Using lay counsellors to promote community-based voluntary counselling and HIV testing in rural northern Ghana: a baseline survey on community acceptance and stigma.
Access to voluntary counselling and HIV testing (VCT) remains limited in most parts of Ghana with rural populations being the least served. Services remain facility-based and employ the use of an ever-dwindling number of health workers as counsellors. This study assessed approval for the use of lay counsellors to promote community-based voluntary counselling and testing for HIV and the extent of HIV/AIDS-related stigma in the Kassena-Nankana district of rural northern Ghana. A cross-sectional questionnaire survey was conducted. Logistic regression was used to identify predictors of the tendency to stigmatize people living with HIV/AIDS (PLWHAs). Focus group discussions were held and analytical coding of the data performed. The majority (91.1%) of the 403 respondents indicated a desire to know their HIV status. Most (88.1%) respondents considered locations outside of the health facility as preferred places for VCT. The majority (98.7%) of respondents approved the use of lay counsellors. About a quarter (24%) of respondents believed that it was possible to acquire HIV through sharing a drinking cup with a PLWHA. About half (52.1%) of the respondents considered that a teacher with HIV/AIDS should not be allowed to teach, while 77.2% would not buy vegetables from a PLWHA. Respondents who believed that sharing a drinking cup with a PLWHA could transmit HIV infection (OR 2.50, 95%CI 1.52-4.11) and respondents without formal education (OR 2.94, 95%CI 1.38-6.27) were more likely to stigmatize PLWHAs. In contrast, respondents with knowledge of the availability of antiretroviral (ARV) drugs were less likely to do so (OR 0.40, 95%CI 0.22-0.73). Findings from the thirteen focus group discussions reinforced approval for community-based VCT and lay counsellors but revealed concerns about stigma and confidentiality. In conclusion, community-based VCT and the use of lay counsellors may be acceptable options for promoting access. Interventional studies are required to assess feasibility and cost-effectiveness.


Consent for use of personal information for health research: do people with potentially stigmatizing health conditions and the general public differ in their opinions?
Stigma refers to a distinguishing personal trait that is perceived as or actually is physically, socially, or psychologically disadvantageous. Little is known about the opinion of those who have more or less stigmatizing health conditions regarding the need for consent for use of their personal information for health research. We surveyed the opinions of people 18 years and older with seven health conditions. Participants were drawn from: physicians' offices and clinics in southern Ontario; and from a cross-Canada marketing panel of individuals with the target health conditions. For each of five research scenarios presented, respondents chose one of five consent choices: (1) no need for me to know; (2) notice with opt-out; (3) broad opt-in; (4) project-specific permission; and (5) this information should not be used. Consent choices were regressed onto: demographics; health condition; and attitude measures of privacy, disclosure concern, and the benefits of health research. We conducted focus groups to discuss possible reasons for observed consent choices. We observed substantial variation in the control that people wish to have over use of their personal information for research. However, consent choice profiles were similar across health conditions, possibly due to sampling bias. Research involving profit or requiring linkage of health information with income, education, or occupation were associated with more restrictive consent choices. People were more willing to link their health information with biological samples than with information about their income, occupation, or education. The heterogeneity in consent choices suggests individuals should be offered some choice in use of their information for different types of health research, even if limited to selectively opting-out. Some of the implementation challenges could be designed into the interoperable electronic health record. However, many questions remain, including how best to capture the opinions of those who are more privacy sensitive.


The impact of genomics on public health practice: the case for change.
Public health practice will not be able in the 21st century to ignore the impact of genomics, cell and molecular biology. It will need to take into consideration issues that include, among others: the complementary nature of social and biological models of disease, genetic exceptionalism, the readiness of public and patient to respond to genomic information, the relationship between individuals and populations, and concepts of population stratification. Health systems will need to adapt their practice and organisation to include new sequencing technologies, bioinformatic expertise and proper evaluation of genetic and molecular tests. Links with the commercial sector will increase in importance. The impact on developing countries cannot be ignored and will require special attention.


Genomics of lethal prostate cancer at diagnosis and castration resistance.
The genomics of primary prostate cancer differ from those of metastatic castration-resistant prostate cancer (mCRPC). We studied genomic aberrations in primary prostate cancer biopsies from patients who developed mCRPC, also studying matching, same-patient, diagnostic, and mCRPC biopsies following treatment. We profiled 470 treatment-naive prostate cancer diagnostic biopsies and, for 61 cases, mCRPC biopsies, using targeted and low-pass whole-genome sequencing (n = 52). Descriptive statistics were used to summarize mutation and copy number profile. Prevalence was compared using Fisher's exact test. Survival correlations were studied using log-rank test. TP53 (27%) and PTEN (12%) and DDR gene defects (BRCA2 7%; CDK12 5%; ATM 4%) were commonly detected. TP53, BRCA2, and CDK12 mutations were markedly more common than described in the TCGA cohort. Patients with RB1 loss in the primary tumor had a worse prognosis. Among 61 men with matched hormone-naive and mCRPC biopsies, differences were identified in AR, TP53, RB1, and PI3K/AKT mutational status between same-patient samples. In conclusion, the genomics of diagnostic prostatic biopsies acquired from men who develop mCRPC differ from those of the nonlethal primary prostatic cancers. RB1/TP53/AR aberrations are enriched in later stages, but the prevalence of DDR defects in diagnostic samples is similar to mCRPC.


Assembly of clathrin-coated pits onto purified plasma membranes.
During receptor-mediated endocytosis, coated pits invaginate to form coated vesicles, clathrin and associated proteins dissociate from the vesicle membrane, and these proteins form new coated pits at the cell surface. As a means of elucidating molecular mechanisms that govern the function of coated pits, the assembly phase of this cycle was reconstituted by incubating purified membranes that were treated to remove endogenous coated pits with cytoplasm extracted from cultured cells. The in vitro assembly of coated pits on these membranes satisfactorily mimics many features of coated pit formation in the intact cell. These studies indicate that: the membranes contain a limited number of coated pit assembly sites that bind clathrin with high affinity; the half-time for assembly is 5 minutes both at 4 degrees C and 37 degrees C; during assembly, proteins with molecular sizes of 180, 110, and 36 kilodaltons are recruited to the plasma membrane; and assembly is not dependent on adenosine triphosphate, but this nucleotide triggers a temperature-dependent loss of coated pits that are assembled in the absence of adenosine triphosphate.


Neuropsychiatric Lupus, the Blood Brain Barrier, and the TWEAK/Fn14 Pathway.
Patients with systemic lupus erythematosus (SLE) can experience acute neurological events such as seizures, cerebrovascular accidents, and delirium, psychiatric conditions including depression, anxiety, and psychosis, as well as memory loss and general cognitive decline. Neuropsychiatric SLE (NPSLE) occurs in between 30 and 40% of SLE patients, can constitute the initial patient presentation, and may occur outside the greater context of an SLE flare. Current efforts to elucidate the mechanistic underpinnings of NPSLE are focused on several different and potentially complementary pathways, including thrombosis, brain autoreactive antibodies, and complement deposition. Furthermore, significant effort is dedicated to understanding the contribution of neuroinflammation induced by TNF, IL-1, IL-6, and IFN-γ. More recent studies have pointed to a possible role for the TNF family ligand TWEAK in the pathogenesis of neuropsychiatric disease in human lupus patients, and in a murine model of this disease. The blood brain barrier (BBB) consists of tight junctions between endothelial cells (ECs) and astrocytic projections which regulate paracellular and transcellular flow into the central nervous system (CNS), respectively. Given the privileged environment of the CNS, an important question is whether and how the integrity of the BBB is compromised in NPSLE, and its potential pathogenic role. Evidence of BBB violation in NPSLE includes changes in the albumin quotient (Q alb) between plasma and cerebrospinal fluid, activation of brain ECs, and magnetic resonance imaging. This review summarizes the evidence implicating BBB damage as an important component in NPSLE development, occurring via damage to barrier integrity by environmental triggers such as infection and stress; cerebrovascular ischemia as result of a generally prothrombotic state; and immune mediated EC activation, mediated by antibodies and/or inflammatory cytokines. Additionally, new evidence supporting the role of TWEAK/Fn14 signaling in compromising the integrity of the BBB in lupus will be presented.


Linear metal nanostructures and size effects of supported metal catalysts.
Nickel metal catalysts composed of nanometer by micrometer strips have been produced with solid-state microfabrication techniques. The strips are actually the edges of nickelcatalyst thin films, which are sandwiched between separating support layers, which are also nanometers thick. These linear nanostructures constitute well-defined and well-controlled catalytic entities that reproduce the size of traditional supported metal clusters in one dimension, thus separating size from total number of atoms in the catalyst. Examination of their catalytic activity showed that they duplicate the behavior of conventional supported clusters. A specific rate maximum was observed for the hydrogenolysis of ethane at a nanoscale dimension similar to the cluster size at which the rate is maximum in the case of the supported cluster studies, whereas the hydrogenation of ethylene shows no such size dependency. The results suggest that the surface-to-volume ratio or the number of atoms in the catalytic entity cannot be the source of these size effects and that either support effects or nonequilibrium surface structures are the determining factors.


The RGD domain of human osteopontin promotes tumor growth and metastasis through activation of survival pathways.
Human osteopontin (OPN), a known tumor associated protein, exists in different isoforms, whose function is unclear. It also possesses a RGD domain, which has been implicated in diverse function. Here, we use genetic approaches to systematically investigate the function of the RGD domain in different OPN isoforms on tumor progression and metastasis for 2 different solid tumor models. Using isoform-specific qRT-PCR, we found that OPN-A and B were the main isoforms overexpressed in evaluated human tumors, which included 4 soft tissue sarcomas, 24 lung and 30 head and neck carcinomas. Overexpression of either OPN-A or B in two different cell types promoted local tumor growth and lung metastasis in SCID mouse xenografts. However, expression of either isoform with the RGD domain either mutated or deleted decreased tumor growth and metastasis, and resulted in increased apoptosis by TUNEL staining. In vitro, whereas mutation of the RGD domain did not affect cell-cell adhesion, soft agar growth or cell migration, it increased apoptosis under hypoxia and serum starvation. This effect could be mitigated when the RGD mutant cells were treated with condition media containing WT OPN. Mechanistically, the RGD region of OPN inhibited apoptosis by inducing NF-kappaB activation and FAK phosphorylation. Inhibition of NF-kappaB (by siRNA to the p65 subunit) or FAK activation (by a inhibitor) significantly increased apoptosis under hypoxia in WT OPN cells, but not in RGD mutant cells. Unlike prior reports, our data suggest that the RGD domain of both OPN-A and B promote tumor growth and metastasis mainly by protecting cells against apoptosis under stressed conditions and not via migration or invasion. Future inhibitors directed against OPN should target multiple isoforms and should inhibit cell survival mechanisms that involve the RGD domain, FAK phosphorylation and NF-kappaB activation.


Peripheral vascular disease and peripheral neuropathy in individuals with cardiometabolic clustering and obesity: National Health and Nutrition Examination Survey 2001-2004.
Two lower-extremity diseases (LEDs), including peripheral neuropathy and peripheral vascular disease (PVD), are leading causes of disability in the U.S. Although LEDs can be complications of diabetes, their prevelances and risk factors apart from diabetes are poorly described. This study describes the prevalence of LEDs and examines the association of obesity and cardiometabolic clustering in a population-based sample. Adults aged≥40 years (n=2,514) were evaluated in the 2001-2004 National Health and Nutrition Examination Survey for clustering of two or more cardiometabolic characteristics, including elevated triglycerides or plasma glucose, low HDL cholesterol levels, increased waist circumference, or hypertension. Clustering was combined with BMI (dichotomized at ≥30 kg/m2) to generate three groups: obese (with or without clustering); nonobese with clustering; and nonobese without clustering. Multivariate logistic regression procedures incorporated the complex survey sampling design. Overall, 9.0% of individuals had peripheral neuropathy alone, 8.5% had PVD alone, and 2.4% had both LEDs. The obese group was more likely to have peripheral neuropathy (odds ratio 2.20 [95% CI 1.43-3.39]), PVD (3.10 [1.84-5.22]), and both LEDs (6.91 [2.64-18.06]) compared with nonobese subjects without clustering. Within the nonobese group, clustering increased the odds of peripheral neuropathy (1.50 [1.00-2.25]) and PVD (2.48 [1.38-4.44]) compared with no clustering. Obesity and clustering markedly increased the likelihood of LEDs in this sample and identified a group for whom preventive activities may reduce the risk of future disability.


Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome.
Despite the pronounced neurological deficits associated with mental retardation and autism, it is unknown if altered neocortical circuit function occurs in these prevalent disorders. Here we demonstrate specific alterations in local synaptic connections, membrane excitability, and circuit activity of defined neuron types in sensory neocortex of the mouse model of Fragile X Syndrome-the Fmr1 knockout (KO). Overall, these alterations result in hyperexcitability of neocortical circuits in the Fmr1 KO. Specifically, we observe a substantial deficit in local excitatory drive ( approximately 50%) targeting fast-spiking (FS) inhibitory neurons in layer 4 of somatosensory, barrel cortex. This persists until at least 4 wk of age suggesting it may be permanent. In contrast, monosynaptic GABAergic synaptic transmission was unaffected. Overall, these changes indicate that local feedback inhibition in neocortical layer 4 is severely impaired in the Fmr1 KO mouse. An increase in the intrinsic membrane excitability of excitatory neurons may further contribute to hyperexcitability of cortical networks. In support of this idea, persistent neocortical circuit activity, or UP states, elicited by thalamic stimulation was longer in duration in the Fmr1 KO mouse. In addition, network inhibition during the UP state was less synchronous, including a 14% decrease in synchrony in the gamma frequency range (30-80 Hz). These circuit changes may be involved in sensory stimulus hypersensitivity, epilepsy, and cognitive impairment associated with Fragile X and autism.


Drop spreading on a superhydrophobic surface: pinned contact line and bending liquid surface.
In this study, we employ molecular dynamics (MD) simulations to probe the spreading of a drop on a superhydrophobic (SH) surface. The SH surface consists of nanopillars and the drop spreads while being in the Cassie-Baxter (CB) state on the nanopillared surface. Most remarkably, unlike the spreading on non-SH surfaces, we witness that the spreading on SH surfaces is not dominated by the motion of the three-phase contact line (TPCL). Rather, the TPCL remains pinned at the edge of a nanopillar and the spreading is ensured by the liquid surface or the liquid-vapor interface (of this pinned TPCL) bending down and wetting the solid adjacent to the TPCL. Such bending may actually enforce a progressive temporal increase in the instantaneous local contact angle eventually making it equal to or more than 180°. This is in sharp contrast to the classical spreading dynamics, where, with the spreading being dictated by the TPCL motion, the local contact angle always decreases with time. We carry out simulations where the solids supporting the nanopillars have vastly different wettabilities; however, this principle of bending-driven spreading is invariably witnessed. In fact, given the recent experimental study on the rolling of drops on SH surfaces manifesting exactly identical liquid-surface-bending-driven drop motion, we can infer that regardless of the drop size (e.g., nanoscopic or millimetric) or the nature of drop motion (spreading or rolling), the motion of drops in the CB state on SH surfaces is universally driven by the bending of liquid surfaces and not by the motion of the TPCL.


The impact of chemotherapy-induced nausea and vomiting on health-related quality of life.
The objectives of this prospective observational study were to estimate the frequency of patients who reported an impact of chemotherapy-induced nausea and vomiting (CINV) on their daily life and to evaluate the determinants of such an impact. Adult cancer patients at seven Italian oncology centers who were receiving cisplatin-containing regimens reported incidence and intensity of CINV for eight consecutive days in a diary and completed a Functional Living Index for Emesis (FLIE) questionnaire. Overall, 34% of patients reported vomiting and 62% reported nausea after chemotherapy. On days 1 to 5 after receiving chemotherapy, 67% of patients who had at least one emetic episode and 77% of those who suffered from at least mild nausea experienced an impact on their daily activities as measured on the FLIE questionnaire. More than 90% of all patients with both acute and delayed nausea or vomiting reported an impact on their daily life. Both acute and delayed vomiting contributed in similar measure to impact daily life; however, the importance of delayed nausea was greater than that of acute nausea. Despite antiemetic prophylaxis, CINV is still prevalent and often impacts the daily life of patients in Italy, especially in the delayed phase. The duration more than the severity seems to be responsible for the impact of CINV on the patients' daily lives.


Tools to tipple: ethanol ingestion by wild chimpanzees using leaf-sponges.
African apes and humans share a genetic mutation that enables them to effectively metabolize ethanol. However, voluntary ethanol consumption in this evolutionary radiation is documented only in modern humans. Here, we report evidence of the long-term and recurrent ingestion of ethanol from the raffia palm (Raphia hookeri, Arecaceae) by wild chimpanzees (Pan troglodytes verus) at Bossou in Guinea, West Africa, from 1995 to 2012. Chimpanzees at Bossou ingest this alcoholic beverage, often in large quantities, despite an average presence of ethanol of 3.1% alcohol by volume (ABV) and up to 6.9% ABV. Local people tap raffia palms and the sap collects in plastic containers, and chimpanzees use elementary technology-a leafy tool-to obtain this fermenting sap. These data show that ethanol does not act as a deterrent to feeding in this community of wild apes, supporting the idea that the last common ancestor of living African apes and modern humans was not averse to ingesting foods containing ethanol.


Research priorities of adult intensive care nurses in 20 European countries: a Delphi study.
This paper is a report of a three round Delphi study of intensive care nursing research priorities in Europe (October 2006-April 2009). Internationally, priorities for research in intensive care nursing have received some attention focusing on healthcare interventions and patient needs. Studies as early as the 1980s identified priorities in the United States, United Kingdom, Hong Kong and Australia. Research priorities of intensive care nurses across the European Union are unknown. The participants, invited in 2006, included 110 intensive care nurses, managers, educators and researchers from 20 European Critical Care Nursing Associations. Delphi round one was an emailed questionnaire inviting participants to list important areas for research. The list was content analysed and developed into an online questionnaire for rounds two and three. In round two, participants ranked the topics on a scale of 1-6 (not important to extremely important). Mean scores of round two were added to the questionnaire of round three and participants ranked the topics again. There were 52 research topics in 12 domains. There was a dominance of priorities in five main areas: patient safety; impact of evidence based practice on outcomes; impact of workforce on outcomes; wellbeing of patients and relatives; and impact of end-of-life care on staff and practice. The results reflect worldwide healthcare concerns and objectives and highlight topics that nurses view as fundamental to the care of critically ill patients. These topics provide a platform for future research efforts to improve clinical practice and care of patients in intensive care.


The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins.
Integrins of the beta7 subfamily, alpha4 beta7 and alphaE beta7, contribute to lymphocyte homing and to the development of protective or autoreactive immune responses at mucosal sites. The beta subunits of integrins are considered important for regulation of stimulated cell adhesion and adhesion-dependent signal transduction. Using a yeast interaction trap screen, a human WD repeat protein, termed WAIT-1, was isolated that interacts with the integrin beta7 cytoplasmic tail and is homologous to mouse EED and Drosophila ESC proteins. WAIT-1 also binds to the cytoplasmic domains of alpha4 and alphaE but not to those of integrin beta1, beta2, and alphaL subunits. Association of WAIT-1 and beta7-integrin was confirmed by coprecipitation from transiently transfected 293 cells. The binding site for WAIT-1 was mapped to a short membrane-proximal region of the beta7 cytoplasmic tail with Tyr-735 being of critical importance. Northern blot analysis revealed multiple WAIT-1-related transcripts with differential expression in circulating leukocytes, tissue-resident cells of diverse origin, and lymphoid malignancies. These results suggest that WAIT-1, together with the recently identified RACK1, may define a novel subfamily of WD repeat proteins that interact with distinct subsets of integrin cytoplasmic tails and may act as specific regulators of integrin function.


Evaluation of estrogenic activity of licorice species in comparison with hops used in botanicals for menopausal symptoms.
The increased cancer risk associated with hormone therapies has encouraged many women to seek non-hormonal alternatives including botanical supplements such as hops (Humulus lupulus) and licorice (Glycyrrhiza spec.) to manage menopausal symptoms. Previous studies have shown estrogenic properties for hops, likely due to the presence of 8-prenylnarigenin, and chemopreventive effects mainly attributed to xanthohumol. Similarly, a combination of estrogenic and chemopreventive properties has been reported for various Glycyrrhiza species. The major goal of the current study was to evaluate the potential estrogenic effects of three licorice species (Glycyrrhiza glabra, G. uralensis, and G. inflata) in comparison with hops. Extracts of Glycyrrhiza species and spent hops induced estrogen responsive alkaline phosphatase activity in endometrial cancer cells, estrogen responsive element (ERE)-luciferase in MCF-7 cells, and Tff1 mRNA in T47D cells. The estrogenic activity decreased in the order H. lupulus > G. uralensis > G. inflata > G. glabra. Liquiritigenin was found to be the principle phytoestrogen of the licorice extracts; however, it exhibited lower estrogenic effects compared to 8-prenylnaringenin in functional assays. Isoliquiritigenin, the precursor chalcone of liquiritigenin, demonstrated significant estrogenic activities while xanthohumol, a metabolic precursor of 8-prenylnaringenin, was not estrogenic. Liquiritigenin showed ERβ selectivity in competitive binding assay and isoliquiritigenin was equipotent for ER subtypes. The estrogenic activity of isoliquiritigenin could be the result of its cyclization to liquiritigenin under physiological conditions. 8-Prenylnaringenin had nanomolar estrogenic potency without ER selectivity while xanthohumol did not bind ERs. These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of botanical supplements. Although hops shows strong estrogenic properties via ERα, licorice might have different estrogenic activities due to its ERβ selectivity, partial estrogen agonist activity, and non-enzymatic conversion of isoliquiritigenin to liquiritigenin.


Internal structure and standardized scores of the Spanish adaptation of the EGRA (Early Grade Reading Assessment) for early reading assessment.
The EGRA (Early Grade Reading Assessment) is an assessment tool containing the main predictors of reading learning disabilities based on the National Reading Panel (NRP) (National Institute of Child Health and Human Development, 2000). This study has two main objectives: First, to analyze the internal structure of the EGRA, and second, to examine the validity and normative data for first and second grade primary school students in a Spanish-Speaking population. This study had a sample of 400 children (196 female and 204 male) attending early grades of Primary School, between 6 and 8 years of age. Our findings indicate that the EGRA has acceptable psychometric properties and an internal structure that is based on the two main factors of "decoding and comprehension" and "oral comprehension". We believe that the normative data collected from this study may be useful for the early detection of 'at risk' Spanish children having reading disabilities, as well as for planning of early reading education.


UFLC-Derived CSF Extracellular Vesicle Origin and Proteome.
Cerebrospinal fluid (CSF) extracellular vesicles (EVs) show promise as a source of neurological disease biomarkers, although their precise origin is poorly understood. Current extraction techniques produce disappointing yield and purity. This study describes the application of ultrafiltration LC (UFLC) to CSF-EVs, compared with ultracentrifugation (UC), and explores CSF-EV origin. EVs are extracted from human CSF by UC and UFLC and characterized using nanoparticle tracking analysis, electron microscopy, and immunoblotting. EV and CSF proteomes are analyzed by LC-MS/MS. UFLC-isolated particles have size, morphology, and marker expression characteristic of EVs. UFLC provides greater EV yield (UFLC 7.90 × 108 ± SD 1.31 × 108 EVs mL-1 CSF, UC 1.06 × 108 ± 0.57 × 108 p < 0.001). UFLC enhances purity, proteomic depth (UFLC 622 ± 49, UC 298 ± 50, p = 0.001), and consistency of quantification (CV 17% vs 23%). EVs contain more intracellular proteins (Odds ratio [OR] 2.63 p < 0.001) and fewer plasma proteins than CSF (OR 0.60, p < 0.001). CSF and EV-enriched proteomes show overrepresentation of brain-specific proteins (EV OR 3.18, p < 0.001; CSF OR 3.37, p < 0.001). Overrepresentation of cerebral white matter (OR 1.99, p = 0.015) and choroid plexus proteins (OR 1.87, p<0.001) is observed in EVs. UFLC improves yield and purity of CSF-EVs. The EV-enriched proteome better reflects the intracellular and white matter proteome than whole CSF.


Relocalized redox-active lysosomal iron is an important mediator of oxidative-stress-induced DNA damage.
Oxidative damage to nuclear DNA is known to involve site-specific Fenton-type chemistry catalysed by redox-active iron or copper in the immediate vicinity of DNA. However, the presence of transition metals in the nucleus has not been shown convincingly. Recently, it was proposed that a major part of the cellular pool of loose iron is confined within the acidic vacuolar compartment [Yu, Persson, Eaton and Brunk (2003) Free Radical Biol. Med. 34, 1243-1252; Persson, Yu, Tirosh, Eaton and Brunk (2003) Free Radical Biol. Med. 34, 1295-1305]. Consequently, rupture of secondary lysosomes, as well as subsequent relocation of labile iron to the nucleus, could be an important intermediary step in the generation of oxidative damage to DNA. To test this concept we employed the potent iron chelator DFO (desferrioxamine) conjugated with starch to form an HMM-DFO (high-molecular-mass DFO complex). The HMM-DFO complex will enter cells only via fluid-phase endocytosis and remain within the acidic vacuolar compartment, thereby chelating redox-active iron exclusively inside the endosomal/lysosomal compartment. Both free DFO and HMM-DFO equally protected lysosomal-membrane integrity against H2O2-induced oxidative disruption. More importantly, both forms of DFO prevented H2O2-induced strand breaks in nuclear DNA, including telomeres. To exclude the possibility that lysosomal hydrolases, rather than iron, caused the observed DNA damage, limited lysosomal rupture was induced using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride; subsequently, hardly any DNA damage was found. These observations suggest that rapid oxidative damage to cellular DNA is minimal in the absence of redox-active iron and that oxidant-mediated DNA damage, observed in normal cells, is mainly derived from intralysosomal iron translocated to the nucleus after lysosomal rupture.


Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics.
In this study, we investigate the use of imaging feature-based outcomes research ('radiomics') combined with machine learning techniques to develop robust predictive models for the risk of all-cause mortality (ACM), local failure (LF), and distant metastasis (DM) following definitive chemoradiation therapy (CRT). One hundred seventy four patients with stage III-IV oropharyngeal cancer (OC) treated at our institution with CRT with retrievable pre- and post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans were identified. From pre-treatment PET scans, 24 representative imaging features of FDG-avid disease regions were extracted. Using machine learning-based feature selection methods, multiparameter logistic regression models were built incorporating clinical factors and imaging features. All model building methods were tested by cross validation to avoid overfitting, and final outcome models were validated on an independent dataset from a collaborating institution. Multiparameter models were statistically significant on 5 fold cross validation with the area under the receiver operating characteristic curve (AUC) = 0.65 (p = 0.004), 0.73 (p = 0.026), and 0.66 (p = 0.015) for ACM, LF, and DM, respectively. The model for LF retained significance on the independent validation cohort with AUC = 0.68 (p = 0.029) whereas the models for ACM and DM did not reach statistical significance, but resulted in comparable predictive power to the 5 fold cross validation with AUC = 0.60 (p = 0.092) and 0.65 (p = 0.062), respectively. In the largest study of its kind to date, predictive features including increasing metabolic tumor volume, increasing image heterogeneity, and increasing tumor surface irregularity significantly correlated to mortality, LF, and DM on 5 fold cross validation in a relatively uniform single-institution cohort. The LF model also retained significance in an independent population.


Is simple reaction time affected by visual illusions?
A number of studies have shown that while perceptual judgment is deceived by pictorial illusions, grasping and other kinds of motor behaviour are not. This is in keeping with the existence of two different cortical systems: a ventral stream subserving vision-for-perception and a dorsal stream subserving vision-for-action. The former is sensitive to illusions, the latter is not. Given this dissociation of functions, one wonders whether simple visuomotor reaction time (RT) follows the ventral or the dorsal rule in perceiving illusory figures. Answering this question might contribute to a better understanding of the different functions of the two systems. We carried out two experiments, one with the Ponzo and the other with the Ebbinghaus-Titchener illusion and found that RT is sensitive to both illusions with faster responses to stimuli appearing illusorily bigger than the others. These results show that motor action is subserved by the ventral system when that action directly reports the presence or onset of a target rather than when that action requires a spatial adjustment that reflects the physical features of the target.


Improving Adiponectin Levels in Individuals With Diabetes and Obesity: Insights From Look AHEAD.
This study investigated whether fitness changes resulting from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes. Look AHEAD (Action for Health in Diabetes) randomized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention (ILI) for weight loss or to diabetes support and education (DSE). Total and high-molecular weight adiponectin (adiponectins), weight, and cardiorespiratory fitness (submaximal exercise stress test) were measured in 1,397 participants at baseline and at 1 year, when ILI was most intense. Regression analyses examined the associations of 1-year weight and fitness changes with change in adiponectins. ILI resulted in greater improvements in weight, fitness, and adiponectins at 1 year compared with DSE (P < 0.0001). Weight loss and improved fitness were each associated with changes in adiponectins in men and women (P < 0.001 for all), after adjusting for baseline adiponectins, demographics, clinical variables, and treatment arm. Weight loss contributed an additional 4-5% to the variance of change in adiponectins than did increased fitness in men; in women, the contributions of improved fitness (1% greater) and of weight loss were similar. When weight and fitness changes were both accounted for, weight loss in men and increased fitness in women retained their strong associations (P < 0.0001) with adiponectin change. Improvements in fitness and weight with ILI were favorably but distinctly associated with changes in adiponectin levels in overweight/obese men and women with diabetes. Future studies need to investigate whether sex-specific biological determinants contribute to the observed associations.


Duplex DNA engagement and RPA oppositely regulate the DNA-unwinding rate of CMG helicase.
A ring-shaped helicase unwinds DNA during chromosome replication in all organisms. Replicative helicases generally unwind duplex DNA an order of magnitude slower compared to their in vivo replication fork rates. However, the origin of slow DNA unwinding rates by replicative helicases and the mechanism by which other replication components increase helicase speed are unclear. Here, we demonstrate that engagement of the eukaryotic CMG helicase with template DNA at the replication fork impairs its helicase activity, which is alleviated by binding of the single-stranded DNA binding protein, RPA, to the excluded DNA strand. Intriguingly, we found that, when stalled due to interaction with the parental duplex, DNA rezipping-induced helicase backtracking reestablishes productive helicase-fork engagement, underscoring the significance of plasticity in helicase action. Our work provides a mechanistic basis for relatively slow duplex unwinding by replicative helicases and explains how replisome components that interact with the excluded DNA strand stimulate fork rates.


Stereological analysis of amygdala neuron number in autism.
The amygdala is one of several brain regions suspected to be pathological in autism. Previously, we found that young children with autism have a larger amygdala than typically developing children. Past qualitative observations of the autistic brain suggest increased cell density in some nuclei of the postmortem autistic amygdala. In this first, quantitative stereological study of the autistic brain, we counted and measured neurons in several amygdala subdivisions of 9 autism male brains and 10 age-matched male control brains. Cases with comorbid seizure disorder were excluded from the study. The amygdaloid complex was outlined on coronal sections then partitioned into five reliably defined subdivisions: (1) lateral nucleus, (2) basal nucleus, (3) accessory basal nucleus, (4) central nucleus, and (5) remaining nuclei. There is no difference in overall volume of the amygdala or in individual subdivisions. There are also no changes in cell size. However, there are significantly fewer neurons in the autistic amygdala overall and in its lateral nucleus. In conjunction with the findings from previous magnetic resonance imaging studies, the autistic amygdala appears to undergo an abnormal pattern of postnatal development that includes early enlargement and ultimately a reduced number of neurons. It will be important to determine in future studies whether neuron loss in the amygdala is a consistent characteristic of autism and whether cell loss occurs in other brain regions as well.


Manipulation of cellulose nanocrystal surface sulfate groups toward biomimetic nanostructures in aqueous media.
We report a facile aqueous procedure to create multivalent displays of sulfonated ligands on CNCs for future applications as viral inhibitors. CNCs were decorated with model compounds containing sulfonate groups via reactions of epoxides and isothiocyanates with amines under alkaline conditions. At first, surface sulfate groups of CNCs were hydrolytically cleaved by alkaline hydrolysis to increase the number of available surface hydroxyls. Success of desulfation was confirmed via dynamic light scattering (DLS), zeta potential measurements and thermogravimetric analysis (TGA). CNC surface hydroxyl groups were then activated with epichlorohydrin before subsequent reactions. As proof of concept toward aqueous pathways for functionalizing nanoparticles with sulfonated ligands, 3-chloro-2-hydroxy-1-propanesulfonic acid sodium salt hydrate (CPSA) and 4-sulfophenyl isothiocyanate sodium salt monohydrate (4-SPITC) were chosen as model compounds to react with homobifunctional 2,2'-(ethylenedioxy)bis(ethylamine) (EBEA) molecular spacer. The approaches presented are not only applicable to polysaccharide nanocrystals, but also other classes of polymeric and inorganic substrates presenting surface hydroxyl groups, as in the case of poly(2-hydroxyethyl methacrylate) (PHEMA), silica or glass. CNCs carrying sulfonated ligands were characterized by ATR-FTIR and UV-vis spectroscopy. Surface chemical compositions of desired elements were determined via X-ray photoelectron spectroscopy (XPS). We anticipate that with these facile aqueous procedures as the proof of concept, a diverse library of target-specific functionalities can be conjugated to CNCs for applications in nanomedicine, especially related to viral inhibition.


Arsenic metabolism and one-carbon metabolism at low-moderate arsenic exposure: Evidence from the Strong Heart Study.
B-vitamins involved in one-carbon metabolism (OCM) can affect arsenic metabolism efficiency in highly arsenic exposed, undernourished populations. We evaluated whether dietary intake of OCM nutrients (including vitamins B2, B6, folate (B9), and B12) was associated with arsenic metabolism in a more nourished population exposed to lower arsenic than previously studied. Dietary intake of OCM nutrients and urine arsenic was evaluated in 405 participants from the Strong Heart Study. Arsenic exposure was measured as the sum of iAs, monomethylarsonate (MMA) and dimethylarsenate (DMA) in urine. Arsenic metabolism was measured as the individual percentages of each metabolite over their sum (iAs%, MMA%, DMA%). In adjusted models, increasing intake of vitamins B2 and B6 was associated with modest but significant decreases in iAs% and MMA% and increases in DMA%. A significant interaction was found between high folate and B6 with enhanced arsenic metabolism efficiency. Our findings suggest OCM nutrients may influence arsenic metabolism in populations with moderate arsenic exposure. Stronger and independent associations were observed with B2 and B6, vitamins previously understudied in relation to arsenic. Research is needed to evaluate whether targeting B-vitamin intake can serve as a strategy for the prevention of arsenic-related health effects at low-moderate arsenic exposure.


Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis.
Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI. To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI. A prospective birth cohort study was performed in healthy term neonates. Concentrations of 25-hydroxyvitamin D (25-OHD) in cord blood plasma were related to RSV LRTI in the first year of life, defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen. The study population included 156 neonates. Eighteen (12%) developed RSV LRTI. The mean plasma 25-OHD concentration was 82 nmol/L. Overall, 27% of neonates had 25-OHD concentrations < 50 nmol/L, 27% had 50-74 nmol/L and only 46% had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy. Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not (65 nmol/L versus 84 nmol/L, P = .009). Neonates born with 25-OHD concentrations <50 nmol/L had a sixfold (95% confidence interval: 1.6-24.9; P = .01) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥ 75 nmol/L. Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life. Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy.


Mechanism for cryptic splice site activation during pre-mRNA splicing.
The 5' splice site of a pre-mRNA is recognized by U1 small nuclear ribonucleoprotein particles (snRNP) through base pairing with the 5' end of U1 small nuclear RNA (snRNA). Single-base substitutions within a 9-nucleotide 5'-splice-site sequence can abolish or attenuate use of that site and, in higher eukaryotes, can also activate nearby "cryptic" 5' splice sites. Here we show that the effects of single-base substitutions within a 5' splice site can be completely or partially suppressed by cis mutations that improve the overall complementarity of the site to U1 snRNA. We further show that in the presence of the normal 5' splice site, a cryptic 5' splice site can be activated by increasing its complementarity to U1 snRNA. U1 snRNP binding experiments confirm that cryptic 5' splice sites are activated when their affinity for U1 snRNP approaches that of the authentic 5' splice site. Based upon these results, we propose a spliceosome competition model for 5'-splice-site selection and cryptic 5'-splice-site activation. We discuss our results with regard to the factors involved in 5'-splice-site recognition.


Evaluation of endometriosis-associated pain and influence of conventional treatment: a systematic review.
Endometriosis is a chronic gynecological disease characterized by sustained painful symptoms that are responsible for a decline in the quality of life of sufferers. Conventional treatment includes surgical and pharmacological therapy aiming at reducing painful symptoms. This study aimed to evaluate pain levels in women with endometriosis, focusing on the influence of conventional treatment in controlling this variable. To do so, a literature search was conducted in the Medline/Pubmed databases, with 119 scientific articles found. After applying the inclusion and exclusion criteria, 27 were selected for reading and elaboration of this review. Thus, 9 studies evaluated the contribution of surgery, 17 the use of drugs to reduce pain levels in patients with endometriosis and one assessed surgical and medical treatment. The main results of these searches are presented and discussed in this revision. Surgery and the use of drugs provided reduced pain scores in patients with endometriosis but nevertheless exhibit disadvantages, such as risk of recurrence and side effects, respectively. Treatment of endometriosis is, therefore, a challenge for gynecologists and patients, as they must select the best therapeutic approach for this disease. However, improved quality of life in these patients has been obtained with the use of conventional treatment.


Metabolic Profiling of Chicken Embryos Exposed to Perfluorooctanoic Acid (PFOA) and Agonists to Peroxisome Proliferator-Activated Receptors.
Untargeted metabolic profiling of body fluids in experimental animals and humans exposed to chemicals may reveal early signs of toxicity and indicate toxicity pathways. Avian embryos develop separately from their mothers, which gives unique possibilities to study effects of chemicals during embryo development with minimal confounding factors from the mother. In this study we explored blood plasma and allantoic fluid from chicken embryos as matrices for revealing metabolic changes caused by exposure to chemicals during embryonic development. Embryos were exposed via egg injection on day 7 to the environmental pollutant perfluorooctanoic acid (PFOA), and effects on the metabolic profile on day 12 were compared with those caused by GW7647 and rosiglitazone, which are selective agonists to peroxisome-proliferator activated receptor α (PPARα) and PPARγ, respectively. Analysis of the metabolite concentrations from allantoic fluid by Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) showed clear separation between the embryos exposed to GW7647, rosiglitazone, and vehicle control, respectively. In blood plasma only GW7647 caused a significant effect on the metabolic profile. PFOA induced embryo mortality and increased relative liver weight at the highest dose. Sublethal doses of PFOA did not significantly affect the metabolic profile in either matrix, although single metabolites appeared to be altered. Neonatal mortality by PFOA in the mouse has been suggested to be mediated via activation of PPARα. However, we found no similarity in the metabolite profile of chicken embryos exposed to PFOA with those of embryos exposed to PPAR agonists. This indicates that PFOA does not activate PPAR pathways in our model at concentrations in eggs and embryos well above those found in wild birds. The present study suggests that allantoic fluid and plasma from chicken embryos are useful and complementary matrices for exploring effects on the metabolic profile resulting from chemical exposure during embryonic development.


Lipid peroxidation as a measure of oxygen free radical damage in the very low birthweight infant.
(ABSTRACTOxygen free radical mediated tissue injury is implicated as a major factor in the pathogenesis of the long term complications seen in the premature infant, and direct evidence of their role in the development of these long term problems is lacking. A prospective observational study of 78% of very low birthweight infants admitted to a level III neonatal intensive care unit in 1992 was undertaken to determine the relationship between lipid peroxidation products, antioxidant activity, and outcome. Lipid peroxidation (malondialdehyde-thiobarbituric acid, MDA-TBA) and antioxidant activity (vitamin E and glutathione peroxidase activity) were measured in 22 very low birthweight infants in the cord blood and the infant's blood at 24 hours, 48 hours, and 1 week of age and correlated with outcome measures. The normal range for these measures was established in the cord blood samples of 48 consecutive healthy full term infants. The concentration of MDA-TBA at 1 week correlated with the number of days of oxygen treatment and number of days of positive pressure ventilatory support. Controlling for gestational age and antenatal complications simultaneously the MDA-TBA concentration remained significantly associated with the number of days of oxygen treatment and the number of days of positive pressure ventilatory support. Glutathione peroxidase was low in the premature and full term infants consistent with the low concentrations of selenium known to be present in southern New Zealand. There was evidence of a quadratic relationship between vitamin E at 1 week and the total number of days of supplementary oxygen requirement, with both high and low values associated with increased oxygen requirement. This association, however, did not remain after controlling for gestational age and antenatal complications. These results support the role of oxygen free radicals in mediating tissue damage associated with the development of chronic lung disease in the premature infant.


Effects of intravenous thyrotropin-releasing hormone on 18F-fluorodeoxyglucose uptake in human brown adipose tissue: a randomized controlled trial.
Brown adipose tissue (BAT) activity in humans is stimulated by cold and by a limited number of pharmacological agents, including β3-adrenergic agonists and bile acids. Although thyrotropin-releasing hormone (TRH) is known to activate BAT in several mammals, this has not been reported in humans. A randomized, placebo-controlled, double-blind, cross-over trial. We investigated the effects of intravenous bolus administration of 400 µg TRH or 2 mL saline on BAT activity in healthy, lean men. BAT activity was measured as standardized 18F-fluorodeoxyglucose (18F-FDG) uptake and glucose metabolic rate (MRglu) using dynamic PET/CT imaging. The first six individuals were studied at room temperature, while subsequently nine were exposed to mild cold (17°C ± 1°C) for 60 min before imaging. During the dynamic scan, blood was withdrawn for measurement of thyroid hormone and catecholamine concentrations. This trial is registered with The Netherlands National Trial Register (number NTR5512). Sixteen participants were recruited. Six men studied at room temperature showed no visible BAT activity during either session. After exposure to mild cold, four of nine men (44.4%) showed clear increase of 18F-FDG uptake after TRH administration compared to placebo. Maximal standardized 18F-FDG uptake showed a trend toward increase after TRH compared to placebo (P = 0.066). MRglu showed a significant increase after TRH administration (P = 0.014). The increase in 18F-FDG uptake was not paralleled by changes in plasma thyroid hormone or catecholamine concentrations. Systemic TRH administration can increase the activity of cold-stimulated BAT in adult men. These findings may assist developing pharmacological strategies for modulating BAT activity in the management of obesity.


The Betty Neuman Systems Model applied to practice: a client with multiple sclerosis.
The importance of nursing theories and models for the growth and development of the profession of nursing is widely acknowledged. The variety of nursing phenomena and situations demands some flexibility in the choice of specific conceptualizations to be used. This paper demonstrates the goodness of fit of the Betty Neuman Systems Model to the care of clients with multiple sclerosis. An adapted assessment tool, based on Neuman's tool, but more useful in the acute care medical setting, is used to gather data related to a woman with recently diagnosed multiple sclerosis. A nursing care plan illustrating the use of Neuman's model is generated, implemented and evaluated. The Neuman Model is demonstrated to be useful and effective in the implementation of the nursing process in this case.


Improved detection of rare HIV-1 variants using 454 pyrosequencing.
454 pyrosequencing, a massively parallel sequencing (MPS) technology, is often used to study HIV genetic variation. However, the substantial mismatch error rate of the PCR required to prepare HIV-containing samples for pyrosequencing has limited the detection of rare variants within viral populations to those present above ~1%. To improve detection of rare variants, we varied PCR enzymes and conditions to identify those that combined high sensitivity with a low error rate. Substitution errors were found to vary up to 3-fold between the different enzymes tested. The sensitivity of each enzyme, which impacts the number of templates amplified for pyrosequencing, was shown to vary, although not consistently across genes and different samples. We also describe an amplicon-based method to improve the consistency of read coverage over stretches of the HIV-1 genome. Twenty-two primers were designed to amplify 11 overlapping amplicons in the HIV-1 clade B gag-pol and env gp120 coding regions to encompass 4.7 kb of the viral genome per sample at sensitivities as low as 0.01-0.2%.


Synergy of imipenem/colistin methanesulfonate combinations against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii.
The optimal combination ratio of imipenem to colistin methanesulfonate (CMS) against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii (INS-MDRAB) has not been determined in previous studies. To provide an alternative therapeutic option for clinical INS-MDRAB isolates, we investigated whether clinically achievable serum concentrations of CMS in combination with imipenem enhance the in vitro activity of imipenem against the INS-MDRAB isolates. Fifty-nine INS-MDRAB isolates with imipenem minimal inhibitory concentration (MIC) values of ≥8 mg/L were selected randomly from the Clinical Microbiology Laboratory at a university-affiliated medical center between July 1998 and May 2005. The in vitro activity of imipenem among these 59 clinical isolates was explored via serial two-fold dilutions containing a range of imipenem concentration from 0.125 mg/L to 256 mg/L, in combination with two fixed CMS concentrations at 0.5 mg/L and 1 mg/L. Genotype classification was performed using the pulsed-field gel electrophoresis method and infrequent-restriction-site polymerase chain reaction. A significant reversal of imipenem resistance (i.e., MICs ≤ 4 mg/L) was observed in 34 (57.6%) isolates and 44 (74.6%) isolates with the tests of CMS concentrations at 0.5 mg/L and 1 mg/L, respectively (p = 0.041). Genotype 1 was predominant (43 isolates, 72.9%) with imipenem resistance reversal rates of 51.2% and 79.1% (p = 0.004) in the tests of CMS at 0.5 mg/L and 1 mg/L, respectively. The synergy of imipenem/CMS against INS-MDRAB was significantly better for the CMS concentration at 1 mg/L than that at 0.5 mg/L, especially in our predominant clone. Our results provided insightful information for treating INS-MDRAB infections in clinical practice.


The advantage of errorless learning for the acquisition of new concepts' labels in alcoholics.
Previous findings revealed that the acquisition of new semantic concepts' labels was impaired in uncomplicated alcoholic patients. The use of errorless learning may therefore allow them to improve learning performance. However, the flexibility of the new knowledge and the memory processes involved in errorless learning remain unclear. New concepts' labels acquisition was examined in 15 alcoholic patients and 15 control participants in an errorless learning condition compared with 19 alcoholic patients and 19 control subjects in a trial-and-error learning condition. The flexibility of the new information was evaluated using different photographs from those used in the learning sessions but representing the same concepts. All of the participants carried out an additional explicit memory task and an implicit memory task was also performed by subjects in the errorless learning condition. The alcoholic group in the errorless condition differed significantly from the alcoholic group in the trial-and-error condition but did not differ from the two control groups. There was no significant difference between results in the learning test and the flexibility task. Finally, in the alcoholic group, the naming score in the learning test was correlated with the explicit memory score but not with the implicit memory score. Using errorless learning, alcoholics improved their abilities to learn new concepts' labels. Moreover, new knowledge acquired with errorless learning was flexible. The errorless learning advantage may rely on explicit rather than implicit memory processes in these alcohol-dependent patients presenting only mild to moderate deficits of explicit memory capacities.


The use of an e-learning module on return to work advice for physiotherapists - A prospective cohort study.
Background: Nonspecific low back pain (LBP) can progress to chronic disability and prolonged absence from work. Despite clinical and professional guidelines, physiotherapists often fail to address return to work outcomes. Aims: The aim of this exploratory study was to determine whether an e-learning resource tailored to physiotherapy practice could affect physiotherapists' attitudes and beliefs regarding return to work advice for their patients. Design: A prospective interventional cohort study (pilot). Methods: Participants were recruited via the Chartered Society of Physiotherapy website. Responses on a clinical vignette, the Health Care Providers' Pain and Impairment Scale (HC-Pairs), and the Behavioral Constructs Questionnaire (BCQ) were collected online at baseline (Q1) and 2-months post-intervention (Q2). Results: Fifty-four physiotherapists completed Q1 and the response rate for Q2 was 44/54 (81%). Changes in the degree of agreement with guidelines indicated that the intervention made an impact on respondents (kappa 0.345; p = 0.003). HC-Pairs and BCQ results showed a nonstatistically significant trend toward the target behavior. Conclusions: There is a need for interventions to improve adherence with advice for return to work following nonspecific LBP. An e-learning tool for physiotherapists on advising patients regarding return to work has potential to positively affect self-reported clinical behavior.


Development of Novel Non-Contact Electrodes for Mobile Electrocardiogram Monitoring System.
Real-time monitoring of cardiac health is helpful for patients with cardiovascular disease. Many telemedicine systems based on ubiquitous computing and communication techniques have been proposed for monitoring the user's electrocardiogram (ECG) anywhere and anytime. Usually, wet electrodes are used in these telemedicine systems. However, wet electrodes require conduction gels and skin preparation that can be inconvenient and uncomfortable for users. In order to overcome this issue, a new non-contact electrode circuit was proposed and applied in developing a mobile electrocardiogram monitoring system. The proposed non-contact electrode can measure bio-potentials across thin clothing, allowing it to be embedded in a user's normal clothing to monitor ECG in daily life. We attempted to simplify the design of these non-contact electrodes to reduce power consumption while continuing to provide good signal quality. The electrical specifications and the performance of monitoring arrhythmia in clinical settings were also validated to investigate the reliability of the proposed design. Experimental results show that the proposed non-contact electrode provides good signal quality for measuring ECG across thin clothes.


An evaluation of selenium concentrations in water, sediment, invertebrates, and fish from the Solomon River Basin.
The Solomon River Basin is located in north-central Kansas in an area underlain by marine geologic shales. Selenium is an indigenous constituent of these shales and is readily leached into the surrounding groundwater. Portions of the Basin are irrigated primarily through the pumping of selenium-contaminated groundwater from wells onto fields in agricultural production. Water, sediment, macroinvertebrates, and fish were collected from various sites in the Basin in 1998 and analyzed for selenium. Selenium concentrations were analyzed spatially and temporally and compared to reported selenium toxic effect thresholds for specific ecosystem components: water, sediments, food-chain organisms, and wholebody fish. A selenium aquatic hazard assessment for the Basin was determined based on protocol established by Lemly. Throughout the Basin, water, macroinvertebrate, and whole fish samples exceeded levels suspected of causing reproductive impairment in fish. Population structures of several fish species implied that successful reproduction was occurring; however, the influence of immigration of fish from low-selenium habitats could not be discounted. Site-specific fish reproduction studies are needed to determine the true impact of selenium on fishery resources in the Basin.


Flavonoid Extract from Propolis Inhibits Cardiac Fibrosis Triggered by Myocardial Infarction through Upregulation of SIRT1.
The flavonoid extract from propolis (FP) has been shown to protect against heart injury induced by isoproterenol. However, the effect of FP on cardiac fibrosis after myocardial infarction (MI) as well as the underlying mechanisms is not known. In the present study, we used biochemical and histological approaches to examine the effects of FP on MI-induced cardiac fibrosis and the related mechanisms in a rat MI model and in angiotensin II- (Ang II-) treated rat cardiac fibroblasts (CFs). In vivo, MI was generated by ligation of the left anterior descending coronary artery of rats, which remained for 4 weeks. Rats were randomly divided into the sham, MI, FP (12.5 mg/kg/d), and MI+FP groups. We found that FP treatment improved heart function, reduced cardiac fibrosis, and downregulated the expression of fibrosis-related factors including collagen I, collagen III, matrix metalloproteinase-2 (MMP-2), MMP-9, transforming growth factor-β1 (TGF-β1), and p-Smad2/3, which coincided with the upregulated expression of silent information regulator 1 (SIRT1) in the hearts of MI rats. Our in vitro experiments showed that FP inhibited the proliferation and migration of primary cultured rat CFs and downregulated the expression of the above-mentioned fibrosis-related factors in Ang II-stimulated CFs. In addition, FP can decrease ROS production induced by MI and Ang II in vivo and vitro. Notably, silencing SIRT1 counteracted the FP-induced effects on CFs treated with Ang II. We conclude that FP inhibits MI-induced cardiac fibrosis through SIRT1 activation and that FP represents a potential promising drug for the treatment of MI patients in the clinic.


Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension: results of a randomized controlled trial.
To assess if low (1.25 mg) and/or standard (5 mg) doses of the ACE inhibitor ramipril could prevent progression of microalbuminuria (incipient diabetic nephropathy) in normotensive type 1 diabetic patients. This study, using a multicenter randomized placebo-controlled double-blind parallel group, was conducted over 2 years in 28 outpatient diabetic clinics in the U.K. and Ireland. We screened 334 type 1 diabetic patients with suspected microalbuminuria and normal blood pressure; of these, 140 patients 18-65 years of age with a diagnosis of type 1 diabetes and persistent microalbuminuria, defined as urinary albumin excretion rate (AER) of 20-200 microg/min, were enrolled in the study. The proportion of patients progressing to macroalbuminuria was reduced in the ramipril groups but did not reach statistical significance over 2 years. AER was significantly lower at year 2 in the combined ramipril-treated patients versus placebo (P = 0.013). More patients on ramipril regressed to normoalbuminuria (<20 microg/min), with 11% for 1.25 mg ramipril, 20% for 5 mg ramipril, and 4% for placebo (P = 0.053). Blood pressure was significantly reduced to a similar extent with both 1.25 and 5 mg ramipril. Supine systolic blood pressure increased from 130 to 134 mmHg in the placebo group and fell in the 1.25 mg ramipril group (from 132 to 129 mmHg) and in the 5 mg ramipril group (from 134 to 130 mmHg) (P = 0.003, compared with placebo). No statistically significant changes were observed in glomerular filtration rate (GFR) between the placebo- and ramipril-treated groups during the 2-year period. Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension. Although the magnitude of the response was greater, there is no significant difference between responses to 1.25 or 5 mg ramipril. Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients. GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years.


The frequency of vascular complications associated with the use of vascular closure devices varies by indication for cardiac catheterization.
This study aimed at exploring access site-related vascular complication rates associated with the use of the vascular closure device (VCD) Angio-Seal™ in an unselected patient population undergoing elective as well as emergency coronary angiography or intervention. The VCD Angio-Seal™ is widely used to achieve hemostasis after diagnostic and interventional cardiac procedures. There are only little data on the frequency of vascular complications after the use of the VCD Angio-Seal™ in patients in non-elective settings. In-hospital vascular complications were prospectively assessed in 4,653 consecutive cardiac catheterization procedures, which included 2,772 elective diagnostic and 960 elective percutaneous coronary interventions (PCI), and 921 emergency cardiac catheterizations in patients with NSTEMI/STEMI. In 2,077 procedures manual compression (MC) and in 2,576 procedures VCD was applied. Complication rates for manual compression and VCD use were studied and multivariate analyses performed to disclose predictors for access site-related vascular complications. Vascular complication rates in patients receiving MC to achieve hemostasis were similar to those receiving a VCD (MC 3.4% vs. VCD 3.2%, p = n.s.). Separate analysis of vascular complication rates for subgroups revealed a significant reduction in vascular complications for the PCI group using a VCD (MC 7.7% vs. VCD 3.2%, p = 0.003). In emergencies VCD use lead to a rise in vascular complications (MC 0.9% vs. VCD 6.3%, p < 0.001). In contrast to elective settings, the risk of access site-related vascular complications is significantly increased after application of the VCD Angio-Seal™ in patients undergoing emergency catheterizations for NSTEMI/STEMI compared with manual compression.


Optically Transparent Anionic Nanofibrillar Cellulose Is Cytocompatible with Human Adipose Tissue-Derived Stem Cells and Allows Simple Imaging in 3D.
The anti-inflammatory and immunomodulatory properties of human mesenchymal stromal cells (MSCs) are a focus within regenerative medicine. However, 2D cultivation of MSCs for extended periods results in abnormal cell polarity, chromosomal changes, reduction in viability, and altered differentiation potential. As an alternative, various 3D hydrogels have been developed which mimic the endogenous niche of MSCs. Nevertheless, imaging cells embedded within 3D hydrogels often suffers from low signal-to-noise ratios which can be at least partly attributed to the high light absorbance and light scattering of the hydrogels in the visible light spectrum. In this study, human adipose tissue-derived MSCs (ADSCs) are cultivated within an anionic nanofibrillar cellulose (aNFC) hydrogel. It is demonstrated that aNFC forms nanofibres arranged as a porous network with low light absorbance in the visible spectrum. Moreover, it is shown that aNFC is cytocompatible, allowing for MSC proliferation, maintaining cell viability and multilineage differentiation potential. Finally, aNFC is compatible with scanning electron microscopy (SEM) and light microscopy including the application of conventional dyes, fluorescent probes, indirect immunocytochemistry, and calcium imaging. Overall, the results indicate that aNFC represents a promising 3D material for the expansion of MSCs whilst allowing detailed examination of cell morphology and cellular behaviour.


Functional status as an overall measure of health in adults with cystic fibrosis: further validation of a generic health measure.
We studied the validity of a generic health measure in a population with a chronic, life-shortening illness. Thirty-seven adults with cystic fibrosis (CF) and 46 of their healthy peers completed a questionnaire which included 12 questions on functional status from the RAND Health Insurance Study. For the CF group, the questionnaire and a medical chart review yielded data on 7 additional health variables, including pulmonary function. After data collection, members of the CF group were followed for 5 years, by which time 11 had died. The functional status of the CF group was significantly lower than that of the comparison group. Within the CF group, functional status correlated significantly with 6 of the 7 other health variables. Analysis using the Cox proportional hazards model showed that functional status alone was a significant (p less than 0.001) predictor of a CF subject's survival time; in a multivariate model a non-significant trend suggested that lowered functional status may be associated with an increased risk of early death even after adjustment for pulmonary function and percent ideal body weight. These results extend previous findings and suggest that functional status can be used as an overall measure of health in a wide variety of studies.


Selective peak inference: Unbiased estimation of raw and standardized effect size at local maxima.
The spatial signals in neuroimaging mass univariate analyses can be characterized in a number of ways, but one widely used approach is peak inference: the identification of peaks in the image. Peak locations and magnitudes provide a useful summary of activation and are routinely reported, however, the magnitudes reflect selection bias as these points have both survived a threshold and are local maxima. In this paper we propose the use of resampling methods to estimate and correct this bias in order to estimate both the raw units change as well as standardized effect size measured with Cohen's d and partial R2. We evaluate our method with a massive open dataset, and discuss how the corrected estimates can be used to perform power analyses. Keywords: fMRI, selective inference, winner's curse, regression to the mean, bias, bootstrap, local maxima, UK biobank, power analyses, massive linear modeling.


Correlates of serum leptin and insulin-like growth factor-I concentrations in normal weight and overweight/obese Iranian women.
Leptin and insulin-like growth factor-I (IGF-I) are two interrelated hormones that are implicated in the development or progression of coronary artery disease (CAD) and some cancers. The aim of this study was to investigate the relation between serum leptin and total IGF-I concentrations and to identify their correlations with age or anthropometric and body composition variables in healthy normal weight and overweight/obese Iranian women. The percent of body fat (BF%), fat mass (FM), fat-free mass (FFM), and waist/hip ratio (WHR) were determined in 51 healthy normal weight (body mass index [BMI] 18.5-24.9 kg/m(2)) and 50 overweight/obese (BMI > or = 25 kg/m(2)) Iranian reproductive-age women. Serum leptin and total IGF-I concentrations were measured by double-antibody sandwich assay and enzyme-linked immunosorbent assay (ELISA), respectively. Statistical analysis was performed by Mann-Whitney U test and Spearman's rank-correlation test. Multivariate linear regression analysis was performed with ranked-transformed data to obtain partial correlation coefficient. In this group of healthy, premenopausal Iranian women, variance of serum leptin concentration was independently explained by FM (partial rho = 0.295, p < 0.01), and variance of the total IGF-I concentration was explained by age (partial rho = -0.214, p = 0.037) and BMI (partial rho = 0.229, p = 0.026). Overweight/obese women had higher leptin and total IGF-I concentrations than normal weight women (p < 0.01). The serum leptin and total IGF-I concentrations were differentially correlated with age and anthropometric and body composition variables in the two groups. Whereas in normal weight women, leptin was negatively related to BMI (partial rho = -0.356, p = 0.015), in overweight/obese women, BMI, BF%, and FM independently contributed to the serum leptin variability (partial rho = 0.370, p = 0.013; partial rho = -0.320, p = 0.034; partial rho = 0.421, p < 0.01, respectively). There was a weak association between age and total IGF-I concentration in normal weight women, which did not reach statistical significance (partial rho = -0.255, p = 0.091). None of the variables was associated with the total IGF-I in overweight/obese women (p > 0.05). Although the studied anthropometric and body composition variables could explain approximately half of the leptin variance in Iranian women, they explained only a small proportion of total IGF-I variability. Our results indicated that the serum leptin and total IGF-I concentrations are differentially regulated in healthy normal weight and overweight/obese Iranian women.


"If she wants to eat…and eat and eat…fine! It's gonna feed the baby": Pregnant women and partners' perceptions and experiences of pregnancy with a BMI >40kg/m2.
women with a raised BMI are more likely to gain excessive weight in pregnancy compared to women with a BMI in the normal range. Recent behaviour change interventions have had moderate to no influence on GWG, and no effect on other perinatal outcomes. Evidence is required regarding the social and cultural contexts of weight and pregnancy. No studies to date have included the views of partners. to explore the experiences, attitudes and health-related behaviours of pregnant women with a BMI >40kg/m2; and to identify the factors and considerations which shape their beliefs, experiences and behaviours, and how these may change during and after pregnancy. 2. To determine the impact, if any, of the beliefs and attitudes of significant members of the women's families and social networks upon the women's experiences, attitudes and health-related behaviours in relation to weight and pregnancy METHODS: this was a prospective serial interview study. Semi-structured interviews were conducted with 11 pregnant women with a BMI >40kg/m2, during pregnancy and after birth, and once with 7 partners (all male) of women. Interview questions were designed to be appropriately but flexibly framed, in order to explore and gather data on participants' everyday life, lifestyles, views, experiences, relationships and behaviours, focussing more specifically on beliefs about health, pregnancy, weight and diet. Thematic content analysis was used to formally analyse and unearth patterns in the data. the findings can be grouped into six interrelated themes: the complexities of weight histories and relationships with food; resisting risk together; resisting stigma together; pregnancy as a 'pause';receiving dietary advice; postnatal intentions. These themes are interrelated due to the 'spoiled identity' (Goffman, 1963) that the large body represents in western culture and related stigma. this study provides evidence that there exist deeply ingrained social and cultural beliefs among women and in particular their partners, regarding pregnancy diet and weight gain. Further, this study provides evidence that male partners may resist stigmatised risk on behalf of a pregnant partner. All women (and several men) expressed an intention to adopt healthy behaviours and lose weight once their baby was born. Further evidence is required regarding the means by which women who experience stigmatised risk during pregnancy, and their partners, might be engaged and receptive to health advice. Models which draw on ideals of relationship-centred care, and selfefficacy via open discussion with women and families, engaging women and partners by providing them with an opportunity to talk about their beliefs and concerns, could be explored to inform future research and practice.


Managing the risk of injury in sport.
Because the risk of injury in many sports is high, governing bodies and individuals involved with these sports have a responsibility to manage the risks at acceptable levels. Risk management provides a structured framework within which risks can be identified, evaluated, assessed, and controlled through appropriate mitigation strategies. Exploring inferences obtained from the relationship between risk and the incidence and severity of injury contributes to the understanding and control of risks in sport. Studies related to intrinsic and extrinsic risk factors should be focused on determining which factors cause an athlete's risk level to fall within the high-risk or low-risk regions of the population's risk distribution. Risk values can be used to derive risk contours, which illustrate the interdependence of incidence and severity on the development of effective risk mitigation strategies. The wide variation in the levels of risk across different sports is used to demonstrate the impact that athletes' perception and acceptance of risk have on their choice of sport. Finally, the use of incidence and severity data for predicting the prevalence of injury in a team and for the economic evaluation of intervention programmes is discussed.


Alternative tertiary structure of tRNA for recognition by a posttranscriptional modification enzyme.
Transfer RNA (tRNA) canonically has the clover-leaf secondary structure with the acceptor, D, anticodon, and T arms, which are folded into the L-shaped tertiary structure. To strengthen the L form, posttranscriptional modifications occur on nucleotides buried within the core, but the modification enzymes are paradoxically inaccessible to them in the L form. In this study, we determined the crystal structure of tRNA bound with archaeosine tRNA-guanine transglycosylase, which modifies G15 of the D arm in the core. The bound tRNA assumes an alternative conformation ("lambda form") drastically different from the L form. All of the D-arm secondary base pairs and the canonical tertiary interactions are disrupted. Furthermore, a helical structure is reorganized, while the rest of the D arm is single stranded and protruded. Consequently, the enzyme precisely locates the exposed G15 in the active site, by counting the nucleotide number from G1 to G15 in the lambda form.


Overview of anisotropic filtering methods based on partial differential equations for electronic speckle pattern interferometry.
In this paper, we first present the general description for partial differential equations (PDEs) based image processing methods, including the basic idea, the main advantages and disadvantages, a few representative PDE models, and the derivation of PDE models. Then we review our contributions on PDE-based anisotropic filtering methods for electronic speckle pattern interferometry, including the second-order, fourth-order, and coupled nonoriented PDE filtering models and the second-order and coupled nonlinear oriented PDE filtering models. We have summarized the features of each model.


Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders.
The serine hydrolase monoacylglycerol lipase (MGLL) converts the endogenous cannabinoid receptor agonist 2-arachidonoylglycerol (2-AG) and other monoacylglycerols into fatty acids and glycerol. Genetic or pharmacological inactivation of MGLL leads to elevation in 2-AG in the central nervous system and corresponding reductions in arachidonic acid and eicosanoids, producing antinociceptive, anxiolytic, and antineuroinflammatory effects without inducing the full spectrum of psychoactive effects of direct cannabinoid receptor agonists. Here, we report the optimization of hexafluoroisopropyl carbamate-based irreversible inhibitors of MGLL, culminating in a highly potent, selective, and orally available, CNS-penetrant MGLL inhibitor, 28 (ABX-1431). Activity-based protein profiling experiments verify the exquisite selectivity of 28 for MGLL versus other members of the serine hydrolase class. In vivo, 28 inhibits MGLL activity in rodent brain (ED50 = 0.5-1.4 mg/kg), increases brain 2-AG concentrations, and suppresses pain behavior in the rat formalin pain model. ABX-1431 (28) is currently under evaluation in human clinical trials.


Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes.
Human enterovirus 71 (EV-71) is a common causative agent of hand, foot and mouth disease (HFMD). In recent years, the virus has caused several outbreaks with high numbers of deaths and severe neurological complications. Several new EV-71 subgenotypes were identified from these outbreaks. The mechanisms that contributed to the emergence of these subgenotypes are unknown. Six EV-71 isolates from an outbreak in Malaysia, in 1997, were sequenced completely. These isolates were identified as EV-71 subgenotypes, B3, B4 and C2. A phylogenetic tree that correlated well with the present enterovirus classification scheme was established using these full genome sequences and all other available full genome sequences of EV-71 and human enterovirus A (HEV-A). Using the 5' UTR, P2 and P3 genomic regions, however, isolates of EV-71 subgenotypes B3 and C4 segregated away from other EV-71 subgenotypes into a cluster together with coxsackievirus A16 (CV-A16/G10) and EV-71 subgenotype C2 clustered with CV-A8. Results from the similarity plot analyses supported the clustering of these isolates with other HEV-A. In contrast, at the same genomic regions, a CV-A16 isolate, Tainan5079, clustered with EV-71. This suggests that amongst EV-71 and CV-A16, only the structural genes were conserved. The 3' end of the virus genome varied and consisted of sequences highly similar to various HEV-A viruses. Numerous recombination crossover breakpoints were identified within the non-structural genes of some of these newer EV-71 subgenotypes. Phylogenetic evidence obtained from analyses of the full genome sequence supports the possible occurrence of inter-typic recombination involving EV-71 and various HEV-A, including CV-A16, the most common causal agent of HFMD. It is suggested that these recombination events played important roles in the emergence of the various EV-71 subgenotypes.


Tuning the acoustic frequency of a gold nanodisk through its adhesion layer.
To fabricate robust metallic nanostructures with top-down patterning methods such as electron-beam lithography, an initial nanometer-scale layer of a second metal is deposited to promote adhesion of the metal of interest. However, how this nanoscale layer affects the mechanical properties of the nanostructure and how adhesion layer thickness controls the binding strength to the substrate are still open questions. Here we use ultrafast laser pulses to impulsively launch acoustic phonons in single gold nanodisks with variable titanium layer thicknesses, and observe an increase in phonon frequencies as a thicker adhesion layer facilitates stronger binding to the glass substrate. In addition to an all-optical interrogation of nanoscale mechanical properties, our results show that the adhesion layer can be used to controllably modify the acoustic phonon modes of a gold nanodisk. This direct coupling between optically excited plasmon modes and phonon modes can be exploited for a variety of emerging optomechanical applications.


Getting going and letting go: Religiosity fosters opportunity-congruent coping with work-related uncertainties.
This study investigated how religiosity relates to goal engagement (i.e., investing time and effort; overcoming obstacles) and goal disengagement (i.e., protecting self-esteem and motivational resources against failure experiences; distancing from unattainable goals) in coping with perceived work-related uncertainties (e.g., growing risk of job loss) that arise from current social change. We hypothesised that religiosity not only expands individuals' capacities for both engagement and disengagement but also fosters an opportunity-congruent pattern of engagement and disengagement, promoting engagement especially under favourable opportunities for goal-striving in the social ecology and facilitating disengagement especially under unfavourable opportunities. Multilevel analyses in a sample of N = 2089 Polish adults aged 20-46 years partly supported these predictions. Religiosity was associated with higher goal engagement, especially under favourable economic opportunities for goal-striving in the social ecology (as measured by the regional net migration rate). For disengagement, the results were more mixed; religiosity was related to higher self-protection independently of the economic opportunity structure and predicted higher goal-distancing only under the most unfavourable opportunities. These results suggest that religiosity can promote different coping strategies under different conditions, fostering a pattern of opportunity-congruent engagement and, to some extent, disengagement that is likely to be adaptive.


Robots integrated with virtual reality simulations for customized motor training in a person with upper extremity hemiparesis: a case study.
A majority of studies examining repetitive task practice facilitated by robots for the treatment of upper extremity paresis utilize standardized protocols applied to large groups. Others utilize interventions tailored to patients but do not describe the clinical decision-making process utilized to develop and modify interventions. This case study describes a robot-based intervention customized to match the goals and clinical presentation of person with upper extremity hemiparesis secondary to stroke. The patient, P.M., was an 85-year-old man with left hemiparesis secondary to an intracerebral hemorrhage 5 years prior to examination. Outcomes were measured before and after a 1-month period of home therapy and after a 1-month robotic intervention. The intervention was designed to address specific impairments identified during his physical therapy examination. When necessary, activities were modified on the basis of response to the first week of treatment. P.M. trained in 12 sessions, using six virtually simulated activities. Modifications to original configurations of these activities resulted in performance improvements in five of these activities. P.M. demonstrated a 35-second improvement in Jebsen Test of Hand Function time and a 44-second improvement in Wolf Motor Function Test time subsequent to the robotic training intervention. Reaching kinematics, 24-hour activity measurement, and scores on the Hand and Activities of Daily Living scales of the Stroke Impact Scale all improved as well. A customized program of robotically facilitated rehabilitation was associated with short-term improvements in several measurements of upper extremity function in a patient with chronic hemiparesis.


Acceptability and Feasibility of Physical Activity Assessment Methods for an Appalachian Population.
Nowhere is improving understanding and accurate assessment of physical activity more important for disease prevention and health promotion than among health disparities populations such as those residing in rural and Appalachian regions. To enhance accurate assessment of physical activity and potentially improve intervention capacity, we conducted a mixed-methods study examining the acceptability and feasibility of self-report physical activity questionnaires, pedometers, and accelerometers among rural Appalachian children, adolescents, and adults. Most participants reported positive experiences with all three physical activity assessment tools. Several acceptability ratings differed by age group and by sex within each age group. With very few exceptions, no significant differences in acceptability were found by race, education, employment status, health status, BMI categories, income levels, or insurance status within age groups or overall. Several factors may impact the choice of the physical activity assessment method, including target population age, equipment cost, researcher burden, and potential influence on physical activity levels. Children and adolescents appear to have more constraints on when they can wear pedometers and accelerometers. While pedometers are inexpensive and convenient, they may influence physical activity levels, rather than simply measure them. Accelerometers, while less influential on behavior, consume extensive resources, including high purchase costs and researcher burden.


Patient Perspectives on Sharing Anonymized Personal Health Data Using a Digital System for Dynamic Consent and Research Feedback: A Qualitative Study.
Electronic health records are widely acknowledged to provide an important opportunity to anonymize patient-level health care data and collate across populations to support research. Nonetheless, in the wake of public and policy concerns about security and inappropriate use of data, conventional approaches toward data governance may no longer be sufficient to respect and protect individual privacy. One proposed solution to improve transparency and public trust is known as Dynamic Consent, which uses information technology to facilitate a more explicit and accessible opportunity to opt out. In this case, patients can tailor preferences about whom they share their data with and can change their preferences reliably at any time. Furthermore, electronic systems provide opportunities for informing patients about data recipients and the results of research to which their data have contributed. To explore patient perspectives on the use of anonymized health care data for research purposes. To evaluate patient perceptions of a Dynamic Consent model and electronic system to enable and implement ongoing communication and collaboration between patients and researchers. A total of 26 qualitative interviews and three focus groups were conducted that included a video presentation explaining the reuse of anonymized electronic patient records for research. Slides and tablet devices were used to introduce the Dynamic Consent system for discussion. A total of 35 patients with chronic rheumatic disease with varying levels of illness and social deprivation were recruited from a rheumatology outpatient clinic; 5 participants were recruited from a patient and public involvement health research network. Patients were supportive of sharing their anonymized electronic patient record for research, but noted a lack of transparency and awareness around the use of data, making it difficult to secure public trust. While there were general concerns about detrimental consequences of data falling into the wrong hands, such as insurance companies, 39 out of 40 (98%) participants generally considered that the altruistic benefits of sharing health care data outweighed the risks. Views were mostly positive about the use of an electronic interface to enable greater control over consent choices, although some patients were happy to share their data without further engagement. Participants were particularly enthusiastic about the system as a means of enabling feedback regarding data recipients and associated research results, noting that this would improve trust and public engagement in research. This underlines the importance of patient and public involvement and engagement throughout the research process, including the reuse of anonymized health care data for research. More than half of patients found the touch screen interface easy to use, although a significant minority, especially those with limited access to technology, expressed some trepidation and felt they may need support to use the system. Patients from a range of socioeconomic backgrounds viewed a digital system for Dynamic Consent positively, in particular, feedback about data recipients and research results. Implementation of a digital Dynamic Consent system would require careful interface design and would need to be located within a robust data infrastructure; it has the potential to improve trust and engagement in electronic medical record research.


Youth perspectives on weight-related words used by healthcare professionals: A qualitative study.
Although healthcare professionals often consider body weight a sensitive and difficult topic to discuss with children, a contextualized and comprehensive understanding of youth perspectives on weight-related words used in healthcare has yet to be established. This qualitative study aims to explore perspectives of Dutch children on the terminology healthcare professionals use when discussing weight. Fourteen interviews and one focus group discussion were held with children (age 8-16) who were in care because of their weight. A toolkit with customizable interview techniques was used in order to facilitate reflection and tailor the interview to each respondent. A narrative content analysis was conducted. Respondents attached both clear and subtle differences in meanings to (certain) weight-related words. Their perspectives were not unanimous for any single word. Moreover, at times, respondents framed certain words in positive or negative ways or used a word they disliked to describe themselves. This illustrates that meanings of weight-related words are not fixed but context and situation specific. This study revealed that meanings children assign to weight-related words are shaped by their experiences in the broader social context, especially at school, as well as with (previous) healthcare professionals. It pointed towards the importance of bedside manner, acquaintanceship, and support. Healthcare professionals treating children because of their body weight are advised to invest in a good patient-caregiver relationship, pay attention to children's previous (negative) social weight-related experiences, and reflect critically on their own preconceptions about body weight and the impact these preconceptions might have on their patient-caregiver relationships.


Efficacy of local use of probiotics as an adjunct to scaling and root planing in chronic periodontitis and halitosis: A randomized controlled trial.
Periodontitis is known to have multifactorial etiology, involving interplay between environmental, host and microbial factors. The current treatment approaches are aimed at reducing the pathogenic microorganisms. Administration of beneficial bacteria (probiotics) has emerged as a promising concept in the prevention and treatment of periodontitis. Thus, the aim of the present study is to evaluate the efficacy of the local use of probiotics as an adjunct to scaling and root planing (SRP) in the treatment of patients with chronic periodontitis and halitosis. This is a randomized, placebo-controlled, double-blinded trial involving 32 systemically healthy chronic periodontitis patients. After SRP, the subjects were randomly assigned into the test and control groups. Test group (SRP + probiotics) received subgingival delivery of probiotics and probiotic mouthwash, and control group (SRP + placebo) received subgingival delivery of placebo and placebo mouthwash for 15 days. Plaque index (PI), modified gingival index (MGI), and bleeding index (BI) were assessed at baseline, 1 and 3 months thereafter, whereas probing depth (PD) and clinical attachment level were assessed at baseline and after 3 months. Microbial assessment using N-benzoyl-DL-arginine-naphthylamide (BANA) and halitosis assessment using organoleptic scores (ORG) was done at baseline, 1 and 3 months. All the clinical and microbiological parameters were significantly reduced in both groups at the end of the study. Inter-group comparison of PD reduction (PDR) and clinical attachment gain (CAG) revealed no statistical significance except for PDR in moderate pockets for the test group. Test group has shown statistically significant improvement in PI, MGI, and BI at 3 months compared to control group. Inter-group comparison revealed a significant reduction in BANA in test group at 1 month. ORG were significantly reduced in test group when compared to control group. Within the limitations of the study, the present investigation showed that the adjunctive use of probiotics offers clinical benefit in terms of pocket depth reduction in moderate pockets and reduced oral malodor parameters.