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Sri Lanka experienced an unprecedented outbreak of hepatitis A in 2009. We extracted data from different sources to get a proper estimate of actual disease incidence during that period. This data show a total number of 13,477 cases in 2009 which is one of the largest outbreaks in recent history. We confirmed the etiological diagnosis as hepatitis A among armed forces towards the end of the outbreak. This massive outbreak shows the potential risk of future outbreaks due to epidemiological shifts of hepatitis A infection in Sri Lanka.DOI: http://dx.doi.org/10.4038/sljid.v3i2.5640 Sri Lankan Journal of Infectious Diseases 2013; Vol.3(2):28-30

Recent advancements have made two-dimensional (2D) clinical gait analysis systems more accessible and portable than traditional three-dimensional (3D) clinical systems. This study evaluates the reliability and validity of gait measurements using monocular and composite camera setups with VisionPose, comparing them to the Vicon 3D motion capture system as a reference. Key gait parameters-including hip and knee joint angles, and time and distance factors-were assessed under normal, maximum speed, and tandem gait conditions during level walking. The results show that the intraclass correlation coefficient (ICC(1,k)) for the 2D model exceeded 0.969 for the monocular camera and 0.963 for the composite camera for gait parameters. Time-distance gait parameters demonstrated excellent relative agreement across walking styles, while joint range of motion showed overall strong agreement. However, accuracy was lower for measurements during tandem walking. The Cronbach's alpha coefficient for time-distance parameters ranged from 0.932 to 0.999 (monocular) and from 0.823 to 0.998 (composite). In contrast, for joint range of motion, the coefficient varied more widely, ranging from 0.826 to 0.985 (monocular) and from 0.314 to 0.974 (composite). The correlation coefficients for spatiotemporal gait parameters were greater than 0.933 (monocular) and 0.837 (composite). However, for joint angle parameters, the coefficients were lower during tandem walking. This study underscores the potential of 2D models in clinical applications and highlights areas for improvement to enhance their reliability and application scope.

Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD. Here we investigated whether trophoblast cell surface antigen 2 (TROP2) could be a promising therapeutic target for EMPD. We retrospectively collected 108 samples from 54 patients with primary and metastatic EMPD from 10 Japanese institutions, and compared TROP2 expression between primary and metastatic lesions of each paired sample. In vitro assays were performed using a newly established EMPD cell line, KS-EMPD-1. TROP2 was strongly and homogeneously expressed in patient tissues, regardless of primary or metastatic lesions. The KS-EMPD-1 cells were treated with a TROP2-targeted antibody-drug conjugate (ADC), sacituzumab govitecan, and it significantly reduced cell viability in a dose-dependent manner compared with that of the cells treated with sacituzumab alone. Knockdown of TROP2 reduced cell viability and cell migration, and caused slight upregulation of the apoptosis-related factors, together with downregulation of the epithelial-to-mesenchymal transition-related factors. These findings suggest that a TROP2-targeted ADC may be a promising treatment option for unresectable EMPD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Two-dimensional (2D) clinical gait analysis systems are more affordable and portable than contemporary three-dimensional (3D) clinical models. Using the Vicon 3D motion capture system as the standard, we evaluated the internal statistics of the Imasen and open-source OpenPose gait measurement systems, both designed for 2D input, to validate their output based on the similarity of results and the legitimacy of their inner statistical processes. We measured time factors, distance factors, and joint angles of the hip and knee joints in the sagittal plane while varying speeds and gaits during level walking in three in-person walking experiments under normal, maximum-speed, and tandem scenarios. The intraclass correlation coefficients of the 2D models were greater than 0.769 for all gait parameters compared with those of Vicon, except for some knee joint angles. The relative agreement was excellent for the time-distance gait parameter and moderate-to-excellent for each gait motion contraction range, except for hip joint angles. The time-distance gait parameter was high for Cronbach's alpha coefficients of 0.899-0.993 but low for 0.298-0.971. Correlation coefficients were greater than 0.571 for time-distance gait parameters but lower for joint angle parameters, particularly hip joint angles. Our study elucidates areas in which to improve 2D models for their widespread clinical application.

Linear optical transformations of multiple single-photon inputs are fundamental for the development of photonic quantum technologies. Various nonclassical correlations can already be observed directly in states generated using only single-photon inputs and linear optics transformations. However, some quantum correlations require additional operations, and states that exhibit such correlations are classified as non-Fock states. Here, we demonstrate the generation of a two-photon three-mode non-Fock state that exhibits conditional quantum coherences that can only be achieved by non-Fock states. We determine the fidelity of the non-Fock state based on experimentally observed conditional visibilities that characterize the state and compare the result to the fidelity bounds for different classes of Fock and non-Fock states. Our experimental verification of the non-Fock character of the state provides insights into the technological requirements needed to achieve nonclassical correlations in multiphoton quantum optics.

Background: The association between clinical outcomes in ischemic stroke patients and decreases in serum uric acid levels, which often occur during the acute phase, remains unknown. Herein, we aimed to investigate the association using a large-scale, multicenter stroke registry., Methods: We analyzed 4,621 acute ischemic stroke patients enrolled in the Fukuoka Stroke Registry between June 2007 and September 2019 whose uric acid levels were measured at least twice during hospitalization (including on admission). The study outcomes were poor functional outcome (modified Rankin Scale score ≥3) and functional dependence (modified Rankin Scale score 3-5) at 3 months after stroke onset. Changes in uric acid levels after admission were evaluated using a decrease rate that was classified into 4 sex-specific grades ranging from G1 (no change/increase after admission) to G4 (most decreased). Multivariable logistic regression analyses were used to assess the associations between decreases in uric acid levels and the outcomes., Results: The frequencies of the poor functional outcome and functional dependence were lowest in G1 and highest in G4. The odds ratios (95% confidence intervals) of G4 were significantly higher for poor functional outcome (2.66 [2.05-3.44]) and functional dependence (2.61 [2.00-3.42]) when compared with G1 after adjusting for confounding factors. We observed no heterogeneity in results for subgroups categorized according to age, sex, stroke subtype, neurological severity, chronic kidney disease, or uric acid level on admission., Conclusions: Decreases in serum uric acid levels were independently associated with unfavorable outcomes after acute ischemic stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nakamura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although both stellate ganglion blockade and nifekalant are effective treatment options for electrical storm, the clinical effect of their combination is uncertain., Case Summary: A 71-year-old male patient was admitted to our hospital with acute myocardial infarction and heart failure. Emergency coronary angiography revealed triple-vessel disease. Although coronary artery bypass grafting was planned, the patient experienced electrical storm before the surgery could be performed. Despite complete revascularization by percutaneous coronary intervention, mechanical circulatory support and administration of antiarrhythmic agents (amiodarone and lidocaine), electrical storm was not controlled. After stellate ganglion blockade was initiated on the 9th day of hospitalization, ventricular arrhythmia decreased. However, when stellate ganglion blockade was temporarily discontinued, ventricular arrhythmia increased substantially. Subsequently, combination therapy with stellate ganglion blockade and nifekalant was initiated, after which ventricular arrhythmia disappeared completely. Afterwards, the patient had no further ventricular arrhythmia episodes, and his haemodynamic status gradually improved. The patient was discharged from hospital in an ambulatory condition and did not experience arrhythmia during the follow-up., Discussion: This case demonstrates that combination therapy with stellate ganglion blockade and nifekalant can completely suppress ventricular arrhythmia, suggesting that blocking multiple conduction pathways is a key to treating refractory electrical storm., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The transmembrane protein p22 phox heterodimerizes with NADPH oxidase (Nox) 1-4 and is essential for the reactive oxygen species-producing capacity of oxidases. Missense mutations in the p22 phox gene prevent the formation of phagocytic Nox2-based oxidase, which contributes to host defense. This results in chronic granulomatous disease (CGD), a severe primary immunodeficiency syndrome. In this study, we characterized missense mutations in p22 phox (L51Q, L52P, E53V, and P55R) in the A22° type (wherein the p22 phox protein is undetectable) of CGD. We demonstrated that these substitutions enhanced the degradation of the p22 phox protein in the endoplasmic reticulum (ER) and the binding of p22 phox to Derlin-1, a key component of ER-associated degradation (ERAD). Therefore, the L 51 -L 52 -E 53 -P 55 sequence is responsible for protein stability in the ER. We observed that the oxidation of the thiol group of Cys-50, which is adjacent to the L 51 -L 52 -E 53 -P 55 sequence, suppressed p22 phox degradation. However, the suppression effect was markedly attenuated by the serine substitution of Cys-50. Blocking the free thiol of Cys-50 by alkylation or C50S substitution promoted the association of p22 phox with Derlin-1. Derlin-1 depletion partially suppressed the degradation of p22 phox mutant proteins. Furthermore, heterodimerization with p22 phox (C50S) induced rapid degradation of not only Nox2 but also nonphagocytic Nox4 protein, which is responsible for redox signaling. Thus, the redox-sensitive Cys-50 appears to determine whether p22 phox becomes a target for degradation by the ERAD system through its interaction with Derlin-1., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes., (© 2022. The Author(s).)

Antidiabetic sodium-glucose cotransporter 2 (SGLT2) inhibitors have attracted attention for their cardiorenal-protective properties beyond their glucose-lowering effect. However, their benefits in ischemic stroke remain controversial. Here we show the effects of luseogliflozin, a selective SGLT2 inhibitor, in acute ischemic stroke, using a permanent middle cerebral artery occlusion (pMCAO) model in non-diabetic mice. Pretreatment with low-dose luseogliflozin, which does not affect blood glucose levels, significantly attenuated infarct volume, blood-brain barrier disruption, and motor dysfunction after pMCAO. SGLT2 was expressed predominantly in brain pericytes and was upregulated in peri- and intra-infarct areas. Notably, luseogliflozin pretreatment reduced pericyte loss in ischemic areas. In cultured pericytes, luseogliflozin activated AMP-activated protein kinase α and increased mitochondrial transcription factor A expression and number of mitochondria, conferring resistance to oxygen-glucose deprivation. Collectively, pre-stroke inhibition of SGLT2 induces ischemic tolerance in brain pericytes independent of the glucose-lowering effect, contributing to the attenuation of ischemic brain injury., (© 2022. The Author(s).)

is missing (Short communication).

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background and Purpose: Little is known about how β-cell dysfunction affects clinical outcome after ischemic stroke. We examined whether β-cell function is associated with clinical outcome after acute ischemic stroke and if so, whether insulin resistance influences this association in a prospective study of patients with acute stroke., Methods: A total of 3590 nondiabetic patients with acute ischemic stroke (mean age, 71 years) were followed up for 3 months. β-Cell function was assessed using the homeostasis model assessment for β-cell function (HOMA-β). Study outcomes were poor functional outcome (modified Rankin Scale score, 3–6) and stroke recurrence at 3 months after stroke onset and neurological deterioration (≥2-point increase in the National Institutes of Health Stroke Scale score) at discharge. Logistic regression analysis was used to evaluate the association between quintile levels of serum HOMA-β and clinical outcomes., Results: The age- and sex-adjusted odds ratios for poor functional outcome and neurological deterioration increased significantly with decreasing HOMA-β levels (P for trend, <0.001 and 0.001, respectively). These associations became more prominent after adjustment for HOMA-insulin resistance and were substantially unchanged even after further adjustment for other confounders, namely, body mass index, dyslipidemia, hypertension, estimated glomerular filtration rate, stroke subtype, National Institutes of Health Stroke Scale score on admission, and reperfusion therapy (odds ratio [95% CI] for the first versus fifth quintile of HOMA-β, 3.30 [2.15–5.08] for poor functional outcome and 10.69 [4.99–22.90] for neurological deterioration). Such associations were not observed for stroke recurrence. In stratified analysis for the combination of HOMA-β and HOMA-insulin resistance levels, lower HOMA-β and higher HOMA-insulin resistance levels were independently associated with increased risks of poor functional outcome and neurological deterioration., Conclusions: Our findings suggest that β-cell dysfunction is significantly associated with poor short-term clinical outcome independently of insulin resistance in nondiabetic patients with acute ischemic stroke.

We describe a confusing case of GATA3-positive adnexal adenocarcinoma with a potential pitfall of leading to a misdiagnosis of urothelial carcinoma. A 62-year-old male presented with a subcutaneous nodule on the right lower abdomen around a scar from surgery for urothelial carcinoma in the right urinary tract, which had been resected 8 years previously. Histologically, atypical cells possessing ample cytoplasm and partial intracytoplasmic lumens were densely grouped in the subcutaneous expansive nodule and bilateral inguinal lymph nodes dissected. Decapitation secretion could not be seen. Neoplastic cells were positive for CK7, GATA3, and GCDFP15, and negative for CK5/6, CK20, p63, CD10, PAX8, HER-2, and uroplakin-II. Neoplastic cells in the urothelium and the metastasized lung were positive for CK7, CK5/6, and GATA3, and negative for CK20, p63, GCDFP15, and TTF-1. A variable level of GATA3 expression in malignant tumors with apocrine and eccrine differentiation should be recognized by dermatologists., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose., (Copyright © 2020 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Directed migration of endothelial cells (ECs) is an important process during both physiological and pathological angiogenesis. The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the EC surface is necessary for directed migration of these cells. Here, we used TAXIScan, an optically accessible real-time horizontal cell dynamics assay approach, and demonstrate that reactive oxygen species (ROS)-producing NADPH oxidase 4 (NOX4), which is abundantly expressed in ECs, mediates VEGF/VEGFR-2-dependent directed migration. We noted that a continuous supply of endoplasmic reticulum (ER)-retained VEGFR-2 to the plasma membrane is required to maintain VEGFR-2 at the cell surface. siRNA-mediated NOX4 silencing decreased the ER-retained form of VEGFR-2, resulting in decreased cell surface expression levels of the receptor. We also found that ER-localized NOX4 interacts with ER-retained VEGFR-2 and thereby stabilizes this ER-retained form at the protein level in the ER. We conclude that NOX4 contributes to the directed migration of ECs by maintaining VEGFR-2 levels at their surface., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Miyano et al.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

A source to efficiently generate multiple indistinguishable single photons in different spatial modes in parallel (multi-photon parallel state) is indispensable for realizing large-scale photonic quantum circuits. "A naive scheme" may be to use a heralding single photon source with an on-off detector set at each of parallel modes and to select the cases where each mode contains one photon at the same time. However, it is also necessary to suppress the probability of generating more than two photons from a single-photon source. For this requirement, serial-parallel conversion and a multiplexed heralded single photon source (HSPS) have been proposed and demonstrated. In this paper, we propose and demonstrate a novel method to produce a multi-photon parallel state efficiently using multiple HSPSs and an N × N active optical switch. As an advantage over the simple combination of a spatial multiplexed HSPS and a serial-parallel converter, our method, called the "unified integration scheme," can generate a multi-photon parallel state with minimized optical losses in the switch. Using a 2 × 2 active optical switch and a fixed delay, we achieve an enhancement factor of 1.59 ± 0.14, compared with a naive scheme using two HSPSs, and better than the factor of 1.46 using the simple combination scheme. Furthermore, we confirm the reduction of multi-photon events to 62 % of that of the naive scheme.

Since 2017, hepatitis A virus (HAV) infection has been an epidemic among men who have sex with men (MSM) in Japan. We have come across 11 MSM patients with hepatitis A who were also infected with HIV. In 1999-2000, we came across 5 HIV-infected patients with hepatitis A. Since the conditions of current HIV-infected patients have changed owing to the recent progress in anti-HIV therapies, we compared clinical features of hepatitis A between patients in 2017-2018 and those in 1999-2000. By comparing the background characteristics of the patients, we found that the CD4/CD8 ratio was significantly higher in the 2017-2018 group. After the onset of hepatitis, peak levels of hepatic transaminases were found to be higher in the 2017-2018 group, suggesting severe hepatocellular damage. In contrast, neither the peak level of total bilirubin nor the nadir of prothrombin time was significantly different among the 2 groups. We also analyzed the HAV genome derived from some of the recently infected patients, and found that the HAV strains were almost the same among these patients; slight differences were observed from the previously identified strain. Thus, we concluded that the recovery of immunity by recent anti-HIV therapies may result in more severe hepatocellular damages and differences in clinical features.

Background: Population immunity against hepatitis B virus (HBV) in Lao People's Demographic Republic (PDR) has not been examined since the national HBV vaccination program was started in 2002. Vaccine has been observed to be frozen at times during cold-chain transport in vaccination programs in Lao PDR and other developing countries, which will inactivate the vaccine. Therefore, this study used post-vaccination serologic testing to evaluate the effects of HBV immunization in Lao PDR., Methods: A cross-sectional serologic study was conducted among children (age range, 5-9 years) and mothers (15-45 years) who were randomly selected using probability-proportional-to-size sampling from central Lao PDR. Blood samples were collected as dried blood spots (DBS) and analyzed using chemiluminescent microparticle immunoassay to detect anti-hepatitis B surface (HBs) titers. We also evaluated the correlation between anti-HBs levels measured in DBS and serum among healthy healthcare workers in Vientiane., Results: Anti-HBs titers from DBS were strongly correlated with serum levels (correlation coefficient = 0.999) in all 12 healthcare workers evaluated. A linear regression model showed that 10 mIU/mL of serum anti-HBs was equivalent to 3.45 mIU/mL (95% CI: 3.06-3.85) of DBS. Among 911 mother-child pairs tested, 171 children had documentation of vaccination. Of the 147 children who had received ≥3 doses of the hepatitis B vaccine, 1 (0.7%) was positive for anti-HBs. The remaining 24 children received the hepatitis B vaccine only twice, once or no dose., Conclusions: The results showed extremely low positivity for anti-HBs among vaccinated children in central Lao PDR. Therefore, post-vaccination serologic testing is important to evaluate population immunity against HBV infection. DBS testing is a potential low-cost tool to evaluating the effectiveness of HBV vaccination programs.

Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII-coated vesicles en route to the cell surface. Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER. In contrast, Sar1 (H79G) effectively inhibits ER-to-Golgi transport of glycoproteins including the Nox5-related oxidase Nox2. The trafficking of Nox2, but not that of Nox5, is highly sensitive to over-expression of syntaxin 5 (Stx5), a t-SNARE required for COPII ER-to-Golgi transport. Thus, Nox2 and Nox5 mainly traffic via the Sar1/Stx5-dependent and -independent pathways, respectively. Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N-glycosylated forms, one complex and one high mannose, in a Sar1/Stx5-dependent and -independent manner, respectively. Nox2 and Nox5 also can use both pathways: a glycosylation-defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1-dependent manner; N-glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1-dependently, albeit mainly as the high-mannose form in a Sar1-independent manner., (© 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Introduction: Anorectal amelanotic melanoma (AAMM) is a rare disease with poor prognosis. A standard treatment strategy for AAMM has not been established., Presentation of Case: We report a case of successful treatment of AAMM with nivolumab. A 67-year-old man was referred for colonoscopy which revealed type I tumor in the rectum. AAMM was diagnosed with immunostaining histopathological biopsy findings. Enhanced computed tomography (ECT) revealed the rectal tumor without distant organ metastasis. We performed laparoscopy-assisted abdominoperineal resection. ECT at three months after surgery revealed liver metastases and right ischial bone metastasis. Although we had started dacarbazine monotherapy, black spots that were suspicious of skin metastases had appeared on systemic skin. Therefore, we started nivolumab therapy. ECT at 3 months after initiation of nivolumab showed shrinkage of liver metastasis. We have continued strict follow-up every 2 months and checked no oncologic progression at 17 months after initiation of nivolumab., Discussion: The anti-PD-1 antibody have improved prognosis of malignant melanoma. However, there are no reports of nivolumab for treatment of AAMM., Conclusions: Our patient is the first reported case of AAMM treated with nivolumab. We consider that nivolumab will be effective for non-cutaneous malignant melanoma., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Heralded single-photon sources (HSPS) are widely used in experimental quantum science because they have negligibly small jitter and can therefore achieve high visibility for quantum interference. However, it is necessary to decrease the photon generation rate to suppress multi-photon components. To address this problem, two methods have been proposed and discussed: spatial (or temporal) source multiplexing and photon-pair number discrimination. Here, we report the experimental realization of a HSPS combining these two methods that can suppress the two-photon probability to 44.2 ± 0.7% of that of a normal HSPS. We also provide a theoretical analysis and a discussion of the effect of combining the two methods, considering a detector cascade as a practical photon number discriminating detector. The experimental results agreed well with the theoretical predictions.

Sri Lanka is one of the intermediate-endemic areas for hepatitis A virus (HAV), and concerns exist about the increasing HAV-susceptible population. In fact, Sri Lanka recorded a large hepatitis outbreak, possibly hepatitis A, around the end of the Sri Lankan war. It included more than 14,000 patients consisting of local residents, internally displaced personnel, and military personnel in the main combat zone. The outbreak had slowed down by October 2009; however, acute viral hepatitis continued to occur sequentially among military personnel. We obtained clinical information and serum samples from 222 patients with acute hepatitis who visited the Military Hospital Anuradhapura between January and September 2010. Samples were subjected to laboratory testing including HAV-immunoglobulin M and genotyping. Most patients (98.2%) were confirmed as having hepatitis A belonging to two subgenotypes: IA and IIIA. We did not observe any differences in clinical or biochemical features among patients with subgenotypes IA and IIIA except for pale stools and upper abdominal discomfort. During the investigation period, we observed a serial outbreak caused by identical HAV strains with an interval in line with that of typical HAV incubation periods. Most patients in the first outbreak were found in the training center, and patients in the second outbreak were found in multiple places where soldiers were assigned after the training center. These findings indicate that a strain of HAV diffused from one place to another along with movement of infected persons among the HAV-susceptible population. HAV vaccination for high-risk groups, such as young soldiers, is necessary., (© The American Society of Tropical Medicine and Hygiene.)

Background: There is limited information regarding the prevalence of hepatitis B in Lao PDR, where the hepatitis disease burden is substantial. Thus, reliable seroprevalence data is needed for the disease, based on probability sampling., Methods: A stratified, multistage, cluster sampling survey of hepatitis B surface antigen (HBsAg) positivity among children aged 5-9 years and their mothers aged 15-45 years was conducted. Participants were selected randomly from the central region of Lao PDR via probability-proportional-to-size sampling. Blood samples were collected onto filter paper and subsequently analyzed using a chemiluminescent microparticle immunoassay., Results: A total of 911 mother-and-child pairs were collected; the seroprevalence of HBsAg was estimated to be 2.1% (95% confidence interval 0.8-3.4%) among children and 4.1% (95% confidence interval 2.6-5.5%) in their mothers after taking into account the sampling design and the weight of each sample. The children's HBsAg positivity was positively associated with maternal infection and being born in a non-health facility, while the maternal infection status was not associated with any background characteristic., Conclusions: Lao PDR has a relatively lower HBsAg prevalence in the general population compared to surrounding countries. To ensure comparability to other countries and to future data, rapid field tests are recommended for a nationwide prevalence survey., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The phagocyte NADPH oxidase Nox2, heterodimerized with p22(phox) in the membrane, is dormant in resting cells but becomes activated upon cell stimulation to produce superoxide, a precursor of microbicidal oxidants. Nox2 activation requires two switches to be turned on simultaneously: a conformational change of the cytosolic protein p47(phox) and GDP/GTP exchange on the small GTPase Rac. These proteins, in an active form, bind to their respective targets, p22(phox) and p67(phox), leading to productive oxidase assembly at the membrane. Although arachidonic acid (AA) efficiently activates Nox2 both in vivo and in vitro, the mechanism has not been fully understood, except that AA induces p47(phox) conformational change. Here we show that AA elicits GDP-to-GTP exchange on Rac at the cellular level, consistent with its role as a potent Nox2 activator. However, even when constitutively active forms of p47(phox) and Rac1 are both expressed in HeLa cells, superoxide production by Nox2 is scarcely induced in the absence of AA. These active proteins also fail to effectively activate Nox2 in a cell-free reconstituted system without AA. Without affecting Rac-GTP binding to p67(phox), AA induces the direct interaction of Rac-GTP-bound p67(phox) with the C-terminal cytosolic region of Nox2. p67(phox)-Rac-Nox2 assembly and superoxide production are both abrogated by alanine substitution for Tyr-198, Leu-199, and Val-204 in the p67(phox) activation domain that localizes the C-terminal to the Rac-binding domain. Thus the "third" switch (AA-inducible interaction of p67(phox)·Rac-GTP with Nox2) is required to be turned on at the same time for Nox2 activation., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Despite the development and availability of hepatitis A virus (HAV) vaccine, HAV infection is still a major cause of acute hepatitis that occasionally leads to fatal liver disease. HAV internal ribosomal entry-site (IRES) is one of the attractive targets of antiviral agents against HAV. The aim of the present study is to evaluate the impact of La, one of the cellular proteins, on HAV IRES-mediated translation and HAV replication., Methods and Findings: We investigated the therapeutic feasibility of siRNAs specific for cellular cofactors for HAV IRES-mediated translation in cell culture. It was revealed that siRNA against La could inhibit HAV IRES activities as well as HAV subgenomic replication. We also found that the Janus kinase (JAK) inhibitors SD-1029 and AG490, which reduce La expression, could inhibit HAV IRES activities as well as HAV replication., Conclusions: Inhibition of La by siRNAs and chemical agents could lead to the efficient inhibition of HAV IRES-mediated translation and HAV replication in cell culture models. La might play important roles in HAV replication and is being exploited as one of the therapeutic targets of host-targeting antivirals.

Background and Purpose: Several risk scores have been developed to predict the stroke risk after transient ischemic attack (TIA). However, the validation of these scores in different cohorts is still limited. The objective of this study was to elucidate whether these scores were able to predict short-term and long-term risks of stroke in patients with TIA., Methods: From the Fukuoka Stroke Registry, 693 patients with TIA were followed up for 3 years. Multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke. The discriminatory ability of each risk score for incident stroke was estimated by using C-statistics and continuous net reclassification improvement., Results: The multivariable-adjusted Cox proportional hazards model revealed that dual TIA and carotid stenosis were both significant predictors for stroke after TIA, whereas abnormal diffusion-weighted image was not. ABCD3 (C-statistics 0.61) and ABCD3-I (C-statistics 0.66) scores improved the short-term predictive ability for stroke (at 7 days) compared with the ABCD2 score (C-statistics 0.54). Addition of intracranial arterial stenosis (at 3 years, continuous net reclassification improvement 30.5%; P<0.01) and exclusion of abnormal diffusion-weighted imaging (at 3 years, continuous net reclassification improvement 24.0%; P<0.05) further improved the predictive ability for stroke risk until 3 years after TIA., Conclusions: The present study demonstrates that ABCD3 and ABCD3-I scores are superior to the ABCD2 score for the prediction of subsequent stroke in patients with TIA. Addition of neuroimaging in the ABCD3 score may enable prediction of long-term stroke risk after TIA.

Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection.

Erythema multiforme is a relatively common skin disorder; the most common cause is herpes simplex infection, but topical sensitivities reportedly also provoke this reaction. We report here a case that progressed to toxic epidermal necrolysis due to contact with ultraviolet (UV)-cured inks. The diagnosis was confirmed by patch tests to acrylates in the UV-cured inks, histopathological studies of the lesions, and positive patch test to 1,6-hexanediol diacrylate.