Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3

The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, `hereditary motor and autonomic neuronopathy', and attribute the term, `survival of motor and autonomic neurons 1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.

Protein defects in neuromuscular diseases

Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3), from the extracellular matrix (alpha2-laminin, collagen VI), from the sarcomere (telethonin, myotilin, titin, nebulin), from the muscle cytosol (calpain 3, TRIM32), from the nucleus (emerin, lamin A/C, survival motor neuron protein), and from the glycosylation pathway (fukutin, fukutin-related protein) have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

Restless leg syndrome, sleep quality and fatigue in multiple sclerosis patients

We have tested the hypothesis that restless leg syndrome (RLS) is related to quality of sleep, fatigue and clinical disability in multiple sclerosis (MS). The diagnosis of RLS used the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Fatigue was assessed by the Fatigue Severity Scale (FSS >27), quality of sleep by the Pittsburgh Sleep Quality Index (PSQI >6), excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS >10) and clinical disability by the Expanded Disability Status Scale (EDSS). Forty-four patients (32 women) aged 14 to 64 years (43 ± 14) with disease from 0.4 to 23 years (6.7 ± 5.9) were evaluated. Thirty-five were classified as relapsing-remitting, 5 as primary progressive and 4 as secondary progressive. EDSS varied from 0 to 8.0 (3.6 ± 2.0). RLS was detected in 12 cases (27%). Patients with RLS presented greater disability (P = 0.01), poorer sleep (P = 0.02) and greater levels of fatigue (P = 0.03). Impaired sleep was present in 23 (52%) and excessive daytime sleepiness in 3 cases (6.8%). Fatigue was present in 32 subjects (73%) and was associated with clinical disability (P = 0.000) and sleep quality (P = 0.002). Age, gender, disease duration, MS pattern, excessive daytime sleepiness and the presence of upper motor neuron signs were not associated with the presence of RLS. Fatigue was best explained by clinical disability and poor sleep quality. Awareness of RLS among health care professionals may contribute to improvement in MS management.

Exogenous induction of ovarian activity and ovulation and transfer of fresh embryos of domestic cat (Felis catus)

The objective of the present study was the exogenous stimulation of ovarian activity and definition of embryo collection, and transfer protocols, in the domestic cat for potential application in non-domestic endangered species. Sixteen adult queens and two adult male reproducers kept in the experimental cat house at the Morphology sector at the Veterinary Department (DVT), UFV, were used in this study. All the queens received a single application of 150 IU Equine Chorionic Gonadotropin (eCG) in the post estrus to induce ovarian activity and 80 to 84 hours later, received a single application of 100 UI Human Chorionic Gonadotropin (hCG) to induce ovulation. After hCG application, only the donor queens were naturally mated. The receptor queens received extra stimulus for induction of ovulation through manipulation of an intravaginal swab. Five to six days after hCG application, the donor queens were subjected to a laparotomy for embryo collection that was performed by trans-horn uterine washing. On average, six embryos were surgically inovulated. They were classified as type I and III compact morula and blastocysts in four receptor queens. Three animals presented pregnancy confirmed by ultrasound at day 36 and two of these animals gave birth to litters of two and four offsprings, respectively, at 66 and 63 days after induction of ovulation. Except for one still birth, all the offspring developed normally.

Alguns aspectos epidemiológicos da mortalidade por acidentes de trânsito de veículo a motor na Cidade de São Paulo, Brasil

Foram estudadas algumas características dos óbitos por acidentes de trânsito de veículos a motor, no município de São Paulo, ocorridos entre 1.° de janeiro a 31 de dezembro de 1970. Todas as características do falecido e do acidente foram coletadas a partir dos dados registrados nos laudos de necrópsias existentes no Instituto Médico Legal. O estudo evidenciou que a mortalidade por acidentes de veículo a motor é alta, maior no sexo masculino, aumenta com a idade, sendo que o maior coeficiente foi para maiores de 60 anos. A zona da cidade com maior número de acidentes é a zona Sul, existindo áreas (distritos policiais) e vias públicas preferenciais quanto a ocorrência, em todas as 4 zonas do município; a maior ocorrência de acidentes foi aos sábados e domingos; os pedestres compreendem a grande maioria dos falecidos; proporção apreciável dos falecidos recebeu atendimento hospitalar após o acidente. Foram relacionados também o número total de acidentes, vítimas e mortes mostrando que para cada 100 acidentes ocorreram 62,50 vítimas e 5,13 mortes, e para cada 100 vítimas, 18, 22 mortes.

Aspectos epidemiológicos dos acidentes fatais a veículo a motor na cidade do Salvador (Bahia), Brasil

Foi realizado um estudo com o objetivo de descrever certos aspectos epidemiológicos dos acidentes de trânsito de veículo a motor, na cidade do Salvador, Bahia, Brasil, o qual envolveu coleta de informações no Departamento de Trânsito (DETRAN) e no Instituto de Medicina Legal. Ficou demonstrado que os acidentes de trânsito de veículo a motor são mais freqüentes ao fim da tarde e concentram-se, sobretudo, no fim de semana, isto é, sábado e domingo. Motoristas do sexo masculino foram muito mais freqüentemente envolvidos em acidentes de trânsito do que os do sexo feminino. Foi concluído que os acidentes fatais envolvendo pedestres constituem-se importante problema urbano necessitando cuidadosa atenção por parte de educadores e dos serviços públicos responsáveis pelo setor do trânsito. Foi sugerida a necessidade de melhorar e tornar mais uniforme o sistema de notificação e classificação dos acidentes de veículo a motor pelo DETRAN da cidade do Salvador.

Traumatismo crânio-encefálico: diferenças das vítimas pedestres e ocupantes de veículos a motor

OBJETIVO: Caracterizar as diferenças das vítimas com diagnóstico de traumatismo crânio-encefálico envolvidas em diferentes condições, em acidentes de trânsito de veículo a motor e evidenciar indicadores para prevenção e seu atendimento. MÉTODO: Foram analisados os prontuários de todas as vítimas com diagnóstico de trauma crânio-encefálico, assistidas em hospital de referência para atendimento do trauma, entre março e junho de 1993. A população foi de 156 vítimas, sendo 80 pedestres, 50 ocupantes de veículos a motor, exceto de moto e, 26 motociclistas ou passageiros de motos. RESULTADOS E CONCLUSÕES: Os resultados mostraram que a mortalidade entre pedestres foi a mais alta entre os três grupos (25,0%). Os óbitos ocorrem em 19,2% dos ocupantes de motocicleta e 8,0% dos ocupantes de demais veículos a motor. Foram observadas diferenças estatísticas entre os grupos quando a variável gravidade do trauma crânio-encefálico foi analisado. Análise de certas variáveis mostraram importantes diferenças na distribuição dos três grupos.

Oportunidades do ambiente domiciliar para o desenvolvimento motor

OBJETIVO: Avaliar as oportunidades presentes no ambiente domiciliar para o desenvolvimento motor de lactentes. MÉTODOS: Estudo epidemiológico de base populacional, transversal, realizado com 239 lactentes com idade entre três e 18 meses, residentes no município de Juiz de Fora, MG, em 2010. Os participantes foram selecionados por amostragem aleatória estratificada, conglomerada, em múltiplos estágios. Para avaliar a qualidade e quantidade de estímulo motor no ambiente domiciliar foi utilizado o instrumento Affordance in the Home Environment for Motor Development - Infant Scale. Procedeu-se a análise bivariada com aplicação do teste qui-quadrado, seguida de regressão logística multinomial para verificar a associação entre as oportunidades presentes no domicílio e fatores biológicos, comportamentais, demográficos e socioeconômicos. RESULTADOS: As oportunidades de estimulação ambiental foram relativamente baixas. Na análise bivariada, para a faixa etária de três a nove meses, foi encontrada associação com os fatores: ordem de nascimento (p = 0,06), classificação socioeconômica (p = 0,08), renda mensal (p = 0,06) e renda per capita (p = 0,03). No modelo de regressão, prevaleceu a classificação socioeconômica (RC = 7,46; p = 0,03). Para a faixa etária de dez a 18 meses, os fatores associados, na análise bivariada, foram: estado civil materno (p < 0,01), convívio da criança com o pai (p = 0,08), chefe da família (p = 0,04), número de pessoas no domicílio (p = 0,05), escolaridade materna (p < 0,01) e paterna (p < 0,01), classificação socioeconômica (p < 0,01) e renda per capita (p = 0,03). No modelo de regressão, o estado civil materno (RC = 4,83; p = 0,02), escolaridade materna (RC = 0,29; p = 0,03) e paterna (RC = 0,33; p = 0,04) permaneceram associados às oportunidades de estimulação ambiental. CONCLUSÕES: A união estável dos pais, maior escolaridade materna e paterna e maior nível econômico foram os fatores associados às melhores oportunidades de estimulação motora no lar.

Content validity and reliability of test of gross motor development in Chilean children

ABSTRACT OBJECTIVE To validate a Spanish version of the Test of Gross Motor Development (TGMD-2) for the Chilean population. METHODS Descriptive, transversal, non-experimental validity and reliability study. Four translators, three experts and 92 Chilean children, from five to 10 years, students from a primary school in Santiago, Chile, have participated. The Committee of Experts has carried out translation, back-translation and revision processes to determine the translinguistic equivalence and content validity of the test, using the content validity index in 2013. In addition, a pilot implementation was achieved to determine test reliability in Spanish, by using the intraclass correlation coefficient and Bland-Altman method. We evaluated whether the results presented significant differences by replacing the bat with a racket, using T-test. RESULTS We obtained a content validity index higher than 0.80 for language clarity and relevance of the TGMD-2 for children. There were significant differences in the object control subtest when comparing the results with bat and racket. The intraclass correlation coefficient for reliability inter-rater, intra-rater and test-retest reliability was greater than 0.80 in all cases. CONCLUSIONS The TGMD-2 has appropriate content validity to be applied in the Chilean population. The reliability of this test is within the appropriate parameters and its use could be recommended in this population after the establishment of normative data, setting a further precedent for the validation in other Latin American countries.

Induction of iron regulated proteins during normal growth of Neisseria meningitidis in a chemically defined medium

The expression of iron regulated proteins (IRPs) in vitro has been obtained in the past by adding iron chelators to the culture after bacterial growth, in the presence of an organic iron source. We have investigated aspects concerning full expression of the meningococcal IRPs during normal growth, in defined conditions using Catlin medium, Mueller Hinton and Tryptic Soy Broth (TSB). The expression of IRPs varied between different strains with respect to Ethylenediamine Di-ortho-Hidroxy-phenyl-acetic acid (EDDA) concentrations, and according to culture medium, and also between different lots of TSB. For each strain, a specific set of IRPs were expressed and higher EDDA concentrations, or addition of glucose, or use of different culture media did not resulted in a differential expression of IRPs. We were not able to grow N. meningitidis under normal growth conditions using Desferal. We looked for a good yield of outer membrane vesicles (OMVs) expressing IRPs in iron-deficient Catlin medium containing EDDA and Hemin. Culture for 32 h at 30ºC after growing for 16 h at 37ºC supported good bacterial growth. Bacterial lysis was noted after additional 24 h at 30ºC. Approximately 4 times more OMVs was recoverable from a culture supernatant after 24 h at 30ºC than from the cells after 16 h at 37ºC. The IRP were as well expressed in OMVs from culture supernatant obtained after 24 h at 30ºC as from the cells after 16 h at 37ºC.

Induction of phagocytic activity and nitric-oxide production in natural populations of Trypanosoma Cruzi I and II from the state of Paraná, Brazil

Twelve strains of Trypanosoma cruzi isolated from wild reservoirs, triatomines, and chronic chagasic patients in the state of Paraná, southern Brazil, and classified as T. cruzi I and II, were used to test the correlation between genetic and biological diversity. The Phagocytic Index (PI) and nitric-oxide (NO) production in vitro were used as biological parameters. The PI of the T. cruzi I and II strains did not differ significantly, nor did the PI of the T. cruzi strains isolated from humans, triatomines, or wild reservoirs. There was a statistical difference in the inhibition of NO production between T. cruzi I and II and between parasites isolated from humans and the strains isolated from triatomines and wild reservoirs, but there was no correlation between genetics and biology when the strains were analyzed independently of the lineages or hosts from which the strains were isolated. There were significant correlations for Randomly Amplified Polymorphic Deoxyribonucleic acid (RAPD) and biological parameters for T. cruzi I and II, and for humans or wild reservoirs when the lineages or hosts were considered individually.

SURVIVAL, INDUCTION AND RESUSCITATION OF Vibrio cholerae FROM THE VIABLE BUT NON-CULTURABLE STATE IN THE SOUTHERN CARIBBEAN SEA

The causative agent of cholera, Vibrio cholerae, can enter into a viable but non-culturable (VBNC) state in response to unfavorable conditions. The aim of this study was to evaluate the in situ survival of V. cholerae in an aquatic environment of the Southern Caribbean Sea, and its induction and resuscitation from the VBNC state. V. cholerae non-O1, non-O139 was inoculated into diffusion chambers placed at the Cuare Wildlife Refuge, Venezuela, and monitored for plate, total and viable cells counts. At 119 days of exposure to the environment, the colony count was < 10 CFU/mL and a portion of the bacterial population entered the VBNC state. Additionally, the viability decreased two orders of magnitude and morphological changes occurred from rod to coccoid cells. Among the aquatic environmental variables, the salinity had negative correlation with the colony counts in the dry season. Resuscitation studies showed significant recovery of cell cultivability with spent media addition (p < 0.05). These results suggest that V. cholerae can persist in the VBNC state in this Caribbean environment and revert to a cultivable form under favorable conditions. The VBNC state might represent a critical step in cholera transmission in susceptible areas.

Induction of male sterility through manipulation of genetic mechanisms present in vector species of Triatominae. II. Partial restoration of male fertility

The development of integrated measures which involve sterile mate release to supplement the conventional insecticidal techniques used in controlagainst insects of medical importance, raised the question, whether the vectors of Chagas'disease possess the natural mechanisms by manipulation of which they may be controlled. Results of earlier expenments, that had been published previously, were restricted to fragmentary information that raised various questions, the answer to which became available in the study herein described. Interspecific hybrids were produced from reciprocal crosses between T. pseudomaculata and T. sórdida and from unilateral crosses between female T. pseudomaculata and male. T. infestans. These females mated with males, laid less than the normal complement of eggs, but offspring was relatively abundant. When T. pseudomaculata females were paired with T. brasiliensis males, hybridization was more difficult because few of the females mated and those that did had a strongly reduced fertility. Adults emerged from ali crosses but exhibited sex disproportion, females predominating in all populations but one. The two Rhodnius species tested were also found to cross, but only when female R. prolixus were paired with male R. neglectus. These females laid a relatively high complement o f eggs, had a strongly reduced fertility, but 50% of the fertile eggs developed into vigorous adults, males predominating females. Neither type of hybrid male elicited fertilized eggs from either parental type of female, through their vesicula seminal is were found to be packed with spermatozoa, some normal looking and moving, others underdeveloped and motionless. Although, no artificial insemination was performed, the sperm in itself did not appear to be the prime inducer of sterility. Females paired with these hybrids did mate, sperm was transfered, as evidenced by the discharged spermatophores smeared with sperm, but did notcontain spermatozoa in their spermatecae. The failure of the sperm to migrate to the spermatecae indicate prezygotic pos-copulation incompatibility, thus the hybrid male can't be used to suppress populations. The female hybrids mated with parent males of either species had reduced fertility and ther sons were sterile as were those of their fertile daughters. However, continous backcrossing of the hybrid females and their female progeny to parental males partially restored fertility of the males and increased fertility of females, as scored by egg hatchability. Fertility of hybrid females, measured by the yield of adults capable to reproduce, indicated that the reproductive perfomance decreased when hybrid females and their daughters were backcrossed additional generations to parental males. It is tentatively suggested that hybrid females could be used for suppression if they compete efficiently with wild females.

Gallbladder neuron count in cholelithiasis patients with and without Chagas disease

Various investigators agree that the incidence of cholelithiasis is greater in patients with Chagas disease. The most plausible explanation for this is based on the parasympathetic denervation that occurs over the whole digestive tract due to Chagas disease. In order to analyze the occurrence of this alteration, gallbladder neuron counts were performed on cholelithiasis patients with and without Chagas disease who were being treated at the Department of Digestive Surgery, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil. In the present study, a notable reduction in the number of neurons in the gallbladder wall was observed in Chagas patients, in comparison with non-Chagas subjects.