A comprehensive review of reported heritable noggin‐associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG ‐related‐symphalangism spectrum disorder ( NOG ‐SSD)

The NOG gene encodes noggin, a secreted polypeptide that is important for regulating multiple signaling pathways during human development, particularly in cartilage and bone. The hallmark of NOG ‐related syndromes is proximal symphalangism, defined by abnormal fusion of the proximal interphalangeal joints of the hands and feet. Many additional features secondary to NOG mutations are commonly but inconsistently observed, including a characteristic facies with a hemicylindrical nose, congenital conductive hearing loss due to stapes fixation, and hyperopia. The variable clinical presentations led to the designation of five different autosomal dominant syndromes, all subsequently found to have resulted from NOG mutations. These include (1) proximal symphalangism; (2) multiple synostoses syndrome 1; (3) stapes ankylosis with broad thumbs and toes; (4) tarsal‐carpal coalition syndrome; and (5) brachydactyly type B2. Herein, we review the phenotypic features associated with mutations in the NOG gene, demonstrating the overlapping characteristics of these syndromes. Due to the variable phenotypic spectrum within families and among families with the same mutation, we propose a unifying term, NOG ‐related symphalangism spectrum disorder ( NOG ‐SSD), to aid in the clinical recognition and evaluation of all affected individuals with these phenotypes. These NOG gene variants are available in a new locus‐specific database ( https://NOG.lovd.nl ).Hum Mutat 32:1–10, 2011. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87082/1/21515_ftp.pd

Complications after intestinal resection in Crohn's disease: laparoscopic versus conventional approach

AbstractBackgroundsignificant advances in medical therapy for Crohn's disease (CD) occurred in the last 12 years, mainly due to the introduction of anti-TNF therapy. Laparoscopic colorectal surgery represented the most important advance on surgical treatment in the management of CD, as it also had developed in the treatment of other conditions. There is a tendency for lower complication rates after laparoscopic bowel resections as compared to open surgery. The aim of this study was to analyze and compare the complication rates after bowel resections for CD between the two approaches in a Brazilian case series.Methodsthis was a retrospective longitudinal study, including CD patients submitted to bowel resections from a single Brazilian Inflammatory Bowel Diseases (IBD) referral center, treated between January 2008 and June 2012 with laparoscopic approach (LA) or conventional approach (CA).Variables analyzedage at surgery, gender, Montreal classification, smoking, concomitant medication, type of surgery, surgical approach, presence and type of complication up to 30 days after the procedures. Readmission and reoperation rates, as well as mortality, were also analyzed. Patients were allocated in two groups regarding the type of procedure (LA or CA), and complication rates and characteristics were compared. Statistical analysis was performed with Mann-Whitney test (quantitative variables) and chi-square test (qualitative variables), with p < 0.05 considered significant.Resultsa total of 46 patients (25 men) were included (16 submitted to LA), with mean age of 38.1 (± 12.7) years. The groups were considered homogeneous according to age, gender, CD location, perianal disease and concomitant medications. There were more patients with fistulizing CD on the CA group (p = 0.029). The most common procedure performed was ileocolic resection on both groups (56.7% of the CA and 75% of the LA patients – p = 0.566). Overall, total complications (surgical and medical, including minor and major issues) oc- curred in 60% (18/30) of the CA group and 12.5% (2/16) of the LA group (p = 0.002). Wound in- fection was the most frequent complication (10/30 on CA and 1/16 on the LA groups). There were 3 deaths in the CA group. Specific analysis of each complication did not demonstrate any difference between the groups regarding abdominal sepsis, urinary tract infections, pneumonia, readmission, reoperations and deaths (p = 0.074).Conclusionsthere was a higher complication rate in patients operated with CA as compared to LA. This was probably due to patient selection for the laparoscopic approach, with severe cases, mostly due to fistulizing abdominal CD, being operated mainly by open surgery. LA tends to be the recommended approach in most cases of non-complicated CD

Enhancing technology acceptance: The role of the subsurface contaminants focus area external integration team

The US DOE is developing and deploying innovative technologies for cleaning up its contaminated facilities using a market-oriented approach. This report describes the activities of the Subsurface Contaminant Focus Area`s (SCFA) External Integration Team (EIT) in supporting DOE`s technology development program. The SCFA program for technology development is market-oriented, driven by the needs of end users. The purpose of EIT is to understand the technology needs of the DOE sites and identify technology acceptance criteria from users and other stakeholders to enhance deployment of innovative technologies. Stakeholders include regulators, technology users, Native Americans, and environmental and other interest groups. The success of this national program requires close coordination and communication among technology developers and stakeholders to work through all of the various phases of planning and implementation. Staff involved must be willing to commit significant amounts of time to extended discussions with the various stakeholders

Hospital-onset clostridium difficile infection rates in persons with cancer or Hematopoietic stem cell transplant: A C3IC network report

A multicenter survey of 11 cancer centers was performed to determine the rate of hospital-onset Clostridium difficile infection (HO-CDI) and surveillance practices. Pooled rates of HO-CDI in patients with cancer were twice the rates reported for all US patients (15.8 vs 7.4 per 10,000 patient-days). Rates were elevated regardless of diagnostic test used

Viral susceptibility across host species is largely independent of dietary protein to carbohydrate ratios

This is the final version. Available on open access from Wiley via the DOI in this record Data Repository: mcmcglmm_data_diet.csv. figshare. Dataset. https://doi.org/10.6084/m9.figshare.13079465.v1The likelihood of a successful host shift of a parasite to a novel host species can be influenced by environmental factors that can act on both the host and parasite. Changes in nutritional resource availability have been shown to alter pathogen susceptibility and the outcome of infection in a range of systems. Here we examined how dietary protein to carbohydrate altered susceptibility in a large cross infection experiment. We infected 27 species of Drosophilidae with an RNA virus on three food types of differing protein to carbohydrate ratios. We then measured how viral load and mortality across species was affected by changes in diet. We found that changes in the protein:carbohydrate in the diet did not alter the outcomes of infection, with strong positive inter‐species correlations in both viral load and mortality across diets, suggesting no species by diet interaction. Mortality and viral load were strongly positively correlated, and this association was consistent across diets. This suggests changes in diet may give consistent outcomes across host species, and may not be universally important in determining host susceptibility to pathogens.Wellcome TrustRoyal Societ

A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings

Background: Low frequency sensorineural hearing loss (LFSNHL) is an uncommon clinical finding. Mutations within three different identified genes (DIAPH1, MYO7A, and WFS1) are known to cause LFSNHL. The majority of hereditary LFSNHL is associated with heterozygous mutations in the WFS1 gene (wolframin protein). The goal of this study was to use genetic analysis to determine if a small American family's hereditary LFSNHL is linked to a mutation in the WFS1 gene and to use VEMP and EcochG testing to further characterize the family's audiovestibular phenotype. Methods: The clinical phenotype of the American family was characterized by audiologic testing, vestibular evoked myogenic potentials (VEMP), and electrocochleography (EcochG) evaluation. Genetic characterization was performed by microsatellite analysis and direct sequencing of WFS1 for mutation detection. Results: Sequence analysis of the WFS1 gene revealed a novel heterozygous mutation at c.2054G>C predicting a p.R685P amino acid substitution in wolframin. The c.2054G>C mutation segregates faithfully with hearing loss in the family and is absent in 230 control chromosomes. The p.R685 residue is located within the hydrophilic C-terminus of wolframin and is conserved across species. The VEMP and EcochG findings were normal in individuals segregating the WFS1 c.2054G>C mutation. Conclusion: We discovered a novel heterozygous missense mutation in exon 8 of WFS1 predicting a p.R685P amino acid substitution that is likely to underlie the LFSNHL phenotype in the American family. For the first time, we describe VEMP and EcochG findings for individuals segregating a heterozygous WFS1 mutation.NIH grants DC04945 (V.A.S), DC006901 (V.A.S.) and P30 DC04661 (V.M. Bloedel Core)

Women, but not men, have prolonged QT interval if depressed after an acute coronary syndrome

Aims Depression is a mortality risk marker for acute coronary syndrome (ACS) patients. We hypothesized that the QT interval, a predictor for risk of sudden cardiac death, was related to depressive symptoms in ACS. Methods and results We performed an analysis of admission electrocardiograms from hospitalized patients with unstable angina or non-ST elevation myocardial infarction from two prospective observational studies of depression in ACS. Depressive symptoms were assessed with the Beck Depression Inventory (BDI), and depression was defined as BDI score ≥10, compared with <5. Patients with QRS duration ≥120 ms and/or who were prescribed antidepressants were excluded. QT intervals were adjusted for heart rate by two methods. Our analyses included 243 men (40.0% with BDI ≥10) and 139 women (62.0% with BDI ≥ 10). Among women, average QT corrected by Fridericia's method (QTcF) was 435.4 ± 26.6 ms in the depressed group, vs. 408.6 ± 24.3 ms in the non-depressed group (P< 0.01). However, among men, average QTcF was not significantly different between the depressed and non-depressed groups (415.4 ± 23.6 vs. 412.0 ± 25.8 ms, P= 0.29). In multivariable analyses that included hypertension, diabetes, ACS type, left ventricular ejection fraction <0.40, and use of QT-prolonging medication, there was a statistically significant interaction between depressive symptoms and gender (P< 0.001). Conclusions In this ACS sample, prolongation of the QT interval was associated with depressive symptoms in women, but not in men. Further investigation of the mechanism of the relationship between depression and abnormal cardiac repolarization, particularly in women, is warranted to develop treatment strategies

Rationale, design and methodology of a double-blind, randomized, placebo-controlled study of escitalopram in prevention of Depression in Acute Coronary Syndrome (DECARD)

<p>Abstract</p> <p>Background</p> <p>The prevalence of depression in patients with acute coronary syndrome, i.e. myocardial infarction and unstable angina, is higher than in the general population. The prevalence of anxiety is higher as well. Both depression and anxiety are associated with poor cardiac outcomes and higher mortality. Comorbid depression in patients with acute coronary syndrome often goes undiagnosed, and it is therefore a challenging task to prevent this risk factor. The study of DEpression in Coronary ARtery Disease (DECARD) is designed to examine if it is possible to prevent depression in patients with acute coronary syndrome.</p> <p>Methods</p> <p>Two hundred forty non-depressed patients with acute coronary syndrome are randomized to treatment with either escitalopram or placebo for 1 year. Psychiatric and cardiac assessment of patients is performed to evaluate the possibility of preventing depression. Diagnosis of depression and Hamilton Depression Scale are the primary outcome measures.</p> <p>Discussion</p> <p>This is the first study of prevention of depression in patients after acute coronary syndrome with a selective serotonin reuptake inhibitor.</p> <p>Trial Registration</p> <p><url>http://www.ClinicalTrials.gov.</url> Identifier: NCT00140257</p

Angiographically borderline left main coronary artery lesions: correlation of transthoracic doppler echocardiography and intravascular ultrasound: a pilot study

<p>Abstract</p> <p>Background</p> <p>the clinical decision making could be difficult in patients with borderline lesions (visually assessed stenosis severity of 30 to 50%) of the left main coronary artery (LM). The aim of the study was to evaluate the relationship between transthoracic Doppler (TTDE) peak diastolic flow velocity (PDV) and intravascular ultrasound (IVUS) measurements in the assessment of angiographically borderline LM lesions.</p> <p>Methods</p> <p>27 patients (mean age 64 ± 8 years, 21 males) with borderline LM stenosis referred for IVUS examination were included in the study. We performed standard IVUS with minimal lumen area (MLA) and plaque burden (PB) measurement and routine quantitative coronary angiography (QCA) with diameter stenosis (%DS) and area stenosis (%AS) assessment in all. During TTDE, resting PDV was measured in the LM.</p> <p>Results</p> <p>interpretable Doppler signal could be obtained in 24 patients (88% feasibility); therefore these patients entered the final analysis. MLA was 7.1 ± 2.7 mm². TTDE measured PDV correlated significantly with IVUS-derived MLA (r = -0.46, p < 0.05) and plaque burden (r = 0.51, p < 0.05). Using a velocity cut-off of 112 cm/sec TTDE showed a 92% sensitivity and 62% specificity to identify IVUS-significant (MLA < 6 mm²) LM stenosis.</p> <p>Conclusion</p> <p>In angiographically borderline LM disease, resting PDV from transthoracic echocardiography is increased in presence of increased plaque burden by IVUS. TTDE evaluation might be a useful adjunct to other invasive and non-invasive methods in the assessment of borderline LM lesions. Further, large scale studies are needed to establish the exact cut-off value of PDV for routine clinical application.</p

Examining the Link Between Domestic Violence Victimization and Loneliness in a Dutch Community Sample: A Comparison Between Victims and Nonvictims by Type D Personality

The current study investigated whether differences in loneliness scores between individuals with a distressed personality type (type D personality) and subjects without such a personality varied by domestic violence victimization. Participants (N = 625) were recruited by random sampling from the Municipal Basic Administration of the Dutch city of ‘s-Hertogenbosch and were invited to fill out a set of questionnaires on health status. For this study, only ratings for domestic violence victimization, type D personality, feelings of loneliness, and demographics were used. Statistical analyses yielded main effects on loneliness for both type D personality and history of domestic violence victimization. Above and beyond these main effects, their interaction was significantly associated with loneliness as well. However, this result seemed to apply to emotional loneliness in particular. Findings were discussed in light of previous research and study limitations