Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii.

Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)-based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.

Changing Clinical Epidemiology of Plasmodium vivax Malaria as Transmission Decreases: Population-Based Prospective Panel Survey in the Brazilian Amazon.

BACKGROUND: Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear. METHODS: We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention. RESULTS: We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission. CONCLUSIONS: P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases.

Characterization of antimalarial activity of artemisinin-based hybrid drugs.

In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed, and their activity profile was characterized against drug-sensitive and drug-resistant Plasmodium falciparum parasites. Two hybrids were found to display parasite growth reduction, stage-specificity, speed of activity, additivity of activity in drug combinations, and stability in hepatic microsomes of similar levels to those displayed by dihydroartemisinin (DHA). Conversely, the rate of chemical homolysis of the peroxide bonds is slower in hybrids than in DHA. From a mechanistic perspective, heme plays a central role in the chemical homolysis of peroxide, inhibiting heme detoxification and disrupting parasite heme redox homeostasis. The hybrid exhibiting slow homolysis of peroxide bonds was more potent in reducing the viability of ART-resistant parasites in a ring-stage survival assay than the hybrid exhibiting fast homolysis. However, both hybrids showed limited activity against ART-induced quiescent parasites in the quiescent-stage survival assay. Our findings are consistent with previous results showing that slow homolysis of peroxide-containing drugs may retain activity against proliferating ART-resistant parasites. However, our data suggest that this property does not overcome the limited activity of peroxides in killing non-proliferating parasites in a quiescent state.

Influence of sex on chronic steroid-induced glaucoma: 24-Weeks follow-up study in rats.

The objective was to evaluate ocular changes based on sex in steroid-induced glaucoma models in rats comparing healthy controls, over 24 weeks follow-up. Eighty-nine Long-Evans rats (38 males and 51 females) with steroid-induced glaucoma were analysed. Two steroid-induced glaucoma models were generated by injecting poly-co-lactic-glycolic acid microspheres loaded with dexamethasone (MMDEX model) and dexamethasone-fibronectin (MMDEXAFIBRO model) into the ocular anterior chamber. Intraocular pressure was measured by rebound tonometer Tonolab®. Neuroretinal function was analysed using dark- and light-adapted electroretinography (Roland consult® RETIanimal ERG), and structure was analysed using optical coherence tomography (OCT Spectralis, Heidelberg® Engineering) using Retina Posterior Pole, Retinal Nerve Fibre Layer and Ganglion Cell Layer protocols over 24 weeks. Males showed statistically (p < 0.05) higher intraocular pressure measurements. In both sexes and models neuroretinal thickness tended to decrease over time. In the MMDEX model, males showed higher IOP values and greatest percentage thickness loss in the Ganglion Cell Layer (p = 0.015). Females receiving MMDEXAFIBRO experienced large fluctuations in thickness, a higher percentage loss (on average) in Retina Posterior Pole (p = 0.035), Retinal Nerve Fibre Layer and Ganglion Cell Layer than aged-matched males, and the highest thickness loss rate by mmHg. Although no difference was found by sex in dark- and light-adapted electroretinography, increased amplitude in photopic negative response was found in MMDEX males and MMDEXAFIBRO females at 12 weeks. Although both glaucoma models used dexamethasone, different intraocular pressure and neuroretinal changes were observed depending on sex and other influential cofactors (fibronectin). Both sex and the induced glaucoma model influenced neuroretinal degeneration.

Mean age and body mass index at type 2 diabetes diagnosis: Pooled analysis of 56 health surveys across income groups and world regions.

BACKGROUND: Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young-onset T2DM and T2DM patients with lean phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2 ) at T2DM diagnosis in 56 countries. METHODS: Descriptive cross-sectional analysis of WHO STEPS surveys. We analysed adults (25-69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five-year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories. RESULTS: There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25-29 years and 8.5% were 30-34 years old; in women, 8.6% and 12.5% were 25-29 years and 30-34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category. CONCLUSIONS: A non-negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults.

Systematic review and meta-analysis of randomized controlled trials on the effects of exercise interventions on amyloid beta levels in humans.

Alzheimer's disease (AD) represents the most common type of dementia. A crucial mechanism attributed to its development is amyloid beta (Aß) dynamics dysregulation. The extent to which exercise can modulate this phenomenon is uncertain. The aim of this study was to summarize the existing literature evaluating this issue. A comprehensive systematic search was performed in Pubmed, Scopus, Embase, Web of Science, and SciELO databases and completed in August 2023, aiming to identify randomized controlled trials investigating the effect of exercise upon Aß-related pathology. The keywords "exercise" and "amyloid beta", as well as all their equivalents and similar terms, were used. For the analysis, the negative or positive dementia status of the subjects was initially considered and then the soluble amyloid precursor protein (sAPP) components and Aß fragments separately. A meta-analysis was performed and involved eight studies (moderate-to-high quality) and 644 assessments, which were 297 for control and 347 for exercise. No overall effect favoring exercise interventions was observed for both negative (SMD95%=0,286 [-0,131; 0,704]; p = 0,179) or positive AD dementia status (SMD95%=0,110 [-0,155; 0,375]; p = 0,416). The absence of an overall effect favoring exercise interventions was also found for Aß peptides (SMD95%=0,226 [-0,028; 0,480]; p = 0,081) and for sAPP components (SMD95%=-0,038 50 [-0,472; 0,396]; p = 0,863) levels. Our findings suggest that exercise interventions do not improve Aß-related pathology in both healthy individuals and individuals with dementia (SMD95%=0,157 [-0,059; 0,373]; p = 0,155), indicating that the beneficial effects of exercise for AD reported in previous studies are related to other mechanistic effects rather than direct amyloid effects (PROSPERO registration number: CRD42023426912).

Identifying intraoperative events in a simulated laparotomy video: a multinational study of inattentional blindness among anesthesiologists.

PURPOSE: Medical errors may be occasionally explained by inattentional blindness (IB), i.e., failing to notice an event/object that is in plain sight. We aimed to determine whether age/experience, restfulness/fatigue, and previous exposure to simulation education may affect IB in the anesthetic/surgical setting. METHODS: In this multicentre/multinational study, a convenience sample of 280 anesthesiologists watched an attention-demanding video of a simulated trauma patient undergoing laparotomy and (independently/anonymously) recorded the abnormalities they noticed. The video contained four expected/common abnormalities (hypotension, tachycardia, hypoxia, hypothermia) and two prominently displayed unexpected/rare events (patient's head movement, leaky central venous line). We analyzed the participants' ability to notice the expected/unexpected events (primary outcome) and the proportion of expected/unexpected events according to age group and prior exposure to simulation education (secondary outcomes). RESULTS: Anesthesiologists across all ages noticed fewer unexpected/rare events than expected/common ones. Overall, younger anesthesiologists missed fewer common events than older participants did (P = 0.02). There was no consistent association between age and perception of unexpected/rare events (P = 0.28), although the youngest cohort (< 30 yr) outperformed the other age groups. Prior simulation education did not affect the proportion of misses for the unexpected/rare events but was associated with fewer misses for the expected/common events. Self-perceived restfulness did not impact perception of events. CONCLUSION: Anesthesiologists noticed fewer unexpected/rare clinical events than expected/common ones in an attention-demanding video of a simulated trauma patient, in keeping with IB. Prior simulation training was associated with an improved ability to notice anticipated/expected events, but did not reduce IB. Our findings may have implications for understanding medical mishaps, and efforts to improve situational awareness, especially in acute perioperative and critical care settings.

RéSUMé: OBJECTIF: Les erreurs médicales peuvent parfois s'expliquer par la cécité d'inattention, soit le fait de ne pas remarquer un événement/objet qui est à la vue de tous et toutes. Notre objectif était de déterminer si l'âge/l'expérience, le repos/la fatigue et l'exposition antérieure à l'enseignement par simulation pouvaient affecter la cécité d'inattention dans le cadre de l'anesthésie/chirurgie. MéTHODE: Dans cette étude multicentrique/multinationale, un échantillon de convenance de 280 anesthésiologistes ont visionné une vidéo exigeant l'attention portant sur un patient de trauma simulé bénéficiant d'une laparotomie et ont enregistré (de manière indépendante/anonyme) les anomalies qu'ils et elles ont remarquées. La vidéo contenait quatre anomalies attendues/courantes (hypotension, tachycardie, hypoxie, hypothermie) et deux événements inattendus/rares bien en vue (mouvement de la tête du patient, fuite du cathéter veineux central). Nous avons analysé la capacité des participant·es à remarquer les événements attendus/inattendus (critère d'évaluation principal) et la proportion d'événements attendus/inattendus selon le groupe d'âge et l'exposition antérieure à l'enseignement par simulation (critères d'évaluation secondaires). RéSULTATS: Les anesthésiologistes de tous âges ont remarqué moins d'événements inattendus/rares que d'événements attendus/courants. Globalement, les anesthésiologistes plus jeunes ont manqué moins d'événements courants que leurs congénères plus âgé·es (P = 0,02). Il n'y avait pas d'association constante entre l'âge et la perception d'événements inattendus ou rares (P = 0,28), bien que la cohorte la plus jeune (< 30 ans) ait surpassé les autres groupes d'âge. La formation antérieure par simulation n'a pas eu d'incidence sur la proportion d'inobservation des événements inattendus ou rares, mais a été associée à moins de cécité d'inattention envers les événements attendus ou courants. Le repos perçu n'a pas eu d'impact sur la perception des événements. CONCLUSION: Les anesthésiologistes ont remarqué moins d'événements cliniques inattendus/rares que d'événements attendus/courants dans une vidéo exigeant l'attention portant sur la simulation d'un patient traumatisé, ce qui s'inscrit dans la cécité d'inattention. La formation préalable par simulation était associée à une meilleure capacité à remarquer les événements anticipés/attendus, mais ne réduisait pas la cécité d'inattention. Nos résultats peuvent avoir des implications pour la compréhension des accidents médicaux et les efforts visant à améliorer la conscience situationnelle, en particulier dans les contextes de soins périopératoires aigus et de soins intensifs.

Altered sense of self during seizures in the posteromedial cortex.

The posteromedial cortex (PMC) is known to be a core node of the default mode network. Given its anatomical location and blood supply pattern, the effects of targeted disruption of this part of the brain are largely unknown. Here, we report a rare case of a patient (S19_137) with confirmed seizures originating within the PMC. Intracranial recordings confirmed the onset of seizures in the right dorsal posterior cingulate cortex, adjacent to the marginal sulcus, likely corresponding to Brodmann area 31. Upon the onset of seizures, the patient reported a reproducible sense of self-dissociation-a condition he described as a distorted awareness of the position of his body in space and feeling as if he had temporarily become an outside observer to his own thoughts, his "me" having become a separate entity that was listening to different parts of his brain speak to each other. Importantly, 50-Hz electrical stimulation of the seizure zone and a homotopical region within the contralateral PMC induced a subjectively similar state, reproducibly. We supplement our clinical findings with the definition of the patient's network anatomy at sites of interest using cortico-cortical-evoked potentials, experimental and resting-state electrophysiological connectivity, and individual-level functional imaging. This rare case of patient S19_137 highlights the potential causal importance of the PMC for integrating self-referential information and provides clues for future mechanistic studies of self-dissociation in neuropsychiatric populations.

Exploring the impact of high-energy diets on cattle: Insights into subacute rumen acidosis, insulin resistance, and hoof health.

Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows, but their correlation with high-energy diets and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high-starch diet and a conventional diet on the rumen environment, acute-phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. A total of 16 animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood analyses, rumen fluid analyses, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating SARA. The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. We found a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Because both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Recognition of Patient Gender: A Machine Learning Preliminary Analysis Using Heart Sounds from Children and Adolescents.

Research has shown that X-rays and fundus images can classify gender, age group, and race, raising concerns about bias and fairness in medical AI applications. However, the potential for physiological sounds to classify sociodemographic traits has not been investigated. Exploring this gap is crucial for understanding the implications and ensuring fairness in the field of medical sound analysis. We aimed to develop classifiers to determine gender (men/women) based on heart sound recordings and using machine learning (ML). Data-driven ML analysis. We utilized the open-access CirCor DigiScope Phonocardiogram Dataset obtained from cardiac screening programs in Brazil. Volunteers < 21 years of age. Each participant completed a questionnaire and underwent a clinical examination, including electronic auscultation at four cardiac points: aortic (AV), mitral (MV), pulmonary (PV), and tricuspid (TV). We used Mel-frequency cepstral coefficients (MFCCs) to develop the ML classifiers. From each patient and from each auscultation sound recording, we extracted 10 MFCCs. In sensitivity analysis, we additionally extracted 20, 30, 40, and 50 MFCCs. The most effective gender classifier was developed using PV recordings (AUC ROC = 70.3%). The second best came from MV recordings (AUC ROC = 58.8%). AV and TV recordings produced classifiers with an AUC ROC of 56.4% and 56.1%, respectively. Using more MFCCs did not substantially improve the classifiers. It is possible to classify between males and females using phonocardiogram data. As health-related audio recordings become more prominent in ML applications, research is required to explore if these recordings contain signals that could distinguish sociodemographic features.

The spark of synchronization in heterogeneous networks of chaotic maps.

We investigate the emergence of synchronization in heterogeneous networks of chaotic maps. Our findings reveal that a small cluster of highly connected maps is responsible for triggering the spark of synchronization. After the spark, the synchronized cluster grows in size and progressively moves to less connected maps, eventually reaching a cluster that may remain synchronized over time. We explore how the shape of the network degree distribution affects the onset of synchronization and derive an expression based on the network construction that determines the expected time for a network to synchronize. Understanding how the network design affects the spark of synchronization is particularly important for the control and design of more robust systems that require some level of coherence between a subset of units for better functioning. Numerical simulations in finite-sized networks are consistent with this analysis.

Transport Properties in Multicomponent Systems Containing Cyclodextrins and Nickel Ions.

In this work, we propose a comprehensive experimental study of the diffusion of nickel ions in combination with different cyclodextrins as carrier molecules for enhanced solubility and facilitated transport. For this, ternary mutual diffusion coefficients measured by Taylor dispersion method are reported for aqueous solutions containing nickel salts and different cyclodextrins (that is, α-CD, ß-CD, and γ-CD) at 298.15 K. A combination of Taylor dispersion and other methods, such as UV-vis spectroscopy, will be used to obtain complementary information on these systems. The determination of the physicochemical properties of these salts with CDs in aqueous solution provides information that allows us to understand solute-solvent interactions, and gives a significant contribution to understanding the mechanisms underlying diffusional transport in aqueous solutions, and, consequently, to mitigating the potential toxicity associated with these metal ions. For example, using mutual diffusion data, it is possible to estimate the number of moles of each ion transported per mole of the cyclodextrin driven by its own concentration gradient.

Preserved Motility after Neonatal Dopaminergic Lesion Relates to Hyperexcitability of Direct Pathway Medium Spiny Neurons.

In Parkinson's disease patients and rodent models, dopaminergic neuron loss (DAN) results in severe motor disabilities. In contrast, general motility is preserved after early postnatal DAN loss in rodents. Here we used mice of both sexes to show that the preserved motility observed after early DAN loss depends on functional changes taking place in medium spiny neurons (MSN) of the dorsomedial striatum (DMS) that belong to the direct pathway (dMSN). Previous animal model studies showed that adult loss of dopaminergic input depresses dMSN response to cortical input, which likely contributes to Parkinson's disease motor impairments. However, the response of DMS-dMSN to their preferred medial PFC input is preserved after neonatal DAN loss as shown by in vivo studies. Moreover, their response to inputs from adjacent cortical areas is increased, resulting in reduced cortical inputs selectivity. Additional ex vivo studies show that membrane excitability increases in dMSN. Furthermore, chemogenetic inhibition of DMS-dMSN has a more marked inhibitory effect on general motility in lesioned mice than in their control littermates, indicating that expression of normal levels of locomotion and general motility depend on dMSN activity after early DAN loss. Contrastingly, DMS-dMSN inhibition did not ameliorate a characteristic phenotype of the DAN-lesioned animals in a marble burying task demanding higher behavioral control. Thus, increased dMSN excitability likely promoting changes in corticostriatal functional connectivity may contribute to the distinctive behavioral phenotype emerging after developmental DAN loss, with implications for our understanding of the age-dependent effects of forebrain dopamine depletion and neurodevelopment disorders.SIGNIFICANCE STATEMENT The loss of striatal dopamine in the adult brain leads to life-threatening motor impairments. However, general motility remains largely unaffected after its early postnatal loss. Here, we show that the high responsiveness to cortical input of striatal neurons belonging to the direct basal ganglia pathway, crucial for proper motor functioning, is preserved after early dopamine neuron loss, in parallel with an increase in these cells' membrane excitability. Chemogenetic inhibition studies show that the preserved motility depends on this direct pathway hyperexcitability/hyperconnectivity, while other phenotypes characteristic of this condition remained unaltered despite the dMSN inhibition. This insight has implications for our understanding of the mechanism underlying the behavioral impairments observed in neuropsychiatric conditions linked to early dopaminergic hypofunction.

Hemispheric Asymmetries of Individual Differences in Functional Connectivity.

Resting-state fMRI studies have revealed that individuals exhibit stable, functionally meaningful divergences in large-scale network organization. The locations with strongest deviations (called network "variants") have a characteristic spatial distribution, with qualitative evidence from prior reports suggesting that this distribution differs across hemispheres. Hemispheric asymmetries can inform us on constraints guiding the development of these idiosyncratic regions. Here, we used data from the Human Connectome Project to systematically investigate hemispheric differences in network variants. Variants were significantly larger in the right hemisphere, particularly along the frontal operculum and medial frontal cortex. Variants in the left hemisphere appeared most commonly around the TPJ. We investigated how variant asymmetries vary by functional network and how they compare with typical network distributions. For some networks, variants seemingly increase group-average network asymmetries (e.g., the group-average language network is slightly bigger in the left hemisphere and variants also appeared more frequently in that hemisphere). For other networks, variants counter the group-average network asymmetries (e.g., the default mode network is slightly bigger in the left hemisphere, but variants were more frequent in the right hemisphere). Intriguingly, left- and right-handers differed in their network variant asymmetries for the cingulo-opercular and frontoparietal networks, suggesting that variant asymmetries are connected to lateralized traits. These findings demonstrate that idiosyncratic aspects of brain organization differ systematically across the hemispheres. We discuss how these asymmetries in brain organization may inform us on developmental constraints of network variants and how they may relate to functions differentially linked to the two hemispheres.

Short-Finned Pilot Whale Strandings Associated with Pilot Whale Morbillivirus, Brazil.

Cetacean morbillivirus (CeMV) causes illness and death in cetaceans worldwide; the CeMV strains circulating in the Southern Hemisphere are poorly known. We detected a pilot whale CeMV strain in 3 short-finned pilot whales (Globicephala macrorhynchus) stranded in Brazil during July-October 2020. Our results confirm this virus circulates in this species.

Effect of lipid oxidation on the channel properties of Cx26 hemichannels: A molecular dynamics study.

Intercellular communication plays a crucial role in cancer, as well as other diseases, such as inflammation, tissue degeneration, and neurological disorders. One of the proteins responsible for this, are connexins (Cxs), which come together to form a hemichannel. When two hemichannels of opposite cells interact with each other, they form a gap junction (GJ) channel, connecting the intracellular space of these cells. They allow the passage of ions, reactive oxygen and nitrogen species (RONS), and signaling molecules from the interior of one cell to another cell, thus playing an essential role in cell growth, differentiation, and homeostasis. The importance of GJs for disease induction and therapy development is becoming more appreciated, especially in the context of oncology. Studies have shown that one of the mechanisms to control the formation and disruption of GJs is mediated by lipid oxidation pathways, but the underlying mechanisms are not well understood. In this study, we performed atomistic molecular dynamics simulations to evaluate how lipid oxidation influences the channel properties of Cx26 hemichannels, such as channel gating and permeability. Our results demonstrate that the Cx26 hemichannel is more compact in the presence of oxidized lipids, decreasing its pore diameter at the extracellular side and increasing it at the amino terminus domains, respectively. The permeability of the Cx26 hemichannel for water and RONS molecules is higher in the presence of oxidized lipids. The latter may facilitate the intracellular accumulation of RONS, possibly increasing oxidative stress in cells. A better understanding of this process will help to enhance the efficacy of oxidative stress-based cancer treatments.

Use of continuous glucose monitors in low- and middle-income countries: A scoping review.

AIMS: The use of continuous glucose monitors (CGMs) has been shown to have positive impact on diabetes management for people with type 1 diabetes (T1DM), type 2 diabetes (T2DM) and gestational diabetes (GDM) in high-income countries. However, as useful as CGMs are, the experience in low- and middle-income countries (LMICs) is limited and has not been summarized. METHODS: A scoping review of the scientific literature was conducted. Medline, Embase, Global Health and Scopus were used to seek original research conducted in LMICs. The search results were screened by two reviewers independently. We included studies assessing health outcomes following the use of CGMs at the individual level (e.g. glycaemic control or complications) and at the health system level (e.g. barriers, facilitators and cost-effectiveness) in English, Portuguese, Spanish and French. Results were summarized narratively. RESULTS: From 4772 records found in database search, 27 reports were included; most of them from China (n = 7), Colombia (n = 5) and India (n = 4). Thirteen reports studied T1DM, five T2DM, seven both T1DM and T2DM and two GDM. Seven reports presented results of experimental studies (five randomized trials and two quasi-experimental); two on cost-effective analysis and the remaining 18 were observational. Studies showed that CGMs improved surrogate glycaemic outcomes (HbA1c reduction), hard endpoints (lower hospitalization rates and diabetes complications) and patient-oriented outcomes (quality of life). However, several caveats were identified: mostly observational studies, few participants in trials, short follow-up and focused on surrogate outcomes. CONCLUSIONS: The scoping review identified that studies about CGMs in LMICs have several limitations. Stronger study designs, appropriate sample sizes and the inclusion of patient-important outcomes should be considered to inform the evidence about CGMs for the management of people with diabetes in LMICs.

Skeletal muscle mass and all-cause mortality: Findings from the CRONICAS cohort study.

OBJECTIVE: We aimed (1) to evaluate the agreement between two methods (equation and bio-impedance analysis [BIA]) to estimate skeletal muscle mass (SMM), and (2) to assess if SMM was associated with all-cause mortality risk in individuals across different geographical sites in Peru. METHODS: We used data from the CRONICAS Cohort Study (2010-2018), a population-based longitudinal study in Peru to assess cardiopulmonary risk factors from different geographical settings. SMM was computed as a function of weight, height, sex and age (Lee equation) and by BIA. All-cause mortality was retrieved from national vital records. Cox proportional-hazard models were developed and results presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: At baseline, 3216 subjects, 51.5% women, mean age 55.7 years, were analysed. The mean SMM was 23.1 kg (standard deviation [SD]: 6.0) by Lee equation, and 22.7 (SD: 5.6) by BIA. Correlation between SMM estimations was strong (Pearson's ρ coefficient = 0.89, p < 0.001); whereas Bland-Altman analysis showed a small mean difference. Mean follow-up was 7.0 (SD: 1.0) years, and there were 172 deaths. In the multivariable model, each additional kg in SMM was associated with a 19% reduction in mortality risk (HR = 0.81; 95% CI: 0.75-0.88) using the Lee equation, but such estimate was not significant when using BIA (HR = 0.98; 95% CI: 0.94-1.03). Compared to the lowest tertile, subjects at the highest SMM tertile had a 56% reduction in risk of mortality using the Lee equation, but there was no such association when using BIA estimations. CONCLUSION: There is a strong correlation and agreement between SMM estimates obtained by the Lee equation and BIA. However, an association between SMM and all-cause mortality exists only when the Lee equation is used. Our findings call for appropriate use of approaches to estimate SMM, and there should be a focus on muscle mass in promoting healthier ageing.

Optimizing the synthesis of dimeric peptides: influence of the reaction medium and effects that modulate kinetics and reaction yield.

Peptides are remarkably interesting alternatives to several applications. In particular, antimicrobial sequences have raised major interest of the scientific community due to the resistance acquired by commonly used antibiotics. Amongst these, some dimeric peptides have shown very promising characteristics as strong biological activities and resistance against degradation by peptidases. However, despite such promising characteristics, a relatively small number of studies address dimeric peptides, mainly due to the synthesis-related obstacles in their production, whereas the well-implemented routines of solid phase peptide synthesis-which includes the possibility of automation-makes life significantly easier. Here, we present kinetic investigations of the dimerization of a cysteine-containing sequence to obtain the homodimeric antimicrobial peptide homotarsinin. Based on the structural and membrane interaction data already available for the dimer and its monomeric chain, we have proposed distinct dimerization protocols in selected environments, namely, aqueous buffer, TFE:H2O and micellar solutions. The experimental results were adjusted by a theoretical model. Both the kinetic profiles and the reaction yields are dependent on the reaction medium, clearly indicating that aggregation, peptide structure, and peptide-membrane interactions play major roles in the formation of the disulfide bond. Finally, the rationalization of the different aspects addressed here is expected to contribute to research and applications that demand the obtainment of dimeric peptides.