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Abstract In Brazil, there is 13% of the world’s bat diversity, is the second most diverse group of mammals, playing a crucial role in providing ecosystem services that benefit humans. However, anthropogenic disturbances exacerbate processes of species extinction, shifts in geographic distributions, and phenological changes, despite efforts to safeguard biodiversity through the creation of Conservation Units and Indigenous Lands. Moreover, gaps in taxonomic knowledge and challenges related to species distribution hinder the effective implementation of conservation strategies in protected areas. This study assesses the contribution of Brazilian Conservation Units (both Full Protection and Sustainable Use) and Indigenous Lands to the conservation of bat species and their ecosystem services. It also presents maps illustrating species richness by trophic guilds and threat classification according to IUCN, including species listed as Data Deficient. The findings reveal low percentages of potential bat distribution areas within these protected regions, especially for insectivorous, nectarivorous, and frugivorous bats in the Cerrado biome, which are classified as Near Threatened. Additionally, the highest bat species richness was observed in the Amazon and Atlantic Forest biomes.

Abstract Lenvatinib is a multiple receptor tyrosine kinase inhibitor (TKI) approved for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). TKI are suspected of exacerbating muscle loss in patients with cancer. In this study, we analyze the role of muscle loss in patients with advanced HCC treated with lenvatinib. This is a retrospective analysis of a real-life cohort of 25 patients with advanced HCC who were treated with lenvatinib from 2018 to March 2021 in Germany. Patients were stratified for loss of skeletal muscle area during the first three months of lenvatinib therapy. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially regarding loss of muscle before and during the first three months of therapy with lenvatinib. Three months after beginning of therapy with lenvatinib, a significant reduction of muscle mass was observed in 60% of patients (p = 0.035). Despite increase of loss of skeletal muscle, patients benefitted from lenvatinib in our cohort of patients in terms of OS and PFS and did not experience increased toxicity. Furthermore, muscle loss was not a negative predictor of survival in the univariate analysis (p = 0.675). Patients with advanced hepatocellular carcinoma experience muscle loss with lenvatinib therapy. However, despite progressive muscle loss, patients benefit from a therapy with lenvatinib in terms of OS and PFS without increased toxicity. However, assessment and prophylaxis of skeletal muscle status should be recommended during a therapy with lenvatinib.

Abstract The red-legged partridge Alectoris rufa plays a crucial role in the ecosystem of southwestern Europe, and understanding its genetics is vital for conservation and management. Here we sequence, assemble, and annotate a highly contiguous and nearly complete version of its genome. This assembly encompasses 96.9% of the avian genes flagged as essential in the BUSCO aves_odb10 dataset. Moreover, we pinpointed RNA and protein-coding genes, 95% of which had functional annotations. Notably, we observed significant chromosome rearrangements in comparison to quail (Coturnix japonica) and chicken (Gallus gallus). In addition, a comparative phylogenetic analysis of these genomes suggests that A. rufa and C. japonica diverged roughly 20 million years ago and that their common ancestor diverged from G. gallus 35 million years ago. Our assembly represents a significant advancement towards a complete reference genome for A. rufa, facilitating comparative avian genomics, and providing a valuable resource for future research and conservation efforts for the red-legged partridge.

Abstract Background As key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis. Methods Peripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module’s expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis. Results Four modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion. Conclusions We identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.

Purpose Studies have elucidated that heart failure (HF) in people living with HIV manifests differently when compared with HF cases in the general population. This cohort aimed to examine the mortality risk factors, including biological and social factors, as well as suitable medical interventions to prevent death in this population.Participants The New York City Health+Hospitals HIV Heart Failure (NYC4H) cohort encompassed records from 11 major hospital sites. Adult individuals with confirmed HIV and HF were recruited from either inpatient or clinic hospital visits between July 2017 and June 2022. The first follow-up period began on the date of the first clinical encounter until June 2023, and the second follow-up period extended between July 2022 and October 2023.Findings to date In total, 1044 patients were enrolled in the study. The cohort comprised 657 (62.9%) males and 387 (37.1%) females. The average age was 61.6 years at baseline and the average follow-up time was 3.8 years. Overall, a total of 259 (24.8%) deaths were identified, of which 193 occurred in the first follow-up period (enrolling date to June 2022) and 66 during the second follow-up period (June 2022 to October 2023). The most common comorbidities within this population were hypertension (75.3%), chronic obstructive pulmonary disease (39.2%), type II diabetes mellitus (40%) and hyperlipidaemia (35.7%). The most common social adversities were polysubstance use (31.13%), mental health-related issues (20.7%) and lack of family support (14.5%). 601 (57.6%) patients had encountered at least one and more than one social adversity in their lifetime.Future plans Currently, nutritional notes from licensed dietitians and right and left heart catheterisation reports are under review. We are scheduled to complete the data collection for the comprehensive third follow-up period, which includes follow-up psychosocial evaluations, by the end of 2025. In addition, we intend to conduct annual follow-ups for specific high-risk groups, such as individuals with pulmonary hypertension, those facing higher social adversities and participants with poor HIV control.

Introduction Physiotherapists provide non-pharmacological conservative treatment for osteoarthritis (OA) using a wide spectrum of interventions. Previous surveys have identified global physiotherapy OA management practices. However, no review to date summarises the scope and findings of these studies. This article describes a scoping review protocol to map the surveys investigating physiotherapeutic interventions offered to patients with OA to identify the treatment interventions currently used for OA, the physiotherapists’ attributes and organisational practice factors potentially associated with the choice of these interventions and to detect knowledge-practice gaps in the provision of physiotherapeutic interventions in OA treatment, contributing to guiding future research on this topic.Methods and analysis This is a protocol for a scoping review that will be based on Arksey and O’Malley scoping review methodology and the methodological guidance for conducting scoping reviews published by the Joanna Briggs Institute (JBI). Relevant articles will be searched using the following databases: Medline (PubMed), Embase, Web of Science and Google Scholar. Surveys studies addressing physiotherapeutic interventions offered to patients with OA will be included. Study will be selected through title/abstract and full-text screening stages and data will be extracted using an instrument based on the model available in the JBI Manual. The findings will be summarised using descriptive statistics according to our research questions. This review will be reported in accordance with the Preferred Items for Systematic Reviews and Meta-Analyses for Scoping Reviews.Ethics and dissemination Ethical approval is not required for this scoping review. Review findings will be disseminated through peer-reviewed publications, scientific conference presentations and scientific meetings.Study registration This protocol has been registered with the Open Science Framework (DOI 10.17605/OSF.IO/J3RBT).

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in Xenopus, we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active. Metabolic suppression was also achieved using SNC80 in microfluidic human organs-on-chips, as well as in explanted whole porcine hearts and limbs, demonstrating the cross-species relevance of this approach and potential clinical relevance for surgical transplantation. Pharmacological induction of physiological slowing in combination with organ perfusion transport systems may offer a new therapeutic approach for tissue and organ preservation for transplantation, trauma management, and enhancing patient survival in remote and low-resource locations.

Objetivo: construir e validar o guia de aplicação da Dinâmica do Betinho para mediar as ações de educação em saúde com crianças e adolescentes que convivem com Diabetes Mellitus Tipo 1. Método: estudo metodológico realizado em três etapas: revisão de literatura, construção do guia, validação do conteúdo em ambiente virtual e em âmbito nacional. Participaram especialistas da área da saúde por meio de um questionário. Aplicou-se análise estatística descritiva e cálculo do Índice de Validade de Conteúdo (IVC). Resultados: da revisão emergiram 14 temas. Após a construção configurou-se a primeira versão; na etapa de validação obteve IVC de 0,83. As sugestões foram utilizadas na versão final. Conclusão: o guia foi considerado adequado e poderá ser usado quando da aplicação da Dinâmica do Betinho, que é um recurso tecnológico interativo e lúdico.

Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to explain a knowledge to be achieved (the target), with pieces of information already familiar to the learner (the source), keeping in mind the constraints of similarity, structure and purpose. The purpose of this essay is to examine the use of analogies in medicine. We provide a brief review of the theoretical basis of analogical reasoning. This theoretical background is discussed in the light of actual examples of analogies retrieved from medical literature. In medicine, analogies have long been used to explain several physiologic and pathologic processes. Besides deeper structural relations, superficial attribute similarity is extensively used in many medical specialties. These attribute similarities are important in naming, categorizing and classifying, and play a role as learning and memorizing tools. Analogies also serve as basis for medical nomenclature. The choice of the source of analogies is highly dependent on cultural background, and may derive from ancient or diverse cultures. Learning by analogies may thus require research on culture diversity in order to establish an adequate justification and to comprehend the purpose of an analogy. (Contains 1 table.)

Introduction: Sickle cell disease (SCD) is a genetic disorder that is widely observed on a global scale and known for its substantial negative impact on health and mortality. The purpose of this research was to explore how SCD influences the outcomes of acute coronary syndrome (ACS) and Percutaneous Coronary Intervention (PCI). Methods: A retrospective observational analysis was conducted using the National Inpatient Sample (NIS) data for the year 2020. Adult patients with concurrent ACS and SCD diagnoses were included in the study. Demographic information, clinical characteristics, in-hospital outcomes, and PCI complications were examined and compared between ACS patients with and without SCD. Results: Among a total of 779,895 ACS patients, 1495 had coexisting SCD. SCD patiets exhibited distinct demographic features, such as younger age (mean age: 59 vs. 66 years), predominantly female (53% vs. 35%), and primarily African American (91% vs. 11%). Comorbid conditions such as hypertension and chronic lung disease were more prevalent in SCD patients. While inpatient mortality odds did not significantly differ, SCD patients demonstrated slightly shorter lengths of stay in cases of STEMI and NSTEMI/UA. Notably, SCD patients faced a statistically significant increased risk of coronary dissection, highlighting a unique complication in this population. Although an increased incidence of atrial fibrillation and acute heart failure was observed in SCD patients, statistical significance was not achieved. Conclusions: This study provides valuable insight into the intricate interplay between SCD and ACS outcomes. SCD patients presented with distinctive demographic and clinical profiles that influenced their experience with ACS. The elevated risk of coronary dissection emphasizes the necessity for tailored interventions and careful management in SCD patients. These findings underscore the need for further research to elucidate underlying mechanisms and optimize treatment strategies for individuals with both SCD and ACS.

Abstract The recessive T allele of the missense polymorphism rs709596309 C > T of the leptin receptor gene is associated with intramuscular fat. However, its overall impact on pork production is still partial. In this work, we investigated the all-round effects of the TT genotype on lean growth efficiency and carcass, meat and fat quality using data from an experiment that compared the performance of 48 TT and 48 C– (24 CT and 24 CC) Duroc barrows. The TT pigs were less efficient for lean growth than the C– pigs. Although heavier, their carcasses had less lean content, were shorter and had lighter loins. Apart from increasing marbling and saturated fatty acid content, changes caused by the TT genotype in meat and fat quality are likely not enough to be perceived by consumers. The effect on visual marbling score exceeded that on intramuscular fat content, which suggests a direct influence of the T allele on the pattern of fat distribution in muscle. With current low-protein diets, the T allele is expected to be cost-effective only in niche markets where a very high level of marbling is critical.

Abstract We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Abstract The creation of protected areas (PAs) is not always based on science; consequently, some aquatic species may not receive the same level of protection as terrestrial ones. The objective of this study was to identify priority areas for the conservation of chelonians in the Brazilian Amazon basin and assess the contribution of PAs, distinguishing between Full Protection Areas, Sustainable Use Areas, and Indigenous Lands for group protection. The entire species modeling procedure was carried out using Species Distribution Models. Location records were obtained from platforms such as SpeciesLink, GBIF, the Hydroatlas database, and WorldClim for bioclimatic variables adjusted with algorithms like Maximum Entropy, Random Forest, Support Vector Machine, and Gaussian-Bayesian. Indigenous lands cover more than 50% of the distribution areas of chelonian species in the Brazilian Amazon. Protected areas with higher conservation importance (Full Protection Areas and Sustainable Use Areas) hold less than 15% of the combined species distribution. Researchers face significant challenges when making decisions with models, especially in conservation efforts involving diverse taxa that differ significantly from one another within a group of individuals.

Abstract Dreaming is a universal human behavior that has inspired searches for meaning across many disciplines including art, psychology, religion, and politics, yet its function remains poorly understood. Given the suggested role of sleep in emotional memory processing, we investigated whether reported overnight dreaming and dream content are associated with sleep-dependent changes in emotional memory and reactivity, and whether dreaming plays an active or passive role. Participants completed an emotional picture task before and after a full night of sleep and they recorded the presence and content of their dreams upon waking in the morning. The results replicated the emotional memory trade-off (negative images maintained at the cost of neutral memories), but only in those who reported dreaming (Dream-Recallers), and not in Non-Dream-Recallers. Results also replicated sleep-dependent reductions in emotional reactivity, but only in Dream-Recallers, not in Non-Dream-Recallers. Additionally, the more positive the dream report, the more positive the next-day emotional reactivity is compared to the night before. These findings implicate an active role for dreaming in overnight emotional memory processing and suggest a mechanistic framework whereby dreaming may enhance salient emotional experiences via the forgetting of less relevant information.

Abstract Background Natural cytokines are poorly suited as therapeutics for systemic administration due to suboptimal pharmacological and pharmacokinetic (PK) properties. Recombinant human interleukin-2 (rhIL-2) has shown promise for treatment of autoimmune (AI) disorders yet exhibits short systemic half-life and opposing immune responses that negate an appropriate therapeutic index. Methods A semi-synthetic microbial technology platform was used to engineer a site-specifically pegylated form of rhIL-2 with enhanced PK, specificity for induction of immune-suppressive regulatory CD4 + T cells (Tregs), and reduced stimulation of off-target effector T and NK cells. A library of rhIL-2 molecules was constructed with single site-specific, biorthogonal chemistry-compatible non-canonical amino acids installed near the interface where IL-2 engages its cognate receptor βγ (IL-2Rβγ) signaling complex. Biorthogonal site-specific pegylation and functional screening identified variants that retained engagement of the IL-2Rα chain with attenuated potency at the IL-2Rβγ complex. Results Phenotypic screening in mouse identifies SAR444336 (SAR’336; formerly known as THOR-809), rhIL-2 pegylated at H16, as a potential development candidate that specifically expands peripheral CD4+ Tregs with upregulation of markers that correlate with their suppressive function including FoxP3, ICOS and Helios, yet minimally expands CD8 + T or NK cells. In non-human primate, administration of SAR’336 also induces dose-dependent expansion of Tregs and upregulated suppressive markers without significant expansion of CD8 + T or NK cells. SAR’336 administration reduces inflammation in a delayed-type hypersensitivity mouse model, potently suppressing CD4+ and CD8 + T cell proliferation. Conclusion SAR’336 is a specific Treg activator, supporting its further development for the treatment of AI diseases.

Abstract The use of dendrimers as drug and nucleic acid delivery systems requires knowledge of their interactions with objects on their way to the target. In the present work, we investigated the interaction of a new class of carbosilane dendrimers functionalized with polyphenolic and caffeic acid residues with human serum albumin, which is the most abundant blood protein. The addition of dendrimers to albumin solution decreased the zeta potential of albumin/dendrimer complexes as compared to free albumin, increased density of the fibrillary form of albumin, shifted fluorescence spectrum towards longer wavelengths, induced quenching of tryptophan fluorescence, and decreased ellipticity of circular dichroism resulting from a reduction in the albumin α-helix for random coil structural form. Isothermal titration calorimetry showed that, on average, one molecule of albumin was bound by 6–10 molecules of dendrimers. The zeta size confirmed the binding of the dendrimers to albumin. The interaction of dendrimers and albumin depended on the number of caffeic acid residues and polyethylene glycol modifications in the dendrimer structure. In conclusion, carbosilane polyphenolic dendrimers interact with human albumin changing its structure and electrical properties. However, the consequences of such interaction for the efficacy and side effects of these dendrimers as drug/nucleic acid delivery system requires further research.

Abstract Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008–2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2–2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1–8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7–13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population.

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28−/− mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

Abstract Here we present an improved, rapid method for filling quasi-nulls in symmetrical radiation patterns synthesized by equispaced linear arrays, leading to the generation of multiple solutions. Considering the polynomial representation of the pattern, this null-filling is achieved by displacing the roots radially off the unit circle, keeping a constant displacement. This allows analyzing how the potential solutions vary with the quasi-uniform filling and the associated directivity loss. This method is based on the Cardano-Vieta relations, which link the coefficients of a complex Schelkunoff polynomial with its roots. As examples of application, we have considered a 20/100 element Dolph-Chebyshev pattern, with a spacing between the elements $$\lambda / 2$$ λ / 2 , side lobe level of − 20/− 28 dB and three inner sidelobes at − 40/− 50 dB.

Abstract Campylobacter fetus comprises two closely related mammal-associated subspecies: Campylobacter fetus subsp. fetus (Cff) and Campylobacter fetus subsp. venerealis (Cfv). The latter causes bovine genital campylobacteriosis, a sexually-transmitted disease endemic in Spain that results in significant economic losses in the cattle industry. Here, 33 C. fetus Spanish isolates were whole-genome sequenced and compared with 62 publicly available C. fetus genomes from other countries. Genome-based taxonomic identification revealed high concordance with in silico PCR, confirming Spanish isolates as Cff (n = 4), Cfv (n = 9) and Cfv biovar intermedius (Cfvi, n = 20). MLST analysis assigned the Spanish isolates to 6 STs, including three novel: ST-76 and ST-77 for Cfv and ST-78 for Cff. Core genome SNP phylogenetic analysis of the 95 genomes identified multiple clusters, revealing associations at subspecies and biovar level between genomes with the same ST and separating the Cfvi genomes from Spain and other countries. A genome-wide association study identified pqqL as a Cfv-specific gene and a potential candidate for more accurate identification methods. Functionality analysis revealed variations in the accessory genome of C. fetus subspecies and biovars that deserve further studies. These results provide valuable information about the regional variants of C. fetus present in Spain and the genetic diversity and predicted functionality of the different subspecies.

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intraperson before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p

Background/Objectives: Brazilian red propolis has attracted attention for its pharmacological properties. However, signs of toxicity were recently observed in long-term studies using the hydroalcoholic extract of red propolis (RPHE), likely due to polyprenylated benzophenones. This study aimed to develop a benzophenone-free red propolis extract (BFRP) and validate an HPLC-PDA method to quantify its main constituents: isoliquiritigenin, vestitol, neovestitol, medicarpine, and 7-O-methylvestitol. Methods: BFRP’s toxicity was assessed in zebrafish larvae through a vibrational startle response assay (VSRA) and morphological analysis. Genotoxicity was evaluated using the micronucleus test in rodents, and the extract’s effects on chemically induced preneoplastic lesions in rat colon were studied. An HPLC-PDA method was used to quantify BFRP’s main compounds. Results: BFRP primarily contained vestitol (128.24 ± 1.01 μg/mL) along with isoliquiritigenin, medicarpin, neovestitol, and 7-O-methylvestitol. Zebrafish larvae exposed to 40 µg/mL of BFRP exhibited toxicity, higher than the 10 µg/mL for RPHE, though no morphological differences were found. Fluorescent staining in the notochord, branchial arches, and mouth was observed in larvae treated with both BFRP and RPHE. No genotoxic or cytotoxic effects were observed up to 2000 mg/kg in rodents, with no impact on hepatotoxicity or nephrotoxicity markers. Chemoprevention studies showed a 41.6% reduction in preneoplastic lesions in rats treated with 6 mg/kg of BFRP. Conclusions: These findings indicate that BFRP is a safe, effective propolis-based extract with potential applications for human health, demonstrating reduced toxicity and chemopreventive properties.

BackgroundPreclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer.Methods and findingsThis prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial.ConclusionsMRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials.Trial registrationclinicaltrials.gov, identifier NCT04431674.

Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of ribosomal DNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-Seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.

Abstract The ordered porous frameworks like MOFs and COFs are generally constructed using the monomers through distinctive metal-coordinated and covalent linkages. Meanwhile, the inter-structural transition between each class of these porous materials is an under-explored research area. However, such altered frameworks are expected to have exciting features compared to their pristine versions. Herein, we have demonstrated a chemical-induction phase-engineering strategy to transform a two-dimensional conjugated Cu-based SA-MOF (Cu-Tp) into 2D-COFs (Cu-TpCOFs). The structural phase transition offered in-situ pore size engineering from 1.1 nm to 1.5–2.0 nm. Moreover, the Cu-TpCOFs showed uniform and low percentage-doped (~ 1–1.5%) metal distribution and improved crystallinity, porosity, and stability compared to the parent Cu-Tp MOF. The construction of a framework from another framework with new linkages opens interesting opportunities for phase-engineering.

The persistence of the human papillomavirus type 16 (HPV16) infection on the cervical epithelium contributes to the progression of cervical cancer. Studies have demonstrated that HPV16 genetic variants may be associated with different risks of developing cervical cancer. However, the E5 oncoprotein of HPV16, which is related to several cellular mechanisms in the initial phases of the infection and thus contributes to carcinogenesis, is still little studied. Here we investigate the HPV16 E5 oncogene variants to assess the effects of different mutations on the biological function of the E5 protein. We detected and analyzed the HPV16 E5 oncogene polymorphisms and their phylogenetic relationships. After that, we proposed a tertiary structure analysis of the protein variants, preferential codon usage, and functional activity of the HPV16 E5 protein. Intra-type variants were grouped in the lineages A and D using in silico analysis. The mutations in E5 were located in the T-cell epitopes region. We therefore analyzed the interference of the HPV16 E5 protein in the NF-kB pathway. Our results showed that the variants HPV16E5_49PE and HPV16E5_85PE did not increase the potential of the pathway activation capacity. This study provides additional knowledge about the mechanisms of dispersion of the HPV16 E5 variants, providing evidence that these variants may be relevant to the modulation of the NF-κB signaling pathway.

Abstract Siblings strongly influence each other in their social development and are a major source of support and conflict. Yet, studies are mostly observational, and little is known about how adult sibling relationships influence social behavior. Previous tasks exploring dynamically adjusting social interactions have limitations in the level of interactivity and naturalism of the interaction. To address these limitations, we created a cooperative tetris puzzle-solving task and an interactive version of the chicken game task. We validated these two tasks to study cooperative and competitive behavior in real-time interactions (N = 56). Based on a dominance questionnaire (DoPL), sibling pairs were clustered into pairs that were both low in dominance (n = 7), both high in dominance (n = 8), or one low and one high in dominance (n = 13). Consistent with our hypothesis, there were significantly more mutual defections, less use of turn-taking strategies, and a non-significant trend for reduced success in solving tetris puzzles together among high dominance pairs compared to both other pair types. High dominant pairs also had higher Machiavellian and hypercompetitiveness traits and more apathetic sibling relationships. Both tasks constitute powerful and reliable tools to study personality and relationship influences on real and natural social interactions by demonstrating the different cooperative and competitive dynamics between siblings.

Objetivo: relatar a experiência de conscientizar sobre a conservação da fauna e flora silvestre por meio de ferramentas digitais. Materiais e Métodos: trata-se de um relato de experiência de alunos do 3º período do curso de Medicina Veterinária de uma instituição de ensino superior da cidade de Montes Claros-MG, como parte da disciplina de Projeto Integrador Meio Ambiente e Sustentabilidade, no segundo semestre de 2022. Primeiramente foi realizada uma busca sobre o tema para posteriormente construir panfletos digitais e enquetes que seriam vinculados às redes sociais dos integrantes da equipe. Foram utilizadas imagens ilustrativas com animais silvestres e árvores nativas, principalmente de espécies ameaçadas de extinção, com o intuito de envolver os seguidores sobre a importância de conservar a fauna e a flora, preservar os habitats e não contribuir com o comércio ilegal, bem como mostrar os benefícios que essas práticas podem trazer para o futuro do meio ambiente. Resultados: em várias enquetes, tornou-se nítida a empatia que muitas pessoas têm com os animais, incluindo jovens que reproduzem o que lhes foi repassado quando crianças. No entanto, observaram-se dificuldades, uma vez que a maioria das enquetes foi visualizada, porém não respondida, o que pode ser entendido como desinteresse pelo assunto em foco. Mas, por meio das buscas realizadas na coleta de informações para a atividade, foi possível verificar que muito se tem abordado sobre a fauna e a flora nas mídias sociais. Conclusão: ressalta-se a importância do constante conhecimento e conscientização sobre a fauna e flora silvestres, com o objetivo de sensibilizar os cidadãos sobre a problemática ambiental.

Dyads can be challenging to recruit for research studies, but detailed reporting on strategies employed to recruit adult–adolescent dyads is rare. We describe experiences recruiting adult–youth dyads for a hypertension education intervention comparing recruitment in an emergency department (ED) setting with a school-based community setting. We found more success in recruiting dyads through a school-based model that started with adolescent youth (19 dyads in 7 weeks with < 1 hour recruitment) compared to an ED-based model that started with adults (2 dyads in 17 weeks with 350 hours of recruitment). These findings can benefit future adult–youth dyad recruitment for research studies.

BackgroundForcibly displaced adolescents face increased risks for mental illness and distress, with adolescent girls disproportionately affected in part due to heightened gender inequity. Although the family unit has the potential to promote healthy development in adolescents, few family interventions have employed a gender transformative approach or included male siblings to maximize benefits for adolescent girls.MethodsThis study will assess a whole-family and gender transformative intervention-Sibling Support for Adolescent Girls in Emergencies (SSAGE)-to prevent mental health disorders among adolescent girls in Colombia who were recently and forcibly displaced from Venezuela. The study will employ a hybrid type 1 effectiveness-implementation pilot randomized control trial (RCT) to test the program's effectiveness to explore determinants of implementation to establish the feasibility, acceptability, and fidelity of SSAGE. To address these aims, we will enroll 180 recently arrived, forcibly displaced adolescent girls in an RCT and examine the program's effectiveness in the prevention of mental illness (through reduction in anxiety, depression, interpersonal sensitivity, and somatization symptoms) one-month post-intervention. We will use contextually adapted to collect data on the hypothesized mechanistic pathways, including family attachment, gender-equitable family functioning, self-esteem, and coping strategies. The implementation evaluation will employ mixed methods to assess the program's feasibility, acceptability, fidelity, and barriers and facilitators to successful implementation.DiscussionFindings can support humanitarian program implementation, as well as inform policy to support adolescent girls' mental health and to prevent the myriad disorders that can arise as a result of exposure to displacement, conflict, and inequitable gender norms.

BackgroundChildren 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. ObjectiveThe 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. MethodsThis 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. ResultsEnrollment started in September 2021 and ended in March 2023. Endline assessments will take place between August 2023 and September 2024. ConclusionsThis 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 RegistrationClinicalTrials.gov NCT05202106; https://clinicaltrials.gov/ct2/show/NCT05202106 International Registered Report Identifier (IRRID)DERR1-10.2196/50371

Abstract X-ray scatter in planar radiography degrades the contrast resolution of the image, thus reducing its diagnostic utility. Antiscatter grids partially block scattered photons at the cost of increasing the dose delivered by two- to four-fold and posing geometrical restrictions that hinder their use for other acquisition settings, such as portable radiography. The few software-based approaches investigated for planar radiography mainly estimate the scatter map from a low-frequency version of the image. We present a novel method for scatter correction in planar imaging based on direct patient measurements. Samples from the shadowed regions of an additional partially obstructed projection acquired with a beam stopper placed between the X-ray source and the patient are used to estimate the scatter map. Evaluation with simulated and real data showed an increase in contrast resolution for both lung and spine and recovery of ground truth values superior to those of three recently proposed methods. Our method avoids the biases of post-processing methods and yields results similar to those for an antiscatter grid while removing geometrical restrictions at around half the radiation dose. It can be used in unconventional imaging techniques, such as portable radiography, where training datasets needed for deep-learning approaches would be very difficult to obtain.

Highlights A sex difference in the immune response to S. aureus was observed. DHT stimulated a greater release of inflammatory cytokines. DHT promoted the activation of genes involved in this response. DHT suppressed the release of inflammatory markers.

Abstract Brazilian mangroves have been severely impacted by metallurgical, petrochemical, pyrometallurgical smelters and other industrial activities. In Rio de Janeiro, mangroves are part of the Atlantic Rainforest now under the stress of high levels of industrial waste. Therefore, this work aimed to detect potentially toxic elements (PTEs) by evaluating the leaves of Laguncularia racemosa (L.) Gaertn. f. collected from three mangroves with different levels of pollution. To gain further insight toward an accurate diagnosis of the effects of anthropogenic pollution on mangrove stands, we evaluated leaf epicuticular wax composition, as well as morphological and anatomical traits. Samples were analyzed using inductively coupled plasma-optical emission spectroscopy (ICP-OES), gas chromatography (GC) and microscopy. Results revealed variation in the contents of PTEs among the three mangroves from lowest to highest concentration, as follows: Al (0.30–0.73), Pb (0.095–0.325) and Zn (0.25–0.30) mg/kg. Zn was detected in sclerenchyma tissues. Leaf epicuticular wax contained more than 50% of triterpenes, in particular, the pentacyclic triterpenes lupeol (41.61–55.63%) and β-amyrin (8.81–16.35%). Such high concentrations promote the increase in leaf permeability to salts and PTEs. Micromorphology of leaf epicuticular wax in L. racemosa also varied among the three evaluated sites, especially around stomatal openings, but no harmful changes were noted. L. racemosa plays a key role in the rich diversity of mangrove ecosystems. As such, this species could, by the presence of PTEs in its leaves, be a suitable biomonitor of toxic substances in coastal environments of the world and used accordingly in strategies designed for eco-sustainable technologies.

Introduction Children with callous-unemotional (CU) traits are at high lifetime risk of antisocial behaviour. Low affiliation (ie, social bonding difficulties) and fearlessness (ie, low threat sensitivity) are proposed risk factors for CU traits. Parenting practices (eg, harshness and low warmth) also predict risk for CU traits. However, few studies in early childhood have identified attentional or physiological markers of low affiliation and fearlessness. Moreover, no studies have tested whether parenting practices are underpinned by low affiliation or fearlessness shared by parents, which could further shape parent–child interactions and exacerbate risk for CU traits. Addressing these questions will inform knowledge of how CU traits develop and isolate novel parent and child targets for future specialised treatments for CU traits.Methods and analysis The Promoting Empathy and Affiliation in Relationships (PEAR) study aims to establish risk factors for CU traits in children aged 3–6 years. The PEAR study will recruit 500 parent–child dyads from two metropolitan areas of the USA. Parents and children will complete questionnaires, computer tasks and observational assessments, alongside collection of eye-tracking and physiological data, when children are aged 3–4 (time 1) and 5–6 (time 2) years. The moderating roles of child sex, race and ethnicity, family and neighbourhood disadvantage, and parental psychopathology will also be assessed. Study aims will be addressed using structural equation modelling, which will allow for flexible characterisation of low affiliation, fearlessness and parenting practices as risk factors for CU traits across multiple domains.Ethics and dissemination Ethical approval was granted by Boston University (#6158E) and the University of Pennsylvania (#850638). Results will be disseminated through conferences and open-access publications. All study and task materials will be made freely available on lab websites and through the Open Science Framework (OSF).

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Abstract In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Objective: To determine the prevalence of bacteriospermia, the bacterial load, and the potential factors associated with bacterial contamination in boar semen collected by local smallholder artificial insemination operators. Methods: Fifteen individual raw semen samples were collected from locally available artificial insemination boars owned by different smallholder boar operators within the 5th district of Leyte, Philippines and were subjected to standard bacteriological culture and identification, including a survey of potentially associated factors. Prevalence and bacterial count were determined accordingly, while boar characteristics and collection practices were clustered following agglomerative hierarchical clustering technique. Results: One hundred percent contamination with a bacterial count of (2.01±0.38)×103 CFU/mL was observed. At least 73.33% of the samples were positive for Bacillus spp., while other identified isolates included Enterobacter spp., Staphylococcus spp., E. coli, Pseudomonas spp., Citrobacter spp., and Klebsiella spp. Conclusions: Despite the high prevalence of bacteriospermia, the bacterial count is low. Nevertheless, on-farm practices on boar health and management, semen collection, and sanitation as well as the enhancement of basic protocols to control contamination should be conscientiously considered in smallholder artificial insemination operation.

Background: The sciatic nerve (SN) is the widest nerve of the human body that exits the pelvis through the greater sciatic foramen, usually below the piriformis muscle (PM), and descends between the greater trochanter of the femur and ischial tuberosity of the pelvis to the knee. The aim of this paper is to examine and identify the SN variations in relation to the PM, its prevalence, pattern, and course. Methods: A prospective-descriptive cross-sectional study was carried out to determine the frequency of anatomical variations in the exit of the SN in relation with the PM in 20 anatomical bodies (corpses) of both genders, in equal numbers. Results: The dissection of 40 SNs in corpses of both sexes in equal numbers showed that the SN exited inferior to the PM in 37 lower limbs (92.5%); between the fascicles of the PM and inferior to the PM in two lower limbs (5%); and in one thigh, between the fascicles of the PM and superior to the PM (2.5%). Our study reported that the SN divides in its terminal branches more commonly in the proximal part of the popliteal fossa in 55% of cases, in the gluteal region in 35% of cases, and in the middle third of the thigh in 10% of cases. Conclusions: Anatomical variations of the SN in relation to the PM are challenging for the diagnostic and therapeutic procedure in many clinical and surgical cases. Rapid recognition of the SN changes makes surgical approaches more accurate and effective. Our study confirmed that the SN exits the pelvis most commonly below the PM, although some anatomical variations may occur.

Abstract We present a novel approach to model hydro-chemo-mechanical responses in rock formations subject to fracture propagation within chemically active rock formations. The framework developed integrates the mechanisms of reactive transport, fluid flow and transport in porous media, and phase-field modelling of fracture propagation in poroelastic media. The solution approach integrates the geochemical package PHREEQC with a finite-element open-source platform, FEniCs. The PHREEQC solver is used to calculate the localized chemical reaction, including solid dissolution/precipitation. The resulting solid weakening by chemical damage is estimated from the reaction-induced porosity change. The proposed coupled model was verified with previous numerical results and applied to a synthetic case exhibiting hydraulic fracturing enhanced with chemical damage. Simulation results suggest that mechanical failure could be accelerated in the presence of ongoing chemical processes due to rock weakening and porosity changes, allowing the nucleation, growth, and development of fractures.

Abstract Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals’ intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas—ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal–epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.

Purpose: To investigate associations between body mass index (BMI), body fat percentage, and components of sarcopenia (muscle mass and muscle strength/power), with bone microarchitecture measured by high-resolution peripheral computed tomography (HR-pQCT) in older adults with obesity. Methods: Seventy-four adults aged ≥ 55 years with body fat percentage ≥ 30 % (men) or ≥40 % (women) were included. Fat mass, lean mass and total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry. Appendicular lean mass (ALM) was calculated as the sum of lean mass in the upper- and lower-limbs. BMI was calculated and participants completed physical function assessments including stair climb power test. Distal tibial bone microarchitecture was assessed using HR-pQCT. Linear regression (β-coefficients and 95 % confidence intervals) analyses were performed with adjustment for confounders including age, sex, smoking status, vitamin D and self-reported moderate to vigorous physical activity. Results: BMI and ALM/height2 were both positively associated with total hip, femoral neck and lumbar spine aBMD and trabecular bone volume fraction after adjusting for confounders (all p

Aging and the age-associated decline of the proteome is determined in part through neuronal control of evolutionarily conserved transcriptional effectors, which safeguard homeostasis under fluctuating metabolic and stress conditions by regulating an expansive proteostatic network. We have discovered the Caenorhabditis elegans homeodomain-interacting protein kinase (HPK-1) acts as a key transcriptional effector to preserve neuronal integrity, function, and proteostasis during aging. Loss of hpk-1 results in drastic dysregulation in expression of neuronal genes, including genes associated with neuronal aging. During normal aging hpk-1 expression increases throughout the nervous system more broadly than any other kinase. Within the aging nervous system, hpk-1 induction overlaps with key longevity transcription factors, which suggests that hpk-1 expression mitigates natural age-associated physiological decline. Consistently, pan-neuronal overexpression of hpk-1 extends longevity, preserves proteostasis both within and outside of the nervous system, and improves stress resistance. Neuronal HPK-1 improves proteostasis through kinase activity. HPK-1 functions cell non-autonomously within serotonergic and γ-aminobutyric acid (GABA)ergic neurons to improve proteostasis in distal tissues by specifically regulating distinct components of the proteostatic network. Increased serotonergic HPK-1 enhances the heat shock response and survival to acute stress. In contrast, GABAergic HPK-1 induces basal autophagy and extends longevity, which requires mxl-2 (MLX), hlh-30 (TFEB), and daf-16 (FOXO). Our work establishes hpk-1 as a key neuronal transcriptional regulator critical for preservation of neuronal function during aging. Further, these data provide novel insight as to how the nervous system partitions acute and chronic adaptive response pathways to delay aging by maintaining organismal homeostasis.

Abstract This work presents the application of an experimental nematic liquid crystal (LC) mixture (1929) in a large aperture lens. The LC material is composed of terphenyl and biphenyl derivatives compounds with an isothiocyanate terminal group and fluorinated lateral substituents. The substitution with a strongly polar isothiocyanate group and an aromatic rigid core provides $$\pi$$ π -electron coupling, providing high birefringence ( $$\Delta n = 0.3375$$ Δ n = 0.3375 at 636 nm and 23 °C) and low viscosity ( $$\eta$$ η = 17.03 mPa s). In addition, it also shows high values of birefringence at near infrared (0.318 at 1550 nm). The synthesis process is simple when comparing materials with high melting temperatures. The excellent properties of this LC mixture are demonstrated in a large aperture LC-tunable lens based on a transmission electrode structure. Thanks to the particular characteristics of this mixture, the optical power is high. The high birefringence makes this LC of specific interest for lenses and optical phase modulators and devices, both in the visible and infrared regions.

Abstract Zika virus (ZIKV) is an emerging arbovirus associated with neurological disorders. Currently, no specific vaccines or antivirals are available to treat the ZIKV infection. Ouabain, a cardiotonic steroid known as Na+/K+-ATPase inhibitor, has been previously described as an immunomodulatory substance by our group. Here, we evaluated for the first time the antiviral activity of this promising substance against a Brazilian ZIKV strain. Vero cells were treated with different concentrations of ouabain before and after the infection with ZIKV. The antiviral effect was evaluated by the TCID50 method and RT-qPCR. Ouabain presented a dose-dependent inhibitory effect against ZIKV, mainly when added post infection. The reduction of infectious virus was accompanied by a decrease in ZIKV RNA levels, suggesting that the mechanism of ZIKV inhibition by ouabain occurred at the replication step. In addition, our in silico data demonstrated a conformational stability and favorable binding free energy of ouabain in the biding sites of the NS5-RdRp and NS3-helicase proteins, which could be related to its mechanism of action. Taken together, these data demonstrate the antiviral activity of ouabain against a Brazilian ZIKV strain and evidence the potential of cardiotonic steroids as promising antiviral agents.