Abstract Background Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache syndromes.Methods We conducted a cross-sectional study in Latin America to characterize individuals with persistent headache after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identify risk factors associated with NDPH. Participants over 18 years old who tested positive for SARS-CoV-2 infection and reported persistent headache among their symptoms completed an online survey that included demographics, past medical history, persistent headache clinical characteristics, and COVID-19 vaccination status. Based on participants’ responses, NDPH diagnostic criteria were used to group participants into NDPH and non-NDPH groups.Results Four hundred and twenty-one participants from 11 Latin American countries met the inclusion criteria. One in four participants met the diagnostic criteria for NDPH. The mean age was 40 years, with most participants being female (82%). Over 90% of the participants reported having had mild/moderate COVID-19. Most participants had a history of headache before developing COVID-19 (58%), mainly migraine type (32%). The most predominant clinical characteristics in the NDPH group were occipital location, severe/unbearable intensity, burning character, and radiating pain (p < 0.05). A higher proportion of anxiety symptoms, sleep problems, myalgia, mental fog, paresthesia, nausea, sweating of the face or forehead, and ageusia or hypogeusia as concomitant symptoms were reported in participants with NDPH (p < 0.05). Palpebral edema as a concomitant symptom during the acute phase of COVID-19, occipital location, and burning character of the headache were risk factors associated with NDPH.Conclusion This is the first study in Latin America that explored the clinical spectrum of NDPH after SARS-CoV-2 infection and its risk factors. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH.

Communities of practice, which are often a central component of KM, are considered to be used to facilitate information sharing, resolve internal obstacles, and enhance mutual learning. The extensive use of ICT has enabled their transformation into a virtual environment – Professional Virtual Communities of Practice (VCoPs) – which is creating ideal conditions for collaborative information sharing and learning. This research examined factors predicting usage of the VCoP and how Malaysian public sector organisations, through their adoption, can influence their service efficiency. Based on the synthesis of the UTAUT2 and the DeLone & McLean Model of IS Success, a quantitative approach was adopted for this research. 313 valid respondent data was collected using a questionnaire from public sector organisations that had adopted a VCoP as a knowledge sharing tool. A logical sequence of methods, encompassing descriptive and inferential analysis, followed by using Structured Equation Modelling (SEM), and the SmartPLS software was conducted to determine relevant statistical tests. The findings suggest that the Malaysian Public Sector will benefit from improving their knowledge sharing environment with a VCoP system. Establishing appropriate facilitating conditions, quality knowledge and an enjoyable and up-to-date digital tool will ensure continuous usage.

AbstractPiano performance is a complex domain that involves the integration of various skills, including motor, perceptual, cognitive, and emotional abilities. However, research in neuroscience and music cognitive psychology suggests that this integration of distinct abilities may not occur spontaneously, and there may be a mutual attenuation relationship between cognition and emotion. An investigation comparing piano performances focusing attention on cognitive or affective aspects revealed a reciprocal inhibitory influence between them. Analysis of specific musical features, performance mistakes, and comments demonstrated more expressiveness features, as well as inhibition of executive skills and motor control in the piano execution with attention focusing on emotional aspects. In contrast, attention to cognitive aspects of the performances constrained both automatism and expressiveness. In this study, we used fMRI to investigate neural systems concerning cognition and emotion reciprocal modulation in piano performances. Comparing brain activity between performances in cognitive minus affective conditions indicated greater activity in the central executive network (CEN), pre-supplementary motor area (pre-SMA), supplementary motor area (SMA), language, and visual areas. The contrast of affective minus cognitive condition demonstrated greater activity in the anterior medial prefrontal cortex and right dorsolateral prefrontal cortex (DLPFC). The results support the notion of dual meta-systems relying on explicit and implicit neural circuits, respectively, and corroborate the existence of cognitive and emotional reciprocal attenuation influence in pianistic performances.

<h3>Objective:</h3> To assess safety, tolerability, pharmacokinetics, and pharmacodynamics of SAR443820 in first-in-human, Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose (SAD; Part-1a) and multiple-ascending dose (MAD; Part-2) studies in healthy participants. Part-1b was a separate open-label single-dose study for assessing SAR443820 levels in cerebrospinal fluid (CSF). <h3>Background:</h3> Receptor-interacting serine/threonine protein kinase-1 (RIPK1), which regulates inflammatory signaling and necroptotic cell death, is implicated in several neurodegenerative diseases. SAR443820, a central nervous system (CNS) penetrant oral RIPK1 inhibitor, is being developed in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). <h3>Design/Methods:</h3> In Part-1a, 4 cohorts (n=8 each; 6 SAR443820, 2 placebo) received single-ascending doses of SAR443820 (up to 4-fold the lowest dose) or placebo. Part-1b included 2 single-dose cohorts (n=6 each) receiving the lowest and 4-fold the lowest doses of SAR443820. In Part-2, 4 cohorts (n=10 each; 8 SAR443820, 2 placebo) received 14-day SAR443820 or placebo in multiple-ascending doses. <h3>Results:</h3> Overall, SAR443820 was well-tolerated with no treatment-related serious adverse events (AEs) or permanent treatment discontinuation. Most common AEs were dizziness and headache. No clinically meaningful changes were noted in hematology, chemistry, vital signs, or electrocardiogram parameters. There were no major deviations from dose proportionality for maximum concentration (C_max) and area under the curve (AUC) over the range of SAR443820 doses. Mean plasma half-lives ranged between 6–8h and 7–9h in SAD and MAD cohorts, respectively. Mean CSF-to-unbound plasma concentration ratio suggested high CNS-penetrance. Concentration-QTcF analyses did not indicate any potential for SAR443820 to cause relevant change in QTcF. Maximum median inhibition of phosphorylated-Ser166-RIPK1 levels across all SAR443820 groups reflected a marked target engagement. <h3>Conclusions:</h3> The first-in-human study demonstrated that single and repeated SAR443820 doses were generally safe and well-tolerated, with favorable pharmacokinetics, high CNS-penetrance, and robust RIPK1-target engagement, supporting further development in actively recruiting Phase 2 trials in ALS (Himalaya; NCT05237284) and MS (K2; ACT16753). <b>Disclosure:</b> Mrs. HINCELIN-MERY has nothing to disclose. Pascale Lewanczyk has nothing to disclose. Mrs. Cantalloube has received personal compensation for serving as an employee of Sanofi. Mr. Nicolas has nothing to disclose. Myriam Benamor has nothing to disclose. Dr. Pomponio has received personal compensation for serving as an employee of Sanofi. Dr. Pomponio has stock in sanofi. Dr. KRUPKA has nothing to disclose. Dimitry Ofengeim has received personal compensation for serving as an employee of Sanofi. Dimitry Ofengeim has received stock or an ownership interest from Sanofi. Dimitry Ofengeim has received personal compensation in the range of $500-$4,999 for serving as a Study Section Reveiwer with NIH. Dr. Eastenson has nothing to disclose. Dr. Xiong has received personal compensation for serving as an employee of Sanofi. Dr. Atassi has received personal compensation for serving as an employee of Sanofi. Dr. Atassi has stock in Sanofi.

Abstract Background In low- and middle-income countries, pregnant women and newborns are more vulnerable to adverse outcomes from coronavirus disease 2019 (COVID-19). However, in Venezuela, there are no integrated data in a national surveillance system to identify the clinical-epidemiological characteristics and maternal-foetal outcomes of pregnant women hospitalised with COVID-19. Methods A retrospective study was conducted among Venezuelan pregnant women hospitalised with COVID-19 seen at the “Ruiz y Páez” University Hospital Complex and the San Cristobal Central Hospital between June 2020 and September 2021. Information was obtained from physical and digitised clinical records using a form to collect epidemiological, clinical, paraclinical, treatment, obstetric and perinatal complications, and maternal-foetal outcomes data. Results A total of 80 pregnant women with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were tested, 59 (73.8%) survived and 21 (26.2%) deceased. The median age was 29 [IQR —interquartile range— 10] years, the majority being in the third trimester of pregnancy (81.2%). Interestingly, four (5%) pregnant women were co-infected with malaria by Plasmodium vivax and three (3.8%) with syphilis. The most frequent symptoms were fever (75%), dry cough (68.8%), dyspnoea (55%), and headache (53.8%). The most frequent maternal complications were anaemia (51.5%) and hypertensive disorders of pregnancy (17.5%). The most frequent perinatal complications were preterm delivery (39.2%) and oligohydramnios (31.3%). A total of 29 (36.3%) perinatal deaths were documented, 21 stillbirth and eight abortions. Conclusion This is the first study to describe the clinical-epidemiological behaviour of COVID-19 in hospitalised Venezuelan pregnant women. Anaemia, hypertensive disorders of pregnancy, preterm birth, and perinatal death were the most frequent maternal-foetal complications in this population of pregnant women.

This systematic review examined studies that used mediation analysis to investigate the mechanisms of action of cognitive-behavioral, mind-body, and exercise-based interventions for pain and disability in people with chronic primary musculoskeletal pain. We searched 5 electronic databases for articles that conducted mediation analyses of randomized controlled trials to either test or estimate indirect effects. We found 17 studies (n=4423), including 90 mediation models examining the role of 22 putative mediators on pain or disability, of which 4 had partially mediated treatment effect; 8 had mixed results, and 10 did not mediate treatment effect. The conditions studied were chronic whiplash-associated pain, chronic low back pain, chronic knee pain, and mixed group of chronic primary musculoskeletal pain. We observed that several of the studies included in our systematic review identified similar mechanisms of action, even between different interventions and conditions. However, methodological limitations were common. In conclusion, there are still substantial gaps with respect to understanding how cognitive-behavioral, mind-body, and exercise-based interventions work to reduce pain and disability in people with chronic primary musculoskeletal pain.

SUMMARYPandemic viruses remain a global threat to health and economics but how they adapt to become pandemic remains poorly understood. Here we compare pandemic HIV-1(M) and non-pandemic HIV-(O) and HIV-2 strains finding that non-pandemic HIV replicate poorly in myeloid cell models due to activation of cGAS and TRIM5, and ensuing antiviral responses. We use phylogenetics and viral capsid structural biology to define specific differences between pandemic and non-pandemic HIV capsids and demonstrate that their genetic reversal in HIV-1(M) mutants causes TRIM5, cGAS and innate immune activation. We propose a model in which the parental lineage of pandemic HIV-1(M) has uniquely evolved a dynamic capsid that avoids activation of cGAS and TRIM5 to establish cloaked replication in myeloid cells. The unique adaptations of the pandemic virus lineage suggests a role in effective human-to-human transmissibility and highlight the importance of avoiding innate immune activation during pandemic human-to-human viral transmission.

This article aims to identify opportunities and challenges of innovation for sustainability perceived by micro and small enterprises (MSEs) for developing new business models. Questionnaires were applied to companies participating in the local innovation agent (agente local de inovação - ALI) Program in a Brazilian city to survey their perceptions and management practices concerning sustainability and innovation that allow the development of new business models, with 13 responses being obtained. Descriptive statistics analysed the data. The results show that innovation for sustainability generates opportunities such as new businesses, strengthening the supplier network, winning over new customers and generating better results. The study also highlighted challenges in business model innovation for sustainability, such as: finding suppliers and partners for sustainable inputs that practice sustainability, information and incentives from the public authorities, customer culture for acquiring sustainable products and services and lack of financial resources to invest in innovation were found.

Abstract Background: Osteoporosis is characterized by low bone mineral density, which causes fractures and compromises people's quality of life. Diagnostic devices for assessing this health condition, such as Dual Energy X-ray Absorptiometry (DXA), are very costly. Therefore, it is impracticable to meet the demand for tests in Brazil's 5,568 municipalities. Given that, we proposed a pre-clinical validation of a prototype developed to aid bone mineral density classification. Thus, Osseus integrates a microcontroller with other peripheral devices to measure the electromagnetic permittivity at the middle phalanx of the middle finger, with two antennas operating in the 2.45 GHz frequency range. Using Artificial Intelligence to identify risk factors alongside signal attenuation measurement indicates the need for DXA. Results: We conducted tests with plaster, Galliformes, and porcine bones. Comparison of the measurements of the original and mechanically altered samples have demonstrated that the device can handle the complexity of the tissues within the bone structure and characterize its microarchitecture. Conclusions: Osseus is a prototype and has been preliminarily validated. There is a lack of validation studies with the reference/gold standard that are currently under development. Osseus enables early detection of osteoporosis, reduces costs, and optimizes high-complexity testing referrals.