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Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBI) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI by employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the closed-head impact model of engineered rotational acceleration (CHIMERA) model, we conducted rmTBIs or sham (control) procedures on young (2.5–3-months-old) and aged (22-months-old) male and female mice to model high-risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposhigh-risking effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBI.

Abstract Introduction Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top‐down behavior control. However, the neurobiological pathways contributing to stress‐induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha‐converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses. Methods We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re‐experiencing of trauma. Results Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle). Conclusion This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.

Abstract Background Traumatic cervical spinal cord injury (SCI) results in reduced sensorimotor abilities that strongly impact on the achievement of daily living activities involving hand/arm function. Among several technology-based rehabilitative approaches, Brain-Computer Interfaces (BCIs) which enable the modulation of electroencephalographic sensorimotor rhythms, are promising tools to promote the recovery of hand function after SCI. The “DiSCIoser” study proposes a BCI-supported motor imagery (MI) training to engage the sensorimotor system and thus facilitate the neuroplasticity to eventually optimize upper limb sensorimotor functional recovery in patients with SCI during the subacute phase, at the peak of brain and spinal plasticity. To this purpose, we have designed a BCI system fully compatible with a clinical setting whose efficacy in improving hand sensorimotor function outcomes in patients with traumatic cervical SCI will be assessed and compared to the hand MI training not supported by BCI. Methods This randomized controlled trial will include 30 participants with traumatic cervical SCI in the subacute phase randomly assigned to 2 intervention groups: the BCI-assisted hand MI training and the hand MI training not supported by BCI. Both interventions are delivered (3 weekly sessions; 12 weeks) as add-on to standard rehabilitation care. A multidimensional assessment will be performed at: randomization/pre-intervention and post-intervention. Primary outcome measure is the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) somatosensory sub-score. Secondary outcome measures include the motor and functional scores of the GRASSP and other clinical, neuropsychological, neurophysiological and neuroimaging measures. Discussion We expect the BCI-based intervention to promote meaningful cortical sensorimotor plasticity and eventually maximize recovery of arm functions in traumatic cervical subacute SCI. This study will generate a body of knowledge that is fundamental to drive optimization of BCI application in SCI as a top-down therapeutic intervention, thus beyond the canonical use of BCI as assistive tool. Trial registration Name of registry: DiSCIoser: improving arm sensorimotor functions after spinal cord injury via brain-computer interface training (DiSCIoser). Trial registration number: NCT05637775; registration date on the ClinicalTrial.gov platform: 05-12-2022.

Abstract Background Electroencephalography (EEG)-based brain-computer interfaces (BCIs) allow to modulate the sensorimotor rhythms and are emerging technologies for promoting post-stroke motor function recovery. The Promotoer study aims to assess the short and long-term efficacy of the Promotoer system, an EEG-based BCI assisting motor imagery (MI) practice, in enhancing post-stroke functional hand motor recovery. This paper details the statistical analysis plan of the Promotoer study. Methods The Promotoer study is a randomized, controlled, assessor-blinded, single-centre, superiority trial, with two parallel groups and a 1:1 allocation ratio. Subacute stroke patients are randomized to EEG-based BCI-assisted MI training or to MI training alone (i.e. no BCI). An internal pilot study for sample size re-assessment is planned. The primary outcome is the effectiveness of the Upper Extremity Fugl-Meyer Assessment (UE-FMA) score. Secondary outcomes include clinical, functional, and user experience scores assessed at the end of intervention and at follow-up. Neurophysiological assessments are also planned. Effectiveness formulas have been specified, and intention-to-treat and per-protocol populations have been defined. Statistical methods for comparisons of groups and for development of a predictive score of significant improvement are described. Explorative subgroup analyses and methodology to handle missing data are considered. Discussion The Promotoer study will provide robust evidence for the short/long-term efficacy of the Promotoer system in subacute stroke patients undergoing a rehabilitation program. Moreover, the development of a predictive score of response will allow transferring of the Promotoer system to optimal clinical practice. By carefully describing the statistical principles and procedures, the statistical analysis plan provides transparency in the analysis of data. Trial registration ClinicalTrials.gov NCT04353297 . Registered on April 15, 2020.

Like most tumors, glioblastoma multiforme (GBM), the deadliest brain tumor in human adulthood, releases extracellular vesicles (EVs). Their content, reflecting that of the tumor of origin, can be donated to nearby and distant cells which, by acquiring it, become more aggressive. Therefore, the study of EV-transported molecules has become very important. Particular attention has been paid to EV proteins to uncover new GBM biomarkers and potential druggable targets. Proteomic studies have mainly been performed by “bottom-up” mass spectrometry (MS) analysis of EVs isolated by different procedures from conditioned media of cultured GBM cells and biological fluids from GBM patients. Although a great number of dysregulated proteins have been identified, the translation of these findings into clinics remains elusive, probably due to multiple factors, including the lack of standardized procedures for isolation/characterization of EVs and analysis of their proteome. Thus, it is time to change research strategies by adopting, in addition to harmonized EV selection techniques, different MS methods aimed at identifying selected tumoral protein mutations and/or isoforms due to post-translational modifications, which more deeply influence the tumor behavior. Hopefully, these data integrated with those from other “omics” disciplines will lead to the discovery of druggable pathways for novel GBM therapies.

Cardiac magnetic resonance (CMR) has acquired a pivotal role in modern cardiology. It represents the gold standard for biventricular volume and systolic function assessment. Moreover, CMR allows for non-invasive myocardial tissue evaluation, highlighting tissue edema, fibrosis, fibro-fatty infiltration and iron overload. This manuscript aims to review the impact of CMR in the main inflammatory and infiltrative cardiomyopathies, providing details on specific imaging patterns and insights regarding the most relevant trials in the setting.

The EU faces two economic challenges: managing non-performing exposures (NPEs) and climate change. This paper analyzes the relationship between the NPEs of domestic banking groups and climate risks, including macroeconomic variables such as the GDP growth rate, unemployment rate (UnEmp), and the voice and accountability percentile (VCA) and the interaction variable between the GHG and the Rule of Law Percentile (GhGRLP). The estimation uses ordinary least squares with time-fixed and individual effects. Physical and transition risks significantly affect NPEs, showing that both adverse climate events and the transition to a low-carbon economy worsen the financial situation of European banking institutions. The analysis also revealed that increased levels of VCA lead to a rise in NPEs, while an increase in GhGRLP reduces NPEs. In contrast, financial institutions tend to recognize and report NPEs more accurately in contexts with greater transparency and accountability. In comparison, UnEmp negatively affects NPEs, suggesting that economic support measures during high unemployment can reduce NPEs in the subsequent period. In conclusion, climate risk management represents a crucial challenge for the financial stability of banking institutions. Policymakers and financial institutions must continue to develop and implement climate change mitigation and adaptation strategies to preserve financial system stability amid growing climate uncertainties.

BackgroundTenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV.MethodsIMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant.ResultsTwenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF.ConclusionTAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.

IntroductionThe differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation.MethodsWe assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics.ResultsOur results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and during re-testing in a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups.DiscussionThe results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.

The Paleocene–Eocene Thermal Maximum (PETM) represents the most pronounced hyperthermal of the Cenozoic era and is hypothesized to have resulted in an intensification of the paleohydrologic cycle, including enhanced seasonality and increased sediment discharge to the coastal ocean. Although the PETM has been widely documented, there are few records from deposits that form the distal, deepwater components of large sediment-routing systems. This study presents new constraints on the stratigraphic placement of the PETM in the deepwater Gulf of Mexico basin through analysis of geochemical, carbon isotopic, and biostratigraphic data within a ∼124 m cored interval of the Wilcox Group. Biostratigraphic and carbon isotopic data indicate that the PETM extends over ∼13 m based on acmes in the dinoflagellate Apectodinium homomorphum and calcareous nannoplankton Rhomboaster cuspis as well as a ∼-2 ‰ shift in bulk organic δ13C values. A decrease in bioturbation and benthic foraminifera suggests that a reduction in oxygen of Gulf of Mexico bottom waters and/or an increase in sedimentation rates were coincident with the onset of the PETM. A ∼2 m lag in the depositional record separates the onset of the PETM negative carbon isotope excursion (CIE) and deposition of a 5.7 m thick interval of organic-lean claystone and marlstone that reflects a shut-off of the supply of sand, silt, and terrestrial palynomorphs to the basin. We interpret deposits of the PETM in the deepwater Gulf of Mexico to reflect the combined effects of increased erosional denudation and rising sea level that resulted in sequestration of sand and silt near the coastline but that allowed delivery of terrigenous mud to the deep sea. The similarity of oceanographic changes observed in the Gulf of Mexico and Atlantic Ocean during the PETM supports the inference that these water masses were connected during latest Paleocene–earliest Eocene times. Although deposition of typical Wilcox Group facies resumed during and after the PETM recovery, an increased influx of terrestrial detritus (i.e., pollen, spores, terrestrial organic debris) relative to marine dinoflagellates is suggestive of long-lasting effects of the PETM. This study illustrates the profound and prolonged effects of climatic warming on even the most distal reaches of large (≥1×106 km2) sediment-routing systems.

Archaeometry can help archaeologists in many ways, and one of the most common archaeometric objectives is provenance analysis. Volcanic rocks are often found in archaeological sites as materials used to make grinding tools such as millstones and mortars or as building materials. Petrographic characterization is commonly applied to identify their main mineralogical components. However, the provenance study of volcanic stones is usually undertaken by comparing geochemical data from reference outcrops using common descriptive statistical tools such as biplots of chemical elements, and occasionally, unsupervised multivariate data analysis like principal component analysis (PCA) is also used. Recently, the use of supervised classification methods has shown a superior performance in assigning provenance to archaeological samples. However, these methods require the use of reference databases for all the possible provenance classes in order to train the classification models. The existence of comprehensive collections of published geochemical analyses of igneous rocks enables the use of the supervised approach for the provenance determination of volcanic stones. In this paper, the provenance of volcanic grinding tools from two archaeological sites (Iulia Libica, Spain, and Sidi Zahruni, Tunisia) is attempted using data from the GEOROC database through unsupervised and supervised approaches. The materials from Sidi Zahruni have been identified as basalts from Pantelleria (Italy), and the agreement between the different supervised classification models tested is particularly conclusive. In contrast, the provenance of the materials from Iulia Libica remained undetermined. The results illustrate the advantages and limitations of all the examined methods.

Background/Objectives: Semaglutide is the unique once-daily oral glucagon-like receptor agonist presently available. Aims of this study were to describe clinical characteristics of patients with type 2 diabetes (T2D) initiating oral semaglutide, to assess its effects on glycemic control, body weight (BW) and its tolerability in routine clinical practice. Methods: Electronic medical records from two Italian diabetes clinics were evaluated. Mean glycated hemoglobin (HbA1c) and BW were assessed in adults with T2D before and 6 months after oral semaglutide prescription. Treatment discontinuation and safety data were reported. Results: A total of 192 patients initiating oral semaglutide (44% female) presented a mean age of 66 years, a diabetes duration of 10 years, HbA1c of 7.9% and a BW of 82.6 kg. Almost 50% of patients were obese. Mean HbA1c and BW changes from baseline to follow up were −0.7% and −2.6 kg, respectively. Greater HbA1c reduction was observed in patients with baseline HbA1c ≥ 8% and with diabetes duration Conclusions: In a real clinical setting, patients initiating oral semaglutide showed suboptimal metabolic control, short diabetes duration and obesity; a significant improvement in HbA1c and BW was achieved mainly in patients with a more recent diabetes diagnosis, supporting the use of oral semaglutide in the early phase of the disease.

Modularity and resilience are fundamental properties of brain network organization and function. The interplay of these network characteristics is integral to understanding brain vulnerability, network efficiency, and neurocognitive disorders. One potential methodology to explore brain network modularity and resilience is through percolation theory, a sub-branch of graph theory that simulates lesions across brain networks. In this work, percolation theory is applied to connectivity matrices derived from functional MRI from human, mice, and null networks. Nodes, or regions, with the highest betweenness centrality, a graph theory quantifier that examines shortest paths, were sequentially removed from the network. This attack methodology led to a rapid fracturing of the network, resulting in two terminal modules connected by one transfer module. Additionally, preceding the rapid network fracturing, the average betweenness centrality of the network peaked in value, indicating a critical point in brain network functionality. Thus, this work introduces a methodological perspective to identify hubs within the brain based on critical points that can be used as an architectural framework for a neural network. By applying percolation theory to functional brain networks through a network phase-transition lens, network sub-modules are identified using local spikes in betweenness centrality as an indicator of brain criticality. This modularity phase transition provides supporting evidence of the brain functioning at a near-critical point while showcasing a formalism to understand the computational efficiency of the brain as a neural network.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.

Background:. We aimed to investigate the effect of compression dressing on edema, ecchymosis, pain, and ocular surface irritation after ptosis surgery. Methods:. After ptosis correction [anterior levator reinsertion (and resection) (ALR), if necessary additional blepharoplasty], the eye was randomized for compression dressing or transparent eye shield. Edema and ecchymosis were scored on a four-point rating scale by a blinded observer 1 day (D1), 1 week (D7), and 8 weeks (D56) after surgery; the same was done for scar formation regarding redness and bulging at D7 and D56. Aesthetic outcome was ranked by patient and blinded observer using the Global Aesthetic Improvement Score at D1, D7, and D56. Postoperative pain was scored using a visual analogue scale (0 to 10) at D1. Impairment after surgery by dressing or eye shield was evaluated at D1. Results:. Ecchymosis, edema, scar formation, and aesthetic outcome ranked by the patient and blinded observer did not differ between the groups with compression dressing and eye shield at any day of follow-up (P > 0.05). Postoperative pain and impairment were the same in both groups (P > 0.05). One case of corneal erosion occurred in the group with compression dressing at D1 (P = 0.342). At D7, corneal staining was increased in the group without compression dressing (P = 0.930). Conclusions:. Compression dressing after ALR does not reduce ecchymosis, edema, or postoperative pain and has no effect on early scar formation or aesthetic results. To prevent corneal erosion caused by the dressing, it can be omitted after ALR without inferiority for the early postoperative results.

Purpose: To analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA). Design: Observational, cross-sectional study. Participants: Thirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan. Methods: Patients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2). Main Outcome Measures: Fixation location and stability. Results: The median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P

ObjectiveTo evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery.DesignNonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States.MethodsIntensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons.ResultsA total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [n = 12, P = 0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (n = 18, P

ObjectiveTo evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics.DesignOpen-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout.MethodsPregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using liquid chromatography/mass spectrometry. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests.ResultsThirty-one pregnant women receiving TAF 10 mg with cobicistat-boosting and 27 women receiving TAF 25 mg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10 mg with cobicistat. Antepartum TAF exposures with the 25 mg dose were 33-43% lower in comparison with postpartum, but comparable with those measured in nonpregnant adults. TAF was below the lower limit of quantitation in 43 of 44 cord blood, 41 of 45 maternal blood at delivery, and all infant washout samples.ConclusionTAF exposures were comparable or higher than those measured in nonpregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.

This article aims to describe Vertical Edgeless Preparation (VEP), a full-crown vertical preparation technique initially introduced by the Porta Mascarella Group in the 1980s. The method is defined as “periodontally driven” because its main indication is teeth with a loss of periodontal attachment, and it aims to obtain healthier periodontal tissues. This work describes the step-by-step procedure for performing this prosthetic technique and its indications, contraindications, impression phases, temporary crown management, and its biological concept of periodontal dominance.

In a European context in which the objectives of climate neutrality and digitalization appear fundamental, the work analyzes the relationships between the price of the main stock market indices and the most representative variables such as carbon emissions, digitalization, use of renewable energy, research and development expenses, environmental taxes, and all economic and management activities aimed at reducing or eliminating any form of pollution. The analysis was developed through three different regressions involving the long period 1995–2020 and the short period 2017–2020. The results show how increasing carbon emissions and environmental taxes positively impact stock indices. The former is linked to an increase in production and, therefore, economic growth, and the latter encourages sustainability. Taxes on transport and energy in the long term generate higher costs, which damage profitability and negatively impact the performance of stock indices. Finally, in the short term, implementing environmental protection measures or the sustainable management of resources may lead to higher operating costs for the companies involved. These cost increases can negatively impact profit margins and reduce the value of companies. These results, therefore, show us how environmental sustainability has a significant impact on European stock markets; consequently, the relevant regulations and policies should also consider the economic and managerial impacts that companies implement to achieve their objectives of the Green Deal.

The significance of Trypanosoma equiperdum as the causative agent of dourine cannot be understated, especially given its high mortality rate among equids. International movement of equids should be subject to thorough health checks and screenings to ensure that animals are not infected with Trypanosoma equiperdum. This involves the implementation of quarantine protocols, testing procedures, and the issuance of health certificates to certify the health status of the animals. Three proteins, the peptidyl-prolyl cis-trans isomerase (A0A1G4I8N3), the GrpE protein homolog (A0A1G4I464) and the transport protein particle (TRAPP) component, putative (A0A1G4I740) (UniProt accession numbers SCU68469.1, SCU66661.1 and SCU67727.1), were identified as unique to T. equiperdum by bioinformatics analysis. The proteins were expressed as recombinant proteins and tested using an indirect ELISA and immunoblotting test with a panel of horse positive and negative sera for dourine. The diagnostic sensitivity, specificity and accuracy of the i-ELISAs were 86.7%, 53.8% and 59.0% for A0A1G4I8N3; 53.3%, 58.7% and 57.9% for A0A1G4I464; and 73.3%, 65.0% and 66.3% for A0A1G4I740, respectively, while the diagnostic sensitivity, specificity and accuracy of immunoblotting were 86.7%, 92.5% and 91.6% for A0A1G4I8N3; 46.7%, 81.3% and 75.8% for A0A1G4I464; and 80.0%, 63.8% and 66.3% for A0A1G4I740. Among the three proteins evaluated in the present work, A0A1G4I8N3 provided the best results when tested by immunoblotting; diagnostic application of this protein should be further investigated using a greater number of positive and negative sera.

BackgroundAlthough mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission.MethodsA Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis.ResultsForty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding.ConclusionsSubcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.

Abstract Background Brain-Computer Interfaces (BCI) promote upper limb recovery in stroke patients reinforcing motor related brain activity (from electroencephalogaphy, EEG). Hybrid BCIs which include peripheral signals (electromyography, EMG) as control features could be employed to monitor post-stroke motor abnormalities. To ground the use of corticomuscular coherence (CMC) as a hybrid feature for a rehabilitative BCI, we analyzed high-density CMC networks (derived from multiple EEG and EMG channels) and their relation with upper limb motor deficit by comparing data from stroke patients with healthy participants during simple hand tasks. Methods EEG (61 sensors) and EMG (8 muscles per arm) were simultaneously recorded from 12 stroke (EXP) and 12 healthy participants (CTRL) during simple hand movements performed with right/left (CTRL) and unaffected/affected hand (EXP, UH/AH). CMC networks were estimated for each movement and their properties were analyzed by means of indices derived ad-hoc from graph theory and compared among groups. Results Between-group analysis showed that CMC weight of the whole brain network was significantly reduced in patients during AH movements. The network density was increased especially for those connections entailing bilateral non-target muscles. Such reduced muscle-specificity observed in patients was confirmed by muscle degree index (connections per muscle) which indicated a connections’ distribution among non-target and contralateral muscles and revealed a higher involvement of proximal muscles in patients. CMC network properties correlated with upper-limb motor impairment as assessed by Fugl-Meyer Assessment and Manual Muscle Test in patients. Conclusions High-density CMC networks can capture motor abnormalities in stroke patients during simple hand movements. Correlations with upper limb motor impairment support their use in a BCI-based rehabilitative approach.

Venue-based strategies offer effective means of targeting men who have sex with men. Few studies have sought to focus on where younger men congregate and understand risk behaviors that may occur at lower (i.e., community centers) versus higher risk venues. Data from 1,311 young men who have sex with men (YMSM) aged 12- to 24-years-old recruited from publicly accessible venues was used to examine the association between venue type (bar/club, community center, mixed [adjacent to bar/club, including parking lot/alley]) and HIV-related risk factors. YMSM recruited from community venues were more likely than those from bars/clubs to report more partners in last year, receive money in exchange for sex, and to be tested for HIV in prior 6 months, whereas YMSM from mixed-use venues were more likely to have ever received money in exchange for sex, and injected drugs. Community and mixed venues may be key access points for YMSM.