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Introduction Mental disorders represent the second cause of years lived with disability worldwide. Suicide mortality has been targeted as a key public health concern by the WHO. Smartphone technology provides a huge potential to develop massive and fast surveys. Given the vast cultural diversity of Mexico and its abrupt orography, smartphone-based resources are invaluable in order to adequately manage resources, services and preventive measures in the population. The objective of this study is to conduct a universal suicide risk screening in a rural area of Mexico, measuring also other mental health outcomes such as depression, anxiety and alcohol and substance use disorders.Methods and analysis A population-based cross-sectional study with a temporary sampling space of 9 months will be performed between September 2019 and June 2020. We expect to recruit a large percentage of the target population (at least 70%) in a short-term survey of Milpa Alta Delegation, which accounts for 137 927 inhabitants in a territorial extension of 288 km2.They will be recruited via an institutional call and a massive public campaign to fill in an online questionnaire through mobile-assisted or computer-assisted web app. This questionnaire will include data on general health, validated questionnaires including Well-being Index 5, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale 2, Alcohol Use Disorders Identification Test, selected questions of the Drug Abuse Screening Test and Columbia-Suicide Severity Rating Scales and Diagnostic and statistical manual of mental disorders (DSM-5) questions about self-harm.We will take into account information regarding time to mobile app response and geo-spatial location, and aggregated data on social, demographical and environmental variables. Traditional regression modelling, multilevel mixed methods and data-driven machine learning approaches will be used to test hypotheses regarding suicide risk factors at the individual and the population level.Ethics and dissemination Ethical approval (002/2019) was granted by the Ethics Review Board of the Hospital Psiquiátrico Yucatán, Yucatán (Mexico). This protocol has been registered in ClinicalTrials.gov. The starting date of the study is 3 September 2019. Results will serve for the planning and healthcare of groups with greater mental health needs and will be disseminated via publications in peer-reviewed journal and presented at relevant mental health conferences.Trial registration number NCT04067063.

Las comunidades ganaderas, a pequeña y mediana escala, en la provincia del Sumapaz, se encuentran en un periodo de transición hacia la tecnificación en la producción. Así, el objetivo de este estudio fue describir algunos aspectos que actúan como barreras en la tecnificación y limitan la implementación de buenas prácticas ganaderas. Se realizó un diagnóstico participativo en pequeños y medianos ganaderos del Sumapaz, mediante encuesta aleatoria, en nueve municipios de la provincia. Los resultados evidencian que existen diferentes barreras socio-económicas, que obstaculizan el acceso a tecnologías para el mejoramiento de la producción, como el bajo nivel de ingresos económicos, acceso a la educación superior y falta de registros contables y de sanidad en la producción; sin embargo, se observaron indicadores positivos, asociados al manejo ambiental de los recursos naturales, como parte de su legado cultural.

Background: Most of the evidence on risk factors for COVID-19 complications comes from North America or Europe with very little research from Latin-America. We aimed to evaluate the association between sociodemographic, clinical factors and the risk of COVID-19 complications among adults in Chile, the fifth Latin-American country with more COVID-19 reported cases since de beginning of the Pandemic., Methods: A retrospective population-based cohort study using data from electronic health records from a large Primary Care Network, linked to national hospital, immunization, Covid-19 PCR surveillance, mortality and birth records. We included people 18+ years old enrolled in the Primary Care Network between 1st January 2020 and 31st December 2021. Using Multivariate Cox proportional hazard models, we evaluate the association between sociodemographic, clinical characteristics with three COVID-19 complications: (1) a hospital admission, (2) an ICU admission, and (3) death due to a COVID-19 infection that occurred between the 1st January 2020 and the 31st December 2021., Results: 44,674 people were included. The mean age was 44.30 (sd 17.31), 55.6% were female, 15.9% had a type of healthcare insurance for people from the lowest category of income, 11.6% and 9.4% had a record of hypertension or diabetes mellitus diagnosis. Among the 44,674 people, 455 (1.02%) had a hospital admission due to a COVID-19 infection and 216(0.48%) of them also had an ICU admission. Among the 44,674 people,148(0.33%) died due to COVID-19 infection. Older age and male sex were consistently associated with a higher risk of the three COVID-19 complications. Hypertension and diabetes were associated with a higher risk of a hospital admission and death, but not with an ICU admissions due to COVID-19 infection. Having two or more COVID-19 vaccine doses compared with no doses was associated with a lower risk of any hospital admission (HR 0.81; 95% CI 0.77-0.84), an ICU admission (HR 0.60; 95% CI 0.57-0.63) and death (HR 0.50; 95% CI 0.46-0.54). Pregnant or puerperal women were more likely to be admitted to hospital (HR 2.89; 95% CI 1.41-5.89) or ICU (HR 3.04; 95% CI 1.01-9.14)., Conclusions: Sociodemographic and clinical factors associated with COVID-19 complications such as age, sex and pre-existing conditions were comparable to those reported in similar studies from higher-income countries, and can be used to predict severity in COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Leniz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, wastewater from a sewage treatment plant was used to culture the microalga, Verrucodesmus verrucosus. The ability of microalgae to adapt to adverse environments and produce high lipid concentrations was evaluated using different media, including sterile and non-sterile media and a control medium. The analysis showed that the control medium (distilled water sample enriched with fertilizer) removed 80.35% ammonium, 32.71% phosphate, and 83.86% nitrate. The sterile raw effluent removed 78.91% of ammonium, 83.44% of phosphate, and 98.82% of nitrate. The optimal conditions for biomass production were sterile raw wastewater, which produced 383.3 mg L -1 of biomass, 2.5% of total lipids, and an average lipid production of 9.31 mg L -1 . Microalgae can grow and consume inorganic nutrients under adverse environmental conditions such as in raw wastewater, which is of great importance because it is a pollutant that negatively affects the environment and society. However, wastewater may represent a viable alternative substrate, allowing the generation of high-value products, such as lipids. Furthermore, the specificity of microalgal morphotypes must be evaluated, because each has specific metabolic plasticity. Verrucodesmus verrucosus is a microalga that has not been evaluated in bioremediation processes of wastewater with and without the presence of biotic factors. Therefore, the present study provides a viable alternative for this biological process, with the potential to store metabolites of interest in the industry., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study assesses the production potential, environmental impact, and economic viability of generating biohydrogen from biomethane obtained from the organic fraction of municipal solid waste (MSW) using steam methane reforming with carbon capture and storage (CCS). As the emissions are biogenic, CCS results in negative emissions. The methodology is based on a previously developed model, including techno-economic analysis based on the levelised cost of hydrogen (LCOH) and mobility (LCOM), and environmental assessment, focusing on production potential, cost estimates, and emissions impact. A case study is conducted to assess the feasibility of using this biohydrogen with negative emissions to decarbonize Madrid's public bus fleet. The findings reveal that Madrid's MSW could meet the entire hydrogen fuel demand if the fleet consisted of fuel-cell buses. However, given the high costs of replacing the entire fleet, a net-zero solution is proposed, combining 60% fuel-cell buses with existing natural gas-powered buses. In this configuration, the negative emissions from biohydrogen offset the fossil emissions from natural gas and 40% of biomethane is saved. The cost of the net-zero fleet ranges between 192.55 and 209.37 €/100 km, comparable with 100% natural gas fleet, which ranges between 176.19 and 217.69 €/100 km., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Midbrain dopaminergic (mDA) neurons derived from human pluripotent stem cells (hPSCs) offer a promising cell source for cell replacement therapy in Parkinson's disease (PD). Single-cell RNA sequencing (scRNA-seq) of the developing human ventral midbrain has identified four cell types expressing markers used to define correctly patterned mDA progenitors. Here, we use CRISPR/Cas9 to generate a fluorescent human embryonic stem cell line for the isolation of two potential mDA progenitors, Rgl1 and ProgM. We expect that by isolating specific mDA progenitor cell type/s and defining their function, it may be possible to develop more precise cell replacement strategies for PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The burden of cancer is increasing rapidly in Latin America. Primary care has an essential role in cancer prevention, but implementation levels of prevention practices are not well known. This study evaluated implementation levels and associated factors of cancer preventive practices in primary care over time., Study Design: The study incorporated a retrospective multicentre cohort study., Methods: A population of 59,949 patients registered at three primary care clinics was followed from January 2018 to December 2022 in Santiago, Chile. We studied human papillomavirus (HPV) and hepatitis B virus (HBV) immunisation, brief counselling for smoking cessation and alcohol consumption, and cervical and breast cancer screening practices. Standardised electronic medical records were utilised as the source of information. Social, clinical, and organisational factors associated with prevention practices were studied., Results: The cohort attrition level was 17.1%. Most of the population was of a low socioeconomic status, and 70% visited a primary health centre yearly. Implementation rates of immunisation practices were 90.84% for HPV and 80.94% for HBV in 2022. In contrast, brief counselling for smoking and alcohol consumption was below 20% during the study period. Cervical cancer screening decreased by 25.58% between 2018 and 2022, whereas breast cancer screening reached only 41.71% of the target population. Opportunistic medical visits were strongly associated with brief counselling and breast cancer screening., Conclusion: Implementation practices for cancer prevention in a Chilean primary care cohort are high for immunisation and very low for brief counselling and screening practices. A comprehensive non-medical-based model is needed to improve cancer prevention in primary care., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/objectives: Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables., Methods: The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model., Results: No significant associations were found between the SNPs ABCA1 , ADIPOQ , FTO , and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ 2 = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08-2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant ( p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = -26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL)., Conclusions: A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease.

Microbes that use the single-carbon substrates methanol and methane offer great promise to bioindustry along with substantial environmental benefits. Methanotrophs and other methylotrophs can be engineered and optimized to produce a wide range of products, from biopolymers to biofuels and beyond. While significant limitations remain, including delivery of single-carbon feedstock to bioreactors, efficient growth, and scale-up, these challenges are being addressed and notable improvements have been rapid. Development of expression chassis, use of genome-scale and regulatory models based on omics data, improvements in bioreactor design and operation, and development of green product recovery schemes are enabling the rapid development of single-carbon bioconversion in the industrial space., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Anxiety disorders are among the main mental health problems worldwide and are considered one of the most disabling conditions. Therefore, it is essential to have measurement tools that can be used to screen for anxiety symptoms in the general population and thus identify potential cases of people with anxiety symptoms and provide them with timely care. Our aim was to evaluate the psychometric properties of the General Anxiety Disorder-7 scale (GAD-7) in the Peruvian population., Method: Our study was a cross-sectional study. The sample included people aged 12 to 65 years in Peru. Confirmatory factor analysis, analysis of measurement invariance, convergent validity with the Patient Health Questionnaire-9 (PHQ-9) and internal consistency analysis were performed., Results: In total, 4431 participants were included. The one-factor model showed the best fit (CFI = 0.994; TLI = 0.991; RMSEA = 0.068; WRMR = 1.567). The GAD-7 score showed measurement invariance between men and women and between age groups (adults vs. adolescents) (ΔCFI < 0.01). The internal consistency of the one-factor model was satisfactory (ω = 0.90, α = 0.93). The relationship between depressive symptoms (PHQ-9) and anxiety symptoms (GAD-7) presented a moderate correlation (r = 0.77)., Conclusions: Our study concluded that the GAD-7 score shows evidence of validity and reliability for the one-factor model. Furthermore, because the GAD-7 score is invariant, comparisons can be made between groups (i.e., by sex and age group). Finally, we recommend the use of the GAD-7 for the general population in the Peruvian context., (© 2024. The Author(s).)

Mutations in the GBA1 gene increase the risk of developing Parkinson's disease (PD). However, most carriers of GBA1 mutations do not develop PD throughout their lives. The mechanisms of how GBA1 mutations contribute to PD pathogenesis remain unclear. Cerebrospinal fluid (CSF) is used for detecting pathological conditions of diseases, providing insights into the molecular mechanisms underlying neurodegenerative disorders. In this study, we utilized the proximity extension assay to examine the levels of metabolism-linked protein in the CSF from 17 PD patients carrying GBA1 mutations (GBA1-PD) and 17 idiopathic PD (iPD). The analysis of CSF secretome in GBA1-PD identified 11 significantly altered proteins, namely FKBP4, THOP1, GLRX, TXNDC5, GAL, SEMA3F, CRKL, APLP1, LRP11, CD164, and NPTXR. To investigate GBA1 -associated CSF changes attributed to specific neuronal subtypes responsible for PD, we analyzed the cell culture supernatant from GBA1-PD-induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic (mDA) neurons. The secretome analysis of GBA1-PD iPSC-derived mDA neurons revealed that five differently regulated proteins overlapped with those identified in the CSF analysis: FKBP4, THOP1, GLRX, GAL, and CRKL. Reduced intracellular level of the top hit, FKPB4, was confirmed via Western Blot. In conclusion, our findings identify significantly altered CSF GBA1-PD-associated proteins with FKPB4 being firmly attributed to mDA neurons.

Skeletal muscle fibers obtained by enzymatic dissociation of mouse muscles are a useful model for physiological experiments. However, most papers deal with the short fibers of the flexor digitorum brevis (FDB), which restrains the scope of results dealing with fiber types, limits the amount of biological material available, and impedes a clear connection between cellular physiological phenomena and previous biochemical and dynamical knowledge obtained in other muscles. This paper describes how to obtain intact fibers from six muscles with different fiber type profiles and lengths. Using C57BL/6 adult mice, we show the muscle dissection and fiber isolation protocol and demonstrate the suitability of the fibers for Ca 2+ transient studies and their morphometric characterization. The fiber type composition of the muscles is also presented. When dissociated, all muscles rendered intact, living fibers that contract briskly for more than 24 h. FDB gave short (<1 mm), peroneus digiti quarti (PDQA) and peroneus longus (PL) gave intermediate (1-3 mm), while extensor digitorum longus (EDL), extensor hallucis longus (EHL), and soleus muscles released long (3-6 mm) fibers. When recorded with the fast dye Mag-Fluo-4, Ca 2+ transients of PDQA, PL, and EHL fibers showed the fast, narrow kinetics reminiscent of the morphology type II (MT-II), known to correspond to type IIX and IIB fibers. This is consistent with the fact that these muscles have over 90% of type II fibers compared with FDB (~80%) and soleus (~65%). Moving beyond FDB, we demonstrate for the first time the dissociation of several muscles, which render fibers spanning a range of lengths between 1 and 6 mm. These fibers are viable and give fast Ca 2+ transients, indicating that the MT-II can be generalized to IIX and IIB fast fibers, regardless of their muscle source. These results increase the availability of models for mature skeletal muscle studies.

Despite being classified as a high-income country, Panama still faces challenges in providing care for children and adolescents with cancer. Annually, 170 new cases of childhood cancer are diagnosed in Panama, and the survival rate is around 60%. To improve this, the establishment of a Pediatric Cancer Commission comprised of healthcare professionals and nonprofit organizations has been a critical step toward the objectives outlined in the Cure All framework of the World Health Organization Global Initiative for Childhood Cancer (GICC). To improve childhood cancer care in Panama, a workshop for cancer in children and adolescents was conducted with the support of St. Jude Children's Research Hospital, Children's Hospital Colorado, the Ministry of Health of Panama, and the Pan American Health Organization. The commissions established were on: Nursing, Palliative Care, Psychosocial, Hospital Registry, Early Diagnosis, and Health Services. Each commission has a specific project to be implemented in the period 2021-2029 to continue the progress toward improving childhood cancer care. Since the start of implementation of the GICC in Panama, important achievements have included the launch in 2021 of the Guide for the Diagnosis of Cancer in Children and Adolescents, and training programs for primary care health personnel. Through these programs, more than 1 000 health professionals have been trained on diagnosis of cancer in childhood and adolescence. Challenges remain, such as access to quality care, and it is essential to continue efforts to improve childhood cancer care.

The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins and revealing high diversity in midbrain and hindbrain neurons. Astrocytes and oligodendrocyte-lineage cells also exhibited regional diversity at multiple scales. The transcriptomic census of the entire human brain presented in this work provides a resource for understanding the molecular diversity of the human brain in health and disease.

The adult human brain comprises more than a thousand distinct neuronal and glial cell types, a diversity that emerges during early brain development. To reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics and uncovered cell states and trajectories in human brains at 5 to 14 postconceptional weeks (pcw). We identified 12 major classes that are organized as ~600 distinct cell states, which map to precise spatial anatomical domains at 5 pcw. We described detailed differentiation trajectories of the human forebrain and midbrain and found a large number of region-specific glioblasts that mature into distinct pre-astrocytes and pre-oligodendrocyte precursor cells. Our findings reveal the establishment of cell types during the first trimester of human brain development.

Here, we present a protocol for the generation of functional midbrain dopaminergic (mDA) neurons from human embryonic stem cells (hESCs), which mimics the development of the human ventral midbrain. We describe steps for hESC proliferation, induction of mDA progenitors, freezing stocks of mDA progenitors as an intermediate starting point to reduce the time to make mDA neurons, and maturation of mDA neurons. The entire protocol is feeder-free and uses chemically defined materials. For complete details on the use and execution of this protocol, please refer to Nishimura et al. (2023). 1 ., Competing Interests: Declaration of interests E.A. is founder shareholder and scientific advisor of Cholestenix Ltd (08771706)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Corynorhinus mexicanus bat is characterized by a specific form of reproductive asynchrony between males and females. After mating, some sperm remain in the male's epididymis, the organ where the sperm had matured. It has not yet been determined if apoptotic markers participate in the process of the maturation and/or elimination of these cells, so studying this topic is essential for our understanding of this species. Male bats were collected during three stages: Before mating; during the Mating phase; After mating and the final phase, which we call, Storage. Their epididymides were removed, weighed and measured. Sperm were extracted and the following sperm parameters were evaluated: active caspases, phosphatidylserine externalization, and mitochondrial membrane potential. Sperm from the testes enter the epididymis during Before mating, causing the organ to grow. During Mating phase, spermatozoa present a large amount of active caspases with externalization of phosphatidyl serine, even while still alive. This suggests that these two markers could participate in maturation and elimination, respectively., (© 2023 The Authors. Molecular Reproduction and Development published by Wiley Periodicals LLC.)

Temperature is a key abiotic factor that influences performance of several physiological traits in ectotherms. Organisms regulate their body temperature within a range of temperatures to enhance physiological function. The capacity of ectotherms, such as lizards, to maintain their body temperature within their preferred range influences physiological traits such as speed, various reproductive patterns, and critical fitness components, such as growth rates or survival. Here, we evaluate the influence of temperature on locomotor performance, sperm morphology and viability in a high elevation lizard species (Sceloporus aeneus). Whereas maximal values for sprint speed coincides with field active and preferred body temperature, short-term exposure at the same range of temperatures produces abnormalities in sperm morphology, lower sperm concentration and diminishes sperm motility and viability. In conclusion, we confirmed that although locomotor performance is maximized at preferred temperatures, there is a trade-off with male reproductive attributes, which may cause infertility. As a consequence, prolonged exposure to preferred temperatures could threaten the persistence of the species through reduced fertility. Persistence of the species is favored in environments with access to cooler, thermal microhabitats that enhance reproductive parameters., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects elderly people and constitutes a major source of disability worldwide. Notably, the neuropathological hallmarks of PD include nigrostriatal loss and the formation of intracellular inclusion bodies containing misfolded α-synuclein protein aggregates. Cardinal motor symptoms, which include tremor, rigidity and bradykinesia, can effectively be managed with dopaminergic therapy for years following symptom onset. Nonetheless, patients ultimately develop symptoms that no longer fully respond to dopaminergic treatment. Attempts to discover disease-modifying agents have increasingly been supported by translational molecular imaging concepts, targeting the most prominent pathological hallmark of PD, α-synuclein accumulation, as well as other molecular pathways that contribute to the pathophysiology of PD. Indeed, molecular imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can be leveraged to study parkinsonism not only in animal models but also in living patients. For instance, mitochondrial dysfunction can be assessed with probes that target the mitochondrial complex I (MC-I), while nigrostriatal degeneration is typically evaluated with probes designed to non-invasively quantify dopaminergic nerve loss. In addition to dopaminergic imaging, serotonin transporter and N-methyl-D-aspartate (NMDA) receptor probes are increasingly used as research tools to better understand the complexity of neurotransmitter dysregulation in PD. Non-invasive quantification of neuroinflammatory processes is mainly conducted by targeting the translocator protein 18 kDa (TSPO) on activated microglia using established imaging agents. Despite the overwhelming involvement of the brain and brainstem, the pathophysiology of PD is not restricted to the central nervous system (CNS). In fact, PD also affects various peripheral organs such as the heart and gastrointestinal tract - primarily via autonomic dysfunction. As such, research into peripheral biomarkers has taken advantage of cardiac autonomic denervation in PD, allowing the differential diagnosis between PD and multiple system atrophy with probes that visualize sympathetic nerve terminals in the myocardium. Further, α-synuclein has recently gained attention as a potential peripheral biomarker in PD. This review discusses breakthrough discoveries that have led to the contemporary molecular concepts of PD pathophysiology and how they can be harnessed to develop effective imaging probes and therapeutic agents. Further, we will shed light on potential future trends, thereby focusing on potential novel diagnostic tracers and disease-modifying therapeutic interventions., (© 2023. The Author(s).)

Mammalian sperm capacitation involves biochemical and physiological changes, such as an increase in intracellular calcium ion concentration ([Ca2+]i), hyperpolarization of the plasma membrane potential and sperm hyperactivation, among others. These changes provide sperm with the ability to fertilize. In the bat Corynorhinus mexicanus, there is an asynchrony between spermatogenesis and sperm storage in the male with the receptivity of the female. For instance, in C. mexicanus, spermatogenesis occurs before the reproductive season. During the reproductive period, sperm are stored in the epididymis for a few months and the testis undergoes a regression, indicating low or almost null sperm production. Therefore, it is unclear whether the elements necessary for sperm fertilization success undergo maturation or preparation during epididymis storage. Here, we characterized pH-sensitive motility hyperactivation and Ca2+ influx in sperm, regulated by alkalinization and progesterone. In addition, by electrophysiological recordings, we registered currents that were stimulated by alkalinization and inhibited by RU1968 (a CatSper-specific inhibitor), strongly suggesting that these currents were evoked via CatSper, a sperm Ca2+-specific channel indispensable for mammalian fertilization. We also found hyperpolarization of the membrane potential, such as in other mammalian species, which increased according to the month of capture, reaching the biggest hyperpolarization during the mating season. In conclusion, our results suggest that C. mexicanus sperm have functional CatSper and undergo a capacitation-like process such as in other mammals, particularly Ca2+ influx and membrane potential hyperpolarization., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Stem cell technologies provide new opportunities for modeling cells in health and disease and for regenerative medicine. In both cases, developmental knowledge and defining the molecular properties and quality of the cell types is essential. In this study, we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into functional midbrain dopaminergic (mDA) neurons. We found that laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3β inhibition plus FGF8b, improved midbrain patterning. In addition, neurogenesis and differentiation were enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high-quality molecularly defined midbrain cell types, including mDA neurons. Our study identifies novel factors important for human midbrain development and opens the door for a future application of molecularly defined hESC-derived cell types in Parkinson disease., Competing Interests: Conflict of interests E.A. is founder, shareholder and scientific advisor of Cholestenix Ltd (08771706)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Stem cell engineering of striatal medium spiny neurons (MSNs) is a promising strategy to understand diseases affecting the striatum and for cell-replacement therapies in different neurological diseases. Protocols to generate cells from human pluripotent stem cells (PSCs) are scarce and how well they recapitulate the endogenous fetal cells remains poorly understood. We have developed a protocol that modulates cell seeding density and exposure to specific morphogens that generates authentic and functional D1- and D2-MSNs with a high degree of reproducibility in 25 days of differentiation. Single-cell RNA sequencing (scRNA-seq) shows that our cells can mimic the cell-fate acquisition steps observed in vivo in terms of cell type composition, gene expression, and signaling pathways. Finally, by modulating the midkine pathway we show that we can increase the yield of MSNs. We expect that this protocol will help decode pathogenesis factors in striatal diseases and eventually facilitate cell-replacement therapies for Huntington's disease (HD)., Competing Interests: All authors declare no competing interests., (© 2022 The Authors.)

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field., Competing Interests: Declaration of interests S.W.S. is on the scientific advisory council of the Lewy Body Dementia Association and the MSA Coalition. S.W.S. is an editorial board member for the Journal of Parkinson Disease and JAMA Neurology. S.W.S. received research support from Cerevel Therapeutics. M.K. serves on the scientific advisory boards of Engine Biosciences, Casma Therapeutics, Cajal Neuroscience, and Alector and is a consultant to Modulo Bio and Recursion Therapeutics. Participation by researchers from Data Tecnica International, LLC in this project was part of a competitive contract awarded to Data Tecnica International, LLC by the National Institutes of Health to support open science research. M.A.N. also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc. E.A. is founder, shareholder, and scientific advisor of Cholestenix, Ltd., (Published by Elsevier Inc.)

Obesity is a condition that has been linked to male infertility. The current hypothesis regarding the cause of infertility is that sperm are highly sensitive to reactive oxygen species (ROS) during spermatogenesis in the testes and transit through the epididymides, so the increase in ROS brought on by obesity could cause oxidative stress. The aim of this study was to evaluate whether the activity of the enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) is capable of counteracting oxidative stress in sperm. The male Wistar rat was used as an overweight and obesity model, and analysis of fertility in these groups was carried out including the control group. Serum testosterone levels were determined, and the scrotal fat, testes, and epididymides were extracted. The epididymides were separated ini0 3 principal parts (caput, corpus, and cauda) before evaluating sperm viability, sperm morphology, damage to desoxyribonucleic acid of the sperm, and ROS production. The protein content and specific activity of the three enzymes mentioned above were evaluated. Results showed a gain in body weight and scrotal fat in the overweight and obese groups with decreased parameters for serum testosterone levels and sperm viability and morphology. Fertility was not greatly affected and no DNA integrity damage was found, although ROS in the epididymal sperm increased markedly and Raman spectroscopy showed a disulfide bridge collapse associated with DNA. The specific activities of CAT and GPX increased in the overweight and obesity groups, but those of SOD did not change. The amounts of proteins in the testes and epididymides decreased. These findings confirm that overweight and obesity decrease concentrations of free testosterone and seem to decrease protein content, causing poor sperm quality. Implications . An increase in scrotal fat in these conditions fosters an increase of ROS, but the increase of GPX and CAT activity seems to avoid oxidative stress increase in the sperm without damaging your DNA., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Lorena Ruiz-Valderrama et al.)

A new approach is proposed to obtain the kinetic parameters of biomass pyrolysis mixed with calcium catalyst. This approach involves the optimization of least squares (LS) with the Coats-Redfern integral method to avoid mathematical biases that may appear when applying the linear regression approach. The method was applied to the TGA data of pyrolysis of corn cob and corn cob mixed with 20 or 40 % by weight of CaO or CaCO 3 under N 2 atmosphere at temperatures between 25 and 700 °C. For raw cob, r 2 reaches 0.997. For corn cob mixed with 20 % by weight of CaO or CaCO 3 , r 2 reached 0.996-0.998, and for 40 % by weight, r 2 reached 0.836-0.957. Applying this method, the activation energy (EA) value of the raw cob pyrolysis is 58.35 kJ mol -1 , while the addition of CaO or CaCO 3 increases the EA to 69.33 and 66.07 kJ mol -1 , respectively. The method is simple to use and allows reliable values of kinetic parameters., Competing Interests: The authors declare no conflict of interest., (© 2022 Universidad Pontificia Bolivariana.)

Background: Assessing change and comparing groups requires high quality and invariant scales. However, there is limited evidence of simultaneous longitudinal and gender measurement invariance for depression scales. This evidence is even more scant with long-established panel studies from low and middle-income countries., Methods: In this paper, we used three waves (years 2002, 2005, and 2009) of a nationally representative panel study to examine the psychometric properties of the modified Calderon Depression Scale (CAL-DM)-a one-item exclusion of a depression scale designed for a population residing in a middle-income country (i.e., Mexico). Our analytical sample included 16,868 participants: 7,696 men and 9,172 women. Using Confirmatory Factor Analysis (CFA), we first examined overall fit in each wave, and then we tested time, gender, and time-gender measurement invariance across three waves. We also estimated and compared depression score means by gender and time. Finally, we examined the association between depression scores and self-rated health., Results: Our analyses indicated the CAL-DM is a robust scale, suitable for time, gender, and time by gender comparisons. Mean comparisons exemplified how the scale can be used as a latent variable or a summative score. Women have higher depression scores than men and the gap is narrowing from 3.4 in 2002 to 2.5 in 2009., Conclusions: The CAL-DM is a reliable instrument to measure depression in the Mexican general population that can be used for epidemiological research. Our results will contribute to a burgeoning line of research that examines the social determinants of depression, and the risk factors associated with different individuals' depression trajectories over the life course., (© 2022. The Author(s).)

Objective: The objective of this study was to analyze midterm outcomes of endovascular repair (EVAR) versus open repair (OR) for treatment of infrarenal abdominal aortic aneurysms (AAAs) in low surgical risk patients., Methods: Elective patients with AAAs undergoing treatment from 2003 to 2017 in a single, tertiary-care institution were evaluated. All patients with a low preoperative risk of complications and perioperative mortality (Medicare Aneurysm Scoring System <3) were included, and rates of perioperative and long-term mortality, adverse events, and reintervention were evaluated for EVAR and OR. A propensity score-matched cohort, leveling age, risk factors, and comorbidities was additionally performed., Results: A total of 227 patients were included (EVAR 59.9% and OR 40.1%) and followed for a mean of 80 ± 48 months. Patients undergoing EVAR were older (66.6 ± 5 vs. 64.1 ± 6 years; P <.001), had a higher body mass index (29.6 ± 4 vs 28.1 ± 3 kg/m 2 ; P = .005), a higher prevalence of chronic obstructive pulmonary disease (27.3% vs 9.9%; P = .001), and lower prevalence of dyslipidaemia (46.3% vs 65.9%; P = .004). Patients undergoing OR had a higher rate of major adverse events (19.7% vs 2.6%; P = .001) and 30-day reinterventions (8.8% vs. 1.5%; P = .016), with 30-day mortality being 0% in both groups. The propensity-score matched cohort included 76 matched pairs (1:1), with differences in hospital stay and major complications remaining significant, without affecting mortality. At 5-year follow-up, there were no significant differences in the reintervention rate (EVAR 18.5% vs OR 17.6%; P = .67) or survival (EVAR 85% vs OR 91%; P = .195)., Conclusions: In low surgical risk patients with AAAs, EVAR may offer comparable midterm results to OR, with a lower rate of major adverse events and a shorter in-hospital stay. With the current OR-first paradigm in low-risk patients, several factors should be taken into account for decision-making (anatomic suitability, risk of sexual dysfunction, risk of type 2 endoleaks, and need for follow-up)., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Fungal corneal ulcers are an uncommon, yet challenging, cause of vision loss. In the United States, geographic location appears to dictate not only the incidence of fungal ulcers, but also the fungal genera most encountered. These patterns of infection can be linked to environmental factors and individual characteristics of fungal organisms. Successful management of fungal ulcers is dependent on an early diagnosis. New diagnostic modalities like confocal microscopy and polymerase chain reaction are being increasingly used to detect and identify infectious organisms. Several novel therapies, including crosslinking and light therapy, are currently being tested as alternatives to conventional antifungal medications. We explore the biology of Candida, Fusarium, and Aspergillus, the three most common genera of fungi causing corneal ulcers in the United States and discuss current treatment regimens for the management of fungal keratitis., (Copyright © 2021. Published by Elsevier Inc.)

Caloric restriction (CR) has been shown to be an effective nutritional intervention for increasing longevity in some animal species. The objective of this study was to evaluate CR's effects on metabolic and reproductive parameters in 12-month-old male Wistar rats. The rats were distributed in three groups: control, CR at 15%, and CR at 35% for 6 (up to 18 months of age) and 12 months (up to 24 months of age). At the end of CR treatment, we evaluated reproductive (male sexual behavior (MSB), sperm quality) and biochemical parameters (plasma glucose, glucose-regulating hormone, and sex steroid levels), and quantified annexin V in the seminiferous epithelium. Results showed that MSB and sperm quality were improved after 6 months of CR associated with increases in plasma testosterone and decrease annexin V in the seminiferous epithelium of the testicles compared to their control group. The metabolic profile of the CR rats also improved compared to controls. However, these effects of CR on reproductive parameters were not maintained after 12 months of CR. Findings suggest that beginning CR at the age of maturity reestablishes the behavioral sexual response and reproductive function in older animals after 6 months of CR and improves endocrine functioning during aging.

Background: During sanitary emergencies such as the recent pandemic, health services can collapse. In these cases, remote orientation services such as call centers may help to debottleneck these services., Aim: To assess the demand and problem resolution of a clinical guidance telephone service during the COVID-19 pandemic., Material and Methods: The call registry between May and August 2020 of an orientation call center for COVID-19 was analyzed. The number of calls, sociodemographic features of callers, type of enquiry and given indications were described., Results: We analyzed 1,278 telephone calls, corresponding to 655 people. Sixty nine percent of queries were resolved during the call and in 31% of calls, users were referred to face-to-face evaluation. Two percent of these referrals were to an emergency service., Conclusions: The call center had a high level of resolution, favoring remote consultation and reducing face-to-face care, improving users'accessibility.

The development of efficient cell culture strategies for the generation of dopaminergic neurons is an important goal for transplantation-based approaches to treat Parkinson's disease. To identify extracellular matrix molecules that enhance differentiation and might be used in these cell cultures we have used micro-contact printed arrays on glass slides presenting 190 combinations of 19 extracellular matrix molecules selected on the basis of their expression during embryonic development of the ventral midbrain. Using long-term neuroepithelial stem cells (Lt-NES), this approach identified a number of matricellular proteins that enhanced differentiation, with the combination of Sparc, Sparc-like (Sparc-l1) and Nell2 increasing the number of tyrosine hydroxylase+ neurons derived from Lt-NES cells and, critically for further translation, human pluripotent stem cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ahmed, Owens, Toledo, Arenas, Bradley and ffrench-Constant.)

The epididymis is an organ that performs all the biochemical changes responsible for sperm maturation. During ageing, histological alterations in the epididymis and decreased protein synthesis have been found. This might affect the sperm maturation process. The aim of this study was to determine if the changes in the epididymis during ageing might cause alterations in sperm maturation. Wistar rats of 3-4months old (young) and 18-21months old (old) were used. The testosterone concentration was determined and the epididymides were dissected and divided in three regions: caput, corpus, and cauda. The tissues were used for histological processing and sperm extraction. Testosterone concentration decreased 34% in the old animals compared to the young ones. The distribution of mannose, sialic acid, and N-acetylglucosamine in the glycocalyx of the sperm membrane of old animals was different from that of young animals. The same occurred with phosphatidylserine externalisation and protein phosphorylation at tyrosine residues. Epididymis histology in old animals showed tubular and cellular degeneration. Our results suggest that ageing affects maturational markers, likely due to alterations in the epididymis as a result of the testosterone decrease associated with ageing.

Disordered cholesterol metabolism is linked to neurodegeneration. In this study we investigated the profile of cholesterol metabolites found in the cerebrospinal fluid (CSF) of Parkinson's disease (PD) patients. When adjustments were made for confounding variables of age and sex, 7α,(25R)26-dihydroxycholesterol and a second oxysterol 7α,x,y-trihydroxycholest-4-en-3-one (7α,x,y-triHCO), whose exact structure is unknown, were found to be significantly elevated in PD CSF. The likely location of the additional hydroxy groups on the second oxysterol are on the sterol side-chain. We found that CSF 7α-hydroxycholesterol levels correlated positively with depression in PD patients, while two presumptively identified cholestenoic acids correlated negatively with depression., Competing Interests: WG, PC, and YW were listed as inventors on the Swansea University patent “Kit and method for quantitative detection of steroids,” US9851368B2, licensed to Avanti Polar Lipids Inc., and Cayman Chemical Company by Swansea University. WG, JA-K, PC, EY, ST, EA, and YW were shareholders in CholesteniX Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Griffiths, Abdel-Khalik, Moore, Wijeyekoon, Crick, Yutuc, Farrell, Breen, Williams-Gray, Theofilopoulos, Arenas, Trupp, Barker and Wang.)

The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at embryonic day 10.5, profoundly reduced ChP size and development. However, Wnt5a expression was enriched in Foxj1-positive epithelial cells of 4V ChP plexus, and its conditional deletion in these cells affected the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical WNT signaling via ROR1 and ROR2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS transcription factors as upstream regulators of Wnt5a in the 4V ChP epithelium., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

The nitroaromatic compounds, known as organic pollutants, have arising attention due to their carcinogenic character, highly dangerous to human health. In this work, the Ag@ZnO/MWCNT ternary nanocomposite synthesized via conjugation of sonochemical and solvothermal treatments manifests high performance in the reduction of 4-nitrophenol in the aqueous media (TOF value of 246 min -1 μ mol metal -1 ). The incorporation of MWCNT onto the nanocomposite structure favored the reusing of the catalysts even after eight consecutive catalytic runs without catalysts cleaning nor product removal. Obtained samples were characterized by XRD, TEM, UV-vis, Raman and FTIR spectroscopies. It was found that ultrasonic treatment at relatively moderate conditions leads to functionalization of MWCNT, the appearance of C=C and OH groups and change of electronic properties of Ag@ZnO/MWCNT composite which provide its stable material dispersion in aqueous solution and high catalytic performance in the 4-nitrophenol reduction. This technique may be effectively applied for the functionalization of carbon including materials for their usage in an aqueous media., (© 2021 IOP Publishing Ltd.)

The sperm in the female's reproductive tract undergo changes to fertilize the oocyte (sperm capacitation). These changes are regulated by redox system. However, some assisted reproductive technologies require sperm capacitation under in vitro conditions, though this increases the generation of ROS. Therefore, the aim of this study was to evaluate the effect of GSH as an antioxidant agent during the capacitation of boar sperm [evaluated by calcium compartmentalization, tyrosine phosphorylation (Tyr-P), motility, viability, and acrosomal integrity], in vitro fertilization (evaluated by penetration, monospermy, and efficiency %), and later embryo development (evaluated by cleavage and blastocyst rates, total number of cells per blastocyst and blastocyst diameter). Four experimental groups with different GSH concentrations (0-control, 0.5, 1, and 5 mM) were formed. When 1-GSH was added to the medium, the percentage of capacitated sperm increased after 4 h of incubation; the localization of Tyr-P was modified at 1 h and 4 h of incubation depending on the GSH concentration. Percentages of total and progressive sperm motility also increased at 4 h of incubation, but only in the 5-GSH group compared to control. Viability, acrosomal integrity, and general Tyr-P (Western blot) not differ among the experimental groups. The addition of GSH during gamete interaction increased penetration, monospermy, and efficiency rates in the 1-GSH group compared to the others. However, the effect of GSH was not observed in cleavage and blastocyst rates compared to the control. In conclusion, adding GSH modulates sperm capacitation (by means of calcium compartmentalization and tyrosine phosphorilation pattern) depending on its concentration, and improves IVF output at 1-GSH during gamete interaction., (Copyright © 2020. Published by Elsevier Ltd.)

Cadmium (Cd) is a heavy metal related to a decrease in sperm parameters. The transit of spermatozoa through the epididymis is necessary to generate changes in the sperm membrane, such as the assembly of various carbohydrates that are added to the spermatazoan's surface to prepare it for successful fertilisation of the oocyte. No studies have yet analysed whether Cd alters the presence and distribution of these carbohydrates. We aimed to evaluate the changes induced by Cd in the distribution pattern of N-acetylglucosamine, sialic acid, mannose and fucose on the sperm membrane in the epididymis (e.g. caput, corpus, cauda) and if it alters the epididymal epithelium. Male Wistar pups were treated with Cd doses (0.125, 0.25 and 0.5mg/kg) on postnatal days 1-49. At postnatal day 90, they were humanely killed, sperm samples were obtained from the epididymis and tissue samples were taken for histological analysis. Cd concentrations in the blood and epididymis increased in proportion to the dose administered and decreased the serum testosterone levels and sperm quality. Histological analysis revealed alterations in the epithelium in all Cd-treated groups. Cd altered the distribution patterns of carbohydrates and fluorescence indices. All these alterations affected the structure and functioning of sperm.