Search

OBJECTIVE: Black emerging adults are significantly impacted by substance misuse. Posttraumatic stress disorder (PTSD) is associated with heightened substance misuse among Black emerging adults. However, limited research has identified protective factors that may influence the strength of the relation between PTSD and substance misuse in this population. Addressing this important limitation, the present study examined the potential moderating role of perceived social support in the association between PTSD symptoms and substance (i.e., alcohol and drug) misuse. METHODS: Participants were 182 trauma-exposed Black emerging adults (M age = 20.50; 71.3% women) who completed self-report measures assessing PTSD symptoms, alcohol and drug misuse, and perceived social support. RESULTS: PTSD symptoms were significantly and positively correlated with both alcohol and drug misuse. Moderation analyses indicated that positive relations between PTSD symptoms and both alcohol and drug misuse were only significant among Black emerging adults with lower (but not higher) levels of perceived social support. CONCLUSIONS: These findings suggest the potential utility of addressing social support in the assessment and treatment of substance misuse in trauma-exposed Black emerging adults.

OBJECTIVES: Posttraumatic stress disorder (PTSD) is characterized in part by negative alterations of cognition or mood, including alterations in emotional expressivity, or the extent to which one outwardly displays emotions. Yet, research in this area has relied on predominantly White samples and neglected to consider the potential role of gender, despite there being demonstrated gender differences in both PTSD symptom severity and emotional expressivity, separately. The goal of the current study was to fill a critical gap in the literature by examining the moderating role of gender in the relation between PTSD symptom severity and emotional expressivity in a sample of trauma-exposed Black adults. METHODS: Participants were 207 Black individuals enrolled in a historically Black university in the Southern United States (68.6% female; M(age) = 22.32 years). RESULTS: Findings provided support for the moderating role of gender in the association between PTSD symptom severity and emotional expressivity. Specifically, greater PTSD symptom severity was inversely related to emotional expressivity among trauma-exposed Black males and positively associated with emotional expressivity among trauma-exposed Black females. DISCUSSION: These results suggest the potential need for gender-specific assessment and treatment techniques for PTSD symptom severity among trauma-exposed Black college students.

OBJECTIVE There are ethnic-racial differences in the prevalence of posttraumatic stress disorder (PTSD). However, the factors underlying these differences are not well studied or understood. The goal of this study was to explore the relation of strength of ethnic-racial identity to PTSD. Specifically, we examined whether strength of ethnic-racial identity was indirectly related to PTSD symptom severity through positive and negative emotional avoidance. METHOD Participants were 401 trauma-exposed community individuals (Mage = 43.86 years; 70.1% female; 23.4% Asian, 23.7% Black, 25.1% Hispanic, 25.4% White). RESULTS Within the overall sample of ethnic-racial minorities, the indirect effect of strength of ethnic-racial identity on PTSD symptom severity through the pathways of both positive and negative emotional avoidance was significant. However, these findings were not replicated within each of the specific racial-ethnic subsamples. Specifically, while strength of ethnic-racial identity was indirectly associated with PTSD symptom severity through both positive and negative emotional avoidance in the Black subsample, this indirect effect was only significant through the pathway of positive emotional avoidance in the Hispanic subsample, and was nonsignificant in the Asian and White subsamples. CONCLUSIONS Results underscore ethnic-racial differences in the way in which strength of ethnic-racial identity impacts PTSD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Established relationships be­tween researchers, stakeholders and poten­tial participants are integral for recruitment of potential older adult participants and Evidence-Based Programs (EBPs) for chronic disease management have empirically been shown to help improve health and maintain healthy and active lives. To accelerate recruitment in EBPs and potential future research, we propose a Wellness Pathway allowing for delivery within multipurpose senior centers (MPCs) linked with medical facilities among lower-income urban older adults. The study aims were to: 1) assess the effectiveness of three MPC-delivered EBPs on disease management skills, health outcomes, and self-efficacy; and 2) assess the feasibility of the proposed Wellness Pathway for lower-income urban-dwelling older adults of color. Methods: We administered surveys and conducted a pre-post analysis among participants enrolled in any 1 of 3 MPC-based EBPs (n=53). To assess feasibility of the pathway, we analyzed survey data and interviews (EBP participants, MPC staff, physicians, n=10). Results: EBP participation was associated with greater disease management skills (increased time spent stretching and aerobic activity) but not improvements in self-effica­cy or other health outcomes. Interviews re­vealed: 1) older adults valued EBPs and felt the Wellness Pathway feasible; 2) staff felt it feasible given adequate growth manage­ment; 3) physicians felt it feasible provided adequate medical facility integration. Conclusion: MPC-based EBPs were associ­ated with improvements in disease manage­ment skills among older adults; a proposed Wellness Pathway shows early evidence of feasibility and warrants further investigation. Future efforts to implement this model of recruiting older adults of color into EBPs should address barriers for implementation and sustainability. Ethn Dis . 2020;30(Suppl 2):735-744; doi:10.18865/ed.30.S2.735

We have previously shown that in rats, capsaicin (Cap) has antidepressant-like properties when assessed using the forced swimming test (FST) and that a sub-threshold dose of amitriptyline potentiates the effects of Cap. However, synergistic antidepressant-like effects of the joint administration of Cap and the selective serotonin reuptake inhibitor citalopram (Cit) have not been reported. To assess whether combined administration of Cap and Cit has synergistic effects in the FST and to determine whether this combination prevents the side effects of Cit. Cap, Cit, and the co-administration of both substances were evaluated in a modified version of the FST (30-cm water depth) conducted in rats, as well as in the open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM). In line with previous studies, independent administration of Cap and Cit displayed antidepressant-like properties in the FST, while the combined injection had synergistic effects. In the OFT, neither treatment caused significant increments in locomotion. In the EPM, the time spent in the closed arms was lower in groups administered either only Cap or a combination of Cap and Cit than in groups treated with Cit alone. In the MWM, both Cap and the joint treatment (Cap and Cit) improved the working memory of rats in comparison with animals treated only with Cit. Combined administration of Cap and Cit produces a synergistic antidepressant-like effect in the FST and reduces the detrimental effects of Cit on anxiety and working memory.

Currently, it is widely accepted that memory extinction involves the formation of a new associative memory rather than unlearning of the information previously acquired. Nonetheless, the cellular and molecular mechanisms underlying this process are still unclear. In this regard, it has been suggested that while kinases modulate conditioning and LTP, phosphatases are relevant for extinction and LTD. In particular, the protein phosphatase calcineurin (CaN) has been involved in the extinction of some behavioral tasks along with LTD. Indeed, studies of our research group have demonstrated that induction of LTD in the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) pathway facilitates the extinction of conditioned taste aversion (CTA), while the induction of LTP in this pathway slows it down. In addition, we have shown that the extinction of CTA elicits an increase of CaN. The aim of the present study was to evaluate the participation of calcineurin in the extinction of CTA and in the expression of in vivo LTD in the Bla-IC pathway. For this purpose, we chemically inhibited calcineurin in the IC of adult male Wistar rats, either during CTA-extinction or thirty minutes after LTD induction in the Bla-IC pathway. Our results show that calcineurin inhibition slows down the CTA-extinction and blocks the maintenance of LTD. Furthermore, we show that CaN levels increase after LTD induction. These findings support the idea that calcineurin is a key molecular actor for both CTA extinction and LTD expression in the IC, a highly relevant neocortical area for the processing of aversively motivated learning tasks, suggesting that both processes are associated at a molecular level.

CoronaVac vaccine from Sinovac Life Science is currently being used in several countries. In Chile, the effectiveness of preventing hospitalization is higher than 80% with a vaccination schedule. However, to date, there are no data about immune response induction or specific memory. For this reason, we recruited 15 volunteers without previous suspected/diagnosed COVID-19 and with negative PCR over time to evaluate the immune response to CoronaVac 28 and 90 days after the second immunization (dpi). The CoronaVac administration induces total and neutralizing anti-spike antibodies in all vaccinated volunteers at 28 and 90 dpi. Furthermore, using ELISpot analysis to assay cellular immune responses against SARS-CoV-2 spike protein, we found an increase in IFN-gamma- and Granzyme B-producing cells in vaccinated volunteers at 28 and 90 dpi. Together, our results indicate that CoronaVac induces a robust humoral immune response and cellular immune memory of at least 90 dpi.

Sodium voltage-gated channel α subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected/30 mutation carriers) than in females (33.3%, 5 affected/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.

The suprachiasmatic nucleus (SCN) is the main brain clock in mammals. The SCN synchronizes to the light-dark cycle through the retinohypothalamic tract (RHT). RHT axons release glutamate to activate AMPA-kainate and N-methyl-D-aspartate (NMDA) postsynaptic receptors in ventral SCN neurons. Stimulation of SCN NMDA receptors is necessary for the activation of the signaling cascades that govern the advances and delays of phase. To our knowledge, no research has been performed to analyze the functional synaptic modifications occurring during postnatal development that prepare the circadian system for a proper synchronization to light at adult ages. Here, we studied the pre- and postsynaptic developmental changes between the unmyelinated RHT-SCN connections. Spontaneous NMDA excitatory postsynaptic currents (EPSCs) were greater in amplitude and frequency at postnatal day 34 (P34) than at P8. Similarly, both quantal EPSCs (miniature NMDA and evoked quantal AMPA-kainate) showed a development-dependent increase at analyzed stages, P3-5, P7-9, and P13-18. Moreover, the electrically evoked NMDA and AMPA-kainate components were augmented with age, although the increment was larger for the latter, and the membrane resting potential was more depolarized at early postnatal ages. Finally, the short-term synaptic plasticity was significantly modified during postnatal development as was the estimated number of quanta released and the initial release probability. All of these synaptic modifications in the unmyelinated RHT-SCN synapses suggest that synchronization to light at adult ages requires developmental changes similar to those that occur in myelinated fast communication systems.

Resumen La terapia de resincronización cardiaca mediante estimulación hisiana ha demostrado ser efectiva en pacientes con bloqueo de rama izquierda del haz de His e insuficiencia cardiaca. Paciente masculino, con 47 años de edad, con insuficiencia cardiaca, fracción de expulsión del 17% y miocardio dilatada idiopática, electrocardiograma en ritmo sinusal, bloqueo auriculoventricular de 1.er grado, intervalo PR 400 ms, bloqueo completo de rama derecha del haz de His, bloqueo del fascículo anterior de la rama izquierda del haz de His, duración del QRS 200 ms. Se decidió realizar estimulación selectiva del haz de His. La resincronización cardiaca biventricular convencional en pacientes con presencia de bloqueo completo de la rama derecha del haz de His no está indicada debido a la pobre respuesta al tratamiento. La estimulación hisiana permite reclutar la rama bloqueada y reestablecer la conducción a través de ella, de tal forma que, en ausencia de necrosis, se logre sincronía biventricular. En el caso presentado el reclutamiento de la rama derecha mediante estimulación hisiana se reflejó en el restablecimiento de la sincronía biventricular, medida por rastreo de marcas (speckle tracking) e incremento significativo de la fracción de expulsión del ventrículo izquierdo del 17 al 36.6%, con un incremento absoluto del 19.6%.

Alcohol and drug misuse is prevalent and problematic among women who experience intimate partner violence (IPV). Emotional dysfunction has been identified as a key mechanism in the etiology, maintenance, and treatment of alcohol and drug misuse. However, existing research has not considered the role of race/ethnicity in the relations between emotional dysfunction and alcohol and drug misuse. Furthermore, past research in this area has focused almost exclusively on emotional dysfunction stemming from negative (vs. positive) emotions. The goals of the current study were as follows: (a) to explore whether levels of difficulties regulating positive emotions differ among Latina, African American, and White IPV-victimized women, and (b) to examine the moderating role of race/ethnicity in the relations between difficulties regulating positive emotions and alcohol and drug misuse. Participants were 197 IPV-victimized women recruited through the criminal justice system ( Mage = 36.14; 51.8% African American, 31.5% White, and 16.8% Latina). Difficulties regulating positive emotions did not differ as a function of race/ethnicity. However, relations among difficulties regulating positive emotions and alcohol and drug misuse were significant for Latina and White but not African American IPV-victimized women. Moreover, race/ethnicity moderated an association between difficulties regulating positive emotions and drug misuse; this relation was significant and positive for White (compared with African American) IPV-victimized women. While preliminary, these results may inform culturally sensitive interventions for alcohol and drug misuse that are tailored to the unique needs of Latina, African American, and White IPV-victimized women.

The objective of this study was to analyze the mRNA transcription levels of ten functional genes of P-glycoproteins (P-gp) in free life stages, eggs and infective larvae (L3) and in endoparasitic stages, fourth larval stage (L4) and adult males of two native isolates of Haemonchus contortus: resistant and susceptible to IVM. The IVM resistant isolate was obtained from sheep naturally infected with H. contortus, and the susceptible isolate (with no pressure to IVM) conserved since 1990. The lethal effect of IVM was evaluated under in vitro conditions, which showed significant differences between susceptible and resistant H. contortus L3 isolates (P < 0.01). The IVM susceptible isolate revealed a lethal effect of 79.22% at 11.42 mM, whereas that resistant isolate showed no lethal effect at any of the four assessed concentrations (1.43, 2.85, 5.71 and 11.42 mM) of IVM. The expression levels of ten Hco-pgp genes (1, 2, 3, 4, 9, 10, 11, 12, 14, and 16) were evaluated in the resistant isolate of H. contortus and compared to the susceptible isolate (as control), using two constitutive genes (GAPDH and β-tubulin). Up-regulation at two statistical significant values (P ≤ 0.05, 0.1) was the criterion to associate IVM resistance with the free life and endoparasitic stages of H. contortus. The expression levels in H. contortus adult nematodes showed 5.64 to 127.56-fold increase for Hco-pgp genes 1, 9, 12, 14, and 16, followed by an increase for Hco-pgp-2 (49.75-fold) and Hco-pgp-10 (106.40-fold) in L4, and for Hco-pgp-16 (2.90-fold) in eggs (P ≤ 0.05). In addition, high expression levels with P < 0.1 were detected in H. contortus L3, L4, and adults for Hco-pgp genes 1, 4, 11, 12, and 16, with changes ranging from 2.17 to 29.72-fold. In conclusion, the highest expression was observed in the adult stage of H. contortus, and the most frequent gene with a significant P-value was Hco-pgp-16, revealing it plays an important role in IVM resistance.

Although most cases of Brugada syndrome have been described in adults, pediatric patients with the disease have been reported since the original article from Josep and Pedro Brugada. Herein is presented the case series of Brugada syndrome in pediatric population of the National Institute of Cardiology Ignacio Chavez. One boy and two adolescent males had palpitations as clinical presentation of the disease. Atrial arrhythmias were documented in two, in the third case there was a high clinical suspicion and quinidine abolished symptoms. The aim of this report is to highlight the importance of performing a detailed clinical history as well as the usefulness of high precordial leads for the diagnosis of this entity.

Transient receptor potential vanilloid 1 (TRPV1) channels have been implicated in depression and anxiety. The aim of this study was to evaluate the antidepressant-like properties of the TRPV1 agonist capsaicin using the forced swimming test (FST) in rats. Capsaicin (0.001–0.25 mg/kg, i.p.) produced a reduction of immobility in the FST. A maximally effective dose of the tricyclic antidepressant amitriptyline (12 mg/kg) reduced immobility as well. Notably, doses of capsaicin (1 pg/kg, 1 ng/kg, and 0.001 mg/kg) that were ineffective when applied alone produced a significant decrease in immobility when combined with a subthreshold dose of amitriptyline (5 mg/kg). Rats treated with capsaicin (0.01 mg/kg) + amitriptyline (5 mg/kg) displayed less immobility than those treated with a maximally effective dose of amitriptyline. The non-pungent TRPV1 channel agonist palvanil (0.05–0.1 mg/kg, i.p.) also decreased immobility in the FST. Capsaicin (0.05 mg/kg) did not affect general locomotion in the open field test, nor performance in the elevated plus maze, or skeletal muscle contraction strength measured in vitro after the FST (at 0.25 mg/kg). Altogether, our results imply that low doses of capsaicin produce antidepressant-like effects, and enhance the effect of a subthreshold dose of amitriptyline in the FST.

Indexación: Scopus. Synaptic abnormalities have been described in individuals with autism spectrum disorders (ASD). The cell-adhesion molecule Neuroligin-3 (Nlgn3) has an essential role in the function and maturation of synapses and NLGN3 ASD-associated mutations disrupt hippocampal and cortical function. Here we show that Wnt/β-catenin signaling increases Nlgn3 mRNA and protein levels in HT22 mouse hippocampal cells and primary cultures of rat hippocampal neurons. We characterized the activity of mouse and rat Nlgn3 promoter constructs containing conserved putative T-cell factor/lymphoid enhancing factor (TCF/LEF)-binding elements (TBE) and found that their activity is significantly augmented in Wnt/β-catenin cell reporter assays. Chromatin immunoprecipitation (ChIP) assays and site-directed mutagenesis experiments revealed that endogenous β-catenin binds to novel TBE consensus sequences in the Nlgn3 promoter. Moreover, activation of the signaling cascade increased Nlgn3 clustering and co-localization with the scaffold PSD-95 protein in dendritic processes of primary neurons. Our results directly link Wnt/β-catenin signaling to the transcription of the Nlgn3 gene and support a functional role for the signaling pathway in the dysregulation of excitatory/inhibitory neuronal activity, as is observed in animal models of ASD. https://www.nature.com/articles/s41398-018-0093-y.pdf

Anthracycline-based chemotherapy is associated with dose-dependent, irreversible damage to the heart. Childhood cancer survivors with hypertension after anthracycline exposure are at increased risk of cardiotoxicity, leading to the hypothesis that genetic susceptibility loci for hypertension may serve as predictors for development of late cardiotoxicity. Therefore, we determined the association between 12 GWAS-identified hypertension-susceptibility loci and cardiotoxicity in a cohort of long-term childhood cancer survivors (N = 108) who received anthracyclines and were screened for cardiac function via echocardiograms. Hypertension-susceptibility alleles of PLCE1:rs9327264 and ATP2B1:rs17249754 were significantly associated with cardiotoxicity risk conferring a protective effect with a 64% (95% CI: 0.18–0.76, P = 0.0068) and 74% (95% CI: 0.07–0.96, P = 0.040) reduction in risk, respectively. In RNAseq experiments of human induced pluripotent stem cell (iPSC) derived cardiomyocytes treated with doxorubicin, both PLCE1 and ATP2B1 displayed anthracycline-dependent gene expression profiles. In silico functional assessment further supported this relationship - rs9327264 in PLCE1 (P = 0.0080) and ATP2B1 expression (P = 0.0079) were both significantly associated with daunorubicin IC50 values in a panel of lymphoblastoid cell lines. Our findings demonstrate that the hypertension-susceptibility variants in PLCE1 and ATP2B1 confer a protective effect on risk of developing anthracycline-related cardiotoxicity, and functional analyses suggest that these genes are influenced by exposure to anthracyclines.

BACKGROUND: Medical mistrust influences patients’ treatment seeking, adherence, health behaviors, and minority participation in research studies. However, medical mistrust remains understudied within neurological diseases like stroke despite disproportionately affecting minority populations. OBJECTIVE: This study examines the relationship of medical mistrust with stroke knowledge among Black, Latino, Korean and Chinese-Americans. METHODS: Subjects >60 years were enrolled from senior centers to test a culturally-tailored educational curriculum around stroke risk reduction in a randomized controlled trial. A Trust Physician Scale and a modified Trust of Medical Researchers Scale measured medical mistrust. The Stroke Action Test instrument measured stroke knowledge, focusing on intent to call 911 appropriately when presented with stroke symptoms. RESULTS: Of 225 subjects, 69.5% were female (n=157) with an average age of 73.7 years (standard deviation 6.7). Blacks had highest trust scores of physicians relative to Latino/a, Korean or Chinese subjects (p

Background. The National Council on Aging’s Aging Mastery Program (AMP) aims to help older adults implement health behavior and lifestyle changes to promote healthy aging and social engagement. The purpose of the present community-partnered evaluation was to test the effectiveness of AMP implementation in Los Angeles County to improve participants’ quality of life, global physical and mental health, and patient activation. Method. A modified randomized wait-list controlled trial design was used to examine experimental, quasi-experimental, and dose-response evidence in five senior centers. Participants completed questionnaires at baseline and after the 10-week intervention, self-reporting their overall quality of life, physical health, mental health, and patient activation. Results. Experimental, intention-to-treat analyses found AMP assignment did not affect any measured outcomes ( n = 71). Quasi-experimental, “as treated” analyses ( n = 106) controlling for study site and sociodemographic characteristics indicated that participants who attended AMP reported more positive changes in global mental health than the control group. Attending AMP was not associated with changes in quality of life, physical health, or patient activation. Dose-response analyses among AMP participants who attended at least one class ( n = 75) found that attending more classes was not significantly associated with greater improvements in mental health. Conclusions. Experimental, intention-to-treat analyses did not support effectiveness of AMP on quality of life, physical or mental health, or patient activation; quasi-experimental analyses found attending AMP was associated with improvements in mental health. Recruitment challenges and participants’ nonadherence with condition assignment decreased our ability to detect effects. https://clinicaltrials.gov/ct2/show/NCT03342729?term=Aging+Mastery+Program&rank=1 .

Cognitive effects caused by cocaine and crack consumption, especially deficits in executive functions may increase the likelihood of drug-seeking behaviour and interfere with the ability of users to assimilate and participate in rehabilitation programs.To determine in early abstinence the state of executive functions, the impulsiveness and craving in cocaine and crack consumers.This cross-sectional study functions, with a sample of 60 male aged between 31.38 ± 7.26 years old, distributed in three groups: inhaled cocaine users (CDP-I; n = 15), with 23.13 ± 7.2 age of onset of consumption; crack cocaine users (CDP-C; n = 26), with 20.81 ± 4.21 age of onset of consumption, and a control groups of no-addiction individuals (n = 19). Sociodemographic, clinical and cognitive assessments were applied.The data showed that significant differences in socioeconomic level score and impulsiveness. Consumer groups have with lower scores with respect the control group. CDP-C group showed poor performances compared to the CDP-I and control groups, in the Berg Test, Tower of London, numbers in the direct order and subtraction. CDP-I group showed less score in planning compare with the other two groups.In early abstinence crack users manifest a greater number of deficits, mainly in working memory, planning and cognitive flexibility.Funcionamiento cognitivo en sujetos con trastorno de dependencia a cocaina y crack durante la abstinencia temprana.Introduccion. Los efectos cognitivos causados por el consumo de cocaina y crack, especialmente los deficits de las funciones ejecutivas, aumentan la probabilidad de un comportamiento de busqueda de drogas e interfieren en la capacidad de los usuarios de asimilar y participar en los programas de rehabilitacion. Objetivo. Determinar en la abstinencia temprana el estado de las funciones ejecutivas, la impulsividad y la ansiedad (craving) en consumidores de cocaina y crack. Sujetos y metodos. Este estudio transversal tuvo una muestra de 60 hombres, con una edad media de 31,38 ± 7,26 años, distribuidos en tres grupos: usuarios que inhalan cocaina (CDP-I; n = 15), con una edad de inicio de consumo de 23,13 ± 7,2 años; consumidores de cocaina en crack (CDP-C; n = 26), con una edad de inicio de consumo de 20,81 ± 4,21 años, y un grupo control de sujetos sin adiccion (n = 19). Se aplicaron evaluaciones sociodemograficas, clinicas y cognitivas. Resultados. Los datos mostraron diferencias significativas en las puntuaciones del nivel socioeconomico e impulsividad. Los grupos de consumidores tienen puntuaciones mas bajas con respecto al grupo control. El grupo CDP-C mostro rendimientos pobres en comparacion con el grupo CDP-I y el grupo control en las pruebas de Berg, torre de Londres, numeros en orden y sustraccion directos. El grupo CDP-I mostro una menor puntuacion en la planificacion comparada con los otros dos grupos. Conclusiones. En la abstinencia temprana, los consumidores de crack manifiestan mayor numero de deficits, principalmente en la memoria de trabajo, la planificacion y la flexibilidad cognitiva.

Background Racial/ethnic minority older adults have worse stroke burden than non‐Hispanic white and younger counterparts. Our academic‐community partner team tested a culturally tailored 1‐month (8‐session) intervention to increase walking and stroke knowledge among Latino, Korean, Chinese, and black seniors. Methods and Results We conducted a randomized wait‐list controlled trial of 233 adults aged 60 years and older, with a history of hypertension, recruited from senior centers. Outcomes were measured at baseline (T0), immediately after the 1‐month intervention (T1), and 2 months later (T2). The primary outcome was pedometer‐measured change in steps. Secondary outcomes included stroke knowledge (eg, intention to call 911 for stroke symptoms) and other self‐reported and clinical measures of health. Mean age of participants was 74 years; 90% completed T2. Intervention participants had better daily walking change scores than control participants at T1 (489 versus −398 steps; mean difference in change=887; 97.5% CI, 137–1636), but not T2 after adjusting for multiple comparisons (233 versus −714; mean difference in change=947; 97.5% CI, −108 to 2002). The intervention increased the percent of stroke symptoms for which participants would call 911 (from 49% to 68%); the control group did not change (mean difference in change T0–T1=22%; 99.9% CI, 9–34%). This effect persisted at T2. The intervention did not affect measures of health (eg, blood pressure). Conclusions This community‐partnered intervention did not succeed in increasing and sustaining meaningful improvements in walking levels among minority seniors, but it caused large, sustained improvements in stroke preparedness. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02181062.

The emission of 50 kHz frequency-modulated ultrasonic vocalizations (FM USVs) in rats has been associated with positive affective states, while a decrease in FM USVs has been associated with anxiety-like states. We tested the hypothesis in male Sprague-Dawley rats that FM USVs would complement measures of aversive memories (decrease in FM USVs) in a conditioned fear task in which we examined extinction or reconsolidation disruption. In Experiment 1, rats were fear conditioned using low-level footshock followed by extinction while monitoring freezing and FM USVs. In Experiment 2, rats were fear conditioned, the alpha-1 antagonist prazosin was used to disrupt reconsolidation of memory, and freezing and FM USVs were measured. Rats fear conditioned with low-level shock showed minimal freezing that rapidly extinguished, despite a persistent decrease in FM USVs throughout extinction. Prazosin reduced freezing in a memory reactivation-dependent manner as expected, but the reduction in FM USVs after fear conditioning remained decreased, suggesting that an affective component of memory was not impacted by prazosin. These findings indicate that FM USVs may be used as an index of fear- or anxiety-like memory, and their measurement could benefit pre-clinical animal models for assessing reduction of aversive memories.

Background The study of the kidney transplant involves understanding the immunologic basis, such as histocompatibility and the genetic basis of a population. In Mexico, the study of the genetic basis has led to a genetic map by federal entities. Methods We performed an HLA study with 1,276 kidney transplant patients (recipients and donors) in the Hospital of the National Medical Center Twenty-First Century, determining HLA class I (A, B, and Cw) and class II (DRβ1 and DQβ1) antigens with the use of SSOP-PCR. A descriptive analysis was conducted with measures of central tendency (mean, SD). Results Of 1,276 HLA patients studied, we obtained 2,552 results for each class by the composition of the 2 haplotypes, and for HLA-Cw we processed 796 patients, for a total of 1,592 antigens for this class. We found antigens specific to each federal entity, and it was found that the Federal District had the highest number of specific antigens (10) followed by Morelos (7), Queretaro and Mexico State (3 each), and Tamaulipas, Aguascalientes, Michoacan, Guerrero, Puebla, and Oaxaca (1 each). Conclusions The genetic map allows us to know proportions of antigens in every state in the center and south of Mexico owing to the diversity and area of influence of the National Medical Center XXIst Century, as well as the wide number of patients. Furthermore, there are still preserved proportionally distinct genetic roots in every entity.

Objective We performed a study to identify differences between patients with impulsive suicide attempt and those with premeditated suicide attempt in a Mexican population. Method We studied 144 patients who recently attempted suicide. Impulsive and premeditated suicide attempts were evaluated with the Suicide Intent Scale. These data were divided according to the type of attempt. Subsequently, the characteristics between the two groups were compared. Results The rate of patients that made an impulsive attempt was 61.8% and only 9.7% of the patients carried out a premeditated suicide attempt. More years of schooling/education and less severity of the attempt were observed in patients that carried out an impulsive suicide attempt ( p Conclusions Our findings demonstrate that there are clinical differences among the individuals who carried out an impulsive suicide attempt from those who premeditated an attempt in a Mexican population. As a result, when planning interventions and prevention efforts it may be helpful to consider these clinical differences and demographic characteristics.

The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90Tissues and cells derived from Crohn's disease (CD), ulcerative colitis (UC), and healthy individuals (N) were studiedA significant increase in programmed death-ligand 1 (PD-L1) was observed in the inflamed UC colonic mucosa when compared to the non-inflamed matched tissue samples, CD, and healthy controls. UC-CMFs were among the major populations in the colonic mucosa contributing to the enhanced PD-L1 expression. In contrast, PD-L1 expression was decreased in CD-CMFs. When compared to CD-CMFs and N-CMFs, UC-CMFs demonstrated stronger suppression of IL-2, Th1 transcriptional factor Tbet, and IFN-γ expression by CD3/CD28-activated CD4We present evidence showing that increased PD-L1 expression suppresses Th1 cell activity in UC. In contrast, loss of PD-L1 expression observed in CD contributes to the persistence of the Th1 inflammatory milieu in CD. Our data suggest that dysregulation of the Th1 responses in the inflamed colonic mucosa of IBD patients is promoted by the alterations in PD-L1 expression in the mucosal mesenchymal stromal cell compartment.

Alzheimer's disease is a common age associated neurodegenerative disorder associated with an elevated risk of seizures that may be fundamentally connected to cognitive dysfunction. We used 4-9month-old mice of the APP/PS1 mouse model of Alzheimer's disease to study the presence of epileptiform-like discharges and to establish if the amyloid-β plaques affect their generation. The EEG of the APP/PS1 transgenic mice revealed a higher incidence of epileptiform-like discharges i.e. seizure events (interictal spikes, sharp waves, or polyspikes) than in the controls. Also, APP/PS1 mice showed a lower latency to evoke seizure events than in the control animals when pentylenetetrazole (60mg/kg; i.p.) was injected. Moreover, physostigmine injection (1mg/kg; i.p.) also increased the frequency of spontaneous epileptiform-like discharges in the APP/PS1 mice. We also found a correlation between the frequency of epileptiform-like discharges and the number of amyloid-β plaques. Application of N-(2-chloroethyl)-N-ethyl-bromobenzylamine (50mg/kg) generated amyloid-β plaques in the cortex and seizure activity appeared. Taken together, these data indicate that deposits of amyloid-β plaques may be responsible for the epileptiform-like discharges recorded in the APP/PS1 mice and could be responsible for the elevated risk for seizures of Alzheimer's patients.

Although penile carcinoma is a rare malignancy, there is still an unmet need to identify prognostic factors associated with poor survival. In this study, we utilized demographic and clinical information to identify the most informative variables associated with overall survival in patients with penile cancer. From a full model including all covariates found to be statistically significant in univariable analyses, we identified a parsimonious reduced model containing tumor site (penis glans: hazard ratio [HR] = 0.48; 95% CI: 0.28-0.85 and penis not otherwise specified: HR = 0.45; 95% CI: 0.25-0.84), undetermined tumor differentiation (HR = 0.48; 95% CI: 0.27-0.86), and TNM stage III/IV (HR = 2.83; 95% CI: 1.68-4.75). When all of the covariates from the full model were subjected to classification and regression tree analysis, we identified 6 novel risk groups. Of particular interest, we found marriage was associated with substantial improvement in survival among men with the same stage and disease site. Specifically, among single/widowed/divorced men with TNM stage 0-II and prepuce/penis corpus/overlapping lesions had worse survival (5-year survival = 18.2%) versus married men (5-year survival = 62.5%). Since marital status is linked to social support, these findings warrant a deeper investigation into the relationships between disease prognosis and social support in patients with penile carcinoma.

Indexación: Web of Science; Scielo. Objectives: This study investigated the relationship between urease and arginine deiminase system (ADS) activities and dental caries through a cross-sectional study. Material and Methods: Urease and ADS activities were measured in saliva and plaque samples from 10 caries-free subjects and 13 caries-active. Urease activity was obtained from the ammonia produced by incubation of plaque and saliva samples in urea. ADS activity was obtained from the ammonia generated by the arginine-HCl and Tris-maleate buffer. Specific activity was defined as micromoles of ammonia per minute per milligram of protein. Shapiro-Wilk statistical test was used to analyze the distribution of the data, and Mann-Whitney test was used to determine the significance of the data. Results: The specific urease activity in saliva and plaque was significantly higher in individuals with low DMFT scores. ADS activity in saliva (6.050 vs 1.350, p=0.0154) and plaque (8.830 vs 1.210, p=0.025) was also higher in individuals with low DMFT scores. Conclusions: Caries-free subjects had a higher ammonia generation activity by urease and arginine deiminase system for both saliva and plaque samples than low caries-active subjects. High levels of alkali production in oral environment were related to caries-free subjects. http://ref.scielo.org/ch4qbr

The aim of the present study was to assess the expression of cytokines and FCeR1A receptor stimulated by Haemonchus placei larval excretory and secretory (ES) products associated with the pathogenesis in calves. Bovine peripheral blood mononuclear cells (PBMC) were stimulated in in vitro assays with H. placei L4 ES product at 8, 12, 16 and 24 h. ES products were collected in in vitro assays at 48 h with molecular weight of 72/60 kDa and isoelectric point of 7.2 pI. Specific IgG for infected and control calves, positive and negative, were employed to recognise H. placei larval ES products by indirect ELISA, showing a mean of 1.8, 0.83 and 0.28 OD, respectively, (p ≤ 0.001). The quantification of relative gene expression was performed using a set of cytokines (IL-2, IFNγ, TGFβ, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-13), FCeR1A receptor and housekeeping (GAPDH, β-actin and β-2-microglobulin) by RT-qPCR. An early increased expression, 2.2- to 3.4-fold change, of IL-2 (p ≤ 0.001), IL-5 and TGFβ (p ≥ 0.05) was determined, followed by TGFβ (30.7 and 14.14), IL-8 (102.8 and 1504.4) and IL-10 (60.4 and 1.7) (p ≤ 0.05) after 12 and 16 h, respectively, and reducing the expression level at 24 h. In addition, IL-6, IL-13 and FCeR1A receptor also displayed mild expression level, 2.1 – to 7.60-fold change, at 24 h (p ≥ 0.05). We conclude that ES products of 72/60 kDa collected in vitro from H. placei larvae are recognised by infected hosts and have the ability to induce diverse immune factors to modulate the nematode damage.

A new process for obtaining dibenzo[c,f][1,2,5]thiadiazepines (DBTDs) and their effects on GABA(A) receptors of guinea pig myenteric neurons are described. Synthesis of DBTD derivatives began with two commercial aromatic compounds. An azide group was obtained after two sequential reactions, and the central ring was closed via a nitrene to obtain the tricyclic sulfonamides (DBTDs). Whole-cell recordings showed that DBTDs application did not affect the holding current but inhibited the currents induced by GABA (I(GABA)), which are mediated by GABA(A) receptors. These DBTDs effects reached their maximum 3 min after application and were: (i) reversible, (ii) concentration-dependent (with a rank order of potency of 2c = 2d > 2b), (iii) mediated by a non-competitive antagonism, and (iv) only observed when applied extracellularly. Picrotoxin (which binds in the channel mouth) and DBTDs effects were not modified when both substances were simultaneous applied. Our results indicate that DBTD acted on the extracellular domain of GABA(A) channels but independent of the picrotoxin, benzodiazepine, and GABA binding sites. DBTDs used here could be the initial model for synthesizing new GABA(A) receptor inhibitors with a potential to be used as antidotes for positive modulators of these receptors or to induce experimental epilepsy.

Purpose of the study The study identifies differences in age-expectations between older adults from Korean, Chinese, Latino, and African American backgrounds living in the United States. Design and methods This study uses baseline demographic, age-expectation, social, and health data from 229 racial/ethnic minority seniors in a stroke-prevention intervention trial. Unadjusted regression models and pair-wise comparisons tested for racial/ethnic differences in age-expectations, overall, and across domain subscales (e.g., physical-health expectations). Adjusted regression models tested whether age-expectations differed across racial/ethnic groups after controlling for demographic, social, and health variables. Regression and negative binomial models tested whether age-expectations were consistently associated with health and well-being across racial/ethnic groups. Results Age-expectations differed by race/ethnicity, overall and for each subscale. African American participants expected the least age-related functional decline and Chinese American participants expected the most decline. Although African American participants expected less decline than Latino participants in unadjusted models, they had comparable expectations adjusting for education. Latino and African American participants consistently expected less decline than Korean and Chinese Americans. Acculturation was not consistently related to age-expectations among immigrant participants over and above ethnicity. Although some previously observed links between expectations and health replicated across racial/ethnic groups, in adjusted models age-expectations were only related to depression for Latino participants. Implications With a growing racial/ethnic minority older population in the United States, it is important to note older adults' age-expectations differ by race/ethnicity. Moreover, expectation-health associations may not always generalize across diverse samples.

The use of nomograms which include the PSA may improve the predictive power of obtaining a prostate biopsy (PB) positive for cancer. We compare the use of three on-line nomagrams with the detection of primary malignant circulating prostate cells (CPCs) to predict the results of an initial PB in men with suspicion of prostate cancer.Consecutive men with suspicion of prostate cancer underwent a 12 core TRUS prostate biopsy; age, total serum PSA, percent free PSA, family history, ethnic origin and prostate ultrasound results were used for risk assessment using the online nomograms. Mononuclear cells were obtained by differential gel centrifugation from 8ml of blood and CPCs were identified using double immunomarcation with anti-PSA and anti-P504S. A CPC was defined as a cell expressing PSA and P504S and defined as negative/positive. Biopsies were classified as cancer/no-cancer. Areas under the curve (AUC) for each parameter were calculated and compared and diagnostic yields were calculated.1,223 men aged55 years participated, 467 (38.2%) had a biopsy positive for cancer of whom 114/467 (24.4%) complied with the criteria for active observation. Area under the curve analysis showed CPC detection to be superior (p0.001), avoiding 57% of potential biopsies while missing 4% of clinically significant prostate cancers.The CPC detection was superior to the nomograms in predicting the presence of prostate cancer at initial biopsy; its high negative predictive value potentially reduces the number of biopsies while missing few significant cancers, being superior to the nomograms in this aspect. Being a positive/negative test the detection of CPCs avoids defining a cutoff value which may differ between populations.

To investigate the mediators of health-related quality of life (HR-QoL) in colorectal cancer (CRC) patients and effect on overall survival.We analyzed baseline (within 1 year of diagnosis) SF-12v1 questionnaire data from 3734 CRC patients and assessed the differences in mental composite scores (MCS) and physical composite scores (PCS) by socio-demographics and risks of poor HR-QoL by these factors. Hazard ratios were generated using univariate Cox regression for MCS and PCS dichotomized using the normalized scoring-based mean of 50 and survival estimates generated using the Kaplan-Meier method.Differences in MCS and PCS were identified by sex, age, education level, alcohol use, tobacco use, and stage. Race, marital status, and cancer site differed only by PCS. Being female, never married, former alcohol user, or with stage IV disease significantly increased risk of a poor HR-QoL, with magnitudes of risk from 1.25- to 1.97-fold. Higher education level had a protective effect (MCS: POur findings identify potential mediators for HR-QoL and suggest that baseline HR-QoL assessment may be prognostic for CRC.

Cet article rapporte un cas de leishmaniose feline disseminee chez un chat (Felis catus ) de 14 ans, seropositif pour le FIV et vivant dans les Alpes-Maritimes (sud de la France). Le chat presente des papules erythemateuses ulcerees sur la face et l’encolure, et une lesion proliferative ulceree sur l’oreille gauche. C’est l’examen histopathologique des lesions cutanees qui permet le diagnostic d’une leishmaniose disseminee, associee a un carcinome epidermoide de l’oreille. 100 mg d’allopurinol administres une fois par jour per os pendant quatre mois ont permis la remission totale des lesions cutanees. Des prelevements post mortem ont revele la persistance du parasite dans l’organisme apres six mois de traitement. Cet article discute de la sensibilite du chat a la leishmaniose et de son role potentiel de reservoir.

Ca+-induced Ca2+release tightly controls the function of ventricular cardiac myocytes under normal and pathological conditions. Two major factors contributing to the regulation of Ca2+release are the cytosolic free Ca2+concentration and sarcoplasmic reticulum (SR) Ca2+content. We hypothesized that the amount of Ca2+released from the SR during each heart beat strongly defines the refractoriness of Ca2+release. To test this hypothesis, EGTA AM, a high-affinity, slow-association rate Ca2+chelator, was used as a tool to modify luminal SR Ca2+content. An analysis of the cytosolic and luminal SR Ca2+dynamics recorded from the epicardial layer of intact mouse hearts indicated that the presence of EGTA reduced the diastolic SR free Ca2+concentration and fraction of SR Ca2+depletion during each beat. In addition, this maneuver shortened the refractory period and accelerated the restitution of Ca2+release. As a consequence of the accelerated restitution, the frequency dependence of Ca2+alternans was significantly shifted toward higher heart rates, suggesting a role of luminal SR Ca2+in the genesis of this highly arrhythmogenic phenomenon. Thus, intra-SR Ca2+dynamics set the refractoriness and frequency dependence of Ca2+transients in subepicardial ventricular myocytes.

The main objective of this study is to describe the presence of infections in patients with pulmonary haemorrhage and systemic lupus erythematosus. Patients with systemic lupus erythematosus and pulmonary haemorrhage were thoroughly evaluated in the first 48 hours with imaging plus bronchoscopy and bronchoalveolar fluid analysis. If needed, videoassisted thoracoscopy and lung biopsy were performed too. In all, search for bacterial, mycobacterial and fungal infections proceeded. Appropriate blood, bronchoalveolar fluid and tissue cultures were taken. Patients were treated with antibiotics and corticosteroids in case of infection. Otherwise, they received initial intravenous methylprednsiolone pulses for 3 days as standard therapy for pulmonary haemorrhage in systemic lupus erythematosus. Additional treatment with immunosuppressives was further decided by the treating physicians. Fourteen events in 13 patients were evaluated. In eight events (57%), an infection was demonstrated. Aetiological agents included Pseudomonas sp. and Aspergillus fumigatus. Four patients died, three of them because of the pulmonary infection and one because of cerebral haemorrhage secondary to severe systemic hypertension, 48 hours after methylprednisolone treatment. Patients with systemic lupus erythematosus and pulmonary haemorrhage have a high prevalence of infections. The influence of pulmonary haemorrhage in the setting of systemic lupus erythematosus needs further study to establish adequate treatment and to reduce the high mortality of this complication.

Background: The Wnt/β-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high-penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. Methods: We assessed 172 variants in 26 genes from the Wnt/β-catenin pathway in 809 colorectal cancer cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. Results: Eighteen SNPs in the pathway were significantly associated with colorectal cancer risk (P < 0.05) in the discovery phase. We observed a significant dose-response increase in colorectal cancer risk by number of risk genotypes carried (P = 4.19 × 10−8). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for colorectal cancer risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 [95% confidence interval (CI), 0.76–0.94, P = 0.001]. Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis—OR, 1.42; 95% CI, 1.16–1.74; P = 0.00085. Functional assessment identified several potential biologic mechanisms underlying these associations. Conclusions: Our findings suggest that common germline variants in the Wnt/β-catenin pathway may be involved in colorectal cancer development. Impact: These variants may be informative in colorectal cancer risk assessment to identify individuals at increased risk who would be candidates for screening. Cancer Epidemiol Biomarkers Prev; 25(3); 540–6. ©2016 AACR.

The complex adaptive mechanisms that eurythermal fish have evolved in response to the seasonal changes of the environment include the transduction of the physical parameter variations into neuroendocrine signals. Studies in carp (Cyprinus carpio) have indicated that prolactin (PRL) and growth hormone (GH) expression is associated with acclimatization, suggesting that the pituitary gland is a relevant physiological node in this adaptive process. Also, the distinctive pattern of expression that carp prolactin receptor (PRLr) protein depicts upon seasonal acclimatization supports the hypothesis that PRL and its receptor clearly are involved in the new homeostatic stage that the eurythermal fish needs to survive during the cyclical changes of its habitat. Here, we characterize the first prolactin receptor gene in a teleost and show that its expression is not associated with alternative promoters, unlike in humans and rodents. Using the regulatory region to direct the transcription of green fluorescent protein (GFP) in zebrafish embryos, we mapped the appearance of this hormone receptor during fish development. This is the first report identifying a fish prolactin receptor gene expressing transcript isoforms encoding for short forms of the protein (45 kDa). These have been found in osmoregulatory tissues of the carp and are regulated in connection with the seasonal acclimatization of the fish.

Human delay discounting is usually studied with experimental protocols that use symbols to express delay and amount. In order to further understand discounting, we evaluated whether the absence of numbers to represent reward amounts affects discount rate in general, and whether the magnitude effect is generalized to nonsymbolic situations in particular. In Experiment 1, human participants were exposed to a delay-discounting task in which rewards were presented using dots to represent monetary rewards (nonsymbolic); under this condition the magnitude effect did not occur. Nevertheless, the magnitude effect was observed when equivalent reward amounts were presented using numbers (symbolic). Moreover, in estimation tasks, magnitude increments produced underestimation of large amounts. In Experiment 2, participants were exposed only to the nonsymbolic discounting task and were required to estimate reward amounts in each trial. Consistent with Experiment 1, the absence of numbers representing reward amounts produced similar discount rates of small and large rewards. These results suggest that value of nonsymbolic rewards is a nonlinear function of amount and that value attribution depends on perceived difference between the immediate and the delayed nonsymbolic rewards.

Multiple myeloma (MM) is a monoclonal gammopathy characterized by abnormal proliferation of malignant plasma cells. The median overall survival rate has changed from 2-3 to 5-6 or more years with the introduction of novel agents. Recently CD200 protein has been described as an immunosuppressive protein that confers a poor prognostic factor in several neoplastic diseases, including MM. The purpose of our study was to determine CD200 protein in plasma cells of newly diagnosed patients with MM and in CD3+ lymphocytes of healthy donors.35 newly diagnosed MM patients and 25 healthy donors were studied. For flow cytometry tests, a FacsCalibur device and CellQuestPro software were used. Monoclonal antibodies for CD38 (PeCyC5), CD138 (APC), and CD200 (PE) were used. The statistical analysis was performed with SPSS 19v. Mann-Whitney U test, Kaplan-Meier survival curves with Log-Rank tests were done when indicated.The frequencies of anemia, hypercalcemia, increased in LDH, serum creatinine and b2-microglobulin were 68%, 34%, 20%, 22% and 45% respectively. The treatment consisted in MPT 20 (57%), Thal-Dex 8 (23%), and VAD 7 (20%). Five patients (14%) achieved complete response, 17 (49%) partial response, and 13 (37%) minor response or failure to treatment.CD200 is a poor prognostic factor for overall survival in multiple myeloma patients. Bone marrow CD3 lymphocytes from MM patients express CD200 protein in higher proportion than healthy donors.Introducción: el mieloma múltiple (MM) es una gammopatía monoclonal caracterizada por la proliferación anormal de células plasmáticas malignas. La proteína CD200 se ha descrito como una proteína con funciones inmunosupresoras y que es un factor de mal pronóstico en algunas enfermedades malignas, incluyendo al MM. El objetivo de este artículo es determinar la cantidad de proteína CD200 en células plasmáticas de pacientes con MM de reciente diagnóstico y en linfocitos CD3+ de donadores sanos. Métodos: se estudiaron 35 pacientes con diagnóstico reciente de MM y 25 individuos sanos. Se usaron los anticuerpos monoclonales para CD38 (PeCyC5), CD138 (APC), y CD200 (PE). El análisis estadístico fue realizado con el programa SPSS 19v. Se utilizaron las pruebas estadísticas U de Mann Whitney, curvas de supervivencia de Kaplan y Meier y la prueba de log-rank. Resultados: las frecuencias de anemia, hipercalcemia, elevación de DHL, creatinina sérica y beta-2 microglobulina fueron de 68%, 34%, 20%, 22% y 45% respectivamente. El tratamiento administrado fue MPT 20, Tal-Dex 8, y VAD 7. Cinco pacientes lograron respuesta completa, 17 respuesta parcial, y 13 respuesta menor o falla al tratamiento. Conclusiones: el CD200 es un factor de mal pronóstico para supervivencia global en pacientes con mieloma múltiple. Los linfocitos CD3+ de medula ósea de pacientes con MM expresan en mayor proporción CD200 en comparación con sujetos sanos.

The aim of this cross sectional study was to evaluate the ureolytic and arginolytic activities of saliva in children and associate them with their caries status. Study design: 65, 8 year old children, were randomly selected. The ureolytic and arginolytic activity of non stimulated saliva was studied and associated with DMFT and dmft index. Saliva of children were sampled under fasting conditions; Children refrained from any oral hygiene procedures during the 12 hours that preceded the sample collection. Caries activity was scored and divided in 3 groups: Group A: Index zero: without lesions; Group B: Moderate Index: 1 to 3 enamel caries lesions; and Group C: High Index: more than 4 dentin caries lesions. Results: DMFT scores were moderate: 0.4(±0.79) and dmft: 2.78(±2.45). Results expressed in μmol/min/mg/protein, for urease activity were statistically significant (p=0.048): Group A= 0.69 (±0.7); Group B= 0.45 (±0.43); and Group C= 0.39 (±0.55). The arginine deiminase activity was not statistically significant (p=0.16): Group A= 2.53 (±1.42), Group B= 2.31 (±1.57) and Group C= 1.97 (±2.0). Conclusion: Higher levels of ureolytic (statistically significant) and arginolytic activity (trend) in saliva were associated with lower DMFT/dmft scores in 8 year old children. There was a higher production of ammonia from the arginine deiminase system than the urease enzyme in saliva (p>0.05).

Acetylation capacity during drug metabolism differs between species, gender and age groups. Objective The purpose of this work was to determine variations in the acetylating phenotype (AP), in a longitudinal study, as a function of growth and development. Methods Twenty male Wistar rats were studied. AP was determined on days 21, 48, 114, 180, 457 and 780 with oral doses of 30 mg/kg of sulphadiazine (SDZ) by urine collection. The Schroeder and Vree methods were used to obtain SDZ concentrations, both acetylated and not acetylated. Rats were classified as slow or fast acetylators in accordance with previously validated metabolic indicators. Results Of the 20 rats phenotyped at 21 and 48 days of age, 18 were slow and 2 were fast acetylators. As age and consequent growth progressed, changes in the expression of AP were registered. At 114 days, 16 rats were slow and 4 were fast acetylators; at 180 days, 12 were slow and 8 were fast; at 457 days, 6 were slow and 14 were fast; at 780 days, the 20 rats were fast acetylators. Slow acetylation predominates at younger ages. Conclusions The effect of growth and developmental progress on AP is evident and relates to previous reports of changes in AP, determined by age in animal and human models. The relevance of changes determined by growth and development should be considered in rational drug management.

This report from the Australian Rotavirus Surveillance Program, together with collaborating laboratories Australia-wide, describes the rotavirus genotypes responsible for the hospitalisation of children with acute gastroenteritis during the period 1 January to 31 December 2012. During the survey period, 1,300 faecal samples were referred to the centre for rotavirus G and P genotype analysis, and of these 748 were confirmed as rotavirus positive. A total of 491 specimens were collected from children under 5 years of age, while 257 were from older children and adults. Genotype analysis revealed that G1P[8] was the dominant type in this reporting period, identified in 35% of strains nationally. Genotype G2P[4] was the second most common strain nationally, representing 28% of samples, followed by genotype G12P[8] (23%). This represents the first report where G12P[8] strains are a major cause of disease in this community. Fluctuations in genotype distribution were also observed based on the vaccine type in use. Genotype G2P[4] was more common in states and territories using Rotarix while G1P[8] was more common in states using RotaTeq. This survey of rotavirus strains circulating in 2012 highlights the continued fluctuations in rotavirus genotypes, with an annual change in dominant genotypes as well as emergence of a previously rare genotype, suggesting a dynamic wild-type population.

Background Many current therapies for metastatic castration-resistant prostate cancer (mCRPC) are aimed at AR signaling; however, resistance to these therapies is inevitable. To personalize CRPC therapy in an individual with clinical progression despite maximal AR signaling blockade, it is important to characterize the status of AR activity within their cancer. Biopsies of bone metastases are invasive and frequently fail to yield sufficient tissue for further study. Evaluation of circulating tumor cells (CTCs) offers an alternative, minimally invasive mechanism to characterize and study late-stage disease. The goal of this study was to evaluate the utility of CTC interrogation with respect to the AR as a potential novel therapeutic biomarker in patients with mCRPC. Methods Fifteen mL of whole blood was collected from patients with progressive, metastatic mCRPC, the mononuclear cell portion was isolated, and fluorescence-activated cell sorting (FACS) was used to isolate and evaluate CTCs. A novel protocol was optimized to use ImageStreamX to quantitatively analyze AR expression and subcellular localization within CTCs. Co-expression of AR and the proliferation marker Ki67 was also determined using ImageStreamX. Results We found inter-patient and intra-patient heterogeneity in expression and localization of AR. Increased AR expression and nuclear localization are associated with elevated co-expression of Ki-67, consistent with the continued role for AR in castration-resistant disease. Despite intra-patient heterogeneity, CTCs from patients with prior exposure to abiraterone had increased AR expression compared to CTCs from patients who were abiraterone-naïve. Conclusions As our toolbox for targeting AR function expands, our ability to evaluate AR expression and function within tumor samples from patients with late-stage disease will likely be a critical component of the personalized management of advanced prostate cancer. AR expression and nuclear localization varies within patients and between patients; however it remains associated with markers of proliferation. This supports a molecularly diverse AR-centric pathobiology imparting castration-resistance. Electronic supplementary material The online version of this article (doi:10.1186/s12967-014-0313-z) contains supplementary material, which is available to authorized users.

Signaling via programmed death ligand-1 (PD-L1) and PD-L2 is crucial for maintaining peripheral tolerance. CD90+ myofibroblasts/fibroblasts (CMFs) are major programmed cell death-1 (PD-1) ligand–expressing cells in normal human colonic mucosa. CMFs suppress activated CD4+ T cell proliferation via PD-1 ligands. It is not known whether signaling through TLRs contribute to the regulation PD-1 ligands on CMFs upon colonic mucosal tolerance. In this study, we demonstrated that stimulation of TLR4 on human CMFs upregulates PD-L1, but not PD-L2, and reinforces CMF-mediated suppression of CD4+ T cell proliferation and IFN-γ production. TLR4-mediated upregulation of PD-L1 on CMFs involved NF-κB pathways and was JAK2 and MyD88 dependent. MyD88-dependent stimulation of TLR1/2 and TLR5 also upregulated PD-L1 expression on CMFs in culture. PD-L1 expression was drastically decreased in vivo in the colonic mucosa of mice devoid of MyD88. Induction of MyD88 deficiency in CMFs in fibroblast-specific MyD88 conditional knockout mice resulted in a strong increase in a mucosal IFN-γ expression concomitantly with the abrogation of PD-L1 expression in CMFs under homeostasis and epithelial injury induced by dextran sodium sulfate. Together, these data suggest that MyD88-dependent TLR stimulation of CMFs in the normal colonic mucosa may reinforce these cells’ anti-inflammatory capacity and thus contribute to the maintenance of mucosal tolerance.

Objective and Design: ABT-299 is a prodrug that is converted by serum esterase to a potent platelet activating factor (PAF) antagonist (A-85783). In order to evaluate the pharmacological activity of this antagonist in man the effect of ABT-299 given to healthy volunteers on ex vivo PAF-induced β-thromboglobulin (β-TG) release in blood was assessed.¶Subjects: 37 healthy male volunteers, age 18 to 40 (mean age of 23.6 years) and free of medication, participated in the study.¶Treatment: Subjects were administered intravenously 0.8 mg, 2 mg, or 70 mg doses of ABT-299 (6–7 subjects per group) or placebo (9 subjects, pooled).¶Methods: Peripheral blood taken over 12 h after dosing was used for ex vivo β-TG release and, in the case of the 70 mg dose, measurement of plasma drug concentration. Data were compared by Student's t-test.¶Results: All three doses produced highly significant inhibition (p

Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. This may be more so in subsequent biopsies where serum PSA has a decreased diagnostic yield. To evaluate the diagnostic yield of the detection of CPCs as a complementary PC screening test in a population fulfilling criteria for an initial, second and third prostate biopsy for suspicion of PC.A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA4.0 ng/ml, PSA velocity0.35 ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for CPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-his-tochemical staining with anti-PSA and anti-P504S was used to detect CPCs. Both cytologist and pathologist were blinded to the results of the biopsy, CPC results and clinical details. The diagnostic yield of the presence or absence of CPC was evaluated; the prostate biopsy was classified as cancer or no-cancer.282 men participated, 83 undergoing of these undergoing a second and 38 a third biopsy, with a mean age of 66.2 ± 8.9 years and a median serum PSA of 5.10 ng/ml, 5.45 ng/ml and 6.45 ng/ml for first, second and third biopsies. Cancer was detected in 33,6%, 10.8% and 29.0% of first, second and third biopsies respectively, CPCs were detected in 36.9%, 21.7% and 36.8% of the patients. Sensibility, specificity and negative predictive value were 86% ,91% and 94% for the first biopsy, 89%, 87% and 99% for the second and 100% , 89% and 100% for third biopsy respectively. All the CPC determinations were interpretable. There were 11 false negative cases, all with small low grade tumors. Of the 29 men with a false positive CPC, 8/10 had cancer detected in the subsequent biopsy.The use of CPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, and including patients with indications for repeat biopsies. Men with a false positive CPC detection had a high risk of detecting cancer in the succeeding biopsy.

Summary The specific lacrimal fluid IgA levels and the specific serum IgG levels of broiler chicks (meat type hybrids (MT)), brown-egg layer chicks (heavy layer (HL)), and white leghorn chicks (light layer (LL)) were compared after infectious bronchitis virus (IBV) ocular vaccination at 1 day of age. All birds were maintained as a mixed population throughout the experiment of 45 days. The class specific antibody levels were determined at regular intervals by enzyme-linked immunosorbent assays. All birds responded to the vaccination stimulus as shown by a significant increase of antibody levels in both serum and lacrimal fluid. When comparing the IgG response of the chicken lines tested, LL chicks showed higher serum IBV-IgG values at the time of maximal response at days 5 and 9 postvaccination (pv). This bird group also showed a more homogeneous (lowest coefficient of variation of values) serum IgG response. On day 13 pv and until the last serum sampling day (day 41 pv) all three chicken types showed statistically identical serum IBV-IgG levels. The local IgA response detected in lacrimal fluids showed differences between the chicks at the time of maximal levels (days 5 to 14 pv), the response of LL chicks being the highest. LL chicks maintained higher specific IgA levels than MT and HL chicks almost throughout the experimental period. According to the coefficient of variation of the absorbance values (36 %), the IgA response shown by LL chicks was the most homogeneous.

Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR), has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y)-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5) expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways.

We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6Δ3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6Δ3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/β-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6Δ3 isoform is a novel splice variant, which shows diminished Wnt/β-catenin signaling activity and might have a functional role in individuals with AD.