A spatial portrait of the human sebaceous gland transcriptional program.

Sebaceous glands (SG) and their oily secretion (sebum) are indispensable for maintaining skin structure and function, and their deregulation causes skin disorders including but not limited to acne. Recent studies also indicate that sebum may have important immunomodulatory activities and may influence whole-body energy metabolism. However, the progressive transcriptional changes of sebocytes that lead to sebum production have never been characterized in detail. Here, we exploited the high cellular resolution provided by sebaceous hyperplasia and integrated spatial transcriptomics, pseudo time analysis, RNA velocity, and functional enrichment to map the landscape of sebaceous differentiation. Our results were validated by comparison with published SG transcriptome data and further corroborated by assessing the protein expression pattern of a subset of the transcripts in the public repository Human Protein Atlas. Departing from four sebocyte differentiation stages generated by unsupervised clustering, we demonstrate consecutive modulation of cellular functions associable with specific gene sets, from cell proliferation and oxidative phosphorylation via lipid synthesis to cell death. Both validation methods confirmed the biological significance of our results. Our report is complemented by a freely available and browsable online tool. Our data provide the first high-resolution spatial portrait of the SG transcriptional landscape and deliver starting points for experimentally assessing novel candidate molecules for regulating SG homeostasis in health and disease.

Epidemiology and management of gestational diabetes.

Gestational diabetes is defined as hyperglycaemia first detected during pregnancy at glucose concentrations that are less than those of overt diabetes. Around 14% of pregnancies globally are affected by gestational diabetes; its prevalence varies with differences in risk factors and approaches to screening and diagnosis; and it is increasing in parallel with obesity and type 2 diabetes. Gestational diabetes direct costs are US$1·6 billion in the USA alone, largely due to complications including hypertensive disorders, preterm delivery, and neonatal metabolic and respiratory consequences. Between 30% and 70% of gestational diabetes is diagnosed in early pregnancy (ie, early gestational diabetes defined by hyperglycaemia before 20 weeks of gestation). Early gestational diabetes is associated with worse pregnancy outcomes compared with women diagnosed with late gestational diabetes (hyperglycaemia from 24 weeks to 28 weeks of gestation). Randomised controlled trials show benefits of treating gestational diabetes from 24 weeks to 28 weeks of gestation. The WHO 2013 recommendations for diagnosing gestational diabetes (one-step 75 gm 2-h oral glucose tolerance test at 24-28 weeks of gestation) are largely based on the Hyperglycemia and Adverse Pregnancy Outcomes Study, which confirmed the linear association between pregnancy complications and late-pregnancy maternal glycaemia: a phenomenon that has now also been shown in early pregnancy. Recently, the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) trial showed benefit in diagnosis and treatment of early gestational diabetes for women with risk factors. Given the diabesity epidemic, evidence for gestational diabetes heterogeneity by timing and subtype, and advances in technology, a life course precision medicine approach is urgently needed, using evidence-based prevention, diagnostic, and treatment strategies.

A Spatial Transcriptomics Browser for Discovering Gene Expression Landscapes across Microscopic Tissue Sections.

A crucial feature of life is its spatial organization and compartmentalization on the molecular, cellular, and tissue levels. Spatial transcriptomics (ST) technology has opened a new chapter of the sequencing revolution, emerging rapidly with transformative effects across biology. This technique produces extensive and complex sequencing data, raising the need for computational methods for their comprehensive analysis and interpretation. We developed the ST browser web tool for the interactive discovery of ST images, focusing on different functional aspects such as single gene expression, the expression of functional gene sets, as well as the inspection of the spatial patterns of cell-cell interactions. As a unique feature, our tool applies self-organizing map (SOM) machine learning to the ST data. Our SOM data portrayal method generates individual gene expression landscapes for each spot in the ST image, enabling its downstream analysis with high resolution. The performance of the spatial browser is demonstrated by disentangling the intra-tumoral heterogeneity of melanoma and the microarchitecture of the mouse brain. The integration of machine-learning-based SOM portrayal into an interactive ST analysis environment opens novel perspectives for the comprehensive knowledge mining of the organization and interactions of cellular ecosystems.

Single-cell transcriptomics reveals prominent expression of IL-14, IL-18, and IL-32 in psoriasis.

RATIONALE: Psoriasis is a chronic inflammatory skin disease involving different cytokines and chemokines. OBJECTIVES: Here we use single-cell transcriptomic analyses to identify relevant immune cell and nonimmune cell populations for an in-depth characterization of cell types and inflammatory mediators in this disease. METHODS: Psoriasis skin lesions of eight patients are analyzed using single-cell technology. Data are further validated by in situ hybridization (ISH) of human tissues, serum analyses of human samples and tissues of a murine model of psoriasis, and by in vitro cell culture experiments. RESULTS: Several different immune-activated cell types with particular cytokine patterns are identified such as keratinocytes, T-helper cells, dendritic cells, macrophages, and fibroblasts. Apart from well-known factors, IL-14 (TXLNA), IL-18, and IL-32 are identified with prominent expression in individual cell types in psoriasis. The percentage of inflammatory cellular subtypes expressing IL-14, IL-18, and IL-32 was significantly higher in psoriatic skin compared with healthy control skin. These findings were confirmed by ISH of human skin samples, in a murine model of psoriasis, in human serum samples, and in in vitro experiments. CONCLUSIONS: Taken together, we provide a differentiated view of psoriasis immune-cell phenotypes that support the role of IL-14, IL-18, and IL-32 in psoriasis pathogenesis.

Applying Machine Learning to Blood Count Data Predicts Sepsis with ICU Admission.

BACKGROUND: Timely diagnosis is crucial for sepsis treatment. Current machine learning (ML) models suffer from high complexity and limited applicability. We therefore created an ML model using only complete blood count (CBC) diagnostics. METHODS: We collected non-intensive care unit (non-ICU) data from a German tertiary care centre (January 2014 to December 2021). Using patient age, sex, and CBC parameters (haemoglobin, platelets, mean corpuscular volume, white and red blood cells), we trained a boosted random forest, which predicts sepsis with ICU admission. Two external validations were conducted using data from another German tertiary care centre and the Medical Information Mart for Intensive Care IV database (MIMIC-IV). Using the subset of laboratory orders also including procalcitonin (PCT), an analogous model was trained with PCT as an additional feature. RESULTS: After exclusion, 1 381 358 laboratory requests (2016 from sepsis cases) were available. The CBC model shows an area under the receiver operating characteristic (AUROC) of 0.872 (95% CI, 0.857-0.887). External validations show AUROCs of 0.805 (95% CI, 0.787-0.824) for University Medicine Greifswald and 0.845 (95% CI, 0.837-0.852) for MIMIC-IV. The model including PCT revealed a significantly higher AUROC (0.857; 95% CI, 0.836-0.877) than PCT alone (0.790; 95% CI, 0.759-0.821; P < 0.001). CONCLUSIONS: Our results demonstrate that routine CBC results could significantly improve diagnosis of sepsis when combined with ML. The CBC model can facilitate early sepsis prediction in non-ICU patients with high robustness in external validations. Its implementation in clinical decision support systems has strong potential to provide an essential time advantage and increase patient safety.

Fine mapping a QTL for BYDV-PAV resistance in maize.

Barley yellow dwarf (BYD) is one of the economically most important virus diseases of cereals worldwide, causing yield losses up to 80%. The means to control BYD are limited, and the use of genetically resistant cultivars is the most economical and environmentally friendly approach. The objectives of this study were i) to identify the causative gene for BYD virus (BYDV)-PAV resistance in maize, ii) to identify single nucleotide polymorphisms and/or structural variations in the gene sequences, which may cause differing susceptibilities to BYDV-PAV of maize inbreds, and iii) to characterize the effect of BYDV-PAV infection on gene expression of susceptible, tolerant, and resistant maize inbreds. Using two biparental mapping populations, we could reduce a previously published quantitative trait locus for BYDV-PAV resistance in maize to ~ 0.3 Mbp, comprising nine genes. Association mapping and gene expression analysis further reduced the number of candidate genes for BYDV-PAV resistance in maize to two: Zm00001eb428010 and Zm00001eb428020. The predicted functions of these genes suggest that they confer BYDV-PAV resistance either via interfering with virus replication or by inducing reactive oxygen species signaling. The gene sequence of Zm00001eb428010 is affected by a 54 bp deletion in the 5`-UTR and a protein altering variant in BYDV-PAV-resistant maize inbreds but not in BYDV-PAV-susceptible and -tolerant inbreds. This finding suggests that altered abundance and/or properties of the proteins encoded by Zm00001eb428010 may lead to BYDV-PAV resistance.

Optimal cardiovascular health is associated with slower cognitive decline.

BACKGROUND: Life's Simple 7, a lifestyle and cardiovascular index associated with cognition, has been updated to Life's Essential 8 (LE8) to include sleep. LE8 has been related to cardiovascular outcomes but its association with cognition is unclear. METHODS: In this longitudinal analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), LE8 score was based on health behaviors (diet, physical activity, nicotine exposure, and sleep health) as well as health-related factors (body mass index, blood lipids, blood glucose, and blood pressure). Cognition was assessed in three waves, 4 years apart, using the Consortium to Establish a Registry for Alzheimer's Disease - Word List, semantic and phonemic verbal fluency, the Trail-Making Test B (TMT-B), and a global composite score. We used linear mixed-model analysis, inverse probability weighting, and interaction analysis. RESULTS: At baseline, the mean age of the study cohort was 51.4 ± 8.9 years, 56% were women, and 53% were White. Higher baseline LE8 scores were associated with slower decline in global cognition (ß = 0.001, 95% confidence interval [CI] 0.001, 0.002; p < 0.001), memory (ß = 0.001, 95% CI 0.000, 0.002; p = 0.013), verbal fluency (ß = 0.001, 95% CI 0.000, 0.002; p = 0.003), and TMT-B (ß = 0.004, 95% CI 0.003, 0.005; p < 0.001). This association was mainly driven by LE8 health factors, particularly blood glucose and blood pressure. Age, sex, and race were modifiers of the association between LE8 and global cognitive decline (p < 0.001), suggesting it was more pronounced in older, male, and Black participants. CONCLUSIONS: Higher baseline LE8 scores were associated with slower global and domain-specific cognitive decline during 8 years of follow-up, mainly due to health factors such as blood glucose and blood pressure. Sociodemographic factors were modifiers of this association.

Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

OBJECTIVES: To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer. METHODS: Pre-menopausal women aged 40-50 years old were scanned at 3 T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE. Statistical tests were performed to determine inter- and intra-user repeatability, evaluate the symmetry between metrics derived from left and right breasts, and investigate MRBD and BPE differences between the high- and low-risk cohorts. RESULTS: Intra- and inter-user reproducibility in estimates of fibro-glandular tissue volume, MRBD, and median BPE estimations were good, with coefficients of variation < 15%. Coefficients of variation between left and right breasts were also low (< 25%). There were no significant correlations between fibro-glandular tissue volume, MRBD, and BPE for either risk group. However, the high-risk group had higher BPE kurtosis, although linear regression analysis did not reveal significant associations between BPE kurtosis and breast cancer risk. CONCLUSIONS: This study found no significant differences or correlations in fibro-glandular tissue volume, MRBD, or BPE metrics between the two groups of women with different levels of breast cancer risk. However, the results support further investigation into the heterogeneity of parenchymal enhancement. KEY POINTS: • A semi-automated method enabled quantitative measurements of fibro-glandular tissue volume, breast density, and background parenchymal enhancement with minimal user intervention. • Background parenchymal enhancement was quantified over the entire parenchyma, segmented in pre-contrast images, thus avoiding region selection. • No significant differences and correlations in fibro-glandular tissue volume, breast density, and breast background parenchymal enhancement were found between two cohorts of women at high and low levels of breast cancer risk.

Anthropometric trajectory in the course of life and occurrence of sarcopenia in men and women: results from the ELSA-Brasil cohort.

This study aimed to identify patterns of anthropometric trajectories throughout life and to analyse their association with the occurrence of sarcopenia in people from the Longitudinal Study of Adult Health (ELSA-Brasil). It is a cross-sectional study involving 9670 public servants, aged 38-79 years, who answered the call for new data collection and exams, conducted approximately 4 years after the study baseline (2012-2014). Data sequence analysis was used to identify patterns of anthropometric trajectory. A theoretical model was elaborated based on the directed acyclic graph (DAG) to select the variables of minimum adjustment in the analysis of the causal effect between trajectory and sarcopenia. Poisson regression with robust variance was adopted for data analysis. The patterns of change in the anthropometric trajectory were classified in stable weight (T1); change to normal weight (T2); change to excess weight (T3); weight fluctuation (T4) and change to low weight (T5). The prevalence of sarcopenia in men and women who changed the anthropometric path for the low weight was twice as large when compared to participants with a stable weight trajectory. A protective effect of the excess weight trajectory was observed for the occurrence of sarcopenia in them. The results pointed to the need for health policies that encourage the proper management of body components in order to prevent and control obesity, as well as to preserve the quantity and quality of skeletal muscle mass throughout life, especially in older adults.

Challenge in hyponatremic patients - the potential of a laboratory-based decision support system for hyponatremia to improve patient's safety.

OBJECTIVES: Hyponatremia is the most frequent electrolyte disorder in hospitalized patients with increased mortality and morbidity. In this study, we evaluated the follow-up diagnostic, the risk of inadequate fast correction and the outcome of patients with profound hyponatremia (pHN), defined as a blood sodium concentration below 120 mmol/L. The aim was to identify a promising approach for a laboratory-based clinical decision support system (CDSS). METHODS: This retrospective study included 378,980 blood sodium measurements of 83,315 cases at a German tertiary care hospital. Hospitalized cases with pHN (n=211) were categorized into two groups by the time needed for a follow-up measurement to be performed (time to control, TTC) as either <12 h (group 1: "TTC≤12 h", n=118 cases) or >12 h (group 2: "TTC>12 h", n=93 cases). Length of hospital stay, sodium level at discharge, ward transfers, correction of hyponatremia, and risk of osmotic demyelination syndrome (ODS) due to inadequate fast correction were evaluated with regard to the TTC of sodium blood concentration. RESULTS: pHN was detected in 1,050 measurements (0.3%) in 211 cases. Cases, in which follow-up diagnostics took longer (TTC>12 h), achieved a significantly lower sodium correction during their hospitalization (11.2 vs. 16.7 mmol/L, p<0.001), were discharged more frequently in hyponatremic states (<135 mmol/L; 58 (62.4%) vs. 43 (36.4%), p<0.001) and at lower sodium blood levels (131.2 vs. 135.0 mmol/L, p<0.001). Furthermore, for these patients there was a trend toward an increased length of hospital stay (13.1 vs. 8.5 days, p=0.089), as well as an increased risk of inadequate fast correction (p<0.001). CONCLUSIONS: Our study shows that less frequent follow-up sodium measurements in pHN are associated with worse outcomes. Patients with a prolonged TTC are at risk of insufficient correction of hyponatremia, reduced sodium values at discharge, and possible overcorrection. Our results suggest that a CDSS that alerts treating physicians when a control time of >12 h is exceeded could improve patient care in the long term. We are initiating a prospective study to investigate the benefits of our self-invented CDSS (www.ampel.care) for patients with pHN.

Evidence-based cutoffs for total and adjusted calcium: a major factor in detecting severe hypo- and hypercalcemia.

OBJECTIVES: Severe hypo- and hypercalcemia are common and urgent treatment is recommended. Free calcium (fCa) is the gold standard but needs blood gas tests with challenging preanalytics. Total calcium (tCa) and calculated adjusted calcium (aCa) are readily available, but their interpretation is hampered by identical tCa and aCa cutoffs, laborious local aCa calculation and difficult comparability of calcium biomarkers. METHODS: Laboratory results from University Medicine Leipzig were evaluated over a five-year period (236,274 patients). A local aCa equation was derived by linear least squares regression, the agreement between fCa, tCa and aCa assessed with Cohen's κ and decision thresholds derived by this indirect method. RESULTS: The local aCa equation was created from data of 9,756 patients, each with one paired measurement of tCa, fCa and albumin. Derived aCa cutoffs (1.95/3.15 mmol/L) differ markedly from derived tCa cutoffs (1.6/2.9 mmol/L) and severe hypo- and hypercalcemia can be more accurately assessed by aCa (κ=0.489, 0.812) than by tCa (κ=0.445, 0.744). Comparing our approach to standard care (tCa, literature cutoff), a total 3,250 of 3,680 (88.3 %) misclassified measurements were correctly classified when using aCa with evidence-based cutoffs. CONCLUSIONS: Optimized cutoffs for aCa and tCa hold great potential for improved patient care. Locally derived aCa equations differ mostly in the chosen mean normal calcium and provide minimal overall improvement, but entail a close examination of the used cutoffs before application.

Higher troponin T serum concentrations in hospital patients without diagnosed cardiac diseases compared to a population-based cohort.

OBJECTIVES: Upper reference limits of high-sensitivity cardiac troponin T (hs-cTnT) are derived from healthy, population-based cohorts, and are frequently exceeded in hospitalized patients. In this study we aim to systematically examine the differences between in-hospital patients with no diagnosed cardiac diseases and a population-based cohort. METHODS: Retrospective analyses were performed in two independent cohorts. We included 5,652 participants of the prospective population-based LIFE cohort as well as 9,300 patients having been treated at our hospital between 2014 and 2021. In both cohorts, subjects with diagnosed or suspected cardiac diseases were excluded. We used Spearman's rank correlation for correlation analyses of hs-cTnT serum concentrations and age. Sex- and age-adjusted 99th percentiles for hs-cTnT in subjects with preserved renal function were obtained in both cohorts. RESULTS: In both cohorts, hs-cTnT serum concentrations positively correlated with age. Male sex was associated with higher hs-cTnT serum concentrations. Persons treated in hospital showed significantly higher hs-cTnT concentrations in females and males aged above 50. While in the population-based cohort only 99th percentile hs-cTnT results of females aged above 70 and males aged above 60 years exceeded the assay's upper reference limit, the 99th percentiles of in-hospital females over 40 years and males of all age groups exceeded this threshold. CONCLUSIONS: Besides age and sex, hospitalization per se is correlated with higher serum concentrations of hs-cTnT in most age groups. Our results indicate, that unconditionally applying current hs-cTnT cut-offs to inpatients might overestimate myocardial infarction and potentially lead to overdiagnosis.

Risk of stillbirth and preterm birth among undocumented pregnant migrant women in Denmark: A retrospective case-control study.

AIMS: To examine the associations between undocumented pregnant migrant women and the risk of experiencing stillbirth or preterm birth. METHODS: A retrospective case-control study based on nationwide registers from Statistics Denmark and hospital journals from the seven largest hospital wards in Denmark from 1 January 2011 to 31 December 2018. A total of 882 undocumented pregnant migrant women and 3528 matched controls (both documented migrant and non-migrant women) were included. Logistic regression models were used to estimate the risk of undocumented pregnant migrant women experiencing (a) stillbirth and (b) preterm birth compared with the control group. RESULTS: Of the undocumented pregnant migrant women, 33.3% were EU citizens, 16.2% were applicants for residence and 50.5% had an unknown basis for residence. The mean age of the undocumented pregnant migrant women was 28.4 years, whereas the mean age of women in the control group was 30.9 years. Higher adjusted odds of experiencing stillbirth (aOR 3.50; 95% CI 1.31-9.38) and preterm birth (aOR 1.41; 95% CI 1.04-1.93) were observed among the undocumented pregnant migrant women compared with the control group. The basis of residence was not associated with higher odds of experiencing stillbirth or preterm birth. CONCLUSIONS: We found a higher risk of stillbirth and preterm birth among the undocumented pregnant migrant women than in the control group. Our findings suggest a need to increase the focus on providing access to antenatal care among those women currently excluded from this care.

The inflammatory food index and its association with weight gain and incidence of diabetes: Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND AND AIMS: Diet plays a central role in regulating inflammation and is closely related to the development of chronic diseases. We aimed to develop an inflammatory food index (IFI) based on the relationship of food items with biomarkers of inflammation and to evaluate its association with weight gain and type 2 diabetes. METHODS AND RESULTS: A sample of 9909 participants of the ELSA-Brasil study was analyzed. Standardized measurements including interviews, anthropometry, and laboratory exams were performed at baseline and follow-up. A baseline food frequency questionnaire was used to derive IFI scores using reduced rank regression (RRR). The inflammatory pattern derived included 11 pro-inflammatory food groups: processed meat, red meat, pork, sugary soda, and hot dogs. The anti-inflammatory pattern included seven food groups: fruits, nuts, and wine. The IFI score, adjusted through logistic regression for multiple sociodemographic, behavioral, and clinical covariates, including body mass index, predicted the development of a large weight gain (tertile 3 vs. 1: OR = 1.30; 95%CI 1.08-1.55). The score, adjusted for sociodemographic factors through proportional hazard models, predicted incident diabetes (tertile 3 vs. 1: HR = 1.26; 95%CI 1.04-1.52). CONCLUSION: These findings support the hypothesis that subclinical inflammation caused by a pro-inflammatory food pattern, characterized mainly by greater ultra-processed food consumption, underlies weight gain and the development of type 2 diabetes. This study was registered at clinicaltrials.com as NCT02320461.

Incidence of excess body weight and annual weight gain in women and men: Results from the ELSA-Brasil cohort.

OBJECTIVE: To estimate annual weight gain and the incidence of overweight and obesity, stratified according to gender and socioeconomic factors. METHODS: From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we included 13 625 women and men aged 35-74 (2008-2010) who attended a follow-up visit after a mean 3.8-years. Standardized questionnaires were used to record sociodemographic data, and height and weight were measured on all participants during in-person visits at research centers. The incidence rate to overweight was calculated among those not having excess weight at baseline, and incident obesity among those not having this condition at baseline. We evaluated the incidence of overweight and obesity in men and women, adjusted by age, through Poisson regression with robust variance. Large annual weight gain by gender was being defined as ≥90th percentile in the cohort. RESULTS: A global incidence of 7.7% for overweight and 10.6% for obesity was observed, with higher levels seen among black woman (28.5%), young men (21.1%) and woman with low educational level (35.0%). The proportions of overweight and obesity increased with age at both time points, more commonly among those with the lowest levels of per capita income and fewer years of schooling. Large annual weight gain was greater among participants with an intermediate level of education and those who self-identified as black. CONCLUSIONS: A high overall risk of becoming overweight/obese was found, especially among women. The roles of race and education level are fundamental to understanding the effects produced by social inequalities in rates of excess weight.

Increased particle size of triacylglycerol-enriched remnant lipoproteins, but not their plasma concentration or lipid content, augments risk prediction of incident type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes prevention requires the accurate identification of those at high risk. Beyond the association of fasting serum triacylglycerols with diabetes, triacylglycerol-enriched remnant lipoproteins (TRLs) more accurately reflect pathophysiological changes that underlie progression to diabetes, such as hepatic insulin resistance, pancreatic steatosis and systemic inflammation. We hypothesised that TRL-related factors could improve risk prediction for incident diabetes. METHODS: We included individuals from the Brazilian Longitudinal Study of Adult Health cohort. We trained a logistic regression model for the risk of incident diabetes in 80% of the cohort using tenfold cross-validation, and tested the model in the remaining 20% of the cohort (test set). Variables included medical history and traits of the metabolic syndrome, followed by TRL-related measurements (plasma concentration, TRL particle diameter, cholesterol and triacylglycerol content). TRL features were measured using NMR spectroscopy. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). RESULTS: Among 4463 at-risk individuals, there were 366 new cases of diabetes after a mean (±SD) of 3.7 (±0.63) years of follow-up. We derived an 18-variable model with a global AUROC of 0.846 (95% CI: 0.829, 0.869). Overall TRL-related markers were not associated with diabetes. However, TRL particle diameter increased the AUROC, particularly in individuals with HbA1c <39 mmol/mol (5.7%) (hold-out test set [n = 659]; training-validation set [n = 2638]), but not in individuals with baseline HbA1c 39-46 mmol/mol (5.7-6.4%) (hold-out test set [n = 233]; training-validation set [n = 933]). In the subgroup with baseline HbA1c <39 mmol/mol (5.7%), AUROC in the test set increased from 0.717 (95% CI 0.603, 0.818) to 0.794 (95% CI 0.731, 0.862), and AUPRC in the test set rose from 0.582 to 0.701 when using the baseline model and the baseline model plus TRL particle diameter, respectively. TRL particle diameter was highly correlated with obesity, insulin resistance and inflammation in those with impaired fasting glucose at baseline, but less so in those with HbA1c <39 mmol/mol (5.7%). CONCLUSIONS/INTERPRETATION: TRL particle diameter improves the prediction of diabetes, but only in individuals with HbA1c <39 mmol/mol (5.7%) at baseline. These data support TRL particle diameter as a risk factor that is changed early in the course of the pathophysiological processes that lead to the development of type 2 diabetes, even before glucose abnormalities are established. Graphical abstract.

Social Distancing, Mask Use, and Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Brazil, April-June 2020.

We assessed the associations of social distancing and mask use with symptomatic, laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in Porto Alegre, Brazil. We conducted a population-based case-control study during April-June 2020. Municipal authorities furnished case-patients, and controls were taken from representative household surveys. In adjusted logistic regression analyses of 271 case-patients and 1,396 controls, those reporting moderate to greatest adherence to social distancing had 59% (odds ratio [OR] 0.41, 95% CI 0.24-0.70) to 75% (OR 0.25, 95% CI 0.15-0.42) lower odds of infection. Lesser out-of-household exposure (vs. going out every day all day) reduced odds from 52% (OR 0.48, 95% CI 0.29-0.77) to 75% (OR 0.25, 95% CI 0.18-0.36). Mask use reduced odds of infection by 87% (OR 0.13, 95% CI 0.04-0.36). In conclusion, social distancing and mask use while outside the house provided major protection against symptomatic infection.

Treatment of post-prostatectomy urinary incontinence and erectile dysfunction: there is insufficient utilisation of care in German cancer survivors.

PURPOSE: Treatment of post-prostatectomy urinary incontinence (UI) and erectile dysfunction (ED) increases quality of life (QoL). Aim of our study was to evaluate the utilisation of care among patients with post-prostatectomy UI and ED in Germany. METHODS: The HAROW study documented treatment of patients with localised prostate cancer (≤ T2c) in Germany. 1260 patients underwent radical prostatectomy (RP). Patients answered validated questionnaires after a median follow-up of 6.3 years. Response rate was 76.8%. RESULTS: Median age at RP was 65 (IQR 60-69) years. 14% (134/936) used more than one pad per day for UI. 25% (26/104, 30 missing) of UI patients underwent surgery to improve continence. Of patients without surgery, 41% (31/75) reported a moderate-to-severe issue concerning their incontinence with worse mental health and QoL. 81% (755/936) patients were unable to have an erection firm enough for sexual intercourse. Of all ED patients, 40% (319/793) used ED treatment regularly or tried it at least once. 49% (243/499) of patients with interest in sex never tried ED treatment. In multivariate analysis, patients not using ED treatments were older (≥ 70 years OR 4.1), and more often had preoperative ED (OR 2.3) and less interest in sex (OR 2.2). Nevertheless, 30% (73/240) of these patients had moderate-to-severe issues with their ED reporting worse mental health and QoL. CONCLUSION: Almost half of the patients without post-prostatectomy UI and ED treatment reported moderate-to-severe issues with a significant decrease in QoL. This indicates an insufficient utilisation of care in Germany.

Association between control of diabetes mellitus and polypharmacy at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PURPOSE: To determine whether desirable diabetes control is associated with polypharmacy and to evaluate potential drug interactions (DI) in participants with diabetes mellitus in the Brazilian Longitudinal Study on Adult Health (ELSA-Brasil). METHODS: This cross-sectional study included 1418 participants with medical diagnosis of diabetes at study baseline (2008-2010). Polypharmacy was defined as the use of ≥5 drugs. We described the frequency of the most common pharmacological groups used by patients and the potential DI.The association between desirable diabetes control (normal A1c, blood pressure and lipid levels) and polypharmacy was investigated using logistic regression. RESULTS: Most participants were men (52.5%), mean age 57.6 (SD 8.4) years, educated to the university level (39.4%), and self-reported as white (42.9%). In this study, 7.1% (n = 101) of participants had desirable control of diabetes, while 40.4% (n = 573) used polypharmacy, and this use was not significantly associated with better diabetes control (adjusted odds ratio (OR = 1.35 [95%CI 0.86-2.13] P = .19).The pharmacological groups most frequently used were oral antidiabetics followed by acetylsalicylic acid, angiotensin-converting enzyme inhibitors (ACE inhibitors) and statins.The prevalence of potentially mild, moderate and severe DI were, respectively, 2.5%, 14.7% and 0.9%; however, in the desirable control of DM group, these potential DI were related to comorbidity control. CONCLUSION: Faced with the importance of achieving optimal control of diabetes and minimizing risks of potential DI, these results, which are in keeping with previous findings described in the literature, might indicate that guidelines for the patient-centered management of control of diabetes must be revised.

Deciphering the Transcriptomic Heterogeneity of Duodenal Coeliac Disease Biopsies.

Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups-a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease.