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Abstract Objective To describe the frequency and types of congenital anomalies and associated risk factors in Brazilian women with type 2 diabetes. Methods In this retrospective cohort study between 2005 and 2021, we included all pregnant participants with type 2 diabetes from the two major public hospitals in southern Brazil. We collected data from the electronic hospital records. Congenital anomalies were classified by the 10th revised International Classification of Diseases, Q chapter, enhanced by the EUROCAT registry classification, and categorized by type and gravity. We used multiple Poisson regression with robust estimates to estimate risks. Results Among 648 participants, we excluded 19, and 62 were lost to follow-up; therefore, we included 567 participants. Overt diabetes arose in 191 participants (33.7%, 95% CI 30.0% – 38.0%). Less than 20% of the participants supplemented folate. Congenital anomalies occurred in 78 neonates (13.8%, CI 11.0 − 16.9%), 73 babies (93.6%) presented major anomalies, and 20 (10.5%) cases occurred in participants with overt diabetes. Cardiac anomalies were the most frequent (43 isolated and 12 combined). Pre-eclampsia was associated with an increased risk in the analyses including all women (adjusted RR 1.87 (95% CI 1.23–2.85), p = 0.003), but not in analyses including only women with an HbA1c measured up to the 14th gestational age. HbA1c, either measured at any time in pregnancy (adjusted RR 1.21 (95% CI 1.10–1.33), p

ContextCOVID-19 induces complex distress across physical, psychological, and social realms and palliative care (PC) has the potential to mitigate this suffering significantly.ObjectivesTo describe the clinical characteristics and outcomes of COVID-19 patients with an indication of PC, compared to patients who had no indication, in different pandemic waves.MethodsThis retrospective multicenter observational cohort included patients from 40 hospitals, admitted from March 2020 to August 2022. Patients who had an indication of palliative care (PC) described in their medical records were included in the palliative care group (PCG), while those who had no such indication in their medical records were allocated to the non-palliative care group (NPCG).ResultsOut of 21,158 patients, only 6.7% had indication for PC registered in their medical records. The PCG was older, had a higher frequency of comorbidities, exhibited higher frailty, and had a higher prevalence of clinical complications and mortality (81.4% vs. 17.7%, p

ABSTRACT The FreeStyle Libre Flash Glucose Monitoring System allows users to obtain sensor glucose values by scanning with the reader or their mobile phone. We report a case of a 59‐year‐old man with type 1 diabetes mellitus who developed diabetic ketoacidosis due to a sensor defect. After replacing the sensor with a new one, the glucose value shown in the device was much lower than usual, which made him consider that he was hypoglycemic. Accordingly, he reduced his insulin dose and eventually developed diabetic ketoacidosis. He was unaware of the discrepancy due to the lack of self‐monitoring of his blood glucose, although he was educated to do. In sum, glucose monitoring with the FreeStyle Libre is helpful; however, it is necessary to remind the patient that a sensor defect leading to a severe complication frequently happens.

Abstract Brittle fracture of a covalent material is ultimately governed by the strength of the electronic bonds. Recently, attempts have been made to alter the mechanical properties including fracture strength by excess electron/hole doping. However, the underlying mechanics/mechanism of how these doped electrons/holes interact with the bond and changes its strength is yet to be revealed. Here, we perform first-principles density-functional theory calculations to clarify the effect of excess electrons/holes on the bonding strength of covalent Si. We demonstrate that the bond strength of Si decreases or increases monotonically in correspondence with the doping concentration. Surprisingly, change to the extent of 30–40% at the maximum feasible doping concentration could be observed. Furthermore, we demonstrated that the change in the covalent bond strength is determined by the bonding/antibonding state of the doped excess electrons/holes. In summary, this work explains the electronic strengthening mechanism of covalent Si from a quantum mechanical point of view and provides valuable insights into the electronic-level design of strength in covalent materials.

ABSTRACT To verify whether members of the phylum Candidatus Patescibacteria parasitize archaea, we applied cultivation, microscopy, metatranscriptomic, and protein structure prediction analyses on the Patescibacteria-enriched cultures derived from a methanogenic bioreactor. Amendment of cultures with exogenous methanogenic archaea, acetate, amino acids, and nucleoside monophosphates increased the relative abundance of Ca. Patescibacteria. The predominant Ca. Patescibacteria were families Ca. Yanofskyibacteriaceae and Ca. Minisyncoccaceae, and the former showed positive linear relationships (r2 ≥ 0.70) Methanothrix in their relative abundances, suggesting related growth patterns. Methanothrix and Methanospirillum cells with attached Ca. Yanofskyibacteriaceae and Ca. Minisyncoccaceae, respectively, had significantly lower cellular activity than those of the methanogens without Ca. Patescibacteria, as extrapolated from fluorescence in situ hybridization-based fluorescence. We also observed that parasitized methanogens often had cell surface deformations. Some Methanothrix-like filamentous cells were dented where the submicron cells were attached. Ca. Yanofskyibacteriaceae and Ca. Minisyncoccaceae highly expressed extracellular enzymes, and based on structural predictions, some contained peptidoglycan-binding domains with potential involvement in host cell attachment. Collectively, we propose that the interactions of Ca. Yanofskyibacteriaceae and Ca. Minisyncoccaceae with methanogenic archaea are parasitisms.IMPORTANCECulture-independent DNA sequencing approaches have explored diverse yet-to-be-cultured microorganisms and have significantly expanded the tree of life in recent years. One major lineage of the domain Bacteria, Ca. Patescibacteria (also known as candidate phyla radiation), is widely distributed in natural and engineered ecosystems and has been thought to be dependent on host bacteria due to the lack of several biosynthetic pathways and small cell/genome size. Although bacteria-parasitizing or bacteria-preying Ca. Patescibacteria have been described, our recent studies revealed that some lineages can specifically interact with archaea. In this study, we provide strong evidence that the relationship is parasitic, shedding light on overlooked roles of Ca. Patescibacteria in anaerobic habitats.

Abstract Background To determine the incidence and characteristics of the multiple subretinal particles (SRPs) present after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Methods The medical records of 224 eyes of 224 patients that underwent PPV for RRD were reviewed. The presence of SRPs in the subretinal fluid blebs and the presence of subretinal deposits were determined by optical coherence tomography (OCT) and fundus autofluorescence (FAF). The characteristics of the FAF and infrared reflectance (IR) images of a scanning laser ophthalmoscope in eyes with SRPs (SRPs group) were compared to that of eyes without SRPs (control group). Results SRPs were observed in 27 eyes (12%), and they were completely resolved in 20 eyes (74%) after 6 months. The incidence of macula-off RRD (85%) and preoperative precipitates (41%) were significantly higher in the SRPs group than that in the control group (64%, P = 0.046; 12%, P = 0.002). The axial length was significantly shorter in the SRPs group than that in the control group (25.04 ± 1.54 mm, 26.00 ± 1.78 mm, P = 0.012). The preoperative and postoperative best-corrected visual acuity were not significantly different between the two groups (P = 0.702, P = 0.337). The subretinal fluid bleb determined by OCT were hyperfluorescent in the FAF images in 24 eyes (89%), and the subretinal deposits were hypofluorescent with solid appearance by OCT other than fluid in 3 eyes (11%). The hypofluorescent subretinal deposits in the FAF images were bright in the IR images in 2 eyes. Conclusions The SRPs consist of lipofuscin-related hyperfluorescent subretinal fluid and the subretinal deposits containing bright IR melanin particles of proliferating retinal pigment epithelial cells.

Van der Waals (vdW)-layered materials, such as graphite, exhibit unique mechanical properties owing to their structural and mechanical anisotropies. This study reports the development of a mechanical model that reproduces the characteristics of the nonlinear and reversible bending deformation of vdW-layered materials, while taking into account the microscopic mechanism of the discrete interlayer slips. The vdW-layered material was modeled as a stack of interacting discrete deformable layers (semi-discrete layer model), and the interlayer interaction was modeled using a cohesive zone model that reproduced the localized interlayer slip. Using the finite-element method, out-of-plane bending deformation analyses were performed on the cantilevers of the highly oriented pyrolytic graphite (HOPG) and MoTe2, and the validity of the model was verified by comparing it with the experimental results. The model accurately reproduced the loading and unloading behaviors in the experiments for the submicron HOPG cantilevers or the large nonlinear and reversible deformation with a hysteresis loop. Furthermore, the model reproduced well the characteristics of the bending experiments for the micro-MoTe2 cantilevers, or the intermittent decrease in stiffness during the loading process and deformation restoration during the unloading process. These results demonstrated that the designed semi-discrete layer model can be universally applied to reproduce the bending deformation characteristics of a variety of vdW-layered materials and can be employed to effectively elucidate the underlying deformation mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with rheumatologic diseases are monitored fundamentally through metric tools or index calculated from clinical data and patient exams, which allow us to assess the severity of the disease and guide the therapeutic decision. In rheumatoid arthritis (RA), for treatment to be optimized and considered effective, periodic assessment with composite disease activity index and a 'treat-to-target' approach is required. The Routine Assessment of Patient Index Data 3 (RAPID3) in the Multidimensional Health Assessment Questionnaire (MDHAQ) includes only three measures based on the central patient self-reported dataset and can be used in a 'treat-to-target' approach analogous to the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28-joints (DAS28). This tool, however, has not undergone cross-cultural or clinical validation in Brazil. In this research, we performed the MDHAQ cross-cultural and clinical validation for the Brazilian population of RA patients. Methods The Portuguese version of the MDHAQ was created identically in an electronic questionnaire and underwent a cross-cultural validation process with 38 participants. Test–retest was performed in 29 patients. Further, a clinical validation with 129 Rheumatoid Arthritis patients was performed. Electronic MDHAQ was answered through an online platform. We also collected socioeconomic data as well as other clinical (CDAI, SDAI, DAS28) and functional (HAQ) scores during the face-to-face assessment of patients. Results MDHAQ/RAPID3 maintained semantic, idiomatic, as well as conceptual and experience equivalence for the Brazilian population, with 92% acceptance of participants. It showed test–retest reliability, adequate internal consistency (Cronbach's α 0.85) and correlation of the scores obtained with adequate association with the DAS28 gold standard. RAPID3 also had high sensitivity (98%), adequate specificity (48%), high negative predictive value (92%) and negative post-test probability of 8%, attributes expected for a test tool for population screening. Conclusion The use of MDHAQ/RAPID3 associated with traditional clinical measures can adequately allow for remote follow-up based on the 'treat-to-target' approach with performance comparable to the gold standard DAS28, being a viable tool in the sample of Brazilian patients with RA in the current context of telehealth.

Abstract Background Women with diabetes first diagnosed during pregnancy (overt diabetes) may be at the same risk level of adverse outcomes as those with known pregestational diabetes. We compared pregnancy outcomes between these groups. Methods We evaluated pregnant women with type 2 diabetes, pregestational or overt diabetes, attending high risk antenatal care in two public hospitals in Southern Brazil, from May 20, 2005 to June 30, 2021. Outcomes were retrieved from electronic medical records. Risk of adverse outcomes, expressed as relative risk (RR) and 95% confidence interval (CI), were calculated using Poisson regression with robust estimates. Results Of 618 women, 33% were labelled as having overt diabetes and 67%, pregestational diabetes. Baseline maternal characteristics were similar: there was a slight, non-clinically relevant, difference in maternal age (33 ± 5.7 years in women with pregestational diabetes vs. 32 ± 6.0 years in women with overt diabetes, p = 0.004); and women with overt diabetes reported smoking almost twice compared to those with pregestational diabetes (12.3% vs. 6.5%, p = 0.024). There were no relevant differences between the groups regarding pregnancy outcomes, although there was a trend of higher neonatal intensive care admission in the group of women with pregestational diabetes (45.2% vs. 36.1%, p = 0.051). Conclusions Overt diabetes was diagnosed in one third of this cohort of pregnant women with hyperglycemia. Their pregnancy outcomes were similar to those of women with pregestational diabetes and were mostly related to maternal demographic characteristics and metabolic control. A call to action should be made to identify women of childbearing age at risk for pre-pregnancy diabetes; to detect hyperglycemia before conception; and to implement timely preconception care to all women with diabetes.

Abstract Background During the COVID-19 pandemic, some studies describing different aspects of the infection included very similar participants, rising suspicion about double reporting. We aimed to evaluate the Gantt chart as a tool to highlight possible double reporting. The chart is routinely used in business applications to depict tasks of a project, by plotting horizontal bars against time, showing their time span and overlaps. Methods All case reports and case series of pregnant women with COVID-19, published by July 15, 2020, were included. Initial and final dates of participants’ enrollment, country, city, hospital, and number of pregnancies were plotted in the Gantt chart. Bars stand for enrollment dates of each study, according to hospital and city, thus allowing comparisons. Results We included 116 articles in the present analysis. The Gantt chart highlighted papers in which some participants were likely the same, thus allowing easier identification of double reporting of cases. Combining all information and pregnancy characteristics and outcomes helped to recognize duplications when the authors did not acknowledged the previous publication. Conclusions Unintended double reporting may occur, especially in exceptional times. The Gantt chart may help researchers to visually identify potential duplications, thus avoiding biased estimates in systematic reviews or meta-analysis.

ABSTRACT Objective: Pregnancy complicated by type 2 diabetes is rising, while data on type 2 diabetes first diagnosed in pregnancy (overt diabetes) are scarce. We aimed to describe the frequency and characteristics of pregnant women with overt diabetes, compare them to those with known pregestational diabetes, and evaluate the potential predictors for the diagnosis of overt diabetes. Subjects and methods: A retrospective cohort study including all pregnant women with type 2 diabetes evaluated in two public hospitals in Porto Alegre, Brazil, from May 20, 2005, to June 30, 2021. Classic and obstetric factors associated with type 2 diabetes risk were compared between the two groups, using machine learning techniques and multivariable analysis with Poisson regression. Results: Overt diabetes occurred in 33% (95% confidence interval: 29%-37%) of 646 women. Characteristics of women with known or unknown type 2 diabetes were similar; excessive weight was the most common risk factor, affecting ~90% of women. Age >30 years and positive family history of diabetes were inversely related to a diagnosis of overt diabetes, while previous delivery of a macrosomic baby behaved as a risk factor in younger multiparous women; previous gestational diabetes and chronic hypertension were not relevant risk factors. Conclusion: Characteristics of women with overt diabetes are similar to those of women with pregestational diabetes. Classic risk factors for diabetes not included in current questionnaires can help identify women at risk of type 2 diabetes before they become pregnant.

IntroductionThe first-line treatment for Cushing’s disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response.MethodsWe searched for articles that evaluated ketoconazole use in Cushing’s disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels.ResultsAfter applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism.ConclusionKetoconazole can be considered a safe and efficacious option for Cushing’s disease treatment after pituitary surgery.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).

Myocardial injury (MI) is frequent in critically ill patients with COVID-19, but its pathogenesis remains unclear. We hypothesized that MI is not solely due to viral infection by SARS-CoV-2 but rather due to the common pathophysiological mechanisms associated with severe pulmonary infections and respiratory failure. This contemporary cohort study was designed to compare the incidence of MI in patients with acute respiratory failure caused by COVID-19 to patients with other pulmonary infections. In addition, we aimed to investigate whether MI was a distinct risk factor for in-hospital mortality in patients with COVID-19 compared to those with non-COVID-19 infections. This study included 1444 patients with COVID-19 (55.5% men; age 58 (46;68) years) and 182 patients with other pulmonary infections (46.9% men; age 62 (44;73) years). The incidence of MI at ICU admission was lower in COVID-19 patients (36.4%) compared to non-COVID-19 patients (56%), and this difference persisted after adjusting for age, sex, coronary artery disease, heart failure, SOFA score, lactate, and C-reactive protein (RR 0.84 (95% CI, 0.71–0.99)). MI at ICU admission was associated with a 59% increase in mortality (RR 1.59 (1.36–1.86); p < 0.001), and there was no significant difference in the mortality between patients with COVID-19 and those with other pulmonary infections (p = 0.271). We concluded that MI is less frequent in patients with critical COVID-19 pneumonia and respiratory failure compared to those with other types of pneumonia. The occurrence of MI is a significant risk factor for in-hospital mortality, regardless of the etiology of the pulmonary infection.

Abstract Aims Cardiac troponin (cTn) and B‐type natriuretic peptide (BNP) are elevated in haemodialysis (HD) patients, and this elevation is associated with HD‐induced myocardial stunning/myocardial strain. However, studies using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) have shown that these cardiac biomarkers are measured in 0.04 ng/mL) with a median (inter‐quartile range) level of 0.020 (0.005–0.041) ng/mL, and 1140 (99%) patients had elevated NT‐proBNP (cut‐off for heart failure: >125 pg/mL) with a median level of 3658 (1689–9356) pg/mL. There were 167 deaths during a median follow‐up of 2.8 (2.2–2.8) years. Higher levels of both cardiac biomarkers were incrementally associated with mortality after adjustment for potential confounders. Even after adjustment for alternative cardiac biomarkers, the overall P value for the association was 0.04 ng/mL (vs. cTnI 8000 pg/mL (vs. NT‐proBNP

Dando continuidade à série de artigos que pretendem orientar o usuário na utilização da ferramenta PSS Health para o planejamento de uma pesquisa, esta edição apresenta um passo a passo de como realizar o cálculo para tamanho de amostra e de quais informações são necessárias para testar relações estatísticas entre variáveis e um desfecho binário: comparação de proporções entre grupos independentes (dois ou mais), comparação de duas proporções dependentes e regressão logística. Todos os exemplos também são ilustrados e disponibilizados em vídeos no canal da Unidade de Bioestatística.