Late puberty onset and lack of acne during adolescence reduce high-grade prostate cancer at adulthood.

BACKGROUND: The interplay between pubertal events patterns (PEP) and prostate cancer (PCa) remains poorly understood. Therefore, we investigated the association of PEP with the odds of PCa, and PCa histological differentiation in men residents of Mexico city. METHODS: In this case-control study, we analyzed the information of 371 incident prostate cancer cases and 775 controls matched on age (±5 years). High-grade prostate cancer was classified with Gleason score at diagnosis as ≥8. With information related to beard growth, age at maximum height attainment, and acne severity, the k-medoids algorithm was used to identify three mutually exclusive PEP (early, intermediate, and late). This association was evaluated using multivariable nonconditional logistic regression models. RESULTS: Men with late PEP, characterized by age at maximum height attainment at around 23 years and no history of acne, was inversely associated with incident (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.15-0.48, p trend <0.01) and high-grade prostate cancer (OR: 0.24; 95% CI: 0.09-0.59, p trend <0.01). Similar associations were observed even after adjusting by IGF-1 (OR: 0.19; 95% CI: 0.06-0.58) and androgens excretion (OR: 0.21; 95% CI: 0.06-0.66). Only the association between the absence of acne and prostate cancer remained significant after adjustment by these biomarkers. CONCLUSIONS: This study suggests that pubertal characteristics might be helpful in identifying risk groups, among which, secondary prevention strategies could be applied. Also, the results agree with previous work suggesting other potential biological mechanisms involved in the etiology of prostate cancer such as the infectious and inflammatory pathways.

Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk.

Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.

Children and adolescents with neurodevelopmental disorders show cognitive heterogeneity and require a person-centered approach.

We aimed to identify patterns of cognitive differences and characterize subgroups of Mexican children and adolescents with three neurodevelopmental disorders (NDD): intellectual disability (ID), autism spectrum disorders (ASD) and attention deficit/hyperactivity disorder (ADHD). The sample included 74 children and adolescents 6-15 years; 34% had ID, ASD or ADHD, 47% had ID in comorbidity with ASD, ADHD or both, 11% had ASD + ADHD, 8% were children without NDD. We applied WISC-IV, Autism Diagnostic Interview-Revised, Mini-International Neuropsychiatric Structured Interview, Child Behavior Checklist, and UNICEF Child Functioning Module. We evaluated the normality of the WISC-IV sub-scales using the Shapiro-Francia test, then conducted a latent class analysis and assessed inter-class differences in terms of household, parent and child characteristics. The following four-class solution best fit the data: "Lower Cognitive Profile" (LCP), "Lower Working Memory" (LWM), "Higher Working Memory" (HWM), "Higher Cognitive Profile" (HCP). LCP included most of the children with ID, who had a low Working Memory (WM) index score. LWM included mainly children with ASD or ID + ADHD; their Perceptual Reasoning (PR) and Processing Speed (PS) index scores were much higher than those for Verbal Comprehension (VC) and WM. HWM included children with ASD or ADHD; their scores for PR, PS and VC were high with lower WM (although higher than for LWM). HCP included children without NDD and with ASD or ADHD or both and had the highest scores on all indices. Children with NDD show cognitive heterogeneity and thus require individualized treatment plans.

Brief Report: Delayed Diagnosis of Treatable Inborn Errors of Metabolism in Children with Autism and Other Neurodevelopmental Disorders.

The objective of our study was to evaluate the frequency of treatable inborn errors of metabolism (IEM) in a clinical sample of Mexican children and adolescents with neurodevelopmental disorders (NDD). Amino acids and acylcarnitines in blood samples of 51 unrelated children and adolescents were analyzed by tandem mass spectrometry to detect treatable IEM of small molecules. One patient with isovaleric acidemia and autism spectrum disorder (ASD) and another with beta-ketothiolase deficiency and ASD/intellectual disability/attention-deficit/hyperactivity disorder (ADHD) were diagnosed, indicating an IEM frequency of 3.9% (1:26 subjects). The high frequency of treatable IEM indicates the need to perform a minimum metabolic screening as part of the diagnostic approach for patient with NDD, particularly when newborn screening programs are limited to a few disorders.

Communication patterns in the doctor-patient relationship: evaluating determinants associated with low paternalism in Mexico.

BACKGROUND: Paternalism/overprotection limits communication between healthcare professionals and patients and does not promote shared therapeutic decision-making. In the global north, communication patterns have been regulated to promote autonomy, whereas in the global south, they reflect the physician's personal choices. The goal of this study was to contribute to knowledge on the communication patterns used in clinical practice in Mexico and to identify the determinants that favour a doctor-patient relationship characterized by low paternalism/autonomy. METHODS: A self-report study on communication patterns in a sample of 761 mental healthcare professionals in Central and Western Mexico was conducted. Multiple ordinal logistic regression models were used to analyse paternalism and associated factors. RESULTS: A high prevalence (68.7% [95% CI 60.0-70.5]) of paternalism was observed among mental health professionals in Mexico. The main determinants of low paternalism/autonomy were medical specialty (OR 1.67 [95% CI 1.16-2.40]) and gender, with female physicians being more likely to explicitly share diagnoses and therapeutic strategies with patients and their families (OR 1.57 [95% CI 1.11-2.22]). A pattern of highly explicit communication was strongly associated with low paternalism/autonomy (OR 12.13 [95% CI 7.71-19.05]). Finally, a modifying effect of age strata on the association between communication pattern or specialty and low paternalism/autonomy was observed. CONCLUSIONS: Among mental health professionals in Mexico, high paternalism prevailed. Gender, specialty, and a pattern of open communication were closely associated with low paternalism/autonomy. Strengthening health professionals' competencies and promoting explicit communication could contribute to the transition towards more autonomist communication in clinical practice in Mexico. The ethical implications will need to be resolved in the near future.

[Open communication between mental health professionals and parents of patients with intellectual disabilities]. / Comunicación abierta entre profesionales de la salud mental y padres de pacientes con discapacidad intelectual.

OBJECTIVE: To estimate the factors associated with open communication between mental health professionals and parents of patients with intellectual disabilities and other neurodevelopmental disorders. MATERIALS AND METHODS: Cross-sectional survey in 759 mental health professionals. The association between the pattern of open communication and the attributes of communication was estimated through a logistic, ordinal, multivariate model. RESULTS: The prevalence of the pattern of open communication in mental health professionals was 30.6% (95%CI 27.4-34.0). The associated factors were younger age (RM=2.42, 95% CI 1.57-3.75), specialty (RM= 1.56, 95%CI 1.09-2.23), high value to the truth (RM= 4.95, 95% CI 3.21-7.65), low paternalism (RM= 10.93, 95%CI 7.22-16.52) and courses in bioethics (RM= 1.45, 95%CI 1.01-2.09), adjusted for confusing variables. CONCLUSIONS: Mental health professionals reported low levels of open com-munication with parents of people with neurovelopmental disorders, so prioritizing the value to the truth, promoting less paternalism, and respecting the autonomy of patients, can contribute to changing these patterns of communication in clinical practice in Mexico.

OBJETIVO: Estimar los factores asociados con la comunicación abierta entre profesionales de la salud mental y padres de pacientes con discapacidad intelectual y otros trastornos del neurodesarrollo. MATERIAL Y MÉTODOS: Encuesta transversal en 759 profesionales de la salud mental. Se estimó la asociación entre el patrón de comunicación abierto y los atributos de la comunicación a través de un modelo logísti-co, ordinal y multivariado. RESULTADOS: La prevalencia del patrón de comunicación abierta en profesionales de la salud mental fue de 30.6% (IC95% 27.4-34.0). Los factores asocia-dos fueron menor edad (RM=2.42, IC95% 1.57-3.75), espe-cialidad (RM=1.56, IC95% 1.09-2.23), alto valor a la verdad (RM=4.95, IC95% 3.21-7.65), bajo paternalismo (RM=10.93, IC95% 7.22-16.52) y cursos de bioética (RM=1.45, IC95% 1.01-2.09), ajustando por variables confusoras. CONCLUSIONES: Los profesionales de la salud mental reportaron bajos niveles de comunicación abierta con los padres de personas con trastornos del neurodesarrollo, por lo que priorizar el valor a la verdad, promover un menor paternalismo y el respeto a la autonomía de los pacientes puede contribuir a cambiar estos patrones de comunicación en la práctica clínica en México.

Comunicación abierta entre profesionales de la salud mental y padres de pacientes con discapacidad intelectual / Open communication between mental health professionals and parents of patients with intellectual disabilities

Resumen Objetivo: Estimar los factores asociados con la comunicación abierta entre profesionales de la salud mental y padres de pacientes con discapacidad intelectual y otros trastornos del neurodesarrollo. Material y métodos: Encuesta transversal en 759 profesionales de la salud mental. Se estimó la asociación entre el patrón de comunicación abierto y los atributos de la comunicación a través de un modelo logístico, ordinal y multivariado. Resultados: La prevalencia del patrón de comunicación abierta en profesionales de la salud mental fue de 30.6% (IC95% 27.4-34.0). Los factores asociados fueron menor edad (RM=2.42, IC95% 1.57-3.75), especialidad (RM=1.56, IC95% 1.09-2.23), alto valor a la verdad (RM=4.95, IC95% 3.21-7.65), bajo paternalismo (RM=10.93, IC95% 7.22-16.52) y cursos de bioética (RM=1.45, IC95% 1.01-2.09), ajustando por variables confusoras. Conclusión: Los profesionales de la salud mental reportaron bajos niveles de comunicación abierta con los padres de personas con trastornos del neurodesarrollo, por lo que priorizar el valor a la verdad, promover un menor paternalismo y el respeto a la autonomía de los pacientes puede contribuir a cambiar estos patrones de comunicación en la práctica clínica en México.

Abstract Objective: To estimate the factors associated with open communication between mental health professionals and parents of patients with intellectual disabilities and other neurodevelopmental disorders. Materials and methods: Cross-sectional survey in 759 mental health professionals. The association between the pattern of open communication and the attributes of communication was estimated through a logistic, ordinal, multivariate model. Results: The prevalence of the pattern of open communication in mental health professionals was 30.6% (95%CI 27.4-34.0). The associated factors were younger age (RM=2.42, 95% CI 1.57-3.75), specialty (RM= 1.56, 95%CI 1.09-2.23), high value to the truth (RM= 4.95, 95% CI 3.21-7.65), low paternalism (RM= 10.93, 95%CI 7.22-16.52) and courses in bioethics (RM= 1.45, 95%CI 1.01-2.09), adjusted for confusing variables. Conclusion: Mental health professionals reported low levels of open communication with parents of people with neurovelopmental disorders, so prioritizing the value to the truth, promoting less paternalism, and respecting the autonomy of patients, can contribute to changing these patterns of communication in clinical practice in Mexico.

Frequency of the T307A, N680S, and -29G>A single-nucleotide polymorphisms in the follicle-stimulating hormone receptor in Mexican subjects of Hispanic ancestry.

BACKGROUND: FSHR SNPs may influence the ovarian sensitivity to endogenous and exogenous FSH stimulation. Given the paucity of data on the FSHR c.919A > G, c.2039A > G and - 29G > A SNPs in Hispanic population, we here analyzed their frequency distribution in Mexican mestizo women. METHODS: Samples from 224 Mexican mestizo women enrolled in an IVF program as well as a genotype database from 8182 Mexican mestizo subjects, were analyzed for FSHR SNPs at positions c.919, c.2039 and - 29G > A. Association between the genetic variants and reproductive outcomes was assessed. RESULTS: The c.919 and c.2039 SNPs were in strong linkage disequilibrium and their corresponding genotype frequencies in the IVF group were: AA 46.8%, AG 44.2%, and GG 8.9%, and AA 41.9%, AG 48.2% and GG 9.8%, respectively. For the -29G > A SNP, genotype frequencies were 27% (GG), 50% (GA) and 23% (AA). In normal oocyte donors with the c.2039 GG genotype, the number of oocytes recovered after ovarian stimulation (COS) were significantly (p < 0.01) lower than in those bearing other genotypes in this or the -29G > A SNP. Analysis of the large scale database revealed that both allelic and genotype frequencies for the three SNPs were very similar to those detected in the IVF cohort (p ≥ 0.38) and that female carriers of the c.2039 G allele tended to present lower number of pregnancies than women bearing the AA genotype; this trend was stronger when women with more Native American ancestry was separately analyzed (OR = 2.0, C.I. 95% 1.03-3.90, p = 0.04). There were no differences or trends in the number of pregnancies among the different genotypes of the -29G > A SNP. CONCLUSIONS: The frequency of the GG/GG combination genotype for the c.919 and c.2039 SNPs in Mexican hispanics is among the lowest reported. The GG genotype is associated with decreased number of oocytes recovered in response to COS as well as to lower pregnancy rates in Hispanic women from the general population. The absence of any effect of the -29AA genotype on the response to COS, indicates that there is no need to perform this particular genotype testing in Hispanic women with the purpose of providing an individually-tailored COS protocol.

Metabolic screening and metabolomics analysis in the Intellectual Developmental Disorders Mexico Study.

OBJECTIVE: Inborn errors of metabolism (IEM) are genetic conditions that are sometimes associated with intellectual developmental disorders (IDD). The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. MATERIALS AND METHODS: Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition, target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. CONCLUSION: Identification of new metabolomic profiles associated with IDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.

Metabolic screening and metabolomics analysis in the Intellectual Developmental Disorders Mexico Study / Tamiz bioquímico y metabolómico en el estudio de los trastornos del desarrollo intelectual en México

Abstract: Objective: Inborn errors of metabolism (IEM) are genetic conditions that are sometimes associated with intellectual developmental disorders (IDD). The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. Materials and methods: Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition, target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. Conclusion: Identification of new metabolomic profiles associated with IDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.

Resumen: Objetivo: Los errores innatos del metabolismo (EIM) son condiciones genéticas que pueden asociarse con trastornos del desarrollo intelectual (TDI). El objetivo de este estudio es contribuir a la caracterización metabólica de los pacientes con TDI de etiología desconocida. Material y métodos: Se realizará un tamiz metabólico mediante espectrometría de masas-tándem y fluorometría para descartar EIM; además, se analizará el perfil metabolómico de los pacientes con TDI. Conclusión: La identificación de perfiles metabolómicos asociados con los TDI de etiología desconocida contribuirá al desarrollo de nuevos esquemas diagnósticos y terapéuticos para la prevención y tratamiento de los TDI en México.

The intellectual developmental disorders Mexico study: situational diagnosis, burden, genomics and intervention proposal / Estudio sobre trastornos del desarrollo intelectual en México: diagnóstico situacional, carga, genómica y propuesta de intervenciones

Abstract: Objective: This study aims to generate evidence on intellectual development disorders (IDD) in Mexico. Materials and methods: IDD disease burden will be estimated with a probabilistic model, using population-based surveys. Direct and indirect costs of catastrophic expenses of families with a member with an IDD will be evaluated. Genomic characterization of IDD will include: sequencing participant exomes and performing bioinformatics analyses to identify de novo or inherited variants through trio analysis; identifying genetic variants associated with IDD, and validating randomly selected variants by polymerase chain reaction (PCR) and sequencing or real-time quantitative PCR (qPCR). Delphi surveys will be done on best practices for IDD diagnosis and management. An external evaluation will employ qualitative case studies of two social and labor inclusion programs for people with IDD. Conclusions: The results will constitute scientific evidence for the design, promotion and evaluation of public policies, which are currently absent on IDD.

Resumen: Objetivo: Esta investigación busca generar evidencia sobre trastornos del desarrollo intelectual (TDI) en México. Material y métodos: La carga de la enfermedad por TDI se estimará con un modelo probabilístico usando encuestas poblacionales. Se estimarán costos directos e indirectos de gastos catastróficos de familias con un integrante conTDI. La caracterización genómica deTDI incluirá secuenciar exomas, realizar análisis bioinformático para identificar variantes de novo o heredadas a través de análisis de tríos, identificar variantes genéticas asociadas con TDI, y validar variantes aleatoriamente seleccionadas con reacción en cadena de polimerasa y secuenciación o qPCR. Se harán encuestas Delphi sobre mejores prácticas de diagnóstico y manejo de TDI. Una evaluación externa empleará estudios cualitativos de caso de dos programas de inclusión social y laboral para personas con TDI. Conclusiones: Los resultados serán evidencia científica que podrá ser la base para el diseño, promoción y evaluación de políticas públicas, actualmente ausentes para TDI.

The intellectual developmental disorders Mexico study: situational diagnosis, burden, genomics and intervention proposal.

OBJECTIVE:: This study aims to generate evidence on intellectual development disorders (IDD) in Mexico. MATERIALS AND METHODS:: IDD disease burden will be estimated with a probabilistic model, using population-based surveys. Direct and indirect costs of catastrophic expenses of families with a member with an IDD will be evaluated. Genomic characterization of IDD will include: sequencing participant exomes and performing bioinformatics analyses to identify de novo or inherited variants through trio analysis; identifying genetic variants associated with IDD, and validating randomly selected variants by polymerase chain reaction (PCR) and sequencing or real-time quantitative PCR (qPCR). Delphi surveys will be done on best practices for IDD diagnosis and management. An external evaluation will employ qualitative case studies of two social and labor inclusion programs for people with IDD. CONCLUSIONS:: The results will constitute scientific evidence for the design, promotion and evaluation of public policies, which are currently absent on IDD.

The nuclear receptor NR4A1 induces a form of cell death dependent on autophagy in mammalian cells.

The control of cell death is a biological process essential for proper development, and for preventing devastating pathologies like cancer and neurodegeneration. On the other hand, autophagy regulation is essential for protein and organelle degradation, and its dysfunction is associated with overlapping pathologies like cancer and neurodegeneration, but also for microbial infection and aging. In the present report we show that two evolutionarily unrelated receptors--Neurokinin 1 Receptor (NK(1)R,) a G-protein coupled receptor, and Insulin-like Growth Factor 1 Receptor (IGF1R), a tyrosine kinase receptor--both induce non-apoptotic cell death with autophagic features and requiring the activity of the autophagic core machinery proteins PI3K-III, Beclin-1 and Atg7. Remarkably, this form of cell death occurs in apoptosis-competent cells. The signal transduction pathways engaged by these receptors both converged on the activation of the nuclear receptor NR4A1, which has previously been shown to play a critical role in some paradigms of apoptosis and in NK(1)R-induced cell death. The activity of NR4A1 was necessary for IGF1R-induced cell death, as well as for a canonical model of cell death by autophagy induced by the presence of a pan-caspase inhibitor, suggesting that NR4A1 is a general modulator of this kind of cell death. During cell death by autophagy, NR4A1 was transcriptionally competent, even though a fraction of it was present in the cytoplasm. Interestingly, NR4A1 interacts with the tumor suppressor p53 but not with Beclin-1 complex. Therefore the mechanism to promote cell death by autophagy might involve regulation of gene expression, as well as protein interactions. Understanding the molecular basis of autophagy and cell death mediation by NR4A1, should provide novel insights and targets for therapeutic intervention.

Physiological analysis of common bean (Phaseolus vulgaris L.) cultivars uncovers characteristics related to terminal drought resistance.

Terminal drought is a major problem for common bean production because it occurs during the reproductive stage, importantly affecting seed yield. Diverse common bean cultivars with different drought susceptibility have been selected from different gene pools in several drought environments. To better understand the mechanisms associated with terminal drought resistance in a particular common bean race (Durango) and growth habit (type-III), we evaluated several metabolic and physiological parameters using two cultivars, Bayo Madero and Pinto Saltillo, with contrasting drought susceptibility. The common bean cultivars were submitted to moderate and severe terminal drought treatments under greenhouse conditions. We analyzed the following traits: relative growth rate, photosynthesis and transpiration rates, stomatal conductance, water-use efficiency, relative water content, proline accumulation, glycolate oxidase activity and their antioxidant response. Our results indicate that the competence of the drought-resistant cultivar (Pinto Saltillo) to maintain seed production upon terminal drought relies on an early response and fine-tuning of stomatal conductance, CO2 diffusion and fixation, and by an increased water use and avoidance of ROS accumulation.

Oviduct contraction in Drosophila is modulated by a neural network that is both, octopaminergic and glutamatergic.

Fertility is a highly complex and regulated phenomenon essential for the survival of any species. To identify Drosophila fertility-specific neural networks, we used a GAL4/UAS enhancer trap genetic screen that selectively inactivates groups of neurons. We identified a GAL4 line (bwktqs) that has a female sterile phenotype only when it expresses the tetanus toxin light chain (TeTxLC). These flies lack oviduct contraction, lay almost no eggs, sperm accumulate in the oviducts, and fewer than normal are seen in the storage organs. In insects, two neuroactive substances are important for oviduct contraction: octopamine (OA), a monoamine that inhibits oviduct contraction, and glutamate (Glu), a neurotransmitter that induces contraction. It is known that octopaminergic neurons of the thoracic abdominal ganglion (TAG) modulate oviduct contraction, however, the glutamatergic neurons that innervate the oviduct have not been identified yet and the interaction between these two neuroactive substances is not well understood. Immunostaining experiments revealed that the bwktqs line trapped an octopaminergic neural network that innervates the genital tract. We show that wt like oviduct contraction in TeTxLC-inactivated flies can only be rescued by simultaneous application of Glu and OA suggesting that the abdominal bwktqs neurons are both octopaminergic and glutamatergic, the use of an agonist and an antagonist for Glu receptors as well as their direct visualization confirmed its participation in this phenomenon. Our work provides the first evidence that adult abdominal type II visceral innervations co-express Glu and OA and allows us to re-evaluate the previous model of neuronal network controlling insect oviduct contraction.