Advances in the Immunology of the Host-Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics.

Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host's innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection. Since trypanosomes circulate through the host body in blood and lymph fluid and invade various organs, understanding the interaction between trypanosomes and tissue niches is essential. Here, we present an up-to-date overview of host-parasite interactions and survival strategies for trypanosomes by introducing and discussing the latest studies investigating the transcriptomics of parasites according to life cycle stages, as well as host cells in various tissues and organs, using single-cell and spatial sequencing applications. In recent years, this information has improved our understanding of trypanosomosis by deciphering the diverse populations of parasites in the developmental process, as well as the highly heterogeneous immune and tissue-resident cells involved in anti-trypanosome responses. Ultimately, the goal of these approaches is to gain an in-depth understanding of parasite biology and host immunity, potentially leading to new vaccination and therapeutic strategies against trypanosomosis.

Association of Tumor Necrosis Factor Inhibitors with the Risk of Nontuberculous Mycobacterial Infection in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study.

Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior non-TNFi antirheumatic drugs. We aimed to evaluate the NTM infection risk associated with TNFi using a real-world database. Patients with RA treated with TNFi or csDMARDs between 2005 and 2016 were identified utilizing the Korean National Health Insurance Service database. To minimize potential bias, we aligned the initiation year of csDMARDs for both TNFi and csDMARD users and tracked them from their respective treatment start dates. The association of TNFi with NTM infection risk was estimated in a one-to-one matched cohort using a multivariable conditional Cox regression analysis. In the matched cohort (n = 4556), the incidence rates of NTM infection were 2.47 and 3.66 per 1000 person-year in TNFi and csDMARD users. Compared to csDMARDs, TNFi did not increase the risk of NTM infection (adjusted hazard ratio (aHR) 0.517 (95% confidence interval, 0.205-1.301)). The TNFi use in RA patients was not associated with an increased risk of NTM infection compared to csDMARDs. Nevertheless, monitoring during TNFi treatment is crucial.

Neutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis.

Recent blood transcriptomic analysis of rhodesiense sleeping sickness patients has revealed that neutrophil signature genes and activation markers constitute the top indicators of trypanosomiasis-associated inflammation. Here, we show that Trypanosoma brucei infection results in expansion and differentiation of four splenic neutrophil subpopulations, including Mki67+Birc5+Gfi1+Cebpe+ proliferation-competent precursors, two intermediate immature subpopulations and Cebpb+Spi1+Irf7+Mcl1+Csf3r+ inflammation reprogrammed mature neutrophils. Transcriptomic scRNA-seq profiling identified the largest immature subpopulation by Mmp8/9 positive tertiary granule markers. We confirmed the presence of both metalloproteinases in extracellular spleen homogenates and plasma. During infection, these enzymes digest extracellular matrix components in the absence of sufficient TIMP inhibitory activity, driving remodeling of the spleen follicular architecture. Neutrophil depletion prevents the occurrence of organ damage, resulting in increased plasma cell numbers and prolonged host survival. We conclude that trypanosomiasis-associated neutrophil activation is a major contributor to the destruction of the secondary lymphoid architecture, required for maintaining an efficient adaptive immune response.

Development and Degeneration of Retinal Ganglion Cell Axons in Xenopus tropicalis.

Neurons make long-distance connections via their axons, and the accuracy and stability of these connections are crucial for brain function. Research using various animal models showed that the molecular and cellular mechanisms underlying the assembly and maintenance of neuronal circuitry are highly conserved in vertebrates. Therefore, to gain a deeper understanding of brain development and maintenance, an efficient vertebrate model is required, where the axons of a defined neuronal cell type can be genetically manipulated and selectively visualized in vivo. Placental mammals pose an experimental challenge, as time-consuming breeding of genetically modified animals is required due to their in utero development. Xenopus laevis, the most commonly used amphibian model, offers comparative advantages, since their embryos ex utero during which embryological manipulations can be performed. However, the tetraploidy of the X. laevis genome makes them not ideal for genetic studies. Here, we use Xenopus tropicalis, a diploid amphibian species, to visualize axonal pathfinding and degeneration of a single central nervous system neuronal cell type, the retinal ganglion cell (RGC). First, we show that RGC axons follow the developmental trajectory previously described in X. laevis with a slightly different timeline. Second, we demonstrate that co-electroporation of DNA and/or oligonucleotides enables the visualization of gene function-altered RGC axons in an intact brain. Finally, using this method, we show that the axon-autonomous, Sarm1-dependent axon destruction program operates in X. tropicalis. Taken together, the present study demonstrates that the visual system of X. tropicalis is a highly efficient model to identify new molecular mechanisms underlying axon guidance and survival.

The risk of newly diagnosed cancer in patients with rheumatoid arthritis by TNF inhibitor use: a nationwide cohort study.

BACKGROUND: Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. METHODS: Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. RESULTS: Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255-0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235-0.797), breast cancer (0.146; 0.045-0.474), and genitourinary cancer (0.220; 0.059-0.820). CONCLUSIONS: The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.

Vision-Threatening Ocular Adverse Events after Vaccination against Coronavirus Disease 2019.

A single-center retrospective observational case series was conducted. This case series enrolled patients who showed ophthalmic manifestations within one week after COVID-19 vaccination at Korea University Guro Hospital in Seoul, Korea, from May 2021 to January 2022. The medical records of patients who complained of ocular symptoms and showed ophthalmic adverse events within one week after COVID-19 vaccination were reviewed. Seventeen eyes from 16 patients with a mean age of 63.8 (range 33-83) years were included in the case series, and all symptoms developed within 1-7 days following inoculation. Retinal vein occlusion in nine eyes (52.9%), retinal artery occlusion in one eye (5.9%), newly developed anterior uveitis in one eye (5.9%), exacerbation of previously diagnosed panuveitis in two eyes (11.8%), and angle-closure attack with high intraocular pressure in four eyes (23.5%) were included. Twelve patients (75%) had been vaccinated with the AstraZeneca (AZD1222) and four (25%) with the Pfizer (BNT162b2) vaccines. Of these, 10 patients (62.5%) experienced ocular disease exacerbation after the first dose, 4 (25%) after the second dose, and 2 (12.5%) after the third dose (booster shot). Eleven patients (64.7%) underwent tests for hematological abnormalities, and three of them tested positive for anti-PF4 antibodies, but no abnormal findings were noted. A causal relationship between vaccination and the ocular manifestations could not be determined, which is a limitation of this study. However, clinicians should consider the effect of COVID-19 vaccination on ophthalmic disease. Further studies are required to elucidate the possible effects of COVID-19 vaccination on the eye.

Employee Perspectives on Onsite Health Clinics in Semiconductor Company in South Korea.

(1) Background: Onsite clinics are increasingly common features of corporate health promotion programs. These clinics allow employers to offer convenient care to employees at their workplaces, which can lead to reduced healthcare expenditure and improved productivity. The objective of this study was to build basic data by qualitatively exploring employees' experiences and perspectives on onsite clinics in a semiconductor company, as one part of the project to examine and improve the health management system of a large semiconductor company in Korea. (2) Methods: This study adopted the methodology of "Consolidated Criteria for Reporting Qualitative Research" (COREQ-32 checklist). Semi-structured interviews were conducted for this study over a two-month period. For data analysis, a codebook was developed and the constant comparative method was used. (3) Results: Most employees perceived convenience and a sense of belonging as the benefits of onsite clinics, while barriers to the use of onsite clinics included a lack of communication, concerns about confidentiality, and a provider-centered system. Promotion of onsite clinic services and affiliated physicians, employee-centered service provisions, and trust-building in healthcare information privacy were considered necessary to strengthen the role of onsite clinics as a primary care provider in the workplace. (4) Conclusions: The results of this qualitative study help us to gain a better understanding of employees' perspectives on the onsite clinic's service and roles.

Factors Influencing Workplace Health Promotion Interventions for Workers in the Semiconductor Industry According to Risk Levels of Chronic Disease.

(1) Background: This study aimed to analyze the risk of chronic diseases including hypertension, diabetes, and dyslipidemia in workers of a semiconductor manufacturing company and the factors associated with their participation in workplace health promotion (WHP) programs. (2) Methods: Subjects were workers in a semiconductor and liquid crystal display company in South Korea who had undergone regular health checkups. Data from regular health checkups and WHP interventions were analyzed. Health risk was classified based on the diagnosed disease, in-house classification criteria, and pooled cardiovascular risk score. (3) Results: The baseline characteristics of 39,073 participants included the following: male, 67.8%; between 30 and 40 years of age, 74.1%; <2 h of physical activities, 65.9%. Workers at risk of chronic diseases accounted for 22.2%, and 20.1% were suspicious cases of chronic diseases. Body mass index, and cholesterol level were relatively high in workers with the burden of chronic diseases. The participation rate in WHP programs was 28.8% in a high-risk group among workers at risk of chronic diseases. More participation was shown in male, older age groups, production work type, and single-person household. (4) Conclusions: Because of the low participation rate in WHP activities among workers with the burden of chronic diseases, it is necessary to establish measures to encourage their participation.

Prevalence and characteristics of S-point bleeding compared to non S-point bleeding in severe epistaxis / Prevalência e características do sangramento no S-point em comparação com outros pontos sangramento na epistaxe grave

Abstract Introduction Stamm's S-point is gaining importance as a bleeding focus in severe epistaxis. However, prevalence and features of S-point bleeding compared to non S-point bleeding have not been studied. Objective To investigate the characteristics of patients with S-point bleeding among those with severe epistaxis and to compare the factors involved in the treatment of epistaxis. Methods We retrospectively analyzed medical records of 268 patients admitted to the otorhinolaryngology department of Konkuk University Hospital and Chung-Ang University Hospital with epistaxis of which the bleeding focus clarified. Patients with anterior nasal bleeding (n = 129) were excluded. The study was conducted at the department of otorhinolaryngology from January 2008 to August 2019. Collected data included patients' demographic information, bleeding focus, body mass index underlying medical and sinonasal diseases, laboratory test results (initial hemoglobin, platelet count, and triglyceride level), use of anticoagulants, direction of epistaxis, initial and final treatments, and need for blood transfusion. Results The prevalence of S-point bleeding was 28.8% of non-anterior bleeding cases. Mean body mass index score was lower in the S-point group (23.41 ± 3.71) compared to the non S-point group (24.93 ± 3.97) (p = 0.039). Underweight patients tended to show a greater incidence of S-point bleeding (15.0%) than non S-point bleeding (2.0%) (p = 0.010). Incidence of anemia was higher in the S-point group (67.5%) than in the non S-point group (36.4%). Anemia (Odds ratio [OR]: 3.635; 95% confidence interval [CI]: 1.669-7.914, p = 0.001) and underweight (body mass index < 18.5, OR: 8.559, CI: 1.648-44.445, p = 0.011) were significantly associated with S-point bleeding. Conclusion Prevalence of S-point bleeding was significant, underlining the importance of examining the S-point in patients with severe epistaxis. Patients with S-point bleeding had lower body mass index scores and a higher incidence of anemia than those with non S-point bleeding.

Resumo Introdução O S-point de Stamm tem ganhado importância como foco de sangramento na epistaxe grave. Entretanto, a prevalência e as características do sangramento no S-point em comparação com o sangramento em outros locais ainda não foram estudadas. Objetivo Investigar as características dos pacientes com epistaxe grave com sangramento no S-point e comparar os fatores envolvidos no tratamento da epistaxe. Método Analisamos retrospectivamente os prontuários médicos de 268 pacientes internados no Departamento de Otorrinolaringologia do Konkuk University Hospital e do Chung-Ang University Hospital com epistaxe cujo foco hemorrágico foi esclarecido. Pacientes com sangramento anterior (n = 129) foram excluídos. O estudo foi feito no Departamento de Otorrinolaringologia de janeiro de 2008 a agosto de 2019. Os dados coletados incluíram informações demográficas dos pacientes, foco hemorrágico, índice de massa corporal doenças médicas e nasosinusais subjacentes, resultados de exames laboratoriais (hemoglobina, contagem de plaquetas e nível de triglicerídeos iniciais), uso de anticoagulantes, direção da epistaxe, tratamentos iniciais e finais e necessidade de transfusão de sangue. Resultados A prevalência de sangramento no S-point foi de 28,8% dos casos de sangramento não anterior. O índice de massa corpórea médio foi menor no grupo com sangramento no S-point (23,41 ± 3,71) em comparação com o grupo não S-point (24,93 ± 3,97) (p = 0,039). Pacientes com baixo peso tenderam a apresentar maior incidência de sangramento no S-point (15,0%) do que sangramento em ponto não S (2,0%) (p = 0,010). A incidência de anemia foi maior no grupo com sangramento no S-point (67,5%) do que no grupo não S-point (36,4%). A anemia (odds ratio [OR]: 3,635; intervalo de confiança de 95% [IC95%]: 1,669-7,914, p = 0,001) e o baixo peso (IMC < 18,5, OR: 8,559, IC95%: 1,648-44,445, p = 0,011) foram significantemente associados com sangramento no S-point. Conclusão A prevalência de sangramento no S-point foi significativa, enfatizou a importância de examinar o S-point em pacientes com epistaxe grave. Pacientes com sangramento no S-point apresentaram escores mais baixos no índice de massa corpórea e maior incidência de anemia do que aqueles com sangramento em locais que não o S-point.

Nystagmus in adult patients with acute otitis media or otitis media with effusion without dizziness.

The present study aimed to investigate the incidence and patterns of nystagmus in adult patients with acute otitis media (AOM) or otitis media with effusion (OME) without dizziness or vertigo, and discuss possible mechanisms. From February 2018 to November 2018, 34 consecutive patients with AOM or OME without dizziness were included. Nystagmus was examined with video Frenzel glasses. Of 34 adult AOM or OME patients without dizziness, nystagmus was observed in 28 patients (82%). In unilateral AOM or OME (n = 30), the most commonly observed nystagmus pattern was irritative-type direction-fixed nystagmus (n = 13), followed by paretic-type direction-fixed nystagmus (n = 8), and direction-changing positional nystagmus (n = 4). In bilateral AOM or OME (n = 4), direction-fixed nystagmus and direction-changing positional nystagmus were observed in two and one patients, respectively. Nystagmus was observed in as many as 82% of adult AOM or OME patients even though they did not complain of dizziness, and the pattern of nystagmus was either direction-fixed or direction-changing. Direct effect of inflammatory mediators penetrated from the middle ear and biochemical alteration in the inner ear fluids due to blood-perilymph barrier dysfunction may result in the presence of nystagmus in AOM or OME patients without dizziness.

UXT chaperone prevents proteotoxicity by acting as an autophagy adaptor for p62-dependent aggrephagy.

p62/SQSTM1 is known to act as a key mediator in the selective autophagy of protein aggregates, or aggrephagy, by steering ubiquitinated protein aggregates towards the autophagy pathway. Here, we use a yeast two-hybrid screen to identify the prefoldin-like chaperone UXT as an interacting protein of p62. We show that UXT can bind to protein aggregates as well as the LB domain of p62, and, possibly by forming an oligomer, increase p62 clustering for its efficient targeting to protein aggregates, thereby promoting the formation of the p62 body and clearance of its cargo via autophagy. We also find that ectopic expression of human UXT delays SOD1(A4V)-induced degeneration of motor neurons in a Xenopus model system, and that specific disruption of the interaction between UXT and p62 suppresses UXT-mediated protection. Together, these results indicate that UXT functions as an autophagy adaptor of p62-dependent aggrephagy. Furthermore, our study illustrates a cooperative relationship between molecular chaperones and the aggrephagy machinery that efficiently removes misfolded protein aggregates.

Prevalence and characteristics of S-point bleeding compared to non S-point bleeding in severe epistaxis.

INTRODUCTION: Stamm's S-point is gaining importance as a bleeding focus in severe epistaxis. However, prevalence and features of S-point bleeding compared to non S-point bleeding have not been studied. OBJECTIVE: To investigate the characteristics of patients with S-point bleeding among those with severe epistaxis and to compare the factors involved in the treatment of epistaxis. METHODS: We retrospectively analyzed medical records of 268 patients admitted to the otorhinolaryngology department of Konkuk University Hospital and Chung-Ang University Hospital with epistaxis of which the bleeding focus clarified. Patients with anterior nasal bleeding (n=129) were excluded. The study was conducted at the department of otorhinolaryngology from January 2008 to August 2019. Collected data included patients' demographic information, bleeding focus, body mass index underlying medical and sinonasal diseases, laboratory test results (initial hemoglobin, platelet count, and triglyceride level), use of anticoagulants, direction of epistaxis, initial and final treatments, and need for blood transfusion. RESULTS: The prevalence of S-point bleeding was 28.8% of non-anterior bleeding cases. Mean body mass index score was lower in the S-point group (23.41±3.71) compared to the non S-point group (24.93±3.97) (p=0.039). Underweight patients tended to show a greater incidence of S-point bleeding (15.0%) than non S-point bleeding (2.0%) (p=0.010). Incidence of anemia was higher in the S-point group (67.5%) than in the non S-point group (36.4%). Anemia (Odds ratio [OR]: 3.635; 95% confidence interval [CI]: 1.669-7.914, p=0.001) and underweight (body mass index<18.5, OR: 8.559, CI: 1.648-44.445, p=0.011) were significantly associated with S-point bleeding. CONCLUSION: Prevalence of S-point bleeding was significant, underlining the importance of examining the S-point in patients with severe epistaxis. Patients with S-point bleeding had lower body mass index scores and a higher incidence of anemia than those with non S-point bleeding.

Nystagmus in Ramsay Hunt syndrome with or without dizziness.

BACKGROUND: The presence of dizziness has been reported as a negative prognostic factor for recovery of facial palsy in Ramsay Hunt syndrome (RHS). The aim of this study was to investigate the incidence and patterns of nystagmus in RHS patients without dizziness, and discuss possible mechanisms. We also compared the severity and prognosis of facial palsy between RHS patients with and without dizziness. METHODS: From January 2014 to January 2019, 36 patients diagnosed with RHS (27 with dizziness and 9 without dizziness) were included. Patterns of nystagmus were examined and categorized using video-nystagmography. House-Brackmann(HB) grade of facial palsy was compared between RHS patients with and without dizziness. RESULTS: Not only RHS patients with dizziness exhibited nystagmus in most cases (96%, 26 of 27) but also as many as 67% (6 of 9) of RHS patients without dizziness exhibited nystagmus, though the intensity was remarkably weak. In both groups of RHS with and without dizziness, direction-fixed nystagmus and direction-changing positional nystagmus were observed. Initial HB grade and recovery of facial palsy after treatment were not significantly different between RHS with and without dizziness. CONCLUSION: Various patterns of nystagmus including direction-fixed and positional direction-changing nystagmus were observed in RHS patients, and inflammation of the vestibular nerve and inner ear end organs may be responsible for the production of nystagmus in these patients. The results support that the evaluation of vestibular function may be necessary even in RHS patients who do not complain of dizziness or vertigo.

Nystagmus in patients with lateral semicircular canal dysplasia.

BACKGROUND: Dizziness is not a common symptom in the lateral semicircular canal (LSCC) dysplasia, and nystagmus findings has been rarely described in LSCC dysplasia. OBJECTIVE: To investigate the characteristics of spontaneous and positional nystagmus in patients with LSCC dysplasia. METHODS: Patterns of spontaneous and positional nystagmus of twelve patients with LSCC dysplasia, who visited our clinic with a chief complaint of dizziness, were investigated. RESULTS: LSCC dysplasia was observed unilaterally in 4, and bilaterally in 8 patients. Non-rotatory dizziness with various onset times was the most common description of dizziness, and unilateral caloric weakness was observed in 82% of patients. Direction-fixed nystagmus, in which the direction of spontaneous nystagmus was same with that of positional nystagmus, was observed in 9 patients, and direction-changing positional nystagmus, in which the direction of nystagmus was changed from that of spontaneous nystagmus by positioning maneuvers, was observed in 3 patients, of whom down-beating or direction-changing spontaneous nystagmus was observed in one patient each. CONCLUSION: While direction-fixed horizontal nystagmus is the most commonly observed type of nystagmus in LSCC dysplasia, atypical spontaneous nystagmus, such as down-beating nystagmus or direction-changing spontaneous nystagmus, may be observed in patients with bilateral LSCC dysplasia.

Effectiveness and Satisfaction Degree of Transconjunctival-Approach Lower Blepharoplasty Combined With Pinch Skin Excision Technique.

The purpose of this study was to evaluate and compare the effectiveness and satisfaction of transconjunctival-approach lower blepharoplasty combined with a pinch skin excision technique between young patients (younger than 60 years of age) and elderly patients (older than 60 years of age) in Korea. The medical records of 69 patients who underwent transconjunctival-approach lower blepharoplasty combined with a pinch skin excision technique from January 2003 to February 2018 were reviewed. Success rate postoperative complications, and degree of satisfaction with the surgical technique were evaluated and statistically compared between the 2 different age groups. All 69 patients were satisfied with the final result. The average success rate of surgery was 96.7% in the young patients (group A) and 97.4% in the elderly patients (group B) during the mean follow-up period of 6 months. There were 3 cases reported as having persistent complications (2 cases in group A and 1 patient in group B). The satisfaction rating between groups A and B showed no statistically significant difference (P = 0.430). We confirmed lower-eyelid fat prolapse and dermatochalasis can be effectively corrected using transconjunctival lower blepharoplasty with a pinch skin excision technique in patients regardless of age.

Comorbid Cupulolithiasis Is Rare in Patients With Horizontal Semicircular Canal Canalolithiasis.

OBJECTIVES: Considering that otolith particles pass through the canal until attaching to the cupula in the canal-side horizontal semicircular canal (HSCC) cupulolithiasis, comorbidity of HSCC canalolithiasis and cupulolithiasis may occur. We aimed to investigate the incidence of comorbidity of cupulolithiasis in patients with HSCC canalolithiasis and to improve treatment efficacy. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral academic center. PATIENTS: Ninety-seven consecutive patients with HSCC canalolithiasis between March 2017 and March 2019 were included. MAIN OUTCOME MEASURES: Coexistence of HSCC cupulolithiasis was hierarchically investigated. 1) Spontaneous reversal of initial nystagmus is observed bilaterally in a head-roll test (HRT), 2) nystagmus is in the same direction at each of the three times the supine position was tested, and 3) both bowing and leaning nystagmus with opposite direction are observed. RESULTS: Of 97 patients with HSCC canalolithiasis, 2 patients (2%) had comorbid HSCC cupulolithiasis. CONCLUSIONS: Although coexistence of HSCC canalolithiasis and cupulolithiasis should be considered when spontaneous reversal of nystagmus direction is observed without position change during a HRT, the incidence of coexistence is very low. However, canalith repositioning maneuvers for both canalolithiasis and cupulolithiasis should be performed in cases with comorbidity.

Effect of glutathione S-transferase genetic polymorphisms on busulfan pharmacokinetics and veno-occlusive disease in hematopoietic stem cell transplantation: A meta-analysis.

This meta-analysis was conducted to derive an integrated conclusion about the influence of glutathione S-transferase (GST) genetic polymorphisms on busulfan pharmacokinetic (PK) parameters and veno-occlusive disease (VOD). Studies which analysed the effect of GST genetic polymorphisms on area under the curve (AUC), clearance (CL) or VOD were searched for and selected. A pooled analysis was conducted using Comprehensive Meta-Analysis programme. Nineteen studies were included in this meta-analysis. GSTA1*B and GSTM1 null genotypes significantly decreased CLIV of busulfan (standardized difference in means (SDM) = -1.103; P = 0.019 and SDM = -0.418; P = 0.002, respectively). GSTA1*B significantly increased AUCIV of busulfan (SDM = 0.832; P = 0.046), whereas GSTM1 did not (SDM = 0.155; P = 0.478). The PK parameters of oral busulfan did not differ according to GST genotype. GSTA1, GSTM1 and GSTP1 were not significantly associated with VOD occurrence. GSTA1 and GSTM1 genotypes affected CLIV of busulfan, but only GSTA1 affected AUCIV . There was no significant difference in the PK parameters of oral busulfan (CLPO and AUCPO ) and VOD when only GST genotypes were considered.

Strategic Priorities to Improve Effectiveness of Anti-smoking Interventions for the Korean Military: An Application of the Analytic Hierarchy Process.

Introduction: As South Korea remains technically at war with the North, higher smoking prevalence in the military might adversely affect the South Korea's military power and contribute to lifetime smoking in men with mandatory military service. This study was to identify priorities among the anti-smoking strategies to improve the existing smoking cessation programs for the Korean military. Methods: The analytic hierarchy process model with a goal, decision criteria, and sub-criteria as well as candidate strategies, was developed following a literature search and expert group discussion. A survey for pairwise comparison was conducted to determine the priority of the (sub-)criteria and strategies by 14 experts. The Super-Decisions software was used to determine the priorities and to analyze their consistency ratios and sensitivities. The study was approved by the ethics committee of the Korea Ministry of Health and Welfare. Results: Eight candidate strategies were developed to improve the effectiveness of military anti-smoking interventions as follows: (1) development of outcome enhancement plans for smoking cessation programs for the military, (2) development of differentiated smoking cessation programs for specific groups, (3) building of community network for continuity and accessibility of anti-smoking project, (4) building of industry-academia-government networks for anti-smoking project, (5) improvement of the perception of and strengthen the reward for smoking cessation, (6) development of a training system for army clinicians for the delivery of smoking cessation services, (7) creation of a certification system for smoking cessation programs, and (8) development of an evaluation system of project performance for smoking cessation. Through the analytic hierarchy process survey, the military specificity and its sub-criterion of practicality were selected as the top concerns of decision criteria for the anti-smoking strategies among the decision criteria of outcome improvement, military specificity, publicness, and economic efficiency. The most important strategy was to improve the perception of and strengthen the reward for smoking cessation. This strategy was most focused on the creation of an anti-smoking environment and improvement of the effectiveness of the projects. The creation of a training system for army clinicians for the delivery of smoking cessation services ranked second. Conclusion: In conclusion, motivating smoking cessation and utilizing well-trained army clinicians were found to be the most important anti-smoking strategies for the Korean military. This study might provide valuable insights for policy makers to reduce tobacco use in the Korean military.