Exploratory factor and confirmatory analyses of the polycystic ovary syndrome health-related quality of life questionnaire (PCOSQ-50).

BACKGROUND: A condition-specific instrument is necessary to measure the health-related quality of life among those with polycystic ovary syndrome (PCOS), the most common chronic endocrinopathy among women. The first instrument was developed in 1988, followed by several revisions. However, further recommendations from all versions include additional application and measurement among different cultural populations of women with PCOS and psychometric testing based on use among larger samples of women with PCOS. Thus, the purpose of this study was to explore the factor structure of the Polycystic Ovary Syndrome Questionnaire (PCOSQ-50) using an international cross-sectional survey data from women with PCOS aged 18-42 years. METHODS: Using data from the largest known international cross-sectional study of women with PCOS aged 18-42 years (n = 935) to date, exploratory factor and confirmatory analyses were conducted for the PCOSQ-50, followed by factor labeling using a thematic analysis approach. RESULTS: Respondents were 31.0 ± 5.8 years of age, mostly White (72%), well-educated (56% had a college degree), married (69%), and employed full-time (65%). Three-quarters (74%) of the sample had one or more chronic conditions in addition to PCOS. Approximately 20% of the respondents originated from countries such as the United Kingdom, Australia, South Africa, etc. The PCOSQ-50 demonstrated good reliability but may be best described using a 7-factor model. The 7-factor model revealed goodness-of-fit. Thematic analysis suggested the following labels of those seven factors: hirsutism, fertility, isolation/trepidation, sexual function, self-esteem, emotional, and obesity. CONCLUSION: More research is needed to adapt the current PCOSQ-50, as well as to create an age-appropriate PCOS-specific HRQoL instrument for peri-postmenopausal women with PCOS.

Toward Concurrent Identification of Human Activities with a Single Unifying Neural Network Classification: First Step.

The characterization of human behavior in real-world contexts is critical for developing a comprehensive model of human health. Recent technological advancements have enabled wearables and sensors to passively and unobtrusively record and presumably quantify human behavior. Better understanding human activities in unobtrusive and passive ways is an indispensable tool in understanding the relationship between behavioral determinants of health and diseases. Adult individuals (N = 60) emulated the behaviors of smoking, exercising, eating, and medication (pill) taking in a laboratory setting while equipped with smartwatches that captured accelerometer data. The collected data underwent expert annotation and was used to train a deep neural network integrating convolutional and long short-term memory architectures to effectively segment time series into discrete activities. An average macro-F1 score of at least 85.1 resulted from a rigorous leave-one-subject-out cross-validation procedure conducted across participants. The score indicates the method's high performance and potential for real-world applications, such as identifying health behaviors and informing strategies to influence health. Collectively, we demonstrated the potential of AI and its contributing role to healthcare during the early phases of diagnosis, prognosis, and/or intervention. From predictive analytics to personalized treatment plans, AI has the potential to assist healthcare professionals in making informed decisions, leading to more efficient and tailored patient care.

PCOS health-related quality-of-life and depressive symptoms across the lifespan: Comparative study.

The purpose of this cross-sectional study was to compare health-related quality of life (HRQoL) and depressive symptoms among peri-postmenopausal women with polycystic ovary syndrome (PCOS) aged ≥43 years relative to premenopausal women with PCOS aged 18-42 years. An online survey link comprising questionnaires about demographics, HRQoL, and depressive symptoms was posted onto two PCOS-specific Facebook groups. Respondents (n = 1,042) were separated into two age cohorts: women with PCOS aged 18-42 years (n = 935) and women with PCOS aged ≥43 years (n = 107). Data from the online survey were analyzed using descriptive statistics, Pearson correlations, and multiple regression via SAS. Results were interpreted through the lens of life course theory. All demographic variables, except for the number of comorbidities, significantly differed between groups. HRQoL among older women with PCOS was significantly better as compared to those aged 18-42 years. Results indicated significant positive linear associations between the HRQoL psychosocial/emotional subscale and other HRQoL subscales and a significant negative association with age. The fertility and sexual function HRQoL subscales were not significantly associated with the psychosocial/emotional subscale among women aged ≥43 years. Women in both groups had moderate depressive symptoms. Study findings demonstrate the need to tailor PCOS management to women's life stage. This knowledge can inform future research about peri-postmenopausal women with PCOS and age-appropriate and patient-centered healthcare, including requisite clinical screenings (e.g., depressive symptoms) and lifestyle counseling across the lifespan.

Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. METHODS: A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. RESULTS: In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. CONCLUSION: Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Next generation nurse scientists: A systems approach to engaging undergraduate students in research.

BACKGROUND: Nursing Doctor of Philosophy program enrollment has declined. Undergraduate nursing student (UGS) research engagement is associated with future graduate education, an essential element for building the nursing faculty pipeline. PURPOSE: (a) To describe the infrastructure and culture-enhancing resources and strategies associated with building UGS research engagement and (b) to evaluate UGS research engagement. METHODS: Guided by a socioecological systems model university and college documents, databases, and college of nursing survey results were used to identify approaches to, and outcomes of, engaging UGS in research. Descriptive statistics were calculated to illustrate 5-year UGS research engagement trends. FINDINGS: Resources and strategies included grant funding, research assistant funding, student research showcases, and faculty mentorship. UGS research 5-year engagement trends included (a) a 75% increase in the number of students mentored, (b) a 30% rise in funded research proposals, and (c) a 54% increase in paid research assistantships. DISCUSSION: Purposefully using existing resources, growing the college of nursing infrastructure, and cultivating a culture recognizing faculty contributions were approaches associated with increased UGS research engagement.

Newborn Daily Crying Time Duration.

PURPOSE: Current methods for estimating infant crying time are potentially subject to error as they rely on parents to contemporaneously log and calculate crying time. Our aim was to present the average daily infant crying times from a digital recording device, not dependent on parent-based measurement. DESIGN AND METHODS: We conducted a descriptive longitudinal survey of infant crying times. Parents of healthy, term newborns were provided with voice-activated digital recording devices and asked to record infants continuously for randomly selected 24-hour periods during a 4 week time period. We analyzed the daily crying time for infants at different weeks of life. RESULTS: Of 136 families approached, 28 (20.5%) families were consented with 3 families withdrawing and 5 families submitting incomplete datasets, leaving a total of 20 families with complete datasets. During the first week of life, the mean crying time was about 25 minutes/day, which remained stable for the next few weeks until five weeks of life, when mean crying time increased to almost 40 minutes/day with increasing variance. CONCLUSIONS: In our study sample, infant mean daily crying times based on objective data were much less than estimates in recent studies. PRACTICE IMPLICATIONS: This study suggests daily crying times measured by digital recorders are less than daily crying times based on parent diaries published in the literature. With the development of new 'apps' to record duration times, it may be clinically inappropriate to compare data based on digital recorders with norms from studies that use parent-reported crying times.

Social construction of biopsychosocial and medical experiences of women with polycystic ovary syndrome.

AIM: To explore the perceived biopsychosocial and medical experiences of women with polycystic ovary syndrome, as presented in stories written by women on a social support website. DESIGN: Qualitative descriptive using low inference content analysis, guided by the social construction of illness theoretical framework. METHODS: In July 2018, 95 of 379 website stories were randomly selected. The stories were analysed, ending in September 2018. RESULTS: Three major themes aligning with framework constructs were identified: Biopsychosocial struggles and management: "I can't even look in the mirror without wanting to cry," Sociocultural navigation: "I feel all alone and no one understands me." and Healthcare encounters: "I don't feel like I'm getting the help I need". These themes revealed that Polycystic ovary syndrome (PCOS) has biological and experiential components, which exist independently of each other and hold social and cultural meanings. CONCLUSION: Care for women with PCOS should be multidisciplinary, multidimensional, and multi-level to ameliorate biopsychosocial issues. Provider (physicians, nurse practitioners, physician assistants) education about PCOS is necessary to enhance timely diagnosis and implement individualized treatment strategies. Non-advanced practice nurses are in a unique position to have an impact on patient satisfaction and clinical outcomes by providing and reinforcing patient education, coordinating management processes, counselling via telephone or in-person appointments and facilitating referrals to ancillary providers. Evidence-based and accessible psychosocial supports and interventions will lead to improved self-esteem and effective coping skills, and reduced stigma-related stress. Lastly, policy changes are warranted to address access to care, health insurance inequities and inadequate funding for PCOS-related research. IMPACT: Increased awareness of PCOS and its biopsychosocial aspects will aid providers with timely diagnosis and meaningful treatment plans. Women with PCOS will gain acknowledgment, acceptance, and insight towards health care and self-management.

Improvement of Quality of Antenatal Care (ANC) Service Provision at the Public Health Facilities in Lao PDR: Perspective and Experiences of Supply and Demand Sides.

BACKGROUND: The maternal mortality rate in Lao PDR (Laos) is still the highest in Southeast Asia, at 197 per 100,000 live births. Antenatal care (ANC) could contribute to maternal and child mortality reduction. The quality of ANC service remains inadequate and little information is available on the quality of health education and counseling services of health providers in Laos. This study aims to gain insight into the perceptions of stakeholders on both supply and demand sides of public ANC services in Laos and evidence for recommendations to improve the quality of ANC services. METHODS: Semi-structured interviews were conducted with 50 participants from different stakeholder groups; on the demand side, couples with a currently pregnant woman and mothers with children under one year of age and a family member; and on the supply side, health providers, managers, policy makers of the Ministry of Health, and development partners. The interviews were voice recorded and transcribed verbatim for analysis by open and thematic coding, using the MAXQDA software program. RESULTS: All respondents reported that the number of pregnant women who visit ANC services has increased. However, an analysis of the supply side identified issues related to the quality of ANC that need to be improved in the areas of facilities, human resources, privacy and confidentiality, providers' behavior, attitudes, and ineffective communication skills when it comes to providing health education and counseling to pregnant women and their family members. The analysis of the demand side mainly emphasized the issues of providers' behavior, attitude, communication and unequal treatment, and the lack of privacy. Both sides also suggested solutions to the problems, such as training, effective materials, rewarding good role models, and building a feedback system. CONCLUSION: The number of public ANC services has increased, but both supply and demand sides experienced challenges with the quality of ANC. All respondents proposed possible solutions to improve quality of ANC service in public health facilities in Laos.

How have researchers defined and used the concept of 'continuity of care' for chronic conditions in the context of resource-constrained settings? A scoping review of existing literature and a proposed conceptual framework.

BACKGROUND: Within the context of the growing burden of non-communicable diseases (NCDs) globally, there is limited evidence on how researchers have explored the response to chronic health needs in the context of health policy and systems in low- and middle-income countries. Continuity of care (CoC) is one concept that represents several elements of a long-term model of care. This scoping review aims to map and describe the state of knowledge regarding how researchers in resource-constrained settings have defined and used the concept of CoC for chronic conditions in primary healthcare. METHODS: This scoping review adopted the modified framework for interpretive scoping literature reviews. A systematic literature search in PubMed was performed, followed by a study selection process and data extraction, analysis and synthesis. Extracted data regarding the context of using CoC and the definition of CoC were analysed inductively to identify similar patterns; based on this, articles were divided into groups. MaxQDA was then used to re-code each article with themes according to the CoC definition to perform a cross-case synthesis under each identified group. RESULTS: A total of 55 peer-reviewed articles, comprising reviews or commentaries and qualitative or quantitative studies, were included. The number of articles has increased over the years. Five groups were identified as those (1) reflecting a change across stages or systems of care, (2) mentioning continuity or lack of continuity without a detailed definition, (3) researching CoC in HIV/AIDS programmes and its scaling up to support management of NCDs, (4) researching CoC in NCD management, and (5) measuring CoC with validated questionnaires. CONCLUSION: Research or policy documents need to provide an explicit definition of CoC when this terminology is used. A framework for CoC is suggested, acknowledging three components for CoC (i.e. longitudinal care, the nature of the patient-provider relationship and coordinated care) while considering relevant contextual factors, particularly access and quality.

Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation.

OBJECTIVE: AS is a systemic inflammatory disease of the SpA family. Polymorphisms at loci including HLA-B27, IL-23R and ERAP-1 directly implicate immune mechanisms in AS pathogenesis. Previously, in an SpA model, we identified HLA-B27-mediated effects on dendritic cells that promoted disease-associated Th17 cells. Here we extend these studies to AS patients using deep immunophenotyping of candidate pathogenic cell populations. The aim of our study was to functionally characterize the immune populations mediating AS pathology. METHODS: Using 11-parameter flow cytometry, we characterized the phenotype and functions of lymphocyte and myeloid cells from peripheral blood, and the synovial phenotype of AS patients and age-matched healthy controls. RESULTS: Significantly fewer circulating CD1c-expressing dendritic cells were observed in AS patients, offset by an increase in CD14(-) CD16(+) mononuclear cells. Ex vivo functional analysis revealed that this latter population induced CCR6 expression and promoted secretion of IL-1ß and IL-6 when co-cultured with naive CD4(+) T cells. Additionally, systemic inflammation in AS patients significantly correlated with increased proportions of activated CCR9(+) CD4(+) T cells. CONCLUSION: CD14(-) CD16(+) mononuclear cells may contribute to AS by promoting Th17 responses, and antigen-presenting cells of mucosal origin are likely to contribute to systemic inflammation in AS.

Cancer-related fatigue: results from patient experience surveys undertaken in a UK regional cancer centre.

PURPOSE: Cancer-related fatigue (CRF) is a common but under reported symptom significantly impacting on cancer patients' quality of life. The purpose of these surveys was to drive improvements in the provision of support of patients with CRF. METHOD: Two surveys were conducted to determine the incidence and impact of cancer-related fatigue (CRF) amongst patients attending a Cancer Centre (CC) for radiotherapy and/or systemic anti-cancer therapy. RESULTS: Survey 1: retrospective examination of 68 patients' clinical notes. Survey 2: a questionnaire distributed prospectively to 148 patients whilst attending for treatment. Survey 1 identified 29 patients' notes recording the patient experiencing fatigue, but only two were given any advice to manage symptoms. In survey 2, the majority of patients (86%) were advised about the risk of CRF before treatment, but only 67% were assessed and advised about CRF during treatment. Physical fatigue (57%) was more common than emotional (37%) or cognitive fatigue (29%). CONCLUSIONS: Many patients are not being given advice to manage their CRF symptoms. Reasons for this include a lack of awareness regarding the occurrence of CRF and its impact and a misunderstanding by Health Care Professionals (HCPs) about the advice patients should be given. Recommendations include the continued need to improve education of HCPs to ensure patients receive the appropriate advice they need to manage their CRF.

Challenges in detection and treatment of multidrug resistant tuberculosis patients in Vietnam.

BACKGROUND: Vietnam is ranked 14(th) among 27 countries with high burden of multidrug-resistant tuberculosis (MDR-TB). In 2009, the Vietnamese government issued a policy on MDR-TB called Programmatic Management of Drug-resistant Tuberculosis (PMDT) to enhance and scale up diagnosis and treatment services for MDR-TB. Here we assess the PMDT performance in 2013 to determine the challenges to the successful identification and enrollment for treatment of MDR-TB in Vietnam. METHODS: In 35 provinces implementing PMDT, we quantified the number of MDR-TB presumptive patients tested for MDR-TB by Xpert MTB/RIF and the number of MDR-TB patients started on second-line treatment. In addition, existing reports and documents related to MDR-TB policies and guidelines in Vietnam were reviewed, supplemented with focus group discussions and in-depth interviews with MDR-TB key staff members. RESULTS: 5,668 (31.2 %) of estimated 18,165 MDR-TB presumptive cases were tested by Xpert MTB/RIF and second-line treatment was provided to 948 out of 5100 (18.7 %) of MDR-TB patients. Those tested for MDR-TB were 340/3224 (10.5 %) of TB-HIV co-infected patients and 290/2214 (13.1 %) of patients who remained sputum smear-positive after 2 and 3 months of category I TB regimen. Qualitative findings revealed the following challenges to detection and enrollment of MDR-TB in Vietnam: insufficient TB screening capacity at district hospitals where TB units were not available and poor communication and implementation of policy changes. Instructions for policy changes were not always received, and training was inconsistent between training courses. The private sector did not adequately report MDR-TB cases to the NTP. CONCLUSIONS: The proportion of MDR-TB patients diagnosed and enrolled for second-line treatment is less than 20 % of the estimated total. The low enrollment is largely due to the fact that many patients at risk are missed for MDR-TB screening. In order to detect more MDR-TB cases, Vietnam should intensify case finding of MDR-TB by a comprehensive strategy to screen for MDR-TB among new cases rather than targeting previously treated cases, in particular those with HIV co-infection and contacts of MDR-TB patients, and should engage the private sector in PMDT.

The relationships between the use of self-regulated learning strategies and depression among medical students: an accelerated prospective cohort study.

We conducted this study to determine the relationships between the use of self-regulated learning strategies (SRL) and depression scores among medical students. An accelerated prospective cohort study among 623 students at a public medical university in Vietnam was carried out during the academic year 2012-2013. The Depression, Anxiety and Stress Scales (21 items) was used to measure depression scores as the primary research outcome, and to measure anxiety and stress scores as the confounding variables. Fourteen SRL subscales including intrinsic/extrinsic goal orientation, task value, self-efficacy for learning, control of learning beliefs, rehearsal, elaboration, organization, critical thinking, meta-cognitive strategies, time and study environment, effort regulation, peer learning, and help seeking were measured using the Motivated Strategies for Learning Questionnaire. Data were collected at two points in time (once each semester). There were 744 responses at the first time (95.88%) and 623 at time two (drop-out rate of 16.26%). The generalized estimating equation was applied to identify any relationships between the use of each SRL subscale and depression scores at time 2, adjusting for the effects of depression at time 1, anxiety, stress, within cluster correlation, and potential demographic covariates. Separate multivariate GEE analysis indicated that all SRL subscales were significantly negatively associated with depression scores, except for extrinsic goal orientation and peer learning. Whereas full multivariate GEE analysis revealed that self-efficacyT1, help-seekingT1, time and study environmentT2 were found to be significantly negatively associated with depressionT2, adjusting for the effects of depressionT1, anxiety, stress, and demographic covariates. The results should be used to provide appropriate support for medical students to reduce depression.

The VA Caregiver Support Line: A Gateway of Support for Caregivers of Veterans.

In passing the Caregivers and Veterans Omnibus Health Services Act of 2010, Congress created a legislative mandate for the Veterans Administration (VA) to strengthen its program of support services for caregivers of veterans. As part of this expansion, the VA implemented a nationwide toll-free telephone Caregiver Support Line (CSL). The CSL is a single point of entry system to link caregivers to national and local services to support care of a veteran. This article describes the CSL and its role in supporting aging veterans and their caregivers, discusses social workers' contributions to its development and implementation, and reports utilization data.

Climatic-driven seasonality of emerging dengue fever in Hanoi, Vietnam.

BACKGROUND: Dengue fever (DF) has been emerging in Hanoi over the last decade. Both DF epidemiology and climate in Hanoi are strongly seasonal. This study aims at characterizing the seasonality of DF in Hanoi and its links to climatic variables as DF incidence increases from year to year. METHODS: Clinical suspected cases of DF from the 14 central districts of Hanoi were obtained from the Ministry of Health over a 8-year period (2002-2009). Wavelet decompositions were used to characterize the main periodic cycles of DF and climatic variables as well as the mean phase angles of these cycles. Cross-wavelet spectra between DF and each climatic variables were also computed. DF reproductive ratio was calculated from Soper's formula and smoothed to highlight both its long-term trend and seasonality. RESULTS: Temperature, rainfall, and vapor pressure show strong seasonality. DF and relative humidity show both strong seasonality and a sub-annual periodicity. DF reproductive ratio is increasing through time and displays two clear peaks per year, reflecting the sub-annual periodicity of DF incidence. Temperature, rainfall and vapor pressure lead DF incidence by a lag of 8-10 weeks, constant through time. Relative humidity leads DF by a constant lag of 18 weeks for the annual cycle and a lag decreasing from 14 to 5 weeks for the sub-annual cycle. CONCLUSION: Results are interpreted in terms of mosquito population dynamics and immunological interactions between the different dengue serotypes in the human compartment. Given its important population size, its strong seasonality and its dengue emergence, Hanoi offers an ideal natural experiment to test hypotheses on dengue serotypes interactions, knowledge of prime importance for vaccine development.

Exploring the Experiential Journey of Women with PCOS Across the Lifespan: A Qualitative Inquiry.

Introduction: Peri-postmenopausal women with the chronic condition polycystic ovary syndrome (PCOS) remain at cardiometabolic risk and/or subsist with established comorbidity while continuing to manage persistent PCOS signs and symptoms, such as hirsutism. Thus, PCOS transcends the reproductive years, yet there is sparse scientific literature on the peri-postmenopausal years of women with PCOS. Purpose: To explore how peri-postmenopausal women's perceptions about PCOS have changed over the lifespan since their PCOS diagnosis. Methods: A cross-sectional survey with one qualitative question was conducted via Research Electronic Data Capture (REDCap) among women with PCOS aged ≥43 years, who were all recruited from PCOS-specific Facebook pages. Of the 107 women completing the survey, 72 substantively answered the qualitative question. The qualitative responses were analyzed using the steps of reflexive thematic analysis. Themes were interpreted and discussed through the lens of the bioecological conceptual model. Results: Respondents were 47.6 (±4.1) years of age, primarily White (87.5%), employed full time (65.3%), and married (75%) with children (68%). Four overall themes were identified: 1) dismissal 2) information desert, 3) PCOS experience over the lifespan, and 4) mindset. Conclusion: The study findings illustrated the unique healthcare needs among peri-postmenopausal women with PCOS. Further research is needed to further explore their healthcare concerns and psychosocial needs followed by studies that develop and assess interventions that promote symptom and adaptive coping strategies across their lifespan.

Dendritic cells and regulatory T cells in spondyloarthritis.

PURPOSE OF REVIEW: The spondyloarthropathies (SpAs) are a group of interrelated inflammatory disorders with overlapping clinical features. Current SpA treatments only provide partial symptomatic and functional relief in a subgroup of patients. Consequently, there is a need to better understand the pathophysiology of SpA to develop more specific and effective treatments for these conditions. RECENT FINDINGS: Genetic and mechanistic evidence links SpA with inflammatory bowel disease (IBD) and psoriasis, and the symptoms of these diseases partially overlap. Regulatory T cells (Tregs) and dendritic cells control the adaptive immune response, and failures in their functions are likely to contribute to the establishment of chronic inflammation. The contributions of Tregs and dendritic cells to IBD and SpA have been assessed in both animal models of disease and patients. SUMMARY: Although defects in Tregs are important in psoriasis and in animal models of IBD, there is little evidence that they are important in SpA. However, data from animal models indicate that dendritic cells drive pathogenic T-cell responses, partly through the production of interleukin-23 (IL-23). Dendritic cells from SpA patients may also contribute to disease by producing IL-23, therefore supporting the differentiation of the Th17 cells that contribute to inflammation. The driving forces in SpA pathophysiology are now becoming clear; these data may lead to the development of novel therapies to target SpA and related inflammatory disorders.

The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release.

OBJECTIVES: Macrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood. METHODS: We used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8). RESULTS: Using in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion. CONCLUSIONS: The LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.

Expression of HLA-B27 causes loss of migratory dendritic cells in a rat model of spondylarthritis.

OBJECTIVE: In rats transgenic for human HLA-B27 and ß(2) -microglobulin (B27-transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27-transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4+ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4+ T cell differentiation would be aberrant in B27-transgenic rats. METHODS: Migrating intestinal lymph DCs were collected via thoracic duct cannulation from B27-transgenic and control (HLA-B7-transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed. RESULTS: Lymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self-antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27-transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27-transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin-17 (IL-17) production from naive CD4+ T cells. CONCLUSION: We describe 2 different mechanisms by which HLA-B27 may contribute to inflammatory disease: increased apoptotic death of B27-transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL-17 production from CD4+ T cells stimulated by the surviving B27-transgenic DCs.

Depression, anxiety, and suicidal ideation among Vietnamese secondary school students and proposed solutions: a cross-sectional study.

BACKGROUND: There is a rapidly growing public awareness of mental health problems among Vietnamese secondary school students. This study aims to determine the prevalence of anxiety, depression, and suicidal ideation, to identify related risk factors, and to explore students' own proposals for improving their mental health. METHODS: A cross-sectional study was conducted among 1161 secondary students in Can Tho City, Vietnam during September through December, 2011. A structured questionnaire was used to assess anxiety, depression, suicidal ideation and proposed solutions. Depression was measured using the Center for Epidemiology Studies Depression Scale. RESULTS: The prevalence estimates of symptoms reaching a threshold comparable to a diagnosis of anxiety and depression were 22.8% and 41.1%, respectively. Suicide had been seriously considered by 26.3% of the students, while 12.9% had made a suicide plan and 3.8% had attempted suicide. Major risk factors related to anxiety and depression were physical or emotional abuse by the family, and high educational stress. As proposed solutions, nearly 80% of students suggested that the academic workload should be reduced and that confidential counselors should be appointed at schools. About half the students stated that the attitudes of their parents and teachers needed to change. A significant majority said that they would visit a website that provided mental health support for students. CONCLUSIONS: Anxiety, depression, and suicidal ideation are common among Vietnamese secondary school students. There are strong associations with physical and emotional abuse in the family and high educational stress. Academic curricula and attitudes of parents and teachers need to be changed from a punitive to a more supportive approach to reduce the risk of poor mental health. An internet-based mental health intervention could be a feasible and effective first step to improve students' mental health.