Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q™), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women

BACKGROUND: The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. METHODS: The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS) can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL), and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC) via a follow-up questionnaire completed by participants 2 weeks post baseline. RESULTS: 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%), living with someone (74%), and not currently employed (58.7%). 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data). On a scale of 0–100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70) (range 0.72 to 0.89). Reproducibility ranged from 0.62 (Daily Activities) to 0.79 (Side Effects) for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p < 0.001). CONCLUSION: The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite score. They also support the use of the OPSAT-Q to examine the impact of bisphosphonate dosing frequency on patient satisfaction

Hf-based high-k materials for Si nanocrystal floating gate memories

Pure and Si-rich HfO2 layers fabricated by radio frequency sputtering were utilized as alternative tunnel oxide layers for high-k/Si-nanocrystals-SiO2/SiO2 memory structures. The effect of Si incorporation on the properties of Hf-based tunnel layer was investigated. The Si-rich SiO2 active layers were used as charge storage layers, and their properties were studied versus deposition conditions and annealing treatment. The capacitance-voltage measurements were performed to study the charge trapping characteristics of these structures. It was shown that with specific deposition conditions and annealing treatment, a large memory window of about 6.8 V is achievable at a sweeping voltage of ± 6 V, indicating the utility of these stack structures for low-operating-voltage nonvolatile memory devices

Risk Factors, Molecular Epidemiology and Outcomes of Ertapenem-Resistant, Carbapenem-Susceptible Enterobacteriaceae: A Case-Case-Control Study

Background: Increasing prevalence of ertapenem-resistant, carbapenem-susceptible Enterobacteriaceae (ERE) in Singapore presents a major therapeutic problem. Our objective was to determine risk factors associated with the acquisition of ERE in hospitalized patients; to assess associated patient outcomes; and to describe the molecular characteristics of ERE. Methods: A retrospective case-case-control study was conducted in 2009 at a tertiary care hospital. Hospitalized patients with ERE and those with ertapenem-sensitive Enterobacteriaceae (ESE) were compared with a common control group consisting of patients with no prior gram-negative infections. Risk factors analyzed included demographics; co-morbidities; instrumentation and antibiotic exposures. Two parallel multivariate logistic regression models were performed to identify independent variables associated with ERE and ESE acquisition respectively. Clinical outcomes were compared between ERE and ESE patients. Results: Twenty-nine ERE cases, 29 ESE cases and 87 controls were analyzed. Multivariate logistic regression showed that previous hospitalization (Odds ratio [OR], 10.40; 95 % confidence interval [CI], 2.19–49.20) and duration of fluoroquinolones exposure (OR, 1.18 per day increase; 95 % CI, 1.05–1.34) were unique independent predictors for acquiring ERE. Duration of 4 th-generation cephalosporin exposure was found to predict for ESE acquisition (OR, 1.63 per day increase; 95 % CI, 1.05– 2.54). In-hospital mortality rates and clinical response rates were significantly different between ERE and ESE groups

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

BACKGROUND: The phase-space relationship between simultaneously measured myoplasmic [Ca(2+)] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca(2+)] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca(2+ )sensitivity responsible for alterations in Ca(2+)-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. METHODS: We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca(2+)] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. RESULTS: We found that IR injury resulted in reduced myofilament Ca(2+ )sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca(2+ )sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca(2+ )sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca(2+ )sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca(2+ )affinity and cross-bridge kinetics only after ischemia. CONCLUSION: Estimated model parameters reveal mechanistic changes in Ca(2+)-contraction coupling due to IR injury, specifically the inefficient utilization of Ca(2+ )for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca(2+)-contraction coupling before and after IR injury

RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls

<p>Abstract</p> <p>Background</p> <p>RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients.</p> <p>Methods</p> <p>Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups).</p> <p>Results</p> <p>Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production.</p> <p>Conclusions</p> <p>Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down-regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt.</p

Benefits of a ball and chain: simple environmental enrichments improve welfare and reproductive success in farmed American mink (Neovison vison)

Can simple enrichments enhance caged mink welfare? Pilot data from 756 sub-adults spanning three colour-types (strains) identified potentially practical enrichments, and suggested beneficial effects on temperament and fur-chewing. Our main experiment started with 2032 Black mink on three farms: from each of 508 families, one juvenile male-female pair was enriched (E) with two balls and a hanging plastic chain or length of hose, while a second pair was left as a non-enriched (NE) control. At 8 months, more than half the subjects were killed for pelts, and 302 new females were recruited (half enriched: ‘late E’). Several signs of improved welfare or productivity emerged. Access to enrichment increased play in juveniles. E mink were calmer (less aggressive in temperament tests; quieter when handled; less fearful, if male), and less likely to fur-chew, although other stereotypic behaviours were not reduced. On one farm, E females had lower cortisol (inferred from faecal metabolites). E males tended to copulate for longer. E females also weaned more offspring: about 10% more juveniles per E female, primarily caused by reduced rates of barrenness (‘late E’ females also giving birth to bigger litters on one farm), effects that our data cautiously suggest were partly mediated by reduced inactivity and changes in temperament. Pelt quality seemed unaffected, but E animals had cleaner cages. In a subsidiary side-study using 368 mink of a second colour-type (‘Demis’), similar temperament effects emerged, and while E did not reduce fur-chewing or improve reproductive success in this colour-type, E animals were judged to have better pelts. Overall, simple enrichments were thus beneficial. These findings should encourage welfare improvements on fur farms (which house 60-70 million mink p.a.) and in breeding centres where endangered mustelids (e.g. black-footed ferrets) often reproduce poorly. They should also stimulate future research into more effective practical enrichments

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively