Activation of oxytocinergic neurons enhances torpor in mice.

Mus musculus enters a torpid state in response to caloric restriction in sub-thermoneutral ambient temperatures. This torpid state is characterized by an adaptive and controlled decrease in metabolic rate, heart rate, body temperature, and activity. Previous research has identified the paraventricular nucleus (PVN) within the hypothalamus, a region containing oxytocin neurons, as a location that is active during torpor onset. We hypothesized that oxytocin neurons within the PVN are part of this neural circuit and that activation of oxytocin neurons would deepen and lengthen torpor bouts. We report that activation of oxytocin neurons alone is not sufficient to induce a torpor-like state in the fed mouse, with no significant difference in body temperature or heart rate upon activation of oxytocin neurons. However, we found that activation of oxytocin neurons prior to the onset of daily torpor both deepens and lengthens the subsequent bout, with a 1.7 ± 0.4 °C lower body temperature and a 135 ± 32 min increase in length. We therefore conclude that oxytocin neurons are involved in the neural circuitry controlling daily torpor in the mouse.

Nutritional control of puberty in the bovine female: prenatal and early postnatal regulation of the neuroendocrine system.

Puberty is a complex biological event that requires maturation of the reproductive neuroendocrine axis and subsequent initiation of high-frequency, episodic release of GnRH and LH. Nutrition is a critical factor affecting the neuroendocrine control of puberty. Although nutrient restriction during juvenile development delays puberty, elevated rates of body weight gain during this period facilitate pubertal maturation by programming hypothalamic centers that underlie the pubertal process. Recent findings suggest that maternal nutrition during gestation can also modulate the development of the fetal neuroendocrine axis, thus influencing puberty and subsequent reproductive function. Among the several metabolic signals, leptin plays a critical role in conveying metabolic information to the brain and, consequently, controlling puberty. The effects of leptin on GnRH secretion are mediated via an upstream neuronal network because GnRH neurons do not express the leptin receptor. Two neuronal populations located in the arcuate nucleus that express the orexigenic peptide neuropeptide Y (NPY), and the anorexigenic peptide alpha melanocyte-stimulating hormone (αMSH), are key components of the neurocircuitry that conveys inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. In addition, neurons in the arcuate nucleus that coexpress kisspeptin, neurokinin B, and dynorphin (termed KNDy neurons) are also involved in the metabolic control of puberty. Our studies in the bovine female demonstrate that increased planes of nutrition during juvenile development lead to organizational and functional changes in hypothalamic pathways comprising NPY, proopiomelanocortin (POMC, the precursor of αMSH), and kisspeptin neurons. Changes include alterations in the abundance of NPY, POMC, and Kiss1 mRNA and in plasticity of the neuronal projections to GnRH neurons. Our studies also indicate that epigenetic mechanisms, such as modifications in the DNA methylation pattern, are involved in this process. Finally, our most recent data demonstrate that maternal nutrition during gestation can also induce morphological and functional changes in the hypothalamic NPY system in the heifer offspring that are likely to persist long after birth. These organizational changes occurring during fetal development have the potential to not only impact puberty but also influence reproductive performance throughout adulthood in the bovine female.

The heat is on: A device that reduces cold stress-induced tachycardia in laboratory mice.

Mouse vivaria are typically maintained at an ambient temperature (Ta) of 20-26 °C which is comfortable for human researchers. However, as this Ta is well below the mouse thermoneutral zone (TNZ) of 30-32 °C, typical vivarium temperatures result in cold stress for mice. Recently, a cage has been developed that provides variable cage floor heating, allowing mice to behaviorally regulate body temperature through thermotaxis. A hand warmer provides supplemental heat, elevating cage floor surface temperature for 13 + hours up to 30 °C. This provides a heated surface for the entirety of the light phase. Here, we test the ability of these local heat sources to remove physiological signs of cold stress in mice housed at room temperature by analyzing heart rate (HR), activity, and body temperature in three experimental conditions: 23 °C, 23 °C + heated surface, or 30 °C. The location of C57Bl/6 J mice within the cage was recorded using an infrared camera. In the presence of supplemental heat at a Ta of 23 °C, mice resided atop of the area of the heated surface 85 ±â€¯3% of the 12-h light phase, as compared to 7 ±â€¯2% in the absence of supplemental heat. Further, addition of supplemental heat lowered light phase HR and activity to that seen at a Ta of 30 °C. These results indicate that provision of a local heat source is successful in reducing cold-induced tachycardia in mice housed at typical vivarium temperatures without increasing the ambient temperature of the entire laboratory and subjecting researchers to heat stress.

The frequency of the C9orf72 expansion in a Brazilian population.

G4C2 hexanucleotide repeat expansions in the C9orf72 gene seem to be the cause of numerous cases of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD). In this study, we investigated the presence of the G4C2 repeat expansion in 463 Brazilian probands, of whom 404 had ALS/motor neuron disease and 67 FTD, and in 63 healthy controls in the southeastern region of Brazil. The highest frequencies of the C9orf72 mutation were in the ALS-FTD group (50% of familial and 17.6% of sporadic cases), although it was also present in 5% of pure ALS/motor neuron disease patients (11.8% of familial and 3.6% of sporadic cases) and in 7.1% of pure familial FTD. Among G4C2 repeat mutation carriers, 68.8% of the subjects who developed dementia symptoms were females. This frequency was significantly higher than the percentage reached by men with C9orf72 expansion who had this phenotype (p = 0.047). No abnormal repeat expansion was found in control groups. Inclusion of the C9orf72 genetic test in the molecular panels for Brazilian populations with these neurodegenerative diseases should be strongly considered.

Health Information Exchange for Continuity of Maternal and Neonatal Care Supporting: A Proof-of-Concept Based on ISO Standard.

Background Around the world, people receive care at various institutions; therefore, clinical information is recorded either on paper or distributed on different information systems with reduced capabilities for sharing data. One approach to handling the complex nature of the health information systems and making it interoperable is the two-level modeling, and the ISO 13606 standard is an option to support this model. A regionally governed EHR program in Brazil proposed to use the ISO 13606 standard and archetypes. This program includes an EHR repository for consolidating the longitudinal electronic record of patients' health. Objective This article aims to present the results and lessons learned from a proof-of-concept (POC) for integrating the Maternal and Neonatal Healthcare Information System (SISMater) developed by the Federal University of Minas Gerais (UFMG) with the EHR system developed by the Department of Healthcare for the State of Minas Gerais (SES/MG). Methods The design of the architecture and software development were driven by the content to be exchanged between the SISMater system and the EHR system and the usage of XML transformation to translate an ISO 13606 EHR extract and vice versa. This POC did not include tests related to revision objects according to ISO 13606 reference model. Results The software architecture and software components required for this POC were proposed and tested. The EHR system validated the syntax and semantic and persisted the extract in the EHR repository. Complete results can be accessed at https://github.com/pocppsus/repository. Conclusion The approach for using XML transformations could make easier the process for ISO 13606 noncompliant EMR systems to exchange EHR data with the SES/MG EHR system.

Repellency and Larvicidal Activity of Essential oils from Xylopia laevigata, Xylopia frutescens, Lippia pedunculosa, and Their Individual Compounds against Aedes aegypti Linnaeus.

In order to find new alternatives for vector control and personal protection, we evaluated the larvicidal and repellent activity of essentials oils from plants found in the Northeast of Brazil against Aedes aegypti Linnaeus mosquitoes. The plants tested include Xylopia laevigata, Xylopia frutescens, and Lippia pedunculosa and their major compounds, piperitenone oxide, and (R)-limonene. The essential oil of L. pedunculosa and its major volatile compounds were shown to be toxic for Ae. aegypti larvae with a LC50 lower than 60 ppm. The essential oil of plants from the Xylopia genus, on the other hand, showed no activity against Ae. aegypti, proving to be toxic to mosquito larvae only when concentrations were higher than 1000 ppm. All plants tested provided some degree of protection against mosquitoes landing, but only the essential oil of L. pedunculosa and the volatile compound piperitenone oxide suppressed 100% of mosquitoes landing on human skin, in concentrations lower than 1%. Among the plants studied, the essential oil of L. pedunculosa and its volatiles compounds have shown the potential for the development of safe alternative for mosquito larvae control and protection against Ae. aegypti mosquito bites.

An Event-Related Potential Study on the Effects of Cannabis on Emotion Processing.

The effect of cannabis on emotional processing was investigated using event-related potential paradigms (ERPs). ERPs associated with emotional processing of cannabis users, and non-using controls, were recorded and compared during an implicit and explicit emotional expression recognition and empathy task. Comparisons in P3 component mean amplitudes were made between cannabis users and controls. Results showed a significant decrease in the P3 amplitude in cannabis users compared to controls. Specifically, cannabis users showed reduced P3 amplitudes for implicit compared to explicit processing over centro-parietal sites which reversed, and was enhanced, at fronto-central sites. Cannabis users also showed a decreased P3 to happy faces, with an increase to angry faces, compared to controls. These effects appear to increase with those participants that self-reported the highest levels of cannabis consumption. Those cannabis users with the greatest consumption rates showed the largest P3 deficits for explicit processing and negative emotions. These data suggest that there is a complex relationship between cannabis consumption and emotion processing that appears to be modulated by attention.

Spinopelvic parameters evaluation in a Brazilian population sample.

INTRODUCTION: The morphology of the spine is variable within a population, and its maintenance in appropriate values implies a decrease in the energy expended. We need to know their normal values in population. This study aims to carry out a literature review and evaluate published papers on spinopelvic parameters in a Brazilian population sample. METHODS AND POPULATION: Eleven potentially eligible papers were initially identified for inclusion in this review: three papers from PubMed and eight from Medicine. Out of these, only five papers contained methodology and relevant significance level, and therefore, they were included in the final analytical run. DISCUSSION: According to a Brazilian study, Pratali mentions no significant difference in the average values of spinopelvic balance in the Brazilian population and those found in the literature; there was also no significant difference comparing Brazilian and Korean population; however, a difference was found in comparison with European population regarding PI parameters and SS, but the latter with higher values. According to Kulcheski (Column/Columna 12:224-227, 2013), the values of pelvic tilt in the Brazilian population evaluated in his research were 19° (10°-35°) and the sacral inclination was 38° (30°-55°), presenting similar values concerning the European population. In another Brazilian paper, Oliveira (Rev Bras Ort 49:189-193, 2014) reports that the research population had PI average of 45° (41.9°-48.1°). CONCLUSION: The values obtained are relatively minor when compared to the European population. However, all of these are within the normal margin considered in the worldwide literature.

Spinal cord atrophy correlates with disease duration and severity in amyotrophic lateral sclerosis.

Our objective was to investigate spinal cord (SC) atrophy in amyotrophic lateral sclerosis (ALS) patients, and to determine whether it correlates with clinical parameters. Forty-three patients with ALS (25 males) and 43 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images covering the whole brain and the cervical SC to estimate cervical SC area and eccentricity at C2/C3 level using validated software (SpineSeg). Disease severity was quantified with the ALSFRS-R and ALS Severity scores. SC areas of patients and controls were compared with a Mann-Whitney test. We used linear regression to investigate association between SC area and clinical parameters. Results showed that mean age of patients and disease duration were 53.1 ± 12.2 years and 34.0 ± 29.8 months, respectively. The two groups were significantly different regarding SC areas (67.8 ± 6.8 mm² vs. 59.5 ± 8.4 mm², p < 0.001). Eccentricity values were similar in both groups (p = 0.394). SC areas correlated with disease duration (r = - 0.585, p < 0.001), ALSFRS-R score (r = 0.309, p = 0.044) and ALS Severity scale (r = 0.347, p = 0.022). In conclusion, patients with ALS have SC atrophy, but no flattening. In addition, SC areas correlated with disease duration and functional status. These data suggest that quantitative MRI of the SC may be a useful biomarker in the disease.

Interaction of threat expressions and eye gaze: an event-related potential study.

The current study examined the interaction of fearful, angry, happy, and neutral expressions with left, straight, and right eye gaze directions. Human participants viewed faces consisting of various expression and eye gaze combinations while event-related potential (ERP) data were collected. The results showed that angry expressions modulated the mean amplitude of the P1, whereas fearful and happy expressions modulated the mean amplitude of the N170. No influence of eye gaze on mean amplitudes for the P1 and N170 emerged. Fearful, angry, and happy expressions began to interact with eye gaze to influence mean amplitudes in the time window of 200-400 ms. The results suggest early processing of expression influence ERPs independent of eye gaze, whereas expression and gaze interact to influence later ERPs.

Hypokinetic stress and neuronal porosome complex in the rat brain: the electron microscopic study.

Porosomes are the universal secretory machinery in cells, where membrane-bound secretory vesicles transiently dock and fuse to release intravesicular contents to the outside of the cell during cell secretion. Studies using atomic force microscopy, electron microscopy, electron density and 3D contour mapping, provided rich nanoscale information on the structure and assembly of proteins within the neuronal porosome complex in normal brain. However it remains uncertain whether pathological conditions that alter process of neurotransmission, provoke alterations in the porosome structure also. To determine if porosomes are altered in disease states, the current study was undertaken for first time using high resolution electron microscope. One of pathologies that produce subtle alteration at the presynaptic terminals has been demonstrated to be hypokinetic stress. The central nucleus of amygdale is the brain region, where such alterations are mostly expressed. We have examined the width and depth of the neuronal porosome complex and their alterations provoked by chronic hypokinetic stress in above mentioned limbic region. Specifically, we have demonstrated that despite alterations in the presynaptic terminals and synaptic transmission provoked by this pathological condition in this region, the final step/structure in neurosecretion--the porosome--remains unaffected: the morphometric analysis of the depth and diameter of this cup-shaped structure at the presynaptic membrane point out to the heterogeneity of porosome dimensions, but with unchanged fluctuation in norm and pathology.

Polyomavirus-infected decoy cells in cytocentrifuged urine cytology specimens from renal transplant recipients.

OBJECTIVE: To evaluate the prevalence of BK virus (BKV) infection in renal transplant recipients based on the detection of urinary decoy cells. METHODS: Fifty transplantation patients (56% males) aged 39.9 ± 11 years were screened for urinary decoy cells. The majority (86%) had received grafts from living donors. The inclusion criteria were graft dysfunction, hematuria, and/or leukocyturia. Creatinine and urea serum levels were monitored for 6 months. RESULTS: Decoy cells were found in the urine of 12 (24%) patients 1-2 years after transplantation. The immunosuppression regimens most frequently adopted by BKV-positive patients were cyclosporine + azathiprine (50%) and FK + mycophenolate mofetyl + prednisone (25%). A renal biopsy revealed normal structures in 7 patients (58.4%), BKV nephropathy with lymphomononuclear infiltrate and fibrosis in 4 patients (33.3%), and acute cellular rejection with lymphomononuclear infiltrate without fibrosis in 1 patient (8.3%). In the latter patient, BKV-associated nephropathy was confirmed by immunohistochemistry. During the first month, creatinine and urea serum levels were higher among patients with urinary decoy cells. Creatinine levels decreased between the first and the sixth months. CONCLUSION: The finding of BKV-associated nephropathy in 33.3% of the patients with urinary decoy cells stresses the importance of screening for BKV with urinary cytology.

Increased immunogenicity to LipL32 of Leptospira interrogans when expressed as a fusion protein with the cholera toxin B subunit.

Leptospirosis is one of the most widespread zoonosis in the world. The development of a recombinant leptospira vaccine remains a challenge. In this study, we cloned the Leptospira interrogans open reading frame (ORF) coding the external membrane protein LipL32, an immunodominant antigen found in all pathogenic leptospira, downstream of the highly immunogenic cholera toxin B subunit (CTB) ORF. Expression and assembly of the CTB-LipL32 fusion protein into oligomeric structures of pentameric size were observed in soluble fractions by Western blot analysis. The CTB-LipL32 protein demonstrated strong affinity for monosialotetrahexosylgaglioside (GM1-ganglioside) in an enzyme-linked immunosorbent assay (ELISA), suggesting that the antigenic sites for binding and proper folding of the pentameric CTB structure were conserved. Furthermore, antisera against LipL32 also recognized the CTB-LipL32 fusion protein, suggesting that LipL32 also conserved its antigenic sites, a fact confirmed by an ELISA assay showing soluble CTB-LipL32 recognition by sera from convalescent patients. In addition, soluble CTB-LipL32 generated higher specific titers in mice immunized without external adjuvant than co-administration of CTB with LipL32. The data presented here provide support for CTB-LipL32 as a promising antigen for use in the control and study of leptospirosis.

Trypanosomiasis by Trypanosoma vivax in cattle in the Brazilian semiarid: Description of an outbreak and lesions in the nervous system.

An outbreak of trypanosomiasis by Trypanosoma vivax is reported in the semiarid of Paraíba, Northeastern Brazil from May to August 2002. Sixty-four cows out of 130 were affected; 11 died and the other recovered after treatment with diminazene aceturate. Affected animals had fever, anemia, weight loss, hypoglycemia, increased serum levels of aspartate aminotransferase and, in nine cows, nervous signs. All cows with nervous signs died; six of them recovered after treatment, but the disease relapsed. Six cows aborted and one delivered a calf that died immediately after parturition. Thirty-two out of 100 calves were affected and five died. Nervous signs were not observed in the calves. Gross lesions were thickening of the meninges, enlarged lymph nodes and prominent white pulp of the spleen. The main histological lesion was meningoencephalitis and malacia in the brain of cows with nervous signs. No antibodies against trypanosomes were found in 33 blood samples collected before the outbreak in the affected farm and in 29 samples collected at the same time in two other neighbor farms. Until January 2003, all 89 animals tested had antibodies against T. vivax, suggesting the occurrence of sub clinical infections in cattle without clinical signs. Only two out of 85 serum samples collected on April 2004 were positive for T. vivax antibodies. Data obtained suggested that the semiarid region is non-endemic for trypanosomiasis and that disease occurred due to introduction of the parasite in a susceptible population after an apparent rise in the Tabanus spp. population.

Spinal cord compression by ectopic calcinosis in scleroderma.

Systemic sclerosis (SS) is a chronic, multisystemic disease, characterized by inflammation associated with fibrosis. Calcinosis is one of the manifestations of this disorder, observed in 10 to 20% of cases. It is usually located on the extensor surface of the phalanges, peri-articular tissue and near the bone prominences. There are only a few cases reported of SS with vertebral column involvement and spinal cord compression by calcinosis causing serious neurological complications. We describe a fatal case of SS who showed tetraplegia secondary to ectopic calcinosis in the cervical medulla and present a review of the literature on the subject.

[Intravenous terbutaline in children] / Terbutalina endovenosa em crianças.

OBJECTIVE: The authors describe their experience with theuse of intravenous Beta2 adrenergic (IV terbutaline) in patientsadmitted to a PICU with severe lower airway obstruction. PATIENTS AND METHODS: A retrospective study of all admissions to a PICU was conducted in Santo Antonio Hospital in Porto Alegre (Brazil) during the winter of 1995. The files ofall the patients that were treated with intravenous Beta2 adrenergicas a bronchodilator were selected. The analysis included lengthof use, initial doses, maximal doses, associated phenomena,arterial blood gases and plasma level of potassium. RESULTS: During the three months of study 367 patients wereadmitted to the PICU and 38 (10.3%) used IV terbutaline. Thisgroup of patients had a mean age of 13.8-/+12.2 months old andused IV terbutaline for a mean length of 7.24-/+3.6 days. Theinitial rate of infusion was 0.55-/+0.25 mcg/kg/min with a meantherapeutic dose of 2.45-/+1.18 mcg/kg/min. Twelve patients(31.5%) had increase in their heart rate (over 180 bpm) thatprevented increases in the infusion rate. However this was atemporary effect. The patients under 12 months of age startedwith low infusion rates (0.45-/+0.22 mcg/kg/min), when comparedto children over 1 year old (0.57-/+0.3 mcg/kg/min), p <0.01. No patient developed pathologic heart rate attributed to the drug. The serum levels of potassium decreased significantly (p <0.01) only in the group of patients under 1 year (4.1-/+0.7 to 3.47-/+0.52 mEq/L), but this difference had no clinical relevance. COMMENTS: In view of these results the authors showed that the infusion of IV terbutaline in children is safe and presents alow risk if the criteria of administration and monitoring are followed. In this manner, IV terbutaline is an excellent therapeuticoption for children with severe lower airway obstruction andno response to the conventional treatment.

Tuberculose ganglionar em pacientes co-infectados pelo HIV-1: estudo clínico e laboratorial / Ganglionic tuberculosis in patients co-infected by HIV-1: clinical and laboratorial study

Estudos clínicos e laboratoriais apontam diferenças marcantes entre pacientes soropositivos para HIV-1 e imunocompetentes. A tuberculose ganglionar é uma forma freqüente de apresentaçäo extrapulmonar nestes pacientes. A apresentaçäo histopatológica é muito diferente dos pacientes imunocompetentes, com mais de 70 por cento dos casos de várias séries näo apresentando granulomas ou, quando presentes, malformados, com extensa necrose caseosa, raras células gigantes e presença de muitos bacilos álcool-ácido resistentes, denotando uma resposta imune incompleta. Estudamos os diversos aspectos clínicos e laboratoriais, incluídos exames microbiológicos e histopatológicos de 27 pacientes encaminhados para tratamento e diagnóstico no Hospital Evandro Chagas/FIOCRUZ. De acordo com o diagnóstico histopatológico, os casos foram subdivididos em três grupos: Grupo I (n = 7): tuberculose ganglionar sem infecçäo pelo HIV - 1; Grupo II (n = 9): tuberculose ganglionar em pacientes co-infectados por HIV - 1; Grupo III (n = 11): linfadenite reativa associada à AIDS. No grupo de pacientes co-infectados em relaçäo aos imunocompetentes, verificou-se grannulomas malformados, verificou-se granulomas malformados, extensa necrose e grande riqueza bacilar, além de queda acentuada de hemácias e linfócitos e grande freqüência de infecçöes oportunísticas denotando grave defeito na resposta imune, explicando a apresentaçäo de formas bem mais severas e nao usuais de tuberculose nos pacientes com AIDS.

[Accidental extubation in a pediatric intensive care unit]. / Extubação acidental em uma Unidade de Terapia Intensiva.

It is an on-going practice in the pediatric ICUs to obtain and to maintain a working artificial airway. Nevertheless this procedure bears not infrequent risks of accidental extubation (AE) which ranges in several services from 0.9 to 3.3 for each 100 days of intubation. The risk factors that are involved in AE are related to: sedation level, age-group, intubation path, and others. The purpose of the authors in this article was to observe the incidence of AE in their service and to compare the relative risk in the rate of AE among orotracheal and nasotracheal intubation population. A prospective study was taken during six months, in which every patients with artificial airway admitted at the PICU of the Santo Antonio Hospital in Porto Alegre (Brazil) was included except those with tracheostomy. The total number of cases were 673 patients-day with artificial airway, with an average of 3.7 patients with tracheal tube per day. In the period there were 18 AE, with a rate of 2.7 AE/ 100 days. The incidence rate of AE in the orotracheal group was 3.1% and 1.6% in the nasotracheal group with no statistically significant difference (p=0.6). The authors concluded that the pathway of intubation in their study does not carry any additional risk in the incidence of accidental extubation.