Influence of radiologic pattern and the presence of diffuse parenchymal lung disease on outcome in ventilated patients with COVID-19 pneumonia: impact on prognosis.

BACKGROUND: Suspected organising pneumonia (OP) is a common finding in patients with severe coronavirus disease 2019 (COVID-19), but the impact on outcomes of the radiological patterns of diffuse parenchymal lung disease on outcome of these patients is still uncertain. AIMS: Investigate the presence of radiological images compatible with OP and its association with clinical outcomes in patients with COVID-19 submitted to invasive mechanical ventilation (IMV). METHODS: Retrospective, unicentric cohort study composed of patients who required IMV and underwent chest computerized tomography to investigate secondary complications of COVID-19. We compared patients with radiological findings characteristic of suspected OP with those without this condition. The main outcome was hospital mortality. RESULTS: Two hundred and ten patients were included, and 65 had signals compatible with OP. All patients with suspected OP were treated with corticosteroids. There was no difference in IVM-free days until day 28 between the groups (median, 0 days; interquartile range [IQR], 0-14.8) in the group with suspected OP vs 0 days (IQR, 0-11) in the group without suspected OP (P = 0.14). In univariate analysis, the presence of suspected OP was associated with lower hospital mortality; however, after correction for potential confounding variables, it was not associated with the outcome, even after matching by propensity score in patients without this condition. CONCLUSION: OP radiologic pattern in patients with severe COVID-19 is not associated with worse outcomes.

Development a Low-Cost Wireless Smart Meter with Power Quality Measurement for Smart Grid Applications.

Developing a low-cost wireless energy meter with power quality measurements for smart grid applications represents a significant advance in efficient and accurate electric energy monitoring. In increasingly complex and interconnected electric systems, this device will be essential for a wide range of applications, such as smart grids, by introducing a real-time energy monitoring system. In light of this, smart meters can offer greater opportunities for sustainable and efficient energy use and improve the utilization of energy sources, especially those that are nonrenewable. According to the 2020 International Energy Agency (IEA) report, nonrenewable energy sources represent 65% of the global supply chain. The smart meter developed in this work is based on the ESP32 microcontroller and easily accessible components since it includes a user-friendly development platform that offers a cost-effective solution while ensuring reliable performance. The main objective of developing the smart meters was to enhance the software and simplify the hardware. Unlike traditional meters that calculate electrical parameters by means of complex circuits in hardware, this project performed the calculations directly on the microcontroller. This procedure reduced the complexity of the hardware by simplifying the meter design. Owing to the high-performance processing capability of the microcontroller, efficient and accurate calculations of electrical parameters could be achieved without the need for additional circuits. This software-driven approach with simplified hardware led to benefits, such as reduced production costs, lower energy consumption, and a meter with improved accuracy, as well as updates on flexibility. Furthermore, the integrated wireless connectivity in the microcontroller enables the collected data to be transmitted to remote monitoring systems for later analysis. The innovative feature of this smart meter lies in the fact that it has readily available components, along with the ESP32 chip, which results in a low-cost smart meter with performance that is comparable to other meters available on the market. Moreover, it is has the capacity to incorporate IoT and artificial intelligence applications. The developed smart meter is cost effective and energy efficient, and offers benefits with regard to flexibility, and thus represents an innovative, efficient, and versatile solution for smart grid applications.

Translation and Cross-Cultural Adaptation of the "Early Support Monitoring Protocol".

Parents are required to make various decisions after a child's hearing loss diagnosis. With that in mind, one of the researchers of this study, the father of a child with deaf, did not find any available instrument in the Brazilian literature to support was found to the decision-making process for parents. Considering the importance of assisting parents, caretakers, and professionals who work with Deaf and Hard of Hearing children to monitor and assess the child's development, this work aims to translate and adapt a monitoring protocol for professionals and parents. For this, we translated and cross-culturally adapted 452 items of the Early Support instrument. The items corresponded to the domains of communication, attention, listening, and vocalization. We selected 25% of the items to be assessed by specialists, which were divided into the categories: (1) cultural adequacy; (2) concept presented; and (3) target audience adequacy. A reverse translation was conducted in this stage of the research. After compiling the data and correcting the probable translation errors, it was possible to analyze the items that were not included in the specialists' assessment and propose an assessment with new items. Afterward, the translated items were compared with the reviewed version of the instrument (Success From the Start), which comprises 347 items of the two development domains.

The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis.

BACKGROUND: Cannabis consumption is a modifiable risk factor associated with psychosis, but not all cannabis users develop psychosis. Animal studies suggest that an antecedent active immune system interacts with subsequent cannabis exposure and moderates the cannabis-psychosis association, supporting the two-hit hypothesis. The clinical investigations are few, and it is unclear if the immune system is a biological candidate moderating the cannabis-psychosis association or whether cannabis increases inflammation, which in turn, augments psychosis likelihood. METHODS: We explored the mediating and moderating role of blood inflammation using PROCESS macro. We used data from a cross-sectional study, including 153 first-episode psychosis patients and 256 community-based controls. Participants answered the Cannabis Experience Questionnaire (cannabis frequency, age of onset, and duration), and plasma cytokines were measured [interleukin (IL)-1ß, IL-6, IL-4, IL-10, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-ß (TGF-ß); multiplex]. We computed an inflammatory composite score (ICS) to represent the systemic inflammatory state. Confounders included sex, age, ethnicity, educational level, body mass index, tobacco smoking, lifetime use of other drugs, and antipsychotic treatment. RESULTS: Mediation: Cannabis consumption was not associated with increased inflammation, thus not supporting a mediating effect of inflammation. Moderation: Daily use and age of onset <17 interacted significantly with the ICS to increase the odds of psychosis beyond their individual effects and were only associated with psychosis among those scoring medium-high in the ICS. CONCLUSIONS: Immune dysregulation might be part of the pathophysiology of psychosis, not explained by cannabis use or other confounders. We provide the first and initial evidence that immune dysregulation modifies the cannabis-psychosis association, in line with a two-hit hypothesis.

Perceptions about malaria among Brazilian gold miners in an Amazonian border area: perspectives for malaria elimination strategies.

BACKGROUND: Mining in the Amazon exposes gold miners to various diseases, including malaria, whose control is still a major challenge. The environment of the mines contributes to the proliferation of vector mosquitoes and the precarious housing conditions facilitate transmission of the disease. Understanding gold miners' perceptions is essential for the formulation of strategies to fight malaria. A qualitative study was carried out in the municipality of Calçoene, state of Amapá, Brazilian Amazon adjointining the municipality of Oiapoque, that is in the border area with French Guiana and Suriname. METHODS: A semi-structured interview was applied to an intentional sample of 29 miners, a number determined by the theoretical saturation criterion. Thematic analysis was adopted to obtain the results and the Cohen's Kappa index was calculated to verify the agreement between observers during coding. RESULTS: The agreement between observers was verified by a Cohen's Kappa index of 0.82. Analysis of the interviews showed that gold miners were subjected to prejudice from the community due to forest diseases that they can transmit, and their activities are often associated with crime. When the miners return to their hometown after a period of mining, the urban population blames them for the onset of diseases such as malaria. Most participants in the survey did not know how malaria transmission occurs, and associated its occurrence with contaminated water and food. Participants reported not being afraid of the disease, trusting the diagnosis and available treatment, though this depends on where they are treated. The use of therapeutic resources, such as medicinal plants and medicines acquired in the illegal market, is very common in this population. Despite the challenges identified by the research subjects, they believe that the disease can be controlled, or the cases reduced, but there was low acceptability for a possible mass drug administration (MDA) intervention. CONCLUSION: Despite a recent reduction in malaria prevalence in Brazil, there are still vulnerable populations, such as gold miners, who help to perpetuate the existence of the disease in the Amazon. The lack of knowledge regarding how the transmission of malaria occurs, associated with myths regarding this and the use of traditional health practices and illegal drugs for the treatment of the disease without a specific diagnosis, jeopardizes the country's efforts to eliminate malaria. It is necessary to implement control programmes in these populations, especially those who frequently travel around the border region and to remote locations, which are difficult regions for health teams to access, thus hindering diagnostic and treatment actions. For this reason, understanding the perceptions of these individuals as well as their customs, beliefs and lifestyle, can assist in the production of targeted educational material and adoption of strategies in the elimination of malaria in the country.

Understanding UX Better: A New Technique to Go beyond Emotion Assessment.

User experience (UX) is a quality aspect that considers the emotions evoked by the system, extending the usability concept beyond effectiveness, efficiency, and satisfaction. Practitioners and researchers are aware of the importance of evaluating UX. Thus, UX evaluation is a growing field with diverse approaches. Despite various approaches, most of them produce a general indication of the experience as a result and do not seek to capture the problem that gave rise to the bad UX. This information makes it difficult to obtain relevant results to improve the application, making it challenging to identify what caused a negative user experience. To address this gap, we developed a UX evaluation technique called UX-Tips. This paper presents UX-Tips and reports two empirical studies performed in an academic and an industrial setting to evaluate it. Our results show that UX-Tips had good performance in terms of efficiency and effectiveness, making it possible to identify the causes that led to a negative user experience, and it was easy to use. In this sense, we present a new technique suitable for use in both academic and industrial settings, allowing UX evaluation and finding the problems that may lead to a negative experience.

Initial clinical experience with the micromesh Roadsaver carotid artery stent for the treatment of patients with symptomatic carotid artery disease.

PURPOSE: To assess the effectiveness, technical aspects, handling, and safety of the micromesh Roadsaver Carotid Artery Stent in the treatment of atherosclerotic carotid artery stenosis and tandem lesions in ischemic stroke patients. METHODS: Seven patients (5 men; mean age 75±11.4 years, range 53-86) suffering from symptomatic internal carotid artery (ICA) stenosis (mean 76% diameter reduction) were treated with the dual layer closed-cell stent without embolic protection. Postdilation was performed in 6 of 7 patients. Two patients were treated in the context of ischemic stroke and concurrent middle cerebral artery occlusion. Mean National Institutes of Health Stroke Scale score at admission was 12.8±5. RESULTS: All devices were deployed satisfactorily. One wall-adherent thromboembolus in a proximal ICA was covered with the Roadsaver stent in a tandem lesion setting. The modified Rankin Scale (mRS) declined from 3.7±0.7 to 2.4±0.8 in hospital, showing an improvement in clinical symptoms. No complications were detected during or after the procedure. The 30-day mRS was 1.7±1.1. At 6 months, ultrasound examination demonstrated patency of stents and the external carotid arteries. CONCLUSION: The Roadsaver double layer micromesh stent seems to be safe and effective in the treatment of extracranial ICA stenosis and in the context of tandem lesions in ischemic stroke. Further studies with larger populations are warranted.

New LLLT protocol to speed up the bone healing process-histometric and immunohistochemical analysis in rat calvarial bone defect.

A new low-level laser therapy (LLLT) protocol is proposed and compared to another previously studied, in animal models, aiming to establish a more practical LLLT protocol. Protocol 1, the same used in other works and based on the clinical LLLT protocol for bone regeneration, consists of punctual transcutaneous applications in the defect region with fluence of 16 J/cm(2) every 48 h for 15 days. Protocol 2, proposed in this work, consists of three sessions: the first application directly on the defect site with fluency of 3.7 J/cm(2), during the surgical procedure, followed by two transcutaneous applications, 48 and 120 h postoperatively. The Thera Lase® (λ = 830 nm) was used, and the dosimetry of the first application of protocol 2 was calculated based on in vitro studies. Forty-five male rats were used, in which critical-size bone defects with 8 mm of diameter were surgically created in calvaria. The animals were randomly divided into three groups of 15 animals, named group 1 (protocol 1), group 2 (protocol 2), and control, which was not submitted to laser treatment. After 7, 15, and 45 days, five animals of each group were euthanized, and the pieces of calvarial bone were collected for microscopic and immunohistochemistry for vascular endothelial growth factor (VEGF), osteocalcin (OC), and osteopontin (OP) analysis. Histomorphometry showed that newly formed bone of 15-day samples from group 2 is higher than the control group (p < 0.05, ANOVA, Tukey). At 7 days, in the central part of the defect, VEGF expression was the same for all groups, OC was higher for protocol 2, and OP for protocol 1. The results suggest LLLT using the protocol 2 hastened the bone healing process in the early periods after surgery.

Comparison of the performance of natural latex membranes prepared with different procedures and PTFE membrane in guided bone regeneration (GBR) in rabbits.

This work assessed the performance of membranes made of natural latex extracted from Hevea brasiliensis prepared with three different methods: polymerized immediately after collection without the use of ammonia (L1); polymerized after preservation in ammonia solution (L2); and polymerized after storage in ammonia, followed by Soxhlet technique for the extraction of substances (L3). Polytetrafluoroethylene (PTFE) membrane was used as control. Two 10-mm diameter bone defects were surgically made in the calvaria of thirty adult male New Zealand rabbits. Defects (total n = 60) were treated with guided bone regeneration (GBR) using L1, L2, L3 or PTFE membranes (n = 15 for each membrane). Ten animals were euthanized after 7, 20 and 60 days postoperatively so that five samples (n = 5) of each treatment were collected at each time, and bone regeneration was assessed microscopically. The microscopic analysis revealed defects filled with blood clot and new bone formation at the margins of the defect in all 7-day samples, while 20-day defects were mainly filled with fibrous connective tissue. After 60 days defects covered with L1 membranes showed a significantly larger bone formation area in comparison to the other groups (P < 0.05, ANOVA, Tukey). Additionally, bone tissue hypersensitization for L1 and PTFE membranes was also investigated in six additional rabbits. The animals were subjected to the same surgical procedure for the confection of one 10-mm diameter bone defect that was treated with L1 (n = 3) or PTFE (n = 3). Fifty-three days later, a second surgery was performed to make a second defect, which was treated with the same type of membrane used in the first surgery. Seven days later, the animals were euthanized and samples analyzed. No differences among L1 and PTFE samples collected from sensitized and non-sensitized animals were found (P > 0.05, Kruskal-Wallis). Therefore, the results demonstrated that latex membranes presented performance comparable to PTFE membranes, and that L1 membranes induced higher bone formation. L1 and PTFE membranes produced no hypersensitization in the bone tissue.

Role of Gasotransmitters in Inflammatory Edema.

Significance: Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are, to date, the identified members of the gasotransmitter family, which consists of gaseous signaling molecules that play central roles in the regulation of a wide variety of physiological and pathophysiological processes, including inflammatory edema. Recent Advances: Recent studies show the potential anti-inflammatory and antiedematogenic effects of NO-, CO-, and H2S-donors in vivo. In general, it has been observed that the therapeutical effects of NO-donors are more relevant when administered at low doses at the onset of the inflammatory process. Regarding CO-donors, their antiedematogenic effects are mainly associated with inhibition of proinflammatory mediators (such as inducible NO synthase [iNOS]-derived NO), and the observed protective effects of H2S-donors seem to be mediated by reducing some proinflammatory enzyme activities. Critical Issues: The most recent investigations focus on the interactions among the gasotransmitters under different pathophysiological conditions. However, the biochemical/pharmacological nature of these interactions is neither general nor fully understood, although specifically dependent on the site where the inflammatory edema occurs. Future Directions: Considering the nature of the involved mechanisms, a deeper knowledge of the interactions among the gasotransmitters is mandatory. In addition, the development of new pharmacological tools, either donors or synthesis inhibitors of the three gasotransmitters, will certainly aid the basic investigations and open new strategies for the therapeutic treatment of inflammatory edema. Antioxid. Redox Signal. 40, 272-291.

Epidemiological Profile of Hospitalized Patients with Cystic Fibrosis in Brazil Due to Severe Acute Respiratory Infection during the COVID-19 Pandemic and a Systematic Review of Worldwide COVID-19 in Those with Cystic Fibrosis.

Since the onset of the coronavirus disease, COVID-19 pandemic, concern arose for those who might be at higher risk of a worse COVID-19 prognosis, such as those with cystic fibrosis (CF). In this context, we evaluated the features of hospitalized patients with CF due to severe acute respiratory infection (SARI) in Brazil and we also performed a systematic review including all the studies published from the beginning of the first case of COVID-19 (17 November 2019) to the date of this search (23 May 2022) which included, concomitantly, patients with CF and COVID-19 in the worldwide population. In our Brazilian data, we evaluated the period from December 2019 to March 2022, and we included 33 demographical and clinical patients' features. We classified the patients into groups: (G1) SARI due to another viral infection than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (23; 5.4%), (G2) SARI due to an unknown etiological agent (286; 67.1%), and (G3) SARI due to SARS-CoV-2 infection (117; 27.5%). The individuals in G3 tended to be older, especially over 50 years old, and presented a higher prevalence of dyspnea, peripheral capillary oxygen saturation (SpO2) <95%, and cardiopathy. The highest prevalence for intensive care unit (ICU) treatment (52; 44.4%) and invasive mechanical ventilation (29; 24.8%) was for patients in G3. Almost half of the patients in G3 died (51; 43.6%); in contrast, none in G1 died. However, we observed 43 (15.0%) deaths in G2. In addition, 12 (4.2%) and one (0.9%) death not associated with SARI occurred, respectively, in the G2 and G3. The patients who died due to SARS-CoV-2 infection had a higher frequency of SpO2 <95% (46; 90.2%), ICU treatment (34; 66.7%), and invasive mechanical ventilation (27; 52.9%) when compared to those who recovered. The systematic review comprised a total of 31 papers published as observational studies. These studies comprised 661,386 patients in total, including children, adults, and elderly age groups. However, only 19,150 (2.9%) patients were diagnosed with CF and, from these patients, 2523 (0.4%) were diagnosed with both CF and COVID-19. It was observed that the most common outcome was the need for hospitalization (n = 322 patients with CF), and the need for oxygen support (n = 139 patients with CF). One hundred patients with CF needed intensive care units, fifty patients needed non-invasive mechanical ventilation support, and only three patients were described as receiving invasive mechanical ventilation support. Deaths were described in 38 patients with CF. Importantly, lung-transplanted patients with CF represented an increased risk of death in one publication; in accordance, another study described that lung transplantation and moderate to severe lung disease were independent risk factors for severe outcomes after SARS-CoV-2 infection. In contrast with the literature, in conclusion, Brazilian patients in G3 presented a severe phenotype, even though most of the other studies did not observe worse outcomes in patients with CF and COVID-19.

Mechanical Power in Prone Position Intubated Patients with COVID-19-Related ARDS: A Cohort Study.

Background: Respiratory monitoring of mechanical ventilation (MV) is relevant and challenging in COVID-19. Mechanical power (MP) is a novel and promising monitoring tool in acute distress respiratory syndrome (ARDS), representing the amount of energy transferred from the ventilator to the patient. It encompasses several setting parameters and patient-dependent variables that could cause lung injury. MP can therefore be an additional tool in the assessment of these patients. Objective: This study aims to evaluate respiratory monitoring through MP and its relationship with mortality in patients with COVID-19-related ARDS (CARDS) under mechanical ventilation (MV) and prone position (PP) strategies. Methods: Retrospective, unicentric, and cohort studies. We included patients with CARDS under invasive MV and PP strategies. Information regarding MP, ventilation, and gas exchange was collected at 3 moments: (1) prior to the first PP, (2) during the first PP, and (3) during the last PP. We tested the relationship between MP and VR with in-hospital mortality. Results: We included 91 patients. There was a statistically significant difference in MP measurements between survivors and nonsurvivors only in the last prone position (p < 0.001). This is due to the significant increase in MP measurements in nonsurvivors (difference from the baseline: 3.63 J/min; 95% CI: 0.31 to 6.94), which was not observed in the group that survived (difference from the baseline: 0.02 J/min; 95% CI: -2.66 to 2.70). In multivariate analysis, MP (p=0.009) was associated with hospital death when corrected for confounder variables (SAPS 3 score, mechanical ventilation time, age, and number of prone sessions). Conclusions: MP is an independent predictor of mortality in PP patients with CARDS.

Extubation failure and the use of noninvasive ventilation during the weaning process in critically ill COVID-19 patients.

OBJECTIVE: To assess the outcome of extubation in COVID-19 patients and the use of noninvasive ventilation in the weaning process. METHODS: This retrospective, observational, single-center study was conducted in COVID-19 patients aged 18 years or older who were admitted to an intensive care unit between April 2020 and December 2021, placed under mechanical ventilation for more than 48 hours and progressed to weaning. Early extubation was defined as extubation without a spontaneous breathing trial and immediate use of noninvasive ventilation after extubation. In patients who underwent a spontaneous breathing trial, noninvasive ventilation could be used as prophylactic ventilatory assistance when started immediately after extubation (prophylactic noninvasive ventilation) or as rescue therapy in cases of postextubation respiratory failure (therapeutic noninvasive ventilation). The primary outcome was extubation failure during the intensive care unit stay. RESULTS: Three hundred eighty-four extubated patients were included. Extubation failure was observed in 107 (27.9%) patients. Forty-seven (12.2%) patients received prophylactic noninvasive ventilation. In 26 (6.8%) patients, early extubation was performed with immediate use of noninvasive ventilation. Noninvasive ventilation for the management of postextubation respiratory failure was administered to 64 (16.7%) patients. CONCLUSION: We found that COVID-19 patients had a high rate of extubation failure. Despite the high risk of extubation failure, we observed low use of prophylactic noninvasive ventilation in these patients.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study.

BACKGROUND: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. METHODS: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. RESULTS: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. CONCLUSIONS: SMS could assist patients in adhering to prescribed antimalarials.

Epidemiological profile of dog attacks to patients under 14 years old assisted at the pediatric referral emergency unit of a tertiary hospital in Campinas, Brazil.

Introduction: Accidents involving dog attacks are very common, which makes this type of accident a global public health issue. The estimates point to 20% of the victims of such accidents seeking care in health units, and half of them being children. In addition to acute injuries, dog attacks might result in fractures, infections, scars, and psychological traumas. This study aimed to describe the epidemiological profile of dog attacks to children under 14 years old assisted in a pediatric emergency service in Brazil. Methods: The database of the Information and Toxicological Assistance Center of Campinas was surveyed to identify cases of children under 14 years old assisted after a dog attack in a 9-years period. Demographic data, number and type of lesions, type of exposure, part of the body affected, dog origin and condition, and the accident location and cause were analyzed. The data were presented in a descriptive way, and the age groups were classified as follows: 0-3 years old, 4-6 years old, and 7-14 years old. The different age groups were compared one to another regarding the markers evaluated using the chi-square test and the Fisher's exact test. A 0.05 alpha was adopted in all analyses. Results: The number of children assisted in the study period totaled 1,012. The 7-14-year-old group was the most affected (n = 498; 49.2%), male patients were also majority (n = 660; 65.2%). Most injuries were found on the head/neck area (n = 378; 37.4%). However, the older the patients were, the higher the frequency of lesions on upper and lower limbs was, as well as attacks occurred in external environments, thus involving animals that could not be observed. A significant increase in accidents with provoked causes was observed in younger patients. Conclusion: Accidents involving dog attacks are more likely to happen among boys. Younger children run higher risks of becoming victims of these accidents inside homes, being attacked by pets, and showing a greater incidence of head and neck lesions. Older children present more injuries on their limbs, which are caused by dogs that cannot be observed.

An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches.

Metabolic syndrome (MS) is a complex pathology characterized by visceral adiposity, insulin resistance, arterial hypertension, and dyslipidaemia. It has become a global epidemic associated with increased consumption of high-calorie, low-fibre food and sedentary habits. Some of its underlying mechanisms have been identified, with hypoadiponectinemia, inflammation and oxidative stress as important factors for MS establishment and progression. Alterations in adipokine levels may favour glucotoxicity and lipotoxicity which, in turn, contribute to inflammation and cellular stress responses within the adipose, pancreatic and liver tissues, in addition to hepatic steatosis. The multiple mechanisms of MS make its clinical management difficult, involving both non-pharmacological and pharmacological interventions. Transient receptor potential (TRP) channels are non-selective calcium channels involved in a plethora of physiological events, including energy balance, inflammation and oxidative stress. Evidence from animal models of disease has contributed to identify their specific contributions to MS and may help to tailor clinical trials for the disease. In this context, the oxidative stress sensors TRPV1, TRPA1 and TRPC5, play major roles in regulating inflammatory responses, thermogenesis and energy expenditure. Here, the interplay between these TRP channels and oxidative stress in MS is discussed in the light of novel therapies to treat this syndrome.

Vasorelaxant Activity of AP39, a Mitochondria-Targeted H2S Donor, on Mouse Mesenteric Artery Rings In Vitro.

Mitochondria-targeted hydrogen sulfide (H2S) donor compounds, such as compound AP39, supply H2S into the mitochondrial environment and have shown several beneficial in vitro and in vivo effects in cardiovascular conditions such as diabetes and hypertension. However, the study of their direct vascular effects has not been addressed to date. Thus, the objective of the present study was to analyze the effects and describe the mechanisms of action of AP39 on the in vitro vascular reactivity of mouse mesenteric artery. Protein and gene expressions of the H2S-producing enzymes (CBS, CSE, and 3MPST) were respectively analyzed by Western blot and qualitative RT-PCR, as well the in vitro production of H2S by mesenteric artery homogenates. Gene expression of CSE and 3MPST in the vessels has been evidenced by RT-PCR experiments, whereas the protein expression of all the three enzymes was demonstrated by Western blotting experiments. Nonselective inhibition of H2S-producing enzymes by AOAA abolished H2S production, whereas it was partially inhibited by PAG (a CSE selective inhibitor). Vasorelaxation promoted by AP39 and its H2S-releasing moiety (ADT-OH) were significantly reduced after endothelium removal, specifically dependent on NO-cGMP signaling and SKCa channel opening. Endogenous H2S seems to participate in the mechanism of action of AP39, and glibenclamide-induced KATP blockade did not affect the vasorelaxant response. Considering the results of the present study and the previously demonstrated antioxidant and bioenergetic effects of AP39, we conclude that mitochondria-targeted H2S donors may offer a new promising perspective in cardiovascular disease therapeutics.

Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI).

Background: Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19. Methods: We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086. Findings: Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion. Interpretation: In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits. Funding: Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.

Quantitative G6PD Deficiency Screening in Routine Malaria Diagnostic Units in the Brazilian Amazon (SAFEPRIM): An Operational Mixed-Methods Study.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not routinely performed before primaquine treatment in most Plasmodium vivax endemic areas, despite the risk of primaquine-associated hemolysis. This is due to the operational challenges associated with pragmatic G6PD testing and as such needs to be addressed. METHODS AND FINDINGS: This mixed-methods operational study was aimed at implementing the quantitative point-of-care StandardTM G6PD (SD Biosensor, Korea) screening test in malaria treatment units (MTUs) in the municipalities of Rio Preto da Eva and Mâncio Lima, in the Brazilian Amazon, between mid-January 2020 and December 2020. In total, 1286 P. vivax cases were treated based on the Standard G6PD test: 1230 had activity equal to or greater than 4.0 U/g Hb, and 56 less than 4.0 U/g Hb. No G6PD deficient (G6PDd) genotypes were found in 96 samples from the 1230, and only 21 of the 56 G6PDd cases had confirmed G6PDd genotypes. Evaluations were conducted on the proficiency of health care professionals (HCPs) training to perform the test, the reliability of testing performed in the field, and the perceptions of HCPs and patients about the implementation. Post-training proficiency was 73.4% after a 4-hour training session. This study revealed that locations with lower malaria caseloads will need regular refresher training. The test was well accepted by both HCPs and patients. Signs and symptoms of hemolysis were not always associated with malaria treatment drugs by HCPs and patients. INTERPRETATION: Point-of-care quantitative G6PD testing can be performed at MTUs in the Brazilian Amazon to inform treatment decisions with primaquine. Limitations related to technical and cultural aspects need to be addressed further when expanding screening to larger areas.

Validation of a Culturally Relevant Snakebite Envenomation Clinical Practice Guideline in Brazil.

Snakebite envenoming (SBE) is a neglected tropical disease with significant global morbidity and mortality. Even when antivenom is available in low-resource areas, health workers do not receive adequate training to manage SBEs. This study aims to develop and validate a clinical practice guideline (CPG) for SBE management across Brazil. A panel of expert judges with academic and/or technical expertise in SBE management performed content validation. The content validity index (CVI) score was 90% for CPG objectives, 89% for structure and presentation and 92% for relevance and classified the CPG as valid. A semantic validation was performed by analyzing focus group discussions with doctors and nurses from three municipalities of the Brazilian Amazon, after a 5-day meeting during which the CPG was presented. Two central themes emerged: knowledge acquired during the meeting and recommendations for improving the CPG. Based on these results, the CPG was revised into a final version. This study presents the successful development and validation process of a CPG for SBE management, which is targeted to a specific low-resource, high-burden setting. This development and validation process can be adapted to other settings and/or other neglected tropical diseases.