Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling.

When considering the clinical applications of autologous cell replacement therapy of human induced pluripotent stem cells (iPSC)-derived cells, there is a clear need to better understand what the immune response will be before we embark on extensive clinical trials to treat or model human disease. We performed a detailed assessment comparing human fibroblast cell lines (termed F1) reprogrammed into human iPSC and subsequently differentiated back to fibroblast cells (termed F2) or other human iPSC-derived cells including neural stem cells (NSC) made from either retroviral, episomal, or synthetic mRNA cell reprogramming methods. Global proteomic analysis reveals the main differences in signal transduction and immune cell protein expression between F1 and F2 cells, implicating wild type (WT) toll like receptor protein 3 (TLR3). Furthermore, global methylome analysis identified an isoform of the human TLR3 gene that is not epigenetically reset correctly upon differentiation to F2 cells resulting in a hypomethylated transcription start site in the TLR3 isoform promoter and overexpression in most human iPSC-derived cells not seen in normal human tissue. The human TLR3 isoform in human iPSC-NSC functions to suppress NF-KB p65 signaling pathway in response to virus (Poly IC), suggesting suppressed immunity of iPSC-derived cells to viral infection. The sustained WT TLR3 and TLR3 isoform overexpression is central to understanding the altered immunogenicity of human iPSC-derived cells calling for screening of human iPSC-derived cells for TLR3 expression levels before applications. Stem Cells 2019;37:476-488.

Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study.

BACKGROUND: Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE: The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN: A retrospective cohort study. SETTING: Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION: Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS: Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P < 0.001). Median mean arterial pressure was lower in open than in fetoscopic surgery. SBP, DBP and mean blood pressure decreased during uterine exposure, and this descent was more acute in open surgery. Use of vasoconstrictor drugs was related to the time of uterine exposure, but not to surgical technique. Blood gas analysis was not affected by CO2 insufflation during fetoscopic surgery. CONCLUSION: Open surgery was associated with more maternal haemodynamic changes and higher doses of halogenated anaesthetic and tocolytics agents than fetoscopic surgery.

Green spaces and cognitive development in primary schoolchildren.

Exposure to green space has been associated with better physical and mental health. Although this exposure could also influence cognitive development in children, available epidemiological evidence on such an impact is scarce. This study aimed to assess the association between exposure to green space and measures of cognitive development in primary schoolchildren. This study was based on 2,593 schoolchildren in the second to fourth grades (7-10 y) of 36 primary schools in Barcelona, Spain (2012-2013). Cognitive development was assessed as 12-mo change in developmental trajectory of working memory, superior working memory, and inattentiveness by using four repeated (every 3 mo) computerized cognitive tests for each outcome. We assessed exposure to green space by characterizing outdoor surrounding greenness at home and school and during commuting by using high-resolution (5 m × 5 m) satellite data on greenness (normalized difference vegetation index). Multilevel modeling was used to estimate the associations between green spaces and cognitive development. We observed an enhanced 12-mo progress in working memory and superior working memory and a greater 12-mo reduction in inattentiveness associated with greenness within and surrounding school boundaries and with total surrounding greenness index (including greenness surrounding home, commuting route, and school). Adding a traffic-related air pollutant (elemental carbon) to models explained 20-65% of our estimated associations between school greenness and 12-mo cognitive development. Our study showed a beneficial association between exposure to green space and cognitive development among schoolchildren that was partly mediated by reduction in exposure to air pollution.

Green spaces and spectacles use in schoolchildren in Barcelona.

Myopia is one of the major causes of low visual acuity during childhood, and hence of the need for spectacles. It is generally more prevalent in urban areas where children are often less exposed to green spaces than in rural areas. This study evaluated the association between exposure to green space and use of spectacles (as a surrogate measure for myopia) in a cohort of 2727 schoolchildren (7-10 years old) recruited from 39 primary schools in Barcelona (2012-2015). We assessed exposure to green spaces by characterizing outdoor surrounding greenness at home and school and during commuting using satellite data on greenness (Normalized Difference Vegetation Index). We also obtained data on the annual average time children spent playing in green spaces through questionnaires. Cross-sectional analyses were conducted based on prevalent cases of spectacles use at baseline data collection campaign and longitudinal analyses based on incident cases of spectacles use during the three-year period between the baseline and last data collection campaigns. An interquartile range (IQR) increase in exposure to green space at home (500m buffer) and school and during commuting was associated with respectively 14% (95% CI: 2%, 26%), 27% (95% CI: 6%, 44%), and 20% (95% CI: 5%, 33%) decrease in spectacles use in cross-sectional analyses. In longitudinal analyses, we observed a reduction of 23% (95% CI: 4%, 39%) and 34% (95% CI: 2%, 55%) associated with an IQR increase in greenness at home and school, respectively. Moreover, an IQR increase in time playing in green spaces was associated with a 28% (95% CI: 7%, 45%) reduction in the risk of spectacles use in the longitudinal analysis. Our observed reduced risk of spectacles use associated with higher contact with green space calls for more refined studies of the association between green spaces and refractive errors of visions.

Road traffic noise and children's inattention.

BACKGROUND: An increasing number of children are exposed to road traffic noise levels that may lead to adverse effects on health and daily functioning. Childhood is a period of intense growth and brain maturation, and children may therefore be especially vulnerable to road traffic noise. The objective of the present study was to examine whether road traffic noise was associated with reported inattention symptoms in children, and whether this association was mediated by sleep duration. METHODS: This study was based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Parental reports of children's inattention at age 8 were linked to modelled levels of residential road traffic noise. We investigated the association between inattention and noise exposure during pregnancy (n = 1934), noise exposure averaged over 5 years (age 3 to 8 years; n = 1384) and noise exposure at age 8 years (n = 1384), using fractional logit response models. The participants were children from Oslo, Norway. RESULTS: An association with inattention at age 8 years was found for road traffic noise exposure at age 8 years (coef = .0083, CI = [.0012, .0154]; 1.2% point increase in inattention score per 10 dB increase in noise level), road traffic noise exposure average for the last 5 years (coef = .0090, CI = [.0016, .0164]; 1.3% point increase/10 dB), and for pregnancy road traffic noise exposure for boys (coef = .0091, CI = [.0010, .0171]), but not girls (coef = -.0021, CI = [-.0094, .0053]). Criteria for doing mediation analyses were not fulfilled. CONCLUSION: Results indicate that road traffic noise has a negative impact on children's inattention. We found no mediation by sleep duration.

[Concordance and usefulness of a stratification system for clinical decision making]. / Concordancia y utilidad de un sistema de estratificación para la toma de decisiones clínicas.

OBJECTIVES: 1) To analyse concordance between the level of risk classification using the Adjusted Groups Morbidity (GMA) tool and the assigned level of intervention by general practitioners (GP). 2) To study the usefulness of the GMA tool as an aid in electronic medical records (EMR) for decision making. DESIGN: Cross-sectional observational study of concordance. LOCATION: Primary Care. Madrid Health Service. PARTICIPANTS: Twenty eight GPs. A sample of 840 patients assigned to participating GPs was selected by disproportionate stratified random sampling (0.65 kappa, 0.125 precision, 5% positive rate, 95% confidence level). MAIN MEASUREMENTS: Weighted Cohen Kappa index for the degree of concordance between the GMA tool and the GPs. The usefulness of the tool was assessed using an ad hoc developed questionnaire. RESULTS: Kappa weighted index obtained was 0.60 (95%CI: 0.55-0.65). In 3% of cases the disagreement was maximum. The GPs found that the grouping tool had been useful in 76% of cases. CONCLUSION: Moderate strength/good concordance; incorporating a grouping tool in the EMR helps as a reminder for taking more proactive/integrated decisions based on social and health needs of people with chronic diseases.

CuidaCare: effectiveness of a nursing intervention on the quality of life's caregiver: cluster-randomized clinical trial.

BACKGROUND: In Spain, family is the main source of care for dependent people. Numerous studies suggest that providing informal (unpaid) care during a prolonged period of time results in a morbidity-generating burden. Caregivers constitute a high-risk group that experiences elevated stress levels, which reduce their quality of life.Different strategies have been proposed to improve management of this phenomenon in order to minimize its impact, but definitive conclusions regarding their effectiveness are lacking. METHODS/DESIGN: A community clinical trial is proposed, with a 1-year follow-up period, that is multicentric, controlled, parallel, and with randomized allocation of clusters in 20 health care centers within the Community of Madrid. The study's objective is to evaluate the effectiveness of a standard care intervention in primary health care (intervention CuidaCare) to improve the quality of life of the caregivers, measured at 0, 6, and 12 months after the intervention.One hundred and forty two subjects (71 from each group) ≥65 years, identified by the nurse as the main caregivers, and who provide consent to participate in the study will be included.The main outcome variable will be perceived quality of life as measured by the Visual Analogue Scale (VAS) of EuroQol-5D (EQ-5D). The secondary outcome variables will be EQ-5D Dimensions, EQ-5D Index, nursing diagnosis, and Zarit's test. Prognostic variables will be recorded for the dependent patient and the caregiver.The principle analysis will be done by comparing the average change in EQ-5D VAS value before and after intervention between the two groups. All statistical tests will be performed as intention-to-treat. Prognostic factors' estimates will be adjusted by mixed-effects regression models. Possible confounding or effect-modifying factors will be taken into account. DISCUSSION: Assistance for the caregiver should be integrated into primary care services. In order to do so, incorporating standard, effective interventions with relevant outcome variables such as quality of life is necessary. Community care nurses are at a privileged position to develop interventions like the proposed one. TRIAL REGISTRATION: This trial has been registered in ClinicalTrials.gov under code number NCT 01478295.

Occupational Stress in Healthcare Professionals in Spain: A Multicenter Study.

Introduction: Occupational stress significantly impacts healthcare professionals in the Spanish public hospital system. This study, conducted from April to June 2022, focuses on analyzing stress levels using the Nursing Stress Scale through an online survey. Methods: A cross-sectional study was carried out using an online survey from April to June 2022 in four hospitals. The Nursing Stress Scale was used to comprehensively assess stress levels among healthcare professionals. Results: The findings revealed a substantial contrast in stress outcomes based on personal circumstances. Healthcare professionals in stable partnerships and with children exhibited lower stress levels, acting as protective factors during the pandemic. Conversely, those engaged in rotating shifts, especially those working over 60 h per week, showed a sevenfold increase in high-stress probability (p < 0.05). Temporary contract holders and those with heightened exposure to COVID-19 reported elevated stress levels, highlighting the complex dynamics impacting the mental well-being of healthcare workers. Conclusions: Findings emphasize the necessity for targeted interventions to safeguard healthcare professionals' well-being, focusing on the psychological consequences of factors like rotating shifts and extended working hours. Protective elements such as stable partnerships and parenthood could serve as a foundation for initiatives supporting work-life balance, potentially involving government policies and hospital management.

Machine learning-based health environmental-clinical risk scores in European children.

BACKGROUND: Early life environmental stressors play an important role in the development of multiple chronic disorders. Previous studies that used environmental risk scores (ERS) to assess the cumulative impact of environmental exposures on health are limited by the diversity of exposures included, especially for early life determinants. We used machine learning methods to build early life exposome risk scores for three health outcomes using environmental, molecular, and clinical data. METHODS: In this study, we analyzed data from 1622 mother-child pairs from the HELIX European birth cohorts, using over 300 environmental, 100 child peripheral, and 18 mother-child clinical markers to compute environmental-clinical risk scores (ECRS) for child behavioral difficulties, metabolic syndrome, and lung function. ECRS were computed using LASSO, Random Forest and XGBoost. XGBoost ECRS were selected to extract local feature contributions using Shapley values and derive feature importance and interactions. RESULTS: ECRS captured 13%, 50% and 4% of the variance in mental, cardiometabolic, and respiratory health, respectively. We observed no significant differences in predictive performances between the above-mentioned methods.The most important predictive features were maternal stress, noise, and lifestyle exposures for mental health; proteome (mainly IL1B) and metabolome features for cardiometabolic health; child BMI and urine metabolites for respiratory health. CONCLUSIONS: Besides their usefulness for epidemiological research, our risk scores show great potential to capture holistic individual level non-hereditary risk associations that can inform practitioners about actionable factors of high-risk children. As in the post-genetic era personalized prevention medicine will focus more and more on modifiable factors, we believe that such integrative approaches will be instrumental in shaping future healthcare paradigms.

Growing up in different environments can greatly affect children's health later in life. This research looked at how living in cities, being exposed to chemicals, and other experiences before birth and during childhood, work together to influence children's mental, cardiovascular and respiratory health. We used advanced computer programs to help us understand these effects and estimate health risk scores. These scores are simple numerical measures that help us quantify the likelihood of children developing health issues based on their environmental exposures. Using those scores, the study identified key factors impacting children's health, in particular psycho-social, perceived environmental and prenatal pollutant exposures for mental health. It also revealed complex patterns and interactions between environmental factors. The results highlighted the potential of such risk scores to support the identification of actionable factors in high-risk children, informing tailored prevention measures in healthcare.

Impact of the COVID-19 pandemic on the self-care and health condition of the older adults. CUIDAMOS+75. A mixed methods study protocol.

Aims: To assess the impact of the COVID-19 pandemic on the health condition of people ≥75 years of age and on their family caregivers in Spain. Design: Multicentric, mixed method concurrent study. Methods: This work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022). Discussion: The study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic. Trial Registration: Identifier: NCT05249868 [ClinicalTrials.gov].

Renal transplant among type 1 and type 2 diabetes patients in Spain: A population-based study from 2002 to 2013.

BACKGROUND: To describe trends in the rates and short-term outcomes of renal transplants (RTx) among patients with or without diabetes in Spain (2002-2013). METHODS: We used national hospital discharge data to select all hospital admissions for RTx. We divided the study period into four three-year periods. Rates were calculated stratified by diabetes status: type 1 diabetes (T1DM), type 2 diabetes (T2DM) and no-diabetes. We analyzed Charlson comorbidity index (CCI), post-transplant infections, in-hospital complications of RTx, rejection, in-hospital mortality and length of hospital stay. FINDINGS: We identified 25,542 RTx. Rates of RTx increased significantly in T2DM patients over time (from 9.3 cases/100,000 in 2002/2004 to 13.3 cases/100,000 in 2011/2013), with higher rates among people with T2DM for all time periods. T2DM patients were older and had higher CCI values than T1DM and non-diabetic patients (CCI≥1, 31.4%, 20.4% and 21.5%, respectively; P<0.05). Time trend analyses showed significant increases in infections, RTx-associated complications and rejection for all groups (all P values<0.05). Infection rates were greater in people with T2DM (20.8%) and T1DM (23.5%) than in non-diabetic people (18.7%; P<0.05). Time trend analyses (2002-2013) showed significant decreases in mortality during admission for RTx (OR 0.75, 95% CI 0.68-0.83). Diabetes was not associated with a higher in-hospital mortality (OR: 1.20, 95% CI 0.92-1.55). INTERPRETATION: RTx rates were higher and increased over time at a higher rate among T2DM patients. Mortality decreased over time in all groups. Diabetes does not predict mortality during admission for RTx. FUNDING: Instituto Salud Carlos III and URJC-Banco Santander.

Type 2 Diabetes Mellitus and Thoracic Aortic Aneurysm and Dissection: An Observational Population-Based Study in Spain From 2001 to 2012.

To describe trends in the rates of discharge due to thoracic aortic aneurysm and dissection (TAAD) among patients with and without type 2 diabetes in Spain (2001-2012).We used national hospital discharge data to select all of the patients who were discharged from the hospital after TAAD. We focused our analysis on patients with TAAD in the primary diagnosis field. Discharges were grouped by diabetes status (diabetic or nondiabetic). Incidence was calculated overall and stratified by diabetes status. We divided the study period into 4 periods of 3 years each. We analyzed diagnostic and surgical procedures, length of stay, and in-hospital mortality.We identified 48,746 patients who were discharged with TAAD. The rates of discharge due to TAAD increased significantly in both diabetic patients (12.65 cases per 100,000 in 2001/2003 to 23.92 cases per 100,000 in 2010/2012) and nondiabetic patients (17.39 to 21.75, respectively). The incidence was higher among nondiabetic patients than diabetic patients in 3 of the 4 time periods.The percentage of patients who underwent thoracic endovascular aortic repair increased in both groups, whereas the percentage of patients who underwent open repair decreased. The frequency of hospitalization increased at a higher rate among diabetic patients (incidence rate ratio 1.14, 95% confidence interval [CI] 1.07-1.20) than among nondiabetic patients (incidence rate ratio 1.08, 95% CI 1.07-1.11). The in-hospital mortality was lower in diabetic patients than in nondiabetic patients (odds ratio 0.83, 95% CI 0.69-0.99).The incidence rates were higher in nondiabetic patients. Hospitalizations seemed to increase at a higher rate among diabetic patients. Diabetic patients had a significantly lower mortality, possibly because of earlier diagnoses, and improved and more readily available treatments.

Hereditary familial polyposis and Gardner's syndrome: contribution of the odonto-stomatology examination in its diagnosis and a case description.

Familial Adenomatous Polyposis (FAP) and its phenotype variant, Gardner's syndrome, constitute a rare autosomal dominant inherited disorder. They are characterised by the development, generally during the second and third decades of life, of multiple adenomatous polyps in the colon and rectum. These polyps have a high risk of subsequently becoming malignant, which normally occurs in the third and fourth decades of life. The phenotypical features of FAP can be very variable. As well as colorectal polyps, these individuals can present with extra-colonic symptoms, among which are particularly: gastro-duodenal polyps, dermoid and epidermoid cysts, desmoid tumours, congenital hypertrophy of the retinal pigment epithelium, disorders of the maxillary and skeletal bones and dental anomalies. In this paper the most important aspects of this syndrome are reviewed, showing an example based on a well documented clinical case. The importance of odonto-stomatological examinations should be pointed out, among others, as a means of reaching a presumptive diagnosis, whose confirmation is vital to the patient.

The association between greenness and traffic-related air pollution at schools.

Greenness has been reported to improve mental and physical health. Reduction in exposure to air pollution has been suggested to underlie the health benefits of greenness; however, the available evidence on the mitigating effect of greenness on air pollution remains limited and inconsistent. We investigated the association between greenness within and surrounding school boundaries and monitored indoor and outdoor levels of traffic-related air pollutants (TRAPs) including NO2, ultrafine particles, black carbon, and traffic-related PM2.5 at 39 schools across Barcelona, Spain, in 2012. TRAP levels at schools were measured twice during two one-week campaigns separated by 6months. Greenness within and surrounding school boundaries was measured as the average of satellite-derived normalized difference vegetation index (NDVI) within boundaries of school and a 50m buffer around the school, respectively. Mixed effects models were used to quantify the associations between school greenness and TRAP levels, adjusted for relevant covariates. Higher greenness within and surrounding school boundaries was consistently associated with lower indoor and outdoor TRAP levels. Reduction in indoor TRAP levels was partly mediated by the reduction in outdoor TRAP levels. We also observed some suggestions for stronger associations between school surrounding greenness and outdoor TRAP levels for schools with higher number of trees around them. Our observed reduction of TRAP levels at schools associated with school greenness can be of public importance, considering the burden of health effects of exposure to TRAPs in schoolchildren.

Karyotyping of human synaptonemal complexes by cenM-FISH.

The purpose of this work was to adapt the recently described centromere-specific multicolour (cenM-) FISH technique to human meiotic cells, and evaluate the usefulness of this multiplex fluorescence method for karyotyping human synaptonemal complex (SC), previously analysed by immunocytogenetic approaches. The results obtained demonstrate that cenM-FISH is a reliable one-single-step method, which allows for the identification of all SC present in pachytene spreads. Moreover, when cenM-FISH is applied after immunocytogenetic analysis, the number and distribution of MLH1 foci per chromosome can be established and recombination analysis for each chromosome can be performed easily.

[Efficacy of nursing planning after hospital discharge of patients over 65 to reduce their readmission]. / Eficacia de la planificación del alta de enfermería para disminuir los reingresos en mayores de 65 años.

OBJECTIVES: To evaluate the efficacy of nursing care and monitoring of patients over 65 in primary care, to reduce the rate of readmission and to extend time till readmission. DESIGN: Non-randomised clinical trial with control. SETTING: Base Area 8, Madrid, Spain. Primary and specialist care. PARTICIPANTS: Patients over 65 admitted from home with the pathologies under study. There were 97 patients in the study, 49 in the intervention group and 48 in the control group. INTERVENTIONS: In the intervention group, link nursing conducted visits every 48 hours and provided health education to carer and patient. Patients in the control group received conventional care. Patients in both groups were contacted by phone by primary care nurses 2, 6, 12, and 24 weeks after their hospital discharge. MEASUREMENTS: Readmission for the same reason was recorded. As a secondary variable, time till readmission was recorded. RESULTS: Patients in the control group were admitted more often than those in the experimental group (OR, 3.3; 95% CI, 1.13-9.52; adjusted for the admission diagnosis). The result was consistent, on conducting an analysis of the time elapsed before readmission (HR, 2.29; 95% CI, 1.03-5.10; adjusted in the same way). CONCLUSIONS: A planned intervention into discharges with full, individual evaluation reduces readmissions and increases the time till readmission in patients over 65.

Micro-array analyses decipher exceptional complex familial chromosomal rearrangement.

Recently there has been an increased interest in large-scale genomic variation and clinically in the consequences of haploinsufficiency of genomic segments or disruption of normal gene function by chromosome rearrangements. Here, we present an extraordinary case in which both mother and daughter presented with unexpected chromosomal rearrangement complexity, which we characterized with array-CGH, array painting and multicolor large insert clone hybridizations. We found the same 12 breakpoints involving four chromosomes in both mother and daughter. In addition, the daughter inherited a microdeletion from her father. We mapped all breakpoints to the resolution level of breakpoint spanning clones. Genes were found within 7 of the 12 breakpoint regions, some of which were disrupted by the chromosome rearrangement. One of the rearrangements disrupted a locus, which has been discussed as a quantitative trait locus for fetal hemoglobin expression in adults. Interestingly, both mother and daughter show persistent fetal hemoglobin levels. We detail the most complicated familial complex chromosomal rearrangement reported to date and thus an extreme example of inheritance of chromosomal rearrangements without error in meiotic segregation.

Synapsis and meiotic recombination analyses: MLH1 focus in the XY pair as an indicator.

BACKGROUND: Anomalies in meiotic prophase I have been related to partial or total meiotic arrest. These anomalies include an abnormal synaptic process, resulting in disorders in meiotic recombination. METHODS: In the present study, we analyse primary spermatocytes from 12 infertile men (four with non-obstructive azoospermia, six with oligoastenoteratozoospermia, one with astenoteratozoospermia and one normozoospermic) and five control fertile donors using immunocytological techniques for synaptonemal complex, meiotic recombination and centromeric proteins. RESULTS: Mean numbers of MLH1 foci per cell, frequencies of cells presenting an MLH1 focus in the XY pair and percentages of cells affected by abnormal synaptic patterns (gaps and splits) are reported for each of the infertile patients and control men. A positive correlation between the frequency of cells showing a recombination focus in the XY pair and the number of autosomal recombination foci per cell is found. CONCLUSIONS: Reduced recombination in the XY pair and an increased number of cells affected by gaps may explain some idiopathic male infertility cases. The results suggest that recombination in the XY pair could be an indicator for general recombination frequency and for a successful meiotic process.