A multidisciplinary effort to increase COVID-19 vaccination among the older adults.

Background: COVID-19 vaccination significantly reduces the risk of infection and its associated morbidity and mortality. However, poor uptake of the COVID-19 vaccination was reported among the high-risk group of older people amidst emerging variants of concern. This community case study reports an outreach program in Singapore, COVE (COVID-19 Vaccination for the Elderly) initiated by healthcare workers in a cluster of primary care clinics. They assessed the vaccine hesitancy among these older persons, addressed their concerns and facilitated their vaccination appointment during a brief phone conversation. Method: Twenty one thousand six hundred and sixty three unvaccinated adults aged ≥60 years were contacted by healthcare worker volunteers over two phases from June to October 2021. In phase I, they contacted adults aged above 70 years over 2 weeks. Adults who were uncontactable in phase I and those aged 60-69 years were sent SMS in phase II. Data were analyzed via descriptive data analysis. Results: After phase 1, 65.5% (n = 5,646/8,617) of older adults had received at least one dose of the COVID-19 vaccine. The respondents expressed intention to vaccinate (39%, n = 3,390), requested to seek further information (25%, n = 2,138), reported access barrier (8%, n = 715), or were concerned of the vaccine adverse effects (3%, n = 288). Vaccination was refused by 24% (n = 2,086) of the respondents. Eventually 60.4% (n = 13,082/21,663) of them were vaccinated 3 months after COVE implementation. Conclusion: The COVE program increased the COVID-19 vaccination uptake of older adults from 84.6 to 96.3%. A person-centric proactive approach by healthcare workers addressed vaccine hesitancy and optimized vaccination. The outreach scheduling of vaccination appointments is key in promoting vaccination uptake among older adults.

Surgical site infection and development of antimicrobial sutures: a review.

Sutures are used to facilitate wound healing and play an important role in ensuring the success of surgical interventions in healthcare facilities. Suture-associated surgical site infection (SSI) may develop when bacterial contaminants colonize the suture surface and establish biofilms that are highly resistant to antibiotic treatment. The outcome of SSI affects postoperative care, leading to high rates of morbidity and mortality, prolonged hospitalization, and increased financial burden. Antimicrobial sutures coated with antiseptics such as triclosan and chlorhexidine have been used to minimize the occurrence of SSI. However, as the efficacy of antiseptic-based sutures may be affected due to the emergence of resistant strains, new approaches for the development of alternative antimicrobial sutures are necessary. This review provides an update and outlook of various approaches in the design and development of antimicrobial sutures. Attaining a zero SSI rate will be possible with the advancement in suturing technology and implementation of good infection control practice in clinical settings.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

[Suicidality in the perinatal period: Descriptive study on factors associated with suicidal ideation among women hospitalized in the perinatal period at the specialized hospital center]. / Suicidalité en période périnatale : quels sont les facteurs associés ?

OBJECTIVES: Suicide is the leading cause of maternal mortality in high-resource countries. The onset of suicidal ideation is a major risk factor for suicide attempts. Suicidality has a major impact on the mother-baby relationship and on child development. The main objective of the study was to identify factors associated with the occurrence of perinatal suicidal ideation in women requiring hospitalization. The secondary objectives of the study were to describe the socio-demographic and clinical characteristics of this specific population, to specify the follow-up procedures at hospital discharge and to develop a semi-directed interview framework for psychiatric evaluation of perinatal patients admitted to a psychiatric hospital in order to better identify those at risk of suicide and improve overall management, particularly in terms of referral to existing perinatal care services. METHODS: Descriptive and retrospective study carried out at the Specialized Hospital Center of women hospitalized in the perinatal period between 2014 and 2019. The inclusion criteria were: inpatient pregnant or postpartum within one year of delivery, 16 to 43 years. A keyword search was performed to retrieve the computerized records. All records matching the inclusion criteria were included. We studied the occurrence of suicidal ideation according to the main known clinical and socio-demographic risk factors. RESULTS: The sample included 25 pregnant patients and 57 post-partum patients. The presence of a psychiatric history increased the risk of suicidal ideation by 4.38 (P<0.03). The association between the occurrence of a stressful life event and the risk of suicidal ideation onset was close to significant (P<0.10). One third of the patients had been admitted for a reason related to suicidality. Less than one-third of the patients had been referred to existing perinatal services. CONCLUSIONS: Suicidality in the perinatal period has a major impact on the dyad as well as on the whole family. The search for suicidal ideas must be systematic during psychiatric interviews, a fortiori when a psychiatric history has been authenticated. Every patient hospitalized in adult psychiatry should be referred to specialized outpatient perinatal psychiatry services. Prevention involves raising awareness and training of all health professionals, networking, but also informing the general public.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.

Adipokines and the risk of active TB: a nested case-control study.

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.

Tobacco use and other aspects related to smoking among school-going adolescents aged 13-15 years in Malaysia: Analysis of three cross-sectional nationally representative surveys in 2003, 2009 and 2016.

INTRODUCTION: Periodic surveys on tobacco use patterns and other aspects of tobacco use among school-going adolescents in Malaysia provide information on the effectiveness of anti-smoking measures implemented. However, such information is limited in Malaysia. We investigated the prevalence of smoking and other related aspects among middle-secondary school students in Malaysia from the years 2003-2016 to fill this gap. METHODS: We analyzed data from the Global Youth Tobacco Survey (GYTS) 2003, GYTS 2009, and the Tobacco and Electronic Cigarette Survey among Malaysia Adolescents (TECMA) 2016. The surveys employed multistage sampling to select representative samples of adolescents attending secondary school in Malaysia. Data were collected using a pre-validated self-administered anonymous questionnaire adopted from the GYTS. RESULTS: Between 2003 and 2016, major changes occurred in which there were reductions in the prevalence of ever smoking, current smoking, and susceptibility to smoking. Reductions were also observed in exposure to SHS in public places and in the home. The proportion of school-going adolescents who support a ban on smoking in public places increased between 2013 to 2016, and there was a significant reduction in the proportion of respondents that were offered 'free' cigarettes by tobacco company representatives. However, there was no difference in the proportion of adolescents who initiated smoking before the age of 10 years and current smokers seeking advice to quit smoking across the time period. CONCLUSIONS: Our study indicates that the smoking policies and measures have been effective in reducing smoking prevalence, secondhand smoke exposure, and access to cigarettes, among school-going adolescents in Malaysia. However, measures to reduce smoking initiation and increase smoking cessation need to be strengthened to reduce the burden of smoking-related diseases in Malaysia in the long-term.

Malaysian adolescents' exposure to secondhand smoke in the car of their parents/guardians: A nationwide cross-sectional school-based study.

INTRODUCTION: We investigated the prevalence of children's exposure to secondhand smoke (SHS) in the car of their parents/guardians and the associated factors. METHODS: A self-administered validated questionnaire was used to obtain data from the nationally representative samples of school-going adolescents aged 11-19 years in Malaysia. Prevalence rates were computed and chi-squared tests and multiple logistic regression were conducted. RESULTS: Of the participants, 23.3% reported exposure to SHS at least once in the car of their parents/guardians during the last 7 days before the survey. The prevalence and likelihood of SHS exposure were significantly higher in Malays, descendants of natives of Sabah and Sarawak, schools in rural areas, females, and current smokers. However, age group and knowledge on the harmful effects of SHS were not significant after adjusting for confounding effects. CONCLUSIONS: A substantial proportion of school-going adolescents were exposed to secondhand smoke in the car of their parents/guardians. This highlights the need for effective tobacco control measures to include health promotion and smoke-free car regulations to be introduced to prevent severe health hazards and to reduce smoking initiation among non-smoking adolescents.

Real-time visualization of titin dynamics reveals extensive reversible photobleaching in human induced pluripotent stem cell-derived cardiomyocytes.

Fluorescence recovery after photobleaching (FRAP) has been useful in delineating cardiac myofilament biology, and innovations in fluorophore chemistry have expanded the array of microscopic assays used. However, one assumption in FRAP is the irreversible photobleaching of fluorescent proteins after laser excitation. Here we demonstrate reversible photobleaching regarding the photoconvertible fluorescent protein mEos3.2. We used CRISPR/Cas9 genome editing in human induced pluripotent stem cells (hiPSCs) to knock-in mEos3.2 into the COOH terminus of titin to visualize sarcomeric titin incorporation and turnover. Upon cardiac induction, the titin-mEos3.2 fusion protein is expressed and integrated in the sarcomeres of hiPSC-derived cardiomyocytes (CMs). STORM imaging shows M-band clustered regions of bound titin-mEos3.2 with few soluble titin-mEos3.2 molecules. FRAP revealed a baseline titin-mEos3.2 fluorescence recovery of 68% and half-life of ~1.2 h, suggesting a rapid exchange of sarcomeric titin with soluble titin. However, paraformaldehyde-fixed and permeabilized titin-mEos3.2 hiPSC-CMs surprisingly revealed a 55% fluorescence recovery. Whole cell FRAP analysis in paraformaldehyde-fixed, cycloheximide-treated, and untreated titin-mEos3.2 hiPSC-CMs displayed no significant differences in fluorescence recovery. FRAP in fixed HEK 293T expressing cytosolic mEos3.2 demonstrates a 58% fluorescence recovery. These data suggest that titin-mEos3.2 is subject to reversible photobleaching following FRAP. Using a mouse titin-eGFP model, we demonstrate that no reversible photobleaching occurs. Our results reveal that reversible photobleaching accounts for the majority of titin recovery in the titin-mEos3.2 hiPSC-CM model and should warrant as a caution in the extrapolation of reliable FRAP data from specific fluorescent proteins in long-term cell imaging.

Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

BACKGROUND: Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors. PATIENTS AND METHODS: This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21 days on, 7 days off. Atezolizumab was dosed at 800 mg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival. RESULTS: Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n = 84), melanoma (n = 22), non-small-cell lung cancer (NSCLC; n = 28), and other solid tumors (n = 16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases. CONCLUSIONS: Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study. CLINICALTRIALS.GOV IDENTIFIER: NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix, available at Annals of Oncology online).

Diabetes and body mass index in relation to risk of active tuberculosis: a prospective population-based cohort.

SETTING: Although diabetes (DM) and low body mass index (BMI) are established risk factors for active tuberculosis (TB), the joint effect of type 2 diabetes (T2D) and BMI is unclear.DESIGN: A prospective cohort of 63,257 adults aged 45-74 years were recruited from 1993 to 1998 in Singapore. Active TB cases were identified via linkage with the National TB Registry up to December 2014. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relations of T2D and BMI, independently and jointly, with TB risk.RESULTS: T2D was associated with increased TB risk (HR 2.31, 95% CI 1.93-2.78). Conversely, BMI was inversely associated with TB risk: HR for underweight (BMI < 18.5 kg/m²) was 2.87 (95% CI 2.15-3.82) compared to obese (BMI ≥ 27.5 kg/m²) individuals. Compared to obese individuals without T2D, HR for active TB among underweight individuals with T2D was 8.30 (95% CI 4.43-15.54). There was no statistically significant interaction between BMI and T2D on TB risk (Pinteraction = 0.85).CONCLUSION: Underweight and T2D are independent determinants for active TB. This has important public health implications in Asia where prevalence of tuberculous infection is high, and T2D occurs at lower levels of BMI.

MRI Features of Aquaporin-4 Antibody-Positive Longitudinally Extensive Transverse Myelitis: Insights into the Diagnosis of Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND PURPOSE: Longitudinally extensive transverse myelitis is a well-documented spinal manifestation of neuromyelitis optica spectrum disorders, however, other forms of nontumorous myelopathy can also manifest as longitudinally extensive transverse myelitis. Our aim was to evaluate the MR imaging features of aquaporin-4 antibody-positive longitudinally extensive transverse myelitis, which is strongly associated with neuromyelitis optica spectrum disorders. MATERIALS AND METHODS: We evaluated cervicomedullary junction involvement, cord expansion ratios, bright spotty lesions, the number of involved segments, skipped lesions, enhancement patterns, and axial distribution patterns using spinal MR imaging of 41 patients with longitudinally extensive transverse myelitis who underwent aquaporin-4 antibody testing. Univariate logistic regression analysis was performed to identify factors associated with aquaporin-4 antibody seropositivity, which were then used to develop a scoring system for diagnosing aquaporin-4 antibody-positive longitudinally extensive transverse myelitis. Interrater reliability for cord expansion ratio measurement and bright spotty lesions was determined using intraclass correlation coefficients and κ values, respectively. RESULTS: Fifteen patients with longitudinally extensive transverse myelitis were aquaporin-4 antibody-positive. Sex (female), cervicomedullary junction involvement, a cord expansion ratio of >1.4, and bright spotty lesions were significantly associated with aquaporin-4 antibody seropositivity. The sensitivity and specificity of the scoring system were 73.3% and 96.2%, respectively. The interclass correlation value for the cord expansion ratio was 0.78, and the κ value for bright spotty lesions was 0.61. CONCLUSIONS: Our scoring system, based on cervicomedullary junction involvement, higher cord expansion ratio, bright spotty lesions, and female sex, can facilitate the timely diagnosis of neuromyelitis optica spectrum disorders.

The role of chronic viral hepatitis on tuberculosis treatment interruption.

BACKGROUND: Tuberculosis (TB) drug-induced liver injury (TB-DILI) usually occurs within 8 weeks of anti-tuberculosis drug initiation. In Singapore, we suspected that the onset of TB drug-induced transaminitis may be confounded with hepatitis C virus (HCV) and hepatitis B (HBV) virus co-infection. OBJECTIVE: To determine the impact of HCV/HBV co-infection on the course of treatment in patients with TB treatment interrupted due to transaminitis. DESIGN: TB patients with treatment interruption during 2013-2014 were identified through the Singapore national TB registry. Case notes of those with transaminitis were perused. RESULTS: Of 3860 TB patients notified, 140 had suspected TB-DILI. Of these, respectively 20/140 (14.3%) and 16/140 (11.4%) were HCV- or HBV-positive. The median time to treatment interruption/transaminitis was 5 weeks vs. 9.9 weeks and 9.6 weeks for transaminitis patients without chronic liver disease and with HCV/HBV co-infection (P < 0.01). Multivariate logistic regression analysis revealed that having HCV/HBV co-infection was associated with treatment interruption occurring beyond 8 weeks (adjusted OR [aOR] 4.06, 95%CI 1.28-12.85); HCV transaminitis patients were more likely to take 10 months to complete anti-tuberculosis treatment (aOR 5.11, 95%CI 1.21-21.67) than those without chronic liver disease. CONCLUSION: TB treatment interruption due to transaminitis in HCV/HBV co-infected patients occurred later than in those without liver disease. Most had completed 2 months of pyrazinamide-containing intensive phase treatment before the onset of transaminitis.

Prevalence and factors associated with smoking among adults in Malaysia: Findings from the National Health and Morbidity Survey (NHMS) 2015.

INTRODUCTION: The continuous monitoring of smoking prevalence and its associated factors is an integral part of anti-smoking programmes and valuable for the evaluation of the effectiveness of anti-smoking measures and policies. This study aimed at determining prevalence of smoking and identifying socio-demographic factors associated with smoking among adults in Malaysia aged 15 years and over. METHODS: This is a cross-sectional study with a representative sample of 21 445 adults in Malaysia, aged 15 years and over, selected via a stratified, two-stage proportionate-to-size sampling method. Data were obtained from face-to-face interviews by trained research assistants, using a standard validated questionnaire. Multivariable logistic regression was performed to determine socio-demographic factors associated with smoking among Malaysians. RESULTS: The overall prevalence of smoking was 22.8% (95% CI: 21.9-23.8%), with males having a significantly higher prevalence compared to females (43.0%, 95% CI: 41.1-44.6 vs 1.4%, 95% CI: 1.1-1.7). The highest smoking prevalence was observed among other ethnicities (35.7%), those aged 25-44 years (59.3%), and low educational attainment (25.2%). Males, those with lower educational attainment and Malays were significantly associated with smoking. CONCLUSIONS: The prevalence of smoking among Malaysians, aged 15 years and over, remains high despite the implementation of several anti-smoking measures over the past decades. Specially tailored anti-smoking policies or measures, particularly targeting males, the Malays, younger adults and those with lower educational attainment, are greatly warranted to reduce the prevalence of smoking in Malaysia.

[The psychiatric hospital discharge database (RIM-P): An essential tool for the surveillance of hospitalization after a suicide attempt]. / Le Recueil d'information médicalisé en psychiatrie (RIM-P) : un outil nécessaire pour la surveillance des hospitalisations suite à une tentative de suicide.

BACKGROUND: Epidemiological surveillance of suicide attempts is essential for monitoring indicator trends in the evaluation of prevention actions. As part of this surveillance, analysis of data from hospitalization for suicide attempts is particularly useful. METHODS: For the first time, data from two national hospital discharge databases, the "Programme de médicalisation des systèmes d'information en médecine, chirurgie, obstétrique" (PMSI-MCO) and the " Recueil d'information médicalisé en psychiatrie" (RIM-P) have been analyzed jointly. All patients aged 10 or more hospitalized in 2012 in medicine, surgery or psychiatry departments in metropolitan France have were included. RESULTS: Through 2012, 89,072 patients (62% females and 38% males) totalized 134,051 hospital stays following a suicide attempt, with 93.4% (n=83,196) in medicine or surgery wards and 32.1% (n=28,594) in psychiatry wards (solely or transferred after a stay in medicine or surgery). However, among the patients transferred to psychiatry after hospitalization in medicine or surgery for suicide attempt, 82.4% had no suicide attempt code noted at their discharge from psychiatry. One or more psychiatric diagnoses were observed in 75% of the patients hospitalized for suicide attempt. The most common diagnoses in men and in women were mood disorders (46%), particularly depression (42%; 44% in women and 38% in men). Mental disorders related to alcohol use were noted in more than a quarter of the patients, more frequently in men (37%) than in women (21%). Some diagnoses were rarely noted in medicine or surgery, such as anxiety disorders and disorders of adult personality and behavior. CONCLUSION: Improvement of the epidemiological surveillance of suicide attempts requires a systematic coding of hospitalizations in psychiatry as well as in medicine and surgery. Data from hospitalization in psychiatry yield a more precise identification of psychiatric co-morbidities associated with suicide attempts. The frequent presence of mental problems associated with suicide attempts should encourage clinicians to search for these symptoms systematically as soon as possible after admission of the patient.

I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology.

Engineered 3D cardiac tissue constructs (ECTCs) can replicate complex cardiac physiology under normal and pathological conditions. Currently, most measurements of ECTC contractility are either made isometrically, with fixed length and without control of the applied force, or auxotonically against a variable force, with the length changing during the contraction. The "I-Wire" platform addresses the unmet need to control the force applied to ECTCs while interrogating their passive and active mechanical and electrical characteristics. A six-well plate with inserted PDMS casting molds containing neonatal rat cardiomyocytes cultured with fibrin for 13-15days is mounted on the motorized mechanical stage of an inverted microscope equipped with a fast sCMOS camera. A calibrated flexible probe provides strain load of the ECTC via lateral displacement, and the microscope detects the deflections of both the probe and the ECTC. The ECTCs exhibited longitudinally aligned cardiomyocytes with well-developed sarcomeric structure, recapitulated the Frank-Starling force-tension relationship, and demonstrated expected transmembrane action potentials, electrical and mechanical restitutions, and responses to both ß-adrenergic stimulation and blebbistatin. The I-Wire platform enables creation and mechanical and electrical characterization of ECTCs, and hence can be valuable in the study of cardiac diseases, drug screening, drug development, and the qualification of cells for tissue-engineered regenerative medicine. STATEMENT OF SIGNIFICANCE: There is a growing interest in creating engineered heart tissue constructs for basic cardiac research, applied research in cardiac pharmacology, and repair of damaged hearts. We address an unmet need to characterize fully the performance of these tissues with our simple "I-Wire" assay that allows application of controlled forces to three-dimensional cardiac fiber constructs and measurement of both the electrical and mechanical properties of the construct. The advantage of I-Wire over other approaches is that the constructs being measured are truly three-dimensional, rather than a single layer of cells grown within a microfluidic device. We anticipate that the I-Wire will be extremely useful for the evaluation of myocardial constructs created using cardiomyocytes derived from human induced pluripotent stem cells.

[Factors associated with suicide attempts by sexual minorities: Results from the 2011 gay and lesbian survey]. / Facteurs associés aux tentatives de suicide chez les minorités sexuelles : résultats de l'enquête presse gays et lesbiennes 2011.

BACKGROUND: Since the 1990s, several studies have found higher rates of suicide attempts in homosexuals and bisexuals than in heterosexuals. The current challenge is to identify risk factors for targeting prevention. The aim of this paper was to determine, for the first time in France, the prevalence of suicide attempts over a 12-month period and associated factors in a population of men and women who self-identified as homosexuals or bisexuals. METHODS: A convenience sample cross-sectional survey was conducted in 2011 using an anonymous self-administered questionnaire made available in the gay press, and Internet sites targeting the gay or lesbian community. Among the persons completing the questionnaire, 10,100 men and 2963 women residing in France answered the questions on suicide attempts. The factors associated with suicide attempts during the previous 12 months were identified by logistic regression. RESULTS: Lifetime prevalence for suicide attempts was 16% in men and 18% in women; 12-month prevalence was 1.6% in men and 1.9% in women. Factors independently associated with suicide attempts in the past 12 months in men and women were lack of occupational activity, victim of sexual abuse, termination of a long-term relationship, excessive alcohol consumption in the past 12 months, depression, and in addition, in men, living in a small locality, victim of verbal or physical aggression and use of anxiolytics. CONCLUSION: According to our results, the fight against homophobia is an important element for the prevention of suicide attempts among homosexual and bisexual men. Indeed, in addition to traditional risk factors for suicide attempt, a significant association was also found with homophobic aggression in the past year.

Targeted inhibition of ANKRD1 disrupts sarcomeric ERK-GATA4 signal transduction and abrogates phenylephrine-induced cardiomyocyte hypertrophy.

AIMS: Accumulating evidence suggest that sarcomere signalling complexes play a pivotal role in cardiomyocyte hypertrophy by communicating stress signals to the nucleus to induce gene expression. Ankyrin repeat domain 1 (ANKRD1) is a transcriptional regulatory protein that also associates with sarcomeric titin; however, the exact role of ANKRD1 in the heart remains to be elucidated. We therefore aimed to examine the role of ANKRD1 in cardiomyocyte hypertrophic signalling. METHODS AND RESULTS: In neonatal rat ventricular myocytes, we found that ANKRD1 is part of a sarcomeric signalling complex that includes ERK1/2 and cardiac transcription factor GATA4. Treatment with hypertrophic agonist phenylephrine (PE) resulted in phosphorylation of ERK1/2 and GATA4 followed by nuclear translocation of the ANKRD1/ERK/GATA4 complex. Knockdown of Ankrd1 attenuated PE-induced phosphorylation of ERK1/2 and GATA4, inhibited nuclear translocation of the ANKRD1 complex, and prevented cardiomyocyte growth. Mice lacking Ankrd1 are viable with normal cardiac function. Chronic PE infusion in wild-type mice induced significant cardiac hypertrophy with reactivation of the cardiac fetal gene program which was completely abrogated in Ankrd1 null mice. In contrast, ANKRD1 does not play a role in haemodynamic overload as Ankrd1 null mice subjected to transverse aortic constriction developed cardiac hypertrophy comparable to wild-type mice. CONCLUSION: Our study reveals a novel role for ANKRD1 as a selective regulator of PE-induced signalling whereby ANKRD1 recruits and localizes GATA4 and ERK1/2 in a sarcomeric macro-molecular complex to enhance GATA4 phosphorylation with subsequent nuclear translocation of the ANKRD1 complex to induce hypertrophic gene expression.