Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border.

The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA. When 5 mM ZnSO4 accompanied 3 mM EDTA in the preincubation mix, preservation of both enzyme activities occurred, demonstrating a requirement of Zn for the activity of both these phosphatases. These studies support the earlier contention that HCO3-ATPase and alkaline phosphatase activities may be different properties of the same enzyme, and raise the possibility that the ATPase could play a role in intestinal ion transport. The failure to identify a membrane-bound HCO3-ATPase by other workers could be due to the exposure of EDTA which occurred in their tissue preparation

Cerebellar defects in Pdss2 conditional knockout mice during embryonic development and in adulthood

PDSS2 is a gene that encodes one of the two subunits of trans-prenyl diphosphate synthase that is essential for ubiquinone biosynthesis. It is known that mutations in PDSS2 can cause primary ubiquinone deficiency in humans and a similar disease in mice. Cerebellum is the most often affected organ in ubiquinone deficiency, and cerebellar atrophy has been diagnosed in many infants with this disease. In this study, two Pdss2 conditional knockout mouse lines directed by Pax2-cre and Pcp2-cre were generated to investigate the effect of ubiquinone deficiency on cerebellum during embryonic development and in adulthood, respectively. The Pdss2 f/-; Pax2-cre mouse recapitulates some symptoms of ubiquinone deficiency in infants, including severe cerebellum hypoplasia and lipid accumulation in skeletal muscles at birth. During early cerebellum development (E12.5-14.5), Pdss2 knockout initially causes the delay of radial glial cell growth and neuron progenitor migration, so the growth of mutant cerebellum is retarded. During later development (E15.5-P0), increased ectopic apoptosis of neuroblasts and impaired cell proliferation result in the progression of cerebellum hypoplasia in the mutant. Thus, the mutant cerebellum contains fewer neurons at birth, and the cells are disorganized. The developmental defect of mutant cerebellum does not result from reduced Fgf8 expression before E12.5. Electron microscopy reveals mitochondrial defects and increased autophagic-like vacuolization that may arise in response to abnormal mitochondria in the mutant cerebellum. Nevertheless, the mutant mice die soon after birth probably due to cleft palate and micrognathia, which may result from Pdss2 knockout caused by ectopic Pax2-cre expression in the first branchial arch. On the other hand, the Pdss2 f/-; Pcp2-cre mouse is healthy at birth but gradually loses cerebellar Purkinje cells and develops ataxia-like symptoms at 9.5months; thus this conditional knockout mouse may serve as a model for ubiquinone deficiency in adult patients. In conclusion, this study provides two mouse models of Pdss2 based ubiquinone deficiency. During cerebellum development, Pdss2 knockout results in severe cerebellum hypoplasia by impairing cell migration and eliciting ectopic apoptosis, whereas Pdss2 knockout in Purkinje cells at postnatal stages leads to the development of cerebellar ataxia. © 2011 Elsevier Inc.postprin

Utility of Whole Genome Sequencing in Assessing and Enhancing Partner Notification of Neisseria gonorrhoeae Infection

Background: Gonorrhea is a sexually transmitted infection of global concern. We investigated whole genome sequencing (WGS) as a tool to measure and enhance partner notification (PN) in gonorrhea management. / Methods: Between May-November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, UK, underwent WGS. Reports listing sequences within 20 single nucleotide polymorphisms (SNPs) of study isolates within a database containing select isolates from April 1 2016 to November 15 2018 were issued to clinicians. The proportion of cases with a potential transmission partner identified by PN was determined from patient and PN data. WGS reports were reviewed to identify additional cases within ≤6 SNPs and verified for PN concordance. / Results: 380 isolates from 377 cases were successfully sequenced; 292 had traceable/contactable partners and 69 (18%) had a potential transmission partner identified by PN. Concordant PN and WGS links were identified in 47 partner pairs. Of 308 cases with no transmission partner by PN, 185 (60%) had a case within ≤6 SNPs; examination of these cases’ PN data identified seven partner pairs with previously unrecognized PN link, giving a total of 54 pairs; all had ≤4 SNP differences. WGS clusters confirmed gaps in partner finding, at individual and group levels. Despite the clinic providing sexual health services to the whole city, 35 cases with multiple partners had no genetically related case, suggesting multiple undiagnosed infections. / Conclusions: WGS could improve gonorrhea PN and control by identifying new links and clusters with significant gaps in partner finding

Treatment of insomnia in myasthenia gravis-A prospective study on non-benzodiazepine hypnotics in the treatment of myasthenia gravis patients with insomnia

Objectives: This study aimed to evaluate the efficacy and safety of non-benzodiazepine hypnotics in the treatment of myasthenia gravis (MG) patients with insomnia. Methods: This is a prospective longitudinal study. Outpatients who met the criteria for stable MG and insomnia diagnosis according to the International Classification of Sleep Disorders (third edition) were included in the study. They took a regular dose of non-benzodiazepine hypnotics (zolpidem 10 mg per night or zopiclone 7.5 mg per night) based on their own preferences. Patients received psychotherapy (including sleep health education) and were followed up for 4–5 weeks. Cases with lung diseases, respiratory disorders, or inappropriate use of hypnotic medications were excluded. The primary outcome is the difference in total Pittsburgh Sleep Quality Index (PSQI) score between baseline and the end of follow-up period. Secondary outcomes include the difference in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, 7-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) between baseline and the end of follow-up period and the safety of medication. Results: A total of 75 MG patients with insomnia were included in this study. After 4–5 weeks of treatment, the total PSQI score and MG-ADL score were lower than baseline (p < 0.01). No patients had an increased MG-ADL score. The incidence rate of adverse events was 16.0% (12 cases), including dizziness (6 cases, 8.0%), drowsiness (3 cases, 4.0%), fatigue (2 cases, 2.7%), and nausea (1 case, 1.3%), all of which were mild. No patients had new onset breathing disorders. Conclusion: Non-benzodiazepine hypnotics are safe and effective for stable MG patients who need insomnia treatment

Atomic-scale combination of germanium-zinc nanofibers for structural and electrochemical evolution

Alloys are recently receiving considerable attention in the community of rechargeable batteries as possible alternatives to carbonaceous negative electrodes; however, challenges remain for the practical utilization of these materials. Herein, we report the synthesis of germanium-zinc alloy nanofibers through electrospinning and a subsequent calcination step. Evidenced by in situ transmission electron microscopy and electrochemical impedance spectroscopy characterizations, this one-dimensional design possesses unique structures. Both germanium and zinc atoms are homogenously distributed allowing for outstanding electronic conductivity and high available capacity for lithium storage. The as-prepared materials present high rate capability (capacity of similar to 50% at 20 C compared to that at 0.2 C-rate) and cycle retention (73% at 3.0 C-rate) with a retaining capacity of 546 mAh g(-1) even after 1000 cycles. When assembled in a full cell, high energy density can be maintained during 400 cycles, which indicates that the current material has the potential to be used in a large-scale energy storage system

Relationship between subcellular localisation of Foscan® and caspase activation in photosensitised MCF-7 cells

The present study investigates the relationship between the subcellular localisation of Foscan® and intrinsic apoptotic pathway post Foscan®-based photodynamic therapy (PDT). With this purpose, mammary carcinoma MCF-7 cells were incubated with Foscan® for 3 or 24 h and then subjected to equitoxic light doses. Fluorescence microscopy revealed very good Foscan® co-localization to endoplasmic reticulum (ER) and Golgi apparatus after 3 h incubation with MCF-7 cells. Progressive increase in incubation time shows leakage of Foscan® from Golgi apparatus. Twenty-four hours incubation yielded a fluence-dependent enhanced induction of the ER-resident glucose-regulated protein 78 (Bip/GRP78), along with a weak mitochondrial damage, thus underscoring the ER as the main site of photodamage after prolonged incubation. Analysis of events implicated in apoptotic pathway after 24 h incubation demonstrated photodamage to Bcl-2 protein in total cellular extract, but not in the mitochondrial fraction. We further determined an increase in caspases-7 and -6 activation, which was strongly related to the expression of GRP78. The above findings demonstrate that Foscan® localisation in ER improves the photoactivation of the caspase-7 apoptotic pathway, which is poorly related to mitochondrial damage

Local steroid injection for moderately severe idiopathic carpal tunnel syndrome: Protocol of a randomized double-blind placebo-controlled trial (NCT 00806871)

<p>Abstract</p> <p>Background</p> <p>Patients with idiopathic carpal tunnel syndrome (CTS) are commonly treated with steroid injection into or proximal to the carpal tunnel. However, evidence for its efficacy beyond one month has not been established in randomized placebo-controlled trials. The primary aim of this randomized trial is to assess the efficacy of steroid injection into the carpal tunnel in relieving symptoms of CTS in patients with symptoms of such severity to warrant surgical treatment but have not been treated with steroid injection.</p> <p>Methods/Design</p> <p>The study is a randomized double-blind placebo-controlled trial. Patients referred to one orthopedic department because of CTS are screened. Eligibility criteria are age 18 to 70 years, clinical diagnosis of primary idiopathic CTS and abnormal nerve conduction tests or clinical diagnosis made independently by two orthopedic surgeons, failed treatment with wrist splinting, symptom severity of such magnitude that the patient is willing to undergo surgery, no severe sensory loss or thenar muscle atrophy, and no previous steroid injection for CTS. A total of 120 patients will be randomized to injection of 80 mg Methylprednisolone, 40 mg Methylprednisolone, or normal saline, each also containing 10 mg Lidocaine. Evaluation at baseline and at 5, 10, 24 and 52 weeks after injection includes validated questionnaires (CTS symptom severity scale, <it>Quick</it>DASH and SF-6D), adverse events, physical examination by a blinded assessor, and nerve conduction tests. The primary outcome measures are change in the CTS symptom severity score at 10 weeks and the rate of surgery at 52 weeks. The secondary outcome measures are the score change in the CTS symptom severity scale at 52 weeks, time to surgery, and change in <it>Quick</it>DASH and SF-6D scores and patient satisfaction at 10 and 52 weeks. The primary analysis will be carried out using mixed model analysis of repeated measures.</p> <p>Discussion</p> <p>This paper describes the rationale and design of a double-blind, randomized placebo-controlled trial that aims to determine the efficacy of two different doses of steroid injected into the carpal tunnel in patients with moderately severe idiopathic CTS.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier NCT00806871</p