Search

Objectives Hearing loss (HL) is one of the most common sensorineural disorders. In the present study, we identified two novel missense mutations in BSND gene causing Bartter syndrome type IV which is a genetic disease with an autosomal recessive transmission, characterized by hypokalaemia, metabolic alkalosis, an elevation in plasma renin activity and hyperaldosteronism as well as sensorineural deafness. Methods Whole-exome sequencing was performed to study the genetic causes of Hearing loss in two unrelated patients from two Moroccan families. Results The two novel homozygous mutations p.Arg8Gly (c.22C > G), p.Thr36Asn (c.107C > A) in exon 1 of BSND gene which encodes barttin were identified in 7 patients belonging to two unrelated families originated from central region of Morocco. Conclusion We identified two novel missense mutations p.Arg8Gly and p.Thr36Asn in exon 1 of BSND gene; both mutations were described for the first time in Moroccan patients with Bartter syndrome type IV.

Introduction Numerous studies have indicated that poor sleep quality is relatively common among young adults and is related to less than optimal decision-making behavior. In order to assess decision-making behavior, we utilize a new variant of a Balloon Analogue Risk Task (BART) to assess sleep efficiency and other self-report measures’ relation to risky decision-making in young adults. We hypothesize that individuals who have poorer sleep will make more risky decisions than those who have better sleep in a novel measure called the One-Shot BART. Methods 200 undergraduate participants were recruited from the University of Arizona Psychology subject pool. Participants completed sleep quality questionnaires including the Sleep Condition Indicator and Split-Week Self-Assessment of Sleep-Y. Participants also completed a battery of self-report measures to assess exposure to traumatic events and trauma-related symptoms through the PTSD Checklist and Adverse Childhood Experiences Questionnaire. Lastly, participants were also tasked with completing a novel risk-taking task measure (the One-Shot BART) to assess risk-taking propensity and elucidate the cognitive processes underlying the risk-taking behavior. This task showed a significant correlation with (r=.24, p Results We found that better sleep efficiency showed a positive relationship with risk-taking(r=21, p Conclusion Behavioral results from the One-Shot BART are affected by Sleep Efficiency in a college student population. Interestingly, Sleep Efficiency was positively correlated with risky decision making in the One-Shot BART, indicating more optimal risk-taking in the game that may be mirrored in real-world decisions. Support (if any)

// Yue Han 1, 2 , Yi Lin 3 , Qing Sun 4 , Shujuan Wang 2 , Yanxia Gao 5 and Leping Shao 1, 2 1 Central Laboratory, Affiliated Hospital, Qingdao University, Qingdao 266003, P.R. China 2 Department of Nephrology, Affiliated Hospital, Qingdao University, Qingdao 266003, P.R. China 3 Pediatrics, Affiliated Hospital, Qingdao University, Qingdao 266003, P.R. China 4 Department of Nephrology, Qingdao Women and Children's Hospital, Qingdao University, Qingdao 266011, P.R. China 5 Department of Nephrology, Qingdao Branch of Qilu Hospital of Shandong University, Qingdao, Shandong 266000, P.R. China Correspondence to: Leping Shao, email: lepingshao@163.com Yanxia Gao, email: gaoyanxia31@163.com Keywords: bartter syndrome; CLCNKB gene; SLC12A1 gene; BSND gene; genotype and phenotype Received: June 27, 2017 Accepted: August 29, 2017 Published: September 27, 2017 ABSTRACT Objective: Bartter syndrome (BS) has been rarely reported in Chinese population except for a few case reports. This investigation was aimed to analyze the mutations of the causal genes in sixteen Chinese patients with BS, and review their followup and treatment. Methods: Identify mutations by the next generation sequencing and the multiplex ligation-dependent probe amplification (MLPA). Clinical characteristics and biochemical findings at the first presentation as well as follow-up were reviewed. Results: 15 different CLCNKB gene mutations were identified in fourteen patients with BS, including 11 novel ones. A novel missense mutation and a novel small deletion were found from SLC12A1 gene. A novel gross deletion was found in CLCNKA gene. A recurrent missense mutation was identified from BSND gene. We found that the whole gene deletion mutation of CLCNKB gene was the most frequent mutation (32%), and the rate of gross deletion was up to 50 percent in this group of Chinese patients. Conclusion: The present study has found 19 mutations, including 14 novel ones, which would enrich the human gene mutation database (HGMD) and provide valuable references to the genetic counseling and diagnosis of the Chinese population.

Background Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFire® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods. Methods Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures. Results A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes. Conclusion The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs. Disclosures Benjamin von Bredow, PhD, BioFire (Grant/Research Support) Jennifer Dien Bard, PhD, BioFire Diagnostic (Consultant, Scientific Research Study Investigator) Bart Kensinger, PhD, BioFire Diagnostics (Employee) Benedicte Pons, PhD, bioMerieux SA (Employee) Corinne Jay, PhD, bioMerieux SA (Employee)

Background Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, that has broad-spectrum activity against both yeasts, molds, and dimorphic fungi, including fungi resistant to other antifungal agents. FMGX has a favorable safety profile, reduced potential for clinically significant drug-drug interactions, and is formulated for IV and oral administration. Methods This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp. within 96 hrs prior to study entry, with ≤2 days of prior antifungal treatment were eligible. Patients with neutropenia, C. krusei infection, or deep-seated Candida infections were excluded. Patients were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Short-term fluconazole (or appropriate alternative) could follow if treatment was required beyond 14 days. Patients with a diagnosis of candidemia within 96 hrs of start of study drug who received at least 1 dose of FMGX were included in the mITT population. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee (DRC). Successful outcome was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at EOST. All Candida isolates were tested for antifungal susceptibility. Results A total of 21 subjects were enrolled in the study: 20 were included in the mITT. Median duration of FMGX was 11 days (range 5–14). All subjects received IV FMGX, 48% (10/21) received PO FMGX. The DRC-assessed success rate at EOST was 80% (16/20). Survival at day 30 was 85% (17/20); 3 deaths were not related FMGX. FMGX was well-tolerated with no treatment-related serious adverse events or discontinuations. FMGX had potent in vitro activity against all study Candida spp. (EUCAST MIC range 0.001–0.03 µg/ml) including those resistant to other antifungal agents. Conclusion FMGX was safe, well-tolerated, and demonstrated proof of concept with a high level of treatment success in patients with candidemia. Disclosures Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Ricard Ferrer, MD, PhD, Shionogi B.V. (Advisor or Review Panel member) Todd P. McCarty, MD, Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Iwonka Oborska, PhD, Amplyx Pharmaceuticals (Consultant, Independent Contractor) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

Objective To examine test-retest reliability of common behavioral decision making tasks. Method A total of 98 undergraduate students completed two administrations of the Iowa Gambling Task (IGT), Balloon Analogue Risk Task (BART), Columbia Card Task (CCT), and Game of Dice Task (GDT), three weeks apart. Results The BART, CCT, and GDT showed moderately strong correlations across time. On the IGT, no correlations were seen between Time 1 Trials 1-40 and Time 2 performance; however, weak correlations were observed between Time 1 Trials 41-100 and Time 2 performance. Paired-samples t-tests indicated participants were riskier at Time 1 than Time 2 on the IGT and GDT, but riskier at Time 2 on the BART. Conclusions The BART, CCT, and GDT showed moderate test-retest reliability, with the IGT showing weak reliability during the decision making under risk trials only. Implications for repeated test administration in clinical and non-clinical settings are discussed.

Bartter syndrome type IV, also known as Bartter syndrome with sensorineural deafness (BSND), is caused by loss-of-function mutations in the BSND gene, which encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Patients with BS IV have a highly variable clinical phenotype. This report concerns a Korean male patient with antenatal Bartter syndrome due to a homozygous BSND p.G47R mutation, who presented with severe perinatal symptoms followed by a relatively benign course with preserved renal function after early infancy. In addition, the clinical features and the laboratory data of the patient were compared with those of previously reported patients with the same mutation.

BSND gene mutations usually cause severe forms of antenatal Bartter syndrome and sensorineural deafness (SND). Chronic renal failure and transient hypercalciuria are reported as controversial symptoms of this syndrome. All twelve reported BSND mutations cause SND, whereas only two of the mutations give rise to normal glomerular filtration rate (GFR) and two other mutations cause hypercalciuria. The case we report here, where the patient presented with severe clinical symptoms and deletion on exons 2–4 of the BSND gene, has not been reported previously. Decreased GFR, along with hypercalciuria and difficulties in managing fluid and electrolyte requirements, are the reasons why this patient was brought to attention.

WE THANK THE 3483 PEER REVIEWERS WHO COMpleted JAMA manuscript reviews in 2001 and whose names appear on pages 901-914. In 2001, it took an average of 40 calendar days from manuscript receipt to rejection; 115 days from receipt to acceptance; and 162 days from receipt to publication. A mean of 23 days was required for peer review. Fifty-six percent of the 4189 manuscripts we received were sent for external peer review. Forty-two percent of manuscripts were rejected without external review. Two percent of accepted manuscripts (mostly invited editorials and cover stories) did not have external review. The total acceptance rate for manuscripts in 2001 was 12%, and the acceptance rate for unsolicited manuscripts was 8%.