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Objectives Anal cytology is a modality for anal cancer screening in high-risk women. In this retrospective study, we review risk factors associated with abnormal anal cytology and unsatisfactory anal cytology rates, and correlate findings of cytology with histological results. Methods A retrospective cohort study of anal cytology screening in women at Mayo Clinic in Rochester, Minnesota from 2002 to 2018 was conducted. Results Three hundred fifty-seven women had a total of 592 anal cytologies performed. Three hundred seventeen women had screening anal cytology, whereas 40 women had anal cytology for surveillance given a history of anal intraepithelial neoplasia (AIN) or anal cancer. An unsatisfactory anal cytology result was found in 14.7%. Risk factors, type of follow-up, and correlation with histologic specimens were also reviewed. Histologic finding of AIN 2/3 correlated with abnormal anal cytology 84% of the time in this cohort. Conclusions High-risk women should be screened on a periodic basis for anal cancer. Anal cytology is one possible modality that can be used. Further insight into AIN progression, regression, recurrence, and outcome after treatment will help direct future screening recommendations.

Objective Optimal prescriptions practices of opioids in the post-cesarean period remain controversial. The primary aim of this initiative was to minimize unused prescription narcotic medication, with a goal of ≤4 leftover pills of 5-mg oxycodone at postoperative day (POD) 14 without affecting pain or satisfaction measures. Study Design This was a prospective longitudinal quality improvement (QI) initiative starting in 2017 utilizing the DMAIC methodology. The measurement phase consisted of validated surveys over 3 months, along with chart review to determine current institutional prescription practices and predictors of outpatient opioid use. Resulting recommendations were adopted, and 1 year later, all patients undergoing cesarean were surveyed for 3 months to determine the effectiveness of the intervention. The study was approved by the Department's QI Committee. Results The response rate was 48%, with 50 of 101 patients completing surveys pre-intervention and 52 of 111 post-intervention. Pre-intervention, surplus medication was predicted (p Conclusion This initiative highlights a practical approach to QI utilizing industry techniques in health care. This approach resulted in significant reductions in over-prescription and unused medication, without impacting pain or satisfaction scores. Key Points

Background Given the unprecedented nature of the COVID-19 pandemic, it is important to understand how those with eating disorders (EDs) are affected by the pandemic. Using data from the Understanding America Study (UAS), we examined the association between EDs and mental health and how the relationship changed over time across the months following the institution of virus containment procedures (e.g., social distancing, quarantine). Method The analytic sample consisted of 7137 adults (Mage =50.58 years; SD =16.10) who completed surveys between waves 1–11 of the UAS study. Participants self-reported ED diagnosis (i.e., yes, no, or unsure) and completed self-report measures of psychological distress, perceived stress, and loneliness. Multilevel models were used to compare trajectories of psychological distress, perceived stress, and loneliness among ED groups. Results Individuals with EDs and unsure EDs had higher levels of psychological distress, perceived stress, and loneliness compared to those without EDs. Those unsure about their EDs showed initial decreases in perceived stress and loneliness but started increasing again after some time. Levels of loneliness among those with EDs increased initially but later began to decrease; individuals with EDs showed steady decreases in perceived stress. Limitations Type, severity, and duration of EDs were unspecified in the self-reported measure of EDs, which could differentiate the trajectories of outcomes. Conclusions Intervention is crucial for mitigating mental health problems among those with a history of ED symptoms during COVID-19. Further, results showed that individuals who are unsure about their ED status may be experiencing more fluctuation in mental health across the pandemic.

The coronavirus disease 2019 (COVID-19) pandemic provided our institution a unique opportunity to develop a new procedural curriculum for our fourth-year, emergency medicine-bound medical students. A significant portion of our ED’s fourth-year elective has traditionally been centered in our simulation center, using high-fidelity simulation models to practice important emergency medicine procedures. Due to the pandemic, the simulation center was unavailable for our use, and this new curriculum was created in an effort to fill this gap in procedural education.

Currently-placed protocols for extended culture for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are not uniformly standardized in determining the optimal stage of oocyte maturation for maximizing clinical outcomes. The objective of this systematic review is to elucidate the relationship between extended cumulus-oocyte culture and its effect on the clinical outcomes of IVF/ICSI. We included an electronic search on PubMed Central as well as the Journal of Fertility and Sterility to yield seven studies on extended oocyte culture for IVF/ICSI. Four of the seven investigations illustrate the promising beneficial relationship of extended culture with conditioned or supplemented media to mimic physiological uterine conditions. Three studies did not capture beneficial relationships between extended oocyte culture and clinical outcomes with unconditioned, unsupplemented maturation medium. Improvement in fertilization rates, oocyte development, and live birth rates may be achieved by extended culture with the addition of supplemental biochemicals. The usage of follicular fluid, cumulus cells, and meiotic inhibitors imitates the physiological in vivo conditions, whereas extended oocyte culture imitates in vivo temporal conditions. The conjunction of extended oocyte culture with supplemented metabolites, either added in maturation media manually or secreted by cumulus-oocyte complexes, mimics natural uterine physiological conditions to improve clinical outcomes for patients seeking IVF/ICSI. Key words: Cumulus Cells; Extended Culture; In vitro Fertilization; Intracytoplasmic Sperm Injection; Oocyte

BACKGROUND Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. OBJECTIVES We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. METHODS Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-α concentrations, gut microbiota, and liver TNF-α and fatty acid synthase (Fasn) mRNA concentrations were assessed. RESULTS F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P

Children in Sub-Saharan Africa (SSA) are burdened by significant unmet mental health needs. Despite the successes of numerous school-based interventions for promoting child mental health, most evidence-based interventions (EBIs) are not available in SSA. This study investigated the implementation quality and effectiveness of one component of an EBI from a developed country (United States) to a SSA country (Uganda). The EBI component, Professional Development, was provided by trained Ugandan mental health workers to Ugandan primary school teachers. It included large group experiential training and small group coaching to introduce and support a range of evidence-based practices (EBPs) to create nurturing and predictable classroom experiences. The study was guided by the Consolidated Framework for Implementation Research, the Teacher Training Implementation Model and the RE-AIM evaluation framework. Effectiveness outcomes were studied using a cluster randomized design, in which 10 schools were randomized to intervention and wait-list control conditions. A total of 79 early childhood teachers participated. Teacher knowledge and use of evidence-based practices (EBPs) were assessed at baseline and immediately post-intervention (4–5 months later). A sample of 154 parents was randomly selected to report on child behavior at baseline and post-intervention. Linear mixed effect modeling was applied to examine effectiveness outcomes. Findings support the feasibility of training Ugandan mental health professionals to provide Professional Development for Ugandan teachers. Professional Development was delivered with high levels of fidelity and resulted in improved teacher EBP knowledge and use of EBPs in the classroom, and child social competence.

Background Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma occurring mainly in the anogenital region. Traditional management with wide local excision has shown high recurrence rates, thus Mohs micrographic surgery (MMS) has emerged as a promising treatment option. Objective To compare long-term outcomes after treatment with MMS or excision for primary EMPD. Methods and materials Retrospective cohort review was conducted for 207 patients with EMPD treated at Mayo Clinic in Rochester, MN, between 1961 and 2012. Results Of the 25 patients treated with MMS, 19 primary tumors were included for outcome analysis, with an estimated 5-year recurrence-free survival rate of 91% (95% confidence interval [CI], 75-100) using Kaplan-Meier curve analysis. Of 158 patients treated with local excision, 124 were included for the analysis, with an estimated 5-year recurrence-free survival rate of 66% (95% CI, 56-78). The hazard ratio (HR) for association of treatment was 0.4 (95% CI, 0.10-1.65; p = .20). Estimated 5-year overall survival rates were 79% for MMS (95% CI, 61-100) and 68% for excision (95% CI, 59-78) (HR, 1.39 [95% CI, 0.69-2.82]; p = .36). Conclusion Although treatment of primary EMPD with MMS versus excision did not show statistical difference, MMS demonstrated favorable long-term outcomes and was associated with a higher recurrence-free survival rate.

Aneuploidy—or an unbalanced karyotype in which whole chromosomes are gained or lost—causes reduced fitness at both the cellular and organismal levels but is also a hallmark of human cancers. Aneuploidy causes a variety of cellular stresses, including genomic instability, proteotoxic and oxidative stresses, and impaired protein trafficking. The deubiquitinase Ubp3, which was identified by a genome-wide screen for gene deletions that impair the fitness of aneuploid yeast, is a key regulator of aneuploid cell homeostasis. We show that deletion of UBP3 exacerbates both karyotype-specific phenotypes and global stresses of aneuploid cells, including oxidative and proteotoxic stress. Indeed, Ubp3 is essential for proper proteasome function in euploid cells, and deletion of this deubiquitinase leads to further proteasome-mediated proteotoxicity in aneuploid yeast. Notably, the importance of UBP3 in aneuploid cells is conserved. Depletion of the human homolog of UBP3, USP10, is detrimental to the fitness of human cells upon chromosome missegregation, and this fitness defect is accompanied by autophagy inhibition. We thus used a genome-wide screen in yeast to identify a guardian of aneuploid cell fitness conserved across species. We propose that interfering with Ubp3/USP10 function could be a productive avenue in the development of novel cancer therapeutics.

The most common methods of sterilization during cesarean delivery rely on excision of a mid-segment of the fallopian tube. Contemporary data suggest ovarian cancers may originate in the fimbriae of the fallopian tube; therefore, a strategy of prophylactic salpingectomy (SL) has been adopted during gynecologic surgery. The purpose of this study was to evaluate the safety of SL compared to traditional mid-segment excision at time of cesarean and after vaginal delivery through change in perioperative hemoglobin (Hgb).We retrospectively evaluated patients undergoing sterilization concurrent with cesarean delivery or in the post-vaginal delivery period between 1 January 2015 and 31 December 2017 in the Mayo Clinic Health System; a community-based practice. In order to test for non-inferiority, 30 patients in each arm (tubal ligation (TL) and SL) were required to detect a pre- and post-operative Hgb difference of 0.5 mg/dL between groups with a power of 80%. Exclusion criteria included: age 18 years, BMI50 kg/mOne hundred fifty-two patients met inclusion criteria. There was no evidence of inferiority in either the post-vaginal delivery or the cesarean groups with a mean difference in pre- and post-op Hgb of 0.18 mg/dL (This study provides evidence that the practice of salpingectomy at the time of cesarean and post-vaginal delivery may be safe and should form the basis of prospective trials.

OBJECTIVES: Epidemiological studies have shown that consumption of fruits and vegetables (F&V) is inversely associated with incidence of cardiovascular disease (CVD). However, the evidence for causality and underlying mechanisms is lacking. Our objective was to determine if increased consumption of F&V could prevent atherosclerosis and its underlying mechanisms. METHODS: A unique blend of the most commonly consumed 24 F&V was freeze-dried into a powder and mixed into diets. Thirty six 4-week old male LDL receptor knockout mice were randomly assigned to one of 3 diet groups (12/group): low fat (LF, 10 kcal% fat), high-fat (27 kcal% fat) with 0% F&V (HF), and HF plus 15% F&V diet (HF + FV, equivalent to 8–9 servings for humans). After 20 weeks, mice were euthanized and blood, aorta, and liver tissue were collected. Aortic atherosclerotic lesion, hepatic steatosis, plasma lipid profile and pro-inflammatory cytokine levels were measured. RESULTS: No significant differences were found in body weight among the 3 groups. Mice fed HF diet had larger aortic atherosclerotic lesion and hepatic steatosis area than mice fed LF diet by 6.5 and 1.9 fold, respectively (p

Author(s): dela Cruz, Jonathan; Fulks, Tyler; Baker, Mark; Kegg, Jason; Austin, Richard; Jain, Jimmy; Boehler, Michael; Kim, Sharon; Jaeger, Cassie

BACKGROUND Commonly consumed mushrooms, portobello (PBM) and shiitake (SHM), are abundant in nutrients, soluble dietary fibers, and bioactive compounds that have been implicated as beneficial in reducing inflammation, improving lipid profiles, and ameliorating heart disease and atherosclerosis, an inflammatory disease of the arteries. OBJECTIVE The aim of this study was to determine effects of PBM and SHM in preventing atherosclerosis and associated inflammation in an animal model. METHODS Four-week-old Ldlr-/- male mice were divided into 5 dietary groups for 16 wk: a low-fat control (LF-C, 11 kcal% fat), high-fat control (HF-C, 18.9 kcal% fat), HF + 10% (wt:wt) PBM (HF-PBM, 19.5 kcal% fat) or SHM (HF-SHM, 19.7 kcal% fat) powder, and HF + mushroom control mix (MIX-C, 19.6 kcal% fat), a diet best matched to the average macronutrient content of both mushrooms. Body composition was measured using MRI. Aortic tricuspid valves and aortas were collected and stained to quantify plaque formation. Adhesion molecule expression was quantified by immunohistochemistry. Plasma lipid and cytokine concentrations were measured. RESULTS We found that mice fed a HF-SHM diet had ∼86% smaller aortic lesion area than mice in both HF-C (P

The authors evaluated an unfolding case-based approach to a practicum in counseling course infusing crisis, trauma, and disaster preparation for changes in students’ crisis self-efficacy across a semester. The course, informed by constructivist-developmental pedagogy and centered on the unfolding case, resulted in significant increases in students’ crisis self-efficacy.

To investigate whether implementing a bundle, defined as a set of evidence-based practices performed collectively, can reduce 30-day surgical site infections.Baseline surgical site infection rates were determined retrospectively for cases of open uterine cancer, ovarian cancer without bowel resection, and ovarian cancer with bowel resection between January 1, 2010, and December 31, 2012, at an academic center. A perioperative bundle was prospectively implemented during the intervention period (August 1, 2013, to September 30, 2014). Prior established elements were: patient education, 4% chlorhexidine gluconate shower before surgery, antibiotic administration, 2% chlorhexidine gluconate and 70% isopropyl alcohol coverage of incisional area, and cefazolin redosing 3-4 hours after incision. New elements initiated were: sterile closing tray and staff glove change for fascia and skin closure, dressing removal at 24-48 hours, dismissal with 4% chlorhexidine gluconate, and follow-up nursing phone call. Surgical site infection rates were examined using control charts, compared between periods using χ or Fisher exact test, and validated against the American College of Surgeons National Surgical Quality Improvement Program decile ranking.The overall 30-day surgical site infection rate was 38 of 635 (6.0%) among all cases in the preintervention period, with 11 superficial (1.7%), two deep (0.3%), and 25 organ or space infections (3.9%). In the intervention period, the overall rate was 2 of 190 (1.1%), with two organ or space infections (1.1%). Overall, the relative risk reduction in surgical site infection was 82.4% (P=.01). The surgical site infection relative risk reduction was 77.6% among ovarian cancer with bowel resection, 79.3% among ovarian cancer without bowel resection, and 100% among uterine cancer. The American College of Surgeons National Surgical Quality Improvement Program decile ranking improved from the 10th decile to first decile; risk-adjusted odds ratio for surgical site infection decreased from 1.6 (95% confidence interval 1.0-2.6) to 0.6 (0.3-1.1).Implementation of an evidence-based surgical site infection reduction bundle was associated with substantial reductions in surgical site infection in high-risk cancer procedures.

This paper examines the degree to which structural family therapy has adapted effectively to client families and professional demands of the twenty-first century. A review of the current professional literature was conducted to assess the structural model’s continued clinical relevance, how the model has changed in adapting to contemporary social and professional contexts, and whether or not the integrity of the model’s core proposition has been eroded or confounded as a result of adaptive changes.

Objectives Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5-year period. Methods This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30-day mortality. Results A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100-300 IU/L), moderate (300-1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37-10,006) IU/L and aspartate aminotransferase was 253 (84-12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease. Conclusions Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure.

Background Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur’s bioavailability and efficacy, may be candidate agents for controlling body fat, metabolism and low grade inflammation. Methods 47 eight-week-old male C57BL/6 mice were fed a high fat diet (HFD) for 23 weeks to induce obesity. Then, mice were divided into 5 groups. Group 1 continued on HFD ad libitum. The other 4 groups underwent CR (reduced 10% HFD intake for 10 weeks, 20% for 20 weeks) with Cur, Pip, Cur + Pip or none of these. Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-γ, interleukin (IL)-10, IL-12 p70, IL-1β, IL-6 and KC/GRO), plasma Cur metabolites and liver telomere length were measured. Results Compared to the other groups, obese mice who underwent CR and received Cur + Pip in their diet lost more fat and had significantly lower IL-1β and KC/GRO. Tandem mass spectrometry analysis of plasma from obese mice under CR showed no difference in Cur metabolite levels between groups supplemented with Cur alone or combined with Pip. However, plasma IL-1β levels were inversely correlated with curcumin glucuronide. Minor modulation of telomere length were observed. Conclusions It is plausible that supplementing the high fat diet of CR mice with Cur + Pip may increase loss of body fat and suppresses HFD induced inflammation. Combination of Cur and Pip has potential to enhance CR effects for the prevention of metabolic syndrome.

Oats, in addition to cholesterol-lowering properties, contain unique antioxidants called avenanthramides (Avns), which inhibit both inflammatory cytokines and adhesion molecules in endothelial cells in culture. This study evaluated the effects of Avns of oats on atherosclerosis in Ldlr–/– mice, one of the most commonly used atherosclerosis mouse models with their similar cholesterol distributions to humans. The Ldlr–/– mice were fed a low fat, high fat, high fat containing regular oat brans with low levels of Avns (HFLA), or high fat containing regular oat brans with high levels of Avns (HFHA) diet. After 16 weeks of intervention, blood cholesterol and extent of aortic lesions were evaluated. We found that both oat-based diets reduced high fat diet-induced atheroma lesions in the aortic valve (p < 0.01). Furthermore, the effects of oat-based diets are more profound in HFHA mice than mice fed HFLA. Total plasma cholesterol levels were similarly reduced in both oat-supplemented mice. We concluded that oat b...

Routine prenatal care in the United States includes screening for asymptomatic bacteriuria (ASB), which occurs in 2 to 7 percent of pregnant women and can cause urinary tract infection and pyelonephritis. We present the case of a pregnant woman affected by multidrug resistant Klebsiella induced ASB during her prenatal screen, which was untreated due to a repeat urine culture showing mixed flora; subsequently, the patient’s postpartum course was complicated by pyelonephritis and perinephric abscess, concluding in a radical nephrectomy. Current recommendations are to treat ASB after two consecutive voided urine cultures showing the same bacterial strain in quantitative counts of =/> 10(5) colony forming units (cfu)/mL or a single-catheterized specimen with quantitative count of =/> 10(2) cfu/mL. For women with ASB in their prenatal screen or other high risk factors, consideration should be given to testing urine cultures every trimester until the completion of pregnancy to prevent the complications of persistent bacteriuria.

Highlights • Inflammatory myofibroblastic tumor (IMT) tends to locally recur but rarely metastasizes. • IMT tends to locally recur but rarely metastasizes. • IMTs that do not express anaplastic lymphoma kinase (ALK) have worse prognosis. • Current trials for ALK targeted therapies show promise in treating this neoplasm.

Twist transcription factors, members of the basic helix-loop-helix family, play crucial roles in mesoderm development in all animals. Humans have two paralogous genes, TWIST1 and TWIST2, and mutations in each gene have been identified in specific craniofacial disorders. Here, we describe a new clinical entity, Sweeney-Cox syndrome, associated with distinct de novo amino acid substitutions (p.Glu117Val and p.Glu117Gly) at a highly conserved glutamic acid residue located in the basic DNA binding domain of TWIST1, in two subjects with frontonasal dysplasia and additional malformations. Although about one hundred different TWIST1 mutations have been reported in patients with the dominant haploinsufficiency Saethre-Chotzen syndrome (typically associated with craniosynostosis), substitutions uniquely affecting the Glu117 codon were not observed previously. Recently, subjects with Barber-Say and Ablepharon-Macrostomia syndromes were found to harbor heterozygous missense substitutions in the paralogous glutamic acid residue in TWIST2 (p.Glu75Ala, p.Glu75Gln and p.Glu75Lys). To study systematically the effects of these substitutions in individual cells of the developing mesoderm, we engineered all five disease-associated alleles into the equivalent Glu29 residue encoded by hlh-8, the single Twist homolog present in Caenorhabditis elegans. This allelic series revealed that different substitutions exhibit graded severity, in terms of both gene expression and cellular phenotype, which we incorporate into a model explaining the various human disease phenotypes. The genetic analysis favors a predominantly dominant-negative mechanism for the action of amino acid substitutions at this highly conserved glutamic acid residue and illustrates the value of systematic mutagenesis of C. elegans for focused investigation of human disease processes.

Neurofibromatosis type 2 (NF2) is a genetic tumor disorder of the nervous system caused by inactivation of the merlin tumor suppressor gene. The hallmark of the disease is the development of schwannomas along the acoustic nerve, and multiple other tumors for which there is no effective treatment. Production of peroxynitrite and subsequent tyrosine (Tyr) nitration of proteins occurs in multiple tumor types. However, the role of Tyr nitration in tumorigenesis is unknown. We showed that schwannomas from NF2 patients and merlin-deficient (MD)-Schwann cells (NF2-associated schwannoma cell culture models) have significantly increased levels of Tyr nitration compared to wild-type (WT) Schwann cells. Further, prevention of tyrosine nitration significantly and selectively decreases MD-Schwann cell survival. Here we show that endogenous tyrosine nitration induces a metabolic reprogramming in human MD-Schwann cells characterized by: 1) decreased oxidative phosphorylation activity due to cytochrome coxidase inhibition, 2) increased glycolysis, and 3) almost complete glutamine dependency. Prevention of Tyr nitration reversed the metabolic phenotype of MD-Schwann cells back to that of WT-Schwann cells. We demonstrated that nitration of the chaperone Heat shock protein 90 (Hsp90) in tumor cells decreases mitochondrial metabolism. We show here that the intracellular delivery of nitrated Hsp90 in WT-Schwann cells significantly decreases mitochondrial oxygen consumption to levels comparable to those of MD-Schwann cells containing endogenous nitrated Hsp90. These observations suggest that nitrated Hsp90 participates in the metabolic reprogramming of MD-Schwann cells. Importantly, Hsp90 is not nitrated in any normal nervous tissue we have tested so far; implying that the nitrated form of Hsp90 could be an exceptional tumor-directed target for NF2 treatment in the short term. The identification of additional nitrated proteins that promote schwannoma metabolic reprogramming and growth could provide novel targets for the treatment of NF2 and potentially other tumor associated disorders. Supported by DoD, NRP, W81XWH-17-1-0409 (to MCF).

Table of contents A1 Point-of-care ultrasound examination of cervical spine in emergency department Yahya Acar, Onur Tezel, Necati Salman A2 A new technique in verifying the placement of a nasogastric tube: obtaining the longitudinal view of nasogastric tube in addition to transverse view with ultrasound Yahya Acar, Necati Salman, Onur Tezel, Erdem Cevik A3 Pseudoaneurysm of the femoral artery after cannulation of a central venous line. Should we always use ultrasound in these procedures? Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A4 Ultrasound-guided supraclavicular subclavian vein catheterization. A novel approach in emergency department Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A5 Clinical ultrasound in a septic and jaundice patient in the emergency department Margarita Algaba-Montes, Alberto Oviedo-García, Mayra Patricio-Bordomás A6 Characterization of the eyes in preoperative cataract Saudi patients by using medical diagnostic ultrasound Mustafa Z. Mahmoud, Abdelmoneim Sulieman A7 High-frequency ultrasound in determining the causes of acute shoulder joint pain Mustafa Z. Mahmoud A8 Teaching WINFOCUS Ultrasound Life Support Basic Level 1 for Providers in resource-limited countries Abbas Ali, Alrayah Mustafa, Ihab Abdelrahman, Mustafa Bahar, Osama Ali, H. Lester Kirchner, Gregor Prosen A9 Changes of arterial stiffness and endothelial function during uncomplicated pregnancy Ajda Anzic, Paul Leeson A10 Cardiovascular haemodynamic properties before, during and after pregnancy Ajda Anzic, Paul Leeson A11 An old man with generalized weakness Maryam Bahreini, Fatemeh Rasooli A12 Ultrasonography for non-specific presentations of abdominal pain Maryam Bahreini, Houman Hosseinnejad A13 Introduction of a new imaging guideline for suspected renal colic in the emergency department: effect on CT Urogram utilisation Gabriel Blecher, Robert Meek, Diana Egerton-Warburton A14 Transabdominal ultrasound screening for pancreatic cancer in Croatian military veterans: a retrospective analysis from the first Croatian veteran’s hospital Edina Ćatić Ćuti, Stanko Belina, Tihomir Vančina, Idriz Kovačević A15 The challenge of AAA: unusual case of obstructive jaundice Edina Ćatić Ćuti, Nadan Rustemović A16 Educational effectiveness of easy-made new simulator model for ultrasound-guided procedures in pediatric patients: vascular access and foreign body management Ikwan Chang, Jin Hee Lee, Young Ho Kwak, Do Kyun Kim A17 Detection of uterine rupture by point-of-care ultrasound at emergency department: a case report Chi-Yung Cheng, Hsiu-Yung Pan, Chia-Te Kung A18 Abdominal probe in the hands of interns as a relevant diagnostic tool in revealing the cause of heart failure Ela Ćurčić, Ena Pritišanac, Ivo Planinc, Marijana Grgić Medić, Radovan Radonić A19 Needs assessment of the potential utility of point-of-care ultrasound within the Zanzibar health system Abiola Fasina, Anthony J. Dean, Nova L. Panebianco, Patricia S. Henwood A20 Ultrasonographic diagnosis of tracheal compression Oliviero Fochi, Moreno Favarato, Ezio Bonanomi A21 The role of ultrasound in the detection of lung infiltrates in critically ill patients: a pilot study Marijana Grgić Medić, Ivan Tomić, Radovan Radonić A22 The SAFER Lasso; a novel approach using point-of-care ultrasound to evaluate patients with abdominal complaints in the emergency department Youngrock Ha, Hongchuen Toh A23 Awareness and use of clinician-performed ultrasound among clinical clerkship faculty Elizabeth Harmon, Wilma Chan, Cameron Baston, Gail Morrison, Frances Shofer, Nova Panebianco, Anthony J. Dean A24 Clinical outcomes in the use of lung ultrasound for the diagnosis of pediatric pneumonias Angela Hua, Sharon Kim, James Tsung A25 Effectiveness of ultrasound in hypotensive patients Isa Gunaydin, Zeynep Kekec, Mehmet Oguzhan Ay A26 Moderate-to-severe left ventricular ejection fraction related to short-term mortality of patients with post-cardiac arrest syndrome after out-of-hospital cardiac arrest Jinjoo Kim, Jinhyun Kim, Gyoosung Choi, Dowon Shim A27 Usefulness of abdominal ultrasound for acute pyelonephritis diagnosis after kidney transplantation Ji-Han Lee A28 Lung ultrasound for assessing fluid tolerance in severe preeclampsia Jana Ambrozic, Katja Prokselj, Miha Lucovnik A29 Optic nerve sheath ultrasound in severe preeclampsia Gabrijela Brzan Simenc, Jana Ambrozic, Miha Lucovnik A30 Focused echocardiography monitoring in the postoperative period for non-cardiac patients Asta Mačiulienė, Almantas Maleckas, Algimantas Kriščiukaitis, Vytautas Mačiulis, Andrius Macas A31 POCUS-guided paediatric upper limb fracture reduction: algorithm, tricks, and tips Sharad Mohite A32 Point-of-care lung ultrasound: a good diagnostic tool for pneumonia in a septic patient Zoltan Narancsik, Hugon Možina A33 A case of undergraduate POCUS (r)evolution Sara Nikolić, Jan Hansel, Rok Petrovčič, Una Mršić, Gregor Prosen A34 The Graz Summer School for ultrasound: from first contact to bedside application: three-and-a-half-day undergraduate ultrasound training: résumé after two years of continuous development Simon Orlob, Markus Lerchbaumer, Niklas Schönegger, Reinhard Kaufmann A35 Usefulness of point-of-care ultrasound in the emergency room in a patient with acute abdominal pain Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A36 Use of bedside ultrasound in a critically ill patient. A case report Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A37 Diagnostic yield of clinical echocardiography for the emergency physician Alberto Oviedo-García, Margarita Algaba-Montes, Mayra Patricio-Bordomás A38 Focused cardiac ultrasound in early diagnosis of type A aortic dissection with atypical presentation Chun-I Pan, Hsiu-Yung Pan, Chien-Hung Wu A39 Detection of imperforated hymen by point-of-care ultrasound Hsiu-yung Pan, Chia-Te Kung A40 Developing a point-of-care ultrasound curriculum for pediatric nurse practitioners practicing in the pediatric emergency department Sarah Pasquale, Stephanie J. Doniger, Sharon Yellin, Gerardo Chiricolo A41 Use of transthoracic echocardiography in emergency setting: patient with mitral valve abscess Maja Potisek, Borut Drnovšek, Boštjan Leskovar A42 A young man with syncope Fatemeh Rasooli, Maryam Bahreini A43 Work-related repetitive use injuries in ultrasound fellows Kristine Robinson, Clara Kraft, Benjamin Moser, Stephen Davis, Shelley Layman, Yusef Sayeed, Joseph Minardi A44 Lung ultrasonography in the evaluation of pneumonia in children Irmina Sefic Pasic, Amra Dzananovic, Anes Pasic, Sandra Vegar Zubovic A45 Central venous catheter placement with the ultrasound aid: two years’ experience of the Interventional unit, Division of Intensive Care Medicine, KBC Zagreb Ana Godan Hauptman, Marijana Grgic Medic, Ivan Tomic, Ana Vujaklija Brajkovic, Jaksa Babel, Marina Peklic, Radovan Radonic A46 Duplicitas casui: two patients admitted due to acute liver failure Vedran Radonic, Ivan Tomic, Luka Bielen, Marijana Grgic Medic A47 A pilot survey on an understanding of Bedside Point-of-Care Ultrasound (POCUS) among medical doctors in internal medicine: exposure, perceptions, interest, and barriers to training Peh Wee Ming A48 Unusual case of defecation syncope Nur hafiza Yezid, Fatahul Laham Mohammed A49 A case report of massive pulmonary embolism; a multidisciplinary approach Zainal Abidin Huda, Wan Nasarudin Wan Ismail, W.Yus Haniff W.Isa, Hashairi Fauzi, Praveena Seeva, Mohd Zulfakar Mazlan

The consumption of oatmeal and oat bran has been shown to reduce total and low density lipoprotein (LDL) cholesterol levels in plasma, which are major risk factors for coronary heart disease (CHD)....

Aneuploidy, an unbalanced karyotype in which one or more chromosomes are present in excess or reduced copy number, causes an array of known phenotypes including proteotoxicity, genomic instability, and slowed proliferation. However, the molecular consequences of aneuploidy are poorly understood and an unbiased investigation into aneuploid cell biology is lacking. We performed high-throughput screens for genes the deletion of which has a synthetic fitness cost in aneuploid Saccharomyces cerevisiae cells containing single extra chromosomes. This analysis identified genes that, when deleted, decrease the fitness of specific disomic strains as well as those that impair the proliferation of a broad range of aneuploidies. In one case, a chromosome-specific synthetic growth defect could be explained fully by the specific duplication of a single gene on the aneuploid chromosome, highlighting the ability of individual dosage imbalances to cause chromosome-specific phenotypes in aneuploid cells. Deletion of other genes, particularly those involved in protein transport, however, confers synthetic sickness on a broad array of aneuploid strains. Indeed, aneuploid cells, regardless of karyotype, exhibit protein secretion and cell-wall integrity defects. Thus, we were able to use this screen to identify novel cellular consequences of aneuploidy, dependent on both specific chromosome imbalances and caused by many different aneuploid karyotypes. Interestingly, the vast majority of cancer cells are highly aneuploid, so this approach could be of further use in identifying both karyotype-specific and nonspecific stresses exhibited by cancer cells as potential targets for the development of novel cancer therapeutics.

OBJECTIVES In drug trials involving subjects with irritable bowel syndrome (IBS), the placebo effect seems to be very important. However, events even before starting the study may also impact patient expectations. In this study, we utilized consent language from prior studies of diarrhea predominant IBS (D-IBS) drug trials to determine whether the knowledge imparted during this process affects the response to different therapies. METHODS Consecutive IBS subjects who met the Rome III criteria for IBS were enrolled. Patients were presented with a mock trial and randomized to 1 of 3 questionnaires with consent using similar language from consent forms of 3 drugs used in D-IBS: desipramine, alosetron, and rifaximin. Demographics, IBS symptoms using visual analog scale, and percent improvement needed for patients to report adequate relief of IBS from theoretically taking their assigned drug was asked. Data were expressed as mean ± SE. RESULTS Subjects who were anticipating rifaximin had the highest expectation of improvement to determine adequate relief of 87.3 ± 10.9% compared with 73.4 ± 18.0% for desipramine (P

Congenital long QT syndrome (LQTS) is a potentially lethal but highly treatable channelopathy. Along with multiple risk reduction measures, a recommendation for left sympathetic cardiac denervation therapy and/or implantable cardioverter defibrillator is made for higher risk patients. Despite its relatively common incidence in paediatric patients, there are no formal recommendations regarding perioperative management and discharge criteria for LQTS patients undergoing ambulatory surgery. This report describes a 17-year-old girl, diagnosed with congenital LQTS at 9 years of age, who had an episode of ventricular fibrillation the day after elective ear, nose and throat surgery. Despite several risk factors, she had a same-day dismissal, was not adequately monitored postoperatively and her cardiologists were not notified of her procedure. For the high-risk LQTS patient, we recommend monitoring of perioperative electrolytes and rhythm, postoperative ECG, adequate β-blockade therapy, avoidance of particular pharmacological agents, consideration of overnight observation and communication with the patient's cardiologist prior to procedure, and at discharge.

INTRODUCTION:Obesity is associated with postnatal depression; however, the prevalence of postnatal depression in women after bariatric surgery has not been further evaluated.METHODS:For this observational investigation, women, ages 18-45 years, with pregnancy from 1989-2015 and bariatric surgery wer

Pancreas cancer remains a formidable challenge. We report the first prospective analysis of the 3-drug combination of gemcitabine (G), docetaxel (T) and capecitabine (X) (mGTX) with schedule modification to maximize biomodulation of X.We conducted a dose escalation study of mGTX in first-line treatment of metastatic pancreas cancer using three dose levels (DL 1-3). Patients received docetaxel on days 1 and 8, gemcitabine on days 8 and 15, and capecitabine on days 8 through 21. Gemcitabine dose was fixed at 750 mg/m² over 75 min, capecitabine was given twice daily and escalated from 500 to 650 mg/m² at DL2 and docetaxel increased from 30 to 36 mg/m² at DL3.Twenty-one patients (18 evaluable) were enrolled in the study. MTD was reached at DL3 and one DLT was observed at DL2 (prolonged neutropenia). The most common grade 3/4 toxicities were leukopenia (29%) and neutropenia (29%) and fatigue (25%). Tumor growth control rate was 80% (11% PR; 69% SD lasting at least 3 months). Median progression-free-survival was 5.8 months (95% CI 2.7, 10.6) and median overall survival was 7.4 months (95% CI 3.8 16.8). CA 19-9 decreased by at least 50% from baseline in half the patients.mGTX demonstrates acceptable tolerability with interesting activity in patients with pancreatic cancer. The recommended doses for phase II studies are docetaxel 36 mg/m² days 1 and 8, gemcitabine 750 mg/m² over 75 min days 8 and 15, and capecitabine 625 mg/m² twice daily days 8 through 21.

Background: Restoring sensory innervation may be a useful adjunct in free flap head and neck reconstruction but, as yet, has not been shown to improve outcomes of breast reconstruction. The authors’ previous study demonstrated objectively improved sensation in a group of innervated transverse rectus abdominis musculocutaneous (TRAM) flap breast reconstruction patients relative to noninnervated flaps. This study compared patient-rated outcomes of free TRAM breast reconstruction in innervated versus noninnervated flaps. Methods: Twenty-seven women were randomized prospectively to undergo either innervated or noninnervated free TRAM flap breast reconstruction. For innervated flaps, the T10 intercostal nerve was harvested with the TRAM flap and neurotized to the T4 sensory nerve at the recipient site. Three validated outcome tools were administered after surgery: the Medical Outcomes Study 36-Item Short Form Health Survey, the Body Image after Breast Cancer Questionnaire, and the Functional Assessment of Cancer Therapy–Breast. Results were correlated with previously reported objective sensibility outcomes. Results: Eighteen of 27 women returned their questionnaires a mean 48 months after free TRAM flap reconstruction. Demographic analysis revealed no significant differences in patient age, height, smoking, radiation therapy, and nipple-areola complex reconstruction between randomized patient groups. There was a statistically significant improvement in all three measures in patients who were randomized to receive innervated free TRAM flaps compared with those receiving noninnervated flaps. Conclusion: This study demonstrates that innervation of free TRAM flaps used for breast reconstruction not only improves sensibility but also has a positive effect on patient-rated quality of life.

Subcutaneous nodules occur in approximately 20–25% of rheumatoid factor (RF)-positive rheumatoid patients. In this paper, we present a unique case of a 47-year-old healthy RF-negative woman with a 3-year history of necrobiotic nodules over the dorsum of her hands, extensor forearms, and lower extremities. This may represent an atypical presentation or a new rheumatoid variant.

Background: Coronal incisions are used in traumatic, reconstructive, and cosmetic procedures to access the lateral facial skeleton. Temporal hollowing is a common complication following coronal incision that affects the patient both physically and psychologically. Several dissections have been recommended through this area to avoid injury to the frontal branch of the facial nerve and the temporal fat pad, which is thought to be the cause of hollowing. The purpose of this study was to identify the cause of postoperative temporal hollowing. Methods: Patients requiring a coronal incision were recruited prospectively. Each side of the head in all patients was randomized to suprafascial, subfascial, or deep dissection. An unmarked envelope containing the type of dissection to be performed for each side was used. All envelopes contained equal distributions of all groups. The incidence and severity of temporal hollowing 6 months postoperatively were measured clinically and by computed tomographic volume analysis. Results: Twenty-seven patients with 54 sides (18 suprafascial, 15 subfascial, and 21 deep) completed the study. There were no demographic differences among the three groups. The incidence and severity of temporal hollowing were lowest with suprafascial dissection. Other factors associated with the presence of temporal hollowing included a reduction in body mass index. There were no injuries to the frontal nerve in any of the dissections. Postoperative temporal hollowing was associated with surgical approach and postoperative weight loss. Conclusion: Elevation of a coronal flap in the suprafascial plane and minimization of patient weight loss may decrease the incidence of postoperative temporal hollowing.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.

Papuloerythroderma of Ofuji (PEO), a rare skin disorder fi rst described by Ofuji et al . in 1984, is a pruritic eruption of fl at-topped papules in a background of erythroderma characteristically sparing skin folds ( “ deck chair sign ” ) [1]. Th e disorder usually aff ects Asians with a mean age of 73.4 years. Classic laboratory fi ndings include peripheral eosinophilia, lymphocytopenia and increased immunoglobulin E (IgE) [2]. Malignancy is commonly associated with PEO, with some reports stating an association as high as 54.5% [3]. Non-Hodgkin lymphoma (NHL) is the second most common malignancy associated with PEO after gastric cancer [2]. We report a case of PEO complicated by a peripheral T-cell lymphoma not otherwise specifi ed (PTCL-NOS) with the uncommon phenotype of CD3 /CD4 /T-cell receptor (TCR) null. A 51-year-old Japanese male with a long history of atopic rhinitis reported a 6-year history of pruritic, red-brown papules and plaques that began on his legs and then spread to his trunk and arms but sparing skin folds (Figure 1). He also had a 5-year history of secondary Staphylococcus aureus infection of the skin treated with cephalexin and topical mupirocin. Th is was accompanied by hypereosinophilia ( 2500/L) and an elevated IgE level (1980 – 3980/L) as well as a skin biopsy that showed a lichenoid dermatitis with a normal epidermis, perivascular lymphohistiocytic infi ltrate with eosinophils and papillary dermal edema. He was given the diagnosis of severe atopic dermatitis and possibly a hypersensitivity reaction. Th e rash did not respond to any topical steroids or antihistamines. Th e extreme pruritus was temporarily controlled with steroids orally, topically and intramuscularly. His eruption fl ared after aspergillosis infection and had remission with itraconazole. However, a year later, his rash worsened, and he developed lymphadenopathy and subcutaneous nodules on his right elbow. Th e fi ne needle aspiration (FNA) of a nodule showed atypical lymphocytes with scattered eosinophils, suggestive of lymphoma. Flow cytometry demonstrated a T-cell population representing 75% of atypical lymphocytes with the abnormal phenotype: CD1( ), CD2( ), CD3( ), CD4( ), CD5(bright), CD7(partial), CD8( ), CD25( ), CD26(dim)

ABSRACT: Background: Understanding the association between caregiver belief systems and practice patterns is an emerging area of research. We hypothesized an association between a maternity caregiver’s belief system and his or her behavior. The study objective was to determine if a family physician’s overall approach to maternity care, as measured by average use of epidural analgesia, was associated with maternal and fetal outcomes. Methods: Retrospective analysis was conducted of the births of three cohorts of 1992 nulliparous, low-risk women attended by 96 family physicians within an 18-month period in the department of family practice at the largest maternity hospital in Canada. Cohorts were based on the physicians’ mean use of epidural analgesia for the women. Family physicians attending fewer than 5 births were excluded. The main outcome measures, by physician epidural utilization cohort, were maternal/newborn morbidity, procedure rates, consultation rates, and length of stay. Results: Family physicians were separated into cohorts based on their mean use of epidural analgesia at rates of: low, 0–30 percent (15 physicians, 263 births); medium, 31–50 percent (55 physicians, 1323 births); and high, 51–100 percent (26 physicians, 406 births). After adjustment for maternal age and race, patients of low versus high epidural users were admitted at a later state of cervical dilation (mean 4.0 vs 3.1 cm), received less electronic fetal monitoring (76.4 vs 87.2%) and oxytocin augmentation (12.2 vs 29.8%), sustained fewer malpositions (occiput posterior or transverse)(23.2 vs 34.2%), had fewer cesarean sections (14.0 vs 24.4%), less obstetric consultation (47.9 vs 63.8%), and fewer newborn special care admissions (7.2 vs 12.8%). Conclusions: In our setting, high use of epidural analgesia is a marker for a style of practice characterized by malpositions leading to dysfunctional labors and higher intervention rates leading, in turn, to excess maternal/newborn morbidity. (BIRTH 28:4 December 2001)

Anecdotal experience has suggested that there is a higher frequency of maxillofacial injuries among motor vehicle collisions involving moose.A retrospective cohort study design was used to investigate the incidence of various injuries resulting from moose-motor vehicle collisions versus other high-speed motor vehicle collisions.A chart review was conducted among patients presenting to a Canadian regional trauma centre during the five-year period from 1996 to 2000.Fifty-seven moose-motor vehicle collisions were identified; 121 high-speed collisions were randomly selected as a control group. Demographic, collision and injury data were collected from these charts and statistically analyzed. The general demographic features of the two groups were similar. Moose collisions were typically frontal impact resulting in windshield damage. The overall injury severity was similar in both groups. Likewise, the frequency of intracranial, spinal, thoracic and extremity injuries was similar for both groups. The group involved in collisions with moose, however, was 1.8 times more likely then controls to sustain a maxillofacial injury (P=0.004) and four times more likely to sustain a maxillofacial fracture (P=0.006).Occupants of motor vehicles colliding with moose are more likely to sustain maxillofacial injuries than those involved in other types of motor vehicle collisions. It is speculated that this distribution of injuries relates to the mechanism of collision with these large mammals with a high centre of gravity.L’expérience de cas isolés laisse supposer que les traumatismes maxillofaciaux sont plus fréquents en cas de collisions entre une automobile et un orignal.Une étude rétrospective de cohortes a été utilisée pour examiner l’incidence de divers traumatismes découlant de collisions entre une automobile et un orignal par rapport à d’autres collisions à haute vitesse en automobile.L’examen des dossiers des patients s’étant présentés à un centre canadien de traumatologie pendant le quinquennat de 1996 à 2000 a été effectué.Cinquante-sept collisions entre une automobile et un orignal ont été repérées, et 121 collisions à haute vitesse ont été sélectionnées au hasard pour servir de groupe témoin. Les données démographiques, relatives à la collision et au traumatisme ont été colligées à partir de ces dossiers et ont fait l’objet d’une analyse statistique. Les caractéristiques démographiques générales des deux groupes étaient similaires. Les collisions avec un orignal provoquaient généralement un choc frontal entraînant des dommages au pare-brise. La gravité globale des traumatismes était similaire dans les deux groupes, de même que la fréquence des traumatismes intracrâniens, médullaires, thoraciques et des extrémités. Le groupe impliqué dans une collision avec un orignal était toutefois 1,8 fois plus susceptible de subir un traumatisme maxillofacial (P=0,004) que le groupe témoin, et quatre fois plus susceptible de subir une fracture maxillofaciale (P=0,006).Les occupants des véhicules automobiles sont plus susceptibles de subir des traumatismes maxillofaciaux dans le cadre d’une collision avec un orignal. On postule que cette répartition des traumatismes découle du mécanisme de la collision avec ces gros mammifères au centre de gravité élevé.

BACKGROUND Hospital-acquired venous thromboembolic (HA-VTE) events are an important, preventable cause of morbidity and death, but accurately identifying HA-VTE events requires labor-intensive chart review. Administrative diagnosis codes and their associated "present-on-admission" (POA) indicator might allow automated identification of HA-VTE events, but only if VTE codes are accurately flagged "not present-on-admission" (POA=N). New codes were introduced in 2009 to improve accuracy. METHODS We identified all medical patients with at least 1 VTE "other" discharge diagnosis code from 5 academic medical centers over a 24-month period. We then sampled, within each center, patients with VTE codes flagged POA=N or POA=U (insufficient documentation) and POA=Y or POA=W (timing clinically uncertain) and abstracted each chart to clarify VTE timing. All events that were not clearly POA were classified as HA-VTE. We then calculated predictive values of the POA=N/U flags for HA-VTE and the POA=Y/W flags for non-HA-VTE. RESULTS Among 2070 cases with at least 1 "other" VTE code, we found 339 codes flagged POA=N/U and 1941 flagged POA=Y/W. Among 275 POA=N/U abstracted codes, 75.6% (95% CI, 70.1%-80.6%) were HA-VTE; among 291 POA=Y/W abstracted events, 73.5% (95% CI, 68.0%-78.5%) were non-HA-VTE. Extrapolating from this sample, we estimated that 59% of actual HA-VTE codes were incorrectly flagged POA=Y/W. POA indicator predictive values did not improve after new codes were introduced in 2009. CONCLUSIONS The predictive value of VTE events flagged POA=N/U for HA-VTE was 75%. However, sole reliance on this flag may substantially underestimate the incidence of HA-VTE.

Rifaximin is a non-absorbed antibiotic relative of rifampicin. The location of effect and staphylococcal resistance are two recent potential concerns with rifaximin. In this study we evaluate the location of effect of rifaximin as well as the development of staphylococcal rifampicin resistance.Rats were divided into three groups. Group 1 gavaged for 10 days with PBS, group 2 gavaged with rifaximin for 10 days, and group 3 gavaged with rifaximin for 10 days and housed for 30 days. In each group, stool was collected daily for quantitative culture of Staphylococcus spp. and coliforms. After euthanasia luminal bacterial counts were determined at multiple gut locations by qPCR. Rifampicin susceptibility was tested on Staphylococcus pre and post rifaximin.At baseline, rats had a median of 2.90 × 10(6) cfu/ml Staphylococcus spp. in stool. After 10 days of rifaximin, this dropped to 1.20 × 10(5) cfu/ml (P0.01). With coliform counts, rats had a median of 1.86 × 10(4) cfu/ml at baseline which dropped to 2.2 × 10(3) cfu/ml (P0.01) after rifaximin. After cessation of rifaximin, coliform counts recovered within 3 days. When examining the total bacterial counts by qPCR, rifaximin reduced small bowel bacterial levels, but not colon. This reduction was sustained for 30 days. No colonies of Staphylococcus became resistant and only one colony was intermediate. The mean inhibitory concentration for rifampicin was not different before and after rifaximin.Staphylococcal spp. fail to demonstrate resistance to rifampicin after rifaximin. The transient reductions in stool coliform counts recover while rifaximin appears to produce durable reductions in duodenal bacteria.

OBJECTIVES: This prospective, randomized controlled trial explored the feasibility and efficacy of a group program of mindfulness training, a cognitive-behavioral technique, for women with irritable bowel syndrome (IBS). The technique involves training in intentionally attending to present-moment experience and non-judgmental awareness of body sensations and emotions. METHODS: Seventy-five female IBS patients were randomly assigned to eight weekly and one half-day intensive sessions of either mindfulness group (MG) training or a support group (SG). Participants completed the IBS severity scale (primary outcome), IBS-quality of life, brief symptom inventory-18, visceral sensitivity index, treatment credibility scale, and five-facet mindfulness questionnaire before and after treatment and at 3-month follow-up. RESULTS: Women in the MG showed greater reductions in IBS symptom severity immediately after training (26.4% vs. 6.2% reduction; P= 0.006) and at 3-month follow-up (38.2% vs. 11.8%; P= 0.001) relative to SG. Changes in quality of life, psychological distress, and visceral anxiety were not significantly different between groups immediately after treatment, but evidenced significantly greater improvements in the MG than in the SG at the 3-month follow-up. Mindfulness scores increased significantly more in the MG after treatment, confirming effective learning of mindfulness skills. Participants’ ratings of the credibility of their assigned interventions, measured after the first group session, were not different between groups. CONCLUSIONS: This randomized controlled trial demonstrated that mindfulness training has a substantial therapeutic effect on bowel symptom severity, improves health-related quality of life, and reduces distress. The beneficial effects persist for at least 3 months after group training.

In the trivial, ugly, sordid, and vulgar, a young James Joyce noted sudden perceptions that he called epiphany. The chatter in a pub, fake condolences, a bit of seaweed on a girl’s thigh—such negligible things unexpectedly lit up in the mind and sparked the writing of texts. Joyce wrote his epiphanies into a notebook then later spun them into poems and novels. Although he experimented with them for decades, casting them into a startling verbal pyrotechnics by Finnegans Wake (1939), Joyce never defined epiphany except through the manuscript Stephen Hero (1904–1906).

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) syndromes in which both GI and psychological symptoms have been shown to negatively impact health-related quality of life (HRQOL). The objective of this study was to use structural equation modeling (SEM) to characterize the interrelationships among HRQOL, GI, and psychological symptoms to improve our understanding of the illness processes in both conditions.Study participants included 564 Rome positive IBS patients and 126 IBD patients diagnosed via endoscopic and/or tissue confirmation. All patients completed questionnaires to assess bowel symptoms, psychological symptoms (SCL-90R), and HRQOL (SF-36). SEM with its two components of confirmatory analyses and structural modeling were applied to determine the relationships between GI and psychological symptoms and HRQOL within the IBS and IBD groups.For both IBD and IBS, psychological distress was found to have a stronger direct effect on HRQOL (-0.51 and -0.48 for IBS and IBD, respectively) than GI symptoms (-0.25 and -0.28). The impact of GI symptoms on psychological distress was stronger in IBD compared with IBS (0.43 vs. 0.22; P0.05). The indirect effect of GI symptoms on HRQOL operating through psychological distress was significantly higher in IBD than IBS (-0.21 vs. -0.11; P0.05).Psychological distress is less dependent on GI symptom severity in IBS compared with IBD even though the degree that psychological distress impacts HRQOL is similar. The findings emphasize the importance of addressing psychological symptoms in both syndromes.

Objective Current treatment options for irritable bowel syndrome are limited and often poorly studied. A select few drugs have been studied in irritable bowel syndrome, and the number needed to treat is frequently used to assess the relative efficacy of these treatments. However, side effects are an important consideration in the clinical decision on which particular treatment to use. This study examines trials of subjects with irritable bowel syndrome with diarrhea and constipation who are receiving a drug intervention deemed of merit by the American College of Gastroenterology task force and compares these therapies to examine the number needed to harm using a systematic review and meta-analysis approach. Methods Potential studies of irritable bowel syndrome treatments were identified through a search of MEDLINE (1950 to April 2011), EMBASE (1980 to April 2011), the Cochrane central register of controlled trials, and the bibliography of recent meta-analyses. Clinical trials of pharmacotherapy for irritable bowel syndrome were eligible for inclusion only if a description of adverse events and the number of patients who discontinued treatment because of adverse events were reported. The relative risk of experiencing an adverse event requiring discontinuation of treatment was used to determine the number needed to harm. In addition, the number and severity of adverse events were summarized. Results Twenty-six clinical trials (4 with selective serotonin reuptake inhibitors, 3 with lubiprostone, 6 with tricyclic antidepressants, 8 with alosetron, and 5 with rifaximin) were included. Lubiprostone was safe with insignificant harm in one combined phase III trial. Selective serotonin reuptake inhibitors did not have enough data for a reliable meta-analysis of harm but seemed to be safe. More rigorous data were available for tricyclic antidepressants, alosetron, and rifaximin; the numbers needed to harm were 18.3, 19.4, and 8971, respectively, and the numbers needed to treat were 8, 7.5, and 10.6, respectively. For tricyclic antidepressant and alosetron, an adverse event resulting in discontinuation of the study medication occurred for every 2.3 and 2.6 patients who benefited from a drug, respectively. For rifaximin, this number was 846 patients. In addition, adverse events were more common with tricyclic antidepressants and alosetron. Conclusion In irritable bowel syndrome with diarrhea, tricyclic antidepressants and alosetron are associated with a significant number needed to harm compared with rifaximin. Apart from lubiprostone, treatment of irritable bowel syndrome with constipation is limited to small studies (with poor descriptions of side effects), although lubiprostone and selective serotonin reuptake inhibitors appear safe.

The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits.

Bowen's disease (BD), or cutaneous squamous cell carcinoma (SCC) in situ, is rare in children. BD usually occurs in Caucasian adults on sun-exposed areas and may progress to invasive cutaneous SCC. Most cases of periungual BD have been linked to human papillomavirus infection. We report an immunocompetent child with periungual BD.

Although gait disturbance is frequently documented among patients with traumatic brain injury (TBI), gait data from animal models of TBI are lacking. To determine the effect of TBI on gait function in adult mice, we assessed gait changes following unilateral controlled cortical impact (CCI) using a computer-assisted automated gait analysis system. Three days after CCI, intensity, area or width of paw contact were significantly decreased in forepaw(s) while the relative paw placement between the fore and hindpaws altered, suggesting that TBI affected sensorimotor status and reduced inter-limb coordination. Similar to TBI patients, CCI decreased gait velocity and stride length, and prolonged stance and swing phase in mice. Following CCI, step pattern was also changed with increasing use in the ipsilateral-diagonal limb sequence. Our results indicate that gait analysis provides great insight into both spatial and temporal aspects of limb function changes during overground locomotion in quadruped species with head injury that are valuable for the purpose of treatment and rehabilitation. Our study also provides additional functional validation for the established mouse CCI model that is relevant to human head injury.

Background: Alcoholism-related deficits in cognition and emotion point toward frontal and limbic dysfunction, particularly in the right hemisphere. Prefrontal and anterior cingulate cortices are involved in cognitive and emotional functions and play critical roles in the oversight of the limbic reward system. In the present study, we examined the integrity of white matter tracts that are critical to frontal and limbic connectivity. Methods: Diffusion tensor magnetic resonance imaging (DT-MRI) was used to assess functional anisotropy (FA), a measure of white matter integrity, in 15 abstinent long-term chronic alcoholic and 15 demographically equivalent control men. Voxel-based and region-based analyses of group FA differences were applied to these scans. Results: Alcoholic subjects had diminished frontal lobe FA in the right superior longitudinal fascicles II and III, orbitofrontal cortex white matter, and cingulum bundle, but not in corresponding left hemisphere regions. These right frontal and cingulum white matter regional FA measures provided 97% correct group discrimination. Working Memory scores positively correlated with superior longitudinal fascicle III FA measures in control subjects only. Conclusions: The findings demonstrate white matter microstructure deficits in abstinent alcoholic men in several right hemisphere tracts connecting prefrontal and limbic systems. These white matter deficits may contribute to underlying dysfunction in memory, emotion, and reward response in alcoholism.

Background Reinforcement of behavioral responses involves a complex cerebral circuit engaging specific neuronal networks that are modulated by cortical oversight systems affiliated with emotion, memory, judgment, and decision making (collectively referred to in this study as the "extended reward and oversight system" or "reward network"). We examined whether reward-network brain volumes are reduced in alcoholics and how volumes of subcomponents within this system are correlated with memory and drinking history. Methods Morphometric analysis was performed on magnetic resonance brain scans in 21 abstinent long-term chronic alcoholic men and 21 healthy control men, group-matched on age, verbal IQ, and education. We derived volumes of total brain and volumes of cortical and subcortical reward-related structures including the dorsolateral-prefrontal, orbitofrontal, cingulate cortices, and the insula, as well as the amygdala, hippocampus, nucleus accumbens septi (NAc), and ventral diencephalon. Results Morphometric analyses of reward-related regions revealed decreased total reward-network volume in alcoholic subjects. Volume reduction was most pronounced in right dorsolateral-prefrontal cortex, right anterior insula, and right NAc, as well as left amygdala. In alcoholics, NAc and anterior insula volumes increased with length of abstinence, and total reward-network and amygdala volumes correlated positively with memory scores. Conclusions The observation of decreased reward-network volume suggests that alcoholism is associated with alterations in this neural reward system. These structural reward system deficits and their correlation with memory scores elucidate underlying structural-functional relationships between alcoholism and emotional and cognitive processes.