Evaluation of the antioxidant and antityrosinase activities of Prosopis juliflora fruit extract as a novel multifunctional bioactive ingredient and its potential applicability in pro-ageing and skin colour harmonization cosmetic products.

OBJECTIVE: Prosopis juliflora, commonly known as algaroba or mesquite, was introduced and has since proliferated throughout the semi-arid region of the Caatinga biome. Various studies have documented its properties, including antimicrobial, antioxidant, and antitumor activities, attributed to the presence of diverse secondary metabolites such as alkaloids, terpenoids, tannins, and flavonoids. The objective of this study was to evaluate the antioxidant and antityrosinase activities of P. juliflora fruit extract as a multifunctional active ingredient, and to develop cosmetic formulations containing this vegetal extract for potential applications in skincare products targeting pro-ageing and skin colour homogenization properties. METHODS: The extraction process followed established protocols. Chemical characterization of the extract involved quantification of total flavonoids and phenolic compounds, along with Liquid Chromatography-Mass Spectrometry (LC-MS) analysis. In vitro antioxidant activity was assessed using different methods. Antityrosinase activity was determined by employing enzymatic assays. Cosmetic formulations containing Disodium EDTA, Phenoxyethanol (and) Ethylhexyl Glycerin, Distilled Water, Sodium Acrylates Copolymer Lecithin, Polyacrylamide (and) C13-14 Isoparaffin (and) Laureth-7, and 3.0% of the investigated plant extract were subjected to preliminary and accelerated stability tests. RESULTS: The extract demonstrated a concentration of total flavonoids (1.71 ± 0.26 µg EQ/mg) and exhibited concentrations of phenolic compounds at 0.21 ± 0.01 mg EAG/g. Metabolites such as flavonoids and saponins were annotated, as well as some of their respective glycosidic derivatives. The extract showed antioxidant potential and the ability to inhibit the oxidation cascade in both the initiation and propagation phases. Moreover, the extract exhibited noteworthy inhibition of antityrosinase activity, presenting 62.48 ± 2.09 at a concentration of 30.00 mg/mL. The formulations were stable in accelerated stability tests over a 60-day period. CONCLUSION: This research not only demonstrates scientifically by demonstrating the potential of a plant from the Caatinga biome with antioxidant and antityrosinase properties in the development of cosmetic products aimed at pro-ageing effects and skin colour harmonization, but also adds value to the P. juliflora production chain. This valorization encompasses various aspects which include environmental, social, and biodiversity responsibilities.

OBJECTIF: Prosopis juliflora, communément appelée algaroba ou mesquite, a été introduite et s'est depuis proliférée dans la région semi­aride du biome de la Caatinga. Diverses études ont documenté ses propriétés, y compris des activités antimicrobiennes, antioxydantes et antitumorales, attribuées à la présence de divers métabolites secondaires tels que les alcaloïdes, les terpénoïdes, les tanins et les flavonoïdes. L'objectif de cette étude était d'évaluer les activités antioxydantes et antityrosinases de l'extrait de fruit de P. juliflora en tant qu'ingrédient actif multifonctionnel, et de développer des formulations cosmétiques contenant cet extrait végétal pour des applications potentielles dans des produits de soins de la peau ciblant les propriétés anti­âge et d'homogénéisation de la couleur de la peau. MÉTHODES: Le processus d'extraction a suivi des protocoles établis. La caractérisation chimique de l'extrait a impliqué la quantification des flavonoïdes totaux et des composés phénoliques, ainsi qu'une analyse par chromatographie liquide­spectrométrie de masse. L'activité antioxydante in vitro a été évaluée en utilisant différentes méthodes. L'activité antityrosinase a été déterminée en utilisant des essais enzymatiques. Les formulations cosmétiques contenant du Disodium EDTA, du Phenoxyethanol (et) Ethylhexyl Glycerin, de l'Eau Distillée, du Copolymère de Sodium Acrylates Lecithin, du Polyacrylamide (et) C13­14 Isoparaffin (et) Laureth­7, et 3.0 % de l'extrait végétal investigué ont été soumises à des tests de stabilité préliminaires et accélérés. RÉSULTATS: L'extrait a montré une concentration totale de flavonoïdes (1.71 ± 0.26 µg EQ/mg) et des concentrations de composés phénoliques à 0.21 ± 0.01 mg EAG/g. Des métabolites tels que les flavonoïdes et les saponines ont été annotés, ainsi que certains de leurs dérivés glycosidiques respectifs. L'extrait a montré un potentiel antioxydant et la capacité d'inhiber la cascade d'oxydation tant dans les phases d'initiation que de propagation. De plus, l'extrait a présenté une inhibition notable de l'activité antityrosinase, avec un résultat de 62.48 ± 2.09 à une concentration de 30.00 mg/mL. Les formulations ont été stables lors des tests de stabilité accélérés sur une période de 60 jours. CONCLUSION: Cette recherche démontre scientifiquement le potentiel d'une plante du biome de la Caatinga avec des propriétés antioxydantes et antityrosinases dans le développement de produits cosmétiques visant les effets anti­âge et l'harmonisation de la couleur de la peau, tout en ajoutant de la valeur à la chaîne de production de P. juliflora. Cette valorisation englobe divers aspects incluant des responsabilités environnementales, sociales et liées à la biodiversité.

An improved SNAP-ADAR tool enables efficient RNA base editing to interfere with post-translational protein modification.

RNA base editing relies on the introduction of adenosine-to-inosine changes into target RNAs in a highly programmable manner in order to repair disease-causing mutations. Here, we propose that RNA base editing could be broadly applied to perturb protein function by removal of regulatory phosphorylation and acetylation sites. We demonstrate the feasibility on more than 70 sites in various signaling proteins and identify key determinants for high editing efficiency and potent down-stream effects. For the JAK/STAT pathway, we demonstrate both, negative and positive regulation. To achieve high editing efficiency over a broad codon scope, we applied an improved version of the SNAP-ADAR tool. The transient nature of RNA base editing enables the comparably fast (hours to days), dose-dependent (thus partial) and reversible manipulation of regulatory sites, which is a key advantage over DNA (base) editing approaches. In summary, PTM interference might become a valuable field of application of RNA base editing.

Sexual function in patients with bipolar disorder type I evaluated in symptomatic remission: a cross-sectional study.

INTRODUCTION: Bipolar disorder (BD) is a chronic pathology that is associated with several impairments throughout a patient's life, including decreased sexual function. Despite the importance in quality of life (QoL), functionality and medication adherence, it is still little investigated in these patients. OBJECTIVE: To compare the sexual function of patients with Bipolar Disorder type I (BD-I), in remission, with healthy controls (HC) and to investigate the clinical and socio-demographic characteristics associated with sexual function in these individuals. Also, to assess the QoL in patients with and without sexual dysfunction (SD). METHODS: Cross-sectional study with 132 patients with BD-I in euthymic phase and 61 HCs from an outpatient clinic. All the participants were evaluated through the Arizona Sexual Scale (ASEX) and the brief version of the World Health Organization Quality of Life Assessment (WHOQoL-BREF). The patients with BD-I were compared with the HCs. The patients were divided into two groups: the ones diagnosed with SD and the ones without it. RESULTS: The patients with BD-I had higher rates of SD (42.4%) compared to the HCs (16.4%) (OR 3.67, 95% CI 1.55 - 8.67; p=0.003). SD in patients was associated with being women (p=0.001), older age (p=0.003) and having a longer duration of untreated illness (p=0.010). Patients with SD had worse QoL scores compared to those without SD. CONCLUSION: Patients with BD-I have a high prevalence of SD and this was associated with worse QoL scores in all domains.

Sulfonamide resistance evaluation in five animal species and first report of sul4 in companion animals.

Sulfonamides are one of the oldest groups of antibacterial agents with a broad-spectrum, used as first line treatment in bacterial infections. Their widespread use produced a selective pressure on bacteria, as observed by the high incidence of sulfonamides resistance mainly in Gram negative bacteria isolated from animals. In this research, the presence of sulfonamide resistance genes (sul1, sul2, sul3, and sul4) in phenotypically resistant Escherichia coli isolates has been studied. These genes were amplified in isolates recovered from five animal species, with different interactions to humans: cattle, swine, poultry as livestock, and dogs and cats as companion animals. Isolates were collected according to their phenotypic resistance, and the magnetic bead-based Luminex technology was applied to simultaneously detect sul target genes. The frequency of sul genes was highest in swine, among livestock isolates. The sul1 and sul2 were the most frequently sulfonamide resistance genes detected in all phenotypically resistant isolates. Notably, in companion animals, with a closest interaction with human, sul4 gene was detected. To our knowledge, this is the first report of the presence of sul4 gene in E. coli collected from animals, whereas previously the presence of this gene was reported in environmental, municipal wastewater and human clinical isolates. These results highlighted the importance of continuous antimicrobial resistant genes monitoring in animal species, with a special care to companion animals.

Person-centred care for older adults living with HIV in sub-Saharan Africa.

More than a fifth of people living with HIV in the US President's Emergency Plan for AIDS Relief-supported programmes are older individuals, defined as aged 50 years and older, yet optimal person-centred models of care for older adults with HIV in sub-Saharan Africa, including screening and treatment for geriatric syndromes and common comorbidities associated with ageing, remain undefined. This Position Paper explores the disproportionate burden of comorbidities and geriatric syndromes faced by older adults with HIV, with a special focus on women. We seek to motivate global interest in improving quality of life for older people with HIV by presenting available research and identifying research gaps for common geriatric syndromes, including frailty and cognitive decline, and multimorbidity among older people with HIV in sub-Saharan Africa. We share two successful models of holistic care for older people with HIV that are ongoing in Zimbabwe and Kenya. Lastly, we provide policy, research, and implementation considerations to best serve this growing population.

Detection and genetic characterization of chicken astrovirus and avian nephritis virus from hatchery to farm.

RESEARCH HIGHLIGHTS: Identified the role of the hatchery in astrovirus transmission.Sequenced the avian nephritis virus complete genome.Investigated tissue distribution of astrovirus from egg to chicks.Demonstrated co-infection of ANV/CAstV.

Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Cytokine biomarkers of exacerbations in sputum from Chronic Obstructive Pulmonary Disease patients: a prospective cohort study.

BACKGROUND: We determined the relationships between cytokine expression in sputum and clinical data to characterise and understand Chronic Obstructive Pulmonary Disease (COPD) exacerbations in COPD patients. METHODS: We measured 30 cytokines in 936 sputum samples, collected at stable state (ST) and exacerbation (EX) visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (NCT01360398, www.clinicaltrials.gov). We determined their longitudinal expression and examined differential expression based on disease status or exacerbation type. RESULTS: Of the cytokines, 17 were suitable for analysis. As for disease states, in EX sputum samples, IL-17A, TNF-α, IL-1ß, and IL-10 were significantly increased compared to ST sputum samples, but a logistic mixed model could not predict disease state. As for exacerbation types, bacteria-associated exacerbations showed higher expression of IL-17A, TNF-α, IL-1ß, and IL-1α. IL-1α, IL-1ß, and TNF-α were identified as suitable biomarkers for bacteria-associated exacerbation. Bacteria-associated exacerbations also formed a cluster separate from other exacerbation types in principal component analysis. CONCLUSIONS: Measurement of cytokines in sputum from COPD patients could help identify bacteria-associated exacerbations based on increased concentrations of IL-1α, IL-1ß, or TNF-α. This finding may provide a point-of-care assessment to distinguish a bacterial exacerbation of COPD from other exacerbation types.

A compared histopathological study on kidneys and eye bulbs in distinct clinical presentations of canine leishmaniasis by Leishmania infantum.

Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease.

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

Pre-pregnancy body mass index and caesarean section in Andean women in Peru: a prospective cohort study.

BACKGROUND: During the last two decades, Caesarean section rates (C-sections), overweight and obesity rates increased in rural Peru. We examined the association between pre-pregnancy body mass index (BMI) and C-section in the province of San Marcos, Northern Andes-Peru. METHODS: This is a prospective cohort study. Participants were women receiving antenatal care in public health establishments from February 2020 to January 2022, who were recruited and interviewed during pregnancy or shortly after childbirth. They answered a questionnaire, underwent a physical examination and gave access to their antenatal care card information. BMI was calculated using maternal height, measured by the study team and self-reported pre-pregnancy weight measured at the first antenatal care visit. For 348/965 (36%) women, weight information was completed using self-reported data collected during the cohort baseline. Information about birth was obtained from the health centre's pregnancy surveillance system. Regression models were used to assess associations between C-section and BMI. Covariates that changed BMI estimates by at least 5% were included in the multivariable model. RESULTS: This study found that 121/965 (12.5%) women gave birth by C-section. Out of 495 women with pre-pregnancy normal weight, 46 (9.3%) had C-sections. Among the 335 women with pre-pregnancy overweight, 53 (15.5%) underwent C-sections, while 23 (18.5%) of the 124 with pre-pregnancy obesity had C-sections. After adjusting for age, parity, altitude, food and participation in a cash transfer programme pre-pregnancy overweight and obesity increased the odds of C-section by more than 80% (aOR 1.82; 95% CI 1.16-2.87 and aOR 1.85; 95% CI 1.02-3.38) compared to women with a normal BMI. CONCLUSIONS: High pre-pregnancy BMI is associated with an increased odds of having a C-section. Furthermore, our results suggest that high BMI is a major risk factor for C-section in this population. The effect of obesity on C-section was partially mediated by the development of preeclampsia, suggesting that C-sections are being performed due to medical reasons.

In vitro effects of different ozone preparations on microorganisms responsible for endometritis in the mare.

Infectious endometritis is considered one of the major causes of infertility and it can affect up to 60% of barren mares. It is characterized by the presence of one or more microorganisms in the reproductive tract and it is treated with the administration of antibiotics, ecbolic agents and uterine lavages. Ozone, thanks to its antimicrobial properties that are based on its high oxidative potential, could represent an effective alternative treatment for endometritis. The aim of this study was to test in vitro the bactericidal and fungicidal properties of different ozone formulations, either as gas (experiment 1) or dissolved in two liquid matrices (experiment 2), specifically distilled water or oil (Neozone 4000, Cosmoproject, Parma, Italy), onto 6 different species of microorganisms isolated from mares with clinical endometritis, namely Escherichia coli, Staphylococcus aureus, Streptococcus equi subsp. Zooepidemicus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans. In the first experiment, 3 clinical antibiotic-resistant strains per each species were exposed to different conditions: to O2O3 gas mixtures (15 and 40 µg/ml for 1, 3 and 5 min), to 100 % O2 or left untreated. The results showed a reduction of the microbial count of over 99,9% for every pathogen, time and concentration of O2O3 gas mixtures tested. Furthermore, gaseous ozone showed both a time-dependant effect (5 vs 3 vs 1 min of exposure) and a concentration-dependant effect (40 vs 15 µg/ml) at 1 and 3 min, while after 5 min no differences were observed. In the second experiment, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration (MBC, MFC) of ozonated distilled water and ozonated oil were evaluated. Ozonated oil showed a bactericidal/fungicidal activity against all the strains tested (MIC range 12.5-25 % v/v, MBC/MFC range 12.5-50 % v/v) while ozonated distilled water didn't show an observable antimicrobial effect, discouraging its use as an antimicrobial agent for the treatment of endometritis. The results of this in vitro study indicate that both gaseous ozone and ozonated oil exerted remarkable antimicrobial activities and are promising alternative treatments for infectious endometritis, even when caused by antibiotic-resistant bacteria, and encourage further experiments in an effort to scale down or even prevent the use of antibiotics in equine reproduction.

Cognitive domains affected post-COVID-19; a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. METHODS: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection. Studies were deemed high-quality if they had >40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. RESULTS: Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) -0.45), learning and memory (SMD -0.55), complex attention (SMD -0.54) and language (SMD -0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD -0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. CONCLUSIONS: This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment.

Moving from left ventricular ejection fraction to deformation imaging in mitral valve regurgitation.

The increasing prevalence of valvular heart diseases, specifically mitral regurgitation (MR), underscores the need for a careful and timely approach to intervention. Severe MR, whether primary or secondary, when left untreated leads to adverse outcomes, emphasizing the critical role of a timely surgical or transcatheter intervention. While left ventricular ejection fraction (LVEF) remains the guideline-recommended measure for assessing left ventricle damage, emerging evidence raises concerns regarding its reliability in MR due to its volume-dependent nature. This review summarizes the existing literature on the role of LVEF and deformation imaging techniques, emphasizing the latter's potential in providing a more accurate evaluation of intrinsic myocardial function. Moreover, it advocates the need for an integrated approach that combines traditional with emerging measures, aiming to optimize the management of patients with MR. It attempts to highlight the need for future research to validate the clinical application of deformation imaging techniques through large-scale studies.

Recent advances in HIV-associated neurocognitive disorders: a focus on older adults and sub-Saharan Africa.

PURPOSE OF REVIEW: We reviewed recent literature on prevalence and interventional approaches for cognitive impairment in the context of HIV infection alongside current controversies and challenges around its nomenclature, screening, and diagnosis. RECENT FINDINGS: Prevalence estimates for HIV-associated neurocognitive disorder (HAND) indicate that HAND remains highly prevalent despite combination antiretroviral treatment (cART) widely used. The available data are heterogeneous, particularly in sub-Saharan Africa (SSA) where recent reviews indicate substantial heterogeneity, wide prevalence estimates and lack of data from the majority SSA countries, despite them currently experiencing the greatest burden worldwide of both HIV and HAND.Several alternative approaches to diagnosis and classification of cognitive impairment in HIV have been published, taking into account changing clinical phenotypes. SUMMARY: Cognitive impairment remains a significant challenge in the care of people living with HIV despite advances in treatment. Ongoing controversies exist around nomenclature and classification, screening measures, and the phenotype and aetiology of observed impairments. Two current areas of research priority and focus include understanding current phenotypes of individuals living and ageing with treated HIV and differing levels of risk for HAND in these phenotypes, alongside the effects of commonly occurring comorbidities.The current evidence base for interventional approaches is limited, but growing. The most promising avenues appear to be multidisciplinary. These are currently focussed on high income settings rather than SSA where the majority of people living with HIV, and affected by cognitive impairment in the context of HIV, currently reside.

Current perspectives on prevention of vascular cognitive impairment and promotion of vascular brain health.

INTRODUCTION: The true global burden of vascular cognitive impairment (VCI) is unknown. Reducing risk factors for stroke and cardiovascular disease would inevitably curtail VCI. AREAS COVERED: The authors review current diagnosis, epidemiology, and risk factors for VCI. VCI increases in older age and by inheritance of known genetic traits. They emphasize modifiable risk factors identified by the 2020 Lancet Dementia Commission. The most profound risks for VCI also include lower education, cardiometabolic factors, and compromised cognitive reserve. Finally, they discuss pharmacological and non-pharmacological interventions. EXPERT OPINION: By virtue of the high frequencies of stroke and cardiovascular disease the global prevalence of VCI is expectedly higher than prevalent neurodegenerative disorders causing dementia. Since ~ 90% of the global burden of stroke can be attributed to modifiable risk factors, a formidable opportunity arises to reduce the burden of not only stroke but VCI outcomes including progression from mild to the major in form of vascular dementia. Strict control of vascular risk factors and secondary prevention of cerebrovascular disease via pharmacological interventions will impact on burden of VCI. Non-pharmacological measures by adopting healthy diets and encouraging physical and cognitive activities and urging multidomain approaches are important for prevention of VCI and preservation of vascular brain health.

Digital Support Systems to Improve Child Health and Development in Peru: Protocol for a Randomized Controlled Trial.

BACKGROUND: Children living in low and middle-income countries (LMICs) are at greater risk for experiencing adversities that can undermine their health and early development. Recently launched digital early childhood development (ECD) programs attempt to support families with young children in their home environments using digital technologies. However, relatively little is known regarding the effectiveness of these new technologies. OBJECTIVE: The goal of this study is to rigorously assess the reach, effectiveness, and cost-effectiveness of a newly developed digital ECD platform called Afini. The Afini platform was designed to support parents of young children in low-resource settings to improve ECD and interact with caregivers through messenger services and a chatbot. METHODS: This is a 3-arm cluster randomized controlled trial. In total, 2471 caregivers and their 3- to 9-month-old children were enrolled in the study across 164 study clusters in the San Marcos, Cajabamba, and Cajamarca provinces of Peru. Clusters of participants were randomly assigned to 1 of 3 groups: a control group (72 community clusters and 980 caregiver-child dyads), a home visit intervention group (20 community clusters and 316 caregiver-child dyads), and an Afini intervention group (72 community clusters and 1175 caregiver-child dyads). Families in the control group receive no focused ECD intervention. The home visit group is receiving biweekly home visits by a trained field staff following the national ECD program (Programa Nacional Cuna Más) curriculum and training guidelines. Caregivers in the Afini group are receiving ECD activities and advice through the digital platform. The primary study outcome is children's overall development at the age of 2.5 years, using the internationally validated long form of the Global Scales for Early Development. Secondary outcomes include caregiver engagement; caregiver mental health; screen time; as well as caregiver reports of children's motor, cognitive, language, and socioemotional development measured through locally piloted and validated tools. RESULTS: Enrollment started in September 2021 and ended in March 2023. Endline assessments will take place between August 2023 and September 2024. CONCLUSIONS: This study is, to our knowledge, the first to rigorously assess the effectiveness and cost-effectiveness of digital ECD technologies in LMICs. Given the large number of children in LMICs currently receiving only limited external support, the evaluated platform has the potential to improve the short- and long-term well-being of millions of children and their parents globally. TRIAL REGISTRATION: ClinicalTrials.gov NCT05202106; https://clinicaltrials.gov/ct2/show/NCT05202106. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50371.

Influence of concentration, irrigation method, and root canal third on intratubular penetration of sodium hypochlorite - a broad statistical analysis.

Background: The permanence of microorganisms in the root canal system represents the main cause of endodontic failure. Considering the impossibility of effective action of the endodontic files in ramifications of the main canal and mainly inside the dentinal tubules, a better understanding of the irrigation dynamics to enhance endodontic prognosis is essential. Objective: To evaluate the depth of intratubular penetration values of sodium hypochlorite (NaOCl) (dependent variable) by comparing different concentrations, methods of irrigation, and root canal thirds (independent variables) and to investigate the existence of interactions among them, capable of influencing the dependent variable. Material and Methods: 40 roots from extracted human maxillary central incisors were stained and instrumented according to four irrigation protocols (n. 10): conventional irrigation (CI) at each use or change of instrument, and final irrigation with 5ml of 2.5% or 5.25% NaOCl, with or without passive ultrasonic irrigation (PUI), respectivelly. Measurements based on stereomicroscopic images were obtained, and the data were subjected to statistical analysis (p< 0.05). Results: The highest depth values of intratubular penetration of NaOCl were observed in the cervical third, at 5.25%, and by PUI. When only two independent variables were analyzed in association, the highest penetration depth values of NaOCl were obtained at 5.25%, regardless of irrigation method, at 5,25%, in the cervical third, and; in the cervical third, despite of irrigation method. Considering the three independent variables simultaneously, the highest depth values of intratubular penetration of NaOCl were observed in the cervical third, at 5.25%, no matter the irrigation method. The interaction between the independent variables on the penetration depth values of NaOCl was only confirmed considering the irrigation method and root canal third. Conclusions: Intratubular penetration of NaOCl was influenced by the three independent variables individually and when the irrigation method and root canal third were considered simultaneously. Key words:Dentinal tubules, Depth, Disinfection, Irrigation, Root canal system, Sodium hypochlorite.