Enhancing functional recovery following postpartum femoral neuropathy: early neurorehabilitation and multidisciplinary obstetric care.

Postpartum femoral neuropathy has a reported incidence of less than 1% and its total recovery time extends up to 6 months to a year. A multidisciplinary approach is vital to rule out permanent disability and to assure a correct diagnosis and earlier rehabilitation. We report a case of a 37-year-old puerperal woman with a history of intrapartum epidural analgesia, who presented post-labor unilateral lower-limb motor weakness and sensory loss, with functional compromise on independent gait. A multidisciplinary team consisting of an anesthesiologist, a physiatrist, a neurologist, and an obstetrician was then established. In the initial physiatry and neurology assessment, the patient reported pain (numerical rating scale 7/10) over the inguinal ligament, lower limb hypoesthesia, and muscle weakness. Femoral neuropathy was suspected. Magnetic resonance imaging ruled out potential complications related to the anesthetic procedure. The patient was then enrolled in a supervised rehabilitation program and, 3 weeks later, electrodiagnostic studies confirmed the initial suspicion. Two months later, the patient had regained lower-limb active range of motion and no pain nor paresthesia was reported. Our case report describes how an early multimodal rehabilitation program within a multidisciplinary framework allows for sooner neuromotor function improvement and activities of daily living independence.

A hitchhikers' guide to the terminology of accreditation processes for health professionals and institutions.

Accreditation processes for health care professions are designed to ensure that individuals and programs in these fields meet established standards of quality and effectiveness. The accelerating pace of globalization in the health care professions has increased the need for a shared understanding of the vocabulary of evaluation, assessment, and accreditation. The psychometric principles of valid and reliable assessment are commonly accepted, but the terminology is confusing. We believe that all stakeholders - evaluators, faculty, students but also the community - will benefit from a shared language and common set of definitions. We recognize that not all readers will agree with the definitions we propose, but we hope that this guide will help to ensure clarity, consistency, transparency, and fairness, and that it will promote through the stimulation of a debate greater collaboration across national and international boundaries.

Repetitive mRNA vaccination is required to improve the quality of broad-spectrum anti-SARS-CoV-2 antibodies in the absence of CXCL13.

Since the initial spread of severe acute respiratory syndrome coronavirus 2 infection, several viral variants have emerged and represent a major challenge for immune control, particularly in the context of vaccination. We evaluated the quantity, quality, and persistence of immunoglobulin G (IgG) and IgA in individuals who received two or three doses of messenger RNA (mRNA) vaccines, compared with previously infected vaccinated individuals. We show that three doses of mRNA vaccine were required to match the humoral responses of preinfected vaccinees. Given the importance of antibody-dependent cell-mediated immunity against viral infections, we also measured the capacity of IgG to recognize spike variants expressed on the cell surface and found that cross-reactivity was also strongly improved by repeated vaccination. Last, we report low levels of CXCL13, a surrogate marker of germinal center activation and formation, in vaccinees both after two and three doses compared with preinfected individuals, providing a potential explanation for the short duration and low quality of Ig induced.

Post-acute sequelae of COVID-19 is characterized by diminished peripheral CD8+ß7 integrin+ T cells and anti-SARS-CoV-2 IgA response.

Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8+ T cell percentages, however, the proportion of blood CD8+ T cells expressing the mucosal homing receptor ß7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8+ß7Integrin+ T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.

Morphological and physiological traits of the respiratory system in Iguana iguana and other non-avian reptiles.

Functional morphology considers form and function to be intrinsically related. To understand organismal functions, a detailed knowledge of morphological and physiological traits is necessary. Regarding the respiratory system, the combined knowledge about pulmonary morphology and respiratory physiology is fundamental to understand how animals exchange gases and regulate critical functions to sustain metabolic activity. In the present study, the paucicameral lungs of Iguana iguana were analyzed morphometrically through stereological analysis using light and transmission electron images and compared with unicameral and multicameral lungs of six other non-avian reptiles. The morphological data were combined with physiological information to perform a principal component analysis (PCA) and phylogenetic tests of the relationship of the respiratory system. Iguana iguana, Lacerta viridis, and Salvator merianae presented similar pulmonary morphologies and physiologies when compared to Varanus examthematicus, Gekko gecko, Trachemys scripta, and Crocodylus niloticus. The former species showed an elevated respiratory surface area (%AR), a high diffusion capacity, a low volume of total parenchyma (VP), a low percentage of parenchyma concerning the lung volume (VL), and a higher surface/volume ratio of the parenchyma (SAR/VP), with high respiratory frequency (fR) and consequently total ventilation. The total parenchymal surface area (SA), effective parenchymal surface-to-volume ratio (SAR/VP), respiratory surface area (SAR), and anatomical diffusion factor (ADF) showed a phylogenetic signal, evidence that the morphological traits are more strongly correlated with the species' phylogeny than the physiological traits. In sum, our results indicated that the pulmonary morphology is intrinsically related to physiological traits of the respiratory system. Furthermore, phylogenetic signal tests also indicate that morphological traits are more likely to be evolutionary conserved than physiological traits, suggesting that evolutive physiological adaptations in the respiratory system could happen faster than morphological changes.

Show me your best side: Lateralization of social and resting behaviors in feral horses.

Growing evidence shows a variety of sensorial and motor asymmetries in social and non-social interactions in various species, indicating a lateralized processing of information by the brain. Using digital video cameras on tripods and drones, this study investigated lateralization in frequency and duration of social behavior patterns, in affiliative, agonistic, and resting contexts, in a feral population of horses (Equus ferus caballus) in Northern Portugal, consisting of 37 individuals organized in eight harem groups. Affiliative interactions (including grooming) were more often performed, and lasted longer, when recipients were positioned to the right side. In recumbent resting (animals lying down) episodes on the left side lasted longer. Our results of an affiliative behavior having a right side tendency, provide partial support to the valence-specific hypothesis of Ahern and Schwartz (1979) - left hemisphere dominance for positive affect, affiliative behaviors. Longer recumbent resting episodes on the left side may be due to synchronization. However, in both instances it is discussed how lateralization may be context dependent. Investigating the position asymmetries of social behaviors in feral equids will contribute to a better understanding of differential lateralization and hemispheric specialization from the ecological and evolutionary perspectives.

Prediction of Noninvasive Ventilation Failure in COVID-19 Patients: When Shall We Stop?

INTRODUCTION: In coronavirus disease 2019 (COVID-19), there are no tools available for the difficult task of recognizing which patients do not benefit from maintaining respiratory support, such as noninvasive ventilation (NIV). Identifying treatment failure is crucial to provide the best possible care and optimizing resources. Therefore, this study aimed to build a model that predicts NIV failure in patients who did not progress to invasive mechanical ventilation (IMV). METHODS: This retrospective observational study included critical COVID-19 patients treated with NIV who did not progress to IMV. Patients were admitted to a Portuguese tertiary hospital between October 1, 2020, and March 31, 2021. The outcome of interest was NIV failure, defined as COVID-19-related in-hospital death. A binary logistic regression was performed, where the outcome (mortality) was the dependent variable. Using the independent variables of the logistic regression a decision-tree classification model was implemented. RESULTS: The study sample, composed of 103 patients, had a mean age of 66.3 years (SD=14.9), of which 38.8% (40 patients) were female. Most patients (82.5%) were autonomous for basic activities of daily living. The prediction model was statistically significant with an area under the curve of 0.994 and a precision of 0.950. Higher age, a higher number of days with increases in the fraction of inspired oxygen (FiO2), a higher number of days of maximum expiratory positive airway pressure, a lower number of days on NIV, and a lower number of days from disease onset to hospital admission were, with statistical significance, associated with increased odds of death. A decision-tree classification model was then obtained to achieve the best combination of variables to predict the outcome of interest. CONCLUSIONS: This study presents a model to predict death in COVID-19 patients treated with NIV in patients who did not progress to IMV, based on easily applicable variables that mainly reflect patients' evolution during hospitalization. Along with the decision-tree classification model, these original findings may help clinicians define the best therapeutical approach to each patient, prioritizing life-comforting measures when adequate, and optimizing resources, which is crucial within limited or overloaded healthcare systems. Further research is needed on this subject of treatment failure, not only to understand if these results are reproducible but also, in a broader sense, helping to fill this gap in modern medicine guidelines.

miR-29c Increases Protein Synthesis in Skeletal Muscle Independently of AKT/mTOR.

microRNAs negatively regulate gene expression by blocking translation or increasing mRNA degradation. In skeletal muscle, these molecules play important roles in adaptive responses, and ongoing investigations are necessary to understand the fine-tune regulation of skeletal muscle mass. Herein we showed that skeletal muscle overexpression of miR-29c increased fiber size and force at 7 and 30 days after electrotransfer. At both time points, AKT/mTOR pathway components were downregulated, and, surprisingly, overall protein synthesis was strongly elevated at day 7, which normalized by day 30 after pCMVmiR-29c electrotransfer. These results indicate that miR-29c expression induces skeletal muscle hypertrophy and gain of function, which involves increased overall protein synthesis in spite of the deactivation of the AKT/mTOR pathway.

Essential oils from Cymbopogon citratus and Lippia sidoides in the anesthetic induction and transport of ornamental fish Pterophyllum scalare.

This study verified the effects of essential oils from Lippia sidoides (EOLS) and Cymbopogon citratus (EOCC) on the anesthesia of freshwater angelfish (Pterophyllum scalare) of two different sizes (juveniles I (0.82 g) and II (2.40 g)) and the transport (8 h) of juveniles II. Fish were exposed to different concentrations of EOLS and EOCC: 0, 10, 25, 50, 75, 100, 150, 200, and 250 mg L-1. Ventilatory rate (VR) and transport for 8 h with 0, 10, and 15 mg L-1 of each essential oil were evaluated in juveniles II. The major components found in EOLS and EOCC were carvacrol (44.50%) and α-citral (73.56%), respectively. The best sedation and anesthesia times for both essential oils were obtained with 10 and 25 mg L-1 and 200 and 250 mg L-1 for juveniles I and II, respectively. Fish sedated with EOLS had lower VR values than the other treatments. Blood glucose levels were higher in ornamental fish transported with 10 and 15 mg EOLS L-1 and 15 mg EOCC L-1. Hepatic glycogen values were higher in the control group. In general, fish transported with 10 mg EOLS L-1 showed fewer gill histological alterations than other transported fish. When the type of lesion was evaluated, the highest gill alterations occurred in fish transported with EOCC. In conclusion, 10 mg EOLS L-1 could be used to transport of juveniles II because although this concentration increased blood glucose levels, it decreased the VR and muscle glycogen levels and caused only mild alterations to the gills.

Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists.

INTRODUCTION: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer. METHODS: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored. RESULTS: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted. CONCLUSION: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown.

This study was an online survey of Portuguese medical oncologists to determine how they managed patients with breast cancer during the COVID-19 pandemic. Forty-two questions covered topics such as how COVID testing was done, the types of cancer treatments used, and how this compared to before the pandemic. It also examined whether the geographic region, the number of patients each doctor was responsible for (caseload), and the type of medical institution influenced how patients with breast cancer were managed. One hundred and twenty-nine oncologists completed the survey, of whom 108 worked in the public health system, making this survey representative of breast cancer management during the COVID-19 pandemic across Portugal. Most (71%) said there were fewer visits for new cases of breast cancer during lockdown. The use of telemedicine increased, as did the use of pre-surgery hormone therapy or chemotherapy when access to surgery was difficult, and the use of anticancer medications taken orally or metronomically (low doses given frequently over a long time period). Chemotherapy given very frequently (dose-dense) was used less often, and fewer patients participated in clinical trials. Treatment decisions for patients with aggressive breast cancer types (e.g., triple-negative breast cancer) were largely unchanged, except for greater use of cyclin-dependent kinase 4/6 inhibitors­drugs targeting the cell cycle and cell division control. Geographic region and caseload influenced treatment decisions. All of these changes in breast cancer treatment during the COVID-19 pandemic were logical and reasonable for the circumstances, but their long-term impact is not yet known.

T cell apoptosis characterizes severe Covid-19 disease.

Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.

Patterns of energetic substrate modifications in response to feeding in boas, Boa constrictor (Serpentes, Boidae).

Ambush-foraging snakes that ingest large meals might undergo several months without eating when they use the internal reserves to support the energetic costs of living. Then, morphological and physiological processes might be orchestrated during the transition from fasting to the postprandial period to rapidly use the energetic stores while the metabolic rate is elevated in response to food intake. To understand the patterns of substrates deposition after feeding, we accessed the morphological and biochemical response in Boa constrictor snakes after two months of fasting and six days after feeding. We followed the plasma levels of glucose, total proteins, and total lipids, and we performed the stereological ultrastructural analysis of the liver and the proximal region of the intestine to quantify glycogen granules and lipid droplets. In the same tissues and stomach, we measured the activity of the enzyme fructose-1,6-biphosphatase (FBPase1) involved in the gluconeogenic pathway, and we measured pyruvate kinase (PK) and lactate dehydrogenase (LDH) enzymatic activities involved in the anaerobic pathway in the liver. Briefly, our results indicated an increase in boas' plasma glucose one day after meal intake compared to unfed snakes. The hepatic glycogen reserves were continuously restored within days after feeding. Also, the enzymes involved in the energetic pathways increased activity six days after feeding in the liver. These findings suggest a quick restoring pattern of energetic stores during the postprandial period.

Gill Histopathological Biomarkers in Fish Exposed to Trace Metals in the Todos os Santos Bay, Brazil.

Histopathologies are widely recognized as biomarkers of environmental pollution. In this sense, we evaluated the putative relationship of gill histopathologies and distinct ecological impacts in two regions of Todos os Santos Bay (BTS), Brazil, the largest bay in Northeastern Brazil, South Atlantic. We compared the presence and concentration of metals (Al, As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, V, and Zn) in water, sediments, and gills and gill histopathologies of a demersal fish (Diapterus rhombeus) and a benthic fish (Ogcocephalus vespertilio). As expected, fish and sediment samples from historically contaminated areas (Aratu) showed more remarkable traces of metals than apparently low-impact areas (Jaguaripe). Likewise, the DTC (degree of tissue change) index and the volume densities were higher in fish caught in Aratu. In addition, the Diapterus rhombeus species showed more potential than Ogcocephalus vespertilio for risk assessment as it showed more responses to the environment reflected on more histopathologies. These data support the effectiveness of incorporating functional gill morphology to monitor impacts on estuarine biota that can be used as a reference to improve the management of ecosystems and prevent harm to human health.

Feeding effects on liver mitochondrial bioenergetics of Boa constrictor (Serpentes: Boidae).

Snakes are interesting examples of taxa that can overcome energy metabolism challenges, as many species can endure long periods without feeding, and their eventual meals are of reasonably large sizes, thus exhibiting dual extreme adaptations. Consequently, metabolic rate increases considerably to attend to the energetic demand of digestion, absorption and protein synthesis. These animals should be adapted to transition from these two opposite states of energy fairly quickly, and therefore we investigated mitochondrial function plasticity in these states. Herein, we compared liver mitochondrial bioenergetics of the boid snake Boa constrictor during fasting and after meal intake. We fasted the snakes for 60 days, and then we fed a subgroup with 30% of their body size and evaluated their maximum postprandial response. We measured liver respiration rates from permeabilized tissue and isolated mitochondria. From isolated mitochondria, we also measured Ca2+ retention capacity and redox status. Mitochondrial respiration rates were maximized after feeding, reaching an approximately 60% increase from fasting levels when energized with complex I-linked substrates. Interestingly, fasting and fed snakes exhibited similar respiratory control ratios and citrate synthase activity. Furthermore, we found no differences in Ca2+ retention capacity, indicating no increase in susceptibility to mitochondrial permeability transition, and no changes in mitochondrial redox state, although fed animals exhibited increases in the release of H2O2. Thus, we conclude that liver mitochondria from B. constrictor snakes increase respiration rates during the postprandial period and quickly improve the bioenergetic capacity without compromising redox balance.

Sampling Methods and Risk Stratification Regarding Environmental Contamination by SARS-CoV-2.

INTRODUCTION: Transmission of COVID-19 through close contact and droplets is well established, but the influence of aerosol and surface contamination remains to be determined. Literature is scarce and inconsistent about the viable virus particles free-distance from infected patients, as well as about different swabbing methods for surface contamination evaluation. The aim of this study was to evaluate the most sensitive method for the assessment of surface contamination, classify the likelihood of environmental contamination in risk zones and compare the environmental contamination between oxygenation and ventilatory support. MATERIAL AND METHODS: Swabs from potentially contaminated surfaces in a COVID-19 ward, with patients treated with different types of oxygen and ventilatory support, were collected. Three types of swabs were compared in order to evaluate the most sensitive collection method. For risk zone categorization, areas were divided according to the distance from the patient. RESULTS: Of the 63 swabs collected, 17 (27%) tested positive for the presence of SARS-CoV-2. The highest positivity rate was observed with the sterile premoistened swab with saline (n = 8; 38%), but without statistically significant differences. The highest number of positive samples were collected from the high-risk zones, specifically those located one meter from the patient (n = 13; 48%), with statistically significant differences. Only the rooms of patients supported with non-invasive ventilation or high-flow nasal cannula had evidence of bedroom contamination, with 45% and 27% of swab positivity, with statistically significant differences. DISCUSSION: Our findings favour the premoistened swab without transport medium for surface contamination assessment, even though without statistical differences. A statistically significant trend supporting the division in risk zones, according to the distance from the patient, was also identified. The higher positivity rate from the non-invasive ventilation and high-flow nasal cannula bedrooms suggests a significant association between ventilatory strategies and surface contamination, probably due to higher particle dispersion. CONCLUSION: Our findings support the use of the sterile premoistened swab without preservation medium, the classification of risk areas considering the distance from the patient, and the variability of RNA dispersion between oxygenation and ventilatory support.

Introdução: A transmissão da COVID-19 através do contacto e gotículas está bem estabelecida, mas a importância da sua transmissão através do aerossol e da contaminação das superfícies permanece por determinar. A literatura é escassa e inconsistente em relação à distância mínima livre de partículas víricas, desde um paciente, e também acerca dos mais adequados métodos de colheita de zaragatoas para avaliação da contaminação das superfícies. Os objectivos deste estudo foram avaliar qual o método mais sensível para avaliação da contaminação de superfícies, classificar a contaminação ambiental de acordo com zonas de risco e comparar a contaminação ambiental sob diferentes dispositivos para oxigenoterapia e suporte ventilatório. Material e Métodos: Realizamos colheitas de zaragatoas em superfícies potencialmente contaminadas numa ala COVID-19, onde se encontravam doentes sob diferentes dispositivos para oxigenoterapia e suporte ventilatório. Para avaliar o método de recolha mais sensível para verificação da contaminação das superfícies, comparámos três tipos de zaragatoas. Para a classificação das zonas de risco, dividimos as áreas de acordo com a distância ao doente. Resultados: Das 63 zaragatoas, 17 (27%) testaram positivo para SARS-CoV-2 (27%). A maior positividade foi observada na zaragatoa estéril pré-humedecida com soro fisiológico (n = 8; 38%), mas sem significância estatística. O maior número de amostras positivas obteve-se nas zonas de alto risco, especialmente aquelas a um metro do paciente (n = 13; 48%), com diferenças significativas. Apenas os quartos dos doentes sob ventilação não invasiva e cânula nasal de alto fluxo tiveram evidência de contaminação com 45% e 27% de positividade das zaragatoas, e significância estatística. Discussão: Os nossos resultados favorecem a zaragatoa estéril pré-humedecida sem meio de preservação para avaliação da contaminação das superfícies, embora sem significância estatística. Os resultados suportam também com significância estatística a divisão em zonas de risco de acordo com a distância ao doente. A maior positividade obtida nos quartos dos pacientes que se encontravam a utilizar ventilação não invasiva e cânula nasal de alto fluxo sugere uma associação, com significância, entre as estratégias ventilatória e a contaminação ambiental, provavelmente relacionada com uma maior dispersão das partículas. Conclusão: Os nossos resultados apoiam o uso da zaragatoa estéril pré-humedecida sem meio de preservação, a classificação das áreas de risco considerando a distância ao doente, e a variabilidade da dispersão do RNA entre diferentes dispositivos para oxigenoterapia e ventilação.

Effects of polycyclic aromatic hydrocarbons on biomarker responses in Gambusia yucatana, an endemic fish from Yucatán Peninsula, Mexico.

Polycyclic aromatic hydrocarbons (PAHs) are petroleum components that, when dissolved in the aquatic environment, can disrupt normal animal physiological functions and negatively affect species populations. Gambusia yucatana is an endemic fish of the Yucatán Peninsula that seems to be particularly sensitive to the presence of PAHs dissolved in the water. Here, we examined PAH effects on gene expressions linked to endocrine disruption and biotransformation in this species. Specifically, we examined the expression of vitellogenin I (vtg1), vitellogenin II (vtg2), oestrogen receptor α (esr1), oestrogen receptor ß (esr2), aryl hydrocarbon receptor (AhR) and the cytochrome P4503A (CYP3A) genes. We exposed G. yucatana to different concentrations of PAHs (3.89, 9.27, 19.51 µg/L) over a period of 72 h and found changes associated with reproduction, such as increases in hepatic expression of vtg, esr, AhR and CYP3A, mainly at concentrations of 9.27 and 19.51 µg/L. Our results also indicate that benzo[a]pyrene was probably the main PAH responsible for the observed effects. The genes examined here can be used as molecular markers of endocrine-disrupting compounds, as the PAHs, present in the environment, as gene expression increases could be observed as early as after 24 h. These biomarkers can help researchers and conservationists rapidly identify the impacts of oil spills and improve mitigation before the detrimental effects of environmental stressors become irreversible.

Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1.

The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog. MuRF1 and MuRF2-KO (knockout) mice have elevated serum glucose, elevated triglycerides, and reduced glucose tolerance. In addition, MuRF2-KO mice have a reduced tolerance to a fat-rich diet. Western blot and enzymatic studies on MuRF1-KO skeletal muscle showed perturbed FoxO-Akt signaling, elevated Akt-Ser-473 activation, and downregulated oxidative mitochondrial metabolism, indicating potential mechanisms for MuRF1,2-dependent glucose and fat metabolism regulation. Consistent with this, the adenoviral re-expression of MuRF1 in KO mice normalized Akt-Ser-473, serum glucose, and triglycerides. Finally, we tested the MuRF1/2 inhibitors MyoMed-205 and MyoMed-946 in a mouse model for type 2 diabetes mellitus (T2DM). After 28 days of treatment, T2DM mice developed progressive muscle weakness detected by wire hang tests, but this was attenuated by the MyoMed-205 treatment. While MyoMed-205 and MyoMed-946 had no significant effects on serum glucose, they did normalize the lymphocyte-granulocyte counts in diabetic sera as indicators of the immune response. Thus, small molecules directed to MuRF1 may be useful in attenuating skeletal muscle strength loss in T2DM conditions.

Interleukin-6 Is a Biomarker for the Development of Fatal Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

Hyper-inflammatory responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major cause of disease severity and death. Predictive prognosis biomarkers to guide therapeutics are critically lacking. Several studies have indicated a "cytokine storm" with the release of interleukin-1 (IL-1), IL-6, and IL-8, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. Here, we proposed to assess the relationship between IL-6 and outcomes of patients with coronavirus disease 2019 (COVID-19). Our cohort consisted of 46 adult patients with PCR-proven SARS-CoV-2 infection admitted in a COVID-19 ward of the Hospital de Braga (HB) from April 7 to May 7, 2020, whose IL-6 levels were followed over time. We found that IL-6 levels were significantly different between the disease stages. Also, we found a significant negative correlation between IL-6 levels during stages IIb and III, peripheral oxygen saturation (SpO2), and partial pressure of oxygen in arterial blood (PaO2), showing that IL-6 correlates with respiratory failure. Compared to the inflammatory markers available in the clinic routine, we found a positive correlation between IL-6 and C-reactive protein (CRP). However, when we assessed the predictive value of these two markers, IL-6 behaves as a better predictor of disease progression. In a binary logistic regression, IL-6 level was the most significant predictor of the non-survivors group, when compared to age and CRP. Herein, we present IL-6 as a relevant tool for prognostic evaluation, mainly as a predictor of outcome.

Dielectric-Loaded Waveguides as Advanced Platforms for Diagnostics and Application of Transparent Thin Films.

An alternative approach to classical surface plasmon resonance spectroscopy is dielectric-loaded waveguide (DLWG) spectroscopy, widely used in the past decades to investigate bio-interaction kinetics. Despite their wide application, a successful and clear approach to use the DLWGs for the one-step simultaneous determination of both the thickness and refractive index of organic thin films is absent in the literature. We propose here, for the first time, an experimental protocol based on the multimodal nature of DLWGs to be followed in order to evaluate the optical constants and thickness of transparent thin films with a unique measurement. The proposed method is general and can be applied to every class of transparent organic materials, with a resolution and accuracy which depend on the nature of the external medium (gaseous or liquid), the geometrical characteristics of the DLWG, and the values of both the thickness and dielectric constant of the thin film. From the experimental point of view, the method is demonstrated in a nitrogen environment with an accuracy of about 3%, for the special case of electroluminescent thin films of Eu3+ß-diketonate complexes, with an average thickness of about 20 nm. The high value of the refractive index measured for the thin film with the Eu(btfa)3(t-bpete) complex was confirmed by the use of a spectroscopic model based on the Judd-Ofelt theory, in which the magnetic dipole transition 5D0 → 7F1 (Eu3+) for similar films containing Eu3+ complexes is taken as a reference. The DLWGs are finally applied to control the refractive index changes of the organic thin films under UVA irradiation, with potential applications in dosimetry and monitoring light-induced transformation in organic thin films.