Evaluation of adherence to antipsychotics: A real-world data study using four different dosing assumptions.

AIMS: This study aimed to assess the frequency of dosing inconsistencies in prescription data and the effect of four dosing assumption strategies on adherence estimates for antipsychotic treatment. METHODS: A retrospective cohort, which linked prescription and dispensing data of adult patients with ≥1 antipsychotic prescription between 2015-2016 and followed up until 2019, in Catalonia (Spain). Four strategies were proposed for selecting the recommended dosing in overlapping prescription periods for the same patient and antipsychotic drug: (i) the minimum dosing prescribed; (ii) the dose corresponding to the latest prescription issued; (iii) the highest dosing prescribed; and (iv) all doses included in the overlapped period. For each strategy, one treatment episode per patient was selected, and the Continuous Medication Availability measure was used to assess adherence. Descriptive statistics were used to describe results by strategy. RESULTS: Of the 277 324 prescriptions included, 76% overlapped with other prescriptions (40% with different recommended dosing instructions). The number and characteristics of patients and treatment episodes (18 292, 18 303, 18 339 and 18 536, respectively per strategy) were similar across strategies. Mean adherence was similar between strategies, ranging from 57 to 60%. However, the proportion of patients with adherence ≥90% was lower when selecting all doses (28%) compared with the other strategies (35%). CONCLUSION: Despite the high prevalence of overlapping prescriptions, the strategies proposed did not show a major effect on the adherence estimates for antipsychotic treatment. Taking into consideration the particularities of antipsychotic prescription practices, selecting the highest dose in the overlapped period seemed to provide a more accurate adherence estimate.

Prevalence and risk factors of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 mental health cohort.

BACKGROUND: There is mixed evidence on increasing rates of psychiatric disorders and symptoms during the coronavirus disease 2019 (COVID-19) pandemic in 2020. We evaluated pandemic-related psychopathology and psychiatry diagnoses and their determinants in the Brazilian Longitudinal Study of Health (ELSA-Brasil) São Paulo Research Center. METHODS: Between pre-pandemic ELSA-Brasil assessments in 2008-2010 (wave-1), 2012-2014 (wave-2), 2016-2018 (wave-3) and three pandemic assessments in 2020 (COVID-19 waves in May-July, July-September, and October-December), rates of common psychiatric symptoms, and depressive, anxiety, and common mental disorders (CMDs) were compared using the Clinical Interview Scheduled-Revised (CIS-R) and the Depression Anxiety Stress Scale-21 (DASS-21). Multivariable generalized linear models, adjusted by age, gender, educational level, and ethnicity identified variables associated with an elevated risk for mental disorders. RESULTS: In 2117 participants (mean age 62.3 years, 58.2% females), rates of CMDs and depressive disorders did not significantly change over time, oscillating from 23.5% to 21.1%, and 3.3% to 2.8%, respectively; whereas rate of anxiety disorders significantly decreased (2008-2010: 13.8%; 2016-2018: 9.8%; 2020: 8%). There was a decrease along three wave-COVID assessments for depression [ß = -0.37, 99.5% confidence interval (CI) -0.50 to -0.23], anxiety (ß = -0.37, 99.5% CI -0.48 to -0.26), and stress (ß = -0.48, 99.5% CI -0.64 to -0.33) symptoms (all ps < 0.001). Younger age, female sex, lower educational level, non-white ethnicity, and previous psychiatric disorders were associated with increased odds for psychiatric disorders, whereas self-evaluated good health and good quality of relationships with decreased risk. CONCLUSION: No consistent evidence of pandemic-related worsening psychopathology in our cohort was found. Indeed, psychiatric symptoms slightly decreased along 2020. Risk factors representing socioeconomic disadvantages were associated with increased odds of psychiatric disorders.

Pirfenidone Protects from UVB-Induced Photodamage in Hairless Mice.

BACKGROUND: Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized. Pirfenidone (PFD) has emerged as an antifibrogenic, anti-inflammatory and antioxidant agent, and in this work its efficacy was evaluated in a model of UVB-induced photodamage. METHODS: Epidermal, dermal, and inflammatory changes were measured by histomorphometric parameters. In addition, gene, and protein expression of key molecules in these processes were evaluated. RESULTS: Our results revealed an anti-photodamage effect of topical PFD with absence of inflammatory skin lesions determined by dermoscopy. In addition, PFD reduced elastosis, improved organization, arrangement, and deposition of dermal collagens, downregulated several pro-inflammatory markers such as NF-kB, IL-1, IL-6 and TNFα, and decreased keratinocyte damage. CONCLUSION: Topical pirfenidone represents a promising agent for the treatment of cell photodamage in humans. Clinical trials need to be carried out to explore this premise.

Maternity care changes and postpartum mental health during the COVID-19 pandemic: a Spanish cross-sectional study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to abrupt changes in maternity care, but the impact of these changes has not yet been deeply evaluated. This study aimed to assess the impact of the unexpected changes in maternity care due to the COVID-19 pandemic on postpartum mental health (depression, anxiety and posttraumatic stress disorder). METHODS: A cross-sectional, web-based study was conducted in Spain during the second half of 2020. The eligibility criteria were women≥18 years with a child≤6 months. The Edinburgh Postnatal Depression Scale (EPDS), the Generalized Anxiety Disorder-7 Screener (GAD-7) and a subset of the PTSD checklist (PCL-5) were used to assess postpartum mental health. Information regarding sociodemographic characteristics and maternity care changes was collected, and multivariate regression models were used. RESULTS: Among 1781 participants, 29.3% and 33% had clinically significant depressive and anxiety symptoms, respectively. The most prevalent unexpected changes reported were related to the exclusion of supportive relatives during birth and postpartum. Changes reported during birth showed a minor association with PTSD symptomatology, and those that occurred during the postpartum period were associated with clinical depression, anxiety and PTSD symptoms. CONCLUSIONS: The unexpected changes in maternity care due to the COVID-19 pandemic, especially those that occurred during the postpartum period, increased the risk of mental health problems.

Subclinical Left Ventricular Systolic Dysfunction in Hospitalized Patients with COVID-19 by Strain: A 30-Day Echocardiographic Follow-Up.

Background and Objectives: Available studies confirm myocardial injury and its association with mortality in patients with COVID-19, but few data have been reported from echocardiographic studies. The aim of this study was to identify subclinical left ventricular dysfunction by global longitudinal strain (GLS) and its evolution in the short term in hospitalized patients with COVID-19. Materials and Methods: Thirty-one consecutive noncritical patients admitted for COVID-19 were included. Information on demographics, laboratory results, comorbidities, and medications was collected. Transthoracic echocardiograms were performed using a Philips Affinity 50, at the acute stage and at a 30-day follow-up. Automated left ventricular GLS was measured using a Philips Qlab 13.0. A GLS of <-15.9% was defined as abnormal. Results: The mean age was 65 ± 15.2 years, and 61.3% of patients were male. Nine patients (29%) had elevated levels of high-sensitivity troponin I. Left ventricular ejection fraction was preserved in all; however, 11 of them (35.5%) showed reduced GLS. These patients had higher troponin levels (median, 23.7 vs. 3.2 ng/L; p < 0.05) and NT-proBNP (median, 753 vs. 81 pg/mL; p < 0.05). The multivariate analysis revealed that myocardial injury, defined as increased troponin, was significantly associated with GLS values (coefficient B; p < 0.05). Follow-up at 30 days showed an improvement in GLS values in patients with subclinical left ventricular dysfunction (-16.4 ± 2.07% vs. -13.2 ± 2.40%; p < 0.01), without changes in the normal GLS group. Conclusions: Subclinical left ventricular dysfunction is common in noncritical hospitalized patients with COVID-19 (one in every three patients), even with preserved left ventricular ejection fraction. This impairment tends to be reversible on clinical recovery.

Trajectories of common mental disorders symptoms before and during the COVID-19 pandemic: findings from the ELSA-Brasil COVID-19 Mental Health Cohort.

AIM: Evidence indicates most people were resilient to the impact of the COVID-19 pandemic on mental health. However, evidence also suggests the pandemic effect on mental health may be heterogeneous. Therefore, we aimed to identify groups of trajectories of common mental disorders' (CMD) symptoms assessed before (2017-19) and during the COVID-19 pandemic (2020-2021), and to investigate predictors of trajectories. METHODS: We assessed 2,705 participants of the ELSA-Brasil COVID-19 Mental Health Cohort study who reported Clinical Interview Scheduled-Revised (CIS-R) data in 2017-19 and Depression Anxiety Stress Scale-21 (DASS-21) data in May-July 2020, July-September 2020, October-December 2020, and April-June 2021. We used an equi-percentile approach to link the CIS-R total score in 2017-19 with the DASS-21 total score. Group-based trajectory modeling was used to identify CMD trajectories and adjusted multinomial logistic regression was used to investigate predictors of trajectories. RESULTS: Six groups of CMD symptoms trajectories were identified: low symptoms (17.6%), low-decreasing symptoms (13.7%), low-increasing symptoms (23.9%), moderate-decreasing symptoms (16.8%), low-increasing symptoms (23.3%), severe-decreasing symptoms (4.7%). The severe-decreasing trajectory was characterized by age < 60 years, female sex, low family income, sedentary behavior, previous mental disorders, and the experience of adverse events in life. LIMITATIONS: Pre-pandemic characteristics were associated with lack of response to assessments. Our occupational cohort sample is not representative. CONCLUSION: More than half of the sample presented low levels of CMD symptoms. Predictors of trajectories could be used to detect individuals at-risk for presenting CMD symptoms in the context of global adverse events.

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.

Transgenerational Tolerance to Salt and Osmotic Stresses Induced by Plant Virus Infection.

Following pathogen infection, plants have developed diverse mechanisms that direct their immune systems towards more robust induction of defense responses against recurrent environmental stresses. The induced resistances could be inherited by the progenies, rendering them more tolerant to stressful events. Although within-generational induction of tolerance to abiotic stress is a well-documented phenomenon in virus-infected plants, the transgenerational inheritance of tolerance to abiotic stresses in their progenies has not been explored. Here, we show that infection of Nicotiana benthamiana plants by Potato virus X (PVX) and by a chimeric Plum pox virus (PPV) expressing the P25 pathogenicity protein of PVX (PPV-P25), but not by PPV, conferred tolerance to both salt and osmotic stresses to the progeny, which correlated with the level of virulence of the pathogen. This transgenerational tolerance to abiotic stresses in the progeny was partially sustained even if the plants experience a virus-free generation. Moreover, progenies from a Dicer-like3 mutant mimicked the enhanced tolerance to abiotic stress observed in progenies of PVX-infected wild-type plants. This phenotype was shown irrespective of whether Dicer-like3 parents were infected, suggesting the involvement of 24-nt small interfering RNAs in the transgenerational tolerance to abiotic stress induced by virus infection. RNAseq analysis supported the upregulation of genes related to protein folding and response to stress in the progeny of PVX-infected plants. From an environmental point of view, the significance of virus-induced transgenerational tolerance to abiotic stress could be questionable, as its induction was offset by major reproductive costs arising from a detrimental effect on seed production.

Cognitive outcomes of the bipolar depression electrical treatment trial (BETTER): a randomized, double-blind, sham-controlled study.

Bipolar depression is associated with marked cognitive deficits. Pharmacological treatments for this condition are limited and may aggravate depressive and cognitive symptoms. Therefore, therapeutic interventions that preserve adequate cognitive functioning are necessary. Our previous results demonstrated significant clinical efficacy of transcranial direct current stimulation (tDCS) in the Bipolar Depression Electrical Treatment Trial (BETTER). Here, cognitive outcomes of this study are reported. We randomized 59 patients with bipolar disorder I or II in an acute depressive episode to receive active (12 2 mA, 30-min, anodal-left, cathodal-right prefrontal cortex tDCS sessions) or sham tDCS. Patients were on stable pharmacological regimen for at least 2 weeks. A battery of 12 neuropsychological assessments in five cognitive domains (attention and processing speed, memory, language, inhibitory control, and working memory and executive function) was performed at baseline, after two weeks and at endpoint (week 6). No significant differences between groups over 6 weeks of treatment were observed for any cognitive outcomes. Moreover, no decrease in cognitive performance was observed. Our findings warrant further replication in larger studies. Trial Registration: clinicaltrials.gov Identifier: NCT02152878.

Habitual Caffeine Consumption Does Not Interfere With the Acute Caffeine Supplementation Effects on Strength Endurance and Jumping Performance in Trained Individuals.

The long-standing caffeine habituation paradigm was never investigated in strength endurance and jumping exercise performance through a straightforward methodology. The authors examined if habitual caffeine consumption would influence the caffeine ergogenic effects on strength endurance and jumping performance as well as perceptual responses. Thirty-six strength-trained individuals were mathematically allocated into tertiles according to their habitual caffeine consumption: low (20 ± 11 mg/day), moderate (88 ± 33 mg/day), and high consumers (281 ± 167 mg/day). Then, in a double-blind, crossover, counterbalanced fashion, they performed a countermovement vertical jump test and a strength endurance test either after caffeine (6 mg/kg) and placebo supplementation or after no supplementation (control). Perceptual responses such as ratings of perceived exertion and pain were measured at the termination of the exercises. Acute caffeine supplementation improved countermovement vertical jump performance (p = .001) and total repetitions (p = .004), regardless of caffeine habituation. Accordingly, analysis of absolute change from the control session showed that caffeine promoted a significantly greater improvement in both countermovement vertical jump performance (p = .004) and total repetitions (p = .0001) compared with placebo. Caffeine did not affect the rating of perceived exertion and pain in any exercise tests, irrespective of tertiles (for all comparisons, p > .05 for both measures). Caffeine side effects were similar in low, moderate, and high caffeine consumers. These results show that habitual caffeine consumption does not influence the potential of caffeine as an ergogenic aid in strength endurance and jumping exercise performance, thus challenging recommendations to withdraw from the habitual caffeine consumption before supplementing with caffeine.

PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases.

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs' critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

Hepatocarcinogenesis Prevention by Pirfenidone Is PPARγ Mediated and Involves Modification of Nuclear NF-kB p65/p50 Ratio.

Targeted therapies for regulating processes such as inflammation, apoptosis, and fibrogenesis might modulate human HCC development. Pirfenidone (PFD) has shown anti-fibrotic and anti-inflammatory functions in both clinical and experimental studies. The aim of this study was to evaluate PPARγ expression and localization in samples of primary human tumors and assess PFD-effect in early phases of hepatocarcinogenic process. Human HCC tissue samples were obtained by surgical resection. Experimental hepatocarcinogenesis was induced in male Fischer-344 rats. TGF-ß1 and α-SMA expression was evaluated as fibrosis markers. NF-kB cascade, TNFα, IL-6, and COX-2 expression and localization were evaluated as inflammation indicators. Caspase-3, p53, and PARP-1 were used as apoptosis markers, PCNA for proliferation. Finally, PPARα and PPARγ expression were evaluated to understand the effect of PFD on the activation of such pathways. PPARγ expression was predominantly localized in cytoplasm in human HCC tissue. PFD was effective to prevent histopathological damage and TGF-ß1 and α-SMA overexpression in the experimental model. Anti-inflammatory effects of PFD correlate with diminished IKK and decrease in both IkB-phosphorylation/NF-kB p65 expression and p65-translocation into the nucleus. Pro-apoptotic PFD-induced effects are related with p53 expression, Caspase-3 p17 activation, and PARP-1-cleavage. In conclusion, PFD acts as a tumor suppressor by preventing fibrosis, reducing inflammation, and promoting apoptosis in MRHM.

Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression.

BACKGROUND: We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression. METHODS: In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS: A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS: In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815 .).

Depth of cure of bulk fill resin composites: A systematic review.

OBJECTIVE: To evaluate scientific evidence regarding depth of cure of bulk-fill resin composites (BFRCs) and related factors. MATERIAL AND METHODS: PubMed/Medline, Embase, Scopus, and ISI Web of Science databases were accessed from October 2016 to May 2017. Investigations published in English language, assessing depth of cure of BFRCs by microhardness test and/or degree of conversion (DC) were included. Studies using exclusively ISO 4049, employing specimens deepness less than 4 mm, as well as those not reporting exposure time and/or irradiance from light curing units (LCUs) were excluded. RESULTS: In total, 742 studies were found from which 33 were included. From 21 studies evaluating BFRCs microhardness, 10 showed acceptable bottom/top ratios (≥0.8) for all tested materials. However, material-dependent results and non-satisfactory bottom/top microhardness ratios (<0.8) were reported in 9 and 2 investigations, respectively. From 19 studies that assessed DC, 11 showed acceptable results (≥50%) for all tested BFRCs, while 8 studies reported material-dependent outcomes. Overall, irradiance from LCUs ranged from 650 to 1330 mW/cm2 and exposure time from 5 to 60 seconds. Favorable depth of cure results were observed with the use of LCUs emitting irradiance ≥1000 mW/cm2 and exposure times ≥20 seconds. CONCLUSIONS: High depth of cure rates by BFRCs, depends on some factors as material, irradiance and exposure time. Polywave LCUs were useful but not essential on polymerizing alternative photoinitiator-containing BFRC. CLINICAL SIGNIFICANCE: LED curing devices (polywave or monowave) displaying an irradiance ≥1000 mW/cm2 and 20 seconds of exposure time are imperative to accomplish successful polymerization of most BFRCs.

Cyclooxygenase-2 expression in hepatocytes attenuates non-alcoholic steatohepatitis and liver fibrosis in mice.

Cyclooxygenase-2 (COX-2) is involved in different liver diseases but little is known about the significance of COX-2 in the development and progression of non-alcoholic steatohepatitis (NASH). This study was designed to elucidate the role of COX-2 expression in hepatocytes in the pathogenesis of steatohepatitis and hepatic fibrosis. In the present work, hepatocyte-specific COX-2 transgenic mice (hCOX-2-Tg) and their wild-type (Wt) littermates were either fed methionine-and-choline deficient (MCD) diet to establish an experimental non-alcoholic steatohepatitis (NASH) model or injected with carbon tetrachloride (CCl4) to induce liver fibrosis. In our animal model, hCOX-2-Tg mice fed MCD diet showed lower grades of steatosis, ballooning and inflammation than Wt mice, in part by reduced recruitment and infiltration of hepatic macrophages, with a corresponding decrease in serum levels of pro-inflammatory cytokines. Furthermore, hCOX-2-Tg mice showed a significant attenuation of the MCD diet-induced increase in oxidative stress and hepatic apoptosis observed in Wt mice. Even more, hCOX-2-Tg mice treated with CCl4 had significantly lower stages of fibrosis and less hepatic content of collagen, hydroxyproline and pro-fibrogenic markers than Wt controls. Collectively, our data indicates that constitutive hepatocyte COX-2 expression ameliorates NASH and liver fibrosis development in mice by reducing inflammation, oxidative stress and apoptosis and by modulating activation of hepatic stellate cells, respectively, suggesting a possible protective role for COX-2 induction in NASH/NAFLD progression.

First Characterization of CTX-M-15-Producing Escherichia coli Strains Belonging to Sequence Type (ST) 410, ST224, and ST1284 from Commercial Swine in South America.

We report for the first time the isolation of CTX-M-15-producingEscherichia colistrains belonging to sequence type (ST) 410, ST224, and ST1284 in commercial swine in Brazil. TheblaCTX-M-15gene was located on F-::A9::B1 and C1::A9::B1 IncF-type plasmids, surrounded by a new genetic context comprising the IS26insertion sequence truncated with the ISEcp1element upstream ofblaCTX-M-15 These results reveal that commercial swine have become a new reservoir of CTX-M-15-producing bacteria in South America.

Vancomycin-intermediate livestock-associated methicillin-resistant Staphylococcus aureus ST398/t9538 from swine in Brazil.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been mainly related with pig farming, in Europe and North America, with the ST398 as the most commonly identified type of LA-MRSA. Here we present the draft genome of the first vancomycin-intermediate MRSA ST398/t9538 isolated from a swine presenting exudative epidermitis in Brazil.

Incidence of Suicidal Ideation in a Civil Servants Cohort During the COVID-19 Pandemic in Brazil: Insights from the ELSA-Brasil Study.

OBJECTIVE: This study investigated the incidence of suicidal ideation and its associated risk factors in the São Paulo state of ELSA-Brasil cohort during the COVID-19 pandemic. METHODS: During a pre-pandemic ELSA-Brasil onsite assessment in 2016-2018 (wave 3) and a pandemic online assessment in May-July 2020 (wave COVID), we assessed suicidal ideation using the Clinical Interview Scheduled-Revised (CIS-R). Single and multi predictor logistic regressions were performed using sociodemographic characteristics, household finance impact during pandemic, presence of previous chronic diseases, alcohol abuse, adverse childhood experiences (ACE), living alone, and previous CMD as predictors. Suicidal ideation incidence was used as outcome. RESULTS: Out of 4191 participants of wave 3, 2117 (50.5%) answered wave COVID. There was a threefold increase in suicide ideation, from 34 (1.8%) to 104 (5.6%).In multiple predictor models, we found that previous CMD (OR 7.17; 95% CI 4.43 - 11.58) and ACE (OR 1.72; 95% CI 1.09 - 2.72) increased the odds of incident suicidal ideation. The sociodemographic predictors female sex, younger age and low income were significant risk factors only in the single predictor model. Conclusions These findings underscore the importance of monitoring and supporting individuals who suffered ACE and have a history of mental health disorders. This is especially critical in times of heightened societal stress, such as the COVID-19 pandemic. CONCLUSIONS: These findings underscore the importance of monitoring and supporting individuals who suffered ACE and have a history of mental health disorders. This is especially critical in times of heightened societal stress, such as the COVID-19 pandemic.

Regulation of respiratory complex I assembly by FMN cofactor targeting.

Respiratory complex I plays a crucial role in the mitochondrial electron transport chain and shows promise as a therapeutic target for various human diseases. While most studies focus on inhibiting complex I at the Q-site, little is known about inhibitors targeting other sites within the complex. In this study, we demonstrate that diphenyleneiodonium (DPI), a N-site inhibitor, uniquely affects the stability of complex I by reacting with its flavin cofactor FMN. Treatment with DPI blocks the final stage of complex I assembly, leading to the complete and reversible degradation of complex I in different cellular models. Growing cells in medium lacking the FMN precursor riboflavin or knocking out the mitochondrial flavin carrier gene SLC25A32 results in a similar complex I degradation. Overall, our findings establish a direct connection between mitochondrial flavin homeostasis and complex I stability and assembly, paving the way for novel pharmacological strategies to regulate respiratory complex I.