Comparative transcriptional analysis between susceptible and resistant populations of Aedes (Stegomyia) aegypti (Linnaeus, 1762) after malathion exposure.

Aedes aegypti is an important vector of arboviruses, including dengue, chikungunya and Zika. The application of synthetic insecticides is a frequently used strategy to control this insect. Malathion is an organophosphate insecticide that was widely used in Brazil in the 1980s and 1990s to control the adult form of A. aegypti. In situations where resistance to currently used insecticides is detected, the use of malathion may be resumed as a control measure. Many studies have confirmed resistance to malathion, however, comparative studies of differential gene expression of the entire transcriptome of resistant and susceptible insects are scarce. Therefore, understanding the molecular basis of resistance to this insecticide in this species is extremely important. In this paper, we present the first transcriptomic description of susceptible and resistant strains of A. aegypti challenged with malathion. Guided transcriptome assembly resulted in 39,904 transcripts, where 2133 differentially expressed transcripts were detected, and three were validated by RT-qPCR. Enrichment analysis for these identified transcripts resulted in 13 significant pathways (padj < 0.05), 8 associated with down-regulated and 5 with up-regulated transcripts in treated resistant insects. It was possible to divide the transcripts according to the mechanism of action into three main groups: (i) genes involved in detoxification metabolic pathways; (ii) genes of proteins located in the membrane/extracellular region; and (iii) genes related to DNA integration/function. These results are important in advancing knowledge of genes related to resistance mechanisms in this insect, enabling the development of effective technologies and strategies for managing insecticide resistance.

Management of pulmonary hypertension in special conditions.

Care of pulmonary hypertension (PH) patients in special situations requires insightful knowledge of the pathophysiology of the cardiopulmonary system and close interaction with different specialists, depending on the situation. The role of this task force was to gather knowledge about five conditions that PH patients may be faced with. These conditions are 1) perioperative care; 2) management of pregnancy; 3) medication adherence; 4) palliative care; and 5) the influence of climate on PH. Many of these aspects have not been covered by previous World Symposia on Pulmonary Hypertension. All of the above conditions are highly affected by psychological, geographical and socioeconomic factors, and share the need for adequate healthcare provision. The task force identified significant gaps in information and research in these areas. The current recommendations are based on detailed literature search and expert opinion. The task force calls for further studies and research to better understand and address the special circumstances that PH patients may encounter.

Differential Gene Expression in Contrasting Common Bean Cultivars for Drought Tolerance during an Extended Dry Period.

Common beans (Phaseolus vulgaris L.), besides being an important source of nutrients such as iron, magnesium, and protein, are crucial for food security, especially in developing countries. Common bean cultivation areas commonly face production challenges due to drought occurrences, mainly during the reproductive period. Dry spells last approximately 20 days, enough time to compromise production. Hence, it is crucial to understand the genetic and molecular mechanisms that confer drought tolerance to improve common bean cultivars' adaptation to drought. Sixty six RNASeq libraries, generated from tolerant and sensitive cultivars in drought time sourced from the R5 phenological stage at 0 to 20 days of water deficit were sequenced, generated over 1.5 billion reads, that aligned to 62,524 transcripts originating from a reference transcriptome, as well as 6673 transcripts obtained via de novo assembly. Differentially expressed transcripts were functionally annotated, revealing a variety of genes associated with molecular functions such as oxidoreductase and transferase activity, as well as biological processes related to stress response and signaling. The presence of regulatory genes involved in signaling cascades and transcriptional control was also highlighted, for example, LEA proteins and dehydrins associated with dehydration protection, and transcription factors such as WRKY, MYB, and NAC, which modulate plant response to water deficit. Additionally, genes related to membrane and protein protection, as well as water and ion uptake and transport, were identified, including aquaporins, RING-type E3 ubiquitin transferases, antioxidant enzymes such as GSTs and CYPs, and thioredoxins. This study highlights the complexity of plant response to water scarcity, focusing on the functional diversity of the genes involved and their participation in the biological processes essential for plant adaptation to water stress. The identification of regulatory and cell protection genes offers promising prospects for genetic improvement aiming at the production of common bean varieties more resistant to drought. These findings have the potential to drive sustainable agriculture, providing valuable insights to ensure food security in a context of climate change.

Safety climate in the operating room in the pre-pandemic and pandemic period of COVID-19: A mixed method study.

INTRODUCTION: To verify whether the COVID-19 pandemic has had an impact on the safety climate based on the perception of the multiprofessional team in the operating room and to analyze the domains of the safety climate during the pre-pandemic and pandemic period of COVID-19, demonstrating the intersections of quantitative and qualitative approaches. METHODS: Mixed-method research using a convergent approach strategy, carried out in the operating room of a university hospital, located in Rio de Janeiro, Brazil. The nature of the quantitative phase was cross-sectional, and the nature of the qualitative phase was descriptive. We used the Pillar Integration Process to integrate the data. This research considered the pre-pandemic period was defined as before March 2020 and for the pandemic period, the 2nd and 3rd global waves. Research was approved by the institution's board management and ethics committee. RESULTS: 145 health professionals participated in the quantitative approach, and 20 in the qualitative approach. The impact of the COVID-19 pandemic was highlighted in the domains 'Perceived stress' (p-value = 0.017); 'Working conditions' (p-value = 0.040). Six categories emerged from the qualitative analysis, namely: Stress and professional performance due to COVID-19; Patient safety protocols in the operating room; Responsibility for patient safety, lack of effective communication and performance feedback; Biosafety of the professional staff in the operating room; Security culture maturity; Fair culture, organizational learning, and reporting mistakes. As a result of the data integration, 6 pillars were identified: Perception of communication in the operating room; Evolution of safety culture; Overview of protocol management and implementation; Fair organizational culture; Perception of stress due to COVID-19; Perception of professional performance due to COVID-19. CONCLUSIONS: The impact that COVID-19 had on the safety climate in the operating room is evident. It underlines the need to implement strategies that support the solidification of attitudes aimed at patient safety, even in emergencies.

Application of REVEAL Lite 2 and COMPERA 2.0 risk scores to patients with pulmonary arterial hypertension switching to riociguat in the REPLACE study.

In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement. The proportions of riociguat- and PDE5i-treated patients achieving the primary end-point at REVEAL Lite 2 low, intermediate, and high baseline risk reflected the overall population. Proportions of riociguat-treated patients achieving the primary end-point were comparable between the COMPERA 2.0 intermediate-low risk (39%) and intermediate-high risk (43%) groups. Our findings show that patients in REPLACE achieved clinical improvement by switching from PDE5i to riociguat across all COMPERA 2.0 and most REVEAL Lite 2 baseline risk strata.

Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial.

BACKGROUND: In the phase 3 STELLAR trial, sotatercept, an investigational first-in-class activin signalling inhibitor, demonstrated beneficial effects on 6-min walk distance and additional efficacy endpoints in pre-treated participants with pulmonary arterial hypertension (PAH). METHODS: This post hoc analysis evaluated data from right heart catheterisation (RHC) and echocardiography (ECHO) obtained from the STELLAR trial. Changes from baseline in RHC and ECHO parameters were assessed at 24 weeks. An analysis of covariance (ANCOVA) model was used to estimate differences in least squares means with treatment and randomisation stratification (mono/double versus triple therapy; World Health Organization functional class II versus III) as fixed factors, and baseline value as covariate. RESULTS: Relative to placebo, treatment with sotatercept led to significant (all p<0.0001 except where noted) improvements from baseline in mean pulmonary artery (PA) pressure (-13.9 mmHg), pulmonary vascular resistance (-254.8 dyn·s·cm-5), mean right atrial pressure (-2.7 mmHg), mixed venous oxygen saturation (3.84%), PA elastance (-0.42 mmHg·mL-1·beat-1), PA compliance (0.58 mL·mmHg-1), cardiac efficiency (0.48 mL·beat-1·mmHg-1), right ventricular (RV) work (-0.85 g·m) and RV power (-32.70 mmHg·L·min-1). ECHO showed improvements in tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure ratio (0.12 mm·mmHg-1), end-systolic and end-diastolic RV areas (-4.39 cm2 and -5.31 cm2, respectively), tricuspid regurgitation and RV fractional area change (2.04% p<0.050). No significant between-group changes from baseline were seen for TAPSE, heart rate, cardiac output, stroke volume or their indices. CONCLUSION: In pre-treated patients with PAH, sotatercept demonstrated substantial improvements in PA pressures, PA compliance, PA-RV coupling and right heart function.

Annotation of transposable elements in the transcriptome of the Neotropical brown stink bug Euschistus heros and its chromosomal distribution.

Transposable elements (TEs) are DNA sequences capable of moving within the genome. Their distribution is very dynamic among organisms, and despite advances, there are still gaps in the understanding of the diversity and evolution of TEs in many insect species. In the case of Euschistus heros, considered the main stink bug in the soybean crop in Brazil, little is known about the participation of these elements. Therefore, the objective of the current work was to identify the different groups of transposable elements present in the E. heros transcriptome, evidencing their chromosomal distribution. Through RNA-Seq and de novo assembly, 60,009 transcripts were obtained, which were annotated locally via Blastn against specific databases. Of the 367 transcripts identified as TEs, 202 belong to Class II, with emphasis on the TIR order. Among Class I elements or retrotransposons, most were characterized as LINE. Phylogenetic analyses were performed with the protein domains, evidencing differences between Tc1-mariner sequences, which may be related to possible horizontal transfer events. The transposable elements that stood out in the transcriptome were selected for fluorescent in situ hybridization. DNA transposon probes hAT, Helitron, and Tc1-mariner showed mostly scattered signals, with the presence of some blocks. Retrotransposon probes Copia, Gypsy, Jockey, and RTE showed a more pulverized hybridization pattern, with the presence of small interstitial and/or terminal blocks. Studies like this one, integrating functional genomics and molecular cytogenetic tools, are essential to expanding knowledge about transcriptionally active mobile elements, and their behavior in the chromosomes.

Influence of temperature variation on gene expression and cocoon production in Bombyx mori Linnaeus, 1758 (Lepidoptera: Bombycidae).

Silkworms (Bombyx mori) are lepidopterans of economic importance for global silk production. However, factors that directly affect the yield and quality of silkworm cocoon production, such as diseases and temperature fluctuations, cause great economic losses. Knowing how they respond to rearing temperature during the most critical stage of their life cycle (i.e., fifth instar) could provide information on their adaptation and improve silk production. In the current work, we analyzed transcriptional data from two groups of B. mori that were reared at 26 °C and 34 °C throughout the fifth instar. The silkworms and cocoons were weighed. In total, 3115 transcripts were differentially expressed (DE; including 1696 down-regulated and 1419 up-regulated) among the 29,157 sequences found by transcriptome assembly. We emphasize the genes associated with immunological response, transcription factors, silk biosynthesis, and heat shock proteins, among the DE transcripts in response to the temperature conditions. Silkworms reared at 34 °C presented a reduced mean body weight (-0.944 g in comparison to the 26 °C group), which had a direct impact on the weight of cocoons formed and the silk conversion rate. These changes were statistically significant when compared to silkworms reared at 26 °C. Mortality rates (6 and 9 %, at 26 °C and 34 °C, respectively) were similar to those obtained in breeding fields. The findings provide information on the biological processes involved in the temperature response mechanism of silkworms, as well as information that may be used in future climatization processes at rearing facilities and in breeding for improved thermotolerance.

Effectiveness of Neurofunctional Physical Therapy on the Quality of Sleep of Individuals with Parkinson's Disease: Case Series.

Objective Sleep disorders are disabling and highly prevalent comorbidities in Parkinson's disease (PD). This study's objective was to verify the effectiveness of neurofunctional physiotherapy in sleep quality, objectively and subjectively assessing it among individuals with PD. Methods A sample of individuals with PD was assessed before and after 32 physiotherapy sessions and three months later (follow-up). The following instruments were used: Pittsburgh Sleep Quality Index (PSQI); Epworth Sleepiness Scale (ESS); Parkinson's Disease Sleep Scale (PDSS), and actigraphy. Results Nineteen individuals aged 67.37 years old ( ± 8.03) on average were included. No differences were found in any of the variables measured by the actigraphy or the ESS. Improvement was found from pre- to post-intervention in terms of nocturnal movements (p = 0.04; d = 0.46) and total score (p = 0.03; d = 0.53) obtained on the PDSS. Improvement was also found in the PDSS sleep onset/maintenance domain (p = 0.001; d = 0.75) between pre-intervention and follow-up. The participants' total score obtained in the PSQI improved from pre- to post-intervention (p = 0.03; d = 0.44). Significant differences were found in nighttime sleep (p = 0.02; d = 0.51) and nocturnal movements (p = 0.02; d = 0.55), and in the PDSS total score (p = 0.04; d = 0.63) between pre- and post-intervention when only the poor sleepers subgroup (n = 13) was considered, while improvements were found in sleep onset/maintenance (p = 0.003; d = 0.91) between pre-intervention and follow-up. Discussion Neurofunctional physiotherapy was ineffective in improving objective parameters of sleep but was effective in improving the perception of sleep quality subjectively assessed among individuals with PD, especially those who perceived themselves to be poor sleepers.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

Predictors of invasive mechanical ventilation use in patients with acute decompensated pulmonary hypertension admitted to the intensive care unit.

In acute decompensated pulmonary hypertension, elevated nonrespiratory SOFA was associated with a higher use of invasive mechanical ventilation independently of the hypoxaemia on ICU admission and pulmonary hypertension severity https://bit.ly/3YdOHpn.

Challenges of acute febrile illness diagnosis in a national infectious diseases center in Rio de Janeiro: 16-year experience of syndromic surveillance.

INTRODUCTION: Acute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. Understanding the distribution of causes of AFI can improve patient outcomes. This study aims to describe the most common etiologies diagnosed over a 16-years period in a national reference center for tropical diseases in a large urban center in Rio de Janeiro, Brazil. METHODS: From August 2004-December 2019, 3591 patients > 12 years old, with AFI and/or rash were eligible. Complementary exams for etiological investigation were requested using syndromic classification as a decision guide. Results. Among the 3591 patients included, endemic arboviruses such as chikungunya (21%), dengue (15%) and zika (6%) were the most common laboratory-confirmed diagnosis, together with travel-related malaria (11%). Clinical presumptive diagnosis lacked sensitivity for emerging diseases such as zika (31%). Rickettsia disease and leptospirosis were rarely investigated and an infrequent finding when based purely on clinical features. Respiratory symptoms increased the odds for the diagnostic remaining inconclusive. CONCLUSIONS: Numerous patients did not have a conclusive etiologic diagnosis. Since syndromic classification used for standardization of etiological investigation and presumptive clinical diagnosis had moderate accuracy, it is necessary to incorporate new diagnostic technologies to improve diagnostic accuracy and surveillance capacity.

Risk assessment validation in patients with pulmonary arterial hypertension: Data from a Southern Brazil registry (RESPHIRAR study).

Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Registries are a valuable tool in the research of rare conditions such as PAH. Moreover, the risk assessment strategy has been validated in European and North American registries and has been reported to provide an accurate prediction of mortality and the clinical advantage of reaching low-risk status. However, there is no available data from Brazil. Thus, the aim of the present study was to describe the characteristics of a sample of PAH from Southern Brazil and to retrospectively validate the risk assessment at our population. The RESPHIRAR is a retrospective and multicentric registry on pulmonary hypertension. With a join collaboration from nine centers in Southern Brazil, demographics, clinical presentation, and hemodynamics data of PAH were collected between 2007 and 2017. Moreover, the REVEAL 2.0 and REVEAL 2.0 Lite risk assessments were validated in our population. Overall, 370 PAH patients were included in the present study. Patients were predominantly female (78.5%) and had a mean age of 41.8 ± 18.8 years. Most patients (33.4%) had idiopathic PAH, 30.2% had PAH associated with congenital heart disease, and 23.5% had PAH associated with connective tissue disease. The low-risk group showed significantly lower mortality than the intermediated- or high-risk group at diagnosis (p < 0.05). In conclusion, our data suggest that REVEAL 2.0 and REVEAL 2.0 Lite risk assessments can predict mortality risk in PAH patients in Southern Brazil.

Transposable elements in the transcriptome of the velvetbean caterpillar Anticarsia gemmatalis Hübner, 1818 (Lepidoptera: Erebidae).

Transposable elements (TEs) are DNA sequences that possess the ability to move from one genomic location to another. These sequences contribute to a significant fraction of the genomes of most eukaryotes and can impact their architecture and regulation. In this paper, we present the first data related to the identification and characterization of TEs present in the transcriptome of Anticarsia gemmatalis. Approximately, 835 transcripts showed significant similarity to TEs and (or) characteristic domains. Retrotransposons accounted for 71.2% (595 sequences) of the identified elements, while DNA transposons were less abundant, with 240 annotations (28.8%). TEs were classified into 30 superfamilies, with SINE3/5S and Gypsy being the most abundant. Based on the sequences of TEs found in the transcriptome, we were able to locate conserved regions in the chromosomes of this species. The analysis of differential expression of TEs in susceptible and resistant strains, challenged and not challenged with Bacillus thuringiensis (Bt) from in silico analysis, indicated that exposure to Bt can regulate the transcription of mobile genetic elements in the velvetbean caterpillar. Thus, these data contribute significantly to the knowledge of the structure and composition of these elements in the genome of this species, and suggest the role of stress on their expression.

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension. METHODS: We conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro-B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit. RESULTS: A total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, -0.3 to 3.5) in the placebo group. The Hodges-Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure. CONCLUSIONS: In patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988.).

Acute effects of transcranial direct current stimulation combined with physical therapy on the balance and gait in individuals with Parkinson's disease: A randomized controlled trial.

Application methods of transcranial direct current stimulation (tDCS) in Parkinson's disease (PD) are quite divergent making it difficult to define the clinical effectiveness of the tDCS on PD. Thus, the aim of this study was to verify the acute effects of tDCS when applied to different targets (Cz or C3-Cz-C4) combined to physical therapy to improve balance and gait in individuals with PD. A randomized controlled trial was conducted, with 50 individuals who were separated into four groups: 1) Real tDCS (Cz) + physical therapy, 2) Real tDCS (C3-Cz-C4) + physical therapy, 3) Sham tDCS + physical therapy and 4) Educational lecture + physical therapy. The current intensity was 2 mA, applied for 20 min. For the instrumental assessment of balance and gait, the 3D motion analysis system was used. For the biomechanical analysis of gait, three different conditions were performed: normal gait, dual task gait and obstacle gait. For balance analysis, the following positions were utilized: Romberg with eyes opened, Romberg with eyes closed, Tandem with eyes opened and Tandem with eyes closed. All evaluations were performed pre-intervention, post-intervention (immediately at the end of the intervention) and were followed-up on (24 h after the end of the intervention). No statistically significant differences were found for all gait and balance outcomes when considering the interaction between time (pre, post and follow-up assessments) versus group (Education, Sham, Cz and C3-Cz-C4). In conclusion, it was found that one session of tDCS, stimulating Cz or C3-Cz-C4 combined with physical therapy, was not effective in improving the balance and gait in people with PD as compared to sham tDCS or educational lecture plus physiotherapy.