Identifying genes of gene regulatory networks using formal concept analysis

In order to understand the behavior of a gene regulatory network, it is essential to know the genes that belong to it. Identifying the correct members (e.g. in order to build a model) is a difficult task even for small subnetworks. Usually only few members of a network are known and one needs to guess the missing members based on experience or informed speculation. It is beneficial if one can additionally rely on experimental data to support this guess. In this work we present a new method based on formal concept analysis to detect unknown members of a gene regulatory network from gene expression time series data. We show that formal concept analysis is able to find a list of candidate genes for inclusion into a partially known basic network. This list can then be reduced by a statistical analysis so that the resulting genes interact strongly with the basic network and therefore should be included when modeling the network. The method has been applied to the DNA repair system of Mycobacterium tuberculosis. In this application our method produces comparable results to an already existing method of component selection while it is applicable to a broader range of problems

Prevalence of metabolic syndrome in patients with schizophrenia, and metabolic changes after 3 months of treatment with antipsychotics - results from a German observational study

<p>Abstract</p> <p>Background</p> <p>This observational study explored the prevalence of metabolic syndrome (MetS) in adult in- and outpatients with untreated or treated schizophrenia at baseline, and month-3 after initiation or switch of antipsychotic treatment.</p> <p>Methods</p> <p>MetS-prevalence (AHA/NHLB-definition) was assessed and Clopper-Pearson 95% confidence intervals (CIs) were calculated. Factors associated with MetS were explored through univariate and multivariate logistic regressions (both visits).</p> <p>Results</p> <p>MetS-prevalence was 44.3% (CI 39.8;48.9) at baseline and 49.6% (CI 45.0;54.2) at month-3. Previously unmedicated patients showed the lowest baseline MetS-prevalence (24.7%, CI 18.3;32.1). MetS-prevalence was not significantly different, regardless if patients previously received typical or atypical antipsychotics. Increased MetS-risk was associated with somatic comorbidity and non-smoking at both visits, and with non-psychiatric co-medication, male sex, and increased C-reactive protein at month-3.</p> <p>Conclusions</p> <p>At baseline, MetS was most prevalent in patients with previous antipsychotic medication. Limited metabolic changes were observed 3 months after switch/initiation of antipsychotic therapy.</p> <p>Trial Registration Number</p> <p>ClinicalTrials.gov Identifier: n.a.</p

Bryophyllum pinnatum and Improvement of Nocturia and Sleep Quality in Women: A Multicentre, Nonrandomised Prospective Trial

Nocturia is a pathologic condition that significantly affects the quality of sleep. The aetiology of nocturia is multifactorial, and the evidence available on its management remains limited. Besides behavioural measures, validated pharmaceutical treatment options exist but are, however, associated with marked side effects. Prospective clinical studies with tablets prepared from the leaf press juice of the plant Bryophyllum pinnatum revealed a tendency towards reduction of micturition in patients with overactive bladder (OAB) and several improvements in sleep quality. These observations are in part supported by in vitro and in vivo data. In the present study, we investigated the effectiveness of Bryophyllum 50% chewable tablets in the treatment of nocturia and associated sleep disorders. Altogether, 49 women with idiopathic OAB and nocturia of ≥2 voids/night were treated with Bryophyllum 50% tablets for 3 weeks (350 mg chewable tablets, dosage 0-0-2-2 oral tablets; WELEDA AG, Arlesheim, Switzerland). Nocturia, voiding volumes at night (ml), quality of life, sleep quality, and daily sleepiness were assessed before and after treatment with a 3-day micturition diary, the International Consultation on Incontinence evaluating overactive bladder and related impact on quality of life (QoL) [ICIQ-OAB], the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS), respectively. The age of the study population was 68.5 ± 11.6 y. After treatment, nocturia diminished from 3.2 ± 1.4 to 2.3 ± 1.3 ( ) and the PSQI score decreased from 7.7 ± 3.7 to 6.6 ± 3.4 ( ). Urgency, the ICIQ score, and the ESS lowered significantly, and the micturition volume showed a tendency to increase. No serious adverse drug reactions were reported, and compliance was good. The results show a beneficial effect on the nocturnal voids and sleep quality of women with OAB. Bryophyllum 50% tablets can be regarded as a well-tolerated alternative in the treatment of nocturia and broaden the repertoire of standard management

Urotherapist activities in caring for patients with pelvic floor disorders: a prospective single-center observational study

Purpose: Patients with pelvic floor disorders are growing in number. The aim of this study is to outline the main activities of a urotherapist, an advanced nurse practitioner, in the care of patients with pelvic floor disorders and to evaluate patient satisfaction with the service urotherapists provide. Methods: The prospective single-center observational study was carried out from July 2016 to June 2018. Parameters used to assess the urotherapist activities included the number of consultations, type of counselling, time frame of consultations and therapy and patient satisfaction. In a subgroup of 38 patients, satisfaction with the urotherapy sessions was evaluated by a questionnaire. Results: Totally, 1709 patients were examined by urogynecologists. Five hundred and fourteen (30%) with chronic pelvic floor disorders were subsequently referred to a urotherapist. Of these patients, 60% were at least 65 years old. The most common pelvic floor disorders (221 patients; 43%) were an overactive bladder, recurrent urinary tract infections, chronic cystitis and pelvic pain syndrome; the second most common pelvic floor disorder was pelvic organ prolapsed (151 patients; 29%). Of the study subgroup comprising 38 patients, 32 (84%) returned the patient satisfaction questionnaire. All 32 patients specified their level of agreement with the urotherapist's professional competence, empathy, temporal availability and quality of advice as "agree to strongly agree." Conclusions: Management by a urotherapist was highly appreciated. The role of the urotherapist as a care coordinator, their level of autonomy and barriers to the implementation in primary care requires further exploration. Keywords: Advanced nurse practitioner; Interprofessional collaboration; Patient satisfaction; Pelvic floor disorders; Urotherapy

Third trimester plasma neurokinin B levels in women with and without preeclampsia

This study was undertaken to measure neurokinin B (NKB) levels in pregnant women with and without preeclampsia (PE) in the third trimester. The study focused on the Black (sub-Saharan ancestry) and 'mixed ancestry' (synonymous with 'colored' and denotes an established race group of Khoisan, European, Malay, Malagascan, African, and South Indian ancestry) populations, constituting the majority of inhabitants of the Western Cape Province of South Africa

Effect of high fat diet on pulmonary expression of parathyroid hormone-related protein and its downstream targets

Aims: Parathyroid hormone-related protein (PTHrP) is involved in lung development and surfactant production. The latter one requires a paracrine interaction between type II alveolar cells and lipofibroblasts in which leptin triggers PTHrP-induced effects. Whether increased plasma leptin levels, as they occur in high fat diet, modify the expression of PTHrP remains unclear. Furthermore, the effect of high fat diet under conditions of forced pulmonary remodelling such as response to post myocardial infarction remains to be defined. Materials and methods: C57 bl/6 mice were randomized to either normal diet or high fat diet at an age of 6 weeks. Seven months later, the mice were euthanized and the lung was removed and frozen in fluid nitrogen until use. Samples were analyzed by real-time RT-PCR and western blot. Leptin deficient mice were used to investigate the effect of leptin on pulmonary expression of PTHrP more directly. A subgroup of mice with and without high fat diet underwent in vivo ischemia (45 min) and reperfusion (4 weeks). Finally, experiments were repeated with prolonged high-fat diet. Key findings: High fat diet increased plasma leptin levels by 30.4% and the pulmonary mRNA expression of PTHrP (1,447-fold), PTH-1 receptor (4.21-fold), and PTHrP-downstream targets ADRP (7.54-fold) and PPARγ (5.27-fold). Pulmonary PTHrP expression was reduced in leptin deficient mice by 88% indicating leptin dependent regulation. High fat diet further improved changes in pulmonary adaptation caused by ischemia/reperfusion (1.48-fold increased PTH-1 receptor protein expression). These effects were lost during prolonged high fat diet. Significance: This study established that physiological regulation of leptin plasma levels by high fat diet affects the pulmonary PTHrP expression and of PTHrP downstream targets. Modification of pulmonary expression of PTH-1 receptors by high fat diet after myocardial infarction suggests that the identified interaction may participate in the obesity paradox