Craniofrontonasal syndrome (CFNS) is an X-linked disorder that exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis, and additional minor malformations, but males are usually mildly affected with hypertelorism only. Despite this, males appear underrepresented in CFNS pedigrees, with carrier males encountered infrequently compared with affected females. To investigate these unusual genetic features of CFNS, we exploited the recent discovery of causative mutations in the EFNB1 gene, which encodes ephrin-B1, to survey the molecular alterations in 59 families (39 newly investigated and 20 published elsewhere). We identified the first complete deletions of EFNB1, catalogued 27 novel intragenic mutations, and used Pyrosequencing and analysis of nearby polymorphic alleles to quantify mosaic cases and to determine the parental origin of verified germline mutations. Somatic mosaicism was demonstrated in 6 of 53 informative families, and, of 17 germline mutations in individuals for whom the parental origin of mutation could be demonstrated, 15 arose from the father. We conclude that the major factor accounting for the relative scarcity of carrier males is the bias toward mutations in the paternal germline (which present as affected female offspring) combined with reduced reproductive fitness in affected females. Postzygotic mutations also contribute to the female preponderance, whereas true nonpenetrance in males who are hemizygous for an EFNB1 mutation appears unusual. These results highlight the importance of considering possible origins of mutation in the counseling of families with CFNS and provide a generally applicable approach to the combined analysis of mosaic and germline mutations.

Têm sido atribuídas à dependência de nicotina 20% das mortes nos EUA. Estudos têm mostrado que 30% a 50% das pessoas que começam a fumar escalam para um uso problemático. Nos últimos 20 anos, a educação e a persuasão não foram suficientes para promover uma mudança política, cultural e social relacionada ao comportamento de fumar. As intervenções para interromper o uso de tabaco ainda não estão integradas às rotinas dos serviços de saúde no mundo. A falta de estratégias de integração, de tempo disponível para acoplar ações assistenciais mais específicas e mesmo a percepção dos profissionais de saúde de que os tratamentos para a dependência de nicotina são pouco efetivos são algumas das barreiras apontadas. Assim, elaborar um consenso sobre a dependência de nicotina teve como objetivos: • levantar dados epidemiológicos relevantes relacionados ao uso do tabaco no mundo e no Brasil; • revisar as ações gerais e centrais da nicotina; • elaborar um protocolo de triagem mínimo para serviços de atenção primária à saúde; • recomendar diretrizes básicas de avaliação, diagnóstico e tratamento para todos os níveis de atenção à saúde em relação à dependência de nicotina; • fornecer sugestões para a abordagem de grupos especiais de pacientes: adolescentes, gestantes, idosos, pacientes em regime de internação, obesos e pacientes com comorbidades psiquiátricas, cardiovasculares e respiratórias.

These results question the benefit of very long-term maintenance of HAART in terms of CD4 gain and HIV-1 DNA reduction.

The metabolic syndrome and its components are associated with depressive symptomatology. This article discusses the rate of co-occurrence and the points of pathophysiologic commonality between the metabolic syndrome and major depressive disorder.

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Major depressive disorder is a prevalent recurrent medical syndrome associated with inter-episodic dysfunction. The metabolic syndrome is comprised of several established risk factors for cardiovascular disease (i.e. abdominal obesity, dyslipidaemia, dysglycaemia and hypertension). The criterion items of the metabolic syndrome collectively represent a multi-dimensional risk factor for cardiovascular disease and type 2 diabetes mellitus. Extant evidence indicates that both major depressive disorder and the metabolic syndrome, albeit distinct, often co-occur and are possibly subserved by overlapping pathophysiology and causative mechanisms. Conventional antidepressants exert variable effects on constituent elements of the metabolic syndrome, inviting the need for careful consideration prior to treatment selection and sequencing. Initiating and maintaining antidepressant therapy should include routine surveillance for clinical and/or biochemical evidence suggestive of the metabolic syndrome.

The prevailing models of disease pathophysiology in DM and major depressive disorder are distinct. Notwithstanding, the common abnormalities observed in disparate effector systems (e.g., insulin resistance, immunoinflammatory activation) as well as brain volume and neurocognitive performance provide the nexus for hypothesizing that both conditions are subserved by overlapping pathophysiology. This conception provides a novel framework for disease modeling and treatment development in mood disorder.

No abstract