Sexual Behavior and Synaptic Plasticity.

Although sex drive is present in many animal species, sexual behavior is not static and, like many other behaviors, can be modified by experience. This modification relies on synaptic plasticity, a sophisticated mechanism through which neurons change how they process a given stimulus, and the neurophysiological basis of learning. This review addresses the main plastic effects of steroid sex hormones in the central nervous system (CNS) and the effects of sexual experience on the CNS, including effects on neurogenesis, intracellular signaling, gene expression, and changes in dendritic spines, as well as behavioral changes.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Psychological distress and its correlates among dental students: a survey of 17 Colombian dental schools.

BACKGROUND: Links between the demanding nature of studies in the health sciences, students' personality traits and psychological distress have been well-established. While considerable amount of work has been done in medicine, evidence from the dental education arena is sparse and data from Latin America are lacking. The authors conducted a large-scale investigation of psychological distress among dental students in Colombia and sought to determine its curriculum and student-level correlates. METHODS: The Spanish version of the Derogatis' Symptoms Checklist Revised (SCL-90-R) was administered to all students officially registered and attending classes or clinics in 17 dental schools in 4 geographic districts of Colombia between January and April 2012. Additional information was collected on participants' socio-demographic information and first career choice, as well as school's characteristics such as class size. The Global Severity Index (GSI) score, a measure of overall psychological distress, served as the primary analytical endpoint. Analyses relied on multilevel mixed-effects linear and log-binomial regression, accounting for study design and sample characteristics. RESULTS: A total of 5700 dental students completed the survey, a response rate of 67%. Pronounced gradients were noted in the association between socio-economic status and psychological distress, with students in higher strata reporting fewer problems. After adjustment for all important covariates, there was an evident pattern of increasing psychological distress corresponding to the transition from the didactic, to the preclinical and clinical phases of training, with few differences between male and female students. Independent of other factors, reliance on own funds for education and having dentistry as the first career choice were associated with lower psychological distress. CONCLUSIONS: Levels of psychological distress correlated with students' socio-economic and study-level characteristics. Above and beyond the influence of person-level factors, variations in levels of distress paralleled specific transitional stages of the 5-year dental curriculum, providing opportunities for targeted interventions.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Variations in Theta/Beta Ratio and Cognitive Performance in Subpopulations of Subjects with ADHD Symptoms: Towards Neuropsychological Profiling for Patient Subgrouping.

ADHD is a neurodevelopmental disorder appearing in childhood but remaining in many cases in adults. There are both pharmacological and non-pharmacological approaches to treating ADHD, but they do not have the same efficacy in all subjects. Better knowledge of the neurophysiological basis of this disorder will allow for the design of more effective treatments. Studies performing qEEG analysis in children suggest the existence of subgroups of ADHD patients with different neurophysiological traits. There are fewer studies in adults, who might have undergone plastic changes allowing them to cope with ADHD symptoms along with brain maturation. Herein, we study cognitive performance and the theta/beta ratio in young adults with ADHD symptoms. We found that subjects with ADHD symptoms and low working memory performance (n = 30) present higher theta/beta ratios than controls (n = 40) at O2 and T6 in the eyes-closed condition, as well as a tendency toward a higher theta/beta ratio at O1 and Cz. Subjects with ADHD and high working memory performance (n = 50) do not differ from the controls in their theta/beta ratios at any derivation. Our results suggest that neuropsychological profiling could be useful for patient subgrouping. Further research will allow for the distinction of neuropsychological profiles and their neurophysiological correlates, leading to a better classification of ADHD subtypes, thus improving treatment selection.

ß-Adrenergic receptors in the insular cortex are differentially involved in aversive vs. incidental context memory formation.

The goal of this research was to determine the effects of ß-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the ß-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition of IA, but had no effect on formation of memory for an inert context (termed incidental memory). These results indicate that IC ß-adrenergic receptors are necessary for memory acquisition of an aversive, but not an inconsequential, context. Nevertheless, subsequent association of a familiar and hitherto inconsequential context with an unconditioned stimulus (US) does require activation of these receptors during its initial acquisition.

Personalization of Pharmacological Treatments for ADHD: Why it is Advisable and Possible Options to Achieve it.

Attention-deficit hyperactivity disorder is a neurodevelopmental disorder diagnosed primarily in children, although it is also present in adults. Patients present inattention, impulsivity, and hyperactivity symptoms that create difficulties in their daily lives. Pharmacological treatment with stimulants or non-stimulants is used most commonly to reduce ADHD symptoms. Although generally effective and safe, pharmacological treatments have different effects among patients, including lack of response and adverse reactions. The reasons for these differences are not fully understood, but they may derive from the highly diverse etiology of ADHD. Strategies to guide optimal pharmacological treatment selection based on individual patients' physiological markers are being developed. In this review, we describe the main pharmacological ADHD treatments used and their main drawbacks. We present alternatives under study that would allow the customization of pharmacological treatments to overcome these drawbacks and achieve more reliable improvement of ADHD symptoms.

ADHD: Reviewing the Causes and Evaluating Solutions.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder in which patients present inattention, hyperactivity, and impulsivity. The etiology of this condition is diverse, including environmental factors and the presence of variants of some genes. However, a great diversity exists among patients regarding the presence of these ADHD-associated factors. Moreover, there are variations in the reported neurophysiological correlates of ADHD. ADHD is often treated pharmacologically, producing an improvement in symptomatology, albeit there are patients who are refractory to the main pharmacological treatments or present side effects to these drugs, highlighting the importance of developing other therapeutic options. Different non-pharmacological treatments are in this review addressed, finding diverse results regarding efficacy. Altogether, ADHD is associated with different etiologies, all of them producing changes in brain development, leading to the characteristic symptomatology of this condition. Given the heterogeneous etiology of ADHD, discussion is presented about the convenience of personalizing ADHD treatment, whether pharmacological or non-pharmacological, to reach an optimum effect in the majority of patients. Approaches to personalizing both pharmacological therapy and neurofeedback are presented.

Mercury distribution in different environmental matrices in aquatic systems of abandoned gold mines, Western Colombia: Focus on human health.

Total mercury (THg), methylmercury (MeHg) in water, sediments, macrophytes, fish and human health risks were analyzed and assessed from abandoned gold mining ponds (AGMPs)/ mining areas in Western Colombia to know its present environmental condition. Concentrations of THg in water (avg. 13.0 ± 13.73 ng L-1) was above the EPA threshold level (12 ng L-1), suggesting possible chronic effects. Sediment sample revealed that the ponds are methylated (%MeHg: 3.3-11). Macrophyte Eleocharis elegans presented higher THg content in the underground biomass (0.16 ± 0.13 µg g-1 dw) than in the aerial biomass (0.05 ± 0.04 µg g-1 dw) indicating accumulation of THg. MeHg was the most abundant chemical species in fish (MeHg/THg: 83.2-95.0%), signifying higher bioavailability and its risk towards human health. Fish samples (15%) indicate that THg were above WHO limit (0.5 µg g), particularly in Ctenolucius beani, Hoplias malabaricus and lowest in Sternopygus aequilabiatus and Geophagus pellegrini. Bioaccumulation and biomagnification of MeHg were higher in the carnivores representing a source of exposure and potential threat to human health. Fulton's condition factor (K) for bioaccumulation indicate a decrease with increasing trophic level of fishes. Overall results suggest, mercury species found in different AGMPs compartments should be monitored in this region.

Blockade of nucleus basalis magnocellularis or activation of insular cortex histamine receptors disrupts formation but not retrieval of aversive taste memory.

Recent research, using several experimental models, demonstrated that the histaminergic system is clearly involved in memory formation. This evidence suggested that during different associative learning tasks, histamine receptor subtypes have opposite functions, related to the regulation of cortical cholinergic activity. Given that cortical cholinergic activity and nucleus basalis magnocellularis (NBM) integrity are needed during taste memory formation, the aim of this study was to determine the role of histamine receptors during conditioned taste aversion (CTA). We evaluated the effects of bilateral infusions of 0.5 microl of pyrilamine (100 mM), an H(1) receptor antagonist, into the NBM, or of R-alpha-methylhistamine (RAMH) (10 mM), an H(3) receptor agonist, into the insular cortex of male Sprague-Dawley rats 20 min before acquisition and/or retrieval of conditioned taste aversion. The results showed that blockade of H(1) receptors in NBM or activation of H(3) receptors in the insular cortex impairs formation but not retrieval of aversive taste memory. These results demonstrated differential roles for histamine receptors in two important areas for taste memory formation and suggest that these effects could be related with the cortical cholinergic activity modulation during CTA acquisition.

Determination of the phenotypic age in residents of Mexico City: effect of accelerated ageing on lung function and structure.

INTRODUCTION: Phenotypic age better represents age-related biological dysregulation than chronological age. Recently, a multisystem-based ageing measure, which integrates chronological age and nine biomarkers, was proposed. METHODS: Phenotypic age was determined in 774 residents of Mexico City over 60 years old and without respiratory problems. We arbitrarily classified as "accelerated" ageing, those showing >4 years compared with their chronological age, and "slowed" ageing, those with <4 years compared with chronological age. Demographic risk factors were analysed with structured questionnaires. Lung structure was evaluated by high-resolution computed tomography and functional competence was analysed by forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), diffusion capacity of carbon monoxide (D LCO), and the 6-minute walk test (6MWT). RESULTS: Overall, 13% of this cohort showed accelerated ageing, which was corroborated with four independent biomarkers of ageing, 42% had normal ageing and 46% had slowed ageing. Risk factors associated with accelerated ageing were male sex (OR 4.4, 95% CI 2.4-7.9; p<0.01), diabetes mellitus (OR 9.7, 95% CI 5.5-17.2; p<0.01), and long-term sleep duration (OR 2.9 95% CI 1.34-6.35, p<0.01). Among smokers, there was a slight but significant association with the number of pack-years. Subjects with accelerated ageing showed decreased FVC (p<0.0001), FEV1 (p<0.0001), D LCO (p<0.02) and walking distance in the 6MWT (p=0.0001). Slowed-ageing subjects presented less frequently with emphysematous lesions compared with those with accelerated ageing. CONCLUSIONS: A small but significant proportion of residents of Mexico City age rapidly, which is associated with male sex, diabetes, and long-term sleep duration. They exhibit lower levels of lung function and develop emphysema more frequently.

Distribution of chemical forms of mercury in sediments from abandoned ponds created during former gold mining operations in Colombia.

Total mercury (THg) and methylmercury (MeHg) were studied in sediments from 27 abandoned gold mining ponds (AGMPs) through small-scale artisanal gold mining in the district of San Juan in Chocó region of Colombia. The AGMPs were abandoned in the last century (1997) and were grouped into three distinct groups (2-6; 7-12; 13-20 years). Overall concentration (in ng g-1) pattern of THg in sediments varied from 39.06 to 1271.32 (avg. 209.57) with 174.81 (13-20 years), 205.56 (7-12 years) and 248.33 (2-6 years) respectively. MeHg concentrations accounted for 3.3-10.9% (avg. 6.5%) of THg and were significantly correlated with THg during all periods. Correlations between organic matter (OM) vs MeHg and THg were negative in the oldest pools, signifying a "dilution effect" or "natural burial" of THg and MeHg. Results for sequential extraction indicate that the fraction of elemental Hg (Hg-e) and organo chelated Hg (Hg-o) represent the main chemical forms of Hg in the sediments, regardless of the abandonment period, whereas the bioavailable fraction was only 0.12-1.65% of THg. The significant statistical relationship between MeHg, THg and OM suggests that these parameters control the distribution, mobility, toxicity and bioavailability of Hg in the sediments of these abandoned ponds. Evaluation of THg with sediment quality guidelines indicates that the values are on the higher side for Threshold effect concentration and Upper continental crust. Comparing of MeHg with many other regions outside Colombia is a worrying factor and needs immediate attention to protect the human health.

Coexistence of thyroid disease and oral lichen planus in a Colombian population.

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease of unknown etiology. OLP has recently been linked to thyroid disease, mainly hypothyroidism. The aim of this study was to determine the prevalence of thyroid disease in Colombian patients with OLP. A total of860 clinical records of patients attending the clinics of oral medicine and oral and maxillofacial surgery at IPS CES Sabaneta, Colombia, between 2010 and 2016 were reviewed. Fourteen patients (1.6%) had a diagnosis of OLP. The prevalence of hypothyroidism in patients with OLP was 35.7%, compared to 3.95% in the entire study population (OR 15.92, 95% CI: 5.63-50.09, P = 0.0001). Patients with concomitant hypothyroidism and OLP presented with less severe oral lesions compared to those without thyroid disease. This study supports the notion that patients with OLP should be screened for thyroid disease.

El liquen plano oral (LPO) es una enfermedad mucocutánea inflamatoria crónica de etiología desconocida. El LPO ha sido asociado recientemente con la enfermedad de la tiroides, especialmente con hipotiroidismo. El objetivo con este estudio fue determinar la prevalencia de la enfermedad de la tiroides en pacientes colombianos con LPO. Un total de 860 historias clínicas de pacientes que asistieron entre 2010 y 2016 a las clínicas de medicina oral y de cirugía oral y maxilofacial de la IPS CES Sabaneta, Colombia, fueron revisadas. Catorce pacientes (1.6%) habían sido diagnosticados con LPO. La prevalencia de hipotiroidismo en pacientes con LPO fue 35.7%, comparada con 3.95% en toda la población de estudio (RM 15.92, 95% IC: 5.63-50.09, P = 0.0001). Pacientes con hipotiroidismo y LPO concomitante presentaron lesiones orales menos severas comparado con aquellos sin enfermedad de la tiroides. Este estudio respalda la idea de que se debe investigar la presencia de enfermedad de la tiroides en pacientes con LPO.

Taste novelty induces intracellular redistribution of NR2A and NR2B subunits of NMDA receptor in the insular cortex.

Taste recognition memory is a process by which animals associate a taste previously experienced with its gastric consequences. Novel taste presentation induces in the insular cortex biochemical modifications that decrease after the taste becomes familiar. Here we show that, in this cortex, consumption of a novel taste produces an increase of the NR2A and NR2B subunits of the NMDA receptor in the detergent resistant membrane (DRM) fraction. This increase did not occur in the adjacent parietal cortex, was not due to a change in the total amount of protein, and is related with the novelty of the stimulus since it was reduced after the taste became familiar. Furthermore, NR2A and NR2B subunits increase in the DRM was blocked by the injection of a muscarinic acetylcholine receptor antagonist. These results suggest that modulation of NMDA receptors in the insular cortex through the increase of its NR2A and NR2B subunits in the DRM is involved in the taste memory formation via a cholinergic process.

A rapid identification technique for drug-resistant Mycobacterium tuberculosis isolates using mismatch specific cleavage enzyme.

The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains is a major health problem for high Tuberculosis (TB) incidence countries. Therefore, it is of interest to identify antibiotic resistant bacteria by mismatch detection using DNA hybridization. We generated PCR products for five genes (rpoB, inhA, katG, gyrA and rrs) associated with drug resistance TB from MDR and XDR Mycobacterium tuberculosis (MTB) DNA samples. These were hybridized to PCR products from MTB H37Rv (pansusceptible laboratory strain) to generate DNA hetero-duplex products, which was digested by Detection Enzyme (GeneArt Genomic Cleavage Detection Kit) and visualized by agarose gel electrophoresis. Results show different bands with sizes of 400 bp and 288 bp (rpoB), 280 bp (inhA), 310 bp (katG), 461 bp (gyrA) and 427 bp (rrs) suggesting mutations in DNA heteroduplex for each gene. Detection Enzyme specifically cleaves DNA hetero-duplex with mismatch. The technique helps in the improved detection of MDR (mutations in rpoB, inhA and katG) and XDR (mutations in rpoB, inhA katG, gyrA and rrs) MTB strains. Moreover, the technique is customized without expensive specialized equipment to detect mutations. It is also fast, efficient and easy to implement in standard molecular biology laboratories.

CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology.

The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1ß and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1ß and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs.

PKC blockade differentially affects aversive but not appetitive gustatory memories.

After consumption of a new taste, there are mainly two possible outcomes for the establishment of a taste memory, either it will be aversive or safe depending on the consequences of taste consumption. It has been proposed that both types of learning share a common initial taste memory trace, which will lead to two different memory traces, safe or aversive. To study the role of PKC activity in aversive or safe taste memory formation, we administered chelerythrine, a PKC inhibitor, into the insular cortex or parietal cortex 20 min before conditioned taste aversion or attenuation of neophobia training. The results suggest that PKC activity is needed in the insular cortex for the establishment of aversive taste memory, but not for safe taste memory.

A Genomic Signature for Genotyping Mycobacterium tuberculosis.

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), has a vast diversity of genotypes including Beijing, CAS, EAI, Haarlem, LAM, X, Ural, T, AFRI1 and AFRI2. However, genotyping can be expensive, time consuming and in some cases, results may vary depending on methodology used. Here, we proposed a new set of 10 SNPs using a total of 249 MTB genomes, and selected by first the inclusion/ exclusion (IE) criteria using spoligotyping and phylogenies, followed by the selection of the nonsynonymous SNPs present in the most conserved cluster of orthologous groups (COG) of each genotype of MTB. Genotype assignment of the new set of 10 SNPs was validated using an additional of 34 MTB genomes and results showed 100% correlation with their known genotypes. Our set of 10 SNPs have not been previously reported and cover the MTB genotypes that are prevalent worldwide. This set of SNPs could be used for molecular epidemiology with drug resistant markers.

Dopaminergic Modulation of Sleep-Wake States.

The role of dopamine in sleep-wake regulation is considered as a wakefulness-promoting agent. For the clinical treatment of excessive daytime sleepiness, drugs have been commonly used to increase dopamine release. However, sleep disorders or lack of sleep are related to several dopaminerelated disorders. The effects of dopaminergic agents, nevertheless, are mediated by two families of dopamine receptors, D1 and D2-like receptors; the first family increases adenylyl cyclase activity and the second inhibits adenylyl cyclase. For this reason, the dopaminergic agonist effects on sleep-wake cycle are complex. Here, we review the state-of-the-art and discuss the different effects of dopaminergic agonists in sleep-wake states, and propose that these receptors account for the affinity, although not the specificity, of several effects on the sleep-wake cycle.

[Characterisation of three polymorphisms of the tryptophan hydroxylase 2 gene in a sample of Colombian population with major depressive disorder]. / Caracterización de tres polimorfismos del gen de la triptófano hidroxilasa 2 en una muestra de población colombiana con trastorno depresivo mayor.

OBJECTIVE: Identify whether rs11179000, rs136494 and rs4570625 polymorphisms of the tryptophan hydroxylase 2 gene, are associated with a major depressive disorder in a sample of the Colombian population. METHODS: Case-control study was conducted in which a comparison was made between subjects diagnosed with major depressive disorder at some point in adulthood or active symptoms at the time of evaluation, and subjects with no psychiatric disease. Subjects were studied in the Department of Psychiatry, Faculty of Medicine and the Institute of Genetics at the National University of Colombia. Polymorphisms were genotyped using Taqman probes in real time PCR. As well as studying the association between major depressive disorder and these (single nucleotide polymorphisms (SNPs), the association with other factors previously associated with depression were also analysed. RESULTS: No statistically significant association between genotypic and allelic frequencies of each polymorphism and major depressive disorder was found. Association between sex and complication during pregnancy / childbirth and major depressive disorder was observed. Association between sex and complication during pregnancy / childbirth and major depressive disorder was observed. CONCLUSIONS: There was no association between any polymorphism and major depressive disorder.