Assessment of gene-covariate interactions by incorporating covariates into association mapping

The HLA region is considered to be the main genetic risk factor for rheumatoid arthritis. Previous research demonstrated that HLA-DRB1 alleles encoding the shared epitope are specific for disease that is characterized by antibodies to cyclic citrullinated peptides (anti-CCP). In the present study, we incorporated the shared epitope and either anti-CCP antibodies or rheumatoid factor into linkage disequilibrium mapping, to assess the association between the shared epitope or antibodies with the disease gene identified. Incorporating the covariates into the association mapping provides a mechanism 1) to evaluate gene-gene and gene-environment interactions and 2) to dissect the pathways underlying disease induction/progress in quantitative antibodies

Persistent and multisite homophobic harassment during childhood and adolescence and its association with school difficulties in gay and bisexual men in Taiwan

Background: Homophobic harassment can compromise mental health of sexual minority youths. Objectives: This study examined the rates of persistent and multisite homophobic harassment and their associations with school difficulties during childhood and adolescence among gay and bisexual men in Taiwan. Methods: Participants were recruited through advertisements on the Facebook, Bulletin Board Systems, and the home pages of health promotion and counseling centers for the gay, lesbian, and bisexual community. The experiences of traditional and cyber harassment based on gender role nonconformity and sexual orientation of 500 gay or bisexual men were examined. The associations of multisite and persistent harassment victimization with school difficulties were evaluated. Results: A total of 239 (47.8%) and 131 (26.2%) participants experienced persistent and multisite harassment victimization, respectively. Harassment victimization was significantly associated with low satisfaction with academic performance in any stage of study. Moreover, the participants who were harassed in senior high schools were more likely to miss classes or be truant than those who were not harassed. The victims of multisite harassment at senior high schools were more likely to miss classes or be truant than those of school-only harassment. Discussion: Prevention and intervention programs are warranted to reduce homophobic harassment in sexual minority youths

Cost-effective upgrade of a focusing system for inelastic X-ray scattering experiments under high pressure

This paper describes a scheme utilizing a set of low-cost and compact Kirkpatrick–Baez mirrors for upgrading the optical system of the Taiwan Inelastic X-ray Scattering beamline at SPring-8 for high-pressure experiments using diamond-anvil cells. The scheme as implemented improves the focus to 13 µm × 16 µm with transmission of up to 72%

Crystallization of Adenylylsulfate Reductase from Desulfovibrio gigas: A Strategy Based on Controlled Protein Oligomerization

Adenylylsulfate reductase (adenosine 5′-phosphosulfate reductase, APS reductase or APSR, E.C.1.8.99.2) catalyzes the conversion of APS to sulfite in dissimilatory sulfate reduction. APSR was isolated and purified directly from massive anaerobically grown Desulfovibrio gigas, a strict anaerobe, for structure and function investigation. Oligomerization of APSR to form dimers–α_2β_2, tetramers–α_4β_4, hexamers–α_6β_6, and larger oligomers was observed during purification of the protein. Dynamic light scattering and ultracentrifugation revealed that the addition of adenosine monophosphate (AMP) or adenosine 5′-phosphosulfate (APS) disrupts the oligomerization, indicating that AMP or APS binding to the APSR dissociates the inactive hexamers into functional dimers. Treatment of APSR with β-mercaptoethanol decreased the enzyme size from a hexamer to a dimer, probably by disrupting the disulfide Cys156—Cys162 toward the C-terminus of the β-subunit. Alignment of the APSR sequences from D. gigas and A. fulgidus revealed the largest differences in this region of the β-subunit, with the D. gigas APSR containing 16 additional amino acids with the Cys156—Cys162 disulfide. Studies in a pH gradient showed that the diameter of the APSR decreased progressively with acidic pH. To crystallize the APSR for structure determination, we optimized conditions to generate a homogeneous and stable form of APSR by combining dynamic light scattering, ultracentrifugation, and electron paramagnetic resonance methods to analyze the various oligomeric states of the enzyme in varied environments

A Rapid and Low-Cost Pathogen Detection Platform by Using a Molecular Agglutination Assay.

Rapid and low-cost pathogen diagnostic approaches are critical for clinical decision-making procedures. Cultivating bacteria often takes days to identify pathogens and provide antimicrobial susceptibilities. The delay in diagnosis may result in compromised treatment and inappropriate antibiotic use. Over the past decades, molecular-based techniques have significantly shortened pathogen identification turnaround time with high accuracy. However, these assays often use complex fluorescent labeling and nucleic acid amplification processes, which limit their use in resource-limited settings. In this work, we demonstrate a wash-free molecular agglutination assay with a straightforward mixing and incubation step that significantly simplifies procedures of molecular testing. By targeting the 16S rRNA gene of pathogens, we perform a rapid pathogen identification within 30 min on a dark-field imaging microfluidic cytometry platform. The dark-field images with low background noise can be obtained using a narrow beam scanning technique with off-the-shelf complementary metal oxide semiconductor (CMOS) imagers such as smartphone cameras. We utilize a machine learning algorithm to deconvolute topological features of agglutinated clusters and thus quantify the abundance of bacteria. Consequently, we unambiguously distinguish Escherichia coli positive from other E. coli negative among 50 clinical urinary tract infection samples with 96% sensitivity and 100% specificity. Furthermore, we also apply this quantitative detection approach to achieve rapid antimicrobial susceptibility testing within 3 h. This work exhibits easy-to-use protocols, high sensitivity, and short turnaround time for point-of-care testing uses

Effects of interventions on trajectories of health-related quality of life among older patients with hip fracture: a prospective randomized controlled trial

Abstract Background Health-related quality of life (HRQoL) has been used to assess subjects’ prognosis and recovery following hip fracture. However, evidence is mixed regarding the effectiveness of interventions to improve HRQoL of elders with hip fracture. The purposes of this study were to identify distinct HRQoL trajectories and to evaluate the effects of two care models on these trajectories over 12 months following hip-fracture surgery. Methods For this secondary analysis, data came from a randomized controlled trial of subjects with hip fracture receiving three treatment care models: interdisciplinary care (n = 97), comprehensive care (n = 91), and usual care (n = 93). Interdisciplinary care consisted of geriatric consultation, discharge planning, and 4 months of in-home rehabilitation. Comprehensive care consisted of interdisciplinary care plus management of malnutrition and depressive symptoms, fall prevention, and 12 months of in-home rehabilitation. Usual care included only in-hospital rehabilitation and occasional discharge planning, without geriatric consultation and in-home rehabilitation. Mental and physical HRQoL were measured at 1, 3, 6, and 12 months after discharge by the physical component summary scale (PCS) and mental component summary scale (MCS), respectively, of the Medical Outcomes Study Short Form 36, Taiwan version. Latent class growth modeling was used to identify PCS and MCS trajectories and to evaluate how they were affected by the interdisciplinary and comprehensive care models. Results We identified three quadratic PCS trajectories: poor PCS (n = 103, 36.6 %), moderate PCS (n = 96, 34.2 %), and good PCS (n = 82, 29.2 %). In contrast, we found three linear MCS trajectories: poor MCS (n = 39, 13.9 %), moderate MCS (n = 84, 29.9 %), and good MCS (n = 158, 56.2 %). Subjects in the comprehensive care and interdisciplinary care groups were more likely to experience a good PCS trajectory (b = 0.99, odds ratio [OR] = 2.69, confidence interval [CI] = 7.24–1.00, p = 0.049, and b = 1.32, OR = 3.75, CI = 10.53–1.33, p = 0.012, respectively) than those who received usual care. However, neither care model improved MCS. Conclusions The interdisciplinary and comprehensive care models improved recovery from hip fracture by increasing subjects’ odds for following a trajectory of good physical functioning after hospitalization. Trial registration ClinicalTrials.gov ( NCT01350557 )http://deepblue.lib.umich.edu/bitstream/2027.42/134528/1/12891_2016_Article_958.pd

Case report: Presentations and cytokine profiles of inflammatory non-pulmonary COVID-19 and related diseases in children

The coronavirus disease 2019 (COVID-19) pandemic has evolved to dynamic waves of different SARS-CoV-2 variants. Initially, children diagnosed with COVID-19 presented pulmonary involvement characterized by mild diseases. In the later waves of the COVID-19 pandemic, life-threatening non-pulmonary inflammatory diseases such as (1) aseptic meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) multisystem inflammatory syndrome in children (MIS-C) have been reported, affecting the pediatric population. To alert timely identification and prevention of the life-threatening non-pulmonary COVID-19, we present the cases of ME, ANE, and MIS-C in terms of clinical manifestation, cytokine profile, and follow-up consequences. Based on the immunopathogenesis and risk factors associated with non-pulmonary COVID-19, we delineate strategies for an early diagnosis and treatment to reduce morbidity and mortality in children