Family environment patterns in families with bipolar children

Background: We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). Methods: We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. Results: Parents of bipolar children reported lower levels of family cohesion (p<0.001), expressiveness (p=0.005), active-recreational orientation (p<0.001), intellectual-cultural orientation (p=0.04) and higher levels of conflict (p<0.001) compared to parents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.03 1) and cohesion (p=0.014) in families where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). Limitations: Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. Conclusion: Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder. (C) 2007 Elsevier B.V. All rights reserved.

CCR2 receptor is essential to activate microbicidal mechanisms to control Toxoplasma gondii infection in the central nervous system

Chemokines comprise a structurally related family of cytokines that regulate leukocyte trafficking. Because infection with Toxoplasma gondii can induce an important inflammatory reaction that, if left uncontrolled, can lead to death, we investigated the role of the chemokine receptor CCR2 in T gondii infection. We orally infected CCR2(-/-) mice with five ME-49 T gondii cysts and monitored morbidity, survival, and immune response thereafter. The CCR2(-/-) mice displayed higher susceptibility to infection as all mice died on day 28 after infection. Despite similar Th1 responses, a more evident anti-inflammatory response was induced in the peripheral organs of CCR2(-/-) mice compared with wild-type C57BL/6 mice. Additionally, CCR2-/- mice presented greater parasitism and a milder inflammatory reaction in their peripheral organs with lesser CD4(+) and MAC-1(+) and greater CD8(+) cell migration. The parasite load decreased in these organs in CCR2(-/-) mice but remained uncontrolled in the central nervous system. Additionally, we observed down-regulated inducible nitric oxide synthase expression in peripheral organs from CCR2(-/-) mice that was associated with a small nitric oxide production by spleen macrophages. In conclusion, in the absence of CCR2, another mechanism is activated to control tissue parasitism in peripheral organs. Nevertheless, CCR2 is essential for the activation of microbicidal mediators that control T gondii replication in the central nervous system.

IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. Previously, we demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17R signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP). It was observed that IL-17R-deficient mice, subjected to CLP-induced non-severe sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with C57BL/6 littermates. As a consequence, the mice showed an increased mortality rate. The ability of IL-17 to induce neutrophil migration was demonstrated in vivo and in vitro. Beside its role in neutrophil recruitment to the infection focus, IL-17 enhanced the microbicidal activity of the migrating neutrophils by a mechanism dependent on NO. Therefore, IL-17 plays a critical role in host protection during polymicrobial sepsis. The Journal of Immunology, 2009, 182: 7846-7854.

Melanoma in adolescents: A case-control study of risk factors in Queensland, Australia

The incidence of melanoma increases markedly in the second decade of life but almost nothing is known of the causes of melanoma in this age group. We report on the first population-based case-control study of risk factors for melanoma in adolescents (15-19 years). Data were collected through personal interviews with cases, controls and parents. A single examiner conducted full-body nevus counts and blood samples were collected from cases for analysis of the CDKN2A melanoma predisposition gene. A total of 201 (80%) of the 250 adolescents with melanoma diagnosed between 1987 and 1994 and registered with the Queensland Cancer Registry and 205 (79%) of 258 age-, gender- and location-matched controls who were contacted agreed to participate. The strongest risk factor associated with melanoma in adolescents in a multivariate model was the presence of more than 100 nevi 2 mm or more in diameter (odds ratio [OR] = 46.5, 95% confidence interval [Cl] = 11.4-190.8). Other risk factors were red hair (OR = 5.4, 95%Cl = 1.0-28.4); blue eyes (OR = 4.5, 95%Cl = 1.5- 13.6); inability to tan after prolonged sun exposure (OR = 4.7, 95%Cl = 0.9-24.6); heavy facial freckling (OR = 3.2, 95% Cl = 0.9-12.3); and family history of melanoma (OR = 4.0, 95%Cl = 0.8-18.9). Only 2 of 147 cases tested had germline variants or mutations in CDKN2A. There was no association with sunscreen use overall, however, never/rare use of sunscreen at home under the age of 5 years was associated with increased risk (OR = 2.2, 95%Cl = 0.7-7.1). There was no difference between cases and controls in cumulative sun exposure in this high-exposure environment. Factors indicating genetic susceptibility to melanoma, in particular, the propensity to develop nevi and freckles, red hair, blue eyes, inability to tan and a family history of the disease are the primary determinants of melanoma among adolescents in this high solar radiation environment. Lack of association with reported sun exposure is consistent with the high genetic susceptibility in this group. (C) 2002 Wiley-Liss, Inc.

N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel golgi-associated protein

Nedd4 belongs to a family of ubiquitin-protein ligases that is characterized by 2-4 WW domains, a carboxyl-terminal Hect ((h) under bar omologous to (E) under bar6-AP (C) under bar arboxyl (t) under bar erminus)-domain and in most cases an amino-terminal C2 domain. We had previously identified a series of proteins that associates with the WW domains of Nedd4. In this paper, we demonstrate that one of the Nedd4-binding proteins, N4WBP5, belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. N4WBP5 binds Nedd4 WW domains via the two PPXY motifs present in the amino terminus of the protein. In addition to Nedd4, N4WBP5 can interact with the WW domains of a number of Nedd4 family members and is ubiquitinated. Endogenous N4WBP5 localizes to the Golgi complex. Ectopic expression of the protein disrupts the structure of the Golgi, suggesting that N4WBP5 forms part of a family of integral Golgi membrane proteins. Based on previous observations in yeast, we propose that N4WBP5 may act as an adaptor for Nedd4-like proteins and their putative targets to control ubiquitin-dependent protein sorting and trafficking.

Farm exposures, parental occupation, and risk of Ewing's sarcoma in Australia: a national case-control study

Objective: It has been suggested that parental occupation, particularly farming, increased the risk of Ewing's sarcoma in the offspring. In a national case-control study we examined the relationship between farm and other parental occupational exposures and the risk of cancer in the offspring. Methods: Cases were 106 persons with confirmed Ewing's sarcoma or peripheral primitive neuroectodermal tumor. Population-based controls (344) were selected randomly via telephone. Information was collected by interview (84% face-to-face). Results: We found an excess of case mothers who worked on farms at conception and/or pregnancy (odds ratio (OR) = 2.3, 95% confidence interval (CI) 0.5-12.0) and a slightly smaller excess of farming fathers; more case mothers usually worked as laborers, machine operators, or drivers (OR = 1.8, 95% CI 0.9-3.9). Risk doubled for those whose mothers handled pesticides and insecticides, or fathers who handled solvents and glues, and oils and greases. Further, more cases lived on farms (OR = 1.6, 95% CI 0.9-2.8). In the 0-20 years group, the risk doubled for those who ever lived on a farm (OR = 2.0, 95% CI 1.0-3.9), and more than tripled for those with farming fathers at conception and/or pregnancy (OR = 3.5, 95% CI 1.0-11.9). Conclusions: Our data support the general hypothesis of an association of Ewing's sarcoma family of tumors with farming, particularly at younger ages, who represent the bulk of cases, and are more likely to share etiologic factors.

An evaluation of a family psychoeducation program in community mental health

The aim of the research project was to identify the efficacy of the family psychoeducation program as a strategy for reducing the hospital admissions of young people. It also aimed to determine if the family psychoeducation program had an impact on the experience of caregiving and knowledge and satisfaction of services provided by the mental health service. A retrospective chart audit compared readmission history of 27 clients whose families attended a psychoeducation program with readmission history of a matched group of young people whose families did not attend the program. A telephone survey was conducted for both groups of families to investigate knowledge and understanding of services and burden of care. The results indicated that family participation in a brief multiple family psychoeducation program did not reduce the number or duration of admissions of the young people. There was no impact on the level of care for families who attended the psychoeducation program, however, this group showed some evidence of increased knowledge and understanding of services as compared to the control group.

Control of familial and renal cardiac diseases in English bull terriers: How to repair a damaged breed?

Control recommendations are presented for four genetic or familial diseases that cause significant morbidity and mortality in affected English Bull Terriers. Bull Terrier polycystic kidney disease is an autosomal dominant disease diagnosed by detecting a minimum of three renal cysts, with cysts present in both kidneys, and similarly affected family members to confirm the inherited nature of the cysts. Bull Terrier hereditary nephritis is an autosomal dominant disease diagnosed in otherwise normal animals with urinary protein: creatinine ratios persistently >0.3 and no significant urinary sediment, a family history of the disease, and characteristic glomerular basement membrane lesions. Mitral valve myxomatous degeneration and left ventricular outflow tract obstruction in Bull Terriers are familial diseases diagnosed by auscultating characteristic murmurs in affected animals. Excluding animals with these clinical signs from the breeding pool will reduce the prevalence rates of these diseases, however maintenance of an effective population size is also important. Providing breeders with information on genetics, including the risks associated with inbreeding and the benefits of outcrossing, is likely to improve canine breeding practices, thus increasing fitness and fecundity of these purebred dogs.

Breast cancer in Mexican women: an epidemiological study with cervical cancer control

INTRODUCTION: In Mexico, breast cancer (BC) is one of the main causes of cancer deaths in women, with increasing incidence and mortality in recent years. Therefore, the aim of the study is identify possible risk factors related to BC. METHODS: An epidemiological study of hospital cases of BC and controls with cervical uterine cancer (CUCA) was carried out at eight third level concentration hospitals in Mexico City. The total of 353 incident cases of BC and 630 controls with CUCA were identified among women younger than 75 years who had been residents of the metropolitan area of Mexico City for at least one year. Diagnosis was confirmed histologically in both groups. Variables were analyzed according to biological and statistical plausibility criteria. Univariate, bivariate and multivariate analyses were carried out. Cases and controls were stratified according to the menopausal hormonal status (pre and post menopause). RESULTS: The factors associated with BC were: higher socioeconomic level (OR= 2.77; 95%CI = 1.77 - 4.35); early menarche (OR= 1.32; 95%CI= 0.88 - 2.00); old age at first pregnancy (>31 years: OR= 5.49; 95%CI= 2.16 - 13.98) and a family history of BC (OR= 4.76; 95% CI= 2.10 - 10.79). In contrast, an increase in the duration of the breastfeeding period was a protective factor (>25 months: OR= 0.38; 95%CI= 0.20 - 0.70). CONCLUSIONS: This study contributes to the identification of risk factors for BC described in the international literature, in the population of Mexican women. Breastfeeding appears to play an important role in protecting women from BC. Because of changes in women`s lifestyles, lactation is decreasing in Mexico, and young women tend not to breastfeed or to shorten the duration of lactation.

Hospital visitors as controls in case-control studies

OBJECTIVE: Selecting controls is one of the most difficult tasks in the design of case-control studies. Hospital controls may be inadequate and random controls drawn from the base population may be unavailable. The aim was to assess the use of hospital visitors as controls in a case-control study on the association of organochlorinated compounds and other risk factors for breast cancer conducted in the main hospital of the "Instituto Nacional de Câncer" -- INCA (National Cancer Institute) in Rio de Janeiro (Brazil). METHODS: The study included 177 incident cases and 377 controls recruited among female visitors. Three different models of control group composition were compared: Model 1, with all selected visitors; Model 2, excluding women visiting relatives with breast cancer; and Model 3, excluding all women visiting relatives with any type of cancer. Odds ratios (OR) and 95% confidence intervals were calculated to test the associations. RESULTS: Age-adjusted OR for breast cancer associated with risk factors other than family history of cancer, except smoking and breast size, were similar in the three models. Regarding family history of all cancers, except for breast cancer, there was a decreased risk in Models 1 and 2, while in Model 3 there was an increased risk, but not statistically significant. Family history of breast cancer was a risk factor in Models 2 and 3, but no association was found in Model 1. In multivariate analysis a significant risk of breast cancer was found when there was a family history of breast cancer in Models 2 and 3 but not in Model 1. CONCLUSIONS: These results indicate that while investigating risk factors unrelated to family history of cancer, the use of hospital visitors as controls may be a valid and feasible alternative.

Entrepreneurship Strategies in Family and Non-family Businesses

The goal of the present paper is to analyse the classic entrepreneurship strategies (Innovation, Risk and Proactivity) in small and medium-sized businesses. However as presented in the title, the study will go further by comparing the results of those strategies in familiar and nonfamiliar businesses. This study was carried on in construction and industry sectors, in the region of Vale do Sousa, in the north of Portugal. In order to classify businesses as familiar or non-familiar types two criterion were adopted: (1) Management Control, (2) Family Employability. On the opposite to some studies that present a larger percentage of familiar businesses in national and European entrepreneurial fabric, the criterion used leaded to a larger number of non-familiar businesses (53%). The results showed that in general SMEs in this region are not following entrepreneurship strategies. Analysing the entire sample without a separation of businesses by nature (familiar/non-familiar) only proactivity showed to be more present in the managerial decisions. There is a lack of innovation and risk culture. Comparing the groups only on proactivity tests was possible to verify some differences. It was concluded that non-familiar businesses are more proactive than familiar ones. Between those groups there are no statistical differences on the means of the variables innovation and risk. At the same time some tests were conducted to test the differences on the variable entrepreneurship. The results were similar to innovation and risk strategies: There are no significant differences on entrepreneurship between these groups of businesses.

Functional and structural characterization of the RNase II-family of enzymes

Dissertation presented to obtain a Doctoral Degree in Biology by Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

On an acute case of Chagas disease in a region under vector control in the state of São Paulo, Brazil

No vector transmitted cases of Chagas disease had been notified in the state of São Paulo since the 1970s. However, in March, 2006, the death of a six-year-old boy from the municipality of Itaporanga was notified to the Center for Epidemiological Survey of the São Paulo State Health Secretariat: an autochthonous case of acute Chagas disease. The postmortem histopathological examination performed in the Hospital das Clínicas of the Botucatu School of Medicine confirmed the diagnosis. Reference to hospital records, consultation with the health professionals involved in the case and interviews with members of the patient's family supplied the basis for this study. We investigated parasite route of transmission, probable local reservoirs and vectors. No further human cases of acute Chagas disease were diagnosed. No locally captured vectors or reservoirs were found infected with Trypanosoma cruzi. Alternative transmission hypotheses - such as the possible ingestion of foods contaminated with vector excreta - are discussed, as well as the need to keep previously endemic regions and infested houses under close surveillance. Clinicians should give due attention to such signs as uni- or bilateral palpebral edema, cardiac failure, myocarditis, pericarditis, anasarca and atypical signs of nephrotic syndrome or nephritis and consider the diagnostic hypothesis of Chagas disease.

CHEMOPROPHYLAXIS TO CONTROL LEPROSY AND THE PERSPECTIVE OF ITS IMPLEMENTATION IN BRAZIL: A PRIMER FOR NON-EPIDEMIOLOGISTS

The occurrence of leprosy has decreased in the world but the perspective of its elimination has been questioned. A proposed control measure is the use of post-exposure chemoprophylaxis (PEP) among contacts, but there are still questions about its operational aspects. In this text we discuss the evidence available in literature, explain some concepts in epidemiology commonly used in the research on this topic, analyze the appropriateness of implementing PEP in the context of Brazil, and answer a set of key questions. We argue some points: (1) the number of contacts that need to receive PEP in order to prevent one additional case of disease is not easy to be generalized from the studies; (2) areas covered by the family health program are the priority settings where PEP could be implemented; (3) there is no need for a second dose; (4) risk for drug resistance seems to be very small; (5) the usefulness of a serological test to identify a higher risk group of individuals among contacts is questionable. Given that, we recommend that, if it is decided to start PEP in Brazil, it should start on a small scale and, as new evidence can be generated in terms of feasibility, sustainability and impact, it could move up a scale, or not, for a wider intervention.

Insights into the role of almond CBF transcription factors in the environmental control of cold acclimation and dormancy break

Dissertation presented to obtain the Ph.D degree in Biology