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Abstract Various public health measures have contained outbreaks of SARS-CoV-2, but concerns remain over the possibility of future surges. Improvements in broadening the vaccine response can stifle new and nascent infections. In this study, we tested the effects of different adjuvant combinations on the immunization of mice with the receptor-binding domain (RBD)-containing the S1-subunit of the spike protein (S1 protein) from SARS-CoV-2 to induce a robust humoral and cellular immune response. We showed that subcutaneous immunization of S1 protein co-delivered with IL-15 and TLR-ligands (MALP-2, poly I: C, and CpG) or with IL-12 and GM-CSF in DOTAP, or Alum induced significantly high titers of durable antibodies, predominantly IgG1, IgG2a, and IgG2b, that could bind to RBD, S1-subunit, and the full-length ectodomain of SARS-CoV-2 spike protein in sera compared to the immunization with S1 protein alone in both B6 wild-type (WT) and the K18-hACE2 transgenic mice. In addition, immunization with S1 protein co-delivered with IL-15 and TLR-ligands induced antibody responses against S1 protein in aged mice, and sera from younger mice reduced plaque formation of live SARS-CoV-2, and had effective binding to S1 protein from ten different variants of SARS-CoV-2, including Omicron (B.1.1.529), and greater neutralization activity as early as day 21 post-immunization measured by inhibition of RBD binding to hACE2 than sera from mice immunized with S1 protein alone or co-delivered with Alum. We also identified antibody-binding epitopes using 18-mer peptides with 9-residue overlaps from the S1 protein. CD8+ T-cell responses specific to RBD and S1 protein peptide pools were observed up to day 200 post-immunization by tetramer staining. These data show the efficacy of specific immunologically targeted adjuvants for increasing S1 protein immunogenicity in mice and can contribute to more effective vaccines.

Background Despite advances in checkpoint inhibitor (CPI) therapy for cancer treatment, many cancers remain resistant. Tumors deemed “cold” based on lack of T cell infiltration show reduced potential for CPI therapy. Cancer vaccines may overcome the inadequacy of existing T cells by inducing the needed antitumor T cell response to synergize with CPIs and overcome resistance.Methods CT26 and TC1 tumor cells were injected subcutaneously into mice. Mice were treated with combinations of CPIs alone or a cancer vaccine specific to the tumor antigen E7 present in TC1 cells. CPIs for the TC1 model were selected because of immunophenotyping TC1 tumors. Antitumor and protumor immunity, tumor size and survival, sequence and timing of vaccine and CPI administration, and efficacy of treatment in young and aged mice were probed.Results While “hot” CT26 tumors are treatable with combinations of second-generation CPIs alone or with anti-TGFβ, “cold” TC1 tumor reduction requires the synergy of a tumor-antigen-specific vaccine in combination with two CPIs, anti-TIGIT and anti-PD-L1, predicted by tumor microenvironment (TME) characterization. The synergistic triple combination delays tumor growth better than any pairwise combination and improves survival in a CD8+T cell-dependent manner. Depletion of CD4+T cells improved the treatment response, and depleting regulatory T cells (Treg) revealed Tregs to be inhibiting the response as also predicted from TME analysis. We found the sequence of CPI and vaccine administration dictates the success of the treatment, and the triple combination administered concurrently induces the highest E7-specific T cell response. Contrary to young mice, in aged mice, the cancer vaccine alone is ineffective, requiring the CPIs to delay tumor growth.Conclusions These findings show how pre-existing or vaccine-mediated de novo T cell responses can both be amplified by and facilitate synergistic CPIs and Treg depletion that together lead to greater survival, and how analysis of the TME can help rationally design combination therapies and precision medicine to enhance clinical response to CPI and cancer vaccine therapy.

Gastrointestinal (GI) cancers represent a complex array of cancers that affect the digestive system. This includes liver, pancreatic, colon, rectal, anal, gastric, esophageal, intestinal and gallbladder cancer. Patients diagnosed with certain GI cancers typically have low survival rates, so new therapeutic approaches are needed. A potential approach is to harness the potent immunoregulatory properties of natural killer T (NKT) cells which are true T cells, not natural killer (NK) cells, that recognize lipid instead of peptide antigens presented by the non-classical major histocompatibility (MHC) molecule CD1d. The NKT cell subpopulation is known to play a vital role in tumor immunity by bridging innate and adaptive immune responses. In GI cancers, NKT cells can contribute to either antitumor or protumor immunity depending on the cytokine profile expressed and type of cancer. This review discusses the complexities of the role of NKT cells in liver, colon, pancreatic and gastric cancers with an emphasis on type I NKT cells.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection rates. Here, we aimed to evaluate immune reconstitution following haplo-HSCT and identify cytokines and cells associated with graft rejection/engraftment. 50 cytokines and 10 immune cell subsets were screened using multiplex-ELISA and flow cytometry, respectively, at baseline and PT-Days 30, 60, 100, and 180. We observed the most significant differences in cytokine levels between the engrafted and rejected groups at PT-Day 60, corresponding with clinical findings of secondary graft rejection. Of the 44 cytokines evaluated, plasma concentrations of 19 cytokines were different between the two groups at PT-Day 60. Factor analysis suggested two independent factors. The first factor (IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, and TGFb1 contributed significantly) was strongly associated with engraftment with OR = 2.7 (95%CI of 1.4 to 5.4), whereas the second factor (GROa and IL-18 contributed significantly) was not significantly associated with engraftment. Sufficient donor myeloid chimerism (DMC) is critical for the success of HSCT; here, we evaluated immune cells among high (H) DMC (DMC≥20%) and low (L) DMC (DMC

Objectives: The objectives of this study were to determine BLLs with a LeadCare II analyzer in children living in Ulaanbaatar, Mongolia and to identify potential risk factors influencing their BLLs with a lifestyle and residential environment questionnaire. Methods: A total of 153 children aged 6-8 years old were tested in 2014. Results: The geometric mean BLL was 5.3 µg/dL (95% CI: 4.9 – 5.7 µg/dL) and 69.3% of the children had blood lead levels ≥5 μg/dL (the United States Centers for Disease Control and Prevention’s current reference level). Factors that were significant (p

Winter air pollution in Ulaanbaatar, Mongolia is among the worst in the world. The health impacts of policy decisions affecting air pollution exposures in Ulaanbaatar were modeled and evaluated under business as usual and two more-strict alternative emissions pathways through 2024. Previous studies have relied on either outdoor or indoor concentrations to assesses the health risks of air pollution, but the burden is really a function of total exposure. This study combined projections of indoor and outdoor concentrations of PM2.5 with population time-activity estimates to develop trajectories of total age-specific PM2.5 exposure for the Ulaanbaatar population. Indoor PM2.5 contributions from secondhand tobacco smoke (SHS) were estimated in order to fill out total exposures, and changes in population and background disease were modeled. The health impacts were derived using integrated exposure-response curves from the Global Burden of Disease Study.Annual average population-weighted PM2.5 exposures at baseline (2014) were estimated at 59 μg/m3. These were dominated by exposures occurring indoors, influenced considerably by infiltrated outdoor pollution. Under current control policies, exposures increased slightly to 60 μg/m3 by 2024; under moderate emissions reductions and under a switch to clean technologies, exposures were reduced from baseline levels by 45% and 80%, respectively. The moderate improvement pathway decreased per capita annual disability-adjusted life year (DALY) and death burdens by approximately 40%. A switch to clean fuels decreased per capita annual DALY and death burdens by about 85% by 2024 with the relative SHS contribution increasing substantially.This study demonstrates a way to combine estimated changes in total exposure, background disease and population levels, and exposure-response functions to project the health impacts of alternative policy pathways. The resulting burden analysis highlights the need for aggressive action, including the elimination of residential coal burning and the reduction of current smoking rates.

The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42) (Abeta(1-11)) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype.We generated pMDC-3Abeta(1-11)-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages.Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials.

Introduction The recent clinical success of checkpoint inhibitors, which manipulate T cell function and extend patient survival in many cases, provides strong motivation to treat cancer by modulating immunity. However, [...], In a structure-function study of sulfatides that typically stimulate type II NKT cells, we made an unexpected discovery. We compared analogs with sphingosine or phytosphingosine chains and 24-carbon acyl chains with 0-1-2 double bonds (C or pC24:0, 24:1, or 24:2). C24:1 and C24:2 sulfatide presented by the CD1d monomer on plastic stimulated type II, not type I, NKT cell hybridomas, as expected. Unexpectedly, when presented by bone marrow- derived DCs (BMDCs), C24:2 reversed specificity to stimulate type I, not type II, NKT cell hybridomas, mimicking the corresponding [beta]-galactosylceramide ([beta]GalCer) without sulfate. C24:2 induced IFN-[gamma]-dependent immunoprotection against CT26 colon cancer lung metastases, skewed the cytokine profile, and activated conventional DC subset 1 cells (cDC1s). This was abrogated by blocking lysosomal processing with bafilomycin A1, or by sulfite blocking of arylsulfatase or deletion of this enyzme that cleaves off sulfate. Thus, C24:2 was unexpectedly processed in BMDCs from a type II to a type I NKT cell- stimulating ligand, promoting tumor immunity. We believe this is the first discovery showing that antigen processing of glycosylceramides alters the specificity for the target cell, reversing the glycolipid's function from stimulating type II NKT cells to stimulating type I NKT cells, thereby introducing protective functional activity in cancer. We also believe our study uncovers a new role for antigen processing that does not involve MHC loading but rather alteration of which type of cell is responding.

Gastrointestinal (GI) cancers represent a complex array of cancers that affect the digestive system. This includes liver, pancreatic, colon, rectal, anal, gastric, esophageal, intestinal and gallbladder cancer. Patients diagnosed with certain GI cancers typically have low survival rates, so new therapeutic approaches are needed. A potential approach is to harness the potent immunoregulatory properties of natural killer T (NKT) cells which are true T cells, not natural killer (NK) cells, that recognize lipid instead of peptide antigens presented by the non-classical major histocompatibility (MHC) molecule CD1d. The NKT cell subpopulation is known to play a vital role in tumor immunity by bridging innate and adaptive immune responses. In GI cancers, NKT cells can contribute to either antitumor or protumor immunity depending on the cytokine profile expressed and type of cancer. This review discusses the complexities of the role of NKT cells in liver, colon, pancreatic and gastric cancers with an emphasis on type I NKT cells. [ABSTRACT FROM AUTHOR]

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a widely available curative option for patients with sickle cell disease (SCD). Our original non-myeloablative haplo-HSCT trial employing post-transplant (PT) cyclophosphamide had a low incidence of GVHD but had high rejection rates. Here, we aimed to evaluate immune reconstitution following haplo-HSCT and identify cytokines and cells associated with graft rejection/engraftment. 50 cytokines and 10 immune cell subsets were screened using multiplex-ELISA and flow cytometry, respectively, at baseline and PT-Days 30, 60, 100, and 180. We observed the most significant differences in cytokine levels between the engrafted and rejected groups at PT-Day 60, corresponding with clinical findings of secondary graft rejection. Of the 44 cytokines evaluated, plasma concentrations of 19 cytokines were different between the two groups at PT-Day 60. Factor analysis suggested two independent factors. The first factor (IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, and TGFb1 contributed significantly) was strongly associated with engraftment with OR = 2.7 (95%CI of 1.4 to 5.4), whereas the second factor (GROa and IL-18 contributed significantly) was not significantly associated with engraftment. Sufficient donor myeloid chimerism (DMC) is critical for the success of HSCT; here, we evaluated immune cells among high (H) DMC (DMC≥20%) and low (L) DMC (DMC<20%) groups along with engrafted and rejected groups. We found that early myeloid-derived suppressor cell (eMDSC) frequencies were elevated in engrafted patients and patients with HDMC at PT-Day 30 (P< 0.04 & P< 0.003, respectively). 9 of 20 patients were evaluated for the source of eMDSCs. The HDMC group had high mixed chimeric eMDSCs as compared to the LDMC group (P< 0.00001). We found a positive correlation between the frequencies of eMDSCs and Tregs at PT-Day 100 (r=0.72, P <0.0007); eMDSCs at BSL and Tregs at PT-Day 100 (r=0.63, P <0.004). Of 10 immune regulatory cells and 50 cytokines, we observed mixed chimeric eMDSCs and IL-17A, IL-10, IL-7, G-CSF, IL-2, MIP-1a, VEGF, TGFb1 as potential hits which could serve as prognostic markers in predicting allograft outcome towards engraftment following haploidentical HSCT employing post-transplant cyclophosphamide. The current findings need to be replicated and further explored in a larger cohort. [ABSTRACT FROM AUTHOR]

Introduction: Winter air pollution in Ulaanbaatar, Mongolia is among the worst in the world. The health impacts of policy decisions affecting air pollution exposures in Ulaanbaatar were modeled and evaluated under business as usual and two more-strict alternative emissions pathways through 2024. Previous studies have relied on either outdoor or indoor concentrations to assesses the health risks of air pollution, but the burden is really a function of total exposure. This study combined projections of indoor and outdoor concentrations of PM2.5 with population time-activity estimates to develop trajectories of total age-specific PM2.5 exposure for the Ulaanbaatar population. Indoor PM2.5 contributions from secondhand tobacco smoke (SHS) were estimated in order to fill out total exposures, and changes in population and background disease were modeled. The health impacts were derived using integrated exposure-response curves from the Global Burden of Disease Study. Results: Annual average population-weighted PM2.5 exposures at baseline (2014) were estimated at 59 μg/m3. These were dominated by exposures occurring indoors, influenced considerably by infiltrated outdoor pollution. Under current control policies, exposures increased slightly to 60 μg/m3 by 2024; under moderate emissions reductions and under a switch to clean technologies, exposures were reduced from baseline levels by 45% and 80%, respectively. The moderate improvement pathway decreased per capita annual disability-adjusted life year (DALY) and death burdens by approximately 40%. A switch to clean fuels decreased per capita annual DALY and death burdens by about 85% by 2024 with the relative SHS contribution increasing substantially. Conclusion: This study demonstrates a way to combine estimated changes in total exposure, background disease and population levels, and exposure-response functions to project the health impacts of alternative policy pathways. The resulting burden analysis highlights the need for aggressive action, including the elimination of residential coal burning and the reduction of current smoking rates. [ABSTRACT FROM AUTHOR]

In Mongolia, horses play important roles, not only in livestock production, but also in terms of culture, tradition, and Mongolian beliefs. Although the presence of non-tsetse-transmitted horse trypanosomoses, which are caused by infections with Trypanosoma evansi (surra) and T. equiperdum (dourine), has been reported in the country, whether there is a nationwide epidemic of these infectious diseases is unknown. In the present study, a nationwide surveillance of horse trypanosomoses was performed. The sample sizes for each province, the whole country, and male and female horses were, respectively, 96, 2,400, and 316 and 306. In total, 3,641 samples of horse sera were collected by simple random sampling. The rTeGM6-4r-based ELISA, which was applied for surra against cattle and water buffalo and dourine against horse, revealed that the overall sero-prevalence of the diseases in Mongolia was 4.8%. Among them, high sero-prevalences were observed in the central provinces (5.2–11.0%, p < 0.05) of the country. The sero-prevalence was significantly higher in females than in males (6.0% and 4.0%, p < 0.05, respectively) and in non-castrated males (8.4%, p < 0.01) compared with castrated males (3.0%). These results suggested that currently, horse trypanosomoses are a nationwide endemic problem in Mongolia. Knowledge of the nationwide endemic status of non-tsetse-transmitted horse trypanosomoses in Mongolia will be useful to prevent these diseases.

Inflammation is a double-edged sword that can promote or suppress cancer progression. In this study, we report that thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs, is also expressed in human and murine cancers. Our studies with murine cancer cells indicate that TSLP plays an essential role in cancer escape, as its inactivation in cancer cells alone was sufficient to almost completely abrogate cancer progression and lung metastasis. The cancer-promoting activity of TSLP primarily required signaling through the TSLP receptor on CD4+ T cells, promoting Th2-skewed immune responses and production of immunosuppressive factors such as IL-10 and IL-13. Expression of TSLP therefore may be a useful prognostic marker, and its targeting could have therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Aβ antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Aβ42 (Aβ1-11) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong antiinflammatory Th2 phenotype. Methods and Findings: We generated pMDC-3Aβ1-11-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Aβ antibody, which in turn inhibited accumulation of Aβ pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. Conclusions: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials. [ABSTRACT FROM AUTHOR]

Biofilms were grown from wild-type (WT) Pseudomonas aeruginosa PAO1 and the cell signaling lasI mutant PAOI-JP1 under laminar and turbulent flows to investigate the relative contributions of hydrodynamics and cell signaling for biofilm formation. Various biofilm morphological parameters were quantified using Image Structure Analyzer software. Multivariate analysis demonstrated that both cell signaling and hydrodynamics significantly (P < 0.000) influenced biofilm structure. In turbulent flow, both biofilms formed streamlined patches, which in some cases developed ripple-like wave structures which flowed downstream along the surface of the flow cell. In laminar flow, both biofilms formed monolayers interspersed with small circular microcolonies. Ripple-like structures also formed in four out of six WT biofilms, although their velocity was approximately 10 times less than that of those that formed in the turbulent flow cells. The movement of biofilm cell clusters over solid surfaces may have important clinical implications for the dissemination of biofilm subject to fluid shear, such as that found in catheters. The ability of the cell signaling mutant to form biofilms in high shear flow demonstrates that signaling mechanisms are not required for the formation of strongly adhered biofilms. Similarity between biofilm morphologies in WT and mutant biofilms suggests that the dilution of signal molecules by mass transfer effects in faster flowing systems mollifies the dramatic influence of signal molecules on biofilm structure reported in previous studies. [ABSTRACT FROM AUTHOR]

Examines the influence of fluid shear and aluminum chloride on the material properties of Pseudomonas aeruginosa PAO1 and Desulfovibrio sp. x265 biofilms. Assessment of the strength of using an elastic coefficient and residual strain; Material properties of biofilm; Increase in elastic coefficient due to aluminum chloride.

Background: The Western Pacific Region has the highest rate of cigarette smoking in the world. In this region, Mongolia has ratified the WHO FCTC treaty and, as part of treaty implementation, has monitored school tobacco use in children using the 2014 Global Youth Tobacco Survey (GYTS) and 2019 GYTS. Our objective was to examine the spatial and economic factors associated with cigarette use in schoolchildren of Mongolia., Methods: The 2014 and 2019 GYTS are the most recent and comprehensive national surveys of tobacco use in schoolchildren in Mongolia and are cross-sectional, stratified, multi-stage cluster surveys of 13-15 year-old schoolchildren (7,298 in 2014, 4,146 in 2019) selected from urban and rural schools. For each survey, we conducted logistic regression modelling to examine whether spatial (proximity of cigarette sales to schools), economic (pocket money available to school children), and other environmental/contextual factors were predictors of cigarette use (all, single sticks) in schoolchildren., Results: We found that 1)the prevalence of vendors selling cigarettes near schools increased from 65% in the 2014 GYTS to 94% in the 2019 GYTS, 2) sales of cigarettes near schools were associated with increased current smoking of all cigarettes and this effect increased from a marginal 31% increase in odds in 2014 (OR [95% confidence interval(CI)]=1.31 [0.99, 1.73]) to a 416% increase in odds in 2019 (OR [95% CI]=5.16[3.31, 8.05]), 3) sales of cigarettes near schools were associated with a substantial increase in odds of smoking single cigarettes in 2014 (OR [95% CI]=1.87 [1.14,3.06]) and in 2019 (OR[95% CI]=2.70 [1.42, 5.12]). We also found that smoking of all cigarettes was higher when student pocket money exceeded the price of the cigarette pack (approximately 1.8 USD) and also when parents and/or peers were smokers., Conclusions: Despite the 2012 National Tobacco Laws banning sales of cigarettes and single cigarettes to schoolchildren near schools, the most recent national surveys (2014-2019) have shown that these sales are increasing. We provide new findings indicating that despite the higher pricing of cigarette packs (relative to the region), illicit sales of single cigarettes are targeting schoolchildren near their schools., Competing Interests: Additional Declarations: No competing interests reported.

Purpose: To compare the outcomes of transcanalicular diode laser-assisted dacryocystorhinostomy (TCL-DCR), nonendoscopic endonasal dacryocystorhinostomy (NEN-DCR), and external dacryocystorhinostomy (EXT-DCR) as first-line treatments for functional epiphora., Methods: This multicenter, retrospective, case-control study included 135 eyes of 135 patients with functional epiphora (86 females and 49 males). Functional epiphora was diagnosed based on a patent lacrimal system with a delay in the fluorescein dye disappearance test (FDDT) or dacryoscintigraphy (DSG) and no ocular surface or eyelid abnormalities. The patients were treated with TCL-DCR (2008-2011) or Ext-DCR (2005-2008, 2011-2017) at Beyoglu Eye Research Hospital (Istanbul, Turkey) and NEN-DCR at Carrot Eye Surgery Clinic affiliated with the McMaster University (Hamilton, ON, Canada) (2010-2016). Success was defined as the absence of epiphora and the normalization of an earlier delayed FDDT after surgery., Results: The TCL-DCR, NEN-DCR, and EXT-DCR groups consisted of 38, 47, and 50 eyes with 25.9, 44.2, and 45.9 months of follow-up. The success rate for TCL-DCR was 65.8%, 70.2% for NEN-DCR, and 84.0% for EXT-DCR. During the follow-up period, 13.2% of TCL-DCR cases and 6.4% of NEN-DCR cases developed an anatomic obstruction of the lacrimal system., Conclusion: The EXT-DCR group had a higher success rate in the management of functional epiphora than the NEN-DCR and TCL-DCR groups and was significantly safer in terms of an iatrogenic anatomic block of the lacrimal system., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Can Ozturker et al.)

Background/objectives: Smoking is the leading risk factor for many chronic diseases. The quantitative analysis of potential health gains from reduced smoking is important for establishing priorities in Mongolia's health policy. This study quantifies the effect of tobacco-tax increases on future smoking prevalence and the associated smoking-related burden of disease in Mongolia., Methods: The dynamic model for health impact assessment (DYNAMO-HIA) tool was used. The most recent data were used as input for evaluating tobacco-taxation scenarios. Demographic data were taken from the Mongolian Statistical Information Services. Smoking data came from a representative population-based STEPS survey, and smoking-related disease data were obtained from the health-information database of Mongolia's National Health Center. Simulation was used to evaluate various levels of one-time price increases on tobacco products (25% and 75%) in Mongolia. Conservative interpretation suggests that the population will eventually adjust to the higher tobacco price and return to baseline smoking behaviors., Results: Over a three-year period, smoking prevalence would be reduced by 1.2% points, corresponding to almost 40 thousand smokers at the population level for a price increase of 75%, compared to the baseline scenario. Projected health benefits of this scenario suggest that more than 137 thousand quality adjusted of life years would be gained by avoiding smoking-related diseases within a population of three million over a 30-year period., Discussion: Prevention through effective tobacco-control policy could yield considerable gains in population health in Mongolia. Compared to current policy, tax increases must be higher to have a significant effect on population health., Implications: Tobacco taxation is an effective policy for reducing the harm of tobacco smoking, while benefiting population health in countries where the tobacco epidemic is still in an early stage. Smoking prevalence and smoking behaviors in these countries differ from those in Western countries. Reducing the uptake of smoking among young people could be a particularly worthwhile benefit of tobacco-tax increases., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

To study the affect of anatomical variance of lacrimal sac fossa on dacryocystorhinostomies (DCR) performed by the traditional external (EX-DCR) approach or an endoscopic (EN-DCR) endonasal approach. A total of 292 consecutive cases with primary nasolacrimal obstruction underwent DCR surgery. Orbital computed tomography scan was used to measure lacrimal sac fossa and other related structures and Lac-Q questionnaire was used to compare surgery result. Maxillary portion of lacrimal sac fossa is thicker in failed surgery group than successful surgery group ( P <0.05). Lateral nasal structures (uncinate process, operculum of the middle turbinate, agger nasi) are dominantly adjusting to lacrimal sac fossa in failed surgery group ( P <0.05). Patients who underwent EX-DCR has a 6.0-point and EN-DCR group 11.0-point improvement ( P <0.016) in Lac-Q questionnaire. Patients who have a thick frontal process of the maxilla and uncinate process, operculum of the middle turbinate, ethmoid cells adjusting to lacrimal fossa are prone to have recurrence of nasolacrimal duct obstruction after DCR surgery. The EN-DCR and the EX-DCR approach have an equivalent surgical success rate but improvement in quality of life by using the Lac-Q questionnaire is greater in the endoscopic group when compared with the external.

Background: This study aimed to identify increases in 100 % alcohol-related death (ARD) and any differences among prefectures between 1995-2016., Methods: Data from the national death registry on 100 % ARDs between 1995-2016 were extracted. Age-standardized mortality rate (ASMR) of 100 % ARD by year, gender, and gender ratio were calculated. After dividing the period into 1995-2005 and 2006-2016, the ASMRs of 100 % ARDs were calculated by prefecture. Additionally, based on geographical area, municipality size, or annual alcohol sales per adult in each prefecture, prefectures were divided into groups and analysed., Results: In total, 95,455 deaths were caused by 100 % ARD from 1995-2016. Men's ASMRs of 100 % ARD markedly increased from 4.0 per 100,000 in 1995 to 5.2 between 2010 and 2013, and gradually declined to 5.0 in 2016. Women's ASMRs increased steadily from 0.3 in 1995 to 0.8 in 2016. The gender ratio of ASMRs decreased from 13.3 in 1995 to 6.3 in 2016. The ASMR of one prefecture, which had reduced alcohol tax rates, was higher for both genders. Both men's and women's ASMRs were higher in the prefectures that had higher alcohol sales (6.3 [5.0-7.7] and 0.8 [0.6-1.1], respectively) compared to the prefectures that had lower alcohol sales (4.3 [4.0-4.7] p < 0.001 and 0.6 [0.5-0.6] p = 0.045, respectively)., Conclusions: The ASMR of 100 % ARD remained high for men and increased for women, and prefecture-level higher alcohol sales and lower tax rates correlated with the higher mortality rate. Increasing prices and taxes and reducing alcohol sales may contribute to a decrease in alcohol-related mortality., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Glanders is caused by the gram-negative bacterium Burkholderia mallei . In this study, we investigated the histopathology and immunohistochemical localization of B. mallei in natural cases of equine glanders. Four horses showing clinical signs of nasal discharge and multiple cutaneous nodules or papulae in the hindlimbs and abdomen were reported in Mongolia. They tested positive for B. mallei infection on complement fixation, Rose Bengal agglutination, and mallein tests. Gross and histological lesions observed in these cases were similar to those previously reported in equine glanders. Immunohistochemistry using a monoclonal antibody to B. mallei BpaB showed localization of the bacterial antigen in the cytoplasm of neutrophils, macrophages, epithelioid cells, and multinucleated giant cells in the pyogranulomas and abscesses in target organs. Some alveolar type II cells and bronchiolar epithelial cells also contained the antigen. These results suggest that the anti-BpaB antibody is useful for identifying B. mallei -infected cell types in naturally infected horses.

Dourine is a deadly protozoan disease in equids caused by infection with Trypanosoma equiperdum. Neurological signs in the later stage of infection may be caused by peripheral polyneuritis and related axonal degeneration. This neuritis involves T lymphocytes, B lymphocytes, and macrophages, and is observed in cases without obvious neurological signs. However, the pathogenesis of neuritis remains unclear. We identified M2 macrophages and CD8 T cells as the predominant phenotypes in neuritis of dourine-affected horses with or without neurological signs. In contrast, the populations of M1 macrophages and CD4 T cells were small. This result indicates that inflammation was chronic and suggests that dourine-associated neuritis occurs at the early stage of infection.

Glanders is a contagious and fatal equine disease caused by the gram-negative bacterium Burkholderia mallei. B. mallei is prevalent among horse populations in Asia, the Middle East, and South America. More than four million horses have been registered in Mongolia in 2020. However, the recent prevalence of glanders has not been well investigated. In this study, we aimed to investigate the seropositivity of B. mallei in horse populations in Mongolia using the complement fixation test (CFT) and Rose Bengal plate agglutination test (RBT). We randomly collected blood samples from horses in central and eastern Mongolia between 2018 and 2019. Of 337 horses, 26 (7.7%) and 28 (8.3%) were seropositive using RBT and CFT, respectively. Interestingly, seropositivity in horses resulting from crossbreeding of Mongolian native horses with thoroughbred horses was higher than that in Mongolian native horses. Our observations suggest that equine glanders are still endemic to Mongolia.

This study examines the prevalence, awareness, treatment, and control of hypertension in Ulaanbaatar, Mongolia, using both the American Heart Association and conventional thresholds (130/80 and 140/90 mm Hg, respectively). In this randomized cross-sectional study, two-stage cluster sampling was used to obtain a sample of 4515 individuals aged ≥20 years. Hypertension was defined by the use of antihypertensives in the last 2 weeks or a blood pressure at or above the thresholds of 140/90 and 130/80 mm Hg. The mean age of the participants was 41.1 ± 14.0 years and 54.5% were women. Hypertension prevalence was 25.6% (using 140/90 mm Hg) and 46.5% (using 130/80 mm Hg). Prevalence increased with age and below 50 years men were consistently more likely to be hypertensive. Among hypertensive participants, the rates of awareness, treatment, and control were 69.7%, 46.8%, and 24.0% (using 140/90 mm Hg) and 49.1%, 25.8%, and 6.4% (using 130/80 mm Hg, respectively). Men had lower rates of awareness, treatment, and control compared with women, with the most pronounced differences at younger ages. This study shows that awareness, treatment, and control rates in Ulaanbaatar are better than in most low- and middle-income countries but are still suboptimal. The largest "care gap" was in young men where a regulatory requirement for annual workplace blood pressure screening has the potential to enhance care. A major hypertension control program has just been initiated in Ulaanbaatar., (© 2020 Wiley Periodicals, Inc.)

Background: Report of three patients with pseudophakic angle-closure from a Soemmering ring. Three mechanisms of the Soemmering ring induced pseudophakic angle-closure in three patients were demonstrated by meticulous anterior segment examination and ultrasound biomicroscopic (UBM) analysis., Case Presentation: In the first case, the Soemmering-capsule-IOL complex caused relative pupillary block similar to a phakic eye and was successfully treated with laser iridotomy alone. In the second case, an enlarged Soemmering ring provided posterior iris support in apposition to the anterior chamber angle. We performed a laser capsulotomy through the iridotomised hole. The last, a protruding Soemmering content causing absolute pupillary block became resolved after laser iridotomy and total Soemmering ring content removal., Conclusion: Angle-closure in pseudophakic eyes is uncommon. Several causes have been reported in the literatures including Soemmering ring. This is the first report on three different mechanisms of Soemmering ring related angle-closure in pseudophakic eyes. Ultrasound biomicroscopic analysis plays a crucial role as a diagnostic tool.

Despite significant attractiveness of antisense oligonucleotide/RNAi technology, its clinical application has been precluded by a lack of methods for targeted delivery and transduction of primary immune cells in vivo. Here, we devised a chemokine CCL17-based strategy (TARC-arp) that transiently silences expression of genes in immune cells by delivering inhibitory oligonucleotides through their chemokine receptors. In modeling studies using mice with established 4T1.2 breast cancer, we show that IL10 produced by CCR4 cells, in particular FoxP3 regulatory T cells (Tregs), plays an important role in lung metastasis. As such, TARC-arp-mediated silencing of IL10 or FoxP3 in CCR4 Tregs is sufficient to block lung metastasis. Thus, we provide a simple solution that circumvents the problems of RNAi use in vivo, indicating that a disease outcome can be successfully controlled by delivering inhibitory oligonucleotides with chemokines to inactivate a selective subset of immune cells.