Helical foldamers incorporating photoswitchable residues for light-mediated modulation of conformational preference

An E unsaturated fumaramide linkage may be introduced into Aib peptide foldamer structures by standard coupling methods and photoisomerized to its Z (maleamide) isomer by irradiation with UV light. As a result of the photoisomerization, a new hydrogen-bonded contact becomes possible between the peptide domains located on either side of the unsaturated linkage. Using the fumaramide/maleamide linker to couple a chiral and an achiral fragment allows the change in hydrogen bond network to communicate a conformational preference, inducing a screw sense preference in the achiral domain of the maleamide-linked foldamers that is absent from the fumaramides. Evidence for the induced screw sense preference is provided by NMR and CD, and also by the turning on by light of the diastereoselectivity of a peptide chain extension reaction. The fumaramide/maleamide linker thus acts as a "conformational photo diode" that conducts stereochemical information as a result of irradiation by UV ligh

ANALYSIS OF THE CONTRACTION OF THE PUBOVISCERAL MUSCLE BASED ON A COMPUTATIONAL MODEL

The Pelvic Floor (PF) is a set of soft parts that close the pelvis. Its function is related with the support and suspension of the pelvic organs maintaining urinary and fecal continence. When the pelvic floor muscles (PFM) are not strengthened, pelvic dysfunctions may appear. The strengthening exercises are performed through contraction of the PF, which are the basis of physiotherapy treatment. The aim of this study is to build the pelvic floor muscle, through magnetic resonance imaging (MRI), and simulate through the finite element method the contraction in an athlete that practices synchronized swimming. The present work shows a methodology that can be applied in the pelvic floor biomechanics

Non-Union Scoring System (NUSS): Is It Enough in Clinical Practice?

Introduction: Bone consolidation defects represent a real orthopedic challenge because of the absence of validated treatment guidelines that can assist the surgeon in his choices. The aim of this study is to evaluate the appropriateness of the Non-Union Scoring System NUSS treatment protocol in the management of long bone non-unions by comparing it to the experience-based therapeutic approach carried out in our facility. Materials and Methods: We conducted a comparative outcome study of a retrospective series of 89 patients surgically treated for long bone non-union in our facility vs. clinical results reported by Calori et al. obtained following the NUSS treatment protocol. Results: Radiographic healing was reached in 13/13 non-unions (100%) in group NUSS 1, in 58/62 (93.5%) in group NUSS 2, and in 13/14 (92.9%) in group NUSS 3. The mean time to radiographic healing was 5.69 ± 2.09 months in group 1, 7.38 ± 3.81 months in group 2 and 9.23 ± 2.31 months in group 3. 91% of patients in group I, 69% in group II and 48% in group III received what would be considered by the NUSS treatment protocol an “overtreatment”, especially from a biological stand point. The comparative outcome analysis shows that our case series achieved significantly higher global healing rates (p value = 0.017) and shorter radiological healing times in groups NUSS 1 and 2 (p value < 0.001). Conclusion: From the results obtained, we can assume that the NUSS treatment protocol might underestimate the necessary therapies, particularly from a biological point of view

Predisposing factors for amputation of lower extremities in diabetic patients with foot ulceration in the state of Sergipe

OBJECTIVE: To determine the predisposing factors for amputation of lower limbs in diabetic patients with foot ulceration. METHODS: The research was carried out in hospitals, and all diabetic patients with foot ulceration were included. Amputation was studied in relation to age, sex, previous amputation, number of ulcers, time of diagnosis of diabetes mellitus, time of ulceration, average number of days in hospital, Wagner's classification, and presence of foot pulse. RESULTS: We verified that 55% (44/80) of the patients progressed to some type of amputation of the lower limbs; mean age was 61 years, but the occurrence of amputation was significantly higher in the age group between 60 and 90 years (P = 0.03). We did not observe a significant variation in the following variables: time of diagnosis of diabetes, time of ulceration, and hospitalization time in relation to the group of patients who were amputated. Nevertheless, the most severe lesions, when evaluated by Wagner's classification (P <0.001) and by the absence of both distal pulses (P <0.001) of lower limbs, turned out to be very significant in relation to the amputation outcome. CONCLUSION: The severity of lesions, the absence of pulse and age over 60 years were considered predisposing factors for amputation in these patients.OBJETIVO: Determinar os fatores predisponentes para a amputação de membros inferiores nos doentes internados com diabetes melito e úlceras nos pés. MÉTODOS: Foram acompanhados os pacientes diabéticos com úlceras nos pés internados no período de 6 meses e analisadas as amputações nesses doentes em relação à idade, sexo, amputação prévia, número de ulcerações, tempo de diagnóstico do diabete, tempo de ulceração, tempo médio de internação, gravidade das lesões, presença de pulso. RESULTADOS: Verificou-se que 55% (44/80) dos doentes evoluíram para algum tipo de amputação de membros inferiores; a mediana das idades foi de 61 anos, porém a ocorrência de amputação foi significativamente maior na faixa etária dos 60 aos 90 anos (P = 0,03). Não se observou uma variação significativa da mediana do tempo de diagnóstico do diabetes, do tempo de ulceração e do tempo médio de internação em relação ao grupo de pacientes que foram amputados. Entretanto, as lesões mais graves, quando avaliadas pela classificação de Wagner (P <0,001) e pela ausência de detecção dos dois pulsos distais (P <0,001) dos membros inferiores, revelaram-se bastante significativas com relação ao desfecho de amputação. CONCLUSÃO: Foram considerados fatores predisponentes para a ocorrência de amputação nesses doentes a gravidade das lesões, a ausência de pulsos e as idades acima de 60 anos.Universidade TiradentesUniversidade Federal de Sergipe Departamento de MedicinaFundação Universitária de Ciências da Saúde de Alagoas Departamento de Medicina SocialEscola de Ciências Médicas de Alagoas Fundação Universitária de Ciências da Saúde de Alagoas Departamento de Clínica CirúrgicaUniversidade Federal de São Paulo (UNIFESP) Departamento de CirurgiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, Depto. de CirurgiaUNIFESP, EPMSciEL

Myticalins: A novel multigenic family of linear, cationic antimicrobial peptides from marine mussels (Mytilus spp.)

The application of high-throughput sequencing technologies to non-model organisms has brought new opportunities for the identification of bioactive peptides from genomes and transcriptomes. From this point of view, marine invertebrates represent a potentially rich, yet largely unexplored resource for de novo discovery due to their adaptation to diverse challenging habitats. Bioinformatics analyses of available genomic and transcriptomic data allowed us to identify myticalins, a novel family of antimicrobial peptides (AMPs) from the mussel Mytilus galloprovincialis, and a similar family of AMPs from Modiolus spp., named modiocalins. Their coding sequence encompasses two conserved N-terminal (signal peptide) and C-terminal (propeptide) regions and a hypervariable central cationic region corresponding to the mature peptide. Myticalins are taxonomically restricted to Mytiloida and they can be classified into four subfamilies. These AMPs are subject to considerable interindividual sequence variability and possibly to presence/absence variation. Functional assays performed on selected members of this family indicate a remarkable tissue-specific expression (in gills) and broad spectrum of activity against both Gram-positive and Gram-negative bacteria. Overall, we present the first linear AMPs ever described in marine mussels and confirm the great potential of bioinformatics tools for the de novo discovery of bioactive peptides in non-model organisms

Impact of coronavirus syndromes on physical and mental health of health care workers:Systematic review and meta-analysis

BackgroundHealth care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined.MethodsPRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I2 statistic, quality assessment and sensitivity analysis.Results115 articles were included (n=60,458 HCW, age 36.1±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9–83.7%, k=12, n=949), 47.9% cough (95%CI=39.2–56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9–56.0%, k=13, n=898), 42.3% chills (95%CI=20.2–67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2–68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1–48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2–40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8–33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9–31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9–28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0–67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9–54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9–45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4–48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3–53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2–50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5–47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2–31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2–96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4–28.1%, k=2, n=411).LimitationsLimited amount of evidence for some outcomes and suboptimal design in several studies included.ConclusionsSARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies

MRI-based radiomic prognostic signature for locally advanced oral cavity squamous cell carcinoma: development, testing and comparison with genomic prognostic signatures

Background. At present, the prognostic prediction in advanced oral cavity squamous cell carcinoma (OCSCC) is based on the tumor-node-metastasis (TNM) staging system, and the most used imaging modality in these patients is magnetic resonance image (MRI). With the aim to improve the prediction, we developed an MRI-based radiomic signature as a prognostic marker for overall survival (OS) in OCSCC patients and compared it with published gene expression signatures for prognosis of OS in head and neck cancer patients, replicated herein on our OCSCC dataset.MethodsFor each patient, 1072 radiomic features were extracted from T1 and T2-weighted MRI (T1w and T2w). Features selection was performed, and an optimal set of five of them was used to fit a Cox proportional hazard regression model for OS. The radiomic signature was developed on a multi-centric locally advanced OCSCC retrospective dataset (n = 123) and validated on a prospective cohort (n = 108).ResultsThe performance of the signature was evaluated in terms of C-index (0.68 (IQR 0.66-0.70)), hazard ratio (HR 2.64 (95% CI 1.62-4.31)), and high/low risk group stratification (log-rank p &lt; 0.001, Kaplan-Meier curves). When tested on a multi-centric prospective cohort (n = 108), the signature had a C-index of 0.62 (IQR 0.58-0.64) and outperformed the clinical and pathologic TNM stage and six out of seven gene expression prognostic signatures. In addition, the significant difference of the radiomic signature between stages III and IVa/b in patients receiving surgery suggests a potential association of MRI features with the pathologic stage.ConclusionsOverall, the present study suggests that MRI signatures, containing non-invasive and cost-effective remarkable information, could be exploited as prognostic tools

Transcathether aortic valve implantation with the new repositionable self-expandable Evolut R versus CoreValve system: A case-matched comparison

Background: Despite promising results following transcatheter aortic valve implantation (TAVI), several relevant challenges still remain. To overcome these issues, new generation devices have been developed. The purpose of the present study was to determine whether TAVI with the new self-expanding repositionable Evolut R offers potential benefits compared to the preceding CoreValve, using propensity matching. Methods: Between June 2007 and November 2015, 2148 consecutive patients undergoing TAVI either CoreValve (n = 1846) or Evolut R (n = 302) were prospectively included in the Italian TAVI ClinicalService® project. For the purpose of our analysis 211 patients treated with the Evolut R were matched to 211 patients treated with the CoreValve. An independent core laboratory reviewed all angiographic procedural data and an independent clinical events committee adjudicated all events. Results: Patients treated with Evolut R experienced higher 1-year overall survival (log rank test p = 0.045) and a significantly lower incidence of major vascular access complications, bleeding events and acute kidney injury compared to patients treated with the CoreValve. Recapture manoeuvres to optimize valve deployment were performed 44 times, allowing a less implantation depth for the Evolut R. As a consequence, the rate of more than mild paravalvular leak and new permanent pacemaker was lower in patients receiving the Evolut R. Conclusion: In this matched comparison of high surgical risk patients undergoing TAVI, the use of Evolut R was associated with a significant survival benefit at 1. year compared with the CoreValve. This was driven by lower incidence of periprocedural complications and higher rates of correct anatomic positioning

Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis

[EN] Background To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). Methods A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I-2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. Results One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. Conclusions Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years