Tibetans exhibit lower hemoglobin concentration and decreased heart response to hypoxia during poikilocapnia at intermediate altitude relative to Han Chinese.

Background: High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia. Methodology: We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300 m (∼4327 ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ V˙I/ΔPetCO2 and ΔHR/ΔPetCO2, respectively). Results: Male Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01). Conclusion: These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

Current status of robotic training during the urology residency: results from a national survey in Spain.

INTRODUCTION AND OBJECTIVES: The increasing number of robotic urological procedures observed in recent years highlights the need to expand training opportunities in robotic surgery. Our objective is to investigate the state of robotic training during urology residency in Spain in order to identify significant deficiencies. MATERIALS AND METHODS: A 20-item online survey was conducted among urology residents in Spain who were registered in the database of the Residents and Young Urologists Group of the Spanish Association of Urology. The survey assessed subjective opinions, institutional aspects, training resources, and experience regarding robotic surgery. A total of 455 email invitations were sent throughout the year 2021. Descriptive analysis of the responses was performed. RESULTS: The participation rate reached 30%, with a total of 135 residents. 52% of respondents lacked access to a robotic system in their institution, of which only 48% could compensate for this deficiency through external rotations. Among those with access to a robotic system, 25% and 23% reported having access to theoretical and practical training, respectively. The existence of a formal training program was low (13%). 85% of the respondents considered robotic surgery training in Spain to be deficient. CONCLUSIONS: Training for Spanish residents in robotic urological surgery is perceived as inadequate, emphasizing the crucial need for improvement in training programs in this field.

Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Women in urology: what is their current situation in Spain?

OBJECTIVE: To analyze the current state of women in urology in Spain. MATERIAL AND METHODS: Descriptive study based on the results of an online survey sent between February and April 2020 through the database of the Residents and Young Urologists group (RAEU) of the Spanish Association of Urology (AEU). Characteristics of the survey and its results were analyzed. RESULTS: In total, 257 responses were obtained from 210 women (81.71%) and 47 men (18.29%) belonging to 111 hospitals. Statistically significant differences were observed (p < 0.001) with a higher proportion of men in all categories except for the group of young female and male attendings (29-39 years, p = 0.789), and the group of female residents against male residents (p = 0.814). The number of men was higher in hospitals with subspecialty units except for the Pelvic Floor Unit, where no statistically significant difference was observed (p = 0.06). Regarding positions of responsibility, only 7 out of 111 hospitals had female Department Chiefs. CONCLUSIONS: Women's representation in urology is increasing, mainly due to the younger generations. However, the access of these women to relevant positions is anecdotal.

Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study.

BACKGROUND: The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward. METHOD: We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses. RESULTS: Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4-12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1-5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49-4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04-0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02-0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20-0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08-7.67, p-value; 0.035) was associated with severe PPD only. CONCLUSION: The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.

Impact of Service-Learning educational interventions on nursing students: An integrative review.

BACKGROUND: Service learning is an innovative educational approach that enables nursing students to directly participate and engage in the community while providing them and the community with benefits. OBJECTIVES: To summarise the evidence from service learning activities for nursing students, the educational and non-educational benefits derived through implementing this methodology, and the participating students' perceptions. DESIGN: An integrative review including qualitative, quantitative, and mixed methods designs was conducted. DATA SOURCES: The articles were identified through a systematic search in the following electronic databases: PubMed, Cochrane Library Plus, Scopus, CINAHL Complete (EBSCOHost), and Education Source (EBSCOHost). REVIEW METHODS: The search for studies was conducted in December 2020 using the following search terms: "Service learning", "Service-learning partnership", "Nursing", "Benefits" and "Intervention". RESULTS: A total of 22 articles were included. A positive relationship was found between the nursing students participating in service learning programmes and the acquisition of educational benefits, such as theoretical and practical learning, communication skills, and teamwork, and non-educational benefits, such as empathy, questioning prejudices, and commitment. In addition, a wide variety of activities and interventions were found to have been implemented using this academic approach, as well as a positive evaluation by the participating students. CONCLUSIONS: Service learning programmes with the active participation of nursing students generate benefits for both them and the community. First, these interventions receive positive evaluations from participating students. Furthermore, the interventions developed using service learning are varied and require motivation and creativity to implement them. However, there is a need for more experimental studies and the use of larger samples in service learning programmes.

Direct introgression of untapped diversity into elite wheat lines.

The effective utilization of natural variation has become essential in addressing the challenges that climate change and population growth pose to global food security. Currently adopted protracted approaches to introgress exotic alleles into elite cultivars need substantial transformation. Here, through a strategic three-way crossing scheme among diverse exotics and the best historical elites (exotic/elite1//elite2), 2,867 pre-breeding lines were developed, genotyped and screened for multiple agronomic traits in four mega-environments. A meta-genome-wide association study, selective sweeps and haplotype-block-based analyses unveiled selection footprints in the genomes of pre-breeding lines as well as exotic-specific associations with agronomic traits. A simulation with a neutrality assumption demonstrated that many pre-breeding lines had significant exotic contributions despite substantial selection bias towards elite genomes. National breeding programmes worldwide have adopted 95 lines for germplasm enhancement, and 7 additional lines are being advanced in varietal release trials. This study presents a great leap forwards in the mobilization of GenBank variation to the breeding pipelines.

Analysis and vulnerability of the international wheat trade network.

Wheat is one of the three basic cereals providing the necessary calorific intake for most of the world's population. For this reason, its trade is critical to many countries in order to fulfil their internal demand and strategic stocks. In this paper, we use complex network analysis tools to study the international wheat trade network and its evolving characteristics for the period 2009-2013. To understand the vulnerability of each country's dependence on the imports of this crop we have performed different analyses, simulating shocks of varying intensities for the main wheat producers, and observed the population affected by the production drop. As a result, we conclude that globally the network is slightly more resilient than four years previously, although at the same time some developing countries have slipped into a vulnerable situation. We have also analysed the effects of a global shock affecting all major producers, assessing its impact on every country. Some comments on the COVID-19 outbreak and the political decisions taken by governments following the pandemic declaration are included, observing that given their capital-intensive characteristics, no negative effects should currently be expected in the wheat market. Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-020-01117-9.

Examining the continuum of psychosis: Frequency and characteristics of psychotic-like symptoms in relatives and non-relatives of patients with schizophrenia.

BACKGROUND: A key finding underlying the continuum of psychosis concept is the presence of psychotic-like experiences (PLEs) in healthy subjects. However, it remains uncertain to what extent these experiences are related to the genetic risk for schizophrenia and how far they actually resemble attenuated forms of psychotic symptoms. METHODS: Forty-nine adults with no history of mental illness in first-degree relatives and 59 siblings of patients with schizophrenia were rated on the psychosis section of the Computerized Diagnostic Interview Schedule IV (C DIS-IV) and the Rust Inventory of Schizotypal Cognitions (RISC). Those who rated positive on the CDIS-IV were re-interviewed using the lifetime version of the Present State Examination 9th edition (PSE-9) and the Structured interview for Schizotypy (SIS). RESULTS: Seventeen (34.69%) of the non-relatives and 22 (37.29%) of the relatives responded positively to one or more of the psychosis questions on the DIS. This difference was not significant. RISC scores were also similar between the groups. At follow-up interview with the PSE-9, 13/40 PLEs (32.50%) in the non-relatives were classified as possible or probable psychotic symptoms compared to 11/46 (23.91%) in the relatives. Using liberal symptom thresholds, 5 of those who attended the follow-up interview (2 non-relatives and 3 relatives) met SIS criteria for schizotypal personality disorder. CONCLUSIONS: Rates of PLEs, however considered, do not differ substantially between relatives and non-relatives of patients with schizophrenia. Only a minority of PLEs picked up by screening interviews resemble attenuated forms of psychotic symptoms.

Genomic prediction models for grain yield of spring bread wheat in diverse agro-ecological zones.

Genomic and pedigree predictions for grain yield and agronomic traits were carried out using high density molecular data on a set of 803 spring wheat lines that were evaluated in 5 sites characterized by several environmental co-variables. Seven statistical models were tested using two random cross-validations schemes. Two other prediction problems were studied, namely predicting the lines' performance at one site with another (pairwise-site) and at untested sites (leave-one-site-out). Grain yield ranged from 3.7 to 9.0 t ha(-1) across sites. The best predictability was observed when genotypic and pedigree data were included in the models and their interaction with sites and the environmental co-variables. The leave-one-site-out increased average prediction accuracy over pairwise-site for all the traits, specifically from 0.27 to 0.36 for grain yield. Days to anthesis, maturity, and plant height predictions had high heritability and gave the highest accuracy for prediction models. Genomic and pedigree models coupled with environmental co-variables gave high prediction accuracy due to high genetic correlation between sites. This study provides an example of model prediction considering climate data along-with genomic and pedigree information. Such comprehensive models can be used to achieve rapid enhancement of wheat yield enhancement in current and future climate change scenario.

Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma.

Glioblastoma are malignant highly vascularized brain tumours, which feature large oedema resulting from tumour-promoted vascular leakage. The pro-permeability factor Semaphorin3A (Sema3A) produced within glioblastoma has been linked to the loss of endothelial barrier integrity. Here, we report that extracellular vesicles (EVs) released by patient-derived glioblastoma cells disrupt the endothelial barrier. EVs expressed Sema3A at their surface, which accounted for in vitro elevation of brain endothelial permeability and in vivo vascular permeability, in both skin and brain vasculature. Blocking Sema3A or its receptor Neuropilin1 (NRP1) hampered EV-mediated permeability. In vivo models using ectopically and orthotopically xenografted mice revealed that Sema3A-containing EVs were efficiently detected in the blood stream. In keeping with this idea, sera from glioblastoma multiforme (GBM) patients also contain high levels of Sema3A carried in the EV fraction that enhanced vascular permeability, in a Sema3A/NRP1-dependent manner. Our results suggest that EV-delivered Sema3A orchestrates loss of barrier integrity in glioblastoma and may be of interest for prognostic purposes.

Euroforgen-NoE collaborative exercise on LRmix to demonstrate standardization of the interpretation of complex DNA profiles.

There has been very little work published on the variation of reporting practices of mixtures between laboratories, but it has been previously demonstrated that there is little consistency. This is because there is no current uniformity of practice, so different laboratories will operate using different rules. The interpretation of mixtures is not solely a matter of using some software to provide 'an answer'. An assessment of a case will usually begin with a consideration of the circumstances of a crime. Assumptions made about the numbers of contributors follow from an examination of the electropherogram(s)--and these may differ between the prosecution and the defence hypotheses. There may be a necessity to evaluate several sets of hypotheses for any given case if the circumstances are uncertain. Once the hypotheses are formulated, the mathematical analysis is complex and can only be accomplished by the use of specialist software. In order to obtain meaningful results, it is essential that scientists are trained, not only in the use of the software, but also in the methodology to understand the likelihood ratio concept that is used. The Euroforgen-NoE initiative has developed a training course that utilizes the LRmix program to carry out the calculations. This software encompasses the recommendations of the ISFG DNA commissions on mixture interpretation and is able to interpret samples that may come from two or more contributors and may also be partial profiles. Recently, eighteen different laboratories were trained in the methodology. Afterwards they were asked to independently analyze two different cases with partial mixture DNA evidence and to write a statement court-report. We show that by introducing a structured training programme, it is possible to demonstrate, for the first time, that a high degree of standardization, leading to uniformity of results can be achieved by participating laboratories.

Assessment of stigma associated with tuberculosis in Mexico.

BACKGROUND: Stigma is a major barrier to health care access and impacts the quality of life for individuals affected by tuberculosis (TB). Assessing TB stigma is essential to addressing health disparities. However, no such instrument was available in Mexico at the time of our study. This study examined the adaptability of the TB and human immunodeficiency virus (HIV) stigma scales previously used in Thailand. METHODS: The original scale, developed in English, was linguistically adapted to Spanish and administered to 217 individuals affected by TB in five states in Mexico. The TB-HIV stigma subscales were designed to assess individual and community perspectives. Additional data collected included general information and socio-demographics. Assessment of psychometric properties included basic statistical tests, evaluation of Cronbach's alpha and factor analysis. RESULTS: We found no significant statistical differences associated with higher stigma scores by location, age, marital status, education and stigma scores. Factor analysis did not create any new factors. Internal consistency reliability coefficients were satisfactory (Cronbach α = 0.876-0.912). CONCLUSION: The use of the stigma scales has implications for 1) health improvements, 2) research on stigma and health disparities, and 3) TB and HIV stigma interventions. Further research is needed to examine transferability among larger and randomly selected Spanish-speaking populations.

Haematopoietic stem cell transplantation for acquired aplastic anaemia.

PURPOSE OF REVIEW: Survival outcomes from haematopoietic stem cell transplantation (HSCT) in severe aplastic anaemia (SAA) have improved steadily over the past decades, largely reflecting progress in supportive care and conditioning regimens. Here we review recently published data that highlight the improvements and current issues. RECENT FINDINGS: Human leukocyte antigen (HLA)-matched sibling donor (MSD) HSCT remains the gold standard for SAA patients younger than 40-50 years, with HLA-matched unrelated donor (MUD) HSCT for second line after failure to respond to immunosuppressive therapy (IST). The use of alternative donor sources for aplastic anaemia patients remains limited and problematic, but novel conditioning regimens, particularly in the haploidentical setting, justify further evaluation. In recent studies when comparing alemtuzumab-based conditioning with standard antithymocyte globulin conditioning regimens, lower rates of acute and chronic graft-versus-host disease and better tolerance in older patients are seen. SUMMARY: Improving outcomes may lead to an expanded frontline HSCT role in the future. In children lacking a MSD, increasingly MUD HSCT is being considered as first-line treatment and is also being considered more for young adults. Further research is needed to advance our understanding of the role HSCT has to play in SAA with particular emphasis on alternative donor sources and identifying optimal conditioning regimens.

P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance.

5-Fluorouracil (5-FU), together with other drugs such as oxaliplatin, is one of the most important pharmacological agents in the treatment of colorectal cancer. Although mitogen-activated protein kinases (MAPKs) have been extensively connected with resistance to platinum compounds, no role has been established in 5-FU resistance. Here we demonstrate that p38MAPK activation is a key determinant in the cellular response to 5-FU. Thus, inhibition of p38MAPKα by SB203580 compound or by short-hairpin RNA interference-specific knockdown correlates with a decrease in the 5-FU-associated apoptosis and chemical resistance in both HaCaT and HCT116 cells. Activation of p38MAPK by 5-FU was dependent on canonical MAP2K, MAPK kinase (MKK)-3 and MKK6. In addition, ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) showed a redundancy of function for the final activation of p38MAPK. Resistance associated with p38MAPK inhibition correlates with an autophagic response that was mediated by a decrease in p53-driven apoptosis, without effect onto p53-dependent autophagy. Moreover, the results with colorectal cancer-derived cell lines with different p53 status and patterns of resistance to 5-FU suggest that de novo and acquired resistance was controlled by similar mechanisms. In summary, our data demonstrate a critical role for the p38MAPK signaling pathway in the cellular response to 5-FU by controlling the balance between apoptosis and autophagy.

[Surgical treatment of diaphyseal and comminuted fractures of the clavicle using a low profile anatomical plate]. / Tratamiento quirúrgico de las fracturas diafisarias y conminutas de la clavícula mediante placa anatómica de bajo perfil.

OBJECTIVES: In this study we evaluate the treatment of displaced mid-shaft clavicle fractures or comminuted fractures with a third fragment using a superior anatomic plate. MATERIALS AND METHODS: A retrospective study was conducted on 34 patients operated on between January 2006 and June 2010 with this type of fracture. Mean follow up was 25 months (6-54 months). By Robinson Classification, 12 cases were type 2B, 17 type 2B1 and 5 type 2B2. Clinical evaluation was performed with the VAS and Constant test. For the radiological evaluation, we used neutral AP projections, and another with 30 degrees of cranio-caudal inclination. RESULTS: The mean pre-operative VAS was 6.5 (4-8) and the postoperative was 1 (0-2). The mean Constant test score was 85, with 30% good results and 70% excellent results. The mean consolidation time was 14 weeks. CONCLUSION: Internal fixation of comminuted fractures with an anatomic plate, particularly those with a vertical third fragment and fractures type 2B, 2B1 and 2B2, provides a good treatment option, as it gives good functional results and minimises the incidence of non-union.

Remodeling of VE-cadherin junctions by the human herpes virus 8 G-protein coupled receptor.

Kaposi Sarcoma (KS) are opportunistic tumors, associated with human herpes virus 8 (HHV8) infection. KS development is highly favored by immune-depression and remains the second most frequent tumor in acquired immune deficiency syndrome patients. Although it has been shown that experimental expression of the HHV8 G-protein-coupled receptor (vGPCR) in the endothelial compartment is alone sufficient to recapitulate the formation and progression of KS-like lesions, its functional effects on endothelial homeostasis are not fully understood. Here we show that vGPCR expression in endothelial cells induces an increase in paracellular permeability both in vivo and in vitro. By using pharmacological inhibitors and small interference RNA-based knockdown, we demonstrate an essential role for the PI(3)Kinase-γ/Rac nexus in vGPCR-mediated permeability. This was further accompanied by dramatic remodeling of VE-cadherin-dependent cell-cell junctions. Importantly, this in vitro vGPCR-initiated signaling signature was observed in a large panel of human KS. Altogether, our results support the hypothesis that endothelial vGPCR signaling is co-opted in KS, and unveil new key cellular targets for therapeutic intervention.

Specific eating disorder clusters based on social anxiety and novelty seeking.

While social avoidance and distress (SAD), a key aspect of social phobia related to behavioral inhibition, is high in different eating disorders (EDs), novelty seeking (NS) is mainly linked to bulimic disorders. Since heterogeneity in NS levels (low/high) exists in social phobia and in about 55% of ED with a highly disturbed personality, we examined ED types based on SAD and NS and their relationships to eating and comorbid features. Scores of 825 ED women on SAD and NS were submitted to cluster analysis. Five clinically differentiated ED clusters emerged: two without SAD (45%) and three with high SAD and low (13%), mid (34%), high NS (8%) levels. High vs. low SAD groups showed greater eating and social impairment, ineffectiveness, ascetism, suicide attempts, and lower education. Among SAD clusters, "SAD-low NS" had the lowest rate of binge eating, vomit, substance use, stealing and compulsive buying, whereas "SAD-high NS" presented the opposite pattern. However, no differences across SAD clusters were found with regard to ED diagnostic category distribution or history of treatment. Findings show that SAD-ED types present heterogeneity of NS and greater severity.