Treatments used for obsessive-compulsive disorder-An international perspective

© 2019 John Wiley & Sons, Ltd.OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.Peer reviewe

Telomerase activity, estrogen receptors (α, β), Bcl-2 expression in human breast cancer and treatment response

BACKGROUND: The mechanism for maintaining telomere integrity is controlled by telomerase, a ribonucleoprotein enzyme that specifically restores telomere sequences, lost during replication by means of an intrinsic RNA component as a template for polymerization. Among the telomerase subunits, hTERT (human telomerase reverse transcriptase) is expressed concomitantly with the activation of telomerase. The role of estrogens and their receptors in the transcriptional regulation of hTERT has been demonstrated. The current study determines the possible association between telomerase activity, the expression of both molecular forms of estrogen receptor (ERα and ERβ) and the protein bcl-2, and their relative associations with clinical parameters. METHODS: Tissue samples from 44 patients with breast cancer were used to assess telomerase activity using the TRAP method and the expression of ERα, ERβ and bcl-2 by means of immunocytochemical techniques. RESULTS: Telomerase activity was detected in 59% of the 44 breast tumors examined. Telomerase activity ranged from 0 to 49.93 units of total product generated (TPG). A correlation was found between telomerase activity and differentiation grade (p = 0.03). The only significant independent marker of response to treatment was clinical stage. We found differences between the frequency of expression of ERα (88%) and ERβ (36%) (p = 0.007); bcl-2 was expressed in 79.5% of invasive breast carcinomas. We also found a significant correlation between low levels of telomerase activity and a lack of ERβ expression (p = 0.03). CONCLUSION: Lower telomerase activity was found among tumors that did not express estrogen receptor beta. This is the first published study demonstrating that the absence of expression of ERβ is associated with low levels of telomerase activity

Effect of Culture at Low Oxygen Tension on the Expression of Heat Shock Proteins in a Panel of Melanoma Cell Lines

Tumours are commonly hypoxic and this can be associated with aggressive tumour type, metastasis and resistance to therapy. Heat shock proteins (hsps) are induced in response to hypoxia, provide cancer cells with protection against tumour-associated stressors and chaperone oncoproteins that drive tumour proliferation. This study examined the effect of different oxygen concentrations on the expression of hsps in melanoma cell lines.Melanoma cell lines were cultured in 2% and 20% O(2). Expression of Hsp90, Hsp70, Hsp60, Hsp40 and Hsp32 proteins were determined by flow cytometry.Growth rates and viability were reduced in the majority of cell lines by culture in 2% O(2). Hsp expression was different in 2% compared to 20% O(2) and changes in Hsp90 expression correlated with cell line generation time (P<0.005) and viability (P<0.01). Greater total hsp expression correlated with improved viability in 2% but not 20% O(2) (P<0.05). Relative expression of the different hsps was consistent across cell lines and each correlated with the others (P = 0.0001) but not with Hsp32. Hsp expression was inversely correlated with cell line adhesion to laminin as well as collagen type IV and Breslow depth of the original primary tumour tissue (P<0.05), but not with Clark level or patient survival. All five hsps were identified on the cell surface.Culture in 2% O(2) variably altered hsp expression in a panel of melanoma cell lines. Hsp expression was associated with certain cell line characteristics and clinical parameters of the originating tumour

A Toxin–Antitoxin System Promotes the Maintenance of an Integrative Conjugative Element

SXT is an integrative and conjugative element (ICE) that confers resistance to multiple antibiotics upon many clinical isolates of Vibrio cholerae. In most cells, this ∼100 Kb element is integrated into the host genome in a site-specific fashion; however, SXT can excise to form an extrachromosomal circle that is thought to be the substrate for conjugative transfer. Daughter cells lacking SXT can theoretically arise if cell division occurs prior to the element's reintegration. Even though ∼2% of SXT-bearing cells contain the excised form of the ICE, cells that have lost the element have not been detected. Here, using a positive selection-based system, SXT loss was detected rarely at a frequency of ∼1×10−7. As expected, excision appears necessary for loss, and factors influencing the frequency of excision altered the frequency of SXT loss. We screened the entire 100 kb SXT genome and identified two genes within SXT, now designated mosA and mosT (for maintenance of SXT Antitoxin and Toxin), that promote SXT stability. These two genes, which lack similarity to any previously characterized genes, encode a novel toxin-antitoxin pair; expression of mosT greatly impaired cell growth and mosA expression ameliorated MosT toxicity. Factors that promote SXT excision upregulate mosAT expression. Thus, when the element is extrachromosomal and vulnerable to loss, SXT activates a TA module to minimize the formation of SXT-free cells

The Gac-Rsm and SadB Signal Transduction Pathways Converge on AlgU to Downregulate Motility in Pseudomonas fluorescens

Flagella mediated motility in Pseudomonas fluorescens F113 is tightly regulated. We have previously shown that motility is repressed by the GacA/GacS system and by SadB through downregulation of the fleQ gene, encoding the master regulator of the synthesis of flagellar components, including the flagellin FliC. Here we show that both regulatory pathways converge in the regulation of transcription and possibly translation of the algU gene, which encodes a sigma factor. AlgU is required for multiple functions, including the expression of the amrZ gene which encodes a transcriptional repressor of fleQ. Gac regulation of algU occurs during exponential growth and is exerted through the RNA binding proteins RsmA and RsmE but not RsmI. RNA immunoprecipitation assays have shown that the RsmA protein binds to a polycistronic mRNA encoding algU, mucA, mucB and mucD, resulting in lower levels of algU. We propose a model for repression of the synthesis of the flagellar apparatus linking extracellular and intracellular signalling with the levels of AlgU and a new physiological role for the Gac system in the downregulation of flagella biosynthesis during exponential growth

ERCC1 expression correlated with EGFR and clinicopathological variables in patients with non-small cell lung cancer. An immunocytochemical study on fine-needle aspiration biopsies samples

Purpose: Expression of ERCC1 has not been well described in fine-needle aspiration biopsies (FNABs) in patients with non-small cell lung cancer (NSCLC). We investigated the expression of ERCC1 in correlation with EGFR expression and clinicopathological factors in patients with NSCLC in order to determine if these play a role in the prognosis of the disease. Methods: We studied 45 patients, 34 with adenocarcinoma and 11 with squamous cell carcinoma. Of these 45 patients, 35 were males and 10 females, aged between 45 and 83 years, 30 smokers and 15 non-smokers. Eighteen (18) tumors were of stage I, twelve (12) stage II and fifteen (15) stage III. To investigate the expression of ERCC1 and EGFR (scores 0, 1, 2, 3), immunocytochemistry was performed on air dried specimens (FNABs) using monoclonal antibodies by alkaline-phosphatase (APAAP) method. Results: ERCC1 expression was detected in tumors from 27 patients (60%) and EGFR in 10 patients (22.2%). ERCC1 was expressed more frequently in males (65.7%) in patients >65 years old (64%), in smokers (66.7%) and in stage I (66.7%). Negative ERCC1 expression was significantly associated with the presence of EGFR. EGFR was expressed only in adenocarcinomas and more frequently in women (70%) and non smokers (53.3%). Conclusions: ERCC1 expression was identified as positive (scores 2+ and 3+) in the majority of NSCLCs and seems to be an independent prognostic marker of longer survival. In addition EGFR expression was positive (scores 2+ and 3+) in the minority of NSCLCs and only in adenocarcinomas, more frequently in ERCC1-negative (scores 0 and 1+) tumors, suggesting that it is not an independent prognostic marker for the outcome of the patients suffering from NSCLC. Resumo: Objetivo: A expressão de ERCC1 não foi ainda suficientemente descrita em biópsias aspirativas por agulha fina (FNAB) em doentes com carcinoma pulmonar de não pequenas células (NSCLC). Investigámos a expressão de ERCC1 em correlação com a expressão EGFR e os fatores clinicopatológicos em doentes com NSCLC para determinar se estes desempenham um papel no prognóstico da doença. Métodos: Estudámos 45 doentes, 34 com adenocarcinoma e 11 com carcinoma de células escamosas. Desses 45 doentes, 35 eram homens e 10 mulheres, com idades entre os 45-83 anos, 30 fumadores e 15 não fumadores. Dezoito tumores encontravam-se no estádio I, 12 no estádio II e 15 no estádio III. Para investigar a expressão de ERCC1 e EGFR (resultados 0, 1, 2, 3), foi realizada imunocitoquímica em espécimes a seco (FNAB), usando anticorpos monoclonais pelo método de fosfatase alcalina (APAAP). Resultados: A expressão ERCC1 foi detetada em tumores de 27 doentes (60%) e a do EGFR em 10 doentes (22,2%). O ERCC1 foi expresso com maior frequência em homens (65,7%), em doentes com mais de 65 anos (64%), em fumadores (66,7%) e no estádio I (66,7%). A expressão ERCC1 negativa foi significativamente associada à presença de EGFR. O EGFR foi expresso apenas em adenocarcinomas e com maior frequência em mulheres (70%) e não fumadores (53,3%). Conclusões: A expressão de ERCC1 foi identificada como positiva (resultados 2+ e 3+) na maioria dos NSCLC e parece ser um marcador de prognóstico independente de maior sobrevivência. Além disso, a expressão de EGFR foi positiva (resultados 2+ e 3+) numa minoria dos NSCLCs e apenas em adenocarcinomas, com maior frequência em tumores ERCC1-negativos (resultados 0 e 1+), sugerindo que não é um marcador de prognóstico independente na evolução de doentes que sofram de NSCLC. Keywords: NSCLC, ERCC1, EGFR, FNABs, Palavras-chave: NSCLC, ERCC1, EGFR, FNAB

Supporting historic queries in sensor networks with flash storage

Many recent sensor devices are being equipped with flash memories due to their unique advantages: non-volatile storage, small size, shock-resistance, fast read access and power efficiency. The ability of storing large amounts of data in sensor devices necessitates the need for efficient indexing structures to locate required information. The challenge with flash memories is that they are unsuitable for maintaining dynamic data structures because of their specific read, write and wear constraints; this combined with very limited data memory on sensor devices prohibits the direct application of most existing indexing methods. In this paper we propose a suite of index structures and algorithms which permit us to efficiently support several types of historical online queries on flash-equipped sensor devices: temporally constrained aggregate queries, historical online sampling queries and pattern matching queries. We have implemented our methods using nesC and have run extensive experiments in TOSSIM, the simulation environment of TinyOS. Our experimental evaluation using trace-driven real world data sets demonstrates the efficiency of our indexing algorithms. © 2012 Elsevier Ltd. All rights reserved