland from September 2014 to May 2017. Patient characteristics, professional affiliation of the FEES examiners (physicians or speech and language therapists), side-effects and cardiorespiratory parameters, severity of dysphagia and clinical consequences of FEES were documented., Results: 2401 patients, mean age 69.8 (14.6) years, 42.3% women, were included in the FEES-registry. The most common main diagnosis was stroke (61%), followed by Parkinson's disease (6.5%). FEES was well tolerated by patients. Complications were reported in 2% of examinations, were all self-limited and resolved without sequelae and showed no correlation to the endoscopist's previous experience. In more than 50% of investigations FEES led to changes of feeding strategies, in the majority of cases an upgrade of oral diet was possible., Discussion: This study confirmed that FEES, even when performed by less experienced clinicians is a safe and well tolerated procedure and significantly impacts on the patients' clinical course. Implementation of a FEES-service in different clinical settings may improve dysphagia care., Trial Registration: ClinicalTrials.gov NCT03037762, registered January 31st 2017., (© The Author(s) 2019.)

Background & Aims: The lipid-binding protein, SEC14L2, is crucial for the efficient viral replication of clinical hepatitis C virus (HCV) isolates in cell culture. Given the role of SEC14L2 in HCV replication, we aimed to study a large number of HCV positive sera carrying genotypes 1-4, to identify viral factors associated with efficient replication in culture. Additionally, we investigated whether 13 single nucleotide polymorphisms (SNPs) of SEC14L2 have an impact on RNA replication of naturally occurring HCV isolates., Methods: We generated Huh-7.5 cell lines overexpressing SEC14L2 or 13 coding SNPs and tested 73 different HCV positive sera for in vitro replication. Furthermore, we genotyped a cohort of 262 patients with chronic HCV for the common SNP (rs757660) and investigated its effect on the clinical phenotype., Results: HCV isolates from genotype 1, 2, 3 and 4 replicate in Huh-7.5 cells overexpressing SEC14L2. Interestingly, only subgenomic replicons from genotypes 1 and 3 showed enhanced replication whereas genotypes 2 and 4 remained unaffected. Furthermore, replication was independent of viral load. Importantly, all tested SNPs supported HCV RNA replication in vitro, while 1 SNP was associated with decreased SEC1L2 expression and viral RNA. All SNPs exhibited comparable cellular cholesterol and vitamin E abundance in naïve Huh-7.5 cells., Conclusions: This large screen of natural HCV isolates of 4 genotypes underscores the relevance of SEC14L2 as an in vitro HCV host factor. Additionally, SEC14L2 variants appear to recapitulate the wild-type enhancement of HCV replication. Variant rs191341134 showed a decreased effect due to lowered stability, whereas variant rs757660, a high prevalence mutant, showed a similar phenotype to the wild-type., Lay Summary: Until the year 2015, consistent replication of patient-derived isolates of hepatitis C virus (HCV) in an in vitro model remained a limitation in HCV research. In 2015 a group of authors identified a protein named SEC14L2 that enabled the replication of HCV isolates in cell culture. We performed a large screen encompassing 73 isolates of 4 different HCV genotypes. Additionally, we replaced the natural SEC14L2 with 13 different mutants to test if the protein variation significantly altered its HCV replication enhancing functions. We showed that different genotypes of HCV react differently to the presence of this protein and the variants of the protein mimic the behavior of the wild-type., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

As part of the U.S. Environmental Protection Agency's (EPA's) continuing assessment of advanced light-duty automotive technologies in support of regulatory and compliance programs, a 2018 Toyota Camry A25A-FKS 4-cylinder, 2.5-liter, naturally aspirated, Atkinson Cycle engine with cooled exhaust gas recirculation (cEGR) was benchmarked. The engine was tested on an engine dynamometer with and without its 8-speed automatic transmission, and with the engine wiring harness tethered to a complete vehicle parked outside of the test cell. Engine and transmission torque, fuel flow, key engine temperatures and pressures, onboard diagnostics (OBD) data, and Controller Area Network (CAN) bus data were recorded. This paper documents the test results under idle, low, medium, and high load engine operation. Motoring torque, wide open throttle (WOT) torque and fuel consumption are measured during transient operation using both EPA Tier 2 and Tier 3 test fuels. The design and performance of this 2018 2.5-liter engine is described and compared to Toyota's published data and to EPA's previous projections of the efficiency of an Atkinson Cycle engine with cEGR. The Brake Thermal Efficiency (BTE) map for the Toyota A25A-FKS engine shows a peak efficiency near 40 percent, which is the highest value of any publicly available map for a non-hybrid production gasoline internal combustion (IC) engine designed to run on 91 RON fuel. Further improvement is possible by application of fixed discrete or full continuous cylinder deactivation, both of which are currently in production on other engines.

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a phosphoprotein with key functions in regulating viral RNA replication and assembly. Two phosphoisoforms are discriminated by their different apparent molecular weights: a basally phosphorylated (p56) and a hyperphosphorylated (p58) variant. The precise mechanisms governing p58 synthesis and specific functions of the isoforms are poorly understood. Our study aimed at a deeper understanding of determinants involved in p58 synthesis. We analyzed two variants of p56 and p58 of isolate JFH-1 separately by mass spectrometry using an expression model and thereby identified a threonine-rich phosphopeptide exclusively found in the hyperphosphorylated variant. Individual exchange of possible phosphoacceptor sites to phosphoablatant or -mimetic residues had little impact on HCV replication or assembly in cell culture. A phosphospecific antibody recognizing pT242 revealed that this position was indeed phosphorylated only in p58 and depended on casein kinase Iα. Importantly, phosphoablative mutations at positions T244 and S247 abrogated pT242 detection without substantial effects on global p58 levels, whereas mutations in the preceding serine-rich cluster dramatically reduced total p58 levels but had minor impact on pT242 levels, suggesting the existence of distinct subspecies of hyperphosphorylated NS5A. Mass spectrometry analyses of different genotypes showed variable phosphorylation patterns across NS5A and suggested that the threonine-rich region is also phosphorylated at T242 in gt4a and at S249 in gt1a, gt1b, and gt4a. Our data therefore indicate that p58 is not a single homogenously phosphorylated protein species but rather a population of various phosphoisoforms, with high variability between genotypes. IMPORTANCE Hepatitis C virus infections affect 71 million people worldwide and cause severe chronic liver disease. Recently, efficient antiviral therapies have been established, with inhibitors of nonstructural protein NS5A as a cornerstone. NS5A is a central regulator of HCV replication and assembly but is still enigmatic in its molecular functions. It exists in two phosphoisoforms, p56 and p58. We identified a phosphopeptide exclusively found in p58 and analyzed the determinants involved in phosphorylation of this region. We found evidence for very different phosphorylation patterns resulting in p58. These results challenge the concept of p58 being a homogenous species of NS5A molecules phosphorylated at the same positions and argues for at least two independently phosphorylated variants showing the same electrophoretic mobility, likely serving different functions., (Copyright © 2018 American Society for Microbiology.)

A chemically assisted top-down method for the synthesis of MOF-nanoplates was developed applying amine based delamination agents. Applied on a well described model structure, the layered MOF Cu 2 (bdc) 2 (DMF) 2 (bdc - 1,4-benzenedicarboxylate), two different strategies of amine assisted delamination turned out to be successful to obtain nanoplates. Particles with thicknesses of around 70 nm were obtained by direct delamination of crystals using octylamine. The surfactant (polyvinylpyrrolidone) assisted synthesis combined with a post-synthetic amine delamination step enabled a further reduction of the thickness of the MOF nanoplates down to 4-14 nm.

Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV). Characteristic membrane alterations induced by ORF1 expression resembled those found in MNV infected cells, consisting of vesicle accumulations likely built from the endoplasmic reticulum (ER) which included single membrane vesicles (SMVs), double membrane vesicles (DMVs) and multi membrane vesicles (MMVs). In-depth analysis using electron tomography suggested that MMVs originate through the enwrapping of SMVs with tubular structures similar to mechanisms reported for picornaviruses. Expression of GII.4 NS1-2, NS3 and NS4 fused to GFP revealed distinct membrane alterations when analyzed by correlative light and electron microscopy. Expression of NS1-2 induced proliferation of smooth ER membranes forming long tubular structures that were affected by mutations in the active center of the putative NS1-2 hydrolase domain. NS3 was associated with ER membranes around lipid droplets (LDs) and induced the formation of convoluted membranes, which were even more pronounced in case of NS4. Interestingly, NS4 was the only GII.4 protein capable of inducing SMV and DMV formation when expressed individually. Our work provides the first ultrastructural analysis of norovirus GII.4 induced vesicle clusters and suggests that their morphology and biogenesis is most similar to picornaviruses. We further identified NS4 as a key factor in the formation of membrane alterations of huNoV and provide models of the putative membrane topologies of NS1-2, NS3 and NS4 to guide future studies.

Background: Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade., Aim/objective: To assess the performance of Watson Elementary™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies., Methods: The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth., Results: The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (P 0.06, χ2 test). Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (P 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (P 0.60, Pearson´s correlation)., Conclusion: The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis.

Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an Aβ(1-42) fibril composed of two intertwined protofilaments determined by cryo-electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Overall, 41% of all work-related accidents lead to a hand injury. In the younger generation, the incidence rate even rises to 50%. In Austria, these accidents result in approximately half a million sick leave days per annum, an average of 12.5 days per accident. In comparison, leisure-time hand injuries show a significantly higher accident rate: 60% of hand injuries occur during leisure time. Far fewer safety measures are taken and a lack of adequate training and a disregard for safety recommendations are observed.This large number of hand injuries led to the launch of a campaign in Austria in 2014-2015 called "Hände gut - Alles Gut", (Hands well - all's well). This campaign was aimed at reducing the costs, a sum of 309 million Euros, incurred solely from work-related hand accidents, by at least 5-10%.These exorbitantly high costs are not only due to severe hand trauma, most result from a multitude of slight and superficial wounds.

Sleep promotes the consolidation of newly acquired associative memories. Here we used neuronal oscillations in the human EEG to investigate sleep-dependent changes in the cortical memory trace. The retrieval activity for object-color associations was assessed immediately after encoding and after 3 hr of sleep or wakefulness. Sleep had beneficial effects on memory performance and led to reduced event-related theta and gamma power during the retrieval of associative memories. Furthermore, event-related alpha suppression was attenuated in the wake group for memorized and novel stimuli. There were no sleep-dependent changes in retrieval activity for missed items or items retrieved without color. Thus, the sleep-dependent reduction in theta and gamma oscillations was specific for the retrieval of associative memories. In line with theoretical accounts on sleep-dependent memory consolidation, decreased theta may indicate reduced mediotemporal activity because of a transfer of information into neocortical networks during sleep, whereas reduced parietal gamma may reflect effects of synaptic downscaling. Changes in alpha suppression in the wake group possibly index reduced attentional resources that may also contribute to a lower memory performance in this group. These findings indicate that the consolidation of associative memories during sleep is associated with profound changes in the cortical memory trace and relies on multiple neuronal processes working in concert.

Background: The foamy viral genome encodes four central purine-rich elements localized in the integrase-coding region of pol. Previously, we have shown that the first two of these RNA elements (A and B) are required for protease dimerization and activation. The D element functions as internal polypurine tract during reverse transcription. Peters et al., described the third element (C) as essential for gag expression suggesting that it might serve as an RNA export element for the unspliced genomic transcript., Results: Here, we analysed env splicing and demonstrate that the described C element composed of three GAA repeats known to bind SR proteins regulates env splicing, thus balancing the amount of gag/pol mRNAs. Deletion of the C element effectively promotes a splice site switch from a newly identified env splice acceptor to the intrinsically strong downstream localised env 3' splice acceptor permitting complete splicing of almost all LTR derived transcripts. We provide evidence that repression of this env splice acceptor is a prerequisite for gag expression. This repression is achieved by the C element, resulting in impaired branch point recognition and SF1/mBBP binding. Separating the branch point from the overlapping purine-rich C element, by insertion of only 20 nucleotides, liberated repression and fully restored splicing to the intrinsically strong env 3' splice site. This indicated that the cis-acting element might repress splicing by blocking the recognition of essential splice site signals., Conclusions: The foamy viral purine-rich C element regulates splicing by suppressing the branch point recognition of the strongest env splice acceptor. It is essential for the formation of unspliced gag and singly spliced pol transcripts.

Introduction: Non-adherence to disease-modifying antirheumatic drugs (DMARDs) is suspected to relate to health care costs. In this study we investigated this relation in the first year of treatment., Methods: In a multi-center cohort study with a one year follow up, non-adherence was continuously measured using electronic monitored medication jars. Non-adherence was defined as the number of days with a negative difference between expected and observed opening of the container. Cost measurement focused on hospital costs in the first year: consultations, emergency room visits, hospitalization, medical procedures, imaging modalities, medication costs, and laboratory tests. Cost volumes were registered from patient medical files. We applied multivariate regression analyses for the association between non-adherence and costs, and other variables (age, sex, center, baseline disease activity, diagnosis, socioeconomic status, anxiety and depression) and costs., Results: Of the 275 invited patients, 206 were willing to participate. 74.2% had rheumatoid arthritis, 20.9% had psoriatic arthritis and 4.9% undifferentiated arthritis. 23.7% of the patients were more than 20% non-adherent over the follow-up period. Mean costs are € 2117.25 (SD € 3020.32). Non-adherence was positively related to costs in addition to baseline anxiety., Conclusion: Non-adherence is associated with health care costs in the first year of treatment for arthritis. This suggests that improving adherence is not only associated with better outcome, but also with savings., Competing Interests: The authors have declared that no competing interests exist.

Preparation of thin-layer chromatographic (TLC) plates based on metal-organic frameworks (MOFs) as porous stationary phases is described. DUT-67 (DUT = Dresden University of Technology), a zirconium based MOF, was used in combination with a fluorescent indicator as stationary phase for analyzing a small selection of a wide spectrum of relevant analytes. The successful separation of benzaldehyde from trans-cinnamaldehyde and 4-aminophenol from 2-aminotoluene is reported as a model system using optimized eluent mixtures containing acetic acid.

With a single exception, all isolates of hepatitis C virus (HCV) require adaptive mutations to replicate efficiently in cell culture. Here, we show that a major class of adaptive mutations regulates the activity of a cellular lipid kinase, phosphatidylinositol 4-kinase IIIα (PI4KA). HCV needs to stimulate PI4KA to create a permissive phosphatidylinositol 4-phosphate-enriched membrane microenvironment in the liver and in primary human hepatocytes (PHHs). In contrast, in Huh7 hepatoma cells, the virus must acquire loss-of-function mutations that prevent PI4KA overactivation. This adaptive mechanism is necessitated by increased PI4KA levels in Huh7 cells compared with PHHs, and is conserved across HCV genotypes. PI4KA-specific inhibitors promote replication of unadapted viral isolates and allow efficient replication of patient-derived virus in cell culture. In summary, this study has uncovered a long-sought mechanism of HCV cell-culture adaptation and demonstrates how a virus can adapt to changes in a cellular environment associated with tumorigenesis.

Objectives: Elevated hip fracture incidence is a major public health problem looming to aggravate in industrialized countries due to demographic developments. We report hip fracture incidence and expected future cases from Vorarlberg, the westernmost province of Austria, results potentially representative of Central European populations., Methods: Crude and standardized hip fracture incidence rates in Vorarlberg 2003-2013 are reported. Based on the age-specific incidence in 2013 or trends 2003-2013, we predict hip fractures till 2050., Results: Female age-standardized hip fracture incidence decreased 2005-2013, whereas for men, the trend was rather unclear. Uncorrected forecasts indicate that by 2050, female and male cases will each have more than doubled from 2015 in all demographic core scenarios. Corrected by incidence trends before 2013, cases are expected to drop among women but rise among men., Conclusions: We anticipate rising hip fracture numbers in Vorarlberg within the next decades, unless prevention programs that presumably account for decreasing incidence rates, particularly among women since 2005, take further effect to counteract the predicted steady increase due to demographic changes. Concomitantly, augmented endeavors to target the male population by these programs are needed.

Total organic gases (TOG) emissions from motor vehicles include air toxic compounds and contribute to formation of ground-level ozone and secondary organic aerosol (SOA). These emissions are known to be affected by temperature; however previous studies have typically focused only on the temperature dependence of total emission factors and select toxic compounds. This study builds on the previous research by performing an evaluation of a comprehensive set of gas-phase organic compounds present in gasoline motor vehicle exhaust. A fleet of five vehicles using port fuel injection engine technology and running on E10 fuel was tested. Overall, three temperatures (0, 20, and 75 °F; or -18, -7, and 24 °C), two driving conditions (urban-FTP75 and aggressive driving-US06) and 161 compounds were evaluated; the emissions distributions were used to construct speciation profiles for each driving cycle and temperature. Overall, the speciation results indicated a significant increase in alkane and methane content, and decrease in alcohol, aldehyde and ketone content with decreasing temperature. These were verified using a statistical significance test. The fraction and composition of Mobile Source Air Toxics (MSATs) were significantly affected by temperature for both driving cycles. The ozone forming potentials of these profiles were evaluated using the maximum incremental reactivity (MIR) scale. Aromatic content was predicted to be a major driver behind the ozone forming potentials. Additionally, the decreasing ozone potential could be attributed to increased methane fractions with increasing temperature.

Femtosecond pump-probe absorption spectroscopy in tetrahydrofuran solution has been used to investigate the dynamics of a metalloid cluster compound {Ge9[Si(SiMe3)3]3}(-). Upon UV photoexcitation, the transients in the near-infrared spectral region showed signatures reminiscent of excess electrons in THF (bound or quasi-free) whereas in the visible part excited state dynamics of the cluster complex dominates.

Hand injuries are a frequent occurrence and account for 41% of all occupational injuries. In general such accidents are the result of stress, inattention, tiredness, use of defective or poorly maintained machinery. However, artention must equally be directed at the large number of accidents occurring in leisure time activities since the inability to work due to a leisure time accident is similarly cost-intensive. Throughout Europe attempts have been made in the past 10 years to improve prevention. At the initiative of the Hand Trauma Committee (HTC) of FESSH prevention conferences were stated in 2009. These have in part reduced the number of hand injuries in -Europe. In Austria a special controlling committee was founded by the Austrian Workers' Compensation Board (AUVA) with the specific objective of reducing the number of hand injuries. Similarly the "Circle for Leisure Time Hand Injury Prevention" was created to specifically deal with hand injuries occurring during leisure time activities. Through the cooperation of these 2 committees and implementation of the thus decided measures, a reduction in the number of accidents involving the hand is to be expected with a concomitant reduction in the associated costs., (© Georg Thieme Verlag KG Stuttgart · New York.)

Small vessel disease (SVD) in the brain manifests in the periventricular and deep white matter and radiographically is described as "leukoaraiosis". It is increasingly recognized as a cause of morbidity from middle age onward and this clinical relevance has paralleled advances in the field of neuroradiology. Overall, SVD is a heterogenous group of vascular disorders that may be asymptomatic, or a harbinger of many conditions that jeopardize brain health. Management and prevention focuses on blood pressure control, lifestyle modification, and symptomatic treatment.

As part of the risk assessment and strategic planning related to the emergence of avian influenza A(H7N9) in China the European Centre for Disease Prevention and Control (ECDC) has considered two major scenarios. The current situation is the one of a zoonotic epidemic (Scenario A) in which the virus might be transmitted sporadically to humans in close contact with an animal reservoir. The second scenario is the movement towards efficient human to human transmission (a pandemic Scenario B). We identified epidemiological events within the different scenarios that would trigger a new risk assessment and a review of the response activities to implement in the European Union (EU). Further, we identified the surveillance activities needed to detect these events. The EU should prepare for importation of isolated human cases infected in the affected area, though this event would not change the level of public health risk. Awareness among clinicians and local public health authorities, combined with nationally available testing, will be crucial. A ’one health’ surveillance strategy is needed to detect extension of the infection towards Europe. The emergence of a novel reassortant influenza A(H7N9) underlines that pandemic preparedness remains important for Europe.

Purpose: We aim to derive an internationally applicable data set to improve prescription safety of psychiatric drugs., Methods: We performed an in-depth analysis of the concordance of prescribing information of 10 key psychiatric drugs across four major drug markets with regard to indications, warnings and precautions, and contraindications., Results: The individual prescribing information covered on average 71.4 ± 30.3% of all named indications, 59.5 ± 17.1% of all potential warnings and precautions and 70.1 ± 24.4% of all applicable contraindications., Conclusion: This substantial variation in key prescribing information across countries highlights the need for a better international cooperation and standardization of prescribing information., (Copyright © 2012 John Wiley & Sons, Ltd.)

Reactions of the extremely bulky amido alkali metal complexes, [KL'(η(6)-toluene)], or in situ generated [LiL'] or [LiL″] {L'/ L″ = N(Ar*)(SiR(3)), where Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4 and R = Me (L') or Ph (L″)} with group 13 metal(I) halides have yielded a series of monomeric metal(I) amide complexes, [ML'] (M = Ga, In, or Tl) and [ML″] (M = Ga or Tl), all but one of which have been crystallographically characterized. The results of the crystallographic studies, in combination with computational analyses, reveal that the metal centers in these compounds are one coordinate and do not exhibit any significant intra- or intermolecular interactions, other than their N-M linkages. One of the complexes, [InL'], represents the first example of a one-coordinate indium(I) amide. Attempts to extend this study to the preparation of the analogous aluminum(I) amide, [AlL'], were not successful. Despite this, a range of novel and potentially synthetically useful aluminum(III) halide and hydride complexes were prepared en route to [AlL'], the majority of which were crystallographically characterized. These include the alkali metal aluminate complexes, [L'AlH(2)(μ-H)Li(OEt(2))(2)(THF)] and [{L'Al(μ-H)(3)K}(2)], the neutral amido-aluminum hydride complex, [{L'AlH(μ-H)}(2)], and the aluminum halide complexes, [L'AlBr(2)(THF)] and [L'AlI(2)]. Reaction of the latter two systems with a variety of reducing agents led only to intractable product mixtures.

We report a case of cerebral air embolism after central dialysis line removal and the role of the fibrin sheath as portal (mechanism) of air entry. This case has been documented with computed tomographic (CT) images of the partially air-filled sheath tract.

A high yield synthesis of a new, extremely bulky anionic gallium(I) N-heterocyclic carbene analogue, [(DAB*)Ga:](-) (DAB* = {N(Ar*)C(H)}(2), Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4) has been developed and four monomeric sodium complexes of the heterocycle have been crystallographically characterised. The gallium(I) heterocycle has been utilised in the preparations of the heteroleptic zinc and cadmium gallyl complexes, [(DAB*)GaMX(tmeda)] (M = Zn or Cd, X = Br or I), which were crystallographically characterised. In addition, [(DAB*)Ga:](-) was oxidatively coupled to give the diamagnetic digallane(4), [(DAB*)GaGa(DAB*)]. The moderate yield synthesis of the six-membered gallium(I) heterocycle, [((But)MesNacnac)Ga:] ((But)MesNacnac = [(MesNCBu(t))(2)CH](-), Mes = mesityl), is described, and the compound found to be a monomer in the solid state by an X-ray crystallographic analysis. A low yield by-product from this synthesis, [Ga(5)I(4)((But)MesNacnac)(3)], was also isolated and shown by X-ray crystallography to be a rare example of a compound bearing a group 13 metal-metal bonded chain stabilised by β-diketiminate ligands. A preliminary analysis of the bonding in the compound was carried out using DFT calculations.

Reductions of the β-diketiminato group 14 metal(II) chloride complexes, [((But)MesNacnac)ECl] ((But)MesNacnac = [(MesNCBu(t))(2)CH](-); Mes = mesityl; E = Ge, Sn or Pb), with a magnesium(I) dimer have led to differing outcomes, which include the formation of the first β-diketiminato group 14 metal(I) dimer, [{((But)MesNacnac)Sn}(2)]., (This journal is © The Royal Society of Chemistry 2012)

Necrotizing fasciitis is a rare, life-threatening and rapidly spreading soft-tissue infection that results in necrosis of the muscle, fascia and surrounding tissue. It can be result of a polymicrobial synergistic infection or a streptococcal infection. The authors report a case of necrotizing fasciitis occurring in the knee of a 65-year-old woman following an uneventful primary total knee arthroplasty and resulting in above-the-knee amputation. Having in mind severe infections like necrotising fasciitis, one should be aware of the possibility of such postoperative complications especially in patients with risk factors even in routine procedures like a total knee arthroplasty.

The reduction of the bulky amido-germanium(II) chloride complex, LGeCl (L = N(SiMe(3))(Ar*); Ar* = C(6)H(2)Me{C(H)Ph(2)}(2)-4,2,6), with the magnesium(I) dimer, [{((Mes)Nacnac)Mg}(2)] ((Mes)Nacnac = [(MesNCMe)(2)CH](-); Mes = mesityl), afforded LGeGeL, which represents the first example of a digermyne with a Ge-Ge single bond. Computational studies of the compound have highlighted significant electronic differences between it and multiply bonded digermynes. LGeGeL was shown to cleanly activate H(2) in solution or the solid state, at temperatures as low as -10 °C, to give the mixed valence compound, LGeGe(H)(2)L.

The preparation of a series of extremely bulky secondary amines, Ar*N(H)SiR(3) (Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4; R(3) = Me(3), MePh(2) or Ph(3)) is described. Their deprotonation with either LiBu(n), NaH or KH yields alkali metal amide complexes, several monomeric examples of which, [Li(L){N(SiMe(3))(Ar*)}] (L = OEt(2) or THF), [Na(THF)(3){N(SiMe(3))(Ar*)}] and [K(OEt(2)){N(SiPh(3))(Ar*)], have been crystallographically characterised. Reactions of the lithium amides with germanium, tin or lead dichloride have yielded the first structurally characterised two-coordinate, monomeric amido germanium(II) and tin(II) chloride complexes, [{(SiR(3))(Ar*)N}ECl] (E = Ge or Sn; R = Me or Ph), and a chloride bridged amido-lead(II) dimer, [{[(SiMe(3))(Ar*)N]Pb(μ-Cl)}(2)]. DFT calculations on [{(SiMe(3))(Ar*)N}GeCl] show its HOMO to exhibit Ge lone pair character and its LUMO to encompass its Ge based p-orbital. A series of bulky amido silicon(IV) chloride complexes have also been prepared and several examples, [{(SiR(3))(Ar*)N}SiCl(3)] (R(3) = Me(3), MePh(2)) and [{(SiMe(3))(Ar*)N}SiHCl(2)], were crystallographically characterised. The sterically hindered group 14 complexes reported in this study hold significant potential as precursors for kinetically stabilised low oxidation state and/or low coordination number group 14 complexes.