Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 346
Filtrar
1.
Biol Psychiatry ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31570195

RESUMO

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

2.
Psychol Med ; : 1-9, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31530330

RESUMO

BACKGROUND: Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity. METHODS: We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators. RESULTS: Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data. CONCLUSIONS: Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.

4.
BMJ Open ; 9(9): e029348, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31537565

RESUMO

INTRODUCTION: Sepsis is a life-threatening, dysregulated response to infection. Both high-density lipoprotein and low-density lipoprotein cholesterol should protect against sepsis by several mechanisms; however, for partially unknown reasons, cholesterol levels become critically low in patients with early sepsis who experience poor outcomes. An anti-inflammatory lipid injectable emulsion containing fish oil is approved by the Food and Drug Administration as parenteral nutrition for critically ill patients and may prevent this decrease in serum cholesterol levels by providing substrate for cholesterol synthesis and may favourably modulate inflammation. This LIPid Intensive Drug therapy for Sepsis Pilot clinical trial is the first study to attempt to stabilise early cholesterol levels using lipid emulsion as a treatment modality for sepsis. METHODS AND ANALYSIS: This is a two-centre, phase I/II clinical trial. Phase I is a non-randomised dose-escalation study using a Bayesian optimal interval design in which up to 16 patients will be enrolled to evaluate the safest and most efficacious dose for stabilising cholesterol levels. Based on phase I results, the two best doses will be used to randomise 48 patients to either lipid injectable emulsion or active control (no treatment). Twenty-four patients will be randomised to one of two doses of the study drug, while 24 control group patients will receive no drug and will be followed during their hospitalisation. The control group will receive all standard treatments mandated by the institutional sepsis alert protocol. The phase II study will employ a permuted blocked randomisation technique, and the primary endpoint will be change in serum total cholesterol level (48 hours - enrolment). Secondary endpoints include change in cholesterol level from enrolment to 7 days, change in Sequential Organ Failure Assessment score over the first 48 hours and 7 days, in-hospital and 28-day mortality, lipid oxidation status, inflammatory biomarkers, and high-density lipoprotein function. ETHICS AND DISSEMINATION: Investigators are trained and follow good clinical practices, and each phase of the study was reviewed and approved by the institutional review boards of each institution. Results of each phase will be disseminated through presentations at national meetings and publication in peer-reviewed journals. If promising, data from the pilot study will be used for a larger, multicentre, phase II clinical trial. TRIAL REGISTRATION NUMBER: NCT03405870.

5.
Child Abuse Negl ; : 104131, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31466859

RESUMO

This invited article is one of several comprising part of a special issue of Child Abuse and Neglect focused on child trafficking and health. The purpose of each invited article is to describe a specific program serving trafficked children. Featuring these programs is intended to raise awareness of innovative counter-trafficking strategies emerging worldwide and facilitate collaboration on program development and outcomes research. This article describes Love146, an international human rights organization based in the United States and dedicated to ending child sex trafficking and exploitation. Love146's work began in Southeast Asia and later expanded to the United Kingdom, Liberia and Madagascar. In the United States, Love146's Survivor Care Program serves as Connecticut's primary provider of specialized services for survivors of DMST. The purpose of the current paper is to detail the successes, challenges, and lessons learned by Love146 in facilitating U.S. survivor access to services that can improve medical and mental health outcomes.

6.
Cochrane Database Syst Rev ; 7: CD011785, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31265739

RESUMO

BACKGROUND: Upper gastrointestinal bleeding is typically a mild, self-limiting condition that can affect both preterm and term neonates, although it can be severe particularly when associated with co-morbidities. Pharmacological interventions with a proton pump inhibitor (PPI), H2 receptor antagonist (H2RA), antacid, bismuth and sucralfate may have effects on both the prevention and treatment of upper gastrointestinal bleeding in infants. OBJECTIVES: To assess how different pharmacological interventions (PPIs, H2RAs, antacids, sucralfate or bismuth salts) administered to preterm and term neonates for the prevention or treatment of upper gastrointestinal bleeding to reduce morbidity and mortality compare with placebo or no treatment, supportive care, or each other. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 6), MEDLINE via PubMed (1966 to 12 July 2018), Embase (1980 to 12 July 2018), and CINAHL (1982 to 12 July 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials, and online for Chinese literature articles. SELECTION CRITERIA: We selected randomised, quasi-randomised and cluster-randomised trials involving preterm and term neonates. Trials were included if they used a proton pump inhibitor, H2 receptor antagonist, antacid, sucralfate or bismuth either for the prevention or treatment of upper gastrointestinal bleeding. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. We conducted meta-analysis using a fixed-effect model. We used the GRADE approach to assess quality of evidence. MAIN RESULTS: Eleven studies with 818 infants met the criteria for inclusion in this review.Four trials with 329 infants assessed the use of an H2 receptor antagonist for prevention of upper gastrointestinal bleeding in high-risk newborn infants. Meta-analysis of these four trials identified a reduction in any upper gastrointestinal bleeding when using an H2 receptor antagonist (typical risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.58; typical risk difference (RD) -0.20, 95% CI -0.28 to -0.11; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 9). The quality of evidence was moderate. A single trial with 53 infants assessing prevention of upper gastrointestinal bleeding reported no difference in mortality in infants assigned H2 receptor antagonist versus no treatment; however the quality of evidence was very low.Seven trials with 489 infants assessed an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) for treatment of gastrointestinal bleeding in newborn infants. Meta-analysis of two trials (131 infants) showed no difference in mortality from use of a H2 receptor antagonist compared to no treatment. The quality of evidence was low. Meta-analysis of two trials (104 infants) showed a reduction in duration of upper gastrointestinal bleeding from use of an inhibitor of gastric acid compared to no treatment (mean difference -1.06 days, 95% CI -1.28 to -0.84). The quality of evidence was very low. Meta-analysis of six trials (451 infants) showed a reduction in continued upper gastrointestinal bleeding from use of any inhibitor of gastric acid compared to no treatment (typical RR 0.36, 95% CI 0.26 to 0.49; typical RD -0.26, 95% CI -0.33, -0.19; NNTB 4, 95% CI 3 to 5). The quality of evidence was low. There were no significant subgroup differences in duration of upper gastrointestinal bleeding or of continued upper gastrointestinal bleeding according to type of inhibitor of gastric acid. A single trial (38 infants) reported no difference in anaemia requiring blood transfusion from use of a H2 receptor antagonist compared to no treatment.Although no serious adverse events were reported from the use of a H2 receptor antagonist or proton pump inhibitor, some neonatal morbidities - including necrotising enterocolitis, ventilator-associated pneumonia, duration of ventilation and respiratory support, and duration of hospital stay - were not reported. Long-term outcome was not reported. AUTHORS' CONCLUSIONS: There is moderate-quality evidence that use of an H2 receptor antagonist reduces the risk of gastrointestinal bleeding in newborn infants at high risk of gastrointestinal bleeding. There is low-quality evidence that use of an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) reduces the duration of upper gastrointestinal bleeding and the incidence of continued gastric bleeding in newborn infants with gastrointestinal bleeding. However, there is no evidence that use of an inhibitor of gastric acid in newborn infants affects mortality or the need for blood transfusion. As no study reported the incidence of necrotising enterocolitis, ventilator- or hospital-associated pneumonia, sepsis, or long-term outcome, the safety of inhibitors of gastric acid secretion is unclear.


Assuntos
Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Antiulcerosos/uso terapêutico , Enterocolite Necrosante/prevenção & controle , Antagonistas dos Receptores Histamínicos H2/uso terapêutico , Humanos , Recém-Nascido , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sucralfato/uso terapêutico
9.
J Community Psychol ; 47(7): 1666-1681, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332818

RESUMO

OBJECTIVE: This project used mixed methods to expand the understanding of social ecological constructs important to youth and develop measures to assess these constructs. METHODS: Eight focus groups and 24 cognitive interviews were conducted with adolescents and caregivers. These were followed by a survey completed by 440 youth ages 10-21 (average age: 16.38, standard deviation[SD] = 3.04). RESULTS: Qualitative data revealed social ecological constructs that have received little prior research attention. These include three psychosocial strengths: relational motivation (inspiration from key adults), group connectedness (bonded to others in teams or organizations), and mattering (knowing your importance to significant others). One outcome was also identified: family well-being (subjective psychological functioning of the family). Psychometric analyses indicated that the new quantitative measures have good to excellent reliability and validity. IMPLICATIONS: The social ecology is complex and extends beyond commonly studied constructs such as social support and collective efficacy. More comprehensive assessments can further research.

10.
Lung Cancer ; 134: 66-71, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31319997

RESUMO

OBJECTIVES: This Liverpool Healthy Lung Programme is a response to high rates of lung cancer and respiratory diseases locally and aims to diagnose lung cancer at an earlier stage by proactive approach to those at high risk of lung cancer. The objective of this study is to evaluate the programme in terms of its likely effect on mortality from lung cancer and its delivery to deprived populations. METHODS: Persons aged 58-75 years, with a history of smoking or a diagnosis of chronic obstructive pulmonary disease (COPD)2 according to general practice records were invited for lung health check in a community health hub setting. A detailed risk assessment and spirometry were performed in eligible patients. Those with a 5% or greater five-year risk of lung cancer were referred for a low dose CT3 scan. RESULTS: A total of 4 566 subjects attended the appointment for risk assessment and 3 591 (79%) consented to data sharing. More than 80% of the patients were in the most deprived quintile of the index of multiple deprivation. Of those attending, 63% underwent spirometry and 43% were recommended for a CT scan. A total of 25 cancers were diagnosed, of which 16 (64%) were stage I. Comparison with the national stage distribution implied that the programme was reducing lung cancer mortality by 22%. CONCLUSIONS: Community based proactive approaches to early diagnosis of lung cancer in health deprived regions are likely to be effective in early detection of lung cancer.

11.
J Biol Chem ; 294(32): 11969-11979, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31262727

RESUMO

Fast photochemical oxidation of proteins (FPOP) is a MS-based method that has proved useful in studies of protein structures, interactions, conformations, and protein folding. The success of this method relies on the irreversible labeling of solvent-exposed amino acid side chains by hydroxyl radicals. FPOP generates these radicals through laser-induced photolysis of hydrogen peroxide. The data obtained provide residue-level resolution of protein structures and interactions on the microsecond timescale, enabling investigations of fast processes such as protein folding and weak protein-protein interactions. An extensive comparison between FPOP and other footprinting techniques gives insight on their complementarity as well as the robustness of FPOP to provide unique structural information once unattainable. The versatility of this method is evidenced by both the heterogeneity of samples that can be analyzed by FPOP and the myriad of applications for which the method has been successfully used: from proteins of varying size to intact cells. This review discusses the wide applications of this technique and highlights its high potential. Applications including, but not limited to, protein folding, membrane proteins, structure elucidation, and epitope mapping are showcased. Furthermore, the use of FPOP has been extended to probing proteins in cells and in vivo These promising developments are also presented herein.

12.
J Interpers Violence ; : 886260519853393, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31179801

RESUMO

There is a current public health emphasis on finding strategies for reducing the risks associated with children's gun violence exposure. This article examines the impact of seeing and hearing gun violence on youth of different ages and living in urban and nonurban areas. Participants were 630 youth, aged 2 to 17. Youth, ages 10 to 17, completed a self-report survey, and caregivers of young children, ages 2 to 9, completed the survey as a proxy for that child. Participants resided in Boston, MA; Philadelphia, PA; and rural areas of eastern TN. Participants were recruited through a variety of techniques including pediatric clinics, housing authorities, youth-serving agencies, festivals, word of mouth, and local e-mail lists for classified advertisements. Data were collected between October 2017 and April 2018 and analyzed in 2019. In total, 41% of youth in this study reported ever seeing or hearing gun violence; 32% had such an experience in the past year. Among exposed youth, 50% took protective action to keep themselves safe, and 58% reported being very or extremely afraid, sad, or upset as a result of the indirect gun violence. More youth living in urban compared with nonurban areas took some protective action. Females and younger children had increased odds of experiencing high fear as a result of the violence. Current gun violence prevention has typically targeted adolescents; however, current findings suggest the need to focus on younger children as well, including the distress resulting from indirect exposure to gun violence.

13.
Water Res ; 161: 335-340, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31212239

RESUMO

Our objective was to determine whether ß-lactamase genes are carried within bacteriophage capsids, as a first step towards exploring the possible role of bacteriophages as vehicles for dispersal of antimicrobial resistance genes through an agricultural region of Washington State. Water samples (n = 178) from municipal wastewater treatment plants, river and irrigation canals were collected over a period of eight months. The occurrence of four ß-lactam resistance gene groups (blaTEM, blaCTX-M, blaPSE and blaCMY-2) and three carbapenem resistance genes (blaKPC, blaOXA-48-like, and blaNDM) in bacterial and phage fractions of water samples was evaluated by PCR. All of the seven targeted resistance genes were detected both in wastewater and river water samples. Relatively high proportions of samples (7.3%-64.9%) positive for resistance genes were found in bacteriophage fractions of water samples compared to the bacterial fractions (5.4%-36.8%). blaOXA-48-like (57.3%) and blaTEM (64.0%) were the most prevalent antimicrobial resistance genes detected at all the sampling points. Resistance genes are commonly present in treated wastewater flowing through municipal and agricultural environments, indicating a plausible role for this water in the dissemination of antimicrobial resistance traits, including blaCTX-M.

14.
Cell Host Microbe ; 26(1): 123-134.e8, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31231046

RESUMO

Despite being a frequent cause of severe diarrheal disease in infants and an opportunistic infection in immunocompromised patients, Cryptosporidium research has lagged due to a lack of facile experimental methods. Here, we describe a platform for complete life cycle development and long-term growth of C. parvum in vitro using "air-liquid interface" (ALI) cultures derived from intestinal epithelial stem cells. Transcriptomic profiling revealed that differentiating epithelial cells grown under ALI conditions undergo profound changes in metabolism and development that enable completion of the parasite life cycle in vitro. ALI cultures support parasite expansion > 100-fold and generate viable oocysts that are transmissible in vitro and to mice, causing infection and animal death. Transgenic parasite lines created using CRISPR/Cas9 were used to complete a genetic cross in vitro, demonstrating Mendelian segregation of chromosomes during meiosis. ALI culture provides an accessible model that will enable innovative studies into Cryptosporidium biology and host interactions.

15.
Nat Commun ; 10(1): 2678, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31213601

RESUMO

Myeloid cells contribute to tumor progression, but how the constellation of receptors they express regulates their functions within the tumor microenvironment (TME) is unclear. We demonstrate that Fcmr (Toso), the putative receptor for soluble IgM, modulates myeloid cell responses to cancer. In a syngeneic melanoma model, Fcmr ablation in myeloid cells suppressed tumor growth and extended mouse survival. Fcmr deficiency increased myeloid cell population density in this malignancy and enhanced anti-tumor immunity. Single-cell RNA sequencing of Fcmr-deficient tumor-associated mononuclear phagocytes revealed a unique subset with enhanced antigen processing/presenting properties. Conversely, Fcmr activity negatively regulated the activation and migratory capacity of myeloid cells in vivo, and T cell activation by bone marrow-derived dendritic cells in vitro. Therapeutic targeting of Fcmr during oncogenesis decreased tumor growth when used as a single agent or in combination with anti-PD-1. Thus, Fcmr regulates myeloid cell activation within the TME and may be a potential therapeutic target.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteínas de Transporte/metabolismo , Melanoma Experimental/imunologia , Proteínas de Membrana/metabolismo , Monócitos/imunologia , Neoplasias Cutâneas/imunologia , Animais , Apresentação do Antígeno/efeitos dos fármacos , Apresentação do Antígeno/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Linhagem Celular Tumoral/transplante , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Feminino , Ativação Linfocitária/imunologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/mortalidade , Melanoma Experimental/patologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Linfócitos T/imunologia , Microambiente Tumoral/imunologia
16.
Psychoneuroendocrinology ; 106: 284-292, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31039525

RESUMO

Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS) summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS) for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD) cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD) cases (68.6% female, mean age: 46.9 years old) and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation.

17.
Biol Psychiatry ; 85(12): 1065-1073, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31003785

RESUMO

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, with a high prevalence and a presumed high heterogeneity. Copy number variants (CNVs) could contribute to the heritable component of risk, but the two previous genome-wide association studies of rare CNVs did not report significant findings. METHODS: In this meta-analysis of four cohorts (5780 patients and 6626 control subjects), we analyzed the association of MDD to 1) genome-wide burden of rare deletions and duplications, partitioned by length (<100 kb or >100 kb) and other characteristics, and 2) individual rare exonic CNVs and CNV regions. RESULTS: Patients with MDD carried significantly more short deletions than control subjects (p = .0059) but not long deletions or short or long duplications. The confidence interval for long deletions overlapped with that for short deletions, but long deletions were 70% less frequent genome-wide, reducing the power to detect increased burden. The increased burden of short deletions was primarily in intergenic regions. Short deletions in cases were also modestly enriched for high-confidence enhancer regions. No individual CNV achieved thresholds for suggestive or significant association after genome-wide correction. p values < .01 were observed for 15q11.2 duplications (TUBGCP5, CYFIP1, NIPA1, and NIPA2), deletions in or near PRKN or MSR1, and exonic duplications of ATG5. CONCLUSIONS: The increased burden of short deletions in patients with MDD suggests that rare CNVs increase the risk of MDD by disrupting regulatory regions. Results for longer deletions were less clear, but no large effects were observed for long multigenic CNVs (as seen in schizophrenia and autism). Further studies with larger sample sizes are warranted.

18.
Bipolar Disord ; 21(6): 547-555, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31004555

RESUMO

OBJECTIVES: It has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether presence of AD was associated with episodic and lifetime clinical features in a large well-characterized bipolar disorder sample. METHOD: The prevalence of agitation, based on semi-structured interview and medical case-notes, in the most severe depressive episode was estimated in 2925 individuals with DSM-IV bipolar disorder recruited into the UK Bipolar Disorder Research Network. Predictors of agitation were ascertained using symptoms within the same episode and lifetime clinical features using multivariate models. RESULTS: 32.3% (n = 946) experienced agitation during the worst depressive episode. Within the same episode, significant predictors of presence of agitation were: insomnia (OR 2.119, P < 0.001), poor concentration (OR 1.966, P = 0.027), decreased libido (OR 1.960, P < 0.001), suicidal ideation (OR 1.861, P < 0.001), slowed activity (OR 1.504, P = 0.001), and poor appetite (OR 1.297, P = 0.029). Over the lifetime illness course, co-morbid panic disorder (OR 2.000, P < 0.001), suicide attempt (OR 1.399, P = 0.007), and dysphoric mania (OR 1.354, P = 0.017) were significantly associated with AD. CONCLUSIONS: Agitation accompanied bipolar depression in at least one-third of cases in our sample and was associated with concurrent somatic depressive symptoms, which are also common features of mixed manic states. Furthermore, AD in our sample was associated with lifetime experience of mixed mania, in addition to severe lifetime illness course including comorbid panic disorder and suicidal behavior. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression.

19.
Anal Chem ; 91(10): 6577-6584, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31025855

RESUMO

Protein footprinting coupled with mass spectrometry is being increasingly used for the study of protein interactions and conformations. The hydroxyl radical footprinting method, fast photochemical oxidation of proteins (FPOP), utilizes hydroxyl radicals to oxidatively modify solvent accessible amino acids. Here, we describe the further development of FPOP for protein structural analysis in vivo (IV-FPOP) with Caenorhabditis elegans. C. elegans, part of the nematode family, are used as model systems for many human diseases. The ability to perform structural studies in these worms would provide insight into the role of structure in disease pathogenesis. Many parameters were optimized for labeling within the worms including the microfluidic flow system and hydrogen peroxide concentration. IV-FPOP was able to modify several hundred proteins in various organs within the worms. The method successfully probed solvent accessibility similarily to in vitro FPOP, demonstrating its potential for use as a structural technique in a multiorgan system. The coupling of the method with mass spectrometry allows for amino-acid-residue-level structural information, a higher resolution than currently available in vivo methods.

20.
Ultrasound Q ; 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30921101

RESUMO

Endometriosis is a common disease of reproductive-age women that is often first encountered with ultrasound. Therefore, familiarity with the variety of manifestations of endometriosis is important for appropriate diagnosis and management. The aim of this article is to review the spectrum of appearance of pelvic endometriosis and to discuss potential mimics on ultrasound. Given that magnetic resonance imaging is an important problem-solving tool in female pelvic imaging, magnetic resonance imaging correlation is also provided.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA