Prolactin promotes the recruitment of main olfactory bulb cells and enhances the behavioral exploration toward a socio-sexual stimulus in female mice.

Olfactory communication is triggered by pheromones that profoundly influence neuroendocrine responses to drive social interactions. Two principal olfactory systems process pheromones: the main and the vomeronasal or accessory system. Prolactin receptors are expressed in both systems suggesting a participation in the processing of olfactory information. We previously reported that prolactin participates in the sexual and olfactory bulb maturation of females. Therefore, we explored the expression of prolactin receptors within the olfactory bulb during sexual maturation and the direct responses of prolactin upon pheromonal exposure. Additionally, we assessed the behavioral response of adult females exposed to male sawdust after prolactin administration and the consequent activation of main and accessory olfactory bulb and their first central relays, the piriform cortex and the medial amygdala. Last, we investigated the intracellular pathway activated by prolactin within the olfactory bulb. Here, prolactin receptor expression remained constant during all maturation stages within the main olfactory bulb but decreased in adulthood in the accessory olfactory bulb. Behaviorally, females that received prolactin actively explored the male stimulus. An increased cFos activation in the amygdala and in the glomerular cells of the whole olfactory bulb was observed, but an augmented response in the mitral cells was only found within the main olfactory bulb after prolactin administration and the exposure to male stimulus. Interestingly, the ERK pathway was upregulated in the main olfactory bulb after exposure to a male stimulus. Overall, our results suggest that, in female mice, prolactin participates in the processing of chemosignals and behavioral responses by activating the main olfactory system and diminishing the classical vomeronasal response to pheromones.

Early and transitory hypoactivity and olfactory alterations after chronic atrazine exposure in female Sprague-Dawley rats.

Several studies have shown that chronic exposure to the herbicide atrazine (ATR) causes alterations in locomotor activity and markers of the dopaminergic systems of male rats. However, few studies have evaluated the sex-dependent effects of atrazine exposure. The aim of the present study was to evaluate whether chronic ATR exposure causes alterations in behavioral performance and dopaminergic systems of female rats. At weaning, two groups of rats were exposed to 1 or 10 mg ATR/kg body weight daily thorough the food, while the control group received food without ATR for 14 months. Spontaneous locomotor activity was evaluated monthly for 12 months, while anxiety, egocentric and spatial memory, motor coordination, and olfactory function tasks were evaluated between 13 and 14 months of ATR exposure. Tyrosine hydroxylase (TH) and monoamine content in brain tissue were assessed at the end of ATR treatment. Female rats treated with 1 or 10 mg ATR showed vertical hypoactivity compared to the control group only in the first month of ATR exposure. Impairments in olfactory functions were found due to ATR exposure. Nevertheless, no alterations in anxiety, spatial and egocentric memory, or motor coordination tasks were observed, while the levels of TH and dopamine and its metabolites in brain tissue were similar among groups. These results suggest that female rats could present greater sensitivity to the neurotoxic effects of ATR on spontaneous locomotor activity in the early stages of development. However, they are unaffected by chronic ATR exposure later in life compared to male rats. More studies are necessary to unravel the sex-related differences observed after chronic ATR exposure.

Targeted Glutamate Supply Boosts Insulin Concentrations, Ovarian Activity, and Ovulation Rate in Yearling Goats during the Anestrous Season.

The neuroendocrine regulation of the seasonal reproductive axis requires the integration of internal and external signals to ensure synchronized physiological and behavioral responses. Seasonal reproductive changes contribute to intermittent production, which poses challenges for optimizing goat product yields. Consequently, a significant objective in seasonal reproduction research is to attain continuous reproduction and enhance profitability in goat farming. Glutamate plays a crucial role as a modulator in several reproductive and metabolic processes. Hence, the aim of this study was to evaluate the potential impact of exogenous glutamate administration on serum insulin concentration and ovarian function during the out-of-season period in yearling goats. During the anestrous season, animals were randomly located in individual pens to form two experimental groups: (1) glutamate (n = 10, live weight (LW) = 29.1 ± 1.02 kg, body condition score (BCS) = 3.4 ± 0.2 units) and (2) control (n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2), with no differences (p < 0.05) regarding LW and BCS. Then, goats were estrus-synchronized, and blood sampling was carried out for insulin quantification. Ovaries were ultrasonographically scanned to assess ovulation rate (OR), number of antral follicles (AFs), and total ovarian activity (TOA = OR + AF). The research outcomes support our working hypothesis. Certainly, our study confirms that those yearling goats treated with exogenous glutamate displayed the largest (p < 0.05) insulin concentrations across time as well as an augmented (p < 0.05) out-of-season ovarian activity.

Goats as Valuable Animal Model to Test the Targeted Glutamate Supplementation upon Antral Follicle Number, Ovulation Rate, and LH-Pulsatility.

The potential effect of intravenous administration of glutamate on the ovarian activity and the LH secretion pattern, considering the anestrous yearling goat as an animal model, were assessed. In late April, yearling goats (n = 20) were randomly assigned to either (1) Glutamate supplemented (GLUT; n = 10, Live Weight (LW) = 29.6 ± 1.02 kg, Body Condition (BCS) = 3.4 ± 0.2 units; i.v. supplemented with 7 mg GLUT kg−1 LW) or (2) Non-supplemented (CONT; n = 10; LW = 29.2 ± 1.07 kg, BCS = 3.5 ± 0.2 units; i.v. saline). The oats were estrus-synchronized; blood sampling (6 h × 15 min) was carried out for LH quantification. Response variables included pulsatility (PULSE), time to first pulse (TTFP), amplitude (AMPL), nadir (NAD), and area under the curve (AUC) of LH. Ovaries were ultra-sonographically scanned to assess ovulation rate (OR), number of antral follicles (AF), and total ovarian activity (TOA = OR + AF). LH-PULSE was quantified with the Munro algorithm; significant treatment x time interactions were evaluated across time. The variables LW and BCS did not differ (p > 0.05) between the experimental groups. Nevertheless, OR (1.77 vs. 0.87 ± 0.20 units), TOA (4.11 vs. 1.87 ± 0.47 units) and LH-PULSE (5.0 vs. 2.2 pulses 6 h-1) favored (p < 0.05) to the GLUT group. Our results reveal that targeted glutamate supplementation, the main central nervous system neurotransmitter, arose as an interesting strategy to enhance the hypothalamic−hypophyseal−ovarian response considering the anestrous-yearling goat as an animal model, with thought-provoking while promising translational applications.

Neuroimmunoendocrine Link Between Chronic Kidney Disease and Olfactory Deficits.

Chronic kidney disease (CKD) is a multifactorial pathology that progressively leads to the deterioration of metabolic functions and results from deficient glomerular filtration and electrolyte imbalance. Its economic impact on public health is challenging. Mexico has a high prevalence of CKD that is strongly associated with some of the most common metabolic disorders like diabetes and hypertension. The gradual loss of kidney functions provokes an inflammatory state and endocrine alterations affecting several systems. High serum levels of prolactin have been associated with CKD progression, inflammation, and olfactory function. Also, the nutritional status is altered due to impaired renal function. The decrease in calorie and protein intake is often accompanied by malnutrition, which can be severe at advanced stages of the disease. Nutrition and olfactory functioning are closely interconnected, and CKD patients often complain of olfactory deficits, which ultimately can lead to deficient food intake. CKD patients present a wide range of deficits in olfaction like odor discrimination, identification, and detection threshold. The chronic inflammatory status in CKD damages the olfactory epithelium leading to deficiencies in the chemical detection of odor molecules. Additionally, the decline in cognitive functioning impairs the capacity of odor differentiation. It is not clear whether peritoneal dialysis and hemodialysis improve the olfactory deficits, but renal transplants have a strong positive effect. In the present review, we discuss whether the olfactory deficiencies caused by CKD are the result of the induced inflammatory state, the hyperprolactinemia, or a combination of both.

Acellular fraction from malignant effusions has cytotoxicity in breast cancer cells.

Malignant ascites (MA) and malignant pleural effusion (MPE) are frequently developed in patients with metastatic cancer; however, the biological properties of these fluids have not been clarified. The present study explored the biological role of a low molecular fraction derived from malignant effusions on the activation of peripheral blood mononuclear cells and on the proliferation of breast cancer cells and fibroblast 55x cells. A <10-kDa fraction from effusions of 41 oncological patients and 34 individuals without cancer was purified, and its potential role in inhibiting nitric oxide (NO) production on lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells was explored, as well as its cytotoxicity on MCF-7 breast cancer cells and fibroblast 55x cells. A significant decrease in NO production was observed in the <10-kDa fraction from malignant effusions. In addition, the acellular fraction from MA decreased the viability of breast cancer cells without affecting human fibroblasts. These data support the presence of low molecular weight molecules in malignant samples with a specific role in inhibiting the defense mechanisms of peripheral blood mononuclear cells and decreasing the viability of breast cancer cells in vitro.

Sexually dimorphic effects of prolactin treatment on the onset of puberty and olfactory function in mice.

The onset of puberty is associated with the psychophysiological maturation of the adolescent to an adult capable of reproduction when olfactory signals play an important role. This period begins with the secretion of the gonadotropin-releasing hormone (GnRH) from GnRH neurons within the hypothalamus. This is regulated by kisspeptin neurons that express high levels of transmembrane prolactin receptors (PRLR) that bind to and are activated by prolactin (PRL). The elevated levels of serum PRL found during lactation, or caused by chronic PRL infusion, decreases the secretion of gonadotropins and kisspeptin and compromised the estrous cyclicity and the ovulation. In the present work, we aimed to evaluate the effects of either increased or decreased PRL circulating levels within the peripubertal murine brain by administration of PRL or treatment with cabergoline (Cab) respectively. We showed that either treatment delayed the onset of puberty in females, but not in males. This was associated with the augmentation of the PRL receptor (Prlr) mRNA expression in the arcuate nucleus and decreased Kiss1 expression in the anteroventral periventricular zone. Then, during adulthood, we assessed the activation of the mitral and granular cells of the main (MOB) and accessory olfactory bulb (AOB) by cFos immunoreactivity (ir) after the exposure to soiled bedding of the opposite sex. In the MOB, the PRL treatment promoted an increased cFos-ir of the mitral cells of males and females. In the granular cells of male of either treatment an augmented activation was observed. In the AOB, an impaired cFos-ir was observed in PRL and Cab treated females after exposure to male soiled bedding. However, in males, only Cab impaired its activation. No effects were observed in the AOB-mitral cells. In conclusion, our results demonstrate that PRL contributes to pubertal development and maturation of the MOB-AOB during the murine juvenile period in a sex-dependent way.

Enfermedad renal crónica y olfato / Chronic kidney disease and the olfactory system

Las alteraciones en el sentido del olfato (disosmia, anosmia, hiposmia) son frecuentes en los pacientes con enfermedad renal crónica; sin embargo, hasta el momento actual las causas, consecuencias y tratamiento de estas alteraciones han sido poco abordadas. Los pacientes con enfermedad renal crónica sin tratamiento de diálisis muestran disminución en la percepción olfativa y existe controversia sobre si estas alteraciones se corrigen con la diálisis. El grado de percepción olfativa es similar cuando se compara la población en diálisis peritoneal y en hemodiálisis. El trasplante renal corrige estos déficits olfativos. Una de las probables consecuencias de esta afección es el impacto en el estado nutricional del paciente

Alterations in the sense of smell (dysosmia, anosmia, hyposmia) are frequently experienced by patients with chronic kidney disease. However, currently, the aetiology and consequences are poorly understood, with no effective treatments available to address such impairment. In general, the capacity of olfactory perception is affected in patients with chronic kidney disease (even in those who have not undergone dialysis therapy), and whether these alterations improve after dialysis is disputed. Patients in peritoneal dialysis and haemodialysis have the same olfactory perception defects. Kidney transplantation improves olfactory perception, and one important consequence of such impairment is the potential impact on the patient's nutritional status

Chronic kidney disease and the olfactory system. / Enfermedad renal crónica y olfato.

Alterations in the sense of smell (dysosmia, anosmia, hyposmia) are frequently experienced by patients with chronic kidney disease. However, currently, the aetiology and consequences are poorly understood, with no effective treatments available to address such impairment. In general, the capacity of olfactory perception is affected in patients with chronic kidney disease (even in those who have not undergone dialysis therapy), and whether these alterations improve after dialysis is disputed. Patients in peritoneal dialysis and haemodialysis have the same olfactory perception defects. Kidney transplantation improves olfactory perception, and one important consequence of such impairment is the potential impact on the patient's nutritional status.

Role for the membrane estrogen receptor alpha in the sexual differentiation of the brain.

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best-characterized responses activated by estrogens in adulthood and largely depend on ERα. Evidence exists that nucleus- and membrane-initiated estrogen signaling cooperate to orchestrate the activation of these behaviors both in short- and long-term. However, questions remain regarding the mechanism(s) and receptor(s) involved in the early brain programming during development to organize the circuits underlying sexually differentiated responses. Taking advantage of a mouse model harboring a mutation of the ERα palmitoylation site, which prevents membrane ERα signaling (mERα; ERα-C451A), this study investigated the role of mERα on the expression of male and female sexual behavior and neuronal populations that differ between sexes. The results revealed no genotype effect on the expression of female sexual behavior, while male sexual behavior was significantly reduced, but not abolished, in males homozygous for the mutation. Similarly, the number of kisspeptin- (Kp-ir) and calbindin-immunoreactive (Cb-ir) neurons in the anteroventral periventricular nucleus (AVPv) and the sexually dimorphic nucleus of the preoptic area (SDN-POA), respectively, were not different between genotypes in females. In contrast, homozygous males showed increased numbers of Kp-ir and decreased numbers of Cb-ir neurons compared to wild-types, thus leading to an intermediate phenotype between females and wild-type males. Importantly, females neonatally treated with estrogens exhibited the same neurochemical phenotype as their corresponding genotype among males. Together, these data provide evidence that mERα is involved in the perinatal programming of the male brain.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Low handgrip strength is associated with a higher incidence of pressure ulcers in hip fractured patients.

Pressure ulcers (PUs) are highly frequent in hip fractured elderly patients. This issue has a direct impact in quality of life, mortality as well as healthcare costs. Handgrip strength (HGS) is an efficient, low-cost and straightfoward method to measure functional capacity, as well as the global muscle strength of elderly patients. In this research we are aiming to analyze if low HGS is associated with higher incidence of pressure ulcers within a population of elderly patients with hip fracture from a tertiary hospital from Monterrey, Mexico. This research, designed as an observational-longi- tudinal cohort, included 462 patients admitted at the Hip and Pelvic Surgery Department of the Hospital of Traumatology and Orthopedics No. 21, of the Mexican Institute of the Social Security (IMSS), in Monterrey, Mexico. HGS measurement was performed by a trained physician, using a Jamar® Hydraulic Hand DynamometerPatients were grouped into tertiles according to their grip strength measurement and sex. Every patient was evaluated for presence or absence of PUs during hospital admission and followed until discharge. The general incidence of PUs was 25.7%. The incidence was higher in the weaker subjects (Tertile one 33%, Tertile two 30%, and Tertile three 15%, P=0.001). Pre-fracture Barthel's index, and Mini Nutritional Assessment Scores were lower among participants with PUs. After multivariate analysis, only HGS remained associated with PUs incidence. Low handgrip strength is associated with a higher incidence of pressure ulcers.

A robust biomarker of differential correlations improves the diagnosis of cytologically indeterminate thyroid cancers.

The fine-needle aspiration of thyroid nodules and subsequent cytological analysis is unable to determine the diagnosis in 15 to 30% of thyroid cancer cases; patients with indeterminate cytological results undergo diagnostic surgery which is potentially unnecessary. Current gene expression biomarkers based on well-determined cytology are complex and their accuracy is inconsistent across public datasets. In the present study, we identified a robust biomarker using the differences in gene expression values specifically from cytologically indeterminate thyroid tumors and a powerful multivariate search tool coupled with a nearest centroid classifier. The biomarker is based on differences in the expression of the following genes: CCND1, CLDN16, CPE, LRP1B, MAGI3, MAPK6, MATN2, MPPED2, PFKFB2, PTPRE, PYGL, SEMA3D, SERGEF, SLC4A4 and TIMP1. This 15-gene biomarker exhibited superior accuracy independently of the cytology in six datasets, including The Cancer Genome Atlas (TCGA) thyroid dataset. In addition, this biomarker exhibited differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power, and these 15 genes have been previously related to cancer in the literature. Thus, this 15-gene biomarker provides advantages in clinical practice for the effective diagnosis of thyroid cancer.

Sexual Stimulation Increases the Survival of New Cells in the Accessory Olfactory Bulb of the Male Rat.

Sexual behavior in rodents is modulated by the olfactory system. The olfactory bulb (OB) is a structure that undergoes continues neurogenesis in adulthood. We have previously shown that 15 days after males rats pace the sexual interaction and ejaculate 1 or 3 times, there is an increase in the density of new cells that reach the accessory olfactory bulb (AOB). The aim of the present study was to evaluate if sexual behavior in male rats increases the density of new neurons that survive 45 days after sexual behavior in the AOB and in the main OB (MOB). Male rats were randomly divided in four groups: (1) Control (Ctr), males without sexual interaction; (2) Exposed (Exp), males only exposed to a sexually receptive female; (3) No pacing (NP), males that mated in conditions in which the female paced the sexual interaction; (4) One ejaculation (1E), males that paced the sexual interaction with a receptive female and ejaculated once; and (5) Three ejaculations (3E), males that paced the sexual interaction and were allowed to ejaculate three times. All males were injected with the DNA synthesis marker 5-bromo-2-deoxyuridine (BrdU), and were tested in one of the above conditions. 45 days later they were sacrificed, and the OBs were processed to identify new cells and evaluate if they had differentiated into neurons. Our data indicate that males that ejaculated three times showed an increase in the density of new cells that survive in the posterior part of the granular cell layer of the AOB and have more new neurons that the control group. However, no significant differences were found in the percentage of new cells that differentiate into neurons. No significant increase in the density of new cells was observed in the MOB. Our data show that pacing the sexual interaction until three ejaculations increases the density of new cells and neurons in the granular layer of the AOB, confirming that sexual behavior induces long-lasting plastic changes in the OB.

Sexual Behavior Increases Cell Proliferation in the Rostral Migratory Stream and Promotes the Differentiation of the New Cells into Neurons in the Accessory Olfactory Bulb of Female Rats.

We have previously demonstrated, that 15 days after female rats pace the sexual interaction, there is an increase in the number of new cells that reach the granular cell layer (GrL) of the accessory olfactory bulb (AOB). The aim of the present study was to evaluate, if the first sexual experience in the female rat increases cell proliferation in the subventricular zone (SVZ) and the rostral migratory stream (RMS). We also tested if this behavior promotes the survival of the new cells that integrate into the main olfactory bulb (MOB) and AOB 45 days after the behavioral test. Sexually, naive female rats were injected with the DNA synthesis marker 5'-bromo-2'-deoxyuridine (BrdU) on the day of the behavioral test. They were randomly divided into the following groups: Female rats placed alone in the mating cage (1); Females exposed to amyl acetate odor [banana scent, (2)]; Females that could see, hear, and smell the male but physical contact was not possible [exposed to male, (3)]; Female rats that could pace the sexual interaction (4); and females that mated without the possibility of pacing the sexual interaction (5). Animals were sacrificed 2 days after the behavioral test (proliferation) or 45 days later (survival). Our results show that 2 days after females were exposed to banana scent or to the male, they had a higher number of cells in the SVZ. Females, that mated in pace and no-paced conditions had more new cells in the RMS. At 45 days, no significant differences were found in the number of new cells that survived in the MOB or in the AOB. However, mating increased the percentage of new cells, that differentiated into neurons in the GrL of the AOB. These new cells expressed c-Fos after a second sexual encounter just before the females were sacrificed. No significant differences in plasma levels of estradiol and progesterone were observed between groups. Our results indicate that the first sexual experience increases cell proliferation in the RMS and mating 45 days later enhances the number of new cells that differentiate into neurons in the AOB. These new neurons are activated by sexual stimulation.

Validation of the FRAIL scale in Mexican elderly: results from the Mexican Health and Aging Study.

BACKGROUND: The aging population in Latin America is characterized by not optimal conditions for good health, experiencing high burden of comorbidity, which contribute to increase the frequency of frailty; thus, identification should be a priority, to classify patients at high risk to develop its negative consequences. AIM: The objective of this analysis was to validate the FRAIL instrument to measure frailty in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). MATERIALS AND METHODS: Prospective, population study in Mexico, that included subjects of 60 years and older who were evaluated for the variables of frailty during the year 2001 (first wave of the study). Frailty was measured with the five-item FRAIL scale (fatigue, resistance, ambulation, illnesses, and weight loss). The robust, pre-frail or intermediate, and the frail group were considered when they had zero, one, and at least two components, respectively. Mortality, hospitalizations, falls, and functional dependency were evaluated during 2003 (second wave of the study). Relative risk was calculated for each complications, as well as hazard ratio (for mortality) through Cox regression model and odds ratio with logistic regression (for the rest of the outcomes), adjusted for covariates. RESULTS: The state of frailty was independently associated with mortality, hospitalizations, functional dependency, and falls. The pre-frailty state was only independently associated with hospitalizations, functional dependency, and falls. CONCLUSIONS: Frailty measured through the FRAIL scale, is associated with an increase in the rate of mortality, hospitalizations, dependency in activities of daily life, and falls.

Integration and comparison of different genomic data for outcome prediction in cancer.

BACKGROUND: In cancer, large-scale technologies such as next-generation sequencing and microarrays have produced a wide number of genomic features such as DNA copy number alterations (CNA), mRNA expression (EXPR), microRNA expression (MIRNA), and DNA somatic mutations (MUT), among others. Several analyses of a specific type of these genomic data have generated many prognostic biomarkers in cancer. However, it is uncertain which of these data is more powerful and whether the best data-type is cancer-type dependent. Therefore, our purpose is to characterize the prognostic power of models obtained from different genomic data types, cancer types, and algorithms. For this, we compared the prognostic power using the concordance and prognostic index of models obtained from EXPR, MIRNA, CNA, MUT data and their integration for ovarian serous cystadenocarcinoma (OV), multiform glioblastoma (GBM), lung adenocarcinoma (LUAD), and breast cancer (BRCA) datasets from The Cancer Genome Atlas repository. We used three different algorithms for prognostic model selection based on constrained particle swarm optimization (CPSO), network feature selection (NFS), and least absolute shrinkage and selection operator (LASSO). RESULTS: The integration of the four genomic data produced models having slightly higher performance than any single genomic data. From the genomic data types, we observed better prediction using EXPR closely followed by MIRNA and CNA depending on the cancer type and method. We observed higher concordance index in BRCA, followed by LUAD, OV, and GBM. We observed very similar results between LASSO and CPSO but smaller values in NFS. Importantly, we observed that model predictions highly concur between algorithms but are highly discordant between data types, which seems to be dependent on the censoring rate of the dataset. CONCLUSIONS: Gene expression (mRNA) generated higher performances, which is marginally improved when other type of genomic data is considered. The level of concordance in prognosis generated from different genomic data types seems to be dependent on censoring rate.

Alelo C del polimorfismo rs2209972 del gen de la enzima degradadora de insulina y enfermedad de Alzheimer en diabéticos tipo 2. Estudio de casos y controles / C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study

Background and objective: In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. General objetive: To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. Materials and methods: This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. Results: Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p > 0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6–3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3–8.2). Conclusions: Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene (AU)

Fundamento y objetivo: En las últimas décadas se ha producido una transformación en las pirámides poblacionales, con un aumento en la expectativa de vida, lo que conlleva un mayor número de enfermedades crónico-degenerativas, como son la diabetes mellitus y la demencia, que han mostrado tener una asociación estrecha, pero cuya etiología aún está por discernir. El objetivo de este estudio fue determinar la asociación entre el alelo C de la enzima degradadora de insulina y la enfermedad de Alzheimer en pacientes con diabetes tipo 2. Material y métodos: Estudio de casos y controles, en el cual se incluyeron pacientes de la clínica de Geriatría del Hospital General del Noreste de México. Los casos fueron aquellos con una puntuación en el Mini-Mental State Examination (MMSE) menor de 24 y criterios para demencia de acuerdo con el DSM-IV. Los controles fueron pacientes con MMSE superior a 24. Resultados: Se analizaron datos de 97 pacientes. No hubo diferencias respecto a las características basales clínicas y de laboratorio entre los casos y los controles (p > 0,05). Se documentó una prevalencia de 98% del alelo C de la enzima degradadora de insulina. Encontramos una asociación entre homocigosidad para el genotipo CC de la enzima degradadora de insulina y enfermedad de Alzheimer, con una OR de 2,5 (IC 95% 1,6–3,3) en el examen bivariado, y en el examen multivariado se encontró asociación con una OR de 3,3 (IC 95% 1,3–8,2). Conclusiones: La evidencia muestra una asociación entre deterioro cognitivo y presencia del alelo C del polimorfismo rs2209972 del gen de la enzima degradadora de insulina (AU)

C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study.

BACKGROUND AND OBJECTIVE: In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. GENERAL OBJETIVE: To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. MATERIALS AND METHODS: This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. RESULTS: Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p>0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6-3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3-8.2). CONCLUSIONS: Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene.

Chemical olfactory signals and parenthood in mammals.

This article is part of a Special Issue "Chemosignals and Reproduction". In mammalian species, odor cues emitted by the newborn are essential to establish maternal behavior at parturition and coordinate early mother-infant interactions. Offspring odors become potent attractive stimuli at parturition promoting the contact with the young to ensure that normal maternal care develops. In some species odors provide a basis for individual recognition of the offspring and highly specialized neural mechanisms for learning the infant signals have evolved. Both the main and the accessory olfactory systems are involved in the onset of maternal care, but only the former contributes to individual odor discrimination of the young. Electrophysiological and neurochemical changes occur in the main olfactory bulb leading to a coding of the olfactory signature of the familiar young. Olfactory neurogenesis could also contribute to motherhood and associated learning. Parturition and interactions with the young influence neurogenesis and some evidence indicates a functional link between olfactory neurogenesis and maternal behavior. Although a simple compound has been found which regulates anogenital licking in the rat, studies identifying the chemical nature of these odors are lacking. Neonatal body odors seem to be particularly salient to human mothers who are able to identify their infant's odors. Recent studies have revealed some neural processing of these cues confirming the importance of mother-young chemical communication in our own species.