Timing of Assessment of Humoral and Cell-Mediated Immunity after Influenza Vaccination.

Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing of immunological assessments after vaccination using markers of humoral and cell-mediated immunity. In the 2018/2019 influenza season, blood was collected from 29 healthy adults before and after vaccination with a quadrivalent inactivated influenza vaccine, and we performed serial measurements of humoral immunity (hemagglutination inhibition [HAI] and neutralizing antibody [NT]) and cell-mediated immunity (interferon-gamma [IFN-γ]). The HAI and NT titers before and after vaccination were strongly correlated, but no correlation was observed between the markers of cell-mediated and humoral immunity. The geometric mean titer and geometric mean concentration of humoral and cellular immune markers increased within 2 weeks after vaccination and had already declined by 8 weeks. This study suggests that the optimal time to assess the immune response is 2 weeks after vaccination. Appropriately timed immunological assessments can help ensure that vaccination is effective.

Spatial Clusters of High Prevalences of Overweight and Obesity Among Children in Indonesia.

Objective Childhood obesity has emerged as a pressing health concern in both high-income and lower-middle-income countries, including Indonesia. The prevalence of overweight and obesity among school children aged 5-12 years has been increasing in Indonesia, with 20% of Indonesian children identified as obese or overweight in 2018. Therefore, addressing this problem will be challenging. This study aims to identify district- and city-level clusters with high prevalences of overweight and obese children aged 5-12 years in Indonesia. Methodology This is an ecological study that utilizes secondary data from the 2018 Basic Health Research report conducted by the Indonesian Ministry of Health. We included 514 districts and cities to detect district- and city-level clusters. Spatial cluster analysis was performed using restricted flexible scan statistics to identify clusters with high prevalences of childhood overweight and obesity in Indonesian districts and cities. Results The findings reveal that childhood overweight and obesity are not randomly distributed. The study detected 20 clusters with high prevalences of childhood overweight and 36 clusters of obesity, with a particular concentration in Western Indonesia. A primary cluster of childhood overweight occurred in Sijunjung, Tanah Datar, Agam, Pasaman, South Solok, Dharmasraya, West Pasaman, Sawah Lunto City, Padang Panjang City, and Kampar. A primary cluster of obesity occurred in Mandailing Natal, South Tapanuli, Central Tapanuli, North Tapanuli, Labuhan Batu, North Padang Lawas, Padang Lawas, North Labuhan Batu, West Pasaman, and Rokan Hilir. Conclusions This study found 20 clusters with high prevalences of childhood overweight and 36 clusters of obesity in Indonesia. Implementing health promotion programs in the identified cluster regions will be crucial to effectively addressing the growing problem of childhood obesity in Indonesia.

Identification of Azalamellarin N as a Pyroptosis Inhibitor.

Pyroptosis is a form of regulated cell death that promotes inflammation; it attracts much attention because its dysregulation leads to various inflammatory diseases. To help explore the precise mechanisms by which pyroptosis is regulated, in this study, we searched for chemical compounds that inhibit pyroptosis. From our original compound library, we identified azalamellarin N (AZL-N), a hexacyclic pyrrole alkaloid, as an inhibitor of pyroptosis induced by R837 (also called imiquimod), which is an agonist of the intracellular multiprotein complex nucleotide-binding and oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. However, whereas the effect of AZL-N on R837-induced pyroptosis was relatively weak, AZL-N strongly inhibited pyroptosis induced by extracellular ATP or nigericin, which are different types of NLRP3 inflammasome agonists. This was in contrast with the results that MCC950, a well-established NLRP3 inhibitor, consistently inhibited pyroptosis irrespective of the type of stimulus. We also found that AZL-N inhibited activation of caspase-1 and apoptosis-associated speck-like proteins containing a caspase activation and recruitment domain (ASC), which are components of the NLRP3 inflammasome. Analysis of the structure-activity relationship revealed that a lactam ring of AZL-N, which has been shown to contribute to the strong binding of AZL-N to its known target protein kinases, is required for its inhibitory effects on pyroptosis. These results suggest that AZL-N inhibits pyroptosis by targeting molecule(s), which may be protein kinase(s), that act upstream of NLRP3 inflammasome activation, rather than by directly targeting the components of the NLRP3 inflammasome. Further identification and analysis of target molecule(s) of AZL-N will shed light on the regulatory mechanisms of pyroptosis, particularly those depending on proinflammatory stimuli.

Factors influencing the recovery-oriented attitudes of nursing directors in psychiatric hospitals: A cross-sectional study in Japan.

WHAT IS KNOWN ON THE SUBJECT?: Recovery-oriented services have been shown to promote recovery in people with mental illness; their implementation is important for current psychiatric practice and is being considered by many professional institutions. The Japanese government released the policy 'A Vision for Reform of Mental Health and Medical Welfare' (Ministry of Health, Labour and Welfare, 2004; https://www.mhlw.go.jp/topics/2004/09/dl/tp0902-1a.pdf), aiming to update public consciousness, reorganize the mental healthcare welfare system and strengthen the foundation of mental healthcare to promote a basic policy focusing on the transition 'from hospital to community life'. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first study to clarify recovery-oriented attitudes among psychiatric nursing directors and related factors in Japan. It shows an association between recovery-oriented attitudes and hospital size. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A relationship exists between the recovery knowledge and recovery-oriented attitudes of psychiatric nursing directors. It may thus be valuable for directors to see and hear about the experiences of patients living in the community during their recovery process. As hospital size and organizational climate may hinder the successful implementation of recovery-oriented practices, these factors must be considered when introducing such practices. Further research is needed on the relationship between psychiatric nursing directors' recovery-oriented attitudes and practices. Moreover, to develop intervention studies that uncover success factors for enhancing recovery-oriented attitudes, organizational factors that enable recovery-oriented practices must be further investigated. ABSTRACT: INTRODUCTION: Recovery-oriented practices in mental health services have become a global priority. Despite their proven effectiveness, Japanese hospitals have not widely implemented such practices. AIM: This study clarified psychiatric nursing directors' recovery-oriented attitudes and factors regarding promoting recovery-oriented practices to identify methods for developing these practices in Japan. METHOD: This cross-sectional study used a questionnaire survey with 250 nursing directors from 1287 Japanese psychiatric hospitals. Multivariable regression analysis assessed how socio-demographic variables and Recovery Knowledge Inventory (RKI) scores affected Recovery Attitudes Questionnaire (RAQ-7) scores. RESULTS: The analysis revealed that more clinical and managerial experience was associated with more negative recovery-oriented attitudes. High RKI scores, knowledge of strength, hospital size and outpatient work experience were associated with more positive recovery-oriented attitudes. DISCUSSION: Implementing recovery practices requires consideration of knowledge and experience in recovery and hospital size alongside recovery training based on a hospital's organizational structure. Although the low response rate could influence the study's generalisability, it could also indicate low interest in recovery-oriented practices among professionals. IMPLICATIONS FOR PRACTICE: Acquiring more knowledge and experience regarding recovery promotes recovery-oriented attitudes among nursing directors. An appropriate organizational culture and consideration of hospital size are required when introducing such recovery practices.

Types and frequency of social participation and comprehensive frailty among community-dwelling older people in Japan.

Although research has established social participation as important for preventing frailty in older people, the association between the type and frequency of social participation and comprehensive frailty remains unclear. This study aimed to reveal the associations between types and frequency of social participation and comprehensive frailty among community-dwelling older people. This was a cross-sectional study conducted in four cities and towns (Inabe City, Nabari City, Odai Town, and Kiho Town) of Mie Prefecture, Japan, among adults who were: (i) aged ≥65 years and (ii) not certified as needing long-term care. We measured comprehensive frailty using the participants' total scores on the Kihon Checklist, developed by Ministry of Health, Labour and Welfare of Japan, which divides frailty status into three categories: robust (0-3 points), prefrail (4-7), and frail (8-25). Types and frequency of social participation were explanatory variables, and ordered logistic regression analysis adjusted for potential confounding factors identified the associations. The frailty status of the 296 participants (age 65-74 years: 44.3 %; female: 74.0 %) was as follows: frail, 21.3 %; prefrail, 40.2 %; and robust, 38.5 %. Lower level of frailty was associated with interaction using smartphones 2-3 times per month, participating in sports ≥4 times per week, participating in local improvement activities several times per year, and engaging in activities for children 2-4 times per month. Social participation among older adults at appropriate frequencies were associated with the lower level of comprehensive frailty. However, future longitudinal studies are needed using populations from more diverse countries or regions and from different cultures.

Factors associated with overweight/obesity of children aged 6-12 years in Indonesia.

BACKGROUND: Globally, the prevalence of childhood obesity has increased considerably, including in Indonesia. Obesity results from multifactorial interactions at the personal, familial, and environmental levels. However, little is known about the factors associated with overweight/obesity among children in Indonesia. This study is intended to identify personal, familial, and environmental factors associated with overweight/obesity in children aged 6-12 years in Indonesia. METHODS: Study design was a secondary data analysis using the Indonesia Family Life Survey in 2014/2015, focusing on 6,090 children aged 6-12 years. The questions covered the child's body mass index and potential personal, familial, and environmental factors. Logistic regression analysis was performed to identify the personal, familial, and environmental factors. RESULTS: The mean age of participants was 8.9 years (SD = 2.0); 51.0% were boys; 9.4% were overweight; and 8.1% were obese. Overweight and obesity were associated with age [AOR 1.09 (95% CI 1.04-1.14)], having an overweight [AOR 1.93 (95% CI 1.58-2.36)] or obese [AOR 3.36 (95% CI 2.43-4.61)] father compared with a normal father, being of Chinese [AOR 9.51 (95% CI 1.43-79.43)] or Javanese [AOR 1.60 (95% CI 1.16-2.24)] ethnicity compared with Sundanese ethnicity, and residing in an urban area [AOR 1.36 (95% CI 1.10-1.70)]. A lower risk of child overweight/obesity was associated with the father's perception [AOR 0.56 (95% CI 0.38-0.80)] and mother's perception [AOR 0.66 (95% CI 0.43-0.98)] of the child's food consumption as being less than adequate compared with adequate. CONCLUSIONS: Risk factors in children for overweight/obesity were older age, having an overweight/obese father, membership of certain ethnic groups, and urban residence. The main protective factor was parents' perception that a child's food consumption was less than adequate. Health promotion programs focused on these factors could help control or prevent childhood obesity in Indonesia.

Protective and high-risk social activities associated with homebound status among older adults in rural Japan.

Becoming homebound can be devastating for older adults in rural communities. This study aimed to identify protective or high-risk social activities associated with homebound status among the rural young old (ages 65-74) and the oldest old (ages ≥ 75). We used data from a survey of older adults in a rural community of Japan in 2014. Questions covered sociodemographic characteristics, homebound status (i.e., going out less than once a week), physical and psychological status, and social activities. Using survey data, we conducted logistic regression analysis to identify protective and high-risk social activities associated with homebound status. Of the 1,564 participants, 51.0 % were the oldest old, and the mean age was 75.2 (±7.0) years. The prevalence of homebound status was 10.5 % total: 5.2 % among the young old and 15.7 % among the oldest old and highest among the female oldest old (19.4 %). The main protective social activity for the young and the oldest old was visiting friends' houses (adjusted odds ratio [AOR] 5.38, 95 % confidence interval [CI] 1.64-17.64 and AOR 3.49, 95 % CI 1.07-11.42, respectively). For the young old, specific high-risk social activities were advising family and friends (AOR 0.07, 95 % CI 0.01-0.62) and activities to support older adults (AOR 0.17, 95 % CI 0.03-0.84). For the oldest old, a protective social activity was participating in long-term care prevention programs (AOR 28.94, 95 % CI 1.90-441.63). To prevent rural older adults from becoming homebound, support should be provided according to protective and high-risk social activities for age groups, with particular attention to safe socialization amid the threat of COVID-19.

Comparison of the Hemagglutination Inhibition Titers against Influenza Vaccine Strains in Japan from the 2017/2018 to 2021/2022 Seasons Using a Single Set of Serum Samples.

In Japan, inactivated influenza vaccines are used. We measured titers of antibodies to vaccine strains of three influenza types-influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria-from the 2017/2018 to 2021/2022 seasons, but not for influenza A (H3N2) from the 2018/2019 season, using a single set of serum samples from 34 healthy volunteers, and assessed the consistency in antibody positivity between seasons. The antibody titers in the 2017/2018 season were used as a reference. The influenza A (H1N1) antibody titer in 2019/2020 did not differ significantly from that in the 2017/2018 season, but the titers varied in the two subsequent seasons. The influenza A (H3N2) antibody titers toward the 2019/2020, 2020/2021, and 2021/2022 seasonal viruses differed significantly from that in the 2017/2018 season. The influenza B/Victoria antibody titer toward the 2019/2020 seasonal antigen differed from that in the 2017/2018 season, and the antibody positivity was inconsistent between seasons; however, the antibody titer in the 2020/2021 season did not differ significantly from those in the prior two seasons, and the antibody positivity was consistent between seasons. Antibody titers and their consistency can be used to evaluate cross-immunity of antibodies.

Marine-derived microbes and molecules for drug discovery.

Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein-protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies.

A Randomized Controlled Trial on Primigravid Women of Text Messaging Intervention Offering Pregnancy and Childbirth Support.

This study aimed to assess the efficacy of a text messaging intervention that offered pregnancy and childbirth support. Participants included 39 primigravid women who were less than 12 weeks pregnant. Text messages were sent twice weekly to the intervention group from week 13 of pregnancy until childbirth. Outcome measures were anxiety levels, lifestyle in the month before birth, pre-birth weight, pregnancy complications, delivery complications, birth weight, thoughts regarding the text messages, and the frequency of viewing of the text messages. For the item "I engage in body stretching," the average value in the intervention group was significantly higher than that in the control group. For the item "I have regular bowel movements," the average value in the intervention group was significantly lower. Most participants reported that the intervention was at least somewhat useful. This study indicates that text messaging intervention is practical and can be used to support numerous pregnant women simultaneously at a relatively low cost. Since this is a study pilot trial, large-scale studies are necessary to improve the method and allow for the generalization of the results.

Itpr1 regulates the formation of anterior eye segment tissues derived from neural crest cells.

Mutations in ITPR1 cause ataxia and aniridia in individuals with Gillespie syndrome (GLSP). However, the pathogenic mechanisms underlying aniridia remain unclear. We identified a de novo GLSP mutation hotspot in the 3'-region of ITPR1 in five individuals with GLSP. Furthermore, RNA-sequencing and immunoblotting revealed an eye-specific transcript of Itpr1, encoding a 218amino acid isoform. This isoform is localized not only in the endoplasmic reticulum, but also in the nuclear and cytoplasmic membranes. Ocular-specific transcription was repressed by SOX9 and induced by MAF in the anterior eye segment (AES) tissues. Mice lacking seven base pairs of the last Itpr1 exon exhibited ataxia and aniridia, in which the iris lymphatic vessels, sphincter and dilator muscles, corneal endothelium and stroma were disrupted, but the neural crest cells persisted after completion of AES formation. Our analyses revealed that the 218-amino acid isoform regulated the directionality of actin fibers and the intensity of focal adhesion. The isoform might control the nuclear entry of transcriptional regulators, such as YAP. It is also possible that ITPR1 regulates both AES differentiation and muscle contraction in the iris.

Changes in Cell-Mediated Immunity (IFN-γ and Granzyme B) Following Influenza Vaccination.

Interferon gamma (IFN-γ) is considered a key moderator of cell-mediated immunity. However, little is known about its association with granzyme B, which plays an important role in the effector function of cytotoxic T lymphocytes (CTLs). In the present study, we collected blood samples from 32 healthy adults before and after vaccination with inactivated influenza vaccine in 2017/18 to measure the levels of IFN-γ and granzyme B, which play roles in cell-mediated immunity, and hemagglutination inhibition (HAI) antibody, which plays a role in humoral immunity. The levels of IFN-γ and granzyme B were significantly correlated both before and after vaccination. Furthermore, the post-vaccine fold increases in the IFN-γ and granzyme B levels were significantly correlated. The levels of IFN-γ and granzyme B decreased five months after vaccination in more than half of the subjects who exhibited an increase in IFN-γ and granzyme B at two weeks post-vaccination. This is the first study to investigate the correlation between IFN-γ and granzyme B levels following influenza vaccination. Our study suggests that both IFN-γ and granzyme B can be used as markers of cell-mediated immunity.

Cleaved PGAM5 dephosphorylates nuclear serine/arginine-rich proteins during mitophagy.

PGAM5 is a protein phosphatase located in the inner mitochondrial membrane through its transmembrane (TM) domain and is cleaved within the TM domain upon mitochondrial dysfunction. We found previously that cleaved PGAM5 is released from mitochondria, following proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy, a selective form of autophagy specific to mitochondria. Here, we examined the role of cleaved PGAM5 outside mitochondria. Deletion mutants that mimic cleaved PGAM5 existed not only in the cytosol but also in the nucleus, and a fraction of cleaved PGAM5 translocated to the nucleus during mitophagy induced by the uncoupler CCCP. We identified serine/arginine-related nuclear matrix protein of 160 kDa (SRm160)/SRRM1, which contains a highly phosphorylated domain rich in arginine/serine dipeptides, called the RS domain, as a nuclear protein that interacts with PGAM5. PGAM5 dephosphorylated SRm160, and incubation of lysates from WT cells, but not of those from PGAM5-deficient cells, induced dephosphorylation of SRm160 and another RS domain-containing protein SRSF1, one of the most characterized serine/arginine-rich (SR) proteins. Moreover, phosphorylation of these proteins and other SR proteins, which are commonly reactive toward the 1H4 monoclonal antibody that detects phosphorylated SR proteins, decreased during mitophagy, largely because of PGAM5 activity. These results suggest that PGAM5 regulates phosphorylation of these nuclear proteins during mitophagy. Because SRm160 and SR proteins play critical roles in mRNA metabolism, PGAM5 may coordinate cellular responses to mitochondrial stress at least in part through post-transcriptional and pre-translational events.

Association between the type of physical activity and metabolic syndrome in middle-aged and older adult residents of a semi-mountainous area in Japan.

BACKGROUND: Physical activity is reported to prevent metabolic syndrome. However, it is unclear whether exercise or daily physical activity is more beneficial for residents of semi-mountainous areas. This study aimed to identify whether daily physical activity is more beneficial than exercise for the prevention of metabolic syndrome among middle-aged and older residents in semi-mountainous areas. METHODS: We analyzed secondary data of 636 people who underwent a specific health checkup in a semi-mountainous area of Japan. Physical activity was classified into four types: inactivity (I-type; without exercise and without daily physical activity), only exercise (E-type; with exercise and without daily physical activity), only daily physical activity (D-type; without exercise and with daily physical activity), and full physical activity type (F-type; with exercise and with daily physical activity). We compared the means of risk factors for metabolic syndrome by these four types, followed by logistic regression analysis, to identify whether and to what extent the D-type was less likely to have metabolic syndrome than the E-type. RESULTS: The prevalence of metabolic syndrome was 28.5% (men 45.7%, women 15.8%). The proportions of men with exercise and daily physical activity were 38.7% and 52.8%, respectively. For women, the proportions were 33.0% and 47.1%, respectively. In women, the D-type had the significantly lowest BMI, smallest waist circumference, highest HDL-C, and lowest prevalence of metabolic syndrome of the four types; the same was not observed in men. Additionally, D-type activity was more strongly associated with a reduced risk of metabolic syndrome than E-type activity in women (adjusted odds ratio 0.24; 95% confidence interval 0.06-0.85, P = 0.028). CONCLUSIONS: Compared to middle-aged and older women residents with exercise in a semi-mountainous area of Japan, those with daily physical activity may effectively prevent metabolic syndrome.

An impact of dietary intervention on blood pressures among diabetic and/or hypertensive patients with high cardiovascular disorders risk in northern Thailand by cluster randomized trial.

BACKGROUND: Global sodium intake remains above the recommended levels to control blood pressure (BP). We aimed to evaluate the efficacy of a dietary intervention on BP through salt reduction among community-dwelling participants with high risk of cardiovascular disorders (CVD). METHODS: This cluster randomized trial (February 2012 to January 2013) included cooking instruction using the pocket salt meter among patients with diabetes and/or hypertension who were treated at health center in Thailand. Based on health centers, 8 clusters of eligible participants were randomly allocated to the 4 intervention and 4 control groups. Dietary intervention was performed at baseline, 1 month, and 3 months in intervention group. In both groups, systolic and diastolic BPs, and estimated 24 hours salt intake based on overnight urine samples were measured at baseline, 6 months, and 12 months. RESULTS: A total of 753 participants were enrolled (374 in the intervention group and 379 in the control group). In the mixed-effects model, there were significant difference in SBP and estimated salt intake after adjusting covariates at 6 months (adjusted differences between groups [95% CI]; -7.55 [-5.61 to -9.49] mm Hg P < .01; -0.66 [-0.40 to -0.92] g/day P = .03). However, these differences were not observed at 12 months (adjusted differences between groups [95% CI]; -1.83 [0.34 to -4.00] mm Hg P = .48; -0.42 [-0.17 to -0.67] g/day P = .16). There were no differences in DBP in both follow-ups. CONCLUSIONS: These results may suggest the effectiveness of a visually based dietary intervention targeting salt intake reduction in short term, but the effectiveness discontinued in long term.Clinical trial number: The International Standard Randomized Controlled Trial Number Register (ISRCTN39416277) on January 3, 2012.

SH3P2 suppresses osteoclast differentiation through restricting membrane localization of myosin 1E.

Osteoclasts are multinucleated cells responsible for bone resorption. Src homology 3 (SH3) domain-containing protein-2 (SH3P2)/osteoclast-stimulating factor-1 regulates osteoclast differentiation, but its exact role remains elusive. Here, we show that SH3P2 suppresses osteoclast differentiation. SH3P2 knockout (KO) mice displayed decreased femoral trabecular bone mass and enhanced localization of osteoclasts on the tibial trabecular bone surface, suggesting that SH3P2 suppresses bone resorption by osteoclasts. Osteoclast differentiation based on cellular multinuclearity induced by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) was enhanced in bone marrow-derived macrophages lacking SH3P2. RANKL induced SH3P2 dephosphorylation, which increased the association of actin-dependent motor protein myosin 1E (Myo1E) with SH3P2 and thereby prevented Myo1E localization to the plasma membrane. Consistent with this, Myo1E in the membrane fraction increased in SH3P2-KO cells. Together with the attenuated osteoclast differentiation in Myo1E knocked down cells, SH3P2 may suppress osteoclast differentiation by preventing their cell-to-cell fusion depending on Myo1E membrane localization.

Sensitivity and specificity of different antibody tests for detecting varicella-zoster virus.

INTRODUCTION: Antibody tests for detecting varicella-zoster virus include the fluorescent-antibody-to-membrane-antigen (FAMA) assay, immune adherence hemagglutination assay (IAHA), enzyme immunoassay (EIA), and the glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). Although FAMA and gpELISA are highly sensitive, FAMA is not available commercially. Therefore, this study was performed to compare potential high-sensitivity tests with commercially available tests. METHODS: Four antibody tests, FAMA, gpELISA, EIA, and IAHA, were performed using sera collected from 32 children aged 7 months-10 years. Using FAMA as a reference, the sensitivity and specificity of gpELISA, EIA, and IAHA were assessed. Subsequently, using gpELISA as a reference, the positive agreement rate of EIA and IAHA was assessed. RESULTS: On a reference scale with FAMA set at 100%, the sensitivity and specificity of the antibody tests were as follows: gpELISA, 67% and 100%; EIA, 67% and 100%; and IAHA, 47% and 100%, respectively. The positive agreement rates of EIA and IAHA relative to gpELISA were 86% and 64%, respectively. CONCLUSIONS: gpELISA had a lower positive rate than did FAMA, and showed comparable sensitivity to that of EIA.

Effectiveness of a new multi-component smoking cessation service package for patients with hypertension and diabetes in northern Thailand: a randomized controlled trial (ESCAPE study).

BACKGROUND: Smoking cessation is an achievable behavioral change, which reduces the risks of cardiovascular diseases, cancers and tobacco-related diseases. There is a need for an effective smoking cessation service for low and middle income country settings where the smoking rate is generally very high whilst a cessation service is not usually accessible. This study devised a new smoking cessation service package and assessed its effectiveness in the primary health care setting of northern Thailand. METHODS: This randomized controlled trial was centered at Maetha district hospital, Lampang province, Thailand, and its network of mobile non-communicable disease clinics at seven primary care units. A total of 319 eligible patients who consented to participate in the study, were randomly allocated to an intervention arm (160) and a control arm (159), applying block randomization. The multi-component intervention service consisted of: (1) regular patient motivation by the same nurse over a 3-month period; (2) a monthly piCO+ Smokerlyzer test for 3 months; (3) continual assistance from a trained family member, using a smoking-cessation- diary; and (4) optional nicotine replacement chewing gum therapy. The control group received the routine service comprising of brief counseling and casual follow-up. Smoking cessation, confirmed by six months of abstinence and the piCo+ Smokerlyzer breath test, was compared between the two services after a year follow-up. The trial is registered as an international current control trial at the ISRCTN registry. ISRCTN89315117. RESULTS: The median age of the participants was 64 years, with females constituting 28.84%. Most of the participants smoke hand-rolled cigarettes (85%). The intervention arm participants achieved a significantly higher smoking cessation rate than the control arm 25.62% vs 11.32%, with an adjusted odd ratio of 2.95 and 95% confidence interval 1.55-5.61. CONCLUSION: In relation to accessing smoking cessation services within the primary health care setting, participants who received the evidence-based intervention package were about three times more likely to succeed in giving up smoking than those who received the routine service. Utilizing community resources as major intervention components, the evidence from this trial may provide a useful and scalable smoking cessation intervention for low and middle income countries. TRIAL REGISTRATION: Current controlled trials ISRCTN89315117 . WHO international clinical trial identifier number: U1111-1145-6916; 3/2013.

Cleaved PGAM5 is released from mitochondria depending on proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy.

PGAM5 is a unique type of protein phosphatase that exists in mitochondria. It has been shown to exist in the inner mitochondrial membrane through its transmembrane domain and to be cleaved within the transmembrane domain upon mitochondrial dysfunction. However, its submitochondrial localization remains controversial; many researchers claim that PGAM5 localizes to the outer mitochondrial membrane based on the findings that PGAM5 associates with many cytoplasmic proteins. Here, we found that cleaved PGAM5 was released from mitochondria during mitophagy, a selective form of autophagy specific for mitochondria, and that the release was inhibited by proteasome inhibitors in HeLa cells stably expressing the E3 ubiquitin ligase Parkin. However, treatment of parental HeLa cells lacking Parkin with mitophagy-inducing agents caused PGAM5 cleavage but did not cause its release from mitochondria. Thus, cleaved PGAM5 appears to be released from mitochondria depending on proteasome-mediated rupture of the outer membrane during mitophagy, which has been previously shown to precede autophagy-mediated degradation of whole mitochondria. This study suggests that PGAM5 senses mitochondrial dysfunction in the inner mitochondrial membrane and serves as a signalling intermediate that regulates the cellular response to mitochondrial stress upon its cleavage and release from mitochondria.

Homecare protective and risk factors for early childhood caries in Japan.

BACKGROUND: Early childhood caries (ECC) affects children across Japan and throughout the world. Thus, it is important to identify dietary and dental care habits that either promote oral health or cause ECC. The objective of this study was to identify protective and risk factors associated with ECC in Japan. METHODS: In a typical rural Japanese community, we selected children born between 2004 and 2008 who had received checkups at their community health center including oral examinations conducted by dentists. We obtained data from children's records and from a questionnaire filled out by parents. We enrolled only children who at their checkup for 18-month-olds had no caries, and we obtained data about them at their checkup for 3-year-olds. We classified children as either having caries (treated or untreated) or being caries-free. We conducted bivariate analyses using data on child/family demographic characteristics, child's dietary habits, and child/parental oral health habits. We also conducted logistic regression analysis to control for variables and identify predictors of the presence/absence of caries. RESULTS: Five hundred sixty six children (278 boys, 288 girls) were enrolled and followed. After 2 years, 173 children (30.6%) presented with caries. Logistic regression analysis predicting caries at follow-up identified the interaction term "bottlefed overnight and brushed irregularly" at 18 months of age as a highly significant predictor of developing caries-adjusted odds ratio (AOR) of 14.27, 95% confidence interval (CI) 1.02-199.71. Two variables measured at follow-up were also significant predictors: having low levels of dental plaque (AOR 2.41, 95% CI 1.34-4.35) and having a mother who had untreated caries (AOR 1.84, 95% CI 1.09-3.12). CONCLUSION: Public health efforts should encourage parents to eliminate bottle feeding overnight and promote brushing twice daily as children's teeth begin to erupt. Greater efforts should be made to teach parents and daytime caregivers how to brush effectively to remove all plaque. Health professionals should pay close attention to mothers' oral health status. Mothers with caries should receive prompt treatment and be assisted in developing better dietary and oral health habits that will benefit themselves and their children. Policies and programs should focus more on family oral health rather than just child oral health.