PEMOCS: Evaluating the effects of a concept-guided, PErsonalised, MOtor-Cognitive exergame training on cognitive functions and gait in chronic Stroke-study protocol for a randomised controlled trial.

BACKGROUND: Many stroke survivors remain with residual cognitive and motor impairments despite receiving timely acute and sub-acute rehabilitation. This indicates that rehabilitation following stroke should be continuous to meet the needs of individual stroke patients. Both cognitive and motor functions are essential for mastering daily life and, therefore, should be aimed at with rehabilitation. Exergames, motor-cognitive exercises performed using video games, are an auspicious method to train both motor and cognitive functions and at the same time may foster the long-term motivation for training. This study aims to assess the effect of concept-guided, personalised, motor-cognitive exergame training on cognitive and motor functions in chronic stroke survivors. METHODS: This study is a single-blinded, randomised controlled trial. Assessments are performed at baseline, after a 12-week intervention, and at a 24-weeks follow-up. Chronic stroke patients (≥ 18 years old, ≥ 6 months post-stroke) able to stand for 3 min, independently walk 10 m, follow a two-stage command, and without other neurological diseases apart from cognitive deficits or dementia are included. Participants in the intervention group perform the exergame training twice per week for 30 (beginning) up to 40 (end) minutes additionally to their usual care programme. Participants in the control group receive usual care without additional intervention(s). Global cognitive functioning (total Montreal Cognitive Assessment (MoCA) score) is the primary outcome. Secondary outcomes include health-related quality of life, specific cognitive functions, single- and dual-task mobility, and spatiotemporal gait parameters. The target sample size for this trial is 38 participants. Linear mixed models with the post-outcome scores as dependent variables and group and time as fixed effects will be performed for analysis. DISCUSSION: Superior improvements in global cognitive functioning and in the abovementioned secondary outcomes in the intervention group compared to the control group are hypothesised. The results of this study may guide future design of long-term rehabilitation interventions after stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05524727). Registered on September 1, 2022.

Has Treatment Seeking Behaviour Changed in People Living with Epilepsy? Experience of People Living with Epilepsy Attending Adult Neurology Clinics in Enugu.

BACKGROUND: Over the years efforts has been made through public health education to change the knowledge, attitude and practice of epilepsy and seizures among the populace in Nigeria. One surrogate method of reviewing the impact of these educational interventions includes changes in treatment-seeking behavior of People Living With Epilepsy and the reasons for their choices of treatment. METHODS: This was a cross-sectional descriptive study. Data were collected from People Living With Epilepsy attending the medical outpatient clinics in two tertiary hospitals in Enugu, Enugu State southeast Nigeria. RESULTS: A total 276 people living with epilepsy were recruited with a mean age of 30.1 years and a median age of 25 years. After the onset of epilepsy, 76(27.5%) and 70(25.4%) visited general hospitals and teaching hospitals respectively, while prayer houses and traditional healing centers were first visited by 54(19.6%) and 40(14.5%) respectively. As a second choice of care 9(3.3%) and 13(4.7%) visited prayer houses and traditional healing centers. Only 42(15.2%) selected their treatment center because they were confident of getting a cure however, this was highest for those that visited traditional healing centers 11(27.5%). The age of onset of epilepsy positively correlated with selecting orthodox treatment at the choice of care, while occupational status negatively correlated with selecting orthodox care at the same period. CONCLUSIONS: Health care seeking behaviors among PLWE in Southeast Nigeria might have changed over the years as more people living with epilepsy were more likely to select orthodox treatment compared to non-orthodox means of treatment.

CONTEXTE: Au fil des ans, des efforts ont été déployés par le biais de l'éducation en santé publique pour changer les connaissances, les attitudes et les pratiques concernant l'épilepsie et les crises d'épilepsie parmi la population au Nigeria. Une méthode indirecte pour examiner l'impact de ces interventions éducatives comprend les changements dans le comportement de recherche de traitement des personnes vivant avec l'épilepsie et les raisons de leurs choix de traitement. MÉTHODES: Il s'agit d'une étude descriptive transversale. Les données ont été collectées auprès de personnes vivant avec l'épilepsie fréquentant les cliniques de consultations externes médicales dans deux hôpitaux tertiaires à Enugu, dans l'État d'Enugu, au sud-est du Nigeria. RÉSULTATS: Au total, 276 personnes vivant avec l'épilepsie ont été recrutées, avec un âge moyen de 30,1 ans et un âge médian de 25 ans. Après le début de l'épilepsie, 76 (27,5 %) et 70 (25,4 %) ont consulté respectivement des hôpitaux généraux et des hôpitaux universitaires, tandis que les lieux de prière et les centres de guérison traditionnelle ont été les premiers consultés par respectivement 54 (19,6 %) et 40 (14,5 %). Comme deuxième choix de soins, 9 (3,3 %) et 13 (4,7 %) ont consulté des lieux de prière et des centres de guérison traditionnelle. Seuls 42 (15,2 %) ont choisi leur centre de traitement parce qu'ils étaient confiants d'obtenir une guérison, cependant, ce taux était le plus élevé pour ceux qui ont consulté les centres de guérison traditionnelle (11 soit 27,5 %). L'âge de début de l'épilepsie était positivement corrélé avec la sélection d'un traitement orthodoxe comme choix de soins, tandis que le statut professionnel était négativement corrélé avec la sélection de soins orthodoxes au même moment. CONCLUSIONS: Les comportements de recherche de soins parmi les personnes vivant avec l'épilepsie dans le sud-est du Nigeria ont peut-être changé au fil des ans, car davantage de personnes vivant avec l'épilepsie étaient plus susceptibles de choisir un traitement orthodoxe par rapport aux moyens de traitement non orthodoxes. MOTS-CLÉS: Épilepsie, Comportement de recherche de soins, Guérisseurs traditionnels, Lieux de prière, Médecine orthodoxe, sud-est du Nigeria.

CLEAR Thrombectomy Score: An Index to Estimate the Probability of Good Functional Outcome With or Without Endovascular Treatment in the Late Window for Anterior Circulation Occlusion.

BACKGROUND: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management. METHODS AND RESULTS: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90-day functional independence (modified Rankin Scale score 0-2), poor outcome (modified Rankin Scale score 5-6), and 90-day survival. The score was externally validated with a single-center cohort (2014-2023). Of the 3231 included patients (n=2499 EVT), a 9-point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70-0.74) and 0.87 (95% CI, 0.84-0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66-0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all Pinteraction<0.001), with greater benefit favoring patients with lower and midrange scores. CONCLUSIONS: This score is a pragmatic tool that can estimate the probability of a good outcome with EVT in the late window. REGISTRATION: URL: https://www.Clinicaltrials.gov; Unique identifier: NCT04096248.

Short- and long-term effects of imatinib in hospitalised COVID-19 patients: A randomised trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

Identification of new benzofuran derivatives as STING agonists with broad-spectrum antiviral activity.

The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-ß promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-ß transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC50 values in the µM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN-dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING-dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals.

Energy and protein levels in dairy cow diets to recover milk ethanol stability.

The objective of this study was to evaluate the effect of energy and protein in the diet on the recovery of milk ethanol stability (MES) induced by feed restriction. Twelve Holstein and Holstein x Jersey crossbred cows with an average of 146 ± 50 d in milk, 575.4 ± 70 kg of body weight, and 18.93 ± 5.46 kg/d of milk yield were distributed in a 3x3 Latin square design with 3 treatments and 3 experimental periods. Each experimental period lasted 24 d, comprising 3 phases: a 13-d adaptation phase (100E+100P), a 4-d induction phase for milk ethanol instability (50E+50P), and a 7-d recovery phase for MES (3 treatments). The 3 treatments during the recovery phase consisted of 3 diets aiming to meet the requirements of energy and protein (100E+100P), only energy (100E+50P), or only protein (50E+100P). The diet during the adaptation and induction phases was common for all cows. The energy and protein levels to meet each cow's requirements were based on the group average. Restriction of energy and protein reduced dry matter, crude protein, and total digestive nutrient intake for cows fed 100E+50P and 50E+100P. The lowest body weight was observed for cows fed 50E+100P, with no difference for body condition score. During the induction phase, MES "was" reduced by 9 percentage units. Cows fed 100E+100P recovered MES in the first days of the recovery phase, while 100E+50P slightly improved MES, and 50E+100P had a constant decrease in MES. Cows fed 100E+50P and 50E+100P produced, respectively, 3.6 and 5.9 kg less milk than those fed 100E+100P. The 50E+100P treatment exhibited the highest milk fat content and somatic cell score, along with the lowest milk lactose content. Protein content was higher in the 100E+100P treatment. Cows fed 50E+100P showed higher serum albumin levels compared with those on the 100E+100P treatment, not differing from the 100E+50P treatment. We concluded that the complete recovery of MES in cows with feed restrictions is possible only by supplying both the energy and protein requirements in the cows' diet. However, restricting energy intake poses a greater limitation on MES recovery compared with restricting protein.

Dynamics and features of transmission clusters of HIV-1 subtypes in the state of São Paulo, Brazil.

Background: Molecular epidemiology techniques allow us to track the HIV-1 transmission dynamics. Herein, we combined genetic, clinical and epidemiological data collected during routine clinical treatment to evaluate the dynamics and characteristics of transmission clusters of the most prevalent HIV-1 subtypes in the state of São Paulo, Brazil. Methods: This was a cross-sectional study conducted with 2,518 persons living with HIV (PLWH) from 53 cities in São Paulo state between Jan 2004 to Feb 2015. The phylogenetic tree of protease/reverse transcriptase (PR/RT) regions was reconstructed by PhyML and ClusterPicker used to infer the transmission clusters based on Shimodaira-Hasegawa (SH) greater than 90% (phylogenetic support) and genetic distance less than 6%. Results: Of a total of 2,518 sequences, 2,260 were pure subtypes at the PR/RT region, being B (88%), F1 (8.1%), and C (4%). About 21.2% were naïve with a transmitted drug resistance (TDR) rate of 11.8%. A total of 414 (18.3%) of the sequences clustered. These clusters were less evident in subtype B (17.7%) and F1 (15.1%) than in subtype C (40.2%). Clustered sequences were from PLWH at least 5 years younger than non-clustered among subtypes B (p < 0.001) and C (p = 0.037). Men who have sex with men (MSM) predominated the cluster in subtype B (51%), C (85.7%), and F1 (63.6%; p < 0.05). The TDR rate in clustered patients was 15.4, 13.6, and 3.1% for subtypes B, F1, and C, respectively. Most of the infections in subtypes B (80%), C (64%), and F1 (59%) occurred within the state of São Paulo. The metropolitan area of São Paulo presented a high level of endogenous clustering for subtypes B and C. The São Paulo city had 46% endogenous clusters of subtype C. Conclusion: Our findings showed that MSM, antiretroviral therapy in Treatment-Naive (ART-naïve) patients, and HIV1-C, played an important role in the HIV epidemic in the São Paulo state. Further studies in transmission clusters are needed to guide the prevention intervention.

Assessment of health problems of sheep and goats based on ante-mortem and post-mortem inspection at Addis Ababa Abattoir, Ethiopia.

Introduction: Ethiopia has a rapidly growing small ruminant sector, which faces low productivity due to husbandry practices and poor health condition of the animals. A study was conducted in Ethiopia's largest municipal abattoir with the objective to assess the health problems of sheep and goats presented for slaughter using standard ante-mortem and post-mortem methodology. Methods: A cross-sectional study using systematic random sampling was conducted on 384 sheep and 384 goats from January to July 2014. Results: Soiled skin (69.1%), poor body condition (24.3%), and nostril discharge (19.5%) were common among both species at ante-mortem examination. Gross lesions were frequent in livers (39.7%) and lungs (37.2%), while pneumonia (18.1%) and adhesions (13.8%) were frequent in the lungs of sheep and goats, indicating stress-related illness. Parasitic lesions, especially fasciolosis (19.3%) and hydatid cysts (8.1%) were significantly more common in sheep livers (p 0.05). The direct financial loss from lesions in both species was 1,077,015 ETB or 53,851 USD per year, most of which was estimated to occur from carcass bruising. Discussion: The findings indicate that reducing parasite burden and preventing carcass bruising through improved handling could significantly increase the profitability of the small ruminant meat sector in Ethiopia.

Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line.

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.

Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Endovascular Thrombectomy Versus Intravenous Thrombolysis of Posterior Cerebral Artery Occlusion Stroke.

BACKGROUND AND PURPOSE: Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone. METHODS: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0-1) and independent outcome (mRS 0-2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment. RESULTS: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3-P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79-1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05-2.12), sICH (aOR 2.87, 95% CI 1.23-6.72), and mortality (aOR 1.77, 95% CI 1.07-2.95). CONCLUSION: Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

BACKGROUND AND PURPOSE: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. METHODS: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). RESULTS: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). CONCLUSION: A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Abundant hydrocarbons in the disk around a very-low-mass star.

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

Short-term effects of the strengthening families Program (SFP 10-14) in Brazil: a cluster randomized controlled trial.

INTRODUCTION: This study reports the evaluation of the short-term effects of the Strengthening Families Program (SFP 10-14), adapted as Famílias Fortes (Strong Families) in Brazil, on preventing adolescent drug use and improving parenting behaviors. METHODS: A two-arm, parallel cluster randomized controlled trial was conducted in 60 Social Assistance Reference Centers (SARC) from 12 Brazilian municipalities. In each city, the SARC were randomly assigned to the intervention or control group. A total of 805 families participated in the study, each contributing data from one parent or legal guardian and one adolescent totaling 1,610 participants. Data collection occurred before intervention implementation and 6 months after baseline collection. Data were analyzed using multilevel mixed-effects modeling with repeated measures in two different paradigms: Intention to Treat (ITT) and Per protocol (PP). The study was registered in the Brazilian Ministry of Health Register of Clinical Trials (REBEC), under protocol no. RBR-5hz9g6z. RESULTS: Considering the ITT paradigm, the program reduced the chance of parents and legal guardians being classified as negligent by 60% (95%CI 0.21; 0.78), increased the use of nonviolent discipline by caregivers (Coef 0.33, 95%CI 0.01; 0.64) and decreased the chance of adults exposing adolescents to their drunken episodes by 80% (95%CI 0.06; 0.54). No program effects were observed on outcomes related to adolescent drug use. Similar results were found for the PP paradigm. CONCLUSION: The positive effects on family outcomes suggest preventive potential of the program among the Brazilian population. Long-term evaluations are necessary to verify if the program can also achieve the drug use reduction goals not observed in the short term.

Endovascular therapy of isolated posterior cerebral artery occlusion stroke with and without general anesthesia.

BACKGROUND: The optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA). METHODS: Patients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality. RESULTS: Among 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups. CONCLUSION: In patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar.

Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes.

BACKGROUND: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. OBJECTIVE: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. STUDY DESIGN: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. LEVEL OF EVIDENCE: Level 3. RESULTS: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. CONCLUSION: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. CLINICAL RELEVANCE: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.

Low phase noise cavity transmission self-injection locked diode laser system for atomic physics experiments.

Lasers with high spectral purity are indispensable for optical clocks and for the coherent manipulation of atomic and molecular qubits in applications such as quantum computing and quantum simulation. While the stabilization of such lasers to a reference can provide a narrow linewidth, the widely used diode lasers exhibit fast phase noise that prevents high-fidelity qubit manipulation. In this paper, we demonstrate a self-injection locked diode laser system that utilizes a high-finesse cavity. This cavity not only provides a stable resonance frequency, it also acts as a low-pass filter for phase noise beyond the cavity linewidth of around 100 kHz, resulting in low phase noise from dc to the injection lock limit. We model the expected laser performance and benchmark it using a single trapped 40Ca+-ion as a spectrum analyzer. We show that the fast phase noise of the laser at relevant Fourier frequencies of 100 kHz to >2 MHz is suppressed to a noise floor of between -110 dBc/Hz and -120 dBc/Hz, an improvement of 20 to 30 dB over state-of-the-art Pound-Drever-Hall-stabilized extended-cavity diode lasers. This strong suppression avoids incoherent (spurious) spin flips during manipulation of optical qubits and improves laser-driven gates when using diode lasers in applications involving quantum logic spectroscopy, quantum simulation, and quantum computation.

Charge density waves tuned by biaxial tensile stress.

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature Tc displays a linear dependence with a / c - 1 while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and Tc in RTe3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter.