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Introduction: The Fertility of Thailand declined to 1.6 in 2014 compared to 6.5 in the early sixties. This fertility revolution was accompanied by a concurrent revolution of contraceptive behavior among Thai people. This study examined the role of individual and geospatial factors to explain the variation in contraceptive method choice among married in two selected districts of Kanchanaburi Province, Thailand. Methods: The sample size in this study was 1468. The study population was currently married women of reproductive age (15-49 years) who were residing in two selected districts of Kanchanaburi province, Sai Yok and Muang districts, collected under the Kanchanaburi Demographic Surveillance Site (KDSS) project from 2004 to 2006. The study performed multinomial logistic regression for statistical analysis and Arc view GIS for spatial analysis to identify the factors associated with contraceptive method choice. Results: The women in the middle age group and urban women were more likely to use permanent methods over non use and temporary methods compared to young and rural women respectively. Women having higher than secondary education used both temporary and permanent contraceptive methods 2.5 times more than uneducated women (AOR 2.43; 95% CI 1.33– 4.46 for temporary versus none and AOR 2.54; 95% CI 1.29 – 5.01 for permanent versus none respectively). If women has no children, they were significantly less likely to use permanent method over non-use as well as over temporary methods. Geo-spatial analysis results showed transportation facilities determine the contraceptive choice. Conclusion: The better transportation network facilitated women to use a permanent contraceptive method rather than the temporary method. It is necessary to establish a better transportation system and education system in the areas, especially in the mountainous regions to improve accessibility and to realize reproductive health services. Further, investments in increasing women's access to various contraceptive options are urgently needed.

To evaluate the efficacy of four decontamination protocols on contaminated healing abutments (HAs) and their effects on surface topography.Eighty contaminated single-use HA samples collected from human participants were stained with phloxine B and examined microscopically. The retrieved HAs were randomly divided into four test groups: (1) Autoclaving only (AU), (2) 5.25% sodium hypochlorite (NaOCl) + AU, (3) Electrochemical treatment (EC) + AU, (4) NaOCl + EC + AU, and positive control (contaminated without any treatment). Four new unused HAs served as negative controls (NC). The surface features were analyzed using stereo microscopy (SM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and optical profilometry.The lowest decontamination efficacy was observed for the AU group. The NaOCl + AU and EC + AU groups effectively removed residual contamination, whereas EC + AU showed better decontamination results than NaOCl + AU. SM, SEM, and EDS analyses revealed the best decontamination efficacy in the combined NaOCl + EC + AU group compared to the other groups. Surface roughness (Sa), developed surface area ratio (Sdr), and texture-aspect ratio (Str) in AU, NaOCl + AU, EC + AU, and NaOCl + EC + AU groups were not statistically significant compared to the NC group.The combination of NaOCl with subsequent EC can remove soft and hard deposits from the surface of HAs compared to NaOCl alone and EC alone, without altering the surface topography of HAs.

To investigate various cleaning protocols employed to enable the reuse of healing abutments in the past decade.The review followed the guidelines set out in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, with guidance from the Cochrane Collaboration Handbook. Electronic searching and handsearching were performed using the National Library of Medicine (MEDLINE via PubMed) and the Cochrane Central Register of Controlled Trials from January 2010 to July 2022, respectively. Studies published in English were evaluated. Two independent examiners conducted the search and the review process. The risk of bias of the included studies was evaluated.In total, 178 articles were evaluated for review, but only 15 of them were selected for full-text reading. Regarding cleaning efficacy, chemical decontamination using sodium hypochlorite produced better results than laser and mechanical decontamination with airflow. Similar efficacy was found between chemical and electrochemical decontamination. Combined use of chemical and electrochemical decontamination protocols demonstrated the greatest efficacy. Chemical and electrochemical decontamination methods were found to achieve better outcomes in preserving the surface properties of decontaminated healing abutments than laser and mechanical methods.The present review found that combined decontamination protocols (chemical, electrochemical processing and autoclave treatment) are favourable for obtaining healing abutments with optimally cleaned surfaces. Moreover, healing abutments located in an area that is difficult to access can be cleaned without affecting the surface properties. This information could benefit researchers and clinicians when multiple-use healing abutments are considered.

Aims Myocardial infarction (MI) accelerates atherosclerosis and greatly increases the risk of recurrent cardiovascular events for many years, in particular, strokes and MIs. Because B cell-derived autoantibodies produced in response to MI also persist for years, we investigated the role of B cells in adaptive immune responses to MI. Methods and results We used an apolipoprotein-E-deficient (ApoE−/−) mouse model of MI-accelerated atherosclerosis to assess the importance of B cells. One week after inducing MI in atherosclerotic mice, we depleted B cells using an anti-CD20 antibody. This treatment prevented subsequent immunoglobulin G accumulation in plaques and MI-induced accelerated atherosclerosis. In gain of function experiments, we purified spleen B cells from mice 1 week after inducing MI and transferred these cells into atherosclerotic ApoE−/− mice, which greatly increased immunoglobulin G (IgG) accumulation in plaque and accelerated atherosclerosis. These B cells expressed many cytokines that promote humoural immunity and in addition, they formed germinal centres within the spleen where they differentiated into antibody-producing plasma cells. Specifically deleting Blimp-1 in B cells, the transcriptional regulator that drives their terminal differentiation into antibody-producing plasma cells prevented MI-accelerated atherosclerosis. Alarmins released from infarcted hearts were responsible for activating B cells via toll-like receptors and deleting MyD88, the canonical adaptor protein for inflammatory signalling downstream of toll-like receptors, prevented B-cell activation and MI-accelerated atherosclerosis. Conclusion Our data implicate early B-cell activation and autoantibodies as a central cause for accelerated atherosclerosis post-MI and identifies novel therapeutic strategies towards preventing recurrent cardiovascular events such as MI and stroke.

Objectives The accuracy of FRAX® as a screening tool to identify osteoporosis and how it compares with tools such as Osteoporosis Self-Assessment Tool for Asians (OSTA), in Southeast Asian women has so far been unexplored. We aimed to determine the FRAX® thresholds that accurately identify densitometric osteoporosis and to compare its performance with that of OSTA for this purpose. Methods Singaporean postmenopausal women (n = 1056) were evaluated. FRAX® Major Osteoporotic Fracture Probability (MOFP), Hip Fracture Probability (HFP) scores, and OSTA indices were calculated. Receiver operating characteristic (ROC) curves were constructed and via the Youden index, the optimal cut-off points of balanced sensitivity and specificity for dual energy X-ray absorptiometry (DXA)-defined osteoporosis were identified and the performance characteristics were compared. Results A FRAX® MOFP threshold of ≥3.7% had sensitivity, specificity, positive predictive value and negative predictive value of 0.78 (0.73–0.83), 0.63 (0.59–0.66), 0.4 (0.36–0.44), and 0.9 (0.87–0.92), respectively in identifying osteoporosis. The corresponding values for a HFP threshold of ≥0.6% were 0.85 (0.80–0.89), 0.58 (0.55–0.62), 0.39 (0.35–0.43), and 0.92 (0.9–0.94) and that for an OSTA index cut-off of ≤ −1.2 were 0.76 (0.70–0.81), 0.74 (0.71–0.77), 0.48 (0.43–0.54), and 0.91 (0.88–0.93). The area under the ROC curves were 82.8% (79.9%–85.6%), 77.6% (74.2%–81%), and 79.6% (76.5%–82.8%) for OSTA, MOFP, and HFP thresholds respectively. Conclusions FRAX® and OSTA perform comparably in identifying osteoporosis in our population. OSTA has only 2 parameters and may be simpler to use. However, FRAX® may also have a role in primary screening to identify the postmenopausal woman to be referred for DXA scanning and may help facilitate fracture risk reduction discussions with the patient.

To assess the association between the continuum of care of mothers and the immunization status of their 12-23 months old children.A secondary data analysis using the Myanmar Demographic and Health Survey (2015-16) data, a cross-sectional, household-based, nationally representative survey conducted during 2015-2016.We included 1669 pairs of mothers and their children in this analysis. We categorized the children into fully immunized and no/not fully immunized children and define a continuum of care (CoC) of the mother if women received antenatal care ≥ four times, delivered with skilled birth attendances, and received postnatal care within 48 h after delivery. We used the multivariable binary logistics regression using STATA version 15.1 with the survey command (svy) and reported the results by adjusted odds ratios (aORs) with 95% confidence intervals (CIs).The mother's CoC prevalence was 42.5%, and that of fully immunized children was 33.5%. However, only one-fifth of mothers and their children received the continuum of care services altogether. The children of mothers who received CoC were more likely to be fully vaccinated than those who did not (aOR = 1.60, 95%CI: 1.21, 2.13,We concluded that receiving the CoC in mothers influenced their children's vaccination status. Hence, integrating maternal health programs and immunization programs is essential to achieving sustainable development goals in Myanmar.

Background To evaluate the effects of electrolysis on cleaning the contaminated healing abutment surface and to detect the optimal condition for cleaning the contaminated healing abutment. Methods Ninety healing abutments removed from patients were placed in 1% sodium dodecyl sulfate solution and randomly divided for electrolysis with 7.5% sodium bicarbonate in the following three different apparatuses (N = 30): two stainless steel electrodes (group I), a copper electrode and a carbon electrode (group II), and two carbon electrodes (group III). The samples were placed on cathode or anode with different electric current (0.5, 1, and 1.5 A) under constant 10 V for 5 min. Electrolyte pH before and after electrolysis were measured. Then, the samples were stained with phloxine B and photographed. The proportion of stained areas was calculated. The surface was examined with a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS). Results Electrolyte pH decreased after electrolysis at 1 A and 1.5 A in group I and II. Applying cathode at 1 A in group III, the amount of residual contamination was the lowest in all the conditions examined in the present study. SEM images revealed that applying cathode at 1.5 A in group I induced a rough surface from the smooth surface before the treatment. EDS analysis confirmed that the surfaces treated on cathode at 1 A in group III revealed no signs of organic contamination. Conclusion Electrolysis of using carbon as electrodes, placing the contaminated healing abutments on cathode, and applying the electric current of 1 A at constant 10 V in 7.5% sodium bicarbonate could completely remove organic contaminants from the surfaces. This optimized electrochemical cleaning method seems to be well worth investigation for the clinical management of peri-implant infections.

The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed in 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets—resident, inflammatory, interferon-inducible cell, and Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages—and identify a new macrophage subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer cells, innate lymphoid cells-2, and CD (cluster of differentiation)-8 T cells form prominent and separate immune cell populations in atherosclerotic aortas. Many CD4 T cells express IL (interleukin)-17 and the chemokine receptor CXCR (C-X-C chemokine receptor)-6. A small number of regulatory T cells and T helper 1 cells is also identified. Immature and naive T cells are present in both healthy and atherosclerotic aortas. Our meta-analysis overcomes limitations of individual studies that, because of their experimental approach, over- or underrepresent certain cell populations. Mass cytometry studies demonstrate that cell surface phenotype provides valuable information beyond the cell transcriptomes. The present analysis helps resolve some long-standing controversies in the field. First, Trem2 + foamy macrophages are not proinflammatory but interferon-inducible cell and inflammatory macrophages are. Second, about half of all foam cells are smooth muscle cell-derived, retaining smooth muscle cell transcripts rather than transdifferentiating to macrophages. Third, Pf4 , which had been considered specific for platelets and megakaryocytes, is also prominently expressed in the main population of resident vascular macrophages. Fourth, a new type of resident macrophage shares transcripts with cavity macrophages. Finally, the discovery of a prominent innate lymphoid cell-2 cluster links the single-cell RNA sequencing work to recent flow cytometry data suggesting a strong atheroprotective role of innate lymphoid cells-2. This resolves apparent discrepancies regarding the role of T helper 2 cells in atherosclerosis based on studies that predated the discovery of innate lymphoid cells-2 cells.

Atherosclerosis is the most common underlying cause of coronary heart disease and cerebrovascular disease and responsible for 17.5 million deaths annually [1]. An early localized build-up of choles...

Cytotoxic lymphocytes (killer cells) play a critical role in host defence mechanisms, protecting against infections and in tumour surveillance. They can also exert detrimental effects in chronic inflammatory disorders and in autoimmune diseases. Tissue cell death and necrosis are prominent features of advanced atherosclerotic lesions including vulnerable/unstable lesions which are largely responsible for most heart attacks and strokes. Evidence for accumulation of killer cells in both human and mouse lesions together with their cytotoxic potential strongly suggest that these cells contribute to cell death and necrosis in lesions leading to vulnerable plaque development and potentially plaque rupture. Killer cells can be divided into two groups, adaptive and innate immune cells depending on whether they require antigen presentation for activation. Activated killer cells detect damaged or stressed cells and kill by cytotoxic mechanisms that include perforin, granzymes, TRAIL or FasL and in some cases TNF-α. In this review, we examine current knowledge on killer cells in atherosclerosis, including CD8 T cells, CD28- CD4 T cells, natural killer cells and γδ-T cells, mechanisms responsible for their activation, their migration to developing lesions and effector functions. We also discuss pharmacological strategies to prevent their deleterious vascular effects by preventing/limiting their cytotoxic effects within atherosclerotic lesions as well as potential immunomodulatory therapies that might better target lesion-resident killer cells, to minimise any compromise of the immune system, which could result in increased susceptibility to infections and reductions in tumour surveillance.

Atherosclerosis is initiated by cholesterol entry into arteries that triggers chronic immune-inflammatory lesions in the vessels. Early lesions are clinically insignificant but advanced complex lesions and vulnerable rupture prone lesions impact on quality of life and can be life threatening. Rupture of vulnerable atherosclerotic lesions initiates thrombotic occlusion of vital arteries precipitating heart attacks and strokes that remain major killers globally despite therapeutic use of statins to lower blood cholesterol levels. Conventional B2 cells are proatherogenic whereas peritoneal Bla cells are atheroprotective. Depletion of B2 cells by administration of mAb to CD20 or to BAFF receptor or in BAFF receptor-deficient mice ameliorates atherosclerosis. B2 cells may promote atherosclerosis by production of IgG, secretion of proinflammatory cytokine TNFα and activation of CD4 T cells. Together these B2 cell mechanisms contribute to generation of rupture-prone vulnerable atherosclerotic plaques characterised by large necrotic cores. In contrast, peritoneal Bla cells protect against atherosclerosis by secretion of natural IgM that scavenges apoptotic cells and oxidised LDL and reduces necrotic cores in atherosclerotic lesions. These atheroprotective effects can be further increased by stimulating Bla cells by administration of apoptotic cells, liposomes of phosphatidylserine abundant on surfaces of apoptotic cell, by mAb to TIM1, a phosphatidylserine receptor expressed by B1a cells and by TLR4-MyD88 activation. Experimental studies of atherosclerosis in mouse models indicate that reductions in atherogenic B2 cells and/or activation of atheroprotective B1a cells protects against atherosclerosis development, findings which have potential for clinical translation to reduce risks of deaths from heart attacks and strokes.

Background/Introduction Pressure overload-induced cardiac fibrosis increases myocardial stiffness leading to reductions in cardiac performances and cardiac failure. CD8+ T cells have been shown to accumulate during development of fibrosis but their role has not been defined. Purpose We examined the role and significance of CD8+ T cells in development of cardiac fibrosis. Methods Trans-aortic constriction (TAC) or 2-kidney-1-clip (2K1C) procedures were used to generate pressure overload-induced cardiac fibrosis in mice. Rat anti-mouse CD8β (lyt-3) monoclonal antibody (clone YTS 156.7) was used to deplete CD8+ T cells. A mixed bone marrow chimera strategy was used to specifically delete innate receptor Natural Killer Group 2D (NKG2D) or cytotoxin perforin from CD8+ T cells. Results Depleting CD8+ T cells in mice subjected to TAC or 2K1C-renal hypertension attenuated left ventricular fibrosis by 93% and 84% without affecting blood pressure. In TAC mice this was associated with a 68% reduction in apoptotic cardiomyocytes, a 74% reduction in macrophage accumulation, a 65% reduction in TGF-beta positive cells and a 95% reduction in TGF-beta positive macrophages, whilst CD4+ T cells were unaffected. Cardiomyocytes in regions of developing cardiac fibrosis contained cytoplasmic DNA and expressed the NKG2D ligand, Rae-1, indicative of activation of a DNA damage response; CD8+ T cells expressed the NKG2D receptor. Deletion of the NKG2D receptor from CD8+ T cells attenuated cardiac fibrosis by 82%; deletion of cytotoxin perforin has similar effects. Conclusion(s) We conclude that CD8+ T cells contribute to development of cardiac fibrosis by targeting stressed/damaged cardiomyocytes via an NKG2D-Rae-1 cytotoxic mechanism inducing their apoptosis. Macrophages then accumulate in the heart in response to increased numbers of apoptotic cardiomyocytes, clearing the apoptotic cells through engulfment and increasing their expression of the pro-fibrotic factor TGF-beta1. Acknowledgement/Funding The National Health and Medical Research Council of Australia

Discussion on Tregs that have anti-inflammatory and anti-atherogenic properties as an ideal therapeutic target to reduce fatal cardiovascular deaths following major noncardiac surgery.

We describe a case of persistent microscopic hematuria in a patient with Takayasu arteritis (TA). Urological cause has been excluded. Classically, TA is found to only involve large arteries like the aorta and its branches. There is some evidence that showed the association of small vessel vasculitis like glomerulonephritis with TA. Histopathological studies showed similar features of vasculitis between the small and large vessel involvement in TA. This may explain the similar disease process that has not been well understood in TA. We believe that the persistent microscopic haematuria in the patient described is caused by TA associated glomerulonephritis. A series of investigations ruled out other causes of glomerular microscopic haematuria like autoimmune or infection related glomerulonephritis.

Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell–activating factor receptor–deficient (BAFF-R −/− ) mice, which lack mature B cells, there was no evidence of Ang II–induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R −/− (Δ30±4 mm Hg) relative to wild-type (Δ41±5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R −/− mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-β expression. BAFF-R −/− mice were also protected from Ang II–induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II–induced hypertension by ≈35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II–induced hypertension and vessel remodeling in mice. Thus, B-cell–targeted therapies—currently used for autoimmune diseases—may hold promise as future treatments for hypertension.

The wettability and formation of intermetallic compounds (IMCs) formed between a Co–Cr–Mo-based alloy and Sn-solder metal were investigated using the reflow soldering method. Soldering was conducted in an electric furnace in separate experiments at temperatures of 533, 553, 573, 623, and 673 K for 600 s. The morphology of the intermetallic layer formed at the Co–Cr–Mo-based/Sn-solder interface was characterized by scanning electron microscopy (SEM). The chemical composition and phase of the formed intermetallic layer were analyzed by electron probe microscopic analysis (EPMA) and X-ray diffraction analysis. Wettability analysis indicated that the soldering temperature influenced the wettability. With increasing soldering temperatures, the spreading factor increased, whereas the contact angle decreased. The intermetallic layers were found in triples in the intermediate zone between the solidified Sn-solder and the Co–Cr–Mo-based substrate. The thickness of the intermetallic layers increased in proportion with increasing soldering temperature. The EPMA analysis indicated only two IMCs formed at the interface of the joint at all of the investigated soldering temperatures, although three interfacial layers were observed by SEM analysis. The Sn-richer phase, Co(Cr,Mo)Sn2, formed adjacent to the Sn-solder matrix, whereas the Co(Cr,Mo)Sn was found near the Co–Cr–Mo-based substrate. The nanoindentation measurement revealed that the formed Co(Cr,Mo)Sn2 and Co(Cr,Mo)Sn IMCs possessed lower hardness values compared to the Sn–Cu intermetallic systems.

Background Peritoneal B1a cells attenuate atherosclerosis by secreting natural polyclonal immunoglobulin M (IgM). Regulatory B cells expressing T‐cell immunoglobulin mucin domain‐1 ( TIM ‐1) expanded through TIM ‐1 ligation by anti‐ TIM ‐1 monoclonal antibody ( RMT 1‐10) induces immune tolerance. Methods and Results We examined the capacity of RMT 1‐10 to expand peritoneal B1a cells to prevent atherosclerosis development and retard progression of established atherosclerosis. RMT 1‐10 treatment selectively doubled peritoneal B1a cells, tripled TIM ‐1 + B1a cells and increased TIM ‐1 + IgM + interleukin (IL)‐10 + by 3‐fold and TIM ‐1 + IgM + IL‐10 − B1a cells by 2.5‐fold. Similar expansion of B1a B cells was observed in spleens. These effects reduced atherosclerotic lesion size, increased plasma IgM and lesion IgM deposits, and decreased oxidatively modified low‐density lipoproteins in lesions. Lesion CD 4 + and CD 8 + T cells, macrophages and monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, expression of proinflammatory cytokines monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, IL 1β, apoptotic cell numbers and necrotic cores were also reduced. RMT 1‐10 treatment failed to expand peritoneal B1a cells and reduce atherosclerosis after splenectomy that reduces B1a cells, indicating that these effects are B1a cell‐dependent. Apolipoprotein E‐ KO mice fed a high‐fat diet for 6 weeks before treatment with RMT 1‐10 also increased TIM ‐1 + IgM + IL ‐10 + and TIM ‐1 + IgM + IL ‐10 − B1a cells and IgM levels and attenuated progression of established atherosclerosis. Conclusions RMT 1‐10 treatment attenuates atherosclerosis development and progression by selectively expanding IgM producing atheroprotective B1a cells. Antibody‐based in vivo expansion of B1a cells could be an attractive approach for treating atherosclerosis.

Aims To investigate whether activation of atheroprotective peritoneal B1a cells by apoptotic cells or phosphatidylserine liposomes (PSLs) can enhance their protective actions during atherosclerosis development. Methods and results Male apolipoprotein E-knockout (ApoE−/−) mice were treated with apoptotic cells or PSLs at the beginning of 8-week high-fat diet. Intraperitoneally administered apoptotic cells attenuated atherosclerosis in hypercholesterolemic ApoE−/− mice by 53% and macrophage accumulation by 52%, effects mimicked by administering PSLs and abolished by B1a cell depletion by splenectomy. These effects were associated with reduced lesion CD4+ and CD8+ T cells, mRNAs of MCP-1, VCAM-1, TNF-α, IL-1β, IL-12, and IL-18 while anti-inflammatory TGF-β mRNA levels doubled. Apoptotic cells or PSLs increased B1a lymphocytes including TIM-1+ B1a cells in vivo and in vitro while other lymphocyte populations were unaffected. Total plasma IgM, anti-leucocyte, anti-CD3, anti-CD4, and anti-oxLDL IgM were elevated. IgM in atherosclerotic lesions was also elevated and this was associated with reduced lesion MDA-LDL (oxLDL), apoptotic cells and necrotic core size. These effects of activating B1a cells could be attributed to B1a-derived polyreactive IgM deposited in lesions that reduce inflammatory cytokines by lowering lesion ox-LDL via anti-oxLDL IgM, T-cells via anti-leucocyte, anti-CD3, and anti-CD4 IgM, apoptotic cells and necrotic core size via IgM binding to apoptotic cells and enhancing phagocytosis, which also elevates anti-inflammatory cytokines. Conclusion Targeting B1a cell activation by PSLs may be a potentially potent therapeutic strategy to attenuate atherosclerosis and reduce the incidence of atherosclerosis-dependent myocardial infarction and stroke.

Objective— B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte–induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. Approach and Results— Using mixed chimeric Ldlr −/− mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T–B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin—including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr −/− mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. Conclusions— The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B–T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications.

Journal of Health Research, 31, 4

Nutritional deficiencies are a major problem among developing countries including Myanmar. They can occur in all age groups, but the impact is more severe among children age 6-23 months as this period is critical for child development, and irreversible damages can occur due to nutritional deficiencies. Proper infant and young child feeding practices are pivotal to tackle nutritional problems and to prevent irreversible consequences among children. To assess the current feeding practices and associations with nutritional status, we conducted a secondary data analysis using the 2015-16 Myanmar Demographic and Health Survey. Multiple logistic regression analysis was done adjusting for covariates and the results were presented by adjusted odds ratios with 95% confidence intervals. A total of 1,222 children age 6-23 months were included in this analysis. Twenty percent were stunted and 43% were moderately anemic. Only 16% of children received a minimum acceptable diet, 25% received diverse food groups, 58% were fed with minimum meal frequency, 85% currently breastfed, and 59% consumed iron-rich foods. Breastfeeding reduced the odds of being stunted. Male sex, perceived small birth size, mother with short stature, and working mother were significant predictors of stunting. Iron-rich food consumption was inversely associated with moderate anemia. Male sex and maternal anemia were also significant predictors of moderate anemia. The study concluded that stunting and anemia among young children in Myanmar are major public health challenges that need urgent action. While further prospective research is needed to determine the effect of feeding practice on linear growth, interventions such as iron supplementation, and nutritional education programs according to the World Health Organization complementary feeding guidelines could help prevent stunting and childhood anemia and might reduce their prevalence in Myanmar.

T-cell regulation by CD52-expressing CD4 T cells appears to operate by two different and possibly synergistic mechanisms. The first is by its release from the cell surface of CD4 T cells that express high levels of CD52 that then binds to the inhibitory sialic acid-binding immunoglobulin-like lectins-10 (Siglec-10) receptor to attenuate effector T-cell activation by impairing phosphorylation of T-cell receptor associated lck and zap-70. The second mechanism appears to be by crosslinkage of the CD52 molecules by an as yet unidentified endogenous ligand that is mimicked by a bivalent anti-CD52 antibody that results in their expansion.

Background We previously identified peritoneal B1a cells that secrete natural IgM as a key atheroprotective B cell subset. However, the molecules that activate atheroprotective B1a cells are unknown. Here, we investigated whether Toll‐like receptors (TLRs) TLR 2, TLR 4, and TLR 9 expressed by B1a cells are required for IgM‐mediated atheroprotection. Methods and Results We adoptively transferred B1a cells from wild‐type mice or from mice deficient in TLR 2, TLR 4, TLR 9, or myeloid differentiation primary response 88 (MyD88) into ApoE −/− mice depleted of peritoneal B1a cells by splenectomy and fed a high‐fat diet for 8 weeks. Elevations in plasma total, anti‐oxLDL (oxidized low‐density lipoprotein), anti‐leukocyte, anti‐ CD 3, anti‐ CD 8, and anti‐ CD 4 IgMs in atherosclerotic mice required B1a cells expressing TLR 4 and MyD88, indicating a critical role for TLR 4‐MyD88 signaling for IgM secretion. Suppression of atherosclerosis was also critically dependent on B1a cells expressing TLR 4‐MyD88. Atherosclerosis suppression was associated not only with reductions in lesion apoptotic cells, necrotic cores, and ox LDL , but also with reduced lesion CD 4 + and CD 8 + T cells. Transforming growth factor beta 1 ( TGF ‐β1) expression, including macrophages expressing TGF ‐β1, was increased, consistent with increased IgM‐mediated phagocytosis of apoptotic cells by macrophages. Reductions in lesion inflammatory cytokines tumor necrosis factor alpha ( TNF ‐α), interleukin ( IL) 1β, and IL ‐18 were consistent with augmented TGF ‐β1 expression. Conclusions TLR 4‐MyD88 expression on B1a cells is critical for their IgM‐dependent atheroprotection that not only reduced lesion apoptotic cells and necrotic cores, but also decreased CD 4 and CD 8 T‐cell infiltrates and augmented TGF ‐β1 expression accompanied by reduced lesion inflammatory cytokines TNF ‐α, IL ‐1β, and IL ‐18.

The idiom “the straw that breaks the camel’s back” describes scenarios where seemingly minor incidents eventuate in a sudden, unexpected, and often detrimental downfall. In the case of atherosclerosis, over time multiple subclinical cellular events result in the development of unstable, vulnerable atherosclerotic lesions, which leads to the rupture of atherosclerotic plaques, culminating in the often catastrophic clinical manifestation of myocardial infarction or ischemic stroke. In this review, we first summarize lessons learned from autopsy studies, clinical investigations, and animal models mainly published in ATVB . We then present recent experimental studies published in ATVB that shed light on the underlying pathophysiological development of plaque instability and disruption, and how differential and sometimes maladaptive responses at cellular levels contribute to this complex process. These many publications in ATVB are a testament to the journal’s leading role in research on atherosclerotic plaque instability, an area of research with utmost translational relevance. Our understanding of the pathology of unstable, vulnerable atherosclerotic plaques is mainly based on a limited number of postmortem examinations of human coronary arteries and the analysis of resected surgical specimens from patients who underwent carotid endarterectomy and performed for primary/secondary prevention of transient ischemia attack or stroke.1–3 The histopathologic definition of unstable plaques includes, as the most central features, thin fibrous caps (thickness 40% of the total lesion volume).4–7 Importantly, repeated subclinical plaque ruptures, histologically and potentially macroscopically visible as intraplaque hemorrhage, are described as an additional cause of plaque instability.8 From an autopsy series of 800 cases of sudden coronary …

Parietal cell antibody is a marker for autoimmune gastritis. With identification of gastric H/K ATPase as its molecular target, ELISAs have been introduced. We compared performance of ELISA with immunofluorescence in a retrospective and prospective sera set and correlated the results with intrinsic factor antibody. In 138 retrospective sera selected for positivity or negativity for intrinsic factor antibody, 87 reacted with gastric H/K ATPase by Euroimm ELISA but only 62 reacted by immunofluorescencence.. Similar results were obtained with Inova ELISA with 78 positives that were also positive by Euroimm ELISA. In 161 prospective sera, 29 sera tested positive by ELISA compared to 24 by immunofluorescence. ELISA positive but immunofluoresnce negative sera are bona fide positives because a representative set of 16 sera reacted with both 95kD α and 60-90kDβ subunits of gastric H/K ATPase. ELISA values rose with age regardless of whether immunofluorescence tests were positive or negative. Of 53 sera containing antibody to intrinsic factor, 46/53 (87%) reacted to gastric H/K ATPase by ELISA. Taken together, the data indicates an enhanced detection rate by ELISA over immunofluorescence and validates it as a robust diagnostic assay for parietal cell antibody. As parietal cell antibody marks asymptomatic autoimmune gastritis that may progress to end stage gastric atrophy and haematological complications, and as autoimmune gastritis is associated with autoimmune thyroiditic and type 1 diabetes mellitus, early detection of parietal cell antibody by a sensitive ELISA will enable early follow-up of at risk subjects.

Atherosclerosis initiated by hyperlipidemia is modulated by immune cells in its development, progression, and rupture that results in thrombotic arterial occlusion leading to strokes and myocardial infarction. B cells initially thought to be atheroprotective provide opposing roles by their different subsets. Unlike B2 cells that are atherogenic, serosal B1a cells are atheroprotective by producing natural IgM antibodies that clear modified low-density lipoprotein and apoptotic and necrotic debris. In addition to natural IgM antibodies, B1a cells may act as regulatory B cells by producing the anti-inflammatory cytokine interleukin-10, which inhibits proinflammatory cytokines secreted by activated macrophages and T cells in atherosclerotic lesions. These findings suggest in vivo expansion of atheroprotective B1a cells as a potential therapeutic strategy to augment the benefits of lipid-lowering statin therapy.

Rationale: Aggravated atherosclerosis in B lymphocyte-deficient chimeric mice and reduced atherosclerosis after transfer of unfractionated spleen B lymphocytes into splenectomized mice have led to the widely held notion that B lymphocytes are atheroprotective. However, B lymphocytes can be pathogenic, because their depletion by anti-CD20 antibody ameliorated atherosclerosis, and transfer of B2 lymphocytes aggravated atherosclerosis. These observations raise the question of the identity of the atheroprotective B-lymphocyte population. Objective: The purpose of the study was to identify an atheroprotective B-lymphocyte subset and mechanisms by which they confer atheroprotection. Methods and Results: Splenectomy of apolipoprotein E–deficient mice selectively reduced peritoneal B1a lymphocytes, plasma IgM, and oxidized low-density lipoprotein IgM levels and lesion IgM deposits. These reductions were accompanied by increased oil red O–stained atherosclerotic lesions and increased necrotic cores, oxidized low-density lipoproteins, and apoptotic cells in lesions. Plasma lipids, body weight, collagen, and smooth muscle content were unaffected. Transfer of B1a lymphocytes into splenectomized mice increased peritoneal B1a lymphocytes; restored plasma IgM, oxidized low-density lipoprotein IgM levels, and lesion IgM deposits; and potently attenuated atherosclerotic lesions, with reduced lesion necrotic cores, oxidized low-density lipoprotein, and apoptotic cells. In contrast, transfer of B1a lymphocytes that cannot secrete IgM failed to protect against atherosclerosis development in splenectomized mice despite reconstitution in the peritoneum. Conclusions: B1a lymphocytes are an atheroprotective B-lymphocyte population. Our data suggest that natural IgM secreted by these lymphocytes offers protection by depositing IgM in atherosclerotic lesions, which reduces the necrotic cores of lesions.

This editorial refers to ‘M1 macrophages act as LTβR-independent lymphoid tissue inducer cells during atherosclerosis-related lymphoid neogenesis’ by K. Guedj et al. , pp. 434–443, this issue. The immune system has evolved to optimize the chances of encounter between rare antigen-specific T and B cells of the adaptive immune system with antigen presenting cells of the innate immune system through development of organized secondary lymphoid organs (SLOs) such as the spleen and lymph nodes. This system efficiently eradicates pathogens, including foreign antigens. However, when antigens are constantly replenished, as in atherosclerosis, this can lead to local or systemic chronic inflammation. Under such conditions, tissues that persistently harbour target antigens are infiltrated by cellular effectors of the immune system, including T cells, B cells, and macrophages as well as dendritic cells and plasma cells. These cellular elements frequently organize themselves anatomically and functionally similar to SLOs, leading to de novo formation of B-cell follicles and T-cell areas by a process called lymphoid neogenesis or tertiary lymphoid organ (TLO) formation. TLOs have been observed in autoimmune diseases such as autoimmune thyroiditis, rheumatoid arthritis, and myasthenia gravis as well as in chronic allograft rejection,1,2 diabetes,3 and in atherosclerosis.4 Whilst the role of TLOs is still yet to be fully elucidated in diseases such as atherosclerosis, there is evidence that like SLOs, they can contribute to immune disease progression.5 For example, B cells in TLOs within lungs of patients with rheumatoid arthritis …

CD4 + NKT cells are atherogenic lymphocytes, but the mechanisms by which they promote atherosclerosis are not known. Here we investigated the role of other lymphocytes and NKT cell-derived cytokines and cytotoxins in NKT cell’s atherogenicity. First, CD4 + NKT cells were adoptively transferred into ApoE -/- mice; deficient in T, B cell and NKT cells (ApoE -/- Rag2 -/- ) and in T, B, NKT and NK cells (ApoE -/- Rag2 -/- γc -/- ). At the end of 8 week high fat diet, CD4 + NKT cells augmented aortic root atherosclerosis assessed by total intimal lesion area, lipid content and macrophage accumulation in both ApoE -/- Rag2 -/- mice and ApoE -/- Rag2 -/- γC -/- mice. These data indicate that CD4 + NKT cells can exert atherogenic effects in the absence of other lymphocytes. As NKT cells secrete cytokines and cytotoxins, we next investigated the role of NKT cell-derived cytokines and cytotoxins in atherosclerosis development. CD4 + NKT cells from mice deficient of IFN-γ, IL-4 and IL-21 cytokines and perforin and granzyme B cytotoxins were transferred into NKT cell-deficient ApoE -/- Jα18 -/- mice; controls were ApoE -/- Jα18 -/- mice that received PBS or wildtype NKT cells. At completion of 8 week high fat diet, wildtype CD4 + NKT cells and those deficient in IL-4, IFN-γ or IL-21 increased total intimal lesion area by ~65%, ~95%, ~80% and ~70% compared to vehicle control mice respectively. In contrast CD4 + NKT cells deficient in perforin or granzyme B failed to augment lesion size, lipid content and macrophage accumulation. Apoptotic cells, necrotic cores and proinflammatory VCAM-1 and MCP-1 were reduced in mice receiving perforin-deficient NKT cells. Our data suggest that CD4 + NKT cells require perforin and granzyme-B for atherosclerosis development, thereby increasing apoptotic and necrotic cells in lesions that in turn augments inflammation. Targeting NKT cell apoptotic cell mediators may be useful in attenuating atherosclerosis.