Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial.

Annual intravenous administration of 5 mg of zoledronate decreases fracture risk over 3 years. The optimal dosing interval of 5 mg of zoledronate is not known. In order to determine the duration of the antiresorptive action of a single 5-mg dose of intravenous zoledronate, we conducted a 3-year double-blind, randomized, placebo-controlled trial in a volunteer sample of 50 postmenopausal women with osteopenia.

Acute effect of milk on serum urate concentrations: a randomised controlled crossover trial.

Objectives: Recent observational studies have highlighted the beneficial role of dairy ingestion in gout prevention. The aims of this study were to determine the acute effects of milk ingestion on serum urate concentrations and examine the mechanisms of these effects.

Methods: This was a short-term randomised controlled crossover trial of milk in 16 healthy male volunteers.

Qualitative findings from a mixed methods evaluation of once-weekly therapeutic community day services for people with personality disorder.

Background: This paper presents qualitative findings from a mixed methods study of four one-day-a-week therapeutic communities (TCs) in the north of England for people with personality disorder. Quantitative findings from the study are presented separately.

Aims: The study aimed to ascertain whether one-day-a-week TCs can be effective in addressing the problems associated with personality disorder.

Current knowledge of the aetiology of human tubal ectopic pregnancy.

BACKGROUND An ectopic pregnancy is a pregnancy which occurs outside of the uterine cavity, and over 98% implant in the Fallopian tube. Tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy. The epidemiological risk factors for tubal ectopic pregnancy are well established and include: tubal damage as a result of surgery or infection (particularly Chlamydia trachomatis), smoking and in vitro fertilization.

Evidence of prokineticin dysregulation in fallopian tube from women with ectopic pregnancy.

Objective: To demonstrate expression and regulation of prokineticins (PROKs) and their receptors (PROKRs) in fallopian tube (FT) from women who are not pregnant and women with ectopic pregnancy (EP).

Design: Tissue analysis.

Setting: Large United Kingdom teaching hospital.

Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) for intraoperative neurochemical monitoring.

The Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) measures extracellular neurotransmitter concentration in vivo and displays the data graphically in nearly real time. WINCS implements two electroanalytical methods, fast-scan cyclic voltammetry (FSCV) and fixed-potential amperometry (FPA), to measure neurotransmitter concentrations at an electrochemical sensor, typically a carbon-fiber microelectrode. WINCS comprises a battery-powered patient module and a custom software application (WINCSware) running on a nearby personal computer.

Economic evaluation of diagnosing and excluding ectopic pregnancy.

Background: The diagnosis of ectopic pregnancy in women presenting in early pregnancy is often protracted, relying on costly investigations that are psychologically burdensome to the patient. The aim of this study was to evaluate the financial costs to the health services in Scotland of the current methods used to diagnose and exclude ectopic pregnancy, and compare these with that of a theoretical single diagnostic serum biomarker.

Methods: We conducted a retrospective cost-description analysis (with and without costs of diagnostic laparoscopy) of the health-care costs incurred by all patients presenting to a large Scottish teaching hospital between June and September 2006 with pain and bleeding in early pregnancy, where ectopic pregnancy was not excluded.

Effects of calcium supplementation on lipids, blood pressure, and body composition in healthy older men: a randomized controlled trial.

Background: Calcium supplementation has been suggested to have beneficial effects on serum lipids, blood pressure, and body weight, but these possibilities have not been rigorously assessed in men.

Objective: This study evaluated the effect of calcium supplementation on the change in the ratio of HDL to LDL cholesterol (primary endpoint) and on changes in cholesterol fractions, triglycerides, blood pressure, and body composition (secondary endpoints).

Design: We carried out a randomized controlled trial of calcium supplementation in 323 generally healthy men over a period of 2 y.

Vitamin D insufficiency and health outcomes over 5 y in older women.

Background: Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies. However, some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [25(OH)D].

Objective: We sought to determine the effect of vitamin D status on health outcomes.

Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancy.

Context: Sex steroid hormone receptor (SHR) dynamics are well-documented in human endometrium but have not been comprehensively studied in Fallopian tube (FT).

Objective: The aim of the study was to compare expression patterns and hormonal regulation of SHR in FT with that described in endometrium and to determine whether SHR expression is altered in FT of women with ectopic pregnancy (EP).

Design: Tissue was analyzed and cultured.

Abdominal aortic calcification on vertebral morphometry images predicts incident myocardial infarction.

Abdominal aortic calcification (AAC) measured on spine X-rays is an established risk factor for cardiovascular disease. We investigated whether AAC assessed using vertebral morphometry and a recently developed scoring system (AAC-8) is reliable and associated with cardiovascular risk factors or events. A total of 1471 healthy postmenopausal women and 323 healthy middle-aged and older men participated in 5 and 2 year trials of calcium supplements, respectively.

The molecular basis for the actions of KVbeta1.2 on the opening and closing of the KV1.2 delayed rectifier channel.

Cytosolic K(V)beta1 subunits co-assemble with transmembrane K(V)1 channel alpha-subunits and have complex effects on channel function. Fast inactivation, the most obvious effect conferred, is due to fast open channel block resulting from the binding of the N-terminus within the inner mouth of the pore. K(V)beta1 subunits also slow current deactivation, enhance slow inactivation and shift channel activation to more negative voltages, but the mechanisms underlying these actions are not known.

Use of voltage clamp fluorimetry in understanding potassium channel gating: a review of Shaker fluorescence data.

Voltage clamp fluorimetry (VCF) utilizes fluorescent probes that covalently bind to cysteine residues introduced into proteins and emit light as a function of their environment. Measurement of this emitted light during membrane depolarization reveals changes in the emission level as the environment of the labelled residue changes. This allows for the correlation of channel gating events with movement of specific protein moieties, at nanosecond time resolution.

Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry.

Object: Emerging evidence supports the hypothesis that modulation of specific central neuronal systems contributes to the clinical efficacy of deep brain stimulation (DBS) and motor cortex stimulation (MCS). Real-time monitoring of the neurochemical output of targeted regions may therefore advance functional neurosurgery by, among other goals, providing a strategy for investigation of mechanisms, identification of new candidate neurotransmitters, and chemically guided placement of the stimulating electrode. The authors report the development of a device called the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for intraoperative neurochemical monitoring during functional neurosurgery.

Evolution of Deep Brain Stimulation: Human Electrometer and Smart Devices Supporting the Next Generation of Therapy.

Deep Brain Stimulation (DBS) provides therapeutic benefit for several neuropathologies including Parkinson's disease (PD), epilepsy, chronic pain, and depression. Despite well established clinical efficacy, the mechanism(s) of DBS remains poorly understood. In this review we begin by summarizing the current understanding of the DBS mechanism.

Serum biomarkers of tubal ectopic pregnancy: current candidates and future possibilities.

Ectopic pregnancy remains a considerable cause of maternal morbidity and mortality worldwide. Currently, it is diagnosed using a combination of transvaginal ultrasound and serial serum beta-human chorionic gonadotrophin levels. Diagnosis is often delayed and these tests are time-consuming and costly, both psychologically to the patient and financially to health services.

Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy.

Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP.

Differential expression and regulation of nuclear oligomerization domain proteins NOD1 and NOD2 in human endometrium: a potential role in innate immune protection and menstruation.

Nuclear oligomerization domains (NODs) are cytosolic pattern recognition receptors (PRRs), present in epithelial cells, monocytes and dendritic cells. This study details their expression, regulation and role in human endometrium. Real-time PCR showed that NOD1 mRNA is constitutively expressed in endometrium.

Decreased bone turnover despite persistent secondary hyperparathyroidism during prolonged treatment with imatinib.

Context: The tyrosine kinase inhibitor imatinib mesylate has an established role in the management of a number of malignant and proliferative conditions. Cross-sectional and short-term prospective studies have demonstrated secondary hyperparathyroidism during imatinib therapy, and variable changes in markers of bone turnover.

Objective: Our objective was to determine the biochemical and skeletal effects of imatinib during long-term therapy.

High-dose oral vitamin D3 supplementation in the elderly.

Summary: Daily dosing with vitamin D often fails to achieve optimal outcomes, and it is uncertain what the target level of 25-hydroxyvitamin D should be. This study found that large loading doses of vitamin D(3) rapidly and safely normalize 25OHD levels, and that monthly dosing is similarly effective after 3-5 months. With baseline 25OHD > 50 nmol/L, vitamin D supplementation does not reduce PTH levels.

Expression of secretory leukocyte protease inhibitor and elafin in human fallopian tube and in an in-vitro model of Chlamydia trachomatis infection.

Background: Secretory leukocyte protease inhibitor (SLPI) and elafin are anti-protease and anti-microbial molecules with a role in innate immune defence. They have been demonstrated at multiple mucosal surfaces including those of the female reproductive tract.

Methods And Results: This study details their expression in human Fallopian tubes (ampullary region) throughout the menstrual cycle (n = 18) and from women with ectopic pregnancy (n = 6), and examined their regulation by infection with Chlamydia trachomatis in an in-vitro model.

CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy.

Background: Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known.