Dietary factors impact on the association between CTSS variants and obesity related traits

BACKGROUND/AIMS: Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology--this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors--increased by high protein, glycemic index and energy diets. METHODS: Four tag SNPs (rs7511673, rs11576175, rs10888390 and rs1136774) were selected to capture all common variation in the CTSS region. Association between these four SNPs and several adiposity measurements (BMI, waist circumference, waist for given BMI and being a weight gainer-experiencing the greatest degree of unexplained annual weight gain during follow-up or not) given, where applicable, both as baseline values and gain during the study period (6-8 years) were tested in 11,091 European individuals (linear or logistic regression models). We also examined the interaction between the CTSS variants and dietary factors--energy density, protein content (in grams or in % of total energy intake) and glycemic index--on these four adiposity phenotypes. RESULTS: We found several associations between CTSS polymorphisms and anthropometric traits including baseline BMI (rs11576175 (SNP N°2), p = 0.02, β = -0.2446), and waist change over time (rs7511673 (SNP N°1), p = 0.01, β = -0.0433 and rs10888390 (SNP N°3), p = 0.04, β = -0.0342). In interaction with the percentage of proteins contained in the diet, rs11576175 (SNP N°2) was also associated with the risk of being a weight gainer (p(interaction) = 0.01, OR = 1.0526)--the risk of being a weight gainer increased with the percentage of proteins contained in the diet. CONCLUSION: CTSS variants seem to be nominally associated to obesity related traits and this association may be modified by dietary protein intake.

Progress in the genetics of common obesity and type 2 diabetes

The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.

Factors contributing to fecal incontinence in older people and outcome of routine management in home, hospital and nursing home settings

Objective: Fecal loading, cognitive impairment, loose stools, functional disability, comorbidity and anorectal incontinence are recognized as factors contributing to loss of fecal continence in older adults. The objective of this project was to assess the relative distribution of these factors in a variety of settings along with the outcome of usual management. Methods: One hundred and twenty adults aged 65 years and over with fecal incontinence recruited by convenience sampling from four different settings were studied. They were either living at home or in a nursing home or receiving care on an acute or rehabilitation elderly care ward. A structured questionnaire was used to elicit which factors associated with fecal incontinence were present from subjects who had given written informed consent or for whom assent for inclusion in the study had been obtained. Results: Fecal loading (Homes 6 [20%]; Acute care wards 17 [57%]; Rehabilitation wards 19 [63%]; Nursing homes 21 [70%]) and functional disability (Homes 5 [17%]; Acute care wards 25 [83%]; Rehabilitation wards 25 [83%]; Nursing homes 20 [67%]) were significantly more prevalent in the hospital and nursing home settings than in those living at home (P < 0.01). Loose stools were more prevalent in the hospital setting than in the other settings (Homes 11 [37%]; Acute care wards 20 [67%]; Rehabilitation wards 17 [57%]; Nursing homes 6 [20%]) (P < 0.01). Cognitive impairment was significantly more common in the nursing home than in the other settings (Nursing homes 26 [87%], Homes 5 [17%], Acute care wards 13 [43%], Rehabilitation wards 14 [47%]) (P < 0.01). Loose stools were the most prevalent factor present at baseline in 13 of the 19 (68%) subjects whose fecal incontinence had resolved at 3 months. Conclusion: The distribution of the factors contributing to fecal incontinence in older people living at home differs from those cared for in nursing home and hospital wards settings. These differences need to be borne in mind when assessing people in different settings. Management appears to result in a cure for those who are not significantly disabled with loose stools as a cause for their fecal incontinence, but this would need to be confirmed by further research.

Cancer patients taking herbal medicines: a review of clinical purposes, associated factors, and perceptions of benefit or harm

Ethnopharmacological relevance: Cancer patients in all cultures are high consumers of herbal medicines (HMs) usually as part of a regime consisting of several complementary and alternative medicine (CAM) modalities, but the type of patient, the reasons for choosing such HM-CAM regimes, and the benefits they perceive from taking them are poorly understood. There are also concerns that local information may be ignored due to language issues. This study investigates aspects of HM-CAM use in cancer patients using two different abstracting sources: Medline, which contains only peer-reviewed studies from SCI journals, and in order to explore whether further data may be available regionally, the Thai national databases of HM and CAM were searched as an example. Materials and methods: the international and Thai language databases were searched separately to identify relevant studies, using key words chosen to include HM use in all traditions. Analysis of these was undertaken to identify socio-demographic and clinical factors, as well as sources of information, which may inform the decision to use HMs. Results: Medline yielded 5,638 records, with 49 papers fitting the criteria for review. The Thai databases yielded 155, with none relevant for review. Factors associated with HM-CAM usage were: a younger age, higher education or economic status, multiple chemotherapy treatment, late stage of disease. The most common purposes for using HM-CAM cited by patients were to improve physical symptoms, support emotional health, stimulate the immune system, improve quality of life, and relieve side-effects of conventional treatment. Conclusions: Several indicators were identified for cancer patients who are most likely to take HM-CAM. However, interpreting the clinical reasons why patients decide to use HM-CAM is hampered by a lack of standard terminology and thematic coding, because patients' own descriptions are too variable and overlapping for meaningful comparison. Nevertheless, fears that the results of local studies published regionally are being missed, at least in the case of Thailand, appeared to be unfounded.

Local adaptation in migrated interior Douglas-fir seedlings is mediated by ectomycorrhizas and other soil factors

Separating edaphic impacts on tree distributions from those of climate and geography is notoriously difficult. Aboveground and belowground factors play important roles, and determining their relative contribution to tree success will greatly assist in refining predictive models and forestry strategies in a changing climate. In a common glasshouse, seedlings of interior Douglas-fir (Pseudotsuga menziesii var. glauca) from multiple populations were grown in multiple forest soils. Fungicide was applied to half of the seedlings to separate soil fungal and nonfungal impacts on seedling performance. Soils of varying geographic and climatic distance from seed origin were compared, using a transfer function approach. Seedling height and biomass were optimized following seed transfer into drier soils, whereas survival was optimized when elevation transfer was minimised. Fungicide application reduced ectomycorrhizal root colonization by c. 50%, with treated seedlings exhibiting greater survival but reduced biomass. Local adaptation of Douglas-fir populations to soils was mediated by soil fungi to some extent in 56% of soil origin by response variable combinations. Mediation by edaphic factors in general occurred in 81% of combinations. Soil biota, hitherto unaccounted for in climate models, interacts with biogeography to influence plant ranges in a changing climate.

A common framework for approaches to extreme event attribution

The extent to which a given extreme weather or climate event is attributable to anthropogenic climate change is a question of considerable public interest. From a scientific perspective, the question can be framed in various ways, and the answer depends very much on the framing. One such framing is a risk-based approach, which answers the question probabilistically, in terms of a change in likelihood of a class of event similar to the one in question, and natural variability is treated as noise. A rather different framing is a storyline approach, which examines the role of the various factors contributing to the event as it unfolded, including the anomalous aspects of natural variability, and answers the question deterministically. It is argued that these two apparently irreconcilable approaches can be viewed within a common framework, where the most useful level of conditioning will depend on the question being asked and the uncertainties involved.

Surveillance for adverse events after DTwP/Hib vaccination in Brazil: Sensitivity and factors associated with reporting

We estimated the sensitivity, i.e., the proportion of all cases of adverse events following immunization (AEFIs) reported to the Brazilian passive surveillance for adverse events following immunization (PSAEFI) with the diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b (DTwP/Hib) vaccine, as well as investigating factors associated with AEFIs reporting. During 2003-2004, 8303 AEFIs associated with DTwP-Hib were reported; hypotonic-hyporesponsive episodes (HHEs), fever and convulsions being the most common. Cure without sequel was achieved in 98.4% of the cases. The mean sensitivity of the PSAEFI was 22.3% and 31.6%, respectively, for HHE and convulsions, varying widely among states. Reporting rates correlated positively with the Human Development Index and coverage of adequate prenatal care, correlating negatively with infant mortality rates. Quality of life indicators and the degree of organization of health services are associated with greater PSAEFI sensitivity. In addition to consistently describing the principal AEFIs, PSAEFI showed the DTwP/Hib vaccine to be safe and allayed public fears related to its use. (C) 2010 Elsevier Ltd. All rights reserved.

Prevalence and risk factors of radiographic vertebral fracture in Brazilian community-dwelling elderly

The prevalence and risk factors of radiographic vertebral fracture were determined among Brazilian community-dwelling elderly. Vertebral fractures were a common condition in this elderly population, and lower hip bone mineral density was a significant risk factor for vertebral fractures in both genders. The aim of the study was to estimate the prevalence of radiographic vertebral fracture and investigate factors associated with this condition in Brazilian community-dwelling elderly. This cross-sectional study included 943 elderly subjects (561 women and 382 men) living in So Paulo, Brazil. Thoracic and lumbar spine radiographs were obtained, and vertebral fractures were evaluated using Genant`s semiquantitative method. Bone mineral density (BMD) was measured by dual X-ray absorptiometry, and bone biochemical markers were also evaluated. Female and male subjects were analyzed independently, and each gender was divided into two groups based on whether vertebral fractures were present. The prevalence of vertebral fracture was 27.5% (95% CI 23.8-31.1) in women and 31.8% in men (95% CI 27.1-36.5) (P = 0.116). Cox regression analyses using variables that were significant in the univariate analysis showed that age (prevalence ratio = 1.03, 95% CI 1.01-1.06; p = 0.019) and total femur BMD (PR = 0.27, 95% CI 0.08-0.98; p = 0.048) were independent factors in predicting vertebral fracture for the female group. In the male group, Cox regression analyses demonstrated that femoral neck BMD (PR = 0.26, 95% CI 0.07-0.98; p = 0.046) was an independent parameter in predicting vertebral fractures. Our results suggest that radiographic vertebral fractures are common in Brazilian community-dwelling elderly and that a low hip BMD was an important risk factor for this condition in both genders. Age was also significantly correlated with the presence of vertebral fractures in women.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.2014

Mitigating high ‘equity capital’ risk exposure to ‘small cap’ sector in India: analysing ‘key factors of success’ for ‘Institutional Investors’ whilst Investing in small cap sector in India

This paper deals with the subject of mitigating high ‘Equity Capital’ Risk Exposure to ‘Small Cap’ Sector in India. Institutional investors in India are prone to be risk averse when it comes to investing in the small cap sector in India as they find the companies risky and volatile. This paper will help analyse ‘Key Factors of success’ for ‘Institutional Investors’ whilst investing in Small Cap sector in India as some of these Indian small cap stocks offer handsome returns despite economic downturn. This paper has been harnessed carefully under the influence of expert investors, which includes Benjamin Graham (Security Analysis); Warren Buffet; Philip Fisher (Common Stocks and Uncommon Profits); and Aswath Damodaran.

Genetic parameters of total milk yield and factors describing the shape of lactation curve in dairy buffaloes

The objective of this study was to apply factor analysis to describe lactation curves in dairy buffaloes in order to estimate the phenotypic and genetic association between common latent factors and cumulative milk yield. A total of 31 257 monthly test-day milk yield records from buffaloes belonging to herds located in the state of São Paulo were used to estimate two common latent factors, which were then analysed in a multi-trait animal model for estimating genetic parameters. Estimates of (co)variance components for the two common latent factors and cumulated 270-d milk yield were obtained by Bayesian inference using a multiple trait animal model. Contemporary group, number of milkings per day (two levels) and age of buffalo cow at calving (linear and quadratic) as covariate were included in the model as fixed effects. The additive genetic, permanent environmental and residual effects were included as random effects. The first common latent factor (F1) was associated with persistency of lactation and the second common latent factor (F2) with the level of production in early lactation. Heritability estimates for Fl and F2 were 0.12 and 0.07, respectively. Genetic correlation estimates between El and F2 with cumulative milk yield were positive and moderate (0.63 and 0.52). Multivariate statistics employing factor analysis allowed the extraction of two variables (latent factors) that described the shape of the lactation curve. It is expected that the response to selection to increase lactation persistency is higher than the response obtained from selecting animals to increase lactation peak. Selection for higher total milk yield would result in a favourable correlated response to increase the level of production in early lactation and the lactation persistency.

Sociodemographic and clinical characteristics, causal factors and evolution of a group of patients with chronic urticaria-angioedema

CONTEXTO E OBJETIVO: Urticária-angioedema crônico é enfermidade freqüente, complexa e multicausal. O objetivo foi estudar as características sociodemográficas, clínicas, os fatores causais, agravantes e a evolução da enfermidade. TIPO DE ESTUDO E LOCAL: Descritivo e prospectivo, realizado no ambulatório de Dermatologia da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (Unesp). MÉTODOS: Foram avaliados pacientes com diagnóstico de urticária-angioedema crônico através de dados sociodemográficos, anamnese, exames dermatológico, clínico e laboratorial, com ênfase nos fatores causais, agravantes e na evolução da enfermidade. RESULTADOS: 125 pacientes foram incluídos, 95 mulheres e 30 homens. Predominaram mulheres de 30 a 40 anos e homens de 10 a 20 anos. A idade média foi de 35 anos para as mulheres e 32 anos para os homens. Predominaram pacientes de raça branca, residentes em zona urbana e casados. O tempo médio de doença foi de 45,6 meses e de cada lesão foi de 5,6 horas. A metade dos casos tinha surtos diariamente e associação de urticária com angioedema. Não houve horário preferencial de aparecimento dos surtos, mas o noturno foi o horário de piora mais citado. A causa foi esclarecida em 37,6%, predominando as infecções. O estresse foi o agravante mais referido. O tempo médio de acompanhamento foi de 11,7 meses e 60% evoluíram para o controle, 32% melhoraram, 9% mantiveram-se inalterados e um caso piorou. CONCLUSÕES: Urticária-angioedema ocorreu mais em mulheres de meia-idade. A causa foi esclarecida em um terço dos pacientes e metade deles teve controle da doença em aproximadamente um ano.

Complications and risk factors in transrectal ultrasound-guided prostate biopsies

CONTEXTO E OBJETIVO: A biópsia da próstata não é um procedimento isento de riscos. Existe preocupação com respeito às complicações e quais seriam os melhores antibióticos usados antes do procedimento. O objetivo foi determinar a taxa de complicações e os possíveis fatores de risco para complicação na biópsia da próstata. TIPO DE ESTUDO E LOCAL: Estudo prospectivo clínico, realizado no Hospital das Clínicas de Botucatu. MÉTODOS: Foram realizadas biópsias em 174 pacientes que apresentavam anormalidade ao exame digital da próstata ou antígeno prostático específico maior que 4 ng/ml ou ambos. Todos os pacientes realizaram enema e antibioticoprofilaxia previamente ao exame. As complicações foram anotadas após o término do procedimento e em consultas posteriores. Algumas condições foram investigadas como possíveis fatores de risco para biópsias de próstata: idade, câncer da próstata, diabetes melito, hipertensão arterial sistêmica, antecedentes de prostatite, uso de ácido acetilsalicílico, volume prostático, número de biópsias e uso de sonda vesical. RESULTADOS: As complicações hemorrágicas foram mais comuns (75,3%) enquanto que as infecciosas ocorreram em 19% dos casos. O tipo mais freqüente foi a hematúria, ocorrendo em 56% dos pacientes. A infecção do trato urinário ocorreu em 16 pacientes (9,2%). Sepse foi observada em três pacientes (1,7%). Não houve óbitos. em 20% dos pacientes não foram observadas complicações após o exame. A presença da sonda vesical foi fator de risco para complicações infecciosas (p < 0,05). O número maior de amostras nas biópsias foi relacionado à hematúria, sangramento retal e complicações infecciosas (p < 0,05). As demais condições investigadas não se relacionaram com complicações pós-biópsia da próstata. CONCLUSÕES: As complicações pós-biópsia da próstata foram em sua maioria autolimitadas. A taxa de complicações graves foi baixa, sendo a biópsia de próstata guiada pelo ultra-som segura e eficaz. A retirada de um maior número de fragmentos na biópsia relaciona-se com hematúria, sangramento retal e complicações infecciosas. A sonda vesical foi um fator de risco para complicações infecciosas.

Venous ulcer: clinical characteristics and risk factors

BackgroundLower limb venous ulceration ranks among the 10 most common medical problems in Western countries and has significant socioeconomic impact. The aim of this study was to identify the risk factors for unhealed, recurrent, and large ulcers and to characterize patients with active or recently healed venous ulcers.MethodsWe identified 97 patients and assessed 103 ulcerated limbs in 90 patients. All patients underwent clinical examination, arterial and venous system evaluation, ankle-brachial index determination, and ultrasound of the affected limb. Clinical characteristics included age, gender, race, ulcer duration, time since first episode, history of recurrence, localization of ulcer, ulcer area, eczema, ochre dermatitis, lipodermatosclerosis, pain, body mass index, and medical history data. Risk factors were identified by univariate analysis and estimated odds ratios.ResultsWe assessed 90 patients (103 limbs) with active or healed venous leg ulcers, of whom 84.4% were Caucasian and 68.9% were female. Mean age was 56.0 +/- 13.3 years. Ulcers had remained unhealed for < 1 year in 40.7%. Lipodermatosclerosis, lower limb hyperpigmentation, edema, and eczema were seen in 96.7%, 95.6%, 94.4%, and 51.1% of patients, respectively. Pain was a frequent symptom in 74.4%. Body mass index was assessed in 85 patients: 30.6% were slightly, 36.5% moderately, and 7% severely obese. Patient age > 60 years (odds ratio [OR] 4.0), extensive lipodermatosclerosis (OR 8.7), and previous history of ulceration (OR 19.9) were risk factors for unhealed ulcers. Time since first ulcer episode >= 2 years (OR 29.2) and incompetence of venous systems (OR 1.6) were risk factors for recurrence.ConclusionsLongstanding and large ulcers and recurrences are the main problems encountered by venous ulcer patients. Severe lipodermatosclerosis, previous ulcer history, and time since first ulcer episode >= 2 years are significant risk factors.

Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)