Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Socioeconomic disparities in obstructive sleep apnea: a systematic review of empirical research.

BACKGROUND: Considering socioeconomic status (SES) in the diagnosis of obstructive sleep apnea (OSA) will enhance our understanding of socioeconomic disparities in clinical practice of sleep medicine. This systematic review analyzes the relations between SES and OSA measures. METHODOLOGY: Eleven articles were identified through the Pubmed database. The National Institute of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to rate the quality of these studies. RESULTS: This systematic review revealed that associations between socioeconomic status and OSA measures are similar for both adults, children, and adolescents. Our findings showed that: (1) A lower SES is associated with an increased risk of OSA, both in adults and children/adolescents as well as for men and women. (2) Several studies assessed sleep outcomes with a single question, an approach that is unable to capture the multi-dimensionality and day-to-day variability of sleep in general or OSA in particular, (3) Low SES has detrimental effects on sleep health. (4) Sleep questionnaires are more commonly used than objective measure to assess OSA. CONCLUSIONS: Interaction between SES and OSA must be better understood to improve current clinical guidelines. Living conditions influence the trajectory of OSA with unknown speed and for an, undetermined period, pointing to the need for more studies on this topic. Future work should identify the effect of SES on the development and progression of OSA, determine the effect of behavioral intervention and local public health programs to reduce social inequalities associated with OSA.

Exploring socio-economic inequalities in the use of medicines: is the relation mediated by health status?

OBJECTIVES: This study evaluated mediating effects of the health status on the association between socio-economic status (SES) and medicine use. It was hypothesized that more privileged people show a reduced use of medicines, as compared with the underprivileged, because of their superior health status. It was further hypothesized that people may apply medication based on their type of health complaint (ill physical versus mental status). STUDY DESIGN: Data were taken from the 2012 German Epidemiological Survey of Substance Abuse, a nationally representative cross-sectional study of n = 9084 individuals of the German general population aged 18-64 years. METHODS: Direct and indirect effects of SES on weekly use of analgesics and sedatives/hypnotics were examined by applying generalized structural equation modeling. Self-rated physical and mental health statuses were considered as potential mediators. SES was measured by using educational level as a proxy. All analyses were gender-stratified. RESULTS: Among men, both physical and mental health mediated the path from SES to the use of analgesics and sedatives/hypnotics, respectively, with a stronger effect of physical health on analgesic use and mental health on sedative/hypnotic use. These effects were only partially found among women. CONCLUSIONS: Social inequalities in health seem to have substantial impact on the prevalence of medicine use. Identification and elimination of the reasons for poor health among people of low SES may, therefore, not only help to reduce health inequalities directly. A decline in the use of medicines would also result in less side-effects and a reduced number of people with medicine-related misuse and addiction.

Characteristics of 1555 childhood-onset lupus in three groups based on distinct time intervals to disease diagnosis: a Brazilian multicenter study.

Objective The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated. Results The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P < 0.0001) and SLEDAI-2 K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B. Conclusions Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.

[Quitting Attempts and Utilisation of Smoking Cessation Aids among Smokers in Germany: Results from the 2012 Epidemiological Survey of Substance Abuse]. / Ausstiegsversuche und Hilfsmittelnutzung unter Rauchern in Deutschland: Ergebnisse aus dem Epidemiologischen Suchtsurvey 2012.

Aim: This study presents current data on smoking cessation and usage of smoking cessation aids among smokers in a representative sample of German smokers. Data of 2012 will be compared with data of the year 2000. Methods: The sample of the 2012 Epidemiological Survey of Substance Abuse (ESA) was randomly drawn from population registers and consisted of 9 084 individuals aged 18-64 years. A mixed-mode design including questionnaires, telephone and Internet interviews was applied. The response rate was 53,6%. Number of smoking cessation attempts and usage of smoking cessation aids were assessed among actual and former smokers. Results: Of the 4 261 persons who had smoked in their lifetime 54,1% are actual and 45,9% former smokers. Among actual smokers 64,5% have tried to quit smoking at least once; 24,3% within the last 12 months. Quit attempts were mostly undertaken without formal help (53,7%). Users of smoking cessation aids report that they used social support (22,6%), self-help material (13,3%), nicotine replacement products (11,3%) and E-cigarettes (8,4%). Conclusions: Compared to the year 2000 the number of former smokers has increased. While the number of smoking cessation attempts among smokers is unchanged, more smokers use smoking cessation aids. Using E-cigarettes for smoking cessation is becoming more important.

Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.

BACKGROUND: Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. CLINICALTRIALSGOV: NCT00450892.

The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts.

Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words "bipolar disorder," "suicide attempts," "cannabis," "marijuana," "early age at onset," and "early onset." Results. The following percentages in bipolar patients were found: suicide attempts 3.6-42%; suicide attempts and substance use 5-60%; suicide attempts and cannabis use 15-42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

Rohdella amazonica n. sp. (Aspidogastrea: Aspidogastridae) from the Amazoninan banded puffer fish Colomesus psittacus (Bloch & Schneider, 1801).

Aspidogastreans are commonly found infecting freshwater and marine molluscs, teleosts fishes and freshwater turtles. The subclass comprises four families - Rugogastridae Schell 1973, Stichocotylidae Faust & Tang 1936, Multicalycidae Gibson & Chinabut 1984 and Aspidogastridae Poche 1907 - and it is characterized by the presence of a ventral adhesive disc divided into rows of alveoli. In the current work, using light and scanning electron microscopy and molecular approaches, a new species of Aspidogastridae of the genus Rohdella Gibson & Chinabut, 1984, is described as a parasite of Colomesus psittacus in Brazil. The new taxon is distinguishable by the presence of oesophageal glands, teguments covered by ciliated papillae, and the position and shape of the hermaphroditic duct. The present work describes the third species of the genus Rohdella, thereby adding new morphological and molecular data regarding Aspidogastridae.

Diffusion-weighted breast imaging at 3 T: preliminary experience.

AIM: To evaluate the performance of diffusion-weighted imaging (DWI) at 3 T for the detection and characterization of breast lesions. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) of the breast, including DWI single-shot spin-echo echo planar images (SS-SE-EPI; eight b-values, 50-3000 s/mm(2)), were acquired in women with a clinical indication for breast MRI. The exclusion criteria were as follows: (1) previous breast surgery, radiotherapy and/or chemotherapy within the prior 48 months (14 women); (2) only cystic lesions (one woman); (3) no detectable enhancing lesion at dynamic contrast-enhanced (DCE)-MRI (15 women); and (4) breast implants (four women). MRI results were corroborated by histopathology or imaging follow-up. Apparent diffusion coefficients (ADCs) were estimated for lesions and normal glandular tissue. Differences in the ADC between tissue types were evaluated and the sensitivity and specificity of the method calculated by receiver operating characteristics (ROC) curves. RESULTS: The final cohort comprised 53 patients with 59 lesions. Histopathology was obtained for 58 lesions. One lesion was validated as benign on imaging follow-up. Mean ADCs of 1.99 ± 0.27 × 10(-3) mm(2)/s, 1.08 ± 0.25 × 10(-3) mm(2)/s, and 1.74 ± 0.35 × 10(-3) mm(2)/s were obtained for normal tissue, malignant, and benign lesions, respectively. Mean ADCs of malignancies were significantly lower than those of benign lesions (p < 0.001) and normal tissue (p < 0.0001). The sensitivity and specificity for stratifying lesions, considering an ADC threshold of 1.41 × 10(-3) mm(2)/s, were 94.3% and 87.5%, respectively; accuracy was 91.5%. CONCLUSION: DWI proved useful for the detection and characterization of breast lesions in the present sample. ADC values provide a high diagnostic performance for differentiation between benign and malignant lesions.

Ultrastructure and phylogeny of the parasite Henneguya carolina sp. nov. (Myxozoa), from the marine fish Trachinotus carolinus in Brazil.

Microscopic and molecular procedures are used to describe a new myxosporean species, Henneguya carolina sp. nov., found infecting the intestine of the marine teleost fish Trachinotus carolinus on the southern Atlantic coast of Brazil. Spherical to ellipsoid cysts, measuring up to ~750 µm, display synchronous development. Mature myxospores are ellipsoidal with a bifurcated caudal process. Myxospore body length, width, and thickness are 12.7 ± 0.8 (12.0-13.4) µm, 8.8 ± 0.6 (7.5-9.6) µm, and 5.8 ± 0.4 (5.0-6.4) µm, respectively; 2 equal caudal processes are 16.8 ± 1.1 (15.9-18.0) µm long, and the total myxospore length is 29.4 ± 0.8 (28.4-30.4) µm. Two pyriform polar capsules measure 5.0 ± 0.5 (4.6-5.6) × 2.4 ± 0.4 (1.9-2.9) µm, and each contains a polar filament forming 3 to 4 coils. Sporoplasm is binucleated and presents a spherical vacuole surrounded by numerous globular sporoplasmosomes. Molecular analysis of the small subunit rRNA gene by maximum parsimony, neighbor joining, and maximum likelihood reveals the parasite clustering together with other myxobolids that are histozoic in marine fish of the order Perciformes, thereby strengthening the contention that the host phylogenetic relationships and aquatic environment are the strongest evolutionary signal for myxosporeans of the family Myxobolidae.

Ultrastructure of novel thrombocytes in the dog snapper Lutjanus jocu.

Myxosporean cysts containing spores of Henneguya sp. were observed in the gills of the dog snapper Lutjanus jocu. Adjacent to the cysts were capillaries, allowing observation of peripheral blood cells. Numerous white blood cells displaying uncommon cytoplasmic projections were observed amongst the erythrocytes. Their morphology allowed them to be identified as thrombocytes (TCs). Each TC displayed 18-26 cytoplasmic projections, most of which were in close proximity to erythrocytes. At their apical end, each cytoplasmic projection presented an ellipsoidal vacuole (c. 0·6 µm × 0·3 µm) from which a secretory tubule, 0·3-0·4 µm long and c. 120 nm in total diameter, extended towards the periphery of the TC plasmalemma and fused with the cellular membrane. From this opening, contents of vacuoles were apparently released into the lumen of the capillaries. Other vacuoles with similar features, and containing an electron-lucent matrix, were observed in the cytoplasm of the TC. This is the first description of fish TC with these ultrastructural features and organization, which suggest that they perform a secretory function.

The impact of saline and water stress on the agronomic performance of beet crops.

Excessive salts in irrigation water and water stress have a negative impact on the productive yield of agricultural crops. In this regard, the objective was to evaluate the effect of combined saline and water stress on the agronomic performance of the beet crop. The experiment was conducted in a greenhouse located at the Universidade da Integração Internacional da Lusofonia Afro-Brasileira, in Redenção, Ceará. The experimental design used was completely randomized with split-plots arrangement. The main plots were formed by the electrical conductivities of the irrigation water (0.8, 1.5, 3.0, 4.5, and 6.0 dS m-1), while the irrigation depths of 50 and 100% of the crop evapotranspiration (ETc) were the subplots, with 6 replications. Saline stress negatively affected growth, biomass, tuber root length, and productivity, while increasing the soluble solids of the beet crop. Excessive salts in the irrigation water caused reductions in physiological indices of the beet crop, although with less severity under the 100% ETc.