Diabetes and hypertension in elderly women: interactions between severity and failure to control inflammation.

Elderly women are more susceptible to the development of chronic non-communicable diseases. Among these, diabetes mellitus (DM) and systemic arterial hypertension (SAH) stand out. This work aimed to carry out an expanded study on the interactions of anthropometric, biochemical and inflammatory parameters associated with the risk of severity in elderly women with hypertension and diabetes. The study involved the evaluation of 126 elderly women with hypertension and diabetes mellitus. The women were divided according disease severity (low, moderate, high and very high). Anthropometric data were collected by bioimpedance analysis. The inflammatory and biochemical data were obtained from volunteer blood samples. Waist circumference, waist circumference/height ratio, and systolic and diastolic pressures increased with severity. Biochemical marker levels increased with risk of severity, except HDLc. In the very high risk group, there was a higher IL-1ß, IFN-γ and TNF-α production, however, lower IL-10 levels were observed. The very high risk group showed change values for the IL-10/IL-1ß, IL-10/IL-17 and IL-10/TNF-α ratios. The results showed to be extensively altered in the very high risk group, where the inflammatory profile loses its responsiveness. This is the first study that shows an expanded view of the different parameters evaluated in elderly women with hypertension and diabetes.

Differential Effect of Positive End-Expiratory Pressure Strategies in Patients With ARDS: A Bayesian Analysis of Clinical Subphenotypes.

BACKGROUND: ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. RESEARCH QUESTION: Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? STUDY DESIGN AND METHODS: We evaluated data from two prior ARDS trials (Higher vs Lower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. RESULTS: We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in patients with subphenotype A disease in the ALVEOLI study (OR, 1.61; 95% credible interval [CrI], 0.90-2.94) and ART (OR, 1.73; 95% CrI, 1.01-2.98), with a probability of harm resulting from higher PEEP in this subphenotype of 94.3% and 97.7% in the ALVEOLI and ART studies, respectively. Higher PEEP was not associated with mortality in patients with subphenotype B disease in each trial (OR, 0.95 [95% CrI, 0.51-1.73] and 1.00 [95% CrI, 0.63-1.55], respectively), with probability of benefit of 56.4% and 50.7% in the ALVEOLI and ART studies, respectively. These effects were not modified by Pao2 to Fio2 ratio, driving pressure, or the severity of illness for the cohorts. INTERPRETATION: We found evidence of differential response to PEEP strategies across two ARDS subphenotypes, suggesting possible harm with a higher PEEP strategy in one subphenotype. These observations may assist with predictive enrichment in future clinical trials.

Evaluation of digoxin-boronate ester formation through in-capillary derivatisation-large volume sample stacking-capillary zone electrophoresis.

Determination of digoxin through in-capillary derivatisation based on the formation of o-tolyl- and 2-naphthyl-anionic boronate esters in combination with large volume sample stacking-capillary electrophoresis is proposed. The derivatisation reaction was performed at basic pH values to obtain compounds with a charge and chromophore group during the stacking process. After stacking, the species were separated and detected at 225 nm using p-nitrophenol as an internal standard. Stacking and derivatisation parameters such as pre-concentration time, preconcentration voltage and injection time (relation between the analyte and the derivatisation agent) were evaluated using a Box-Behnken design. Under optimal conditions, the proposed method exhibits a linear range of 1.08-50.00 µM with a limit of detection of 0.36 µM; additionally, adequate repeatability and reproducibility was obtained (%RSD ≤ 5.0%). The methodology was validated by comparing it to an HPLC-UV established methodology and was successfully applied for the determination of digoxin in pharmaceutical tablets and blood serum samples, showing a positive performance for these matrices.

Impact of digestive-surgical cross-disciplinary management in patients with esophageal atresia. / Impacto del manejo multidisciplinar digestivo-quirúrgico en los pacientes con atresia de esófago.

OBJECTIVE: The objective of this study was to analyze whether patients undergoing esophageal atresia (EA) surgery benefit from a cross-disciplinary follow-up program, based on current clinical guidelines, implemented in our institution. MATERIALS AND METHODS: An observational, analytical, retrospective study of patients undergoing EA surgery from 2012 to 2022 was carried out. The results of a joint pediatric surgery and gastroenterology consultation program -which was implemented in 2018 and applies a protocol based on the new ESPGHAN-NASPGHAN guidelines- were analyzed. Patients were divided according to whether they had been treated before or after 2018. Quantitative variables -follow-up losses, anti-reflux treatment initiation and duration, and enteral nutrition initiation- and qualitative variables -prevalence of gastroesophageal reflux, anti-reflux surgery, respiratory infections, anastomotic stenosis, re-fistulizations, dysphagia, impaction episodes, need for gastrostomy, and endoscopic results- were compared. RESULTS: 38 patients were included. 63.2% had gastroesophageal reflux. 97.4% received anti-reflux treatment in the first year of life, with treatment being subsequently discontinued in 47.4%. Discontinuation time decreased by a mean of 24 months following program implementation (p< 0.05). A 4.6-fold increase in the frequency of pH-metries was noted following program implementation. The protocol standardized endoscopies in asymptomatic patients when they turn 5 and 10 years old. 25 endoscopies with biopsy were carried out after 2018, with histological disorders being detected in 28% of them. The number of follow-up losses significantly decreased following protocol implementation (p< 0.05). CONCLUSIONS: Digestive-surgical cross-disciplinary follow-up of EA patients has a positive impact on patient progression. Applying the guidelines helps optimize treatment and early diagnosis of complications.

OBJETIVOS: El objetivo de este estudio es analizar si los pacientes intervenidos de atresia de esófago (AE) se benefician de un programa de seguimiento multidisciplinar, basado en las guías clínicas actuales, implantado en nuestro centro. MATERIAL Y METODOS: Estudio retrospectivo, observacional y analítico incluyendo los pacientes intervenidos de AE entre 2012 y 2022. Se analizaron los resultados de la implantación en 2018 de un programa de consultas conjuntas de gastroenterología y cirugía pediátrica aplicando un protocolo basado en las nuevas guías ESPGHAN-NASPGHAN. Se dividieron a los pacientes tratados antes y después de 2018 y se compararon las variables cuantitativas: pérdidas de seguimiento, inicio y duración del tratamiento antirreflujo e inicio de nutrición enteral, y cualitativas: prevalencia de reflujo gastroesfoágico, realización de cirugía antirreflujo, infecciones respiratorias, estenosis de la anastomosis, refistulizaciones, disfagia, episodios de impactación, necesidad de gastrostomía y resultados de las endoscopias. RESULTADOS: Se incluyeron 38 pacientes. Un 63,2% presentaron reflujo gastroesofágico. El 97,4% tomaron tratamiento antirreflujo el primer año de vida que posteriormente se retiró en el 47,4%. El tiempo de retirada se redujo una media de 24 meses tras la aplicación del programa (p< 0,05). Se realizaron 4,6 veces más pHmetrías tras la implantación del programa. El protocolo estandarizó la realización de endoscopias en pacientes asintomáticos al cumplir 5 y 10 años. Se realizaron 25 endoscopias con tomas de biopsia después de 2018, detectando alteraciones histológicas en un 28%. El número de pérdidas de seguimiento se redujo de forma significativa tras la implantación del protocolo (p< 0,05). CONCLUSIONES: El seguimiento multidisciplinar digestivo-quirúrgico de los pacientes con AE genera un impacto positivo en su evolución. La aplicación de las guías facilita la optimización del tratamiento y el diagnóstico precoz de las complicaciones.

The Evaluation of Cellulose Acetate Capsules Functionalized for the Removal of Cd(II).

Cellulose acetate is derived from cellulose and has the characteristics of biodegradability and reusability. So, it has been used for the elimination of toxic compounds capable of producing different diseases, such as cadmium, that result from human and industrial activity. For this reason, capsules functionalized with Cyanex 923 were prepared and characterized by FTIR spectroscopy, Energy Dispersive X-ray Spectroscopy (EDX), and SEM. The functionalized capsules were used for removing and recovering Cd(II) by modifying variables such as HCl concentration in the extraction medium and carrier content in the capsules, among others. The extraction of cadmium from battery leachates and the three isotherm models, Langmuir, Freundlich, and Dubinin Radushkevich, were also tested to model the cadmium removal process. The results showed a favorable physical sorption with a good capacity for extraction and the possibility of reusing the capsules for up to seven cycles without a decrease in the percentage of cadmium recovery.

Impacto del manejo multidisciplinar digestivo-quirúrgico en los pacientes con atresia de esófago / Impact of digestive-surgical cross-disciplinary management in patients with esophageal atresia

Objetivos: El objetivo de este estudio es analizar si los pacientesintervenidos de atresia de esófago (AE) se benefician de un programade seguimiento multidisciplinar, basado en las guías clínicas actuales,implantado en nuestro centro. Material y métodos: Estudio retrospectivo, observacional y analí-tico incluyendo los pacientes intervenidos de AE entre 2012 y 2022. Seanalizaron los resultados de la implantación en 2018 de un programa deconsultas conjuntas de gastroenterología y cirugía pediátrica aplicandoun protocolo basado en las nuevas guías ESPGHAN-NASPGHAN. Sedividieron a los pacientes tratados antes y después de 2018 y se compararon las variables cuantitativas: pérdidas de seguimiento, inicio y duracióndel tratamiento antirreflujo e inicio de nutrición enteral, y cualitativas:prevalencia de reflujo gastroesfoágico, realización de cirugía antirreflujo,infecciones respiratorias, estenosis de la anastomosis, refistulizaciones,disfagia, episodios de impactación, necesidad de gastrostomía y resul-tados de las endoscopias. Resultados: Se incluyeron 38 pacientes. Un 63,2% presentaronreflujo gastroesofágico. El 97,4% tomaron tratamiento antirreflujo el primer año de vida que posteriormente se retiró en el 47,4%. El tiempo deretirada se redujo una media de 24 meses tras la aplicación del programa(p< 0,05). Se realizaron 4,6 veces más pHmetrías tras la implantacióndel programa. El protocolo estandarizó la realización de endoscopiasen pacientes asintomáticos al cumplir 5 y 10 años. Se realizaron 25endoscopias con tomas de biopsia después de 2018, detectando alteraciones histológicas en un 28%. El número de pérdidas de seguimiento seredujo de forma significativa tras la implantación del protocolo (p< 0,05). Conclusiones: El seguimiento multidisciplinar digestivo-quirúrgicode los pacientes con AE genera un impacto positivo en su evolución.(AU)

Objective: The objective of this study was to analyze whether patients undergoing esophageal atresia (EA) surgery benefit from a cross-disciplinary follow-up program, based on current clinical guidelines,implemented in our institution. Materials and methods: An observational, analytical, retrospectivestudy of patients undergoing EA surgery from 2012 to 2022 was carriedout. The results of a joint pediatric surgery and gastroenterology consultation program –which was implemented in 2018 and applies a protocolbased on the new ESPGHAN-NASPGHAN guidelines– were analyzed.Patients were divided according to whether they had been treated before or after 2018. Quantitative variables –follow-up losses, anti-refluxtreatment initiation and duration, and enteral nutrition initiation– andqualitative variables –prevalence of gastroesophageal reflux, anti-refluxsurgery, respiratory infections, anastomotic stenosis, re-fistulizations,dysphagia, impaction episodes, need for gastrostomy, and endoscopicresults– were compared. Results: 38 patients were included. 63.2% had gastroesophagealreflux. 97.4% received anti-reflux treatment in the first year of life, withtreatment being subsequently discontinued in 47.4%. Discontinuationtime decreased by a mean of 24 months following program implementation (p< 0.05). A 4.6-fold increase in the frequency of pH-metries wasnoted following program implementation. The protocol standardizedendoscopies in asymptomatic patients when they turn 5 and 10 years old. 25 endoscopies with biopsy were carried out after 2018, with histologicaldisorders being detected in 28% of them. The number of follow-up lossessignificantly decreased following protocol implementation (p< 0.05). Conclusions: Digestive-surgical cross-disciplinary follow-up of EApatients has a positive impact on patient progression. Applying the guidelines helps optimize treatment and early diagnosis of complications.(AU)

Influence of age and education on breast cancer awareness and knowledge among women in South Western Nigeria.

The rising incidence of breast cancer (BC) in sub-Saharan Africa is aggravated by poor prognosis. Health education and several screening methods, including breast self-examination (BSE), clinical breast-examination (CBE) and mammography, have been advanced to achieve early detection and reduction in its mortality rate. This study evaluated the level of awareness and knowledge of BC and BSE amongst female students and staff of six educational institutions in Ota, Southwest Nigeria. The participants, consisting of 917 (80.79%) students and 218 (19.21%) staff, aged between 13 and 60 years, were selected using a stratified random sampling technique and categorized into age groups [adolescents (13-19 years), young adults (21-40 years) and middle-aged adults (41-60 years)] and levels of education. Data was collected via questionnaires and analysed using Epi-info software and SPSS version 20. Frequencies, percentages, regression and correlation co-efficient were calculated and used to determine the levels of association between age groups and levels of education. Mean age of the participants was 21 ± 1.7 years; over 75% were adolescents. BC and BSE awareness was 94.80% and 65.11% respectively, with 7 (0.62%) having BC. The major sources of BC and BSE information were television, health workers and internet. The average BC knowledge score of the participants was 4.06 (40.57%); it was highest among young adults, 4.31 (43.07%), and least among the adolescents, 3.88 (38.78%). The same trend was observed for BSE practice among the age groups. There was a direct relationship between BC knowledge and levels of education; the postgraduates had the highest BC knowledge score of 4.49 (44.89%) while the secondary students had the least score of 3.82 (38.12%). Similar trend was observed for BSE practice and the levels of education. Paucity of BSE knowledge largely accounted for the low BSE practice among the adolescents and secondary students. The huge gap in BC knowledge and BSE practice underscores the need for a structured health education and screening programmes in Nigerian schools to enhance prevention and early detection of BC and other ailments. BSE is free, easy to perform, and able to detect BC at earlier stage. The practice should be encouraged alongside mammography to reduce the burden and mortality rate of BC in Nigeria.

Modified Polysulfone Nanofibers for the Extraction and Preconcentration of Lead from Aqueous Solutions.

Since lead is a highly toxic metal, it is necessary to detect its presence in different samples; unfortunately, analysis can be complicated if the samples contain concentrations below the detection limit of conventional analytical techniques. Solid phase extraction is a technique that allows the carrying out of a pre-concentration process and thus makes it easy to quantify analytes. This work studied the efficiency of sorption and preconcentration of lead utilizing polysulfone (PSf) fibers grafted with acrylic acid (AA). The best conditions for Pb(II) extraction were: pH 5, 0.1 mol L-1 of ionic strength, and 40 mg of sorbent (70% of removal). The sorbed Pb(II) was pre-concentrated by using an HNO3 solution and quantified using flame atomic absorption spectrometry. The described procedure was used to obtain a correlation curve between initial concentrations and those obtained after the preconcentration process. This curve and the developed methodology were applied to the determination of Pb(II) concentration in a water sample contained in a handmade glazed clay vessel. With the implementation of the developed method, it was possible to pre-concentrate and determine a leached Pb(II) concentration of 258 µg L-1.

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Antivirals for adult patients hospitalised with SARS-CoV-2 infection: a randomised, phase II/III, multicentre, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn trial.

Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients. Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087. Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups. Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less. Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).

Physiological and clinical effects of different infusion rates of intravenous fluids for volume expansion: A scoping review.

PURPOSE: To assess the physiological and clinical effects of different rates of intravenous fluids for volume expansion of critically ill and perioperative patients. METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for studies comparing intravenous infusion rates both in animals and studies involving healthy subjects, critically ill, and perioperative care patients of all ages. RESULTS: Seven animal studies, eleven clinical studies and three studies including healthy volunteers were identified. Slower infusion led to lower mortality in two studies, lower blood loss in one study, better or more sustained expansion of plasma volume and less edema in three studies, but slower restoration of blood pressure in one study. Three healthy volunteer studies suggested more effective plasma expansion with slower infusion, whereas one trial with postoperative patients did not show plasma volume differences between different infusion rates. One randomized trial found increased mortality with faster infusion in septic children, whereas a randomized trial found no significant differences in critically ill adults. CONCLUSIONS: In this scoping review, most studies showed that slower intravenous infusion rates result in a more efficient intravascular expansion, with a longer effect, and less edema than faster rates. Effects on clinical outcomes were inconsistent.

Undifferentiated and Dedifferentiated Metastatic Melanomas Masquerading as Soft Tissue Sarcomas: Mutational Signature Analysis and Immunotherapy Response.

The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis. These cases were confirmed as UM/DM by harboring melanoma driver mutations, UV signature, and high tumor mutation burden. One case of DM showed melanoma in situ. Meanwhile, 18 cases represented metastatic UM/DM. Eleven patients had a prior history of melanoma. Thirteen of 19 (68%) of the tumors were immunohistochemically completely negative for 4 melanocytic markers (S100, SOX10, HMB45, and MELAN-A). All cases harbored a dominant UV signature. Frequent driver mutations involved BRAF (26%), NRAS (32%), and NF1 (42%). In contrast, the control cohort of undifferentiated pleomorphic sarcomas (UPS) of deep soft tissue exhibited a dominant aging signature in 46.6% (7/15) without evidence of UV signature. The median tumor mutation burden for DM/UM vs UPS was 31.5 vs 7.0 mutations/Mb (P < .001). A favorable response to immune checkpoint inhibitor therapy was observed in 66.6% (12/18) of patients with UM/DM. Eight patients exhibited a complete response and were alive with no evidence of disease at the last follow-up (median 45.5 months). Our findings support the usefulness of the UV signature in discriminating DM/UM vs UPS. Furthermore, we present evidence suggesting that patients with DM/UM and UV signatures can benefit from immune checkpoint inhibitor therapy.

Evaluation of the Hybrid Membrane of ZnO Particles Supported in Cellulose Acetate for the Removal of Lead.

Water polluted by discarded heavy metals such as lead is creating a global pollution problem. In this work, adsorption of Pb(II) was realized in batch studies by a hybrid membrane of cellulose acetate with ZnO particles. First, ZnO particles were prepared by precipitation and immobilized on the membrane. The hybrid membrane was elaborated by interfacial polymerization. The structure and surface were characterized based on Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Batch experiments were carried out under different conditions where the number of particles of ZnO present in the membrane and the pH of the aqueous solution were varied. The Langmuir and Freundlich isotherm models were evaluated in the best adsorption conditions. Data fitted well with a Langmuir model with a maximum adsorption capacity of 15.55 mg·g-1, which was similar for this type of materials. Thermodynamic parameters such as Gibbs free energy, enthalpy, and entropy showed that the process was spontaneous and favorable. The hybrid membrane was evaluated in simulated wastewater of the battery industry with a superior efficiency of up to 97%; without the medium, it did not generate interference. These results suggest that Pb(II) removal by hybrid membrane is possible.

A Pilot Randomized Controlled Trial (RCT) of Acceptance and Commitment Therapy Versus Cognitive Behavioral Therapy for Chronic Insomnia.

OBJECTIVE: To compare the effectiveness of protocols for acceptance and commitment therapy for insomnia (ACT-I) and cognitive behavioral therapy for insomnia (CBT-I) in adults. METHOD: Participants were 37 adults (74.3% women; M = 43.7 years, SD = 10.7) with chronic insomnia who were randomized to 6 weekly group sessions consisting of ACT-I (n = 19) or CBT-I (n = 18). The primary outcome measures were based on the Insomnia Severity Index (ISI) total score, a measure of insomnia complaints, and included the proportions of treatment responders (defined as a change in score of 8 points or more) and remitters (defined as a final score below 8). RESULTS: Both treatment modalities significantly reduced insomnia severity. Post-treatment, the proportion of treatment responders was higher in the CBT-I than the ACT-I (64.7% vs. 50.0%, respectively) group and six months later, ACT-I made further improvements whereas CBT-I had a reduced treatment response (58.8% vs. 55.6%, respectively). CBT-I was associated with a higher proportion of insomnia remission at post treatment. CONCLUSIONS: Both CBT-I and ACT-I are effective, with a higher proportion of insomnia remitters in CBT-I post-treatment. The different change trajectories for the two therapy groups provide insights into behavioral change via a cognitive versus contextual approach.

Selective TnsC recruitment enhances the fidelity of RNA-guided transposition.

Bacterial transposons are pervasive mobile genetic elements that use distinct DNA-binding proteins for horizontal transmission. For example, Escherichia coli Tn7 homes to a specific attachment site using TnsD1, whereas CRISPR-associated transposons use type I or type V Cas effectors to insert downstream of target sites specified by guide RNAs2,3. Despite this targeting diversity, transposition invariably requires TnsB, a DDE-family transposase that catalyses DNA excision and insertion, and TnsC, a AAA+ ATPase that is thought to communicate between transposase and targeting proteins4. How TnsC mediates this communication and thereby regulates transposition fidelity has remained unclear. Here we use chromatin immunoprecipitation with sequencing to monitor in vivo formation of the type I-F RNA-guided transpososome, enabling us to resolve distinct protein recruitment events before integration. DNA targeting by the TniQ-Cascade complex is surprisingly promiscuous-hundreds of genomic off-target sites are sampled, but only a subset of those sites is licensed for TnsC and TnsB recruitment, revealing a crucial proofreading checkpoint. To advance the mechanistic understanding of interactions responsible for transpososome assembly, we determined structures of TnsC using cryogenic electron microscopy and found that ATP binding drives the formation of heptameric rings that thread DNA through the central pore, thereby positioning the substrate for downstream integration. Collectively, our results highlight the molecular specificity imparted by consecutive factor binding to genomic target sites during RNA-guided transposition, and provide a structural roadmap to guide future engineering efforts.

Physical activity reduces intradermal bacterial load in a murine model submitted to forced swim training - a pilot study.

Regular exercise is beneficial to health. This study evaluated the effects of moderate and intense physical exercise modalities on intradermal infection by Staphylococcus aureus in a murine model. Mice that practiced moderate exercise had lower bacterial load on lymph nodes and less inflammatory infiltrate in dermis. They presented greater weight, however, less amount of epididymal fat: the weight was increased while they had fat diminished. A positive correlation was observed between lipid content and bacterial load in mice trained at moderate intensity. Animals that were under high intensity exercises presented superior bacterial load on the lymph nodes, increased neutrophil count and circulating lymphocytes, and had leukocyte recruitment to the dermis augmented, when compared to the ones in moderate exercise. These findings suggest that moderate physical activity modulates the immune response in dermal infection caused by S. aureus in a murine model.

eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining.

Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases1,2. A key commitment step is when the ribosomal subunits join at a translation start site on a messenger RNA to form a functional ribosome. Here, we combined single-molecule spectroscopy and structural methods using an in vitro reconstituted system to examine how the human ribosomal subunits join. Single-molecule fluorescence revealed when the universally conserved eukaryotic initiation factors eIF1A and eIF5B associate with and depart from initiation complexes. Guided by single-molecule dynamics, we visualized initiation complexes that contained both eIF1A and eIF5B using single-particle cryo-electron microscopy. The resulting structure revealed how eukaryote-specific contacts between the two proteins remodel the initiation complex to orient the initiator aminoacyl-tRNA in a conformation compatible with ribosomal subunit joining. Collectively, our findings provide a quantitative and architectural framework for the molecular choreography orchestrated by eIF1A and eIF5B during translation initiation in humans.

Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66-10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56-1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65-0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT02875873).

Perceptions of Critical Care Shortages, Resource Use, and Provider Well-being During the COVID-19 Pandemic: A Survey of 1,985 Health Care Providers in Brazil.

BACKGROUND: Brazil has been disproportionately affected by COVID-19, placing a high burden on ICUs. RESEARCH QUESTION: Are perceptions of ICU resource availability associated with end-of-life decisions and burnout among health care providers (HCPs) during COVID-19 surges in Brazil? STUDY DESIGN AND METHODS: We electronically administered a survey to multidisciplinary ICU HCPs during two 2-week periods (in June 2020 and March 2021) coinciding with COVID-19 surges. We examined responses across geographical regions and performed multivariate regressions to explore factors associated with reports of: (1) families being allowed less input in decisions about maintaining life-sustaining treatments for patients with COVID-19 and (2) emotional distress and burnout. RESULTS: We included 1,985 respondents (57% physicians, 14% nurses, 12% respiratory therapists, 16% other HCPs). More respondents reported shortages during the second surge compared with the first (P < .05 for all comparisons), including lower availability of intensivists (66% vs 42%), ICU nurses (53% vs 36%), ICU beds (68% vs 22%), and ventilators for patients with COVID-19 (80% vs 70%); shortages were highest in the North. One-quarter of HCPs reported that families were allowed less input in decisions about maintaining life-sustaining treatments for patients with COVID-19, which was associated with lack of intensivists (adjusted relative risk [aRR], 1.37; 95% CI, 1.05-1.80) and ICU beds (aRR, 1.71; 95% CI, 1.16-2.62) during the first surge and lack of N95 masks (aRR, 1.43; 95% CI, 1.10-1.85), noninvasive positive pressure ventilation (aRR, 1.56; 95% CI, 1.18-2.07), and oxygen concentrators (aRR, 1.50; 95% CI, 1.13-2.00) during the second surge. Burnout was higher during the second surge (60% vs 71%; P < .001), associated with witnessing colleagues at one's hospital contract COVID-19 during both surges (aRR, 1.55 [95% CI, 1.25-1.93] and 1.31 [95% CI, 1.11-1.55], respectively), as well as worries about finances (aRR, 1.28; 95% CI, 1.02-1.61) and lack of ICU nurses (aRR, 1.25; 95% CI, 1.02-1.53) during the first surge. INTERPRETATION: During the COVID-19 pandemic, ICU HCPs in Brazil experienced substantial resource shortages, health care disparities between regions, changes in end-of-life care associated with resource shortages, and high proportions of burnout.

High flow nasal catheter therapy versus non-invasive positive pressure ventilation in acute respiratory failure (RENOVATE trial): protocol and statistical analysis plan.

Background: The best way to offer non-invasive respiratory support across several aetiologies of acute respiratory failure (ARF) is presently unclear. Both high flow nasal catheter (HFNC) therapy and non-invasive positive pressure ventilation (NIPPV) may improve outcomes in critically ill patients by avoiding the need for invasive mechanical ventilation (IMV). Objective: Describe the details of the protocol and statistical analysis plan designed to test whether HFNC therapy is non-inferior or even superior to NIPPV in patients with ARF due to different aetiologies. Methods: RENOVATE is a multicentre adaptive randomised controlled trial that is recruiting patients from adult emergency departments, wards and intensive care units (ICUs). It takes advantage of an adaptive Bayesian framework to assess the effectiveness of HFNC therapy versus NIPPV in four subgroups of ARF (hypoxaemic non-immunocompromised, hypoxaemic immunocompromised, chronic obstructive pulmonary disease exacerbations, and acute cardiogenic pulmonary oedema). The study will report the posterior probabilities of non-inferiority, superiority or futility for the comparison between HFNC therapy and NIPPV. The study assumes neutral priors and the final sample size is not fixed. The final sample size will be determined by a priori determined stopping rules for non-inferiority, superiority and futility for each subgroup or by reaching the maximum of 2000 patients. Outcomes: The primary endpoint is endotracheal intubation or death within 7 days. Secondary outcomes are 28-day and 90-day mortality, and ICU-free and IMV-free days in the first 28 days. Results and conclusions: RENOVATE is designed to provide evidence on whether HFNC therapy improves, compared with NIPPV, important patient-centred outcomes in different aetiologies of ARF. Here, we describe the rationale, design and status of the trial. Trial registration:ClinicalTrials.gov NCT03643939.