Occult Intraperitoneal Bladder Injury after a Tension-Free Vaginal Tape Procedure

Occult bladder injury may sometimes go unrecognized during tension-free vaginal tape (TVT) procedures. We report a case of occult intraperitoneal bladder injury that occurred during a TVT procedure. There was no sign of bladder perforation on the initial cystoscopy, which was performed just after the insertion of the trocar. Signs of general peritonitis appeared after the patient started to void the next day. A postoperative cystogram and cystoscopy showed an intraperitoneal bladder injury and a pinhead-sized ulcerative lesion in the right lateral wall of the bladder. We suspect that at the time of initial cystoscopy, the trocar passed through the submucosal area without violating the bladder mucosa. The occult bladder injury may have been caused after the initial cystoscopy by advancing the rough edge of the prolene tape during the extraction of the trocar. This report is the first description of such an occult bladder injury during a TVT procedure

Resolution of Pregabalin and Mirtazapine Associated Restless Legs Syndrome by Bupropion in a Patient with Major Depressive Disorder

Bupropion is a selective norepinephrine and dopamine reuptake inhibitor with no serotonergic activity, and is therefore an antidepressant with unique pharmacological properties. There are some reports that selective serotonin reuptake inhibitors (SSRIs) or mirtazapine can induce adverse effects including restless legs syndrome (RLS) and that bupropion can reverse these adverse effects. Here, we report about a patient with a major depressive disorder who exhibited RLS after being treated with pregabalin and mirtazapine. This adverse effect disappeared after having switched from mirtazapine to bupropion. Bupropion inhibits the reuptake of dopamine and increases dopamine neurotransmission in both the nucleus accumbens and the prefrontal cortex. This pharmacological profile can be effective in patients with RLS related to dopamine hypoactivity. However, the limitations of this single case report mean that further investigations with larger samples are needed

Differential Effects of Influenza Virus NA, HA Head, and HA Stalk Antibodies on Peripheral Blood Leukocyte Gene Expression during Human Infection.

In this study, we examined the relationships between anti-influenza virus serum antibody titers, clinical disease, and peripheral blood leukocyte (PBL) global gene expression during presymptomatic, acute, and convalescent illness in 83 participants infected with 2009 pandemic H1N1 virus in a human influenza challenge model. Using traditional statistical and logistic regression modeling approaches, profiles of differentially expressed genes that correlated with active viral shedding, predicted length of viral shedding, and predicted illness severity were identified. These analyses further demonstrated that challenge participants fell into three peripheral blood leukocyte gene expression phenotypes that significantly correlated with different clinical outcomes and prechallenge serum titers of antibodies specific for the viral neuraminidase, hemagglutinin head, and hemagglutinin stalk. Higher prechallenge serum antibody titers were inversely correlated with leukocyte responsiveness in participants with active disease and could mask expression of peripheral blood markers of clinical disease in some participants, including viral shedding and symptom severity. Consequently, preexisting anti-influenza antibodies may modulate PBL gene expression, and this must be taken into consideration in the development and interpretation of peripheral blood diagnostic and prognostic assays of influenza infection

COPD exacerbations in general practice: variability in oral prednisolone courses

<p>Abstract</p> <p>Background</p> <p>The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable side effects, including hyperglycaemias, so differences in prescribing might be relevant. This study examines the differences between GPs in dosage and duration of prednisolone treatment in patients with a COPD exacerbation. It also investigates the number of general practitioners (GPs) who adjust their treatment according to the presence of diabetic co-morbidity.</p> <p>Methods</p> <p>Cross-sectional study among 219 GPs and 25 GPs in training, located in the Northern part of the Netherlands.</p> <p>Results</p> <p>The response rate was 69%. Nearly every GP prescribed a continuous dose of prednisolone 30 mg per day. Among GPs there were substantial differences in treatment duration. GPs prescribed courses of five, seven, ten, or fourteen days. A course of seven days was most common. The duration of treatment depended on exacerbation and disease severity. A course of five days was especially prescribed in case of a less severe exacerbation. In a more severe exacerbation duration of seven to fourteen days was more common. Hardly any GP adjusted treatment to the presence of diabetic co-morbidity.</p> <p>Conclusion</p> <p>Under normal conditions GPs prescribe prednisolone quite uniformly, within the range of the current Dutch guidelines. There is insufficient guidance regarding how to adjust corticosteroid treatment to exacerbation severity, disease severity and the presence of diabetic co-morbidity. Under these circumstances, there is a substantial variation in treatment duration.</p

Control of substrate access to the active site in methane monooxygenase

Methanotrophs consume methane as their major carbon source and have an essential role in the global carbon cycle by limiting escape of this greenhouse gas to the atmosphere. These bacteria oxidize methane to methanol by soluble and particulate methane monooxygenases (MMOs). Soluble MMO contains three protein components, a 251-kilodalton hydroxylase (MMOH), a 38.6-kilodalton reductase (MMOR), and a 15.9-kilodalton regulatory protein (MMOB), required to couple electron consumption with substrate hydroxylation at the catalytic diiron centre of MMOH. Until now, the role of MMOB has remained ambiguous owing to a lack of atomic-level information about the MMOH–MMOB (hereafter termed H–B) complex. Here we remedy this deficiency by providing a crystal structure of H–B, which reveals the manner by which MMOB controls the conformation of residues in MMOH crucial for substrate access to the active site. MMOB docks at the α[subscript 2]β[subscript 2] interface of α[subscript 2]β[subscript 2]γ[subscript 2] MMOH, and triggers simultaneous conformational changes in the α-subunit that modulate oxygen and methane access as well as proton delivery to the diiron centre. Without such careful control by MMOB of these substrate routes to the diiron active site, the enzyme operates as an NADH oxidase rather than a monooxygenase. Biological catalysis involving small substrates is often accomplished in nature by large proteins and protein complexes. The structure presented in this work provides an elegant example of this principle.National Institute of General Medical Sciences (U.S.) (Grant GM 32114

Communications Biophysics

Contains research objectives and summary of research on thirteen research projects split into four section.National Institutes of Health (Grant 1 RO1 NS10737-01)National Institutes of Health (Grant 1 ROI NS10916-01)National Institutes of Health (Grant 5 RO1 NS11000-02)National Institutes of Health (Grant 1 RO1 NS11153-01)Harvard M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare, Grant 23-P-55854National Institutes of Health (Grant 1 RO1 NS11680-01)Norlin Music, Inc.Clarence J. LeBel FundNational Institutes of Health (Grant 1 RO1 NS11080-01A1)National Institutes of Health (Grant 5 TO1 GM01555-08)M.I.T. Health Sciences FundBoston City Hospital Purchase Order 1176-05-21335-C

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas