Pathophysiological factors of irritable bowel syndrome, and the effects of probiotic supplementation

Gastrointestinal symptoms and impaired quality of life caused by irritable bowel syndrome (IBS) affect up to 20% of the adult population worldwide. The exact aetiology and pathophysiology of IBS are incompletely understood. Clinical studies suggest that supplementation with certain probiotics may be beneficial in IBS, but there is not enough evidence to make general recommendations. The aim of this thesis was to investigate microbiota- and mucosa-associated pathophysiological factors of IBS, and to evaluate the long-term effects of multispecies probiotic supplementation on symptoms, quality of life, intestinal microbiota and systemic inflammatory markers in IBS. The intestinal microbiota composition in IBS patients and healthy control subjects was analysed by quantitative polymerase chain reaction (qPCR). Significantly lower counts for the Clostridium coccoides and the Bifidobacterium catenulatum groups were found in IBS compared to controls. Quantitative differences also appeared in subgroup analysis based on the predominant bowel habit: diarrhoea patients harboured significantly lower numbers of Lactobacillus spp. than the constipation-predominant patients, while higher counts for Veillonella spp. were detected in constipation-predominant patients compared to healthy controls. Analysis of mucosal biopsies by a metabolomic approach revealed multiple differences between patients and controls. The most prominent finding was an upregulation of specific lipid species, principally lysophosphatidylcholines and ceramides, in IBS. The effects of multispecies probiotic supplementation with Lactobacillus rhamnosus GG, Lactobacillus rhamnosus Lc705, Propionibacterium freudenreichii subsp. shermanii JS, and Bifidobacterium breve Bb99 or Bifidobacterium animalis subsp. lactis Bb12 was evaluated in two, randomised, double-blind, placebo-controlled trials. Compared to placebo, the probiotic supplementation significantly reduced the total symptoms of IBS. No effects on bowel habit were seen. Health-related quality of life (HRQOL) is reduced in patients with IBS in comparison with the Finnish population on the whole. The probiotic supplementation improved one IBS-specific domain of quality of life (bowel symptoms), whereas no other effects on HRQOL were seen. The probiotics had no major effects on the predominant microbiota as measured by qPCR, but a microarray-based analysis suggested that the probiotic consumption stabilised the microbiota. No effects on serum sensitive-CRP or cytokines were detected. In conclusion, alterations in the microbiota composition and in the mucosal metabolite profile are potential pathophysiological factors of IBS. Multispecies probiotic supplementation alleviates the gastrointestinal symptoms of IBS, and improves the bowel symptoms domain of HRQOL. Probiotic supplementation in IBS is associated with a stabilisation of microbiota, but it does not influence systemic inflammatory markers.

Prevalence and clinical correlates of obsessive-compulsive disorder in schizophrenia

Obsessive compulsive symptoms frequently occur in a substantial proportion of patients with schizophrenia. The term schizoobsessive has been proposed to delineate this subgroup of schizophrenia patients who present with obsessive compulsive symptoms/disorder. However, whether this co-occurrence is more than just co-morbidity and represents a distinct subgroup remains controversial. A striking variation is noted across studies examining prevalence of obsessive compulsive symptoms/disorder in schizophrenia patients and their impact on clinical profile of schizophrenia. Hence, in this study, we examined the prevalence of obsessive compulsive symptoms/disorder in a large sample of consecutively hospitalized schizophrenia patients and compared the clinical and functional characteristics of schizophrenia patients with and without obsessive compulsive symptoms/disorder. We evaluated 200 consecutive subjects with the DSM-IV diagnosis of schizophrenia using the Structured Clinical Interview for DSM-IV Axis I disorders, Positive and Negative Syndrome Scale, Yale Brown Obsessive Compulsive Scale, Brown Assessment of Beliefs Scale, Clinical Global Impression-Severity scale, Global Assessment of Functioning Scale, Family Interview for Genetic Studies and World Health Organization Quality of Life scale. The prevalence of obsessive compulsive symptoms in patients with schizophrenia was 24% (n = 48); 37 of them had obsessive compulsive disorder (OCD) and II had obsessive compulsive symptoms not amounting to a clinical diagnosis of OCD (OCS). Schizophrenia patients with OCS/OCD had an earlier age at onset of schizophrenia symptoms, lower positive symptoms score, higher co-morbidity with Axis II disorders, higher occurrence of OCD in family and better quality of life. Findings of the study indicate a higher prevalence of OCS/OCD in schizophrenia. Schizophrenia patients with and without OCS/OCD have comparable clinical profile with few exceptions. High rates of OCD in first degree relatives suggest possible genetic contributions and differences in neurobiology. Finally, evidence to consider schizoobsessive as a distinct diagnostic entity is inconclusive and warrants further studies. (C) 2014 Elsevier Inc. All rights reserved.

Measuring the health-related quality of life of people with ischaemic heart disease.

Objectives—To inform researchers and clinicians about the most appropriate generic and disease specific measures of health related quality of life for use among people with ischaemic heart disease. Methods—MEDLINE and BIDS were searched for research papers which contained a report of at least one of the three most common generic instruments or at least one of the five disease specific instruments used with ischaemic heart disease patients. Evidence for the validity, reliability, and sensitivity of these instruments was critically appraised. Results—Of the three generic measures—the Nottingham health profile, sickness impact profile, and short form 36 (SF-36)—the SF-36 appears to offer the most reliable, valid, and sensitive assessment of quality of life. However, a few of the SF-36 subscales lack a sufficient degree of sensitivity to detect change in a patient’s clinical condition. According to the best available evidence, the quality of life after myocardial infarction questionnaire should be preferred to the Seattle angina questionnaire, the quality of life index cardiac version, the angina pectoris quality of life questionnaire, and the summary index. Overall, research on disease specific measures is sparse compared to the number of studies which have investigated generic measures. Conclusions—An assessment of the quality of life of people with ischaemic heart disease should comprise a disease specific measure in addition to a generic measure. The SF-36 and the quality of life after myocardial infarction questionnaire (version 2) are the most appropriate currently available generic and disease specific measures of health related quality of life, respectively. Further research into the measurement of health related quality of life of people with ischaemic heart disease is required in order to address the problems (such as lack of sensitivity to detect change) identified by the review.

Limits of life in hostile environments: no barriers to biosphere function?

Environments that are hostile to life are characterized by reduced microbial activity which results in poor soil- and plant-health, low biomass and biodiversity, and feeble ecosystem development. Whereas the functional biosphere may primarily be constrained by water activity (a w) the mechanism(s) by which this occurs have not been fully elucidated. Remarkably we found that, for diverse species of xerophilic fungi at a w values of = 0.72, water activity per se did not limit cellular function. We provide evidence that chaotropic activity determined their biotic window, and obtained mycelial growth at water activities as low as 0.647 (below that recorded for any microbial species) by addition of compounds that reduced the net chaotropicity. Unexpectedly we found that some fungi grew optimally under chaotropic conditions, providing evidence for a previously uncharacterized class of extremophilic microbes. Further studies to elucidate the way in which solute activities interact to determine the limits of life may lead to enhanced biotechnological processes, and increased productivity of agricultural and natural ecosystems in arid and semiarid regions.

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial:FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2-3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity = 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence onthe role of ILM peeling in FTMH surgery. © 2008 Lois et al; licensee BioMed Central Ltd.

Family attitudes toward the deinstitutionalization of individuals with developmental disabilities in Ontario : a quality of life analysis

The deinstitutionalization of individuals with developmental disabilities to community-based residential services is a pervasive international trend. Although controversial, the remaining three institutions in Ontario were closed in March of 2009. Since these closures, there has been limited research on the effects of deinstitutionalization. The following retrospective study evaluated family perceptions of the impact of deinstitutionalization on the quality of life of fifty-five former residents one year post-closure utilizing a survey design and conceptual quality of life framework. The methods used to analyze the survey results included descriptive statistical analyses and thematic analyses. Overall, the results suggest that most family members are satisfied with community placement and supports, and report an improved quality of life for their family member with a developmental disability. These findings were consistent with previously published studies demonstrating the short-term and long-term benefits of community living for most individuals with developmental disabilities and their families.

Examining Predictors of Quality of Life of Adults with Intellectual Disabilities After Deinstitutionalization

This study examined if a person’s quality of life could be predicted by six relevant factors in a sample of 114 individuals with intellectual disability who had moved from institutional settings to community living settings within Ontario. Further, two aspects of self-efficacy were tested to see if they moderated the relationship between the possible predictors and the quality of life indicator. The initial multiple regression model accounted for a very small amount of the variance in the outcome (r2 = .08). The second analysis included decision-making as a predictor (r2 = .35) but did not find it to be moderator. The third analysis used opportunities for change as a predictor (r2 = .28), and as a moderator with two significant interaction terms, health and years in an institutional setting (r2 = .35). These findings support the often-theorized influence of self-efficacy on quality of life for individuals with intellectual disability.

Measuring quality of life in aphasia: results from two scales

Background: Although aphasia affects quality of life (QoL), the impact within specific domains (e.g., psychosocial, communication) is poorly understood. Moreover, the complex and multidimensional nature of QoL renders it difficult to measure accurately using a single global scale. Aims: Using two recently developed QoL scales, the Stroke and Aphasia Quality of Life Scale-39, (SAQOL; Hilari, Byng, Lamping, & Smith, 2003a) and the American Speech Language Hearing Association’s Quality of Communication Life Scale (QCL; Paul et al., 2004), this study aimed to document the domains of QoL that were most affected for participants with aphasia compared to control participants, as well as to determine the relationship between the two scales, their sub-domains, and linguistic variables in aphasia. Methods & Procedures: The two scales were administered to a group of 19 participants with aphasia (14 male, 5 female), ages ranging from 27 to 79 years, and 19 age- and gender-matched control participants. Various types and severity of aphasia were represented in the aphasia group. The performances of aphasia and control groups were compared, and correlation analyses examined the relationship between the two scales and their sub-domains in the aphasia group only. Outcomes & Results: Compared to control participants, QoL was lower in participants with aphasia, with the communication sub-domain of SAQOL and socialisation/ activities sub-domain of QCL being the most affected areas of functioning. Between the two scales, the communication sub-domain of SAQOL correlated with the socialisation/ activities sub-domain and the QCL mean. Moreover, linguistic variables correlated strongly with psychosocial, communication and socialisation/activities sub-domains of QoL. Conclusions: Measuring QoL using the SAQOL and the QCL captures different but equally important aspects of experiences of living with aphasia. When interpreted together, they provide a holistic picture of functioning in aphasia that includes broad overviews of QoL from the SAQOL and a finer-grained analysis of communication impairments on QoL from the QCL.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Influence of tetracycline in the hepatic and renal development of rat's offspring

O objetivo deste estudo foi avaliar os possíveis efeitos da tetraciclina administrada a ratas, no décimo dia de gestação, no desenvolvimento hepático e renal de seus filhotes. O fígado mostrou vacuolização, necrose, inflamação e dilatação sinusoidal mais evidente em recém-nascidos. Mitoses, aumento precoce da população de células de Kupffer e hipertrofia de hepatócitos com maior síntese de glicogênio estavam presentes no décimo e vigésimo dias de vida. O rim mostrou vacuolização tubular e necrose discretas, mais evidentes nos recém-nascidos, assim como sinais de regeneração tubular no décimo e vigésimo dias. Esses resultados sugeriram que os órgãos estudados sofreram alterações morfológicas transitórias durante o desenvolvimento, mas apresentaram sinais de regeneração ao longo dos primeiros dias de vida.

The effects of professional factors on the quality of life of family health team nurses

The objective of this study was to identify the professional factors affecting the quality of life of nurses working in the family health teams in the Macro Health Region, referred to as the South Triangle, in the State of Minas Gerais. This is a descriptive, cross-sectional study. The participants were 90 nurses, who answered a questionnaire containing the professional variables and the Quality of Life assessment instrument - WHOQOL-100. The results showed a negative impact regarding the number of jobs, unstable jobs, excessive workload and job dissatisfaction in the nurses' Quality of Life domains. There is a need to (re)define the public policies that control the working conditions of these professionals. Actions that contribute towards improving nurses' Quality of Life are important, considering their strong influence on the quality of the healthcare that is delivered.

Clinical characteristics and possible phenotypes of an adult severe asthma population

Background: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. Methods: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. Results: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. Conclusion: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care. (C) 2011 Elsevier Ltd. All rights reserved.

A Communication Platform for Tele-monitoring and Tele-management of Type 1 Diabetes

Type 1 diabetes mellitus is a chronic disease characterized by blood glucose levels out of normal range due to inability of insulin production. This dysfunction leads to many short- and long-term complications. In this paper, a system for tele-monitoring and tele-management of Type 1 diabetes patients is proposed, aiming at reducing the risk of diabetes complications and improving quality of life. The system integrates Wireless Personal Area Networks (WPAN), mobile infrastructure, and Internet technology along with commercially available and novel glucose measurement devices, advanced modeling techniques, and tools for the intelligent processing of the available diabetes patients information. The integration of the above technologies enables intensive monitoring of blood glucose levels, treatment optimisation, continuous medical care, and improvement of quality of life for Type 1 diabetes patients, without restrictions in everyday life activities.

What does your neighbourhood say about you? A study of life expectancy in 1.3 million Swiss neighbourhoods

BACKGROUND Switzerland had the highest life expectancy at 82.8 years among the Organisation for Economic Co-operation and Development (OECD) countries in 2011. Geographical variation of life expectancy and its relation to the socioeconomic position of neighbourhoods are, however, not well understood. METHODS We analysed the Swiss National Cohort, which linked the 2000 census with mortality records 2000-2008 to estimate life expectancy across neighbourhoods. A neighbourhood index of socioeconomic position (SEP) based on the median rent, education and occupation of household heads and crowding was calculated for 1.3 million overlapping neighbourhoods of 50 households. We used skew-normal regression models, including the index and additionally marital status, education, nationality, religion and occupation to calculate crude and adjusted estimates of life expectancy at age 30 years. RESULTS Based on over 4.5 million individuals and over 400 000 deaths, estimates of life expectancy at age 30 in neighbourhoods ranged from 46.9 to 54.2 years in men and from 53.5 to 57.2 years in women. The correlation between life expectancy and neighbourhood SEP was strong (r=0.95 in men and r=0.94 women, both p values <0.0001). In a comparison of the lowest with the highest percentile of neighbourhood SEP, the crude difference in life expectancy from skew-normal regression was 4.5 years in men and 2.5 years in women. The corresponding adjusted differences were 2.8 and 1.9 years, respectively (all p values <0.0001). CONCLUSIONS Although life expectancy is high in Switzerland, there is substantial geographical variation and life expectancy is strongly associated with the social standing of neighbourhoods.