PyGNA:A unified framework for geneset network analysis

Input data and results for the manuscript "PyGNA: a unified framework for geneset network analysis". Manifest files describe the content of each file.This work has been supported by the Wellcome Trust Seed Award in Science (207769/A/17/Z) to G.S

Bipolar disorder in late life: clinical characteristics in a sample of older adults admitted for manic episode

BACKGROUND: Although manic episodes in older adults are not rare, little published data exist on late-life manic episodes. Resistance to treatment and concomitant neurological lesions are frequent correlates of elderly mania. The aim of this study was to investigate the prevalence of hospitalizations due to mania in patients older than 64 years through a period of 5 years in an Italian public psychiatric ward. Moreover, we aimed at describing clinical presentation of elderly manic episodes. METHODS: A retrospective chart review was conducted in order to describe clinical presentation of 20 elderly patients hospitalized for manic episode; moreover, we compared age at onset, the presence of family history for mood disorders, psychosis and irritability between the elderly group and a matched group of 20 younger manic inpatients. RESULTS: Seven percent of the whole inpatient elderly people suffered from mania. Half of those patients had a mood disorder age at onset after 50 years and 5 patients were at their first manic episode. Geriatric- and adulthood mania showed similar clinical presentation but younger people had more frequently a mood disorders family history. CONCLUSION: Half of our older manic inpatients consisted of "classic" bipolar patients with an extension of clinical manifestations into later life; the other half of our sample was heterogeneous, even though it was not possible to identify clearly which patients may have had vascular lesions related to the onset of mania

Prevalence and burden of bipolar disorders in European countries

A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5–1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5–2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization

Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy-and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635-1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient's anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation

Atypical ductal hyperplasia: Our experience in the management and long term clinical follow-up in 71 patients

Abstract Introduction Atypical ductal hyperplasia (ADH) is a high-risk benign lesion found in approximately 1–10% of breast biopsies and associated with a variable incidence of carcinoma after surgical excision. The main goal of our study is to present our experience in the management and long-term follow-up of 71 patients with ADH diagnosed on breast biopsy. Materials and methods Results of 3808 breast biopsy specimens from 1 January 2000 to 31 December 2005 were analyzed to identify all biopsies which resulted in a diagnosis of ADH. The histopathological results of the 45 patients who underwent surgery were analyzed. Long-term follow-up for the remaining patients was carried out. Results 45 of 71 (63.4%) patients with histological diagnosis of ADH on breast biopsy underwent surgery. Definitive histological results revealed invasive carcinoma in 7 cases (15.6%), high grade Ductal Carcinoma in situ (DCIS) in 10 (22.2%) patients, Lobular Carcinoma in situ (LCIS) in 4 cases (8.9%) and benign findings in 24 cases (53.3%). 12 of 71 (16.9%) patients underwent only long term follow-up; one (8,3%) of these developed invasive breast carcinoma after 6 years. Conclusion Atypical ductal hyperplasia diagnosed on breast biopsy is associated with a relatively high incidence of invasive carcinoma and high grade ductal carcinoma in situ at the time of surgical excision. Certain radiological and cytological criteria can be used to help determine which patients should forgo surgery and be followed up with good results. Long term follow-up is always crucial for patients who have not undergone surgery

Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain

The mode of action of antidepressant drugs may be related to mechanisms of receptor adaptation, involving overall the serotonin 1A (5-HT1A) receptor subtype. However, so far, the clinical effectiveness of selective compounds acting at this level has proved disappointing. This could be explained by the heterogeneity of 5-HT1A receptors within the central nervous system. In animals, two 5-HT1A agonists, flibanserin and buspirone, have shown different pharmacological properties, depending on the brain region. Since no evidence supports this observation in humans, this study sought to investigate whether these two drugs exert different effects on 5-HT1A receptor activation in three different human brain areas: the prefrontal cortex, hippocampus and raphe nuclei. 5-HT1A-mediated inhibition of forskolin-stimulated adenylyl cyclase (AC) was taken as an index of 5-HT1A receptor activation. Flibanserin significantly reduced the activity of AC post-synaptically, i.e. in the prefrontal cortex [EC50 (mean +/- S.E.M.), 28 +/- 10.2 nM; Emax, 18 +/- 2.3%] and in the hippocampus (EC50, 3.5 +/- 3.1 nM; Emax, 20 +/- 4.0%), but had no effect in the raphe nuclei, i.e. at pre-synaptic level. Vice versa, buspirone was only slightly but significantly effective in the raphe (EC50, 3.0 +/- 2.8 nM; Emax, 12 +/- 1.9%). Agonist effects were sensitive to the 5-HT1A antagonists WAY-100135 and pindobind 5-HT1A in the cortex and raphe nuclei, whereas buspirone antagonized flibanserin in the hippocampus. These findings suggest a region-related action of flibanserin and buspirone on forskolin-stimulated AC activity in human brain

Immunological backbone of uveal melanoma: is there a rationale for immunotherapy?

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease

Internal consistency and discriminant validity of the Structured Clinical Interview for Panic Agoraphobic Spectrum (SCI-PAS)

This paper reports on the feasibility, acceptability and psychometric properties of the Structured Clinical Interview for Panic-Agoraphobic Spectrum (SCI-PAS). This interview was designed to assess the lifetime presence of symptoms and other clinical features considered to comprise the panic-agoraphobic spectrum. The interview has 114 items grouped into nine domains. A total of 422 subjects, from 11 centres located throughout Italy, participated in this study. Data were collected from three groups of subjects: psychiatric patients meeting DSM-IV criteria for panic disorder (n = 141), cardiovascular patients (n = 140), including 29 with post-myocardial infarction, and university students (n = 141). The inter-rater reliability and the internal consistency of the SCI-PAS measures were assessed using the intra-class correlation coefficient and the Kuder-Richardson coefficient, respectively. Discriminant validity was assessed by comparing results in patients with panic disorder to those in the other groups. The interview required an average of 25 (±5) minutes to administer. Patients and clinicians found the scale to be highly useful, providing information not previously obtained. Internal consistency was good (>0.70) for six out of nine SCI-PAS domains. The inter-rater reliability was excellent (>0.70) for all the domains except for 'other phobias' (0.467). Patients with panic disorder scored significantly higher on each domain, and on the overall panic spectrum, than did the control subjects. In conclusion, the SCI-PAS is a useful clinical interview, which can be administered in a reasonable period of time. This assessment further demonstrates good internal consistency, discriminant validity, and inter-rater reliability. Copyright © 1999 Whurr Publishers Ltd

Alkaline phosphatase affects renal function in never-treated hypertensive patients. effect modification by age

Several studies in patients with chronic kidney disease or normal renal function have shown that high levels of tissue non-specific alkaline phosphatase (ALP) are associated with an increased risk of all cause and cardiovascular (CV) mortality. Considering the independent prognostic role of renal function, we investigated the possible association between ALP levels and estimated glomerular filtration rate (e-GFR) in a large cohort of hypertensive subjects. We enrolled 2157 never-treated uncomplicated hypertensive patients with ALP levels within normal range. In the whole population, e-GFR was strongly related to ALP (r = -0.43, P < 0.0001) with similar magnitude in females and in males, resulting ALP the second independent predictor of renal function. In a multiple linear regression model, both on crude (P < 0.001) and adjusted (P = 0.01) analyses age significantly modified the effect of a fixed increase in ALP (20 UI/L) on renal function so that the reduction in e-GFR associated to a 20 UI/L increase in ALP was of lower magnitude in younger patients and progressively of higher extent from 20 years of age onwards. In conclusion, present data indicate a significant relationship between ALP levels and e-GFR in uncomplicated hypertensive patients that is modulated by age and that persisted after adjusting for several confounders