Genetic variation by birth cohorts in Mexican Americans of Starr County, Texas.
Mexican Americans residing in Starr County, Texas, were grouped by their year of birth (1896-1925, 1926-1955, and 1956-1985) to determine the extent of birth cohort-related genetic variation within this population and the genetic differences, if any, from the Mexican population residing in the Metropolitan Monterrey Area (MMA), Nuevo León, México. Twenty-one genetic markers were analyzed which indicate that the three birth cohort groups are genetically indistinguishable. Gene diversity analysis suggests that more than 99.8% of the total gene diversity can be attributed to variation between individuals within the birth cohort populations and that the subdivision by birth cohort has only a small contribution (0.18%) to the total gene diversity. Genetic admixture analysis indicates a predominant influence from the Spanish, and that the three birth cohort groups were similar in terms of contributions of this ancestral population. The genetic structure of the Mexican American population of Starr County was also similar to the Mexican population from the State of Nuevo León, México. These findings, together with previous results, suggest that the Mexican Americans of Starr County, Texas, classified by gender, birthplace, and age, are not genetically distinguishable and are similar to the Mexican populations of the State of Nuevo León. © 1994 Wiley-Liss, Inc.


Airway clearance techniques for bronchiectasis.
People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production and these features may be associated with progressive decline in clinical status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine the effects of ACTs on the rate of acute exacerbations, incidence of hospitalisation and health-related quality of life in individuals with acute and stable bronchiectasis.Secondary: to determine whether a) ACTs are safe for individuals with acute and stable bronchiectasis and b) ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to October 2012, PEDro in October 2012 and handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT to no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures expected by The Cochrane Collaboration. Five studies involving 51 participants met the inclusion criteria of the review, all of which were cross-over design. Four studies were on adults with stable bronchiectasis, and the other study was on clinically stable children with bronchiectasis. Three studies were single treatment sessions, two were longer-term studies. The interventions varied and some control groups received a sham intervention while others were inactive. The methodological quality of the studies was variable and the studies were not able to blind participants and personal. Heterogeneity between studies precluded these data from meta-analysis and the review was therefore narrative.One study on 20 adults comparing an airway oscillatory device with no treatment found no significant difference in the number of exacerbations at 12 weeks (low-quality evidence). No data were available to assess the impact of ACTs on the time to exacerbation, duration of, incidence of hospitalisation or total number of hospitalised days. The same study reported clinically significant improvements in health-related quality of life in both disease-specific and cough-related measures. While based on a small number of participants and the data were skewed, the median difference in the change in total St George's Respiratory Questionnaire (SGRQ) score over three months in this study was 8.5 units (P value = 0.005 (Wilcoxon), low-quality evidence). Two studies reported mean increases in volume of sputum expectorated with airway oscillatory devices in the short term of 8.4 mL (95% CI 3.4 to 13.4 mL) and in the long term of 3 mL (P value = 0.02), with no significant effect on lung function. One study reported an immediate reduction in pulmonary hyperinflation in adults with non-positive expiratory pressure (PEP) ACTs (difference in functional residual capacity (FRC) of 19%, P value < 0.05) and with airway oscillatory devices (difference in FRC of 30%, P value < 0.05) compared to no ACTs. A similar decrease in pulmonary hyperinflation (difference in FRC of 6%) was found in children using an airway oscillatory device for 3 months compared to sham therapy. No studies reported on the effects of gas exchange, people's symptoms or antibiotic usage. ACTs appear to be safe for individuals (adults and children) with stable bronchiectasis, where there may be improvements in sputum expectoration, selected measures of lung function and health-related quality of life. The role of these techniques in people with an acute exacerbation of bronchiectasis is unknown. In view of the chronic nature of bronchiectasis, more data are needed to establish the clinical value of ACTs over the short and long term on patient-important outcomes, including symptoms, on physiological outcomes which may clarify the rationale for each technique and on long-term parameters that impact on disease progression in individuals with stable bronchiectasis. This is necessary in order to provide further guidance of specific ACT prescription for people with bronchiectasis. It may also be important to establish the comparative effect of different types of ACTs in people with bronchiectasis.


Best practice in the management of behavioural and psychological symptoms of dementia.
Behavioural and psychological symptoms of dementia (BPSD) occur in most patients with dementia. They cause great suffering in patients and caregivers, sometimes more so than the cognitive and functional decline inherent to dementia. The clinical features of BPSD include a wide variety of affective, psychotic and behavioural symptoms and signs. The causes and risk factors for BPSD are multiple and include biological, psychological and environmental variables. Frequently, their combination, rather than any specific factor, explains the occurrence of BPSD in an individual patient. Thus, a sound etiopathogenetic investigation including the patient and the family or care team is essential. The aim is to develop an individualized treatment plan using a therapeutic decision tree modified by the individual and environmental risk profile. Still, treatment may be difficult and challenging. Clinical empiricism often steps in where evidence from controlled studies is lacking. Psychosocial treatment approaches are pivotal for successful treatment of BPSD. Often a combination of different non-pharmacological approaches precedes drug treatment (most of which is off-label). Regular assessments of the treatment plan and any prescriptions must be carried out to detect signs of relapse and to stop any medicines that may have become inappropriate. Even with optimal management, BPSD will not disappear completely in some cases and will remain challenging for all involved parties. This article is a narrative review based closely on the interprofessional Swiss recommendations for the treatment of BPSD. To establish the recommendations, a thorough research of the literature has been carried out. Evidence-based data were provided through searches of Medline, Embase, ISI and Cochrane-Database research. Evidence categories of the World Federation of Biological Societies were used. Additionally, the clinical experience of Swiss medical experts was considered.


Loud noise exposure and acoustic neuroma.
The results from studies of loud noise exposure and acoustic neuroma are conflicting. A population-based case-control study of 451 acoustic neuroma patients and 710 age-, sex-, and region-matched controls was conducted in Sweden between 2002 and 2007. Occupational exposure was based on historical measurements of occupational noise (321 job titles summarized by a job exposure matrix) and compared with self-reported occupational noise exposure. We also evaluated self-reported noise exposure during leisure activity. Conditional logistic regression was used to estimate odds ratios. There was no statistically significant association between acoustic neuroma and persistent occupational noise exposure, either with or without hearing protection. Exposure to loud noise from leisure activity without hearing protection was more common among acoustic neuroma cases (odds ratio = 1.47, 95% confidence interval: 1.06, 2.03). Statistically significant odds ratios were found for specific leisure activities including attending concerts/clubs/sporting events (odds ratio = 1.82, 95% confidence interval: 1.09, 3.04) and participating in workouts accompanied by loud music (odds ratio = 2.84, 95% confidence interval: 1.37, 5.89). Our findings do not support an association between occupational exposure to loud noise and acoustic neuroma. Although we report statistically significant associations between leisure-time exposures to loud noise without hearing protection and acoustic neuroma, especially among women, we cannot rule out recall bias as an alternative explanation.


Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial.
Molnupiravir and ritonavir-boosted nirmatrelvir are the two leading oral COVID-19 antiviral treatments, but their antiviral activities in patients have not been compared directly. The aim of this ongoing platform trial is to compare different antiviral treatments using the rate of viral clearance as the measure of antiviral effect. PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. The component of the trial reported here was conducted in the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. We recruited low-risk adult patients aged 18-50 years with early symptomatic COVID-19 (<4 days of symptoms). Eligible patients were randomly assigned using block randomisation via a centralised web app to one of seven treatment groups: molnupiravir, ritonavir-boosted nirmatrelvir, casirivimab-imdevimab, tixagevimab-cilgavimab, favipiravir, fluoxetine, or no study drug. The no study drug group comprised a minimum proportion of 20% of patients at all times, with uniform randomisation ratios applied across the active treatment groups. Results for the concurrently randomised molnupiravir, ritonavir-boosted nirmatrelvir, and no study drug groups are reported here. The primary endpoint was the rate of oropharyngeal viral clearance assessed in a modified intention-to-treat population, defined as patients with more than 2 days of follow-up. Safety was assessed in all participants who took at least one dose of the medication. The viral clearance rate was derived under a Bayesian hierarchical linear model fitted to the log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 1 week (18 measurements). Treatment groups with a probability of more than 0·9 that viral clearance was accelerated by more than 20% compared with no drug entered a non-inferiority comparison (with a 10% non-inferiority margin) compared with the platform's current most effective drug. This ongoing trial is registered at ClinicalTrials.gov, NCT05041907. Between June 6, 2022, and Feb 23, 2023, 209 patients in Thailand were enrolled and concurrently randomly assigned to molnupiravir (n=65), ritonavir-boosted nirmatrelvir (n=59), or no study drug (n=85). 129 (62%) of the patients were female and 80 (38%) were male. Relative to the no study drug group, the rates of viral clearance were 37% (95% credible interval 16-65) faster with molnupiravir and 84% (54-119) faster with ritonavir-boosted nirmatrelvir. In the non-inferiority comparison, viral clearance was 25% (10-38) slower with molnupiravir than ritonavir-boosted nirmatrelvir. Molnupiravir was removed from the study platform when it reached the prespecified inferiority margin of 10% compared with ritonavir-boosted nirmatrelvir. Median estimated viral clearance half-lives were 8·5 h (IQR 6·7-10·1) with ritonavir-boosted nirmatrelvir, 11·6 h (8·6-15·4) with molnupiravir, and 15·5 h (11·9-21·2) with no study drug. Viral rebound occurred more frequently following nirmatrelvir (six [10%] of 58) compared with the no study drug (one [1%] of 84; p=0·018) or the molnupiravir (one [2%] of 65; p=0·051) groups. Persistent infections following molnupiravir had more viral mutations (three of nine patients had an increased number of single nucleotide polymorphisms in samples collected at 7 or more days compared with those at baseline) than after nirmatrelvir (zero of three) or no study drug (zero of 18). There were no adverse events of grade 3 or worse, or serious adverse events in any of the reported treatment groups. Both molnupiravir and ritonavir-boosted nirmatrelvir accelerate oropharyngeal SARS-CoV-2 viral clearance in patients with COVID-19, but the antiviral effect of ritonavir-boosted nirmatrelvir was substantially greater. Measurement of oropharyngeal viral clearance rates provides a rapid and well tolerated approach to the assessment and comparison of antiviral drugs in patients with COVID-19. It should be evaluated in other acute viral respiratory infections. Wellcome Trust through the COVID-19 Therapeutics Accelerator.


The structure of the human allo-ligand HLA-B*3501 in complex with a cytochrome p450 peptide: steric hindrance influences TCR allo-recognition.
Virus-specific T cell populations have been implicated in allo-recognition. The subdominant T cell receptor JL12 recognizes both HLA-B*0801 presenting the Epstein-Barr virus-derived peptide FLRGRAYGL and also HLA-B*3501 presenting the cytochrome p450 self peptide KPIVVLHGY. This cross-reactivity could promote the rejection of HLA-B*3501-positive cells in Epstein-Barr virus-exposed HLA-B*0801 recipients. LC13, the dominant TCR against the HLA-B*0801:FLRGRAYGL complex, fails to recognize HLA-B*3501:KPIVVLHGY. We report the 1.75-Angstrom resolution crystal structure of the human allo-ligand HLA-B*3501:KPIVVLHGY. Similarities between this structure and that of HLA-B*0801:FLRGRAYGL may facilitate cross-recognition by JL12. Moreover, the elevated peptide position in HLA-B*3501:KPIVVLHGY would provide steric hindrance to LC13, preventing it from interacting in the manner in which it interacts with HLA-B*0801:FLRGRAYGL. These findings are relevant to understanding the basis of T cell cross-reactivity in allo-recognition, optimal transplant donor-recipient matching and developing specific molecular inhibitors of allo-recognition.


HIV type 1 Nef promotes neoplastic transformation of immortalized neural cells.
To study the effects of HIV-1 Nef on CNS-derived cells in vivo, an expression system based on the murine neural stem cell line C17.2 was established. Stable expression of LAV-1(Bru)-nef in these cells induced a transformed phenotype and enhanced cell growth in soft agar. Further experiments using previously established nef-expressing human astrocytoma cell lines as well as nef-expressing murine fibroblasts suggested a brain cell-specific transforming activity of Nef. After implantation into syngeneic or nude mice both murine and human nef-expressing CNS-derived cells induced tumor development. Interestingly, human astrocytoma cells expressing a Nef mutant carrying a disrupted SH3-binding motif involved in protein-protein interactions failed to induce tumor formation. These in vivo data suggest that Nef promotes neoplastic transformation of immortalized murine neural stem cells and enhances malignancy of low-tumorigenic human astrocytoma cells. Nef may therefore be involved in the development of AIDS-associated brain tumors.


Using the PhenX Toolkit to Add Standard Measures to a Study.
The PhenX (consensus measures for Phenotypes and eXposures) Toolkit (https://www.phenxtoolkit.org/) offers high-quality, well-established measures of phenotypes and exposures for use by the scientific community. The Toolkit contains 295 measures drawn from 21 research domains (fields of research). The measures were selected by Working Groups of domain experts using a consensus process that included input from the scientific community. The Toolkit provides a description of each PhenX measure, the rationale for including it in the Toolkit, protocol(s) for collecting the measure, and supporting documentation. Users can browse by measures, domains, or collections, or can search the Toolkit using the Smart Query Tool. Once users have selected some measures, they can download a customized Data Collection Worksheet that specifies what information needs to be collected, and a Data Dictionary that describes each variable included in their Data Collection Worksheet. To help researchers find studies with comparable data, PhenX measures and variables are being mapped to studies in the database of Genotypes and Phenotypes (dbGaP).


The hematopoietic stem cell niche: low in oxygen but a nice place to be.
The enormous regenerative capacity of the blood system to sustain functionally mature cells are generated from highly proliferative, short-lived progenitors, which in turn arise from a rare population of pluripotent and self-renewing hematopoietic stem cells (HSC). In the bone marrow, these stem cells are kept in a low proliferative, relatively quiescent state in close proximity to stromal cells and osteoblasts, forming specialized niches. The interaction in particular to bone is crucial to prevent exhaustion of HSCs from uncontrolled cell-cycle entry and to excessive proliferation. In addition, the niche and its components protect stem cells from stress, such as accumulation of reactive oxygen species and DNA damage. One of the key issues is to identify conditions to increase the number of HSCs, either in vivo or during ex vivo growth cultures. This task has been very difficult to resolve and most attempts have been unsuccessful. However, the mechanistic insights to HSC self-renewal and preservation are gradually increasing and there is now hope that future research will enable scientists and clinicians to modulate the process. In this review, we will focus on the molecular mechanisms of self-renewal and HSC maintenance in the light of novel findings that HSCs reside at the lowest end of an oxygen gradient. Hypoxia appears to regulate hematopoiesis in the bone marrow by maintaining important HSC functions, such as cell cycle control, survival, metabolism, and protection against oxidative stress. To improve the therapeutic expansion of HSCs we need to learn more about the molecular mechanisms of hypoxia-mediated regulation.


Pannexin channels are not gap junction hemichannels.
Pannexins, a class of membrane channels, bear significant sequence homology with the invertebrate gap junction proteins, innexins and more distant similarities in their membrane topologies and pharmacological sensitivities with the gap junction proteins, connexins. However, the functional role for the pannexin oligomers, or pannexons, is different from connexin oligomers, the connexons. Many pannexin publications have used the term "hemichannels" to describe pannexin oligomers while others use the term "channels" instead. This has led to confusion within the literature about the function of pannexins that promotes the idea that pannexons serve as gap junction hemichannels and thus have an assembly and functional state as gap junctional intercellular channels. Here we present the case that unlike the connexin gap junction intercellular channels, so far, pannexin oligomers have repeatedly been shown to be channels that are functional in single membranes, but not as intercellular channel in appositional membranes. Hence, they should be referred to as channels and not hemichannels. Thus, we advocate that in the absence of firm evidence that pannexins form gap junctions, the use of the term "hemichannel" be discontinued within the pannexin literature.


Synaptogenesis in the cerebellar cortex: differential regulation of gephyrin and GABAA receptors at somatic and dendritic synapses of Purkinje cells.
In rodent cerebellar cortex, synaptogenesis occurs entirely postnatally, allowing study of the mechanisms of synapse formation in vivo. Here we monitored the clustering of GABA(A) receptors and the scaffolding protein gephyrin at GABAergic postsynaptic sites during rat cerebellar development. We found that GABA(A) receptors and gephyrin co-aggregate at nascent synapses in the molecular and Purkinje cell layers with a similar time course. With few exceptions, gephyrin and GABA(A) receptor subunits clustered selectively in front of presynaptic boutons expressing the vesicular inhibitory amino acid transporter VIAAT and no ectopic localization of these molecules was observed. Surprisingly, gephyrin clusters outlining the cell body of Purkinje cells were transient, and disappeared rapidly at the end of the second postnatal week. The loss of gephyrin from perisomatic synapses was coincident with a significant reduction in the size of GABA(A) receptor clusters. Furthermore, these changes were accompanied by a developmental decrease in the size of synaptic appositions, as documented by electron microscopy. These findings suggest that gephyrin takes part in the initial assembly of postsynaptic specializations and reveal an unsuspected heterogeneity in the molecular organization of the postsynaptic apparatus at somatic and dendritic synapses of mature Purkinje cells.


A prospective cohort study of injury incidence and risk factors in North Carolina high school competitive cheerleaders.
Cheerleaders suffer nearly half of catastrophic injuries observed in female scholastic athletes in the United States. However, incidence of noncatastrophic injury in this population has not been described. Coach, athlete, and injury circumstance variables may predict the injury rate among cheerleaders. Prospective cohort. The authors investigated injury incidence in a sample of North Carolina female cheerleaders who competed inter-scholastically from 1996 to 1999. Injury, exposure, and demographic data were collected from squads that participated in the North Carolina High School Athletic Injury Study. Cheerleaders suffered 133 injuries during 1701 athlete seasons. More than 21% of the injuries were ankle sprains. The injury rate was 8.7; the 95% confidence interval (CI) was 6.5 to 11.7 per 10,000 athlete exposures. In a multivariate Poisson regression model, cheerleaders supervised by coaches with the most education, qualifications, and training (coach EQT) had a nearly 50% reduction in injury risk (rate ratio [RR], 0.5; 95% CI, 0.3-0.9), and cheerleaders supervised by coaches with medium coach EQT had a nearly 40% reduction in injury risk (RR = 0.6; 95% CI, 0.3-1.2) compared to cheerleaders supervised by coaches with low coach EQT.


Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study.
The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.


Functional diversification of IgGs through Fc glycosylation.
IgG antibodies are secreted from B cells and bind to a variety of pathogens to control infections as well as contribute to inflammatory diseases. Many of the functions of IgGs are mediated through Fcγ receptors (FcγRs), which transduce interactions with immune complexes, leading to a variety of cellular outcomes depending on the FcγRs and cell types engaged. Which FcγRs and cell types will be engaged during an immune response depends on the structure of Fc domains within immune complexes that are formed when IgGs bind to cognate antigen(s). Recent studies have revealed an unexpected degree of structural variability in IgG Fc domains among people, driven primarily by differences in IgG subclasses and N-linked glycosylation of the CH2 domain. This translates, in turn, to functional immune diversification through type I and type II FcγR-mediated cellular functions. For example, Fc domain sialylation triggers conformational changes of IgG1 that enable interactions with type II FcγRs; these receptors mediate cellular functions including antiinflammatory activity or definition of thresholds for B cell selection based on B cell receptor affinity. Similarly, presence or absence of a core fucose alters type I FcγR binding of IgG1 by modulating the Fc's affinity for FcγRIIIa, thereby altering its proinflammatory activity. How heterogeneity in IgG Fc domains contributes to human immune diversity is now being elucidated, including impacts on vaccine responses and susceptibility to disease and its sequelae during infections. Here, we discuss how Fc structures arising from sialylation and fucosylation impact immunity, focusing on responses to vaccination and infection. We also review work defining individual differences in Fc glycosylation, regulation of Fc glycosylation, and clinical implications of these pathways.


Intention-to-treat assessment of glecaprevir + pibrentasvir combination therapy for patients with chronic hepatitis C in the real world.
We assessed the problems and efficacy of glecaprevir + pibrentasvir (GLE/PIB) therapy for patients infected with hepatitis C virus (HCV) in the real world. A total of 423 patients infected with HCV who started treatment at eight different centers in Japan were enrolled in the study. Glecaprevir (300 mg) and pibrentasvir (120 mg) were given once daily for 8 weeks to 246 non-cirrhotic direct-acting antiviral (DAA)-naive patients with HCV genotype (GT)-1 or -2, and for 12 weeks to patients who: were DAA-naive cirrhotic (n = 55), had experienced DAA failure (n = 78), were cirrhotic and had DAA failure (n = 37), and were other GT-1/2 (n = 7). Anti-HCV efficacy was defined as a sustained virologic response 12 weeks post-treatment (SVR12). The evaluation was undertaken in an intention-to-treat (ITT) population and in patients who were assessed at SVR12 (modified ITT population). In the ITT population, 220 (89%) patients on the 8-week regimen and 164 (93%) patients on the 12-week regimen achieved SVR12. The 30 dropout patients were predominantly men and with GT-2. All other DAA-naive GT-1 patients achieved SVR12. The 12-week regimen resulted in 100% SVR12 in 41 GT-2 patients. Nine patients did not achieve SVR12: two DAA naive with GT-2a, two GT-3b patients, two GT-1 patients with discontinuation, and three other GT-1 patients with a history of DAA failure. Four of seven patients who discontinued treatment due to severe adverse effects were more than 75 years old. Glecaprevir + pibrentasvir had a remarkable anti-HCV effect in GT-1 and GT-2 patients, but not in GT-3b patients. Although this therapy was reasonably safe, it is necessary to carefully consider elderly and dropout patients.


Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study.
Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt. We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure. Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA. Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.


Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94).
This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/- concomitant cisplatin in locally advanced head and neck cancer. Patients were retrospectively analyzed from the previously reported randomized phase III trial: SAKK 10/94. Severe late RT-related toxicity was defined as late RTOG ≥ grade 3 toxicity starting 3 months after end of RT and/or potential treatment-related death within 3 years of randomization. Two hundred and thirteen randomized patients were analyzed; 84 (39%) experienced severe late RT-related toxicity. With median follow-up of 9.7 years (range, 0.4-15.4 years), median time to severe late RT-related toxicity was 9.6 years. In the univariate Cox proportional hazards model the following variables were associated with severe late RT-related toxicity: advanced N-classification (p<0.001); technically unresectable disease (p=0.04); weight loss ratio (p=0.003); supportive measures (p=0.009) and severe acute dysphagia (p=0.001). In the subsequent multivariate analysis all variables except use of supportive measures remained statistically significant. Chemotherapy did not appear to affect severe late RT-related toxicity, but advanced N-classification, technically unresectable disease, weight loss ratio, and severe acute dysphagia were independent predictive factors for severe late RT-related toxicity.


Measures of human immunodeficiency virus (HIV) community viral load and HIV incidence among people who inject drugs.
To evaluate the measures of community human immunodeficiency virus (HIV) viral load (VL) and the association with HIV incidence among people who inject drugs (PWID). Data were from 1986 to 1999 Urban Health Study conducted among PWID in the San Francisco Bay Area. Extant measures of community VL use mean VL among HIV + study participants, not accounting for the proportion of HIV- individuals. We compared the strength of the associations between HIV incidence and the traditionally measured mean community VL and a new prevalence-adjusted community VL, calculated by dividing the sum of VL among HIV + participants by the total participants irrespective of HIV status. Mean community VL was not correlated with HIV incidence in this sample of PWID (rs = 0.32, P = .28). However, prevalence-adjusted community VL was strongly correlated with HIV incidence (rs = 0.69, P = .009). Nested complimentary log-log linear models indicated that increases in community VL and prevalence-adjusted community VL were both associated with HIV incidence, but prevalence-adjusted community VL was a more sensitive measure (hazard ratio = 1.28, P = .038 and hazard ratio = 3.29, P < .001, respectively). The effect of community VL on HIV incidence may be stronger than previously reported. Future studies of community VL surveillance should consider accounting for the prevalence of HIV using a prevalence-adjusted community VL measure.


MergeAlign: improving multiple sequence alignment performance by dynamic reconstruction of consensus multiple sequence alignments.
The generation of multiple sequence alignments (MSAs) is a crucial step for many bioinformatic analyses. Thus improving MSA accuracy and identifying potential errors in MSAs is important for a wide range of post-genomic research. We present a novel method called MergeAlign which constructs consensus MSAs from multiple independent MSAs and assigns an alignment precision score to each column. Using conventional benchmark tests we demonstrate that on average MergeAlign MSAs are more accurate than MSAs generated using any single matrix of sequence substitution. We show that MergeAlign column scores are related to alignment precision and hence provide an ab initio method of estimating alignment precision in the absence of curated reference MSAs. Using two novel and independent alignment performance tests that utilise a large set of orthologous gene families we demonstrate that increasing MSA performance leads to an increase in the performance of downstream phylogenetic analyses. Using multiple tests of alignment performance we demonstrate that this novel method has broad general application in biological research.


Vitamin D and calcium status in South African adolescents with alcohol use disorders.
Adequate vitamin D and calcium are essential for optimal adolescent skeletal development. Adolescent vitamin D insufficiency/deficiency and poor calcium intake have been reported worldwide. Heavy alcohol use impacts negatively on skeletal health, which is concerning since heavy adolescent drinking is a rising public health problem. This study aimed to examine biochemical vitamin D status and dietary intakes of calcium and vitamin D in 12-16 year-old adolescents with alcohol use disorders (AUD), but without co-morbid substance use disorders, compared to adolescents without AUD. Substance use, serum 25-hydroxyvitamin D (s-25(OH)D) concentrations, energy, calcium and vitamin D intakes were assessed in heavy drinkers (meeting DSM-IV criteria for AUD) (n = 81) and in light/non-drinkers without AUD (non-AUD) (n = 81), matched for age, gender, language, socio-economic status and education. Lifetime alcohol dose was orders of magnitude higher in AUD adolescents compared to non-AUD adolescents. AUD adolescents had a binge drinking pattern and "weekends-only" style of alcohol consumption. Significantly lower (p = 0.038) s-25(OH)D (adjusted for gender, smoking, vitamin D intake) were evident in AUD adolescents compared to non-AUD adolescents. High levels of vitamin D insufficiency/deficiency (s-25(OH)D < 29.9 ng/mL) were prevalent in both groups, but was significantly higher (p = 0.013) in the AUD group (90%) compared to the non-AUD group (70%). All participants were at risk of inadequate calcium and vitamin D intakes (Estimated Average Requirement cut-point method). Both groups were at risk of inadequate calcium intake and had poor biochemical vitamin D status, with binge drinking potentially increasing the risk of the latter. This may have negative implications for peak bone mass accrual and future osteoporosis risk, particularly with protracted binge drinking.


Immediate and long term results of percutaneous coronary angioplasty in patients aged 70 and over.
To study the immediate and long term clinical success of percutaneous transluminal coronary balloon angioplasty in patients over 70 years old. Patients undergoing percutaneous transluminal angioplasty were prospectively entered in a specially designed database. The clinical and angiographic data of all patients over 70 were reviewed. Follow up data were collected by interview, during outpatient visits, by questionnaire, or through the referring physician. A tertiary referral cardiac centre. 166 patients over 70 (median 73, range 70-84) underwent coronary angioplasty because of unstable angina (81 patients), stable angina (76 patients), or acute myocardial infarction (nine patients). The initial clinical success rate was 86% (142 of 166 patients). A major procedural complication occurred in 10 patients (6%): four patients (2%) died, six patients (4%) underwent emergency bypass surgery, and five patients (3%) sustained an acute myocardial infarction. In 14 patients (8%) coronary angioplasty did not significantly reduce the diameter stenosis but there were no associated complications. A total of 226 lesions were attempted. The initial angiographic success rate was 192 out of 226 lesions (85%). The median follow up was 21 (range 0.5-66) months. Sixteen patients (10%) died during follow up, eight patients (5%) sustained a non-fatal myocardial infarction, 21 patients (13%) underwent a second or third balloon dilatation, and 17 patients (10%) underwent elective bypass surgery. Of the 146 survivors, 99 patients (68%) had sustained clinical improvement. The estimated survival at four years (Kaplan-Meier method) was 89 (SD 4)%. The event free survival at four years for the total study population was 61 (8)%. Multivariate logistic regression analysis showed that the extent of vessel disease was the only independent predictive factor for event free survival: the event free survival rate was 81 (10)% at four years for patients with single vessel disease, compared with 45 (12)% for patients with multivessel disease. Coronary angioplasty in patients over 70 was a safe and effective treatment for obstructive coronary artery disease. The extent of vessel disease, and not the completeness of revascularisation, was the only independent predictive factor for event free survival.


'On line' data handling in a routine haematology department.
The use of a ;stand alone' mini computer, on line, data acquisition system is described utilising a microprocessor as an adjunct to the main central processor to increase data transmission rates. Visual display units (VDU) provide on line flexibility of data input. The system acquires, on line, the Coulter S generated parameters together with the associated patient identification data and other requested tests. Erythrocyte sedimentation rate, platelet count, and B12 and folate results are fed in at will via the VDUs, using rapid entry subroutines. Percentage differential white cell count results and the absolute leucocyte count are calculated by the microprocessor, on line input being facilitated by remote keyboards associated with the VDUs. Total editing of all requests and results is available on all ;current' (unfiled) reports via the VDUs, and this facility includes the entry of film appearances using plus symbols and predetermined comments available against a code number. This editing function is also used to enter all other results that can be made available on the computer-printed report form. The computer system also provides quality control data, immediate printout of Coulter S results outside given limits, cumulative filing for all routine and designated ;priority' results, and a daily alphabetical listing of all patients from whom specimens have been examined together with full blood count, ESR, and platelet results on specimens examined that day.


Overstating the evidence: double counting in meta-analysis and related problems.
The problem of missing studies in meta-analysis has received much attention. Less attention has been paid to the more serious problem of double counting of evidence. Various problems in overstating the precision of results from meta-analyses are described and illustrated with examples, including papers from leading medical journals. These problems include, but are not limited to, simple double counting of the same studies, double counting of some aspects of the studies, inappropriate imputation of results, and assigning spurious precision to individual studies. Some suggestions are made as to how the quality and reliability of meta-analysis can be improved. It is proposed that the key to quality in meta-analysis lies in the results being transparent and checkable. Existing quality check lists for meta-analysis do little to encourage an appropriate attitude to combining evidence and to statistical analysis. Journals and other relevant organisations should encourage authors to make data available and make methods explicit. They should also act promptly to withdraw meta-analyses when mistakes are found.


Special considerations in distracted driving with teens.
Novice teen drivers have long been known to have an increased risk of crashing, as well as increased tendencies toward unsafe and risky driving behaviors. Teens are unique as drivers for several reasons, many of which have implications specifically in the area of distracted driving. This paper reviews several of these features, including the widespread prevalence of mobile device use by teens, their lack of driving experience, the influence of peer passengers as a source of distraction, the role of parents in influencing teens' attitudes and behaviors relevant to distracted driving and the impact of laws designed to prevent mobile device use by teen drivers. Recommendations for future research include understanding how engagement in a variety of secondary tasks by teen drivers affects their driving performance or crash risk; understanding the respective roles of parents, peers and technology in influencing teen driver behavior; and evaluating the impact of public policy on mitigating teen crash risk related to driver distraction.


Single fiber identification with nondestructive excitation-emission spectral cluster analysis.
Identification methods for single textile fibers are in demand for forensic applications, and nondestructive methods with minimal pretreatment have the greatest potential for utility. Excitation-emission luminescence data provide a three-dimensional matrix for comparison of single-fiber dyes, and these data are enhanced by principal component analysis and comparison of fibers using a statistical figure of merit. No dye extraction methods are required to sample the spectra from a single fiber. This approach has been applied to the analysis of single fibers to compare closely matched dye pairs, acid blue (AB) 25 and 41 and direct blue (DB) 1 and 53. In all cases, the accuracy of fiber identification was high and no false positive identifications were made.


A Method for Detecting Atmospheric Lagrangian Coherent Structures Using a Single Fixed-Wing Unmanned Aircraft System.
The transport of material through the atmosphere is an issue with wide ranging implications for fields as diverse as agriculture, aviation, and human health. Due to the unsteady nature of the atmosphere, predicting how material will be transported via the Earth's wind field is challenging. Lagrangian diagnostics, such as Lagrangian coherent structures (LCSs), have been used to discover the most significant regions of material collection or dispersion. However, Lagrangian diagnostics can be time-consuming to calculate and often rely on weather forecasts that may not be completely accurate. Recently, Eulerian diagnostics have been developed which can provide indications of LCS and have computational advantages over their Lagrangian counterparts. In this paper, a methodology is developed for estimating local Eulerian diagnostics from wind velocity data measured by a single fixed-wing unmanned aircraft system (UAS) flying in a circular arc. Using a simulation environment, driven by realistic atmospheric velocity data from the North American Mesoscale (NAM) model, it is shown that the Eulerian diagnostic estimates from UAS measurements approximate the true local Eulerian diagnostics and also predict the passage of LCSs. This methodology requires only a single flying UAS, making it easier and more affordable to implement in the field than existing alternatives, such as multiple UASs and Dopler LiDAR measurements. Our method is general enough to be applied to calculate the gradient of any scalar field.


Dengue Virus-Induced Reactive Oxygen Species Production in Rat Microglial Cells.
Encephalitis has been described worldwide as a severe complication in patients infected by dengue virus. Reactive oxygen species (ROS) production is a key mechanism involved in the neuronal damage caused by viral encephalitis. In the present study, the capability of dengue virus serotypes 2 (DENV2) and DENV4 to induce ROS production was investigated in a rat microglial cell line, HAPI cells. The cells were infected with DENV2 and DENV4 at a multiplicity of infection of 0.1 for a 2-h adsorption period. Japanese encephalitis virus (JEV) was used as the reference. DENV2- and DENV4-induced microglial activation and significantly increased ROS production corresponded to decreased cell viability. The activity of DENV4 was significantly higher than the activities of DENV2 and JEV at 48 and 72 h post infection. DENV4 partly induced ROS production via an iron-induced Fenton reaction, as demonstrated by the treatment with an iron chelator, deferiprone. Despite the induction of increased inducible nitric oxide synthase expression and nitric oxide (NO) production by JEV, DENV2, and DENV4 did not induce NO production, suggesting the activation of different pathways in response to infections by different viruses. In conclusion, DENV2 and DENV4 have the capability to induce ROS production and activate microglia, which have been reported as the key components of neuronal damage.


Development and Delivery of a Physical Activity Intervention for People With Huntington Disease: Facilitating Translation to Clinical Practice.
We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process. Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory. Intervention Delivery: Key components underpinning the delivery of the intervention were implemented including a defined coach training program and intervention fidelity assessment methods. Training of coaches (physical therapists, occupational therapists, research nurses, and exercise trainers) was delivered via group and 1:1 training sessions using a detailed coach's manual, and with ongoing support via video calls, and e-mail communication as needed. Detailed documentation was provided to determine costs of intervention development and coach training. Intervention delivery coaches at 8 sites across the United Kingdom participated in the face-to-face training. Self-report checklists completed by each of the coaches indicated that all components of the intervention were delivered in accordance with the protocol. Mean (standard deviation) intervention fidelity scores (n = 15), as measured using a purpose-developed rating scale, was 11 (2.4) (out of 16 possible points). Coaches' perceptions of intervention fidelity were similarly high. The total cost of developing the intervention and providing training was £30,773 ($47,042 USD). An important consideration in promoting translation of clinical research into practice is the ability to convey the detailed components of how the intervention was delivered to facilitate replication if the results are favorable. This report presents an illustrative example of a physical activity intervention, including the development and the training required to deliver it. This approach has the potential to facilitate reproducibility, evidence synthesis, and implementation in clinical practice.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A122).


Successful 10-second one-legged stance performance predicts survival in middle-aged and older individuals.
Balance quickly diminishes after the mid-50s increasing the risk for falls and other adverse health outcomes. Our aim was to assess whether the ability to complete a 10- s one-legged stance (10-second OLS) is associated with all-cause mortality and whether it adds relevant prognostic information beyond ordinary demographic, anthropometric and clinical data. Anthropometric, clinical and vital status and 10-s OLS data were assessed in 1702 individuals (68% men) aged 51-75 years between 2008 and 2020. Log-rank and Cox modelling were used to compare survival curves and risk of death according to ability (YES) or inability (NO) to complete the 10-s OLS test. Overall, 20.4% of the individuals were classified as NO. During a median follow-up of 7 years, 7.2% died, with 4.6% (YES) and 17.5% (NO) on the 10-s OLS. Survival curves were worse for NO 10-s OLS (log-rank test=85.6; p<0.001). In an adjusted model incorporating age, sex, body mass index and comorbidities, the HR of all-cause mortality was higher (1.84 (95% CI: 1.23 to 2.78) (p<0.001)) for NO individuals. Adding 10-s OLS to a model containing established risk factors was associated with significantly improved mortality risk prediction as measured by differences in -2 log likelihood and integrated discrimination improvement. Within the limitations of uncontrolled variables such as recent history of falls and physical activity, the ability to successfully complete the 10-s OLS is independently associated with all-cause mortality and adds relevant prognostic information beyond age, sex and several other anthropometric and clinical variables. There is potential benefit to including the 10-s OLS as part of routine physical examination in middle-aged and older adults.


Patients with tension-type headaches feel stigmatized.
The author, a sufferer of tension-type headache (TTH), believes that the word "tension" in "tension-type headache" carries a social stigma and that patients do not accept a diagnosis of TTH readily. TTH is the most common primary headache disorder. The disability of TTH as a burden of society is greater than that of migraine. Absenteeism because of TTH is higher than that due to migraine. However, patients with TTH do not go for consultation. Even the prevalence of new daily persistent headache (NDPH) is 12 times higher at the headache clinic than that of chronic TTH (CTTH). These points hint that TTH patients probably do not want to visit the clinic. The author believes that it could be because of the stigma attached to "tension." Herein, the author has noted the first responses given by 50 consecutive patients with TTH when they were told that they had been suffering from TTH. The first answer of 64% of patients with TTH was "I do not have any tension/stress." This denial is similar to the denial declared by patients with depression. Depression and tension are similar in the sense that both are considered as a signs of personal weakness. Such a preconception in the society creates a stigma, and patients deny the diagnosis, conceal symptoms, and become reluctant to seek help and treatment.


The role of cotranscriptional histone methylations.
The carboxy-terminal domain (CTD) of the RNA polymerase II subunit Rpb1 undergoes dynamic phosphorylation, with different phosphorylation sites predominating at different stages of transcription. Our laboratory studies show how various mRNA-processing and chromatin-modifying enzymes interact with the phosphorylated CTD to efficiently produce mRNAs. The H3K36 methyltransferase Set2 interacts with CTD carrying phosphorylations characteristic of downstream elongation complexes, and the resulting cotranscriptional H3K36 methylation targets the Rpd3S histone deacetylase to downstream transcribed regions. Although positively correlated with gene activity, this pathway actually inhibits transcription elongation as well as initiation from cryptic promoters within genes. During early elongation, CTD serine 5 phosphorylation helps recruit the H3K4 methyltransferase complex containing Set1. Within 5' transcribed regions, cotranscriptional H3K4 dimethylation (H3K4me2) by Set1 recruits the deacetylase complex Set3C. Finally, H3K4 trimethylation at the most promoter-proximal nucleosomes is thought to stimulate transcription by promoting histone acetylation by complexes containing the ING/Yng PHD finger proteins. Surprisingly, the Rpd3L histone deacetylase complex, normally a transcription repressor, may also recognize H3K4me3. Together, the cotranscriptional histone methylations appear to function primarily to distinguish active promoter regions, which are marked by high levels of acetylation and nucleosome turnover, from the deacetylated, downstream transcribed regions of genes.


Findings of cecal volvulus at CT.
To assess the diagnostic performance of computed tomographic (CT) and radiographic (as seen on CT topograms) signs of cecal volvulus. In this institutional review board-approved, HIPAA-compliant retrospective study, the CT and CT topogram findings in 11 patients (one man, 10 women; age range, 26-100 years) with surgically confirmed cecal volvulus and 12 control patients were reviewed. The control subjects had suspicious radiographs, had undergone CT within 24 hours of radiography, and had received a clinical diagnosis other than cecal volvulus. Three radiologists independently evaluated the CT topograms for cecal distention, the coffee bean sign, cecal apex location, and distal colon decompression. CT images were analyzed for cecal distention, cecal apex location, distal colon decompression, and presence or absence of the whirl, ileocecal twist, transition point(s), the X-marks-the-spot, and the split wall. Sensitivity, specificity, and predictive values were computed. Baseline statistical values for the cecal volvulus and control groups were analyzed by using a two-tailed Z test to compare proportions with a threshold confidence interval of 95%. CT findings of bowel ischemia (free air or fluid, pneumatosis intestinalis, portal venous gas, mesenteric stranding) were correlated with pathology report findings. On CT topograms, greater than 10-cm cecal distention, coffee bean sign, and left upper quadrant cecal apex had sensitivities of 45% (five of 11 patients), 27% (three of 11 patients), and 45% (five of 11 patients), respectively, and specificities of 100% (12 of 12 control subjects), 92% (11 of 12 control subjects), and 100% (12 of 12 control subjects), respectively. Distal colon decompression had sensitivities and specificities of 91% (10 of 11 patients) and 83% (10 of 12 control subject), respectively, on topograms and of 91% (10 of 11 patients) and 92% (11 of 12 patients), respectively, on CT images. On cross-sectional CT images, greater than 10-cm cecal distention, left upper quadrant cecal apex, whirl, ileocecal twist, transition point(s), X-marks-the-spot, and split wall had sensitivities of 45% (five of 11 patients), 36% (four of 11 patients), 73% (eight of 11 patients), 54% (six of 11 patients), 82% (nine of 11 patients), 27% (three of 11 patients), and 54% (six of 11 patients), respectively; each had 100% specificity. Pneumatosis intestinalis and free air had 100% (four of four control subjects) specificity. Overall, CT signs of bowel ischemia correlated poorly with pathology report findings. When cecal volvulus is suspected, the absence of distal colonic decompression on CT topograms makes the diagnosis very unlikely. Whirl, ileocecal twist, transition points, X-marks-the-spot, and split wall have high specificity for cecal volvulus.


Transforming higher education and the professional preparation of nurses.
Since the early 1990s, nurse education in the UK has been directly influenced by Department of Health policy and by the structure and management of higher education. Market forces, consumer values, increasing demand for quality and accountability, and technological advances have influenced the academic landscape and the provision for nurse education within it. Despite the recent Government confirmation that new nurses will all be educated to degree level from 2013, the future direction of nursing, and nurse education, is still far from certain. The Government proposes significant change to the higher educational sector in order to enhance employer engagement. Foundation degrees are an integral component of the Government's policy for developing the vocational skills and for widening participation in higher education. As a result of this, and other policy initiatives, it is likely that a smaller supply of graduate nurses will provide future leadership and supervision in the delivery of nursing. It is also likely that there will be greater demand for postgraduate-level education for registered nurses.


Exposure to bisphenol A during pregnancy and child neuropsychological development in the INMA-Sabadell cohort.
Bisphenol A (BPA) may be a neurodevelopmental toxicant, but evidence is not consistent in terms of the sex-specific patterns of the associations and the specific behavioral or cognitive domains most affected. To examine the effects of prenatal BPA exposure on cognitive, psychomotor, and behavioral development in 438 children at 1, 4 and 7 years of age. BPA was measured in spot urine samples collected in trimester 1 and 3 of pregnancy from women participating in the INMA-Sabadell birth cohort study. Cognitive and psychomotor development was assessed at 1 and 4 years using psychologist-based scales. Attention deficit hyperactivity disorder (ADHD) symptoms and other behavioral problems were assessed at 4 years by teachers and at 7 years by parents using questionnaire-based rating scales. Geometric mean creatinine-adjusted BPA concentration of the averaged samples was 2.6 μg/g creatinine. BPA exposure was not associated with the cognitive scores or their subscales at 1 and 4 years of age. At 1 year of age, exposure in the highest tertile of BPA concentrations was associated with a reduction of psychomotor scores (T3 vs T1 β=-4.28 points, 95% CI: -8.15, -0.41), but there was no association with psychomotor outcomes at 4 years. At 4 years, BPA exposure was associated with an increased risk of ADHD-hyperactivity symptoms (Incidence Rate Ratio (IRR) per log10 μg BPA/g creatinine increase=1.72; 1.08, 2.73) and this association was stronger in boys than in girls. Further, boys had an increased risk of ADHD-inattention symptoms whereas girls showed a reduced risk (p for interaction <0.1). At 7 years, these associations were not statistically significant nor were any other behavioral problems. These results suggest that prenatal BPA exposure does not affect cognitive development up to age 4 years. Associations are observed with psychomotor development and ADHD-related symptoms at early ages, but these do not appear to persist until later ages.


Chemical amplification of magnetic field effects relevant to avian magnetoreception.
Magnetic fields as weak as the Earth's can change the yields of radical pair reactions even though the energies involved are orders of magnitude smaller than the thermal energy, kBT, at room temperature. Proposed as the source of the light-dependent magnetic compass in migratory birds, the radical pair mechanism is thought to operate in cryptochrome flavoproteins in the retina. Here we demonstrate that the primary magnetic field effect on flavin photoreactions can be amplified chemically by slow radical termination reactions under conditions of continuous photoexcitation. The nature and origin of the amplification are revealed by studies of the intermolecular flavin-tryptophan and flavin-ascorbic acid photocycles and the closely related intramolecular flavin-tryptophan radical pair in cryptochrome. Amplification factors of up to 5.6 were observed for magnetic fields weaker than 1 mT. Substantial chemical amplification could have a significant impact on the viability of a cryptochrome-based magnetic compass sensor.


Diabetes, diabetes treatment and breast cancer prognosis.
The objectives of this study are to assess the impact of pre-existing diabetes and diabetes treatment on breast cancer prognosis. 8,108 women with centrally confirmed invasive breast cancer in the Women's Health Initiative diagnosed between 1998 and 2013 were followed through the date of death or September 20, 2013. Information on diabetes and diabetes therapy were obtained via self-report and face-to-face review of current medication containers, respectively. Cox proportional hazard regression was used to estimate adjusted relative hazard ratios for overall mortality. The proportional subdistribution hazard model was used to estimate hazard ratios for breast cancer-specific mortality. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR 1.26 95 % CI 1.06-1.48), especially among those who took insulin or had longer duration of diabetes. However, diabetes was not associated with increased risk of breast cancer-specific mortality, regardless of type of treatment and duration of diabetes, despite the significant association of diabetes with unfavorable tumor characteristics. Our large prospective cohort study provides additional evidence that pre-existing diabetes increases risk of total mortality among women with breast cancer. The increased total mortality associated with diabetes was mainly driven by increased risk of dying from diseases other than breast cancer. Thus, the continuum of care for breast cancer patients with diabetes should include careful attention to CVD risk factors and other non-cancer conditions.


Ulnar nerve monitoring during percutaneous pinning of supracondylar fractures in children.
Supracondylar fractures of the humerus in children are frequently managed by closed reduction and percutaneous pinning. Insertion of medial and lateral pins is more stable than lateral pinning alone, but carries an increased risk for ulnar nerve damage. This study describes the use of electrical stimulation concurrent with medial pin insertion as a monitoring technique for avoiding iatrogenic ulnar nerve injury. A retrospective review was conducted on 138 children, mean age 5.6 years (SD±2.5), who were admitted to the hospital between 2007 and 2010 with uncomplicated supracondylar fractures, Gartland type II and above, and intact neurovascular presentation. The location of the ulnar nerve was identified and marked preoperatively by observing twitch contractions in response to electrical stimulation. The medial pin served as an active electrode during pin insertion, and repeated stimulation throughout the insertion process ensured no contact with the response of the ulnar nerve. After pin insertion, ulnar nerve stimulation was used again to ensure nerve continuity viability. All fractures were stabilized with 2 to 4 cross K-wires (size 1.6 mm), with number depending on stability of the fracture. The children were discharged home 2 days after fracture fixation, with no iatrogenic ulnar nerve injury observed in any of the children. The only postoperative complication involved 2 cases of anterior interosseus nerve neuropraxia, which resolved spontaneously after 4 to 6 months. Primary fracture healing was achieved without nonunions or delayed unions in all cases. Ulnar nerve stimulation before and during the percutaneous pinning of supracondylar fractures in children is a simple, economical, and easy-to-implement technique that can prevent iatrogenic ulnar nerve injury. Level IV.


Holodiagrams in birefringent media.
The modifications to the holodiagram concept to describe free propagation (the extraordinary ray) inside birefringent materials are described. Holodiagrams are graphs showing the loci where the sum or the difference in the optical path from a generic point to two foci is the same. The holodiagrams obtained in this way give the shape of the surfaces that satisfy Fermat's principle, conjugate by reflection of one focus into the other, and represent the interference fringes obtained if both points are coherent sources. The reflection law in birefringent media is investigated in relation to this diagram. One direction for the optical axis is considered: parallel to the line joining the source and the observation point. Quartz-type and calcite-type crystals are studied.


Cellular response to the redox active lipid peroxidation products: induction of glutathione S-transferase P by 4-hydroxy-2-nonenal.
Membrane lipid peroxidation is known to produce various aldehydic compounds which cause a wide range of biological effects including heart disease, aging, and cancer. To investigate the effect of lipid peroxidation products on the expression of glutathione S-transferases (GSTs), which catalyze the conjugation of reactive chemicals with glutathione and play an important role in protecting cells, normal rat liver epithelial cells (RL34) were exposed to a variety of aldehydic compounds. We found that the GST activity in RL34 cells was induced by alpha,beta-unsaturated aldehydes, such as acrolein (1.3-fold), crotonaldehyde (1.3-fold), 4-hydroxy-2-hexenal (HHE) (1.4-fold), and 4-hydroxy-2-nonenal (HNE) (1.7-fold). The induction of GST activity by HNE was time-dependent, reaching a plateau after 16 h. The immunoblot analysis using the polyclonal antibodies against GST isozymes demonstrated that GST-P (pi-class), a well-known tumor marker, was significantly induced 16 h after the HNE treatment. Also, immunostaining for the presence of GST-P confirmed the enhanced expression of GST-P in the cytoplasm of the cells. Northern blot analysis revealed that the HNE treatment of RL34 cells for 1 h enhanced the expression of GST-P mRNA, which returned to the control level after 16 h. These data suggest that the induction of GST-P by HNE may represent an important cellular defense mechanism against oxidative injury.


Monodisperse hollow silica nanospheres for nano insulation materials: synthesis, characterization, and life cycle assessment.
The application of manufactured nanomaterials provides not only advantages resulting from their unique properties but also disadvantages derived from the high energy use and CO(2) burden related to their manufacture, operation, and disposal. It is therefore important to understand the trade-offs of process economics of nanomaterial production and their associated environmental footprints in order to strengthen the existing advantages while counteracting disadvantages. This work reports the synthesis, characterization, and life cycle assessment (LCA) of a new type of superinsulating materials, nano insulation materials (NIMs), which are made of hollow silica nanospheres (HSNSs) and have great flexibility in modifying their properties by tuning the corresponding structural parameters. The as-prepared HSNSs in this work have a typical inner pore diameter of about 150 nm and a shell thickness of about 10-15 nm and exhibit a reduced thermal conductivity of about 0.02 W/(m K) because of their size-dependent thermal conduction at the nanometer scale. The energy and raw material consumption related to the synthesis of HSNSs have been analyzed by the LCA method. The results indicate that the recycle of chemicals, up-scaling production, and use of environmentally friendly materials can greatly affect the process of environmental footprints. New synthesis routes for NIMs with improved thermal performance and energy and environmental features are also recommended on the basis of the LCA study.


Conservation of reef manta rays (Manta alfredi) in a UNESCO World Heritage Site: Large-scale island development or sustainable tourism?
A large reef manta ray (Manta alfredi) aggregation has been observed off the north Sudanese Red Sea coast since the 1950s. Sightings have been predominantly within the boundaries of a marine protected area (MPA), which was designated a UNESCO World Heritage Site in July 2016. Contrasting economic development trajectories have been proposed for the area (small-scale ecotourism and large-scale island development). To examine space-use, Wildlife Computers® SPOT 5 tags were secured to three manta rays. A two-state switching Bayesian state space model (BSSM), that allowed movement parameters to switch between resident and travelling, was fit to the recorded locations, and 50% and 95% kernel utilization distributions (KUD) home ranges calculated. A total of 682 BSSM locations were recorded between 30 October 2012 and 6 November 2013. Of these, 98.5% fell within the MPA boundaries; 99.5% for manta 1, 91.5% for manta 2, and 100% for manta 3. The BSSM identified that all three mantas were resident during 99% of transmissions, with 50% and 95% KUD home ranges falling mainly within the MPA boundaries. For all three mantas combined (88.4%), and all individuals (manta 1-92.4%, manta 2-64.9%, manta 3-91.9%), the majority of locations occurred within 15 km of the proposed large-scale island development. Results indicated that the MPA boundaries are spatially appropriate for manta rays in the region, however, a close association to the proposed large-scale development highlights the potential threat of disruption. Conversely, the focused nature of spatial use highlights the potential for reliable ecotourism opportunities.


Unnecessary milk elimination diets in children with atopic dermatitis.
Milk elimination diets are frequently adopted in the treatment of atopic dermatitis, although the real prevalence of clinically relevant food allergy remains unclear and reports from different authors are often in disagreement. We investigated the percentage of children allergic to cow's milk compared with the rate of milk exclusion diets in a group of patients with atopic dermatitis. We enrolled 206 children (79 girls, 127 boys), mean age 45.8 (4-68) months, affected by atopic dermatitis into our study. All children underwent radioallergosorbent test for casein, alpha-lactalbumin and beta-lactoglobulin, prick test, atopy patch test, and oral provocation test. Children were followed up at 1, 3, 6, and 12 months. Of the 206 patients, 20 were excluded from statistical analysis, leaving 186. Forty-five (24.2%) were on a milk elimination diet and 141 on a normal diet. Four patients on the milk-free diet (8.9%), accounting for 2.2% of all patients, were found to be allergic. In the others, milk reintroduction did not cause the disease to worsen during the follow-up period. No children on a normal diet were found to be allergic. Our results demonstrated an actual prevalence of cow's milk allergy in patients on milk elimination diets (4%) to be significantly lower than the number of patients prescribed such diets (24.2%)-confirming that this measure is being applied excessively.


The trajectory of maternal perinatal depressive symptoms predicts executive function in early childhood.
Perinatal maternal depression may affect fetal neurodevelopment directly or indirectly via exposures such as smoking, alcohol, or antidepressant use. The relative contribution of these risk factors on child executive function (EF) has not been explored systematically. A prospective pregnancy cohort of 197 women and their children was studied to determine whether maternal depression diagnosis and the trajectory of maternal depressive symptoms (MDSs) from early pregnancy to 12 months postpartum predicts child EF at age 4 (measured using the preschool age psychiatric assessment, NEPSY-II, and Shape School task) using latent growth curve modeling. Indirect effects of smoking, alcohol, and antidepressant use were also formally tested. Increasing maternal perinatal depressive symptoms over time predicted more inattentive symptoms, poorer switching, and motor inhibition, but not cognitive inhibition. When adjusted for multiple comparison, and after accounting for maternal cognition and education, the association with child inattentive symptoms remained significant. However, diagnosed depression did not predict child EF outcomes. Prenatal exposure to smoking, alcohol, and antidepressants also did not mediate pathways from depressive symptoms to EF outcomes. Our findings were limited by sample size and statistical power to detect outcome effects of smaller effect size. This study suggests that increasing MDSs over the perinatal period is associated with poorer EF outcomes in children at age 4 - independent of prenatal smoking, drinking, or antidepressant use. Depressive chronicity, severity, and postpartum influences may play crucial roles in determining childhood outcomes of EF.


Deficits in bioenergetics and impaired immune response in granulocytes from children with autism.
Despite the emerging role of mitochondria in immunity, a link between bioenergetics and the immune response in autism has not been explored. Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of ≥7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing ≥1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2-related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network.


Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis.
Necrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams. This is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent.Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test. Medical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted. Prophylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.


Understanding and Engineering Thermostability in DNA Ligase from Thermococcus sp. 1519.
The physical chemical principles underlying enzymatic thermostability are keys to understand the way evolution has shaped proteins to adapt to a broad range of temperatures. Understanding the molecular determinants at the basis of protein thermostability is also an important factor for engineering more thermoresistant enzymes to be used in the industrial setting, such as, for instance, DNA ligases, which are important for DNA replication and repair and have been long used in molecular biology and biotechnology. Here, we first address the origin of thermostability in the thermophilic DNA ligase from archaeon Thermococcus sp. 1519 and identify thermosensitive regions using molecular modeling and simulations. In addition, we predict mutations that can enhance thermostability of the enzyme through bioinformatics analyses. We show that thermosensitive regions of this enzyme are stabilized at higher temperatures by optimization of charged groups on the surface, and we predict that thermostability can be further increased by further optimization of the network among these charged groups. Engineering this DNA ligase by introducing selected mutations (i.e., A287K, G304D, S364I, and A387K) eventually produced a significant and additive increase in the half-life of the enzyme when compared to that of the wild type.


Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals.
There is great interindividual variability in HIV-1 viral setpoint after seroconversion, some of which is known to be due to genetic differences among infected individuals. Here, our focus is on determining, genome-wide, the contribution of variable gene expression to viral control, and to relate it to genomic DNA polymorphism. RNA was extracted from purified CD4+ T-cells from 137 HIV-1 seroconverters, 16 elite controllers, and 3 healthy blood donors. Expression levels of more than 48,000 mRNA transcripts were assessed by the Human-6 v3 Expression BeadChips (Illumina). Genome-wide SNP data was generated from genomic DNA using the HumanHap550 Genotyping BeadChip (Illumina). We observed two distinct profiles with 260 genes differentially expressed depending on HIV-1 viral load. There was significant upregulation of expression of interferon stimulated genes with increasing viral load, including genes of the intrinsic antiretroviral defense. Upon successful antiretroviral treatment, the transcriptome profile of previously viremic individuals reverted to a pattern comparable to that of elite controllers and of uninfected individuals. Genome-wide evaluation of cis-acting SNPs identified genetic variants modulating expression of 190 genes. Those were compared to the genes whose expression was found associated with viral load: expression of one interferon stimulated gene, OAS1, was found to be regulated by a SNP (rs3177979, p = 4.9E-12); however, we could not detect an independent association of the SNP with viral setpoint. Thus, this study represents an attempt to integrate genome-wide SNP signals with genome-wide expression profiles in the search for biological correlates of HIV-1 control. It underscores the paradox of the association between increasing levels of viral load and greater expression of antiviral defense pathways. It also shows that elite controllers do not have a fully distinctive mRNA expression pattern in CD4+ T cells. Overall, changes in global RNA expression reflect responses to viral replication rather than a mechanism that might explain viral control.


Mature microsatellites: mechanisms underlying dinucleotide microsatellite mutational biases in human cells.
Dinucleotide microsatellites are dynamic DNA sequences that affect genome stability. Here, we focused on mature microsatellites, defined as pure repeats of lengths above the threshold and unlikely to mutate below it in a single mutational event. We investigated the prevalence and mutational behavior of these sequences by using human genome sequence data, human cells in culture, and purified DNA polymerases. Mature dinucleotides (≥10 units) are present within exonic sequences of >350 genes, resulting in vulnerability to cellular genetic integrity. Mature dinucleotide mutagenesis was examined experimentally using ex vivo and in vitro approaches. We observe an expansion bias for dinucleotide microsatellites up to 20 units in length in somatic human cells, in agreement with previous computational analyses of germ-line biases. Using purified DNA polymerases and human cell lines deficient for mismatch repair (MMR), we show that the expansion bias is caused by functional MMR and is not due to DNA polymerase error biases. Specifically, we observe that the MutSα and MutLα complexes protect against expansion mutations. Our data support a model wherein different MMR complexes shift the balance of mutations toward deletion or expansion. Finally, we show that replication fork progression is stalled within long dinucleotides, suggesting that mutational mechanisms within long repeats may be distinct from shorter lengths, depending on the biochemistry of fork resolution. Our work combines computational and experimental approaches to explain the complex mutational behavior of dinucleotide microsatellites in humans.


Accurate and fast stray radiation calculation based on improved backward ray tracing.
An improved method of backward ray tracing is proposed according to the theory of geometrical optics and thermal radiation heat transfer. The accuracy is essentially raised comparing to the traditional backward ray tracing because ray orders and weight factors are taken into account and the process is designed as sequential and recurring steps to trace and calculate different order stray lights. Meanwhile, it needs very small computation comparing to forward ray tracing because irrelevant surfaces and rays are excluded from the tracing. The effectiveness was verified in the stray radiation analysis for a cryogenic infrared (IR) imaging system, as the results coincided with the actual stray radiation irradiance distributions in the real images. The computation amount was compared with that of forward ray tracing in the narcissus calculation for another cryogenic IR imaging system, it was found that to produce the same accuracy result, the computation of the improved backward ray tracing is far smaller than that of forward ray tracing by at least 2 orders of magnitude.


Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron.
Ninety-nine anemic children aged 1-8 y were divided into four groups. Each group was supplemented for 2 mo with vitamin A, iron, vitamin A plus Fe, or a placebo. Clinical, hematological, and Fe biochemical evaluations were performed at the beginning and end of the study. Vitamin A supplementation produced significant elevations in the serum levels of retinol, blood hemoglobin, hematocrit, erythrocytes, serum Fe, and percent transferrin saturation (%TS) and had no effect on total Fe binding capacity (TIBC) or serum ferritin. Fe supplementation did not affect serum retinol. However, it improved hematological and Fe nutrition indicators, including TIBC and serum ferritin. The simultaneous administration of vitamin A and Fe resulted in a better response of serum Fe and %TS than when the supplement consisted only of vitamin A or Fe alone. Vitamin A benefits hematological condition and Fe metabolism.


Machine Learning-Based Risk Stratification for Gestational Diabetes Management.
Gestational diabetes mellitus (GDM) is often diagnosed during the last trimester of pregnancy, leaving only a short timeframe for intervention. However, appropriate assessment, management, and treatment have been shown to reduce the complications of GDM. This study introduces a machine learning-based stratification system for identifying patients at risk of exhibiting high blood glucose levels, based on daily blood glucose measurements and electronic health record (EHR) data from GDM patients. We internally trained and validated our model on a cohort of 1148 pregnancies at Oxford University Hospitals NHS Foundation Trust (OUH), and performed external validation on 709 patients from Royal Berkshire Hospital NHS Foundation Trust (RBH). We trained linear and non-linear tree-based regression models to predict the proportion of high-readings (readings above the UK's National Institute for Health and Care Excellence [NICE] guideline) a patient may exhibit in upcoming days, and found that XGBoost achieved the highest performance during internal validation (0.021 [CI 0.019-0.023], 0.482 [0.442-0.516], and 0.112 [0.109-0.116], for MSE, R2, MAE, respectively). The model also performed similarly during external validation, suggesting that our method is generalizable across different cohorts of GDM patients.


Asymmetric 18F-fluorination for applications in positron emission tomography.
Positron emission tomography (PET) is becoming more frequently used by medicinal chemists to facilitate the selection of the most promising lead compounds for further evaluation. For PET, this entails the preparation of 11C- or 18F-labeled drugs or radioligands. With the importance of chirality and fluorine substitution in drug development, chemists can be faced with the challenge of preparing enantiopure molecules featuring the 18F-tag on a stereogenic carbon. Asymmetric 18F-fluorination is an emerging field of research that provides an alternative to resolution or conventional SN2-based radiochemistry. To date, both transition metal complexes and organomediators have been successfully employed for 18F-incorporation at a stereogenic carbon.


Children's Health Insurance Program (CHIP): accomplishments, challenges, and policy recommendations.
Sixteen years ago, the 105th Congress, responding to the needs of 10 million children in the United States who lacked health insurance, created the State Children's Health Insurance Program (SCHIP) as part of the Balanced Budget Act of 1997. Enacted as Title XXI of the Social Security Act, the Children's Health Insurance Program (CHIP; or SCHIP as it has been known at some points) provided states with federal assistance to create programs specifically designed for children from families with incomes that exceeded Medicaid thresholds but that were insufficient to enable them to afford private health insurance. Congress provided $40 billion in block grants over 10 years for states to expand their existing Medicaid programs to cover the intended populations, to erect new stand-alone SCHIP programs for these children, or to effect some combination of both options. Congress reauthorized CHIP once in 2009 under the Children's Health Insurance Program Reauthorization Act and extended its life further within provisions of the Patient Protection and Affordable Care Act of 2010. The purpose of this statement is to review the features of CHIP as it has evolved over the 16 years of its existence; to summarize what is known about the effects that the program has had on coverage, access, health status, and disparities among participants; to identify challenges that remain with respect to insuring this group of vulnerable children, including the impact that provisions of the new Affordable Care Act will have on the issue of health insurance coverage for near-poor children after 2015; and to offer recommendations on how to expand and strengthen the national commitment to provide health insurance to all children regardless of means.


Application of PCSK9 Inhibitors in Practice.
PCSK9i (protein convertase subtilisin/kexin type 9 inhibitors) are set to revolutionize the treatment of hypercholesterolemia in the management of atherosclerotic risk, but numerous reports have detailed unprecedented barriers to access for these drugs. To overcome these challenges, our group created a model to facilitate provision of this new therapy for patients who qualify according to Food and Drug Administration criteria. This report details the real-world follow-up experience of PCSK9i use in a large patient cohort structured to ensure rigor in data collection, analysis, and interpretation. The 271 patients approved and actively followed in our PCSK9i clinic between July 2015 and August 2018 represent a 97% approval rate from insurance, with 28% of prescriptions requiring at least one appeal. Over 50% of patients were statin intolerant. On average, there was a median lapse of 15 days between initial visit and insurance approval. PCSK9i therapy was affordable for most patients, with an average monthly out-of-pocket expense of $58.05 (median $0). Only 2.3% of patients were unable to initiate or continue therapy because of cost. Reductions from baseline in LDL (low-density lipoprotein) cholesterol and Lp(a) (lipoprotein [a])were comparable to published reports with median reductions of 60% and 23% at 1 year, respectively. PCSK9i therapy was well-tolerated overall, though 9% of patients reported adverse events, and 5% of patients discontinued due mostly to musculoskeletal and flu-like symptoms. Our practice model demonstrates that PCSK9i therapy can be accessed easily and affordably for the majority of eligible patients, resulting in dramatic improvement in lipid profile results. Moreover, our registry data suggest that results from the prospective clinical trials of PCSK9i on LDL and Lp(a) reduction and on tolerability are applicable to a real-world cohort.


Oral HPV infection and sexuality: a cross-sectional study in women.
Human Papillomavirus (HPV) is the main risk factor for cervical cancers and is associated with close to 36% of oropharyngeal cancers. There is increasing evidence that oral HPV transmission is related to sexual behavior but to our knowledge studies that involve women who have sex with women have not been performed. We examined the prevalence of oral HPV according to sexual behavior among a population-based sample of 118 women and have made some inferences of possible predictors of oral HPV infection. Women were categorized as heterosexual (history of vaginal sex and/or oral sex with males only, n = 75), bisexual (history of vaginal sex and oral sex with females, n = 32) and other (no history of vaginal sex but oral sex with females [homosexuals], virgins and women with incomplete sexual exposure data, n = 11) The prevalence of oral HPV infection was 12/118 (10.2%) for the overall study population and was not significantly different between heterosexual and bisexual women (10.7% (8/75) vs. 12.5% (4/32), p = 0.784). There was no oral HPV detected among homosexual women, virgins or among women where sexual exposure was unknown. Never smokers were more likely to be oral HPV+ compared to former smokers (Adjusted Odds Ratio (Adj OR) = 0.1, 95% CI, 0.0-1.1) and there was no difference in risk between never smokers and current smokers (Adj OR = 0.7, 95% CI, 0.1-4.6). Twenty-five percent (3/12) of oral HPV+ women had a history of HPV and/or genital warts compared to 9% (10/106) of oral HPV-women (p = 0.104). For the women with a history of vaginal sex (n = 110), oral HPV status was statistically significantly different according to oral sex exposure (p = 0.039). A higher proportion of oral HPV-positive women reported that they had no history of oral sex exposure compared to oral HPV-negative women (4/12, 33% vs. 7/98, 8%). The prevalence of cervical HPV infection did not vary between heterosexuals and bisexuals (35.7% (25/70) vs. 35.5% (11/31), p-value 0.411) and for all other women the cervical HPV prevalence was significantly lower (11.1%, 1/9). Our study suggests that smoking and sexual behavior involving males rather than female partners may be possible predictors of oral HPV infection in women. Further studies with larger sample size are needed to confirm these findings.


Communication difficulties and the experience of loneliness in patients with cancer dealing with fertility issues: a qualitative study.
To explore communication difficulties and the experience of loneliness among patients with cancer dealing with fertility issues. Qualitative study based on grounded theory principles. One university hospital and two general hospitals in Flanders, Belgium. 21 female and 7 male patients with cancer with potential fertility problems as a result of treatment. Grounded theory approach using the constant comparison method; data collection (semistructured face-to-face interviews) and analysis occurred simultaneously. Loneliness was a central theme in the experience of potential fertility loss among patients with cancer. Feelings of loneliness resulted from communication difficulties between the patient and members of his or her social environment or healthcare professionals because of several underlying processes and influencing factors. Loneliness was a strong and common feeling among patients with cancer. Patients, members of their social environment, and healthcare professionals experienced difficulties in communicating about fertility in the context of cancer, leading to patients' feelings of loneliness. Healthcare professionals must be attentive to signs indicating loneliness regarding fertility concerns, and they should provide adequate information and appropriate guidance to support patients. Professionals need further training to improve knowledge and skills.


Material-independent determination of anchoring properties on rubbed polyimide surfaces.
A material-independent method for determining liquid-crystal (LC) anchoring energy on rubbed polyimide (PI) surfaces has been devised. This method exploits the changes in the easy axis of rubbed PI film induced by exposure to linearly polarized UV (LPUV) light. The distribution of PI chains in a rubbed film is approximated by a Gaussian function and its width determined from the measured rotation of the LC easy axis as a function of exposure time. A quasimicroscopic free energy of the LC-substrate interface is used to model LC anchoring properties. The experimental and calculated values of the azimuthal anchoring energy are in good agreement and found to depend inversely on the width of the distribution function. The measurements of the width of the chain distribution function provide a simple LC material-independent method for determining the LC anchoring properties. With this method, it is also possible to calculate the strength of the interaction between PI chains and LC molecules.


Easy and green preparation of a graphene-TiO2 nanohybrid using a supramolecular biomaterial consisting of artificially bifunctionalized proteins and its application for a perovskite solar cell.
We report a novel preparation method for a graphene/TiO2 nanohybrid using a supramolecular biomaterial (CDT1). CDT1 can offer an increase in the dispersibility of graphene in water and subsequent complexation of graphene and TiO2. This nanohybrid was applied to a perovskite solar cell and success was achieved in improving its photoelectric conversion efficiency.


Level of satiety: fatty acid and glucose metabolism in three brain sites associated with feeding.
Two experiments were conducted to determine if the level of satiety alters fatty acid and glucose metabolism in selected brain areas. Rats received 150, 100, or 50% of normal intake by gastric intubation for 7 days. Thus the impetus for spontaneous feeding would be impaired in 150% fed rats (anoretic), potentiated in 50% fed rats (hungry), and maintained in 100% fed (control) rats. In vitro metabolism of glucose and palmitate was examined in liver, cortex, ventrolateral hypothalamus (VLH), ventromedial hypothalamus (VMH), and area postrema nucleus of the solitary tract. The VLH of hungry (50%) rats had a 40% increase in palmitate oxidation and a 9% decrease in glucose oxidation compared with controls (100%). The VLH of anoretic rats (150%) had a 36% decrease in palmitate oxidation and a 20% increase in glucose oxidation compared with controls. Hepatic metabolic differences were similar to those seen in VLH. Total fatty acid synthesis was 37% higher in anoretic and 29% lower in hungry compared with control rats. Recognition of excess, sufficient, or deficient peripheral energy status may be a process that monitors both VLH energy utilization and VMH energy storage in an attempt to depict metabolic adaptations of the periphery.