Multidimensional Characterization and Differentiation of Neurons in the Anteroventral Cochlear Nucleus

Multiple parallel auditory pathways ascend from the cochlear nucleus. It is generally accepted that the origin of these pathways are distinct groups of neurons differing in their anatomical and physiological properties. In extracellular in vivo recordings these neurons are typically classified on the basis of their peri-stimulus time histogram. In the present study we reconsider the question of classification of neurons in the anteroventral cochlear nucleus (AVCN) by taking a wider range of response properties into account. The study aims at a better understanding of the AVCN's functional organization and its significance as the source of different ascending auditory pathways. The analyses were based on 223 neurons recorded in the AVCN of the Mongolian gerbil. The range of analysed parameters encompassed spontaneous activity, frequency coding, sound level coding, as well as temporal coding. In order to categorize the unit sample without any presumptions as to the relevance of certain response parameters, hierarchical cluster analysis and additional principal component analysis were employed which both allow a classification on the basis of a multitude of parameters simultaneously. Even with the presently considered wider range of parameters, high number of neurons and more advanced analytical methods, no clear boundaries emerged which would separate the neurons based on their physiology. At the current resolution of the analysis, we therefore conclude that the AVCN units more likely constitute a multi-dimensional continuum with different physiological characteristics manifested at different poles. However, more complex stimuli could be useful to uncover physiological differences in future studies

Reliability of Synaptic Transmission at the Synapses of Held In Vivo under Acoustic Stimulation

BACKGROUND:The giant synapses of Held play an important role in high-fidelity auditory processing and provide a model system for synaptic transmission at central synapses. Whether transmission of action potentials can fail at these synapses has been investigated in recent studies. At the endbulbs of Held in the anteroventral cochlear nucleus (AVCN) a consistent picture emerged, whereas at the calyx of Held in the medial nucleus of the trapezoid body (MNTB) results on the reliability of transmission remain inconsistent. In vivo this discrepancy could be due to the difficulty in identifying failures of transmission. METHODS/FINDINGS:We introduce a novel method for detecting unreliable transmission in vivo. Based on the temporal relationship between a cells' waveform and other potentials in the recordings, a statistical test is developed that provides a balanced decision between the presence and the absence of failures. Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy. The method was applied to extracellular recordings from the synapses of Held in vivo. At the calyces of Held failures of transmission were found only rarely. By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions. In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition. CONCLUSIONS/SIGNIFICANCE:Under the investigated activity conditions/anesthesia, transmission seems to remain largely unimpeded in the MNTB, whereas in the AVCN the occurrence of failures is related to inhibition and could be the basis/result of computational mechanisms for temporal processing. More generally, our approach provides a formal tool for studying the reliability of transmission with high statistical accuracy under typical in vivo recording conditions

Endemic cryptosporidiosis and exposure to municipal tap water in persons with acquired immunodeficiency syndrome (AIDS): A case-control study

BACKGROUND: In persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco. METHODS: Among patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4(+ )T lymphocyte count, date of CD4(+ )count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated. RESULTS: The study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95% CI 1.37–33.5, and outside the home: OR 3.16; 95% CI 1.23–8.13). The PAF was 85%; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85%. CONCLUSIONS: Although the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water

Health Disparities Between Appalachian and Non-Appalachian Counties in Virginia USA

The examination of health disparities among people within Appalachian counties compared to people living in other counties is needed to find ways to strategically target improvements in community health in the United States of America (USA). Methods: A telephone survey of a random sample of adults living in households within communities of all counties of the state of Virginia (VA) in the USA was conducted. Findings: Health status was poorer among those in communities within Appalachian counties in VA and health insurance did not make a difference. Health perception was significantly worse in residents within communities in Appalachian counties compared to non-Appalachian community residents (30.5 vs. 17.4% rated their health status as poor/fair), and was worse even among those with no chronic diseases. Within communities in Appalachian counties, black residents report significantly better health perception than do white residents. Conclusion: Residents living in communities in Appalachian counties in VA are not receiving adequate health care, even among those with health insurance. More research with a larger ethnic minority sample is needed to investigate the racial/ethnic disparities in self-reported health and health care utilization within communities

Replicating genotype-phenotype associations

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62757/1/447655a.pd

Astrocytes convert network excitation to tonic inhibition of neurons

<p>Abstract</p> <p>Background</p> <p>Glutamate and γ-aminobutyric acid (GABA) transporters play important roles in balancing excitatory and inhibitory signals in the brain. Increasing evidence suggest that they may act concertedly to regulate extracellular levels of the neurotransmitters.</p> <p>Results</p> <p>Here we present evidence that glutamate uptake-induced release of GABA from astrocytes has a direct impact on the excitability of pyramidal neurons in the hippocampus. We demonstrate that GABA, synthesized from the polyamine putrescine, is released from astrocytes by the reverse action of glial GABA transporter (GAT) subtypes GAT-2 or GAT-3. GABA release can be prevented by blocking glutamate uptake with the non-transportable inhibitor DHK, confirming that it is the glutamate transporter activity that triggers the reversal of GABA transporters, conceivably by elevating the intracellular Na⁺concentration in astrocytes. The released GABA significantly contributes to the tonic inhibition of neurons in a network activity-dependent manner. Blockade of the Glu/GABA exchange mechanism increases the duration of seizure-like events in the low-[Mg²⁺] <it>in vitro </it>model of epilepsy. Under <it>in vivo </it>conditions the increased GABA release modulates the power of gamma range oscillation in the CA1 region, suggesting that the Glu/GABA exchange mechanism is also functioning in the intact hippocampus under physiological conditions.</p> <p>Conclusions</p> <p>The results suggest the existence of a novel molecular mechanism by which astrocytes transform glutamat<it>ergic </it>excitation into GABA<it>ergic </it>inhibition providing an adjustable, <it>in situ </it>negative feedback on the excitability of neurons.</p

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population

Ambiente familiar e transtorno de déficit de atenção e hiperatividade

OBJECTIVE: To analyze factors associated with attention-deficit and hyperactivity disorder in children. METHODS: This is a longitudinal study about behavior problems in schoolchildren that was carried out in the city of São Gonçalo (Southeastern Brazil) in 2005. A total of 479 students from public schools was analyzed, selected through three-stage cluster sampling. The Child Behavior Checklist was used to measure the outcome. A questionnaire was administered to parents/guardians concerning the exposure factors, which were: child's and family's profile, family relationship variables, physical and psychological violence. The log-binomial regression model with a hierarchical approach was employed in the analysis. RESULTS: Higher intelligence quotient was inversely associated with the frequency of the disorder (PR=0.980 [95%CI 0.963;0.998]). The prevalence of the disorder in the children was higher when there was family dysfunction than among families with a better way of relating (PR=2.538 [95%CI 1.572; 4.099]). Children who suffered verbal abuse from the mother had a prevalence 3.7 times higher than the ones not exposed to this situation in the last year (PR=4.7 [95%CI 1.254;17.636]). CONCLUSIONS: Negative family relationships are associated with symptoms of Attention-Deficit and Hyperactivity Disorder. Its association with the intelligence quotient reiterates the importance of the genetic and environmental basis at the origin of the disorder.OBJETIVO: Analisar fatores associados a transtorno de déficit de atenção e hiperatividade em crianças. MÉTODOS: Estudo longitudinal sobre problemas de comportamento em crianças escolares de São Gonçalo, RJ, em 2005. Foram analisados 479 escolares da rede pública selecionados por amostragem por conglomerados em três estágios. Foi utilizada a escala Child Behavior Checklist para medição do desfecho. Foi aplicado um questionário para pais/responsáveis acerca dos fatores de exposição analisados: perfil da criança e da família, variáveis de relacionamento familiar, violências físicas e psicológicas. O modelo regressão log-binomial com enfoque hierarquizado foi empregado para a análise. RESULTADOS: Quociente de inteligência mais alto associou-se inversamente à frequência do transtorno (RP = 0,980 [IC95% 0,963;0,998]). A prevalência de transtorno nas crianças foi maior quando havia disfunção familiar do que entre famílias com melhor forma de se relacionar (RP = 2,538 [IC95% 1,572;4,099]). Crianças que sofriam agressão verbal pela mãe apresentaram prevalência 3,7 vezes maior do que aquelas não expostas a essa situação no último ano (RP = 4,7 [IC95% 1,254;17,636]). CONCLUSÕES: Relações familiares negativas estão associadas aos sintomas de transtorno de déficit de atenção e hiperatividade. Sua associação com quociente de inteligência reitera a importância da base genética e ambiental na origem do transtorno.OBJETIVO: Analizar factores asociados a trastorno por déficit de atención e hiperactividad en niños. MÉTODOS: Estudio longitudinal sobre problemas de comportamiento en niños escolares de Sao Gonçalo, Sureste de Brasil, en 2005. Se analizaron 479 escolares de la red pública seleccionados por muestreo por conglomerados en tres fases. Se utilizó la escala Child Behavior Checklist para medir el resultado. Se aplicó un cuestionario para padres/responsables sobre los factores de exposición analizados: perfil del niño y de la familia, variables de relación familiar, violencias físicas y psicológicas. El modelo de regresión log-binomial con enfoque jerarquizado se empleó en el análisis. RESULTADOS: Cociente de inteligencia elevado se asoció inversamente con la frecuencia del trastorno (RP= 0,980 [IC95% 0,963;0,998]). La prevalencia de trastorno fue mayor en los niños con disfunción familiar que entre las familias con buena relación (RP=2,538 [IC95% 1,572;4,009]). Niños que sufrían agresión verbal por parte de la madre presentaron prevalencia 3,7 veces mayor que aquellos no expuestos a esa situación en el último año (RP=4,7 [IC95% 1,254;17,636]). CONCLUSIONES: Relaciones familiares negativas están asociadas a los síntomas de trastornos por déficit de atención e hiperactividad. Su asociación con el cociente de inteligencia reitera la importancia de la base genética y ambiental en el origen del trastorno