Advances in 3D bioprinting to enhance translational applications in bone tissue engineering and regenerative medicine.

Bone defects are due to trauma, infections, tumors, or aging, including bone fractures, bone metastases, osteoporosis, or osteoarthritis. The global burden of these demands research into innovative strategies that overcome the limitations of conventional autografts. In this sense, the development of three-dimensional (3D) bioprinting has emerged as a promising approach in the field of tissue engineering and regenerative medicine (TERM) for the on-demand generation and transplantation of tissues and organs, including bone. It combines biological materials and living cells, which are precisely positioned layer by layer. Despite obtaining some promising results, 3D bioprinting of bone tissue still faces several challenges, such as generating an effective vascular network to increase tissue viability. In this review, we aim to collect the main knowledge on methods and techniques of 3D bioprinting. Then, we will review the main biomaterials, their composition, and the rationale for their application in 3D bioprinting for the TERM of bone.

Impact of a Regional Pediatric Hematology/Oncology Fellowship Program in Guatemala.

PURPOSE: This study aimed to describe and assess the regional experience of a pediatric hematology/oncology fellowship program based in Guatemala. METHODS: The Unidad Nacional de Oncología Pediátrica (UNOP) in Guatemala City, Guatemala, is the only hospital in Central America dedicated exclusively to childhood and adolescent cancer. To address the regional need for specialists, a fellowship program in pediatric hematology/oncology was launched in 2003. The UNOP fellowship program comprises 3 years of training. Although the program is based at UNOP, it also includes rotations locally and internationally to enhance clinical exposure. The curriculum is based on international standards to cover clinical expertise, research, professionalism, communication, and health advocacy. Trainees are selected according to country or facility-level need for pediatric hematologists/oncologists, with a plan for them to be hired immediately after completing their training. RESULTS: Forty physicians from 10 countries in Latin America have completed training. In addition, there are currently 13 fellows from five countries in training. Of the graduates, 39 (98%) are now practicing in pediatric hematology/oncology in Latin America. Moreover, many of them have leadership positions within their institutions and participate in research, advocacy, and policy making. Graduates from the UNOP program contribute to institutions by providing care for an increasing number of patients with pediatric cancer. The UNOP program is the first pediatric hematology/oncology fellowship program in the world to be accredited by Accreditation Council for Graduate Medical Education-International, an international body accrediting clinical training programs. CONCLUSION: The UNOP program has trained specialists to increase the available care for children with cancer in Latin America. This regional approach to specialist training can maximize resources and serve as a model for other programs and regions.

Public perception of psychiatry, psychology and mental health professionals: a 15-year analysis.

Background: X (previously known as "Twitter") serves as a platform for open discussions on mental health, providing an avenue for scrutinizing public perspectives regarding psychiatry, psychology and their associated professionals. Objective: To analyze the conversations happening on X about psychiatrists, psychologists, and their respective disciplines to understand how the public perception of these professionals and specialties has evolved over the last 15 years. Methods: We collected and analyzed all tweets posted in English or Spanish between 2007 and 2023 referring to psychiatry, psychology, neurology, mental health, psychiatrist, psychologist, or neurologist using advance topic modelling and sentiment analysis. Results: A total of 403,767 tweets were analyzed, 155,217 (38%) were in English and 248,550 (62%) in Spanish. Tweets about mental health and mental health professionals and disciplines showed a consistent volume between 2011 and 2016, followed by a gradual increase from 2016 through 2022. The proportion of tweets discussing mental health doubled from 2016 to 2022, increasing from 20% to 67% in Spanish and from 15% to 45% in English. Several differences were observed on the volume of tweets overtime depending on the language they were written. Users associated each term with varied topics, such as seeking for help and recommendation for therapy, self-help resources, medication and side effects, suicide prevention, mental health in times of crisis, among others. The number of tweets mentioning these topics increased by 5-10% from 2016 to 2022, indicating a growing interest among the population. Emotional analysis showed most of the topics were associated with fear and anger. Conclusion: The increasing trend in discussions about mental health and the related professionals and disciplines over time may signify an elevated collective awareness of mental health. Gaining insights into the topics around these matters and user's corresponding emotions towards them presents an opportunity to combat the stigma surrounding mental health more effectively.

A comprehensive study of the academic benefits and practical recommendations to include resistance training programs in institutional education.

The connection between physical activity and cognitive function has become a focus of attention in educational research in recent years. Regular exercise has been shown to have significant positive effects on physical health, but it also appears to have a significant impact on cognitive function and academic performance. Of all the exercise modalities, resistance training has drawn interest for its ability to improve cerebral abilities in addition to physical well-being. However, there is limited available knowledge exploring the relationship between resistance training regimens and academic performance. This narrative review aims to investigate the underlying mechanisms linking resistance training to academic performance. Firstly, we will examine the biological mechanisms and psychosocial links that potentially connect resistance training to academic performance to find and describe the different mechanisms by which resistance training improves academic performance. In the next part of the work, we delve into the existing observational and intervention studies that have explored the relationship between resistance training and academic performance. Lastly, we provide practical recommendations for including resistance training in institutional education settings, emphasizing the need of dispelling myths and addressing barriers to increase participation as well as the relevance of considering key training variables and adaptation of protocols to developmental stages, always guided by a properly trained professional. Overall, the available evidence supports that resistance training provides potential benefits to the academic performance of youth students with many biological and psychosocial factors that explain this relationship. However, most of the studies are observational, and broader interventional studies are needed to understand and maximize the benefits of this type of physical exercise.

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer.

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan-Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC's pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy.

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC-apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain-caspase 1, caspase 5, caspase 8, and interleukin 1ß) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.

Effect of Tumor Regression Grade on Survival and Disease-Free Interval in Patients Operated on for Locally Advanced Rectal Cancer.

INTRODUCTION: Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming years. There have been significant changes in neoadjuvant therapy regimens, with promising results, as demonstrated by the recent RAPIDO and PRODIGE23 studies. Around 40% of patients diagnosed with locally advanced rectal cancer show some degree of response to neoadjuvant treatment, with complete tumor regression observed in up to one in five patients. MATERIALS AND METHODS: Retrospective observational study. A total of 181 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were analyzed. Clinical and pathological data were collected from the patients, including assessment of tumor regression through histopathological studies after surgery. The Mandard tumor regression grading system was used to categorize tumor response into different grades. RESULTS: The results showed a significant association between the degree of tumor regression and several important clinical outcomes. Specifically, patients with higher tumor regression had significantly better disease-free survival than those with less regression (p = 0.004). In addition, tumor regression was also correlated with the incidence of local recurrence (p = 0.018) and distant metastasis (p = 0.032). These associations suggest that tumor responsiveness to neoadjuvant therapy may influence the long-term progression of the disease. Regarding tumor deposits and the presence of lymphadenopathy, these factors were also found to be significantly associated with clinical outcomes. Patients with tumor deposits had a higher incidence of local recurrence (p = 0.025) and distant metastases (p = 0.041), while the presence of lymphadenopathy increased the risk of local recurrence (p = 0.013). These findings highlight the importance of evaluating not only tumor regression but also other pathological markers to predict prognosis and guide clinical management. CONCLUSIONS: The degree of tumor regression was not an independent predictor of survival compared to other variables such as nodal stage and presence of tumor deposits. This indicates that while tumor regression is an important factor, other elements also play a crucial role in determining the prognosis of patients with locally advanced rectal cancer. This study provides additional evidence for the importance of tumor regression, tumor deposits, and lymphadenopathy as predictors of clinical outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

Oxidative Stress, Lipid Peroxidation and Ferroptosis Are Major Pathophysiological Signatures in the Placental Tissue of Women with Late-Onset Preeclampsia.

Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE (n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe3+) was observed in placenta samples stained with Perls' Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.

Autophagy in Its (Proper) Context: Molecular Basis, Biological Relevance, Pharmacological Modulation, and Lifestyle Medicine.

Autophagy plays a critical role in maintaining cellular homeostasis and responding to various stress conditions by the degradation of intracellular components. In this narrative review, we provide a comprehensive overview of autophagy's cellular and molecular basis, biological significance, pharmacological modulation, and its relevance in lifestyle medicine. We delve into the intricate molecular mechanisms that govern autophagy, including macroautophagy, microautophagy and chaperone-mediated autophagy. Moreover, we highlight the biological significance of autophagy in aging, immunity, metabolism, apoptosis, tissue differentiation and systemic diseases, such as neurodegenerative or cardiovascular diseases and cancer. We also discuss the latest advancements in pharmacological modulation of autophagy and their potential implications in clinical settings. Finally, we explore the intimate connection between lifestyle factors and autophagy, emphasizing how nutrition, exercise, sleep patterns and environmental factors can significantly impact the autophagic process. The integration of lifestyle medicine into autophagy research opens new avenues for promoting health and longevity through personalized interventions.

Sudden Infant Death Syndrome (SIDS): State of the Art and Future Directions.

Sudden infant death syndrome (SIDS) is a type of death that occurs suddenly and without any apparent explanation, affecting infants between 28 days of life and up to a year. Recognition of this entity includes performing an autopsy to determine if there is another explanation for the event and performing both an external and internal examination of the different tissues to search for possible histopathological findings. Despite the relative success of awareness campaigns and the implementation of prevention measures, SIDS still represents one of the leading causes of death among infants worldwide. In addition, although the development of different techniques has made it possible to make significant progress in the characterization of the etiopathogenic mechanisms underlying SIDS, there are still many unknowns to be resolved in this regard and the integrative consideration of this syndrome represents an enormous challenge to face both from a point of view scientific and medical view as humanitarian. For all these reasons, this paper aims to summarize the most relevant current knowledge of SIDS, exploring from the base the characterization and recognition of this condition, its forensic findings, its risk factors, and the main prevention measures to be implemented. Likewise, an attempt will be made to analyze the causes and pathological mechanisms associated with SIDS, as well as potential approaches and future paths that must be followed to reduce the impact of this condition.

Insights from the Twittersphere: a cross-sectional study of public perceptions, usage patterns, and geographical differences of tweets discussing cocaine.

Introduction: Cocaine abuse represents a major public health concern. The social perception of cocaine has been changing over the decades, a phenomenon closely tied to its patterns of use and abuse. Twitter is a valuable tool to understand the status of drug use and abuse globally. However, no specific studies discussing cocaine have been conducted on this platform. Methods: 111,508 English and Spanish tweets containing "cocaine" from 2018 to 2022 were analyzed. 550 were manually studied, and the largest subset underwent automated classification. Then, tweets related to cocaine were analyzed to examine their content, types of Twitter users, usage patterns, health effects, and personal experiences. Geolocation data was also considered to understand regional differences. Results: A total of 71,844 classifiable tweets were obtained. Among these, 15.95% of users discussed the harm of cocaine consumption to health. Media outlets had the highest number of tweets (35.11%) and the most frequent theme was social/political denunciation (67.88%). Regarding the experience related to consumption, there are more tweets with a negative sentiment. The 9.03% of tweets explicitly mention frequent use of the drug. The continent with the highest number of tweets was America (55.44% of the total). Discussion: The findings underscore the significance of cocaine as a current social and political issue, with a predominant focus on political and social denunciation in the majority of tweets. Notably, the study reveals a concentration of tweets from the United States and South American countries, reflecting the high prevalence of cocaine-related disorders and overdose cases in these regions. Alarmingly, the study highlights the trivialization of cocaine consumption on Twitter, accompanied by a misleading promotion of its health benefits, emphasizing the urgent need for targeted interventions and antidrug content on social media platforms. Finally, the unexpected advocacy for cocaine by healthcare professionals raises concerns about potential drug abuse within this demographic, warranting further investigation.

Impact of the COVID-19 pandemic on access to and delivery of maternal and child healthcare services in low-and middle-income countries: a systematic review of the literature.

Background: The COVID-19 pandemic has had a multifaceted impact on maternal and child services and adversely influenced pregnancy outcomes. This systematic review aims to determine the impact of the COVID-19 pandemic on access to and delivery of maternal and child healthcare services in low- and middle-income countries. Methods: The review was reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A primary search of electronic databases was performed using a combination of search terms related to the following areas of interest: "impact' AND 'COVID-19' AND 'maternal and child health services' AND 'low- and middle-income countries. A narrative synthesis approach was used to analyse and integrate the results. Results: Overall, 45 unique studies conducted across 28 low- and middle-income countries met the inclusion criteria for the review. The findings suggest the number of family planning visits, antenatal and postnatal care visits, consultations for sick children, paediatric emergency visits and child immunisation levels decreased compared to the pre-pandemic levels in the majority of included studies. An analytical framework including four main categories was developed based on the concepts that emerged from included studies: the anxiety of not knowing (1), overwhelmed healthcare systems (2), challenges perceived by healthcare professionals (3) and difficulties perceived by service users (4). Conclusion: The COVID-19 pandemic disrupted family planning services, antenatal and postnatal care coverage, and emergency and routine child services. Generalised conclusions are tentative due to the heterogeneity and inconsistent quality of the included studies. Future research is recommended to define the pandemic's impact on women and children worldwide and prepare healthcare systems for future resurgences of COVID-19 and potential challenges beyond. Systematic review registration: PROSPERO (CRD42021285178).

Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics.

Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Maternal, Perinatal and Neonatal Outcomes of Triplet Pregnancies According to Chorionicity: Our 15-Year Experience in a Tertiary-Level Center.

Introduction: The goal of this study was to evaluate the effect of chorionicity on maternal, fetal and neonatal morbidity and mortality in triplet pregnancies in our environment. Methods: A retrospective observational study was carried out on triplet pregnancies that were delivered in a tertiary center between 2006 and 2020. A total of 76 pregnant women, 228 fetuses and 226 live newborns were analyzed. Of these triplet pregnancies, half were non-trichorionic. We analyzed maternal characteristics and obstetric, fetal, perinatal and neonatal complications based on their chorionicity, comparing trichorionic vs. non-trichorionic triplet pregnancies. Prematurity was defined as <34 weeks. We measured perinatal and neonatal mortality, composite neonatal morbidity and composite maternal morbidity. Results: Newborns with a monochorionic component had a lower gestational age at birth, presented greater prematurity under 34 weeks, lower birth weight, greater probability of birth weight under 2000 g and an APGAR score below 7 at 5 min after birth, more respiratory distress syndrome and, overall, higher composite neonatal morbidity. The monochorionic component of triple pregnancies may entail the development of complications intrinsic to shared circulation and require premature elective termination. This greater prematurity is also associated with a lower birth weight and to the main neonatal complications observed. These findings are in line with those that were previously published in the meta-analysis by our research group and previous literature. Discussion: Triplet gestations with a monochorionic component present a higher risk of obstetric, fetal and neonatal morbidity and mortality.

Phenotype-specific melanoma uptake of fatty acid from human adipocytes activates AXL and CAV1-dependent ß-catenin nuclear accumulation.

Phenotypic diversity of cancer cells within tumors generated through bi-directional interactions with the tumor microenvironment has emerged as a major driver of disease progression and therapy resistance. Nutrient availability plays a critical role in determining phenotype, but whether specific nutrients elicit different responses on distinct phenotypes is poorly understood. Here we show, using melanoma as a model, that only MITF Low undifferentiated cells, but not MITF High cells, are competent to drive lipolysis in human adipocytes. In contrast to MITF High melanomas, adipocyte-derived free fatty acids are taken up by undifferentiated MITF Low cells via a fatty acid transporter (FATP)-independent mechanism. Importantly, oleic acid (OA), a monounsaturated long chain fatty acid abundant in adipose tissue and lymph, reprograms MITF Low undifferentiated melanoma cells to a highly invasive state by ligand-independent activation of AXL, a receptor tyrosine kinase associated with therapy resistance in a wide range of cancers. AXL activation by OA then drives SRC-dependent formation and nuclear translocation of a ß-catenin-CAV1 complex. The results highlight how a specific nutritional input drives phenotype-specific activation of a pro-metastasis program with implications for FATP-targeted therapies.

Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies.

Preeclampsia (PE) is a serious hypertensive disorder affecting 4-5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients.

Climate change increases threat to plant diversity in tropical forests of Central America and southern Mexico.

Global biodiversity is negatively affected by anthropogenic climate change. As species distributions shift due to increasing temperatures and precipitation fluctuations, many species face the risk of extinction. In this study, we explore the expected trend for plant species distributions in Central America and southern Mexico under two alternative Representative Concentration Pathways (RCPs) portraying moderate (RCP4.5) and severe (RCP8.5) increases in greenhouse gas emissions, combined with two species dispersal assumptions (limited and unlimited), for the 2061-2080 climate forecast. Using an ensemble approach employing three techniques to generate species distribution models, we classified 1924 plant species from the region's (sub)tropical forests according to IUCN Red List categories. To infer the spatial and taxonomic distribution of species' vulnerability under each scenario, we calculated the proportion of species in a threat category (Vulnerable, Endangered, Critically Endangered) at a pixel resolution of 30 arc seconds and by family. Our results show a high proportion (58-67%) of threatened species among the four experimental scenarios, with the highest proportion under RCP8.5 and limited dispersal. Threatened species were concentrated in montane areas and avoided lowland areas where conditions are likely to be increasingly inhospitable. Annual precipitation and diurnal temperature range were the main drivers of species' relative vulnerability. Our approach identifies strategic montane areas and taxa of conservation concern that merit urgent inclusion in management plans to improve climatic resilience in the Mesoamerican biodiversity hotspot. Such information is necessary to develop policies that prioritize vulnerable elements and mitigate threats to biodiversity under climate change.

Comparative Analysis of the Impact of Training through Simulation Using the Crisis Resource Management Tool for Primary Care Professionals.

This was a prospective observational study based on clinical simulation courses taught in 2017 at the IDEhA Simulation Center of Alcorcón Foundation University Hospital. Two courses in metabolic emergencies (MEs) and respiratory emergencies (REs) were offered to primary care physicians all over Spain. The main objective was to teach nontechnical skills (crisis resource management). Using a modified five-level Kirkpatrick-Phillips education evaluation model, level I (reaction, K1), level II (learning, K2) and level III (behavioral change, K3) changes were evaluated through surveys at the end of the courses and one year later. Thirty courses were held (15 ME courses and 15 RE courses) with 283 primary care physicians. The overall satisfaction (K1) was high: ME courses, 9.5/10; RE courses, 9.6/10. More than 80% of the participants rated the organization, resources, content, debriefing and scenarios as excellent, with no significant differences between the two courses. After one year (156 responses), the respondents for both courses reported that they would repeat the training annually (K2), encourage debriefing with colleagues (K3) and have modified some aspects of their workplace (K3), citing improvements in procedures and in the organization of the health team as the most important. After the ME course, few participants, i.e., 5 (6%), reported providing improved care to patients; after the RE course, 15 (19%) participants reported providing improved care; the difference between groups was significant (p < 0.05). Compared with the ME course, the RE course imparted greater knowledge about patient safety (K2) (38 (49%) vs. 24 (31%) (p < 0.05)) and more useful tools for daily clinical practice (K3) (67% vs. 56.4%) and resulted in participants paying more attention to personal performance and to colleagues when working as a team (K2) (64% vs. 50%). Clinical simulation courses are highly valued and potentially effective for training primary care physicians in patient safety and CRM tools. Future studies with objective measures of long-term impact, behavior in the workplace (K3) and benefits to patients (K4) are needed. Based on the results of our study, the areas that are important are those aimed at improving procedures and the organization of health teams.

Post-COVID-19 condition in pregnant and postpartum women: a long-term follow-up, observational prospective study.

Background: Post-COVID-19 condition has recently been defined as new or persistent common COVID-19 symptoms occurring three months after disease onset. The pathology of the disease is unclear, but immune and vascular factors seem to play a significant role. The incidence, severity, and implications of the disease after COVID-19 infection in pregnancy have not been established. We aimed to study the incidence and main risk factors for post-COVID-19 condition in an obstetric population and their implications for maternal and perinatal morbimortality. Methods: This is a prospective observational cohort study undertaken including women during pregnancy or at admission for labour with acute COVID-19 infection from March 9th, 2020 to June 11th, 2022. The inclusion criteria were confirmed acute COVID-19 infection during the recruitment period, a lack of significant language barrier and consent for follow-up. Patients were clinically followed-up by telephone via semi structured questionnaires. The exclusion criteria were loss to follow-up, spontaneous miscarriage, and legal termination of pregnancy. Patients were classified into groups according to the severity of symptoms at onset. We included patients from the first six first waves of the pandemic according to national epidemiological data in Spain. We studied the incidence of post-COVID-19 condition and their main demographic, clinical and obstetric risk factors. Findings: A total of 409 pregnant women were recruited at acute diagnosis, and 286 were followed-up. The mean time to follow-up was 92 weeks (standard deviation ± 28 weeks; median 100 weeks (Interquartile range: 76; 112)). A total of 140 patients had at least one post-COVID-19 symptom at least three months after acute infection. Neurological (60%) and cutaneous (55%) manifestations were the most frequent findings. The following profiles were identified as presenting a higher risk of post-COVID-19 condition: migrant women born in countries with lower Human Development Index; multiparous women; women with COVID-19 during pregnancy, mainly during the first and third trimesters, and in the first and second waves of the pandemic; women who had a higher number of symptoms; women who had a higher incidence of moderate and severe symptoms; women who required hospitalisation due to COVID-19 complications; and women who were not vaccinated before disease onset. We did not find any significant difference in perinatal results, such as gestational week at delivery, birthweight, the need for neonatal care or 5-min Apgar score, and newborns benefited from a high rate of breastfeeding at discharge. Women who were infected during successive waves of the pandemic had a significant and constant decrease in the risk of post-COVID-19 condition comparing to estimated risk in the first wave (OR: 0.70; 95% CI: 0.62, 0.92). Symptoms tended to resolve over time heterogeneously. Symptoms of myalgia and arthralgia took longer to resolve (mean of 60 weeks and 54 weeks, respectively). In a small but significant proportion of patients, neurological and psycho-emotional symptoms tended to become chronic after 90 weeks. Interpretation: At least 34.2% of obstetric patients from our cohort with acute COVID-19 infection presented post-COVID-19 condition symptoms. Demographic and acute disease characteristics as well as specific pregnancy-related risk factors were identified. This is the first study to assess post-COVID-19 condition in pregnant women. Further analysis on the biological pathophysiology of post-COVID-19 is needed to explain the characteristics of the disease. Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project "PI21/01244" and co-funded by the European Union, as well as P2022/BMD-7321 (Comunidad de Madrid) and ProACapital, Halekulani S.L. and MJR.