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The integrity of fetal membranes enables biological functions that protect the fetus and maintain the pregnancy. Any compromise in fetal membrane function can predispose a pregnant woman to prelabor rupture of the membranes (pPROM) and subsequently to preterm birth (PTB). Epidemiologic data suggest that lead exposure during pregnancy is one of several risk factors associated with PTB and pPROM. This heavy metal can cross placental and fetal membrane barriers, disrupting homeostasis in these tissues. Autophagy contributes to the maintenance of fetal membrane homeostasis during gestation, and dysfunctional autophagy is associated with pPROM. In this study, we determined the mechanistic impact of lead-induced cellular changes, autophagy, senescence, and inflammation in chorion trophoblast cells (CTCs) and amnion epithelial cells (AECs) of the fetal membranes. Lead exposure in CTCs induced autophagy disfunction (increase in LC3B-II), augmented senescence (increased SA-β-galactosidase activity) and increased the release of inflammation. In AECs, lead exposure did effect autophagy, senescence, nor inflammation. The differential changes observed in CTCs and AECs after exposure to high lead concentrations may promote the weakening of fetal membranes and contribute to preterm rupture., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Problem: Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal-fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu., Method of Study: Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal-1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)-9 were measured in both amnion and choriodecidua compartments., Results: In a tissue-specific fashion profile, pretreatment with the physiologic concentration of Gal-1 significantly diminished the LPS-dependent secretion of TNF-α, IL-1β, Il-6, MCP1, MIP1α, RANTES, and MMP-9., Conclusion: Gal-1 elicits an anti-inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal-1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal-fetal interface., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Background: Latinx adults are disproportionately impacted by the interrelated challenges of food insecurity and nutrition sensitive chronic diseases. Food and nutrition insecurity can exacerbate the development and progression of chronic diseases, such as diabetes. Sustainable, effective interventions aimed at improving food insecurity and diabetes management for Latinx populations are needed., Methods: This hybrid type 1 trial evaluates the effectiveness of a multi-level intervention that includes a medically supportive food and behavioral lifestyle program on the primary outcome of Hemoglobin A1c (HbA1c) at 6 months. Latinx adults (n = 355) with type 2 diabetes (HbA1c of 6.0-12.0 %), overweight/obesity (BMI > 25 kg/m 2 ), and self-reported risk of food insecurity will be randomized 1:1 to intervention (12 weekly deliveries of vegetables, fruits, and whole-grain foods + culturally-modified behavioral lifestyle program) versus control (food deliveries after a 6-month delay). Outcome asessments will occur at 0, 6 and 12 months, and include HbA1c, dietary intake, psychosocial health outcomes, and diabetes-related stressors. In addition, food insecurity and the impact of the intervention on up to two household members will be measured. Qualitative interviews with patients, healthcare providers, and community partners will be conducted in accordance with Reach, Effectivenes, Adoption, Implementation, and Maintenence (RE-AIM) framework to identify barriers and best practices for future dissemination., Conclusions: The ADELANTE trial will provide novel insight to the effectiveness of a multi-level intervention on diabetes-related outcomes in Latinx adults. The mixed-method approach will also identity the reach of this 'Food is Medicine' intervention on additional household members to inform diabetes prevention efforts., Clinical Trial Registration: NCT05228860., 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 Elsevier Inc. All rights reserved.)

Purpose: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems., Methods: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay)., Results: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization., Conclusion: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hector J Aguado reports financial support was provided by AO Foundation. Hector J Aguado reports financial support was provided by Government of Castile and Leon Ministry of Health. If there are other authors, they 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. Published by Elsevier Ltd.)

Informal caregivers of older people face demanding responsibilities that can negatively affect their wellbeing, highlighting the relevance of interventions that address their specific needs. This study aimed to assess the effects of a group music therapy program based on different songwriting approaches applied to informal caregivers of older adults with dependency. A sample of 113 caregivers participated, being assigned either to the intervention ( n = 60) or the control group ( n = 53). The intervention group caregivers received 10 weekly sessions of the songwriting program, while the control group continued with their usual care service. Psychological symptoms and health-related quality of life (HRQoL) were assessed at baseline and follow-up using the State-Trait Anxiety Inventory, Beck Depression Inventory-II, Zarit Burden Interview, and SF-36. Group × Time interactions revealed significant improvements in the intervention group compared to the control one in trait anxiety ( p = 0.022), social functioning ( p = 0.013), role limitations due to physical problems ( p = 0.020), and physical component summary ( p = 0.022). These findings provided valuable evidence on this novel intervention, showing positive effects for caregivers' wellbeing. The current research emphasizes the importance of considering music therapy as a potential intervention among caregiver support programs.

Studies of divorce's effects on children have been oriented toward the parents' characteristics, ignoring their extended families. In the current study we collected data from 414 participants, both divorced parents and the children's extended families in Peru (155) and Spain (259). Participants completed a questionnaire on attitudes toward the parents, and the Short Dark Tetrad questionnaire. Multivariate tests were conducted on participants' responses, showing that negative attitudes toward parents are not very strong but that attitudes toward fathers are more negative than attitudes toward mothers. Custodial parents are perceived less negatively, and parents who share custody are perceived the least negatively. Extended family members hold more negative attitudes against parents than the parents themselves. Mothers have significantly more negative attitudes toward fathers than the fathers towards mothers. Dark traits are a significant predictor of negative attitudes toward the mother but not toward the father. The perception of unhappiness in the child was predicted by negative attitudes toward the parents. Non-parents tend to evaluate both parents more negatively compared to parents' mutual perceptions. There was an effect on dark traits, negative attitudes against parents, and perception of unhappiness in the child. Peruvians scored significantly higher in all variables., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Miguel Clemente reports financial support was provided by 10.13039/501100010801Xunta de Galicia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The precise function of specialized GABAergic interneuron subtypes is required to provide appropriate synaptic inhibition for regulating principal neuron excitability and synchronization within brain circuits. Of these, parvalbumin-type (PV neuron) dysfunction is a feature of several sex-biased psychiatric and brain disorders, although, the underlying developmental mechanisms are unclear. While the transcriptional action of sex hormones generates sexual dimorphism during brain development, whether kinase signaling contributes to sex differences in PV neuron function remains unexplored. In the hippocampus, we report that gephyrin, the main inhibitory post-synaptic scaffolding protein, is phosphorylated at serine S268 and S270 in a developmentally-dependent manner in both males and females. When examining Gphn S268A/S270A mice in which site-specific phosphorylation is constitutively blocked, we found that sex differences in PV neuron density in the hippocampal CA1 present in WT mice were abolished, coincident with a female-specific increase in PV neuron-derived terminals and increased inhibitory input onto principal cells. Electrophysiological analysis of CA1 PV neurons indicated that gephyrin phosphorylation is required for sexually dimorphic function. Moreover, while male and female WT mice showed no difference in hippocampus-dependent memory tasks, Gphn S268A/S270A mice exhibited sex- and task-specific deficits, indicating that gephyrin phosphorylation is differentially required by males and females for convergent cognitive function. In fate mapping experiments, we uncovered that gephyrin phosphorylation at S268 and S270 establishes sex differences in putative PV neuron density during early postnatal development. Furthermore, patch-sequencing of putative PV neurons at postnatal day 4 revealed that gephyrin phosphorylation contributes to sex differences in the transcriptomic profile of developing interneurons. Therefore, these early shifts in male-female interneuron development may drive adult sex differences in PV neuron function and connectivity. Our results identify gephyrin phosphorylation as a new substrate organizing PV neuron development at the anatomical, functional, and transcriptional levels in a sex-dependent manner, thus implicating kinase signaling disruption as a new mechanism contributing to the sex-dependent etiology of brain disorders., (© 2024. The Author(s).)

Latina women have a high prevalence of obesity and obesity-related chronic diseases, such as diabetes. Approximately half of Latinas with obesity will also experience food insecurity, or a lack of access to enough food for an active and healthy life. Food insecurity is a barrier for effective prevention and management of obesity-related chronic diseases. The goal of this type 1 hybrid comparative effectiveness trial is to compare a culturally-tailored diabetes prevention intervention with and without medically supportive groceries. Adult Latina women (n = 412) with obesity (Body Mass Index (BMI) of >30 kg/m 2 ) and food insecurity will be 1:1 randomized to the Vida Sana intervention (control), or to Vida Sana y Completa (intervention plus integrated treatment for food insecurity). Vida Sana is an evidence-based culturally tailored, 12-month diabetes prevention intervention that targets at least 5% weight loss and at least 150 min/week of moderate-to-vigorous physical activity. Participants enrolled in Vida Sana y Completa will also receive 12 weekly deliveries of medically supportive groceries. Those in Vida Sana alone will receive information on local food resources. Participants will be assessed at baseline and every 6 months for 24 months. The primary outcome is weight loss at 12 months. Secondary outcomes include weight loss maintenance, diet quality, and quality of life. Barriers and facilitators of implementation will be assessed using mixed methods according to the Consolidated Framework for Implementation Research. This study will provide critical evidence for addressing the combination of obesity and food insecurity in primary care for diabetes prevention. Trial Registration: NCT052111., 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 © 2023. Published by Elsevier Inc.)

Fluvial sediment analysis and water quality assessment are useful to identify anthropic and natural sources of pollution in rivers. Currently, there is a lack of information about water quality in the Pixquiac basin (Veracruz state, Mexico), and this scarcity of data prevents authorities to take adequate measures to protect water resources. The basin is a crucial territory for Xalapa, the capital city of Veracruz state, as it gets 39% of its drinkable water from it. This research analyzed 10 physicochemical parameters and 12 metal concentrations in various rivers and sources during two seasons. Dissolved metals presented average concentrations (µg/L): Al (456.25) > Fe (199.4) > Mn (16.86) > Ba (13.8) > Zn (7.6) > Cu (1.03) > Pb (0.27) > As (0.12) > Ni (0.118) (Cd, Cr and Hg undetectable). Metals in sediment recorded average concentrations (ppm): Fe (38575) > Al (38425) > Mn (460) > Ba (206.2) > Zn (65.1) > Cr (29.8) > Ni (20.9) > Cu (16.4) > Pb (4.8) > As (2.1) (Cd and Hg undetectable). During the rainy season, Water Quality Index (WAWQI) classified stations P17 and P18's water as "unsuitable for drinking" with values of 110.4 and 117.6. Enrichment factor (EF) recorded a "moderate enrichment" of Pb in sediment in P24. Pollution was mainly explained by wastewater discharges in rivers but also because of erosion and rainfall events. Statistical analysis presented strong relationships between trace and major metals which could explain a common natural origin for metals in water and sediment: rock lixiviation., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The interrelation of cancer with venous thromboembolism is established, yet the specific impact on the incidence and progression of superficial vein thrombosis (SVT) remains unclear., Objectives: To investigate the association between SVT and malignancies, focusing on risk factors, presentation, course and complications., Methods: A single-center prospective observational study of patients diagnosed with DVT or SVT referred to a venous thromboembolism clinic between January 2013 and April 2018., Results: Of the 632 patients, 205 presented with SVT at referral, 16.6% having active cancer. Significant associations were found between active cancer and the risk of developing proximal SVT (RR 1.54 [1.18-2.03] p < 0.01), SVT within 3 cm from junction (RR 2.01 [1.13-3.72] p = 0.019), bilateral SVT (RR 8.38 [2.10-33.43] p < 0.01) and SVT affecting multiple veins (RR 2.42 [1.40-4.20] p < 0.01), with a higher risk of persistence (RR 1.51 [1.18-1.95] p < 0.01) and progression (RR 5.75 [2.23-14.79] p < 0.01) at initial assessment. Patients with SVT and no malignancy history demonstrated an elevated risk for new-onset cancer during follow-up (RR 1.43 [1.13-1.18] p = 0.022), especially in cases of proximal or bilateral SVT, initial progression or subsequent DVT or PE. No significant differences were observed in persistence, recurrence or complications during initial evaluation or follow-up across different pharmacological treatments., Conclusions: Research suggests a probable link between cancer history and the development of SVT. SVT presented more severely in cancer patients. SVT, especially in its more complex forms, could serve as a predictive marker for the future development of cancer. Treatment approaches varied, no significant differences in outcomes were noted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.

RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.

Objective: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites., Methods: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis., Results: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites)., Significance: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Leukocyte infiltration into the maternal-fetal interface is a consequence of the robust inflammation in the gestational tissues during term labor and preterm labor with or without infection. During pregnancy, the fetal membranes act as a physical barrier that isolates the fetus into the amniotic cavity, keeping it in an optimal environment for its development. In addition, the fetal membranes possess immunological competencies such as the secretion of cytokines and chemokines in response to different stimuli. Clinical and experimental evidence indicates that these tissues are involved in the extensive chemotaxis of immune cells in normal or pathological conditions.Few studies have evaluated the chemotactic capacities of the fetal membranes considering that this tissue is composed of two adjacent tissues, the amnion and the chorion, which have different characteristics. Although these tissues function as a unit, their response is complex since there is an interaction between them, where each tissue contributes differently. The protocol described here allows us to evaluate the in vitro chemotactic capacities of fetal membranes in response to various applied stimuli, considering the contribution of each of their components (amnion and choriodecidua) using a Boyden chamber assay and phenotyping the chemo-attracted leukocytes by flow cytometry., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The study of the human placenta has always been appealing, given the importance of this temporal organ capable of sustaining the beginning of life and development of a new human being within the womb. Culturing placental explants has been an easy and reliable method to study some placental morphological, biochemical, and physiological features for a very long time. Besides low time consumption, requirement of few resources, and wide versatility, the placental explant in vitro culture retains cell-cell interaction in a 3D structure resembling the in vivo setting, which is why it is the option of choice for many researchers in the field. This chapter will describe a simplified method for culturing explants from human term placentas., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

During pregnancy, the fetal membranes composed of the amnion and chorodecidua constitute a selective barrier separating two distinct environments, maternal and fetal. These tissues have the function of delimiting the amniotic cavity. Their histological complexity gives them physical, mechanical, and immunological properties to protect the fetus. Although the study of the amnion, chorion, and decidua separately provides knowledge about the functions of the fetal membranes, the protocol we describe in this chapter has the advantage of maintaining the biological and functional complexity of these tissues. In addition, this experimental model allows the researcher to recreate various pathological scenarios because this model allows for differential stimulation of the amnion or choriodecidua., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Since the early 1960s, researchers began culturing placental cells to establish an in vitro model to study the biology of human trophoblasts, including their ability to differentiate into syncytiotrophoblasts and secrete steroid and peptide hormones that help sustain a viable pregnancy. This task was addressed by testing different serum concentrations, cell culture media, digestive enzymes, growth factors, substrate coating with diverse proteins from the extracellular matrix, and so on. Among the many methodological challenges, the contamination of trophoblasts with other cell types, such as immune and stromal cells, was a matter of concern. However, introducing the Percoll gradient to isolate cytotrophoblasts was an excellent contribution, and later, the depletion of contaminating cells by using magnetic bead-conjugated antibodies also helped increase the purity of cytotrophoblasts. Herein, with some modifications, we describe a rapid and easy method for cytotrophoblast isolation from the term human placenta based on the previously reported method by Harvey Kliman et al. (Endocrinology 118:1567-1582, 1986). This method yields about 40-90 million cells from a single placenta, with a purity of around 85-90%., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

With funding from the National Institutes of Health's Community Engagement Alliance, starting in fall 2020, 11 academic medical centers and 75 community partners came together as the California Alliance Against COVID-19 to address COVID-19 inequities in California. Using data from focus groups, statewide meetings, and a statewide partner survey, we describe how promotoras and community health workers (P/CHWs; n = 540) helped to promote access to COVID-19 information, testing, and vaccination. We highlight opportunities to promote health equity among other public health collaborators with a P/CHW model. ( Am J Public Health . 2024;114(S1):S45-S49. https://doi.org/10.2105/AJPH.2023.307471).

This article presents a comprehensive genetic study focused on pre-Hispanic individuals who inhabited the Aburrá Valley in Antioquia, Colombia, between the tenth and seventeenth centuries AD. Employing a genetic approach, the study analyzed maternal lineages using DNA samples obtained from skeletal remains. The results illuminate a remarkable degree of biological diversity within these populations and provide insights into their genetic connections with other ancient and indigenous groups across the American continent. The findings strongly support the widely accepted hypothesis that the migration of the first American settlers occurred through Beringia, a land bridge connecting Siberia to North America during the last Ice Age. Subsequently, these early settlers journeyed southward, crossing the North American ice cap. Of particular note, the study unveils the presence of ancestral lineages from Asian populations, which played a pivotal role in populating the Americas. The implications of these results extend beyond delineating migratory routes and settlement patterns of ancient populations. They also enrich our understanding of the genetic diversity inherent in indigenous populations of the region. By revealing the genetic heritage of pre-Hispanic individuals from the Aburrá Valley, this study offers valuable insights into the history of human migration and settlement in the Americas. Furthermore, it enhances our comprehension of the intricate genetic tapestry that characterizes indigenous communities in the area.

Background: Nearly half of Latinx adults in the US are obese, making effective weight loss interventions crucial to prevent associated chronic conditions., Objective: To identify factors associated with increased session attendance and clinically significant weight loss among Latinx adults., Participants: Latinx participants from the Vivamos Activos (n = 207), Vida Sana (n = 191), and HOMBRE (n = 424 Latinx men) randomized clinical trials., Design: Post-hoc analysis of randomized controlled trial data., Intervention: Culturally-adapted behavioral weight loss interventions based on the Diabetes Prevention Program among Latinx adults over 12 months., Main Outcome Measure: Demographic, clinical, and psychosocial predictors of session attendance and 5% weight loss at 12-months., Statistical Analysis Performed: Bi-variable associations between baseline characteristics and outcomes were tested with chi-square and t-tests. Those with p-value< 0.15 were then included in stepwise logistic regressions., Results: Participants (N = 822) were middle age with diverse socioeconomic backgrounds. Older age in the Vivamos Activos and Vida Sana trials, and lower acculturation in the HOMBRE trial were significant predictors of increased session attendance. Factors associated with 5% weight loss varied by trials. These included younger age (OR 0.96 95% CI 0.92, 0.99) in Vivamos Activos, higher acculturation (OR 1.88 95% CI 1.05, 3.37) in Vida Sana, and higher education (OR 3.20 95% CI 1.3, 7.03) and greater body image dissatisfaction (OR 1.29, 95% CI 1.04, 1.6), and lower acculturation (0.69 95% CI 0.5, 0.96) in HOMBRE., Conclusions: Few and conflicting baseline characteristics were associated with session attendance and clinically significant weight loss, suggesting that alternative approaches to optimizing interventions are needed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Purpose: Daily smoking or risky drinking increases the risk of complications after surgery by ~50%. Intensive prehabilitation aimed at complete cessation reduces the complication rate but is time-consuming. The purpose of this study was to carry out preoperative pilot tests (randomized design) of the feasibility (1A) and validation (1B) of two novel prehabilitation apps, habeat® (Ha-app) or rehaviour® (Re-app)., Methods: Patients scheduled for hip or knee arthroplasty with daily smoking, risky drinking, or both were randomised to one of the two apps. In part 1A, eight patients and their staff measured feasibility on a visual analog scale (VAS) and were interviewed about what worked well and the challenges requiring improvement. In part 1B, seven patients and their staff tested the improved apps for up to two weeks before validating the understanding, usability, coverage, and empowerment on a VAS and being interviewed., Results: In 1A, all patients and staff returned scores of ≥5 for understanding the apps and mostly suggested technical improvements. In 1B, the scores varied widely for both apps, with no consensus achieved. Two of four patients (Ha-app) and one-third of the patients (Re-app) found the apps helpful for reducing smoking, but without successful quitting. The staff experienced low app competencies among patients and high time consumption. Specifically, patients most often needed help for the Ha-app, and the staff most often for Re-app; however, the staff reported the Re-app dashboard was more user-friendly. Support and follow-up from an addiction specialist staff member were suggested to complement the apps, thereby increasing the time consumption for staff., Conclusions: This pilot study to test prototype apps generated helpful feedback for the app developers. Based on the patient and staff comments, multiple improvements in functionality seem required before scaling up the evaluation for effect on prehabilitation and postoperative complications., (© 2023. The Author(s).)

Patients with chronic obstructive pulmonary disease (COPD) may experience exacerbations. During severe exacerbations, nutritional and endocrinological comorbidities can play an important role in the clinical and functional aspects of these patients. The aim of this study was to analyse the influence of the presence of diabetes mellitus (DM) and nutritional parameters on the deterioration of symptoms and quality of life during a severe exacerbation in patients with COPD. An observational study was conducted on COPD patients admitted due to an exacerbation. The COPD Assessment Test (CAT) questionnaire was administered, and clinical and functional parameters were compared based on the presence of nutritional and endocrinological alterations. A total of 50 patients were included, of whom 30 (60%) were male. The mean age was 70.5 years (standard deviation (SD) 9.6). The median CAT score during exacerbation was 25 (interquartile range (IQR) 17.5-30), and the baseline score was 13.5 (IQR 7-19), which represented a statistically significant difference ( p < 0.001). Patients with iron deficiencies had a lower total CAT score ( p = 0.041), specifically for items related to daily activity ( p = 0.009) and energy ( p = 0.007). Diabetic patients exhibited a greater decline in pulmonary function during exacerbation ( p = 0.016), while patients with high thyroid-stimulating hormone (TSH) levels had a shorter hospital stay ( p = 0.016). For COPD patients admitted due to an exacerbation, the metabolic assessment is useful and relevant in the clinical set-up, as endocrinological comorbidities negatively affect clinical and functional aspects of these patients.

Introduction: Epilepsy is one of the most common neurological conditions worldwide. Despite many antiseizure medications (ASMs) being available, up to one-third of patients do not achieve seizure control. Preclinical studies have shown treatment with sodium selenate to have a disease-modifying effect in a rat model of chronic temporal lobe epilepsy (TLE)., Aim: This randomised placebo-controlled trial aims to evaluate the antiseizure and disease-modifying effects of sodium selenate in people with drug-resistant TLE., Methods: This will be a randomised placebo-controlled trial of sodium selenate. One hundred and twenty-four adults with drug-resistant TLE and ≥4 countable seizures/month will be recruited. Outcomes of interest will be measured at baseline, week 26 and week 52 and include an 8-week seizure diary, 24-hour electroencephalogram and cognitive, neuropsychiatric and quality of life measures. Participants will then be randomised to receive a sustained release formulation of sodium selenate (initially 10 mg three times a day, increasing to 15 mg three times a day at week 4 if tolerated) or a matching placebo for 26 weeks., Outcomes: The primary outcome will be a consumer codesigned epilepsy-Desirability of Outcome Rank (DOOR), combining change in seizure frequency, adverse events, quality of life and ASM burden measures into a single outcome measure, compared between treatment arms over the whole 52-week period. Secondary outcomes will compare baseline measures to week 26 (antiseizure) and week 52 (disease modification). Exploratory measures will include biomarkers of treatment response., Ethics and Dissemination: The study has been approved by the lead site, Alfred Hospital Ethics Committee (594/20). Each participant will provide written informed consent prior to any trial procedures. The results of the study will be presented at national and international conferences, published in peer-reviewed journals and disseminated through consumer organisations., Conclusion: This study will be the first disease-modification randomised controlled trial in patients with drug-resistant TLE., Trial Registration Number: ANZCTR; ACTRN12623000446662., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

IZUMO1 is an acrosome transmembrane protein implicated in the adhesion and fusion of gametes. This study aims to describe the distribution of IZUMO1 in human sperm under different physiological conditions: before capacitation (NCS), at one-hour capacitation (CS1), after a hyaluronic acid (HA) selection test (mature, MS1 and immature, IS1), and induced acrosome reaction from one-hour-capacitated sperm (ARS1). The data obtained in NCS, CS1, and MS1 significantly highlight dotted fluorescence in the acrosomal region (P1) as the major staining pattern (~70%). Moreover, we describe a new distribution pattern (P2) with a dotted acrosomal region and a labelled equatorial region that significantly increases in HA-bound spermatozoa, suggesting the onset of the migration of IZUMO1. In contrast, unbound spermatozoa presented an increase in P3 (equatorial region labelled) and P4 (not labelled). Finally, costaining to observe IZUMO1 distribution and acrosome status was performed in ARS1. Interestingly, we reported a variety of combinations between the IZUMO1 staining patterns and the acrosomal stages. In conclusion, these data show as a novelty the diffusion of the IZUMO1 protein during different physiological conditions that could contribute to the improvement in sperm selection techniques.

The quality of life and human survival is dependent on sustainable development and sanitation of water bodies in an environment. The present research focuses on cyclicity data of more than 750,000 records of parameters associated with the water quality from a rural-urban river monitoring stations in real-time from River Atoyac in Central Mexico. The events detected in the instrumental records correlated with 2528 laboratory and instrumental determinations. The 64 polluting compounds were grouped into inorganic compounds (metals and metalloids) and organic compounds (pesticides, herbicides, hydrocarbons). Metal associated compounds were grouped along mechanical, pharmaceutical and textile industries which associates itself with the entry of polluting components. The cyclicity of the events was detected through Discrete Fourier Transformation time series analysis identifying the predominant events in each station. These highlight the events at 23-26 h corresponding to a circadian pattern of the metabolism of the city. Likewise, pollution signals were detected at 3.3, 5.5, and 12-14 h, associated with discharges from economic activities. Multivariate statistical techniques were used to identify the circadian extremes of a regionalized cycle of polluting compounds in each of the stations. The results of this research allow pollution prevention using a mathematical analysis of time series of different quality parameters collected at monitoring stations in real-time as a tool for predicting polluting events. The DFT analysis makes it possible to prevent polluting events in different bodies of water, allowing to support the development of public policies based on the supervision and control of pollution., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Given that low physical activity levels and poor dietary intake are co-occurring risk factors for chronic disease, there is a need for interventions that target both health behaviors, either sequentially or simultaneously. Little is known about participant characteristics that are associated with better or worse response to sequential and simultaneous interventions., Method: The 12-month Counseling Advice for Lifestyle Management (CALM) randomized trial (N = 150; M age  = 55.3 years) targeted these two behaviors either via a sequential approach - dietary advice first then exercise advice added ("Diet-First") or exercise advice first then dietary advice added ("Exercise-First") - or via a simultaneous approach. The objective was to examine demographic, clinical, and psychosocial moderators of intervention effects on 12-month change in (1) moderate-to-vigorous physical activity (MVPA), (2) fruit/vegetable intake, (3) caloric intake from saturated fat, and (4) weight. Hierarchical regressions first compared Diet-First to Exercise-First, followed by comparisons of these arms combined ("sequential") to the simultaneous arm., Results: Older age, higher baseline BMI, and lower social support were associated with higher MVPA in Exercise-First vs. Diet-First, while lower tangible support was associated with higher fruit/vegetable intake in Exercise-First but not in Diet-First. Poor sleep was associated with higher levels of MVPA in the sequential arm than in the simultaneous arm. Lower vitality was associated with greater weight loss in the sequential arm than in the simultaneous arm, while the opposite was true for those who were not married., Conclusion: Identifying moderators of treatment response can allow the behavioral medicine field to enhance intervention efficacy by matching participant subgroups to their best-fitting interventions., Trial Registration: NCT00131105., (© 2023. International Society of Behavioral Medicine.)

Multilevel interventions are increasingly recommended to increase physical activity (PA) but can present evaluation challenges. Participatory qualitative evaluation methods can complement standard quantitative methods by identifying participant-centered outcomes and potential mechanisms of individual and community-level change. We assessed the feasibility and utility of Ripple Effects Mapping (REM), a novel qualitative method, within the context of a multi-level cluster randomized trial, Steps for Change. Housing sites with ethnically diverse, low-income aging adults were randomized to a PA behavioral intervention alone or in combination with a citizen science-based intervention (Our Voice) for promoting PA-supportive neighborhoods. Four REM sessions were conducted after 12 months of intervention and involved six housing sites (n = 35 participants) stratified by intervention arm. Interviews (n = 5) were also conducted with housing site staff. Sessions leaders engaged participants in visually mapping intended and unintended outcomes of intervention participation and participant-driven solutions to reported challenges. Maps were analyzed using Excel and Xmind 8 Pro and data were classified according to the socio-ecological model. Eight themes were identified for outcomes, challenges, and solutions. Most themes (6/8) were similar across intervention arms, including increasing PA and PA tracking, improving health outcomes, and increasing social connectedness. Groups (n = 2) engaged in Our Voice additionally identified increased community knowledge and activities directly impacting local environmental change (e.g., pedestrian infrastructure changes). Housing staff interviews revealed additional information to enhance future intervention recruitment, sustainability, and implementation. Such qualitative methodologies can aid in evaluating multi-level, multi-component interventions and inform future intervention optimization, implementation, and dissemination., (© Society of Behavioral Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Developing advanced technologies and their integration into educational spaces generates new training opportunities. Examples of these are Future Classrooms (FC) and Smart Learning Environments (SLE), two concepts linked to educational innovation through technology but also have their differences. This paper aims to identify the similarities and differences between FC developed in the Spanish formal educational context concerning the theory of SLE. This study follows an exploratory research methodology using an ad hoc questionnaire applied transversally to a representative sample of teachers involved in the SLE (N = 66). SPSS V. 28 software was used. In relation to the results, some statistics (mean, standard deviation, kurtosis and skewness) were used to analyse the developed FC practices and professional satisfaction. In conclusion, the FC are at an initial stage of development in Spain, and although they could represent an approximation to what would be the practical basis of SLE, there are still several aspects to be developed, especially in relation to the technologies used and the dimension of attention to diversity. In relation to SLE technologies, they are related to the automation of certain processes and include artificial intelligence, learning analytics and sensors, among others. On the other hand, these technologies are not widely used in the FC, and the use of other more conventional technological resources, such as interactive whiteboards, online collaborative environments, LMS platforms, etc. In terms of attention to diversity, despite the existence of initiatives to personalise the learning experience in FC, assistive technologies are not considered, nor is automatic personalisation through certain SLE technologies., Competing Interests: 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., (© 2023 The Authors.)

This article describes a one-degree-of-freedom haptic device that can be applied to perform three different exercises for shoulder rehabilitation. The device is based on a force control architecture and an adaptive speed PI controller. It is a portable equipment that is easy to use for any patient, and was optimized for rehabilitating external rotation movements of the shoulder in patients in whom this was limited by muscle-skeletal injuries. The sample consisted of 12 shoulder rehabilitation sessions with different shoulder pathologies that limited their range of shoulder mobility. The mean and standard deviations of the external rotation of shoulder were 42.91 ± 4.53° for the pre-intervention measurements and 53.88 ± 4.26° for the post-intervention measurement. In addition, patients reported high levels of acceptance of the device. Scores on the SUS questionnaire ranged from 65 to 97.5, with an average score of 82.70 ± 9.21, indicating a high degree of acceptance. The preliminary results suggest that the use of this device and the incorporation of such equipment into rehabilitation services could be of great help for patients in their rehabilitation process and for physiotherapists in applying their therapies.

The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface., 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 © 2023 Flores-Espinosa, Méndez, Irles, Olmos-Ortiz, Helguera-Repetto, Mancilla-Herrera, Ortuño-Sahagún, Goffin and Zaga-Clavellina.)

Anxiety disorders are the most prevalent co-morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co-occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours. Firstly, we characterize the developmental trajectories of locomotor, social behaviour and anxiety traits in a mouse model of ASD. We highlight that the anxiety phenotype is a late-onset emerging phenotype in mice with a Shank3 Δe4-22 mutation. Consequently, we used an shRNA strategy to model Shank3 insufficiency in the bed nucleus of the stria terminalis (BNST), a brain region exerting a powerful control on anxiety level. We found that Shank3 downregulation in the anteromedial BNST (amBNST) induced anxiogenic effects and enhanced social avoidance after aversive social defeat. Associated with these behavioural defects, we showed alteration of glutamatergic synaptic functions in the amBNST induced by Shank3 insufficiency during adolescence. Our data strongly support the role of Shank3 in the maturation of amBNST, and its key role in anxiety control. Our results may further help to pave the road on a better understanding of the neuronal mechanisms underlying anxiety disorders implicated in ASDs., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background and Objective: The aim of our study is to define the role of Pulsed-Doppler (PW-Doppler) Ultrasound of the Common Femoral Vein (CFV) in the assessment of dilatation Inferior Vena Cava (IVC), probability of Pulmonary Hypertension (PH), Tricuspid Regurgitation (TR), and Tricuspid annular plane systolic excursion (TAPSE)., Methods: This is a prospective two-hospital study in 74 patients admitted with acute heart failure (AHF). We performed PW-Doppler ultrasound of the common femoral vein, Point of Care (POC) cardiac ultrasonography and assessment of the IVC at the time of admission, as well as PW-Doppler and ultrasound of the IVC at hospital discharge., Results: The detection of a pulsatile flow (138 scans) had an excellent ROC curve for the detection of IVC greater than 2cm (AUC 0.931, Sn 95%, Sp 90%, PPV 93%, NPV 94%) with an Odds Ratio (OR) of 211.2 (95% confidence interval 48.13-926.72). The pulsatility of the flow also had the highest performance in the detection of PH (AUC 0.8, Sn 95%, Sp 64%, PPV 84%, NPV 84%) and in the detection of moderate-severe TR (AUC 0.79, Sn 95%, Sp 67%, PPV 88%, NPV 78%). If the flow is continuous, we can reasonably rule out diminished TAPSE (NPV 89%)., Conclussion: Detection of PW-Doppler flow of the CFV may be an alternative window for the detection of an IVC dilation of 2cm, significant TR, and the likelihood of high PH in acute heart failure. It also allows us to reasonably rule out dysfunction of the right ventricle in cases of normality in these patients., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

This systematic review aimed to assess the efficacy of motor adaptation during walking on a split-belt treadmill (SBT) under different learning conditions in adults with stroke. We searched randomized clinical trials and case studies that used SBT under different learning conditions published between January 2011 and April 2022 in four databases: Pubmed, Scopus, Web of Science, and Brain-URJC. The following data were extracted: objectives, interventions, population, number of sessions, outcome measures, and results. The methodological quality of quantitative studies was evaluated using the Critical Review Form. We identified 79 studies, from which six met the criteria for this systematic review (four randomized clinical trials and two case series). The six selected studies included 156 patients with chronic stroke; 62.8% men, age 21-85 years. Walking on a SBT can generate artifacts in the gait pattern depending on the experimental conditions. Two series of cases and one trial reported that the dual motor task - the inclination of the slope of the SBT or the gradual change of speed - promotes the retention of the artifacts generated by the disturbances, resulting in the learning of a new motor pattern. However, combining physical exercise of different intensity and at different times with SBT, maximizing or minimizing errors, or including variable or constant speed disturbances do not seem to affect the locomotor adaptation process.

During fertilization, sperm hyaluronidase activity is essential for spermatozoa to successfully penetrate the hyaluronic acid-enriched extracellular matrix of the cumulus cells. Since molecular chaperones, as the heat shock protein A2, are typically involved in bringing hyaluronic acid receptors to the cell surface, here we evaluated the presence and spatial location of HSPA2 on human spermatozoa based on its hyaluronic acid binding capacity. This study included 16 normozoospermic sperm samples from volunteering donors. The location of HSPA2 was studied in cells before and after 1-h incubation under capacitating conditions, as well as in spermatozoa selected according to their ability of binding to hyaluronic acid. Our results showed no significant differences in HSPA2 immunofluorescent cells before and after 1 h of incubation in capacitating conditions. Nevertheless, after hyaluronic acid selection, the percentage of HSPA2-labelled cells increased significantly, indicating that the interaction with hyaluronic acid may induce the unmasking of HSPA2 epitopes. Furthermore, after swim-up and hyaluronic acid selection, spermatozoa presented a highly immunostained equatorial band with a homogeneous fluorescence throughout the acrosomal region. This distribution has been previously suggested to have important implications in male fertility. Noteworthy, a homogeneous fluorescence among the acrosomal region with a more intense labelling at the apical region was observed only in hyaluronic acid bound sperm cells, which may be associated with primary gamete recognition. Our findings suggest that the hyaluronic acid selection technique and HSPA2 biomarker should be considered candidates to complement the classic seminal analysis before recommending an appropriate assisted reproduction technique., (© 2022. The Author(s).)

Lack of trust in biomedical research, government, and health care systems, especially among racial/ethnic minorities and under-resourced communities, is a longstanding issue rooted in social injustice. The COVID-19 pandemic has further highlighted existing health and socioeconomic inequities and increased the urgency for solutions to provide access to timely, culturally, and linguistically appropriate evidence-based information about COVID-19; and ultimately to promote vaccine uptake. California's statewide alliance STOP COVID-19 CA (comprising eleven sites), leverages long standing community partnerships to better understand concerns, misinformation, and address racial/ethnic inequities in vaccine hesitancy and uptake. Using data from the California CEAL Communication Working Group, we demonstrate the wide range of strategies, communication methods, languages, and trusted messengers that have been effective in reaching diverse communities across the state. We also showcase challenges and lessons learned, such as the importance of including trusted community partners to share information or provide vaccines. These approaches, rooted in community engagement, are crucial for addressing inequities and responding to future public health emergencies., (© 2022. The Author(s).)

Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as E. coli and S. agalactiae , in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 10 5 CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced E. coli counts, as well as decreased S. agalactiae and E. coli invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after S. agalactiae infection and by IL-1β after E. coli infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.

Being a caregiver for a person with dementia has negative health consequences, like depression, stress, anxiety, and burden. Consequently, it is important that caregivers receive social support and social resources during the trajectory of the disease. This study analyzes how different types of social resources impact caregivers' well-being. A cross-sectional sample of 260 caregivers was divided into groups, depending on the social resources they had access to. Namely, social media (N = 157), day-care centers (N = 40) or residential centers (N = 63). Social support, isolation, burden, coping strategies, and satisfaction measures were administered to participants, and groups were compared using ANOVA and SEM models. Help-seeking and social support received through social resources predicted satisfaction and caregivers' burden. Formal resources positively influence care providers and their absence diminishes the impact of social support on perceived burden. This research reflects the importance of formal resources in the lives of caregivers and the benefits they generate throughout the course of the pathology. Supporting caregivers and bringing the social resources closer to them indirectly improves the informal response offered to people with dementia., Competing Interests: Conflict of interests: The authors have declared that there is no conflict of interest.

The unique properties of spermatozoa are established through the spermatogenesis and maturation processes concurrently with its epigenome. It is known that damage to epigenetic mechanisms can lead to reproductive problems. However, scientific reviews addressing the role of the spermatozoa epigenome during the reproductive process are scarce. Therefore, the aim of this review was to offer a detailed overview of current knowledge in the field of spermatozoa epigenetics and its consequent implications. A full search was performed through three databases by combining five keywords. Inclusion criteria were implemented to grant accessibility, relevance, and concretion. Besides, some articles were manually removed or added to obtain an adequate and complete collection of 485 scientific publications. This compilation was used to conduct the bibliometric analysis and the data review separately. Bibliometric results displayed that spermatozoa epigenetics is an active and growing research area. The bibliographic overview showed that sperm epigenome correlates with the development of its function, explaining the environmental influence on reproductive pathologies or abnormal inheritance. The main conclusions were that the normal performance of sperm is heavily reliant on its epigenetics and that this study area is burgeoning, with the potential ability to provide society with clinical innovations in a short-term period.

Graph networks can model data observed across different levels of biological systems that span from population graphs (with patients as network nodes) to molecular graphs that involve omics data. Graph-based approaches have shed light on decoding biological processes modulated by complex interactions. This paper systematically reviews graph-based analysis methods of Graph Signal Processing (GSP), Graph Neural Networks (GNNs) and graph topology inference, and their applications to biological data. This work focuses on the algorithms of graph-based approaches and the constructions of graph-based frameworks that are adapted to a broad range of biological data. We cover the Graph Fourier Transform and the graph filter developed in GSP, which provides tools to investigate biological signals in the graph domain that can potentially benefit from the underlying graph structures. We also review the node, graph, and interaction oriented applications of GNNs with inductive and transductive learning manners for various biological targets. As a key component of graph analysis, we provide a review of graph topology inference methods that incorporate assumptions for specific biological objectives. Finally, we discuss the biological application of graph analysis methods within this exhaustive literature collection, potentially providing insights for future research in biological sciences.

Defining the context dependence of ecological states or processes is a fundamental goal of ecology. Stressor-response functions are the quantitative representation of context dependence, where the context (environmental contingency) is defined by location on the stressor (x) axis, and represents a unifying concept in biological science., Competing Interests: Declaration of interests No interests are declared., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

In addition to playing a central role in the mitochondria as the main producer of ATP, F O F 1 -ATP synthase performs diverse key regulatory functions in the cell membrane. Its malfunction has been linked to a growing number of human diseases, including hypertension, atherosclerosis, cancer, and some neurodegenerative, autoimmune, and aging diseases. Furthermore, inhibition of this enzyme jeopardizes the survival of several bacterial pathogens of public health concern. Therefore, F O F 1 -ATP synthase has emerged as a novel drug target both to treat human diseases and to combat antibiotic resistance. In this work, we carried out a computational characterization of the binding sites of the fungal antibiotic aurovertin in the bovine F 1 subcomplex, which shares a large identity with the human enzyme. Molecular dynamics simulations showed that although the binding sites can be described as preformed, the inhibitor hinders inter-subunit communications and exerts long-range effects on the dynamics of the catalytic site residues. End-point binding free energy calculations revealed hot spot residues for aurovertin recognition. These residues were also relevant to stabilize solvent sites determined from mixed-solvent molecular dynamics, which mimic the interaction between aurovertin and the enzyme, and could be used as pharmacophore constraints in virtual screening campaigns. To explore the possibility of finding species-specific inhibitors targeting the aurovertin binding site, we performed free energy calculations for two bacterial enzymes with experimentally solved 3D structures. Finally, an analysis of bacterial sequences was carried out to determine conservation of the aurovertin binding site. Taken together, our results constitute a first step in paving the way for structure-based development of new allosteric drugs targeting F O F 1 -ATP synthase sites of exogenous inhibitors., (Copyright © 2022 Cofas-Vargas, Mendoza-Espinosa, Avila-Barrientos, Prada-Gracia, Riveros-Rosas and García-Hernández.)

The failures of binding to the oocyte zona pellucida are commonly attributed to defects in the sperm recognition, adhesion, and fusion molecules. SPAM1 (sperm adhesion molecule 1) is a hyaluronidase implicated in the dispersion of the cumulus-oocyte matrix. Therefore, the aim of this study was to characterize the SPAM1 distribution in the different physiological conditions of human sperm. Specifically, we evaluated the location of the SPAM1 protein in human sperm before capacitation, at one and four hours of capacitation and after hyaluronic acid (HA) selection test by fluorescence microscopy. Sperm bound to HA were considered mature and those that crossed it immature. Our results detected three SPAM1 fluorescent patterns: label throughout the head (P1), equatorial segment with acrosomal faith label (P2), and postacrosomal label (P3). The data obtained after recovering the mature sperm by the HA selection significantly (p < 0.05) highlighted the P1 in both capacitation times, being 79.74 and 81.48% after one hour and four hours, respectively. Thus, the HA test identified that human sperm require the presence of SPAM1 throughout the sperm head (P1) to properly contact the cumulus-oocyte matrix. Overall, our results provide novel insights into the physiological basis of sperm capacitation and could contribute to the improvement of selection techniques.

In this issue of Neuron, Bossi, Dhanasobhon, and colleagues uncover the functional relevance of GluN1/GluN3A excitatory glycine receptors (eGlyRs) in the neocortex and amygdala. This study provides exciting new insights into the role of unconventional eGlyRs in brain function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The aim of this study is to evaluate the relevance of pneumoperitoneum on the success rate of non-operative management (NOM) of patients with complicated acute diverticulitis (AD), and the risk factors associated with failure., Methods: Observational retrospective cohort study of patients attended at the emergency department for AD from January 2015-August 2019. Patient demographics, blood tests, radiological data and initial treatment strategies were registered. NOM, based on intravenous antibiotics (ATB) and bowel rest, was defined as unsuccessful when emergency surgery (ES) and/or infection-related death took place. Patients initially treated with ES were excluded. Analysis was done with the IBM SPSS statistics 23.0.0.2 software., Results: According to modified Hinchey and WSES criteria, 99 (12%) of 826 AD episodes were complicated, with pneumoperitoneum on the CT scan in 89 (90.5%). NOM was undertaken in 93 (94%) cases, with a 91.5% success rate. Multivariate analysis revealed ASA class III-IV, and the presence of fluid collections >3 cm in diameter, but not distant free air, to be associated with NOM failure. However, the success rate of NOM was significantly higher in patients with pericolic pneumoperitoneum (98.5%) than in those with distant free air (80%) (P=0.02). Risk factors of NOM failure were an advanced age, high CRP and WBC values, and the presence of free fluid in >2 abdominal quadrants., Conclusions: NOM in hemodynamically stable patients with complicated AD is a safe and feasible approach, even in the context of distant free air. Nevertheless, patients with isolated pericolic air did better in our series.

Spermatozoa motility in freshwater and marine fish is mainly controlled by the difference in osmotic pressure. Specifically, zebrafish (Danio rerio) spermatozoa undergo hypoosmotic shock due to the decrease in extracellular potassium, which leads to membrane hyperpolarization and activation of flagellar motility. Previous studies have concluded that motility activation has a negative effect on the spermatozoa structure. However, no evidence exists about ultrastructural changes in zebrafish spermatozoa after motility activation. In this study, spermatozoa samples were obtained from ten adult zebrafish individuals before and 60 s after motility activation and analyzed using Scanning and Transmission Electron Microscopy. Results showed dramatic morphological and ultrastructural alterations of the zebrafish spermatozoa after activation. In particular, the spermatozoa head underwent severe morphological distortion, including swelling of the nucleus, the bursting of the plasma membrane, and the alteration of the genetic material. Midpieces were also affected after activation since rupture of the cell membrane and lysis of mitochondria occurred. Furthermore, after the hypoosmotic shock, most spermatozoa showed a coiled flagellum and a disaggregated plasma membrane. Overall, our findings show that the activation of motility leads to substantial zebrafish spermatozoa morphological and ultrastructural changes, which could modify their physiology and decrease the fertilizing potential., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prolactin (PRL) is a pleiotropic hormone with a key role in pregnancy. In fetal membranes, PRL can regulate the secretion of pro-inflammatory factors, which induces the activation of matrix metalloproteinases (MMPs). The increase and activation of MMPs deregulate the turnover of the extracellular matrix in the fetal membranes, altering its structure and function, causing premature rupture of the membranes and preterm labor. In this work, we evaluate the effect of PRL upon the secretion of MMP-1, MMP-2, MMP-9, MMP-13, and the tissue inhibitors of metalloproteinases (TIMPs) in human fetal membranes after lipopolysaccharide (LPS) challenge. Nine fetal membranes from healthy non-laboring cesarean deliveries at term were cultured in a 2-independent chamber system and pre-treated with 250, 500, 1000 or 4000 ng/ml of PRL for 24 h, then choriodecidual region was stimulated with 500 ng/ml of LPS plus fresh PRL for 24 h. The MMPs and TIMPs secretion were quantified by ELISA, additionally MMP-2 and MMP-9 gelatinolytic activity was measured by zymography. LPS induced the MMP-9 and MMP-1 secretion, but no MMP-2 or MMP-13 in comparison with basal levels. PRL co-treatment decreased the MMP-2, MMP-9 and MMP-1 secretion induced by LPS. The active forms were present in the tissue extract, showing a response consistent with the secretion profile. TIMP-1 and TIMP-2 secretion was decreased after LPS treatment and the PRL co-treatment reverts this effect. The present results support that PRL may favor the balance between these factors involved in the structural maintenance of fetal membranes in an inflammatory event.

Introduction: HIV is considered one of the most important chronic transmitted diseases worldwide. The Joint United Nations Program on HIV/AIDS in 2020 proposed the strategy "95-95-95" which goals to achieve a 95% of cases identified, receives ART, and will have achieved suppression of the virus. In Ecuador by 2020, according to the Ministry of Public Health, 45,056 persons are living with HIV, principally men between 15 and 49 years, and a mortality rate of 4.8/100,000 habitats. This study aims to determine the cost-utility of applying an early screening to a sexually active population vs. only a high-risk population and if the use of PrEP is justified depending on different contexts., Methods: For the cost-utility evaluation, it was compared: (a) HIV screening performed only in the high-risk population vs. HIV screening in all population sexually active; and (b) the use of ART only for HIV treatment vs. ART as a treatment in diagnosed cases and the use of PrEP (only at a high-risk population of acquiring HIV). Calculation and weight of DALYs for HIV/SIDA were obtained through WHO guidelines. To generate the Markov model for HIV/AIDS, subjects were classified as symptomatic or asymptomatic, as well as the HIV deaths., Results: Cost-benefit analysis (CUA) showed that ICER for early diagnosis had a negative value which means a saving if the strategy will be implemented as a regular test (-$591, -$4,360) and -108 and -934 DALYs, in the case of ART and PrEP, ICER the $30,541-$59,410, which resulted in more than the GDP's threshold and health years between 2,511 and 10,635 in the general population. With a reduction of 70% in the assigned budget for the early diagnosis, Ecuadorian people could lose between 4 and 6 DALYs, while if the budget reduces more than 50% to ART, it will generate a loss of 10-12 years of healthy life., Conclusion: CUA demonstrates that an early diagnosis in a sexually active population is cost-beneficial. This, combined with ART or PrEP, is ideal to add years of healthy life., 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 © 2022 Quirola-Amores, Espinosa, Oleas, Hernandez, Henriquez and Teran.)

Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.