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ABSTRACT Children with severe atopic dermatitis (AD), refractory to conventional systemic treatment as well as single‐agent biologic and Janus kinase inhibitor (JAKi) such as abrocitinib, currently face a lack of treatment options. In response to this clinical conundrum, we present three cases of severe and refractory pediatric AD successfully managed with combined dupilumab and abrocitinib. These children had exhausted all conventional treatments and had undergone treatment with both dupilumab and abrocitinib individually, as well as dupilumab in conjunction with methotrexate. It was only when the combination of dupilumab and abrocitinib was introduced that they finally achieved noticeable and sustained improvements in disease control. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the intricate relationship between salivary IgA antibody levels to PAc (361–386) (PPA), mutans streptococci colonization, and root caries development in older adults. Materials and Methods: This study included 307 participants aged 76 years residing in Niigata city, Japan. Clinical oral examinations were performed at baseline in 2004 and 1 year later, during which the total number of untreated and treated root caries was assessed using the root decayed, filled tooth (DFT) index. The stimulated saliva samples were collected using the spitting method during the baseline survey. Salivary IgA antibody levels to amino acid residues 361–386 of Streptococcus mutans PAc were quantified using an enzyme‐linked immunosorbent assay. Statistical analyses, including the χ2 test, Mann–Whitney U test, and logistic regressions, were performed to examine the association of increased root DFT with the independent variables. Results: Among the 307 participants (53.1% men), the mean root DFT at baseline was 3.77 ± 3.66, and 36.5% of the study sample exhibited increased root DFT after 1 year with a mean increment of 0.36 ± 0.48. Participants with increase in root DFT after 1 year had significantly higher rates of low PPA levels (≤ 25th percentile) than those without increased root DFT (p = 0.020). Low PPA levels (≤ 25th percentile) were significantly more likely to have an increased risk of root caries development compared with PPA levels > 25th percentile (adjusted OR: 1.88, 95% CI: 1.09–3.25). Conclusion: Low PPA levels and root caries incidence correlated significantly, suggesting that low levels of salivary IgA antibody to PAc (361–386) may serve as a risk factor for increased root caries in older adults. [ABSTRACT FROM AUTHOR]

Image processing using traditional photogrammetric methods is a labor‐intensive process. The collection of photogrammetry images during aerial surveys is expanding rapidly, creating new challenges to analyze images promptly and efficiently, while reducing human error during processing. Computer vision‐assisted photogrammetry, a field of artificial intelligence (AI), can automate image processing, greatly enhancing the efficiency of photogrammetry. Here, we present a practical and efficient program capable of automatically extracting the fine‐scale photogrammetry of East Asian finless porpoises (Neophocaena asiaeorientalis sunameri). Our results indicated that computer vision‐assisted photogrammetry could achieve the same accuracy as traditional photogrammetry, and the results of the comparisons were validated against the direct measurements. Three‐dimensional (3D) models using computer vision‐assisted photogrammetric morphometrics generated trustworthy body volume estimates. We also explored the one image‐based 3D modeling technique, which is less accurate, but still useful when only one image of the animal is available. Although several limitations exist in the current program, improvements could be made to narrow the virtual‐reality gap when more images are available for machine learning and training. We recommend this program for analyzing images of marine mammals possessing a similar morphological contour. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the dental caries status of indicator age groups as mentioned in the WHO pathfinder methodology, compare caries experiences among those age groups according to gender and geographical location, and assess the association between dental caries and related risk factors in primary and permanent dentition. Methods: A sample of 5928 participants aged 6, 12, 15–18, 35–44 and 60–74 years were recruited from 21 selected townships in the first Myanmar national oral health survey. Clinical oral examinations and questionnaire‐based surveys were conducted from December 2016 to January 2017. Results: The prevalence of dental caries in primary teeth was 85.3% with a mean dmft of 5.7 at age 6 years. The prevalence of dental caries in permanent teeth and mean DMFT were 36.5% and 0.8 at 12 years, 43.8% and 1.1 at 15–18 years, 64.7% and 3.0 at 35–44 years, and 93.6% and 11.5 at 60–74 years. Missing teeth were higher in 60–74‐year‐olds, with 27 participants being fully edentulous. There were significant differences in caries experiences between males and females aged 15–18, 35–44 and 60–74 years. In the adjusted logistic regression, consumption of sweets or candies three times or more a day showed significantly higher risks of dental caries in primary teeth. Age, gender, consumption of sweets or candies and consumption of sweet drinks were associated factors for dental caries in permanent teeth. Conclusion: The findings from the first national oral health survey indicate that caries in primary teeth is an important oral health problem for Myanmar children. Tooth loss was also found to be a concern in the aging population. National oral health policies and strategies need to be developed to promote awareness and understanding of oral health, in particular the role of risk factors such as sugary foods and drinks in tooth decay in children and adults. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin‐23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis. Objective: To evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo‐controlled, double‐blind, proof‐of‐concept study was conducted. Methods: Patients ≥18 years of age with moderate‐to‐severe HS for ≥1 year were randomized to (1) guselkumab 200 mg by subcutaneous (SC) injection every 4 weeks (q4w) through Week 36 (guselkumab SC); (2) guselkumab 1200 mg intravenously (IV) q4w for 12 weeks, then switched to guselkumab 200 mg SC q4w from Weeks 12 through 36 (guselkumab IV); or (3) placebo for 12 weeks, with re‐randomization to guselkumab 200 mg SC q4w at Weeks 16 through 36 (placebo → guselkumab 200 mg) or guselkumab 100 mg SC at Weeks 16, 20, 28 and 36 and placebo at Weeks 24 and 32 (placebo → guselkumab 100 mg). End points included HS clinical response (HiSCR) and patient‐reported outcomes. Results: Although guselkumab SC or guselkumab IV resulted in numerically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%, respectively), statistical significance was not achieved. Numerically greater improvements in patient‐reported outcomes were also observed for guselkumab SC and guselkumab IV versus placebo at Week 16. Through Week 40, no clear differences to suggest a dose response were observed for HiSCR and patient‐reported outcomes. Conclusions: Despite modest improvements, the primary end point was not met and the overall findings do not support the efficacy of guselkumab in the treatment of HS. Clinicaltrials.gov: NCT 03628924. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the effects of socioeconomic, behavioral, and psychological factors on oral health status and oral health‐related quality of life in Myanmar adults. Methods: Data were from a convenience sample of Myanmar adults who are from a township health center in Yangon city. Face‐to‐face interviews using a paper‐based questionnaire in the Myanmar language and clinical oral examinations were performed at the health center. Mann–Whitney U test and linear regressions were used to assess the association of socio‐demographic, behavioral, and psychological variables with oral health outcomes. Results: In socio‐demographic variables, significant associations were observed in individual income with periodontal pocket and OHIP‐14, and history of COVID‐19 infection with OHIP‐14. However, there were no associations between behavioral factors and oral health outcomes. After adjustment for sex, age, educational level, and individual income, the depression subscale was statistically significant with the number of present teeth, decayed teeth, decayed, missing, and filled teeth, and OHIP‐14. The anxiety subscale remained significant with periodontal pocket, but no stress subscale was associated with oral health outcomes. Conclusion: The experiences of oral health status were high, and the oral health‐related quality of life was unfavorable in Myanmar adults. A large proportion of them suffers from psychological distress. Additionally, individuals with lower income and who experienced a history of COVID‐19 infection were susceptible to poor oral health‐related quality of life. Psychological distress indicates a higher risk for oral health problems in Myanmar adults. [ABSTRACT FROM AUTHOR]

Panax notoginseng saponins (PNS), the active ingredients of the traditional Chinese medicine Panax notoginseng, have strong neuroprotective and anti‐platelet aggregation effects. To investigate whether PNS can promote hair follicle growth in C57BL/6J mice, the optimal concentration of PNS was initially determined, followed by clarification of the mechanism underlying their effects. Twenty‐five male C57BL/6J mice had the hair on a 2 × 3 cm2 area of the dorsal skin shaved and were equally divided into five groups: control group, 5% minoxidil (MXD) group, and three PNS treatment groups [2% (10 mg/kg), 4% (20 mg/kg), and 8% (40 mg/kg) PNS]. They were then intragastrically administered the corresponding drugs for 28 days. The effects of PNS on C57BL/6J mice were analyzed by subjecting their dorsal depilated skin samples to different assessments, including hematoxylin and eosin staining, immunohistochemistry, immunofluorescence, quantitative real‐time polymerase chain reaction (qRT‐PCR), and Western blotting (WB). The group with 8% PNS exhibited the largest number of hair follicles from 14 days onwards. Compared with the control group, the number of hair follicles increased significantly in the mice treated with 8% PNS and 5% MXD, which significantly increased in a PNS‐dose‐dependent manner. Immunohistochemistry and immunofluorescence results revealed that treatment with 8% PNS activated the metabolism of hair follicle cells, with them showing higher rates of proliferation and apoptosis than those in the normal group. In qRT‐PCR and WB analysis, the expression of β‐catenin, Wnt10b, and LEF1 was upregulated in the PNS and MDX groups compared with that in the control group. Examination of the WB bands revealed that the greatest inhibitory effect of Wnt5a occurred in mice in the 8% PNS group. PNS may promote the growth of hair follicles in mice, with 8% PNS demonstrating the strongest effect. The mechanism behind this may be related to the Wnt/β‐catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross‐tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time‐series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health. Plain Language Summary: Desert dust and dust storms are recurring environmental phenomena and have been reported to cause serious health hazards worldwide. A scoping review was conducted of the existing epidemiological literature to identify and categorize the methods used to characterize desert dust exposure and the most likely health effects of desert dust and dust storms. We identified 204 studies that met the inclusion criteria for the scoping review. More than half (52.9%) of the studies employed time series and case‐crossover study designs; 84.8% reported a significant association between desert dust and adverse health outcomes. Although most studies reported adverse health effects, existing studies have significant limitations in exposure measurement and statistical analysis, which may lead to inconsistencies in determining the health effects of desert dust. Key Points: Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwideInconsistencies in exposure definitions and modeling strategies may have contributed to the observed heterogeneity in the effect estimatesDeveloping a standardized research protocol could be a vital step toward better assessing the association between desert dust and health [ABSTRACT FROM AUTHOR]

Reducing sodium content in foods is an important public health measure to reduce salt intake and decrease the incidence of noncommunicable diseases, such as cardiovascular disease and chronic kidney disease. This study quantified the amount of salt intake that could potentially be reduced by using umami substances, including glutamate, inosinate, and guanylate, without compromising taste, for adults in the United Kingdom (UK). We used data comprised of 1834 adults aged 20 years and over from the National Diet and Nutrition Survey (NDNS RP) 2016/2017–2018/2019. Four hypothetical scenarios in which the market share of low‐sodium foods accounts for 0%, 30%, 60%, or 90% of consumed products were considered in the analyses. Per capita daily salt intake corresponding to the NDNS RP food groups was calculated for each scenario, and the salt intake was aggregated by gender and age groups. Replacing salt with umami substances could help UK adults reduce daily salt intake by 9.09%–18.59% (9.21%–18.43% for women; 8.83%–19.43% for men), which is equivalent to 0.45–0.92 g/day of salt reduction (0.41–0.82 g/day for women; 0.50–1.10 g/day for men). The use of umami substances may serve as one method for the UK government to encourage salt intake reduction, particularly in the context of food product reformulation, as 80% of salt consumed in the country comes from processed foods. Empirical studies with sensory evaluation should be conducted to confirm consumer tolerance. The food industry should also be engaged in conversations regarding the addition of umami to food products in the United Kingdom. [ABSTRACT FROM AUTHOR]

Rab11a, which ubiquitously localizes to early and recycling endosomes, is required for regulating the vesicular transport of cellular cargos. Interestingly, our previous study revealed that Rab11a served as a negative regulator of osteoclastogenesis by facilitating the lysosomal proteolysis of (1) colony‐stimulating factor‐1 (c‐fms) receptor and (2) receptor activator of nuclear factor‐κB (RANK) receptor, thereby resulting in inhibition of osteoclast (OC) differentiation, maturation, and bone‐resorbing activity. However, the molecular mechanisms of how Rab11a negatively affected osteoclastogenesis were largely unknown. Heat shock protein (HSP90), including two isoforms HSP90α and HSP90β, necessitates the stability, maturation, and activity of a broad range of its clients, and is essentially required for a vast array of signal transduction pathways in nonstressful conditions. Furthermore, cumulative evidence suggests that HSP90 is a vital element of the vesicular transport network. Indeed, our recent study revealed that HSP90, a novel effector protein of Rab11b, modulated Rab11b‐mediated osteoclastogenesis. In this study, we also found that Rab11a interacted with both HSP90α and HSP90β in OCs. Upon blockade of HSP90 ATPase activity by a specific inhibitor(17‐allylamino‐demethoxygeldanamycin), we showed that (1) the ATPase domain of HSP90 was a prerequisite for the interaction between HSP90 and Rab11a, and (2) the interaction of HSP90 to Rab11a sufficiently maintained the inhibitory effects of Rab11a on osteoclastogenesis. Altogether, our findings undoubtedly indicate a novel role of HSP90 in regulating Rab11a‐mediated osteoclastogenesis. Significance statement: Increasing evidence elucidates that Rab GTPases play a central role in regulating the vesicular transport of subcellular cargos and osteoclastogenesis. Of these, Rab11a was shown to negatively regulate osteoclastogenesis mainly via controlling lysosome‐induced proteolysis of cell surface receptors, c‐fms, and receptor activator of nuclear factor‐κB (RANK) in OCs. Nevertheless, the specific mechanisms underlying the Rab11a‐mediated regulation of osteoclastogenesis are obscure. In this study, we, for the first time, revealed that heat‐shock protein 90 (HSP90) served as a novel effector protein of Rab11a. HSP90 interacted with Rab11a and regulated Rab11a's physiological functions in this process. Specifically, HSP90 accelerated the lysosome‐induced proteolysis of c‐fms and RANK surface receptors, subsequently abolishing c‐fos/nuclear factor of activated T‐cell cytoplasmic‐1 signaling pathways, deteriorating OC differentiation, maturation, and bone resorption, thereby contributing to the dynamic regulation of bone remodeling. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that Rab GTPases representing the largest branch of Ras superfamily have recently emerged as the core factors for the regulation of osteoclastogenesis through modulating vesicular transport amongst specific subcellular compartments. Among these, Rab34 GTPase has been identified to be important for the post‐Golgi secretory pathway and for phagocytosis; nevertheless, its specific role in osteoclastogenesis has been completely obscure. Here, upon the in vitro model of osteoclast formation derived from murine macrophages like RAW‐D cells or bone marrow–derived macrophages, we reveal that Rab34 regulates osteoclastogenesis bidirectionally. More specifically, Rab34 serves as a negative regulator of osteoclast differentiation by promoting the lysosome‐induced proteolysis of two osteoclastogenic surface receptors, c‐fms and RANK, via the axis of early endosomes‐late endosomes–lysosomes, leading to alleviate the transcriptional activity of two of the master regulator of osteoclast differentiation, c‐fos and NFATc‐1, eventually attenuating osteoclast differentiation and bone resorption. Besides, Rab34 plays a crucial role in modulating the secretory network of lysosome‐related proteases including matrix metalloprotease 9 and Cathepsin K across the ruffled borders of osteoclasts, contributing to the regulation of bone resorption. Significance statement: Rab GTPases have emerged as the spatiotemporal regulators of intracellular vesicular transport. Molecular mechanisms illuminating the specific roles of Rab34 in regulating osteoclastogenesis remain elusive. In our current study, Rab34 has been substantiated as a regulatory intermediator of osteoclastogenesis via (1) modulating the abundance of cell surface receptors, c‐fms and RANK receptors, and (2) directing the lysosome movement to ruffled borders of osteoclasts for the secretion of lysosomal proteases including metalloprotease 9 and Cathepsin K. This study has further provided new insights into the regulatory roles of osteoclastogenesis via functional interrelated cooperation of Rab GTPases, at least Rab34, and lysosomes to direct process of bone resorption. [ABSTRACT FROM AUTHOR]

Introduction: Myanmar is a Low‐Middle Income Country (LMIC) in South‐East Asia. Over the last decade, reforms to the health system have included significant improvements in the delivery of radiation therapy services in both government and private‐for‐profit sectors. Methods: This review uses limited cancer registry data, observations from in‐person visits, and data from key informants in Myanmar radiation therapy centres, to report on developments in radiation therapy services in recent years. Results: Rising national cancer incidence estimates presented in this article are supplemented with annual cancer case and radiation therapy course completion statistics from three hospital / regional contexts. Strategies which enabled the increased delivery of radiation therapy services are described. Data regarding the geographic locations of radiation therapy centres, their equipment and software inventories, is tabulated. The impact on clinical practice standards through upgraded equipment and software used for treatment planning and delivery is discussed. Clinical staffing at each centre is catalogued, role descriptions are given, and increases in staff numbers in recent years are documented. The present clinical and academic education challenges for radiation therapy staff and the importance of these issues for technical practice advancements are discussed. Conclusion: Myanmar's successes and continued challenges in radiation therapy service delivery are emulated in other LMIC's. Strategic planning for new and existing radiation therapy centres, further staff increases and improved academic and clinical learning for radiation therapy staff should assist in meeting these challenges. Further international engagement could also enhance these processes. [ABSTRACT FROM AUTHOR]

A number of empirical studies document that people tend to become more risk averse as they get older. But other studies find only little evidence that age matters for financial risk attitudes. This prompts a call for revisiting the relationship between age and risk attitude to better support policy recommendations. The current paper contributes to this effort by utilising large‐scale population data to conduct a dynamic panel analysis. Care is taken to avoid the problem of endogeneity of lagged risk attitude in modelling its effects. Analysis reveals that individuals' past risk attitude has a positive effect on their current risk attitude. However, there is only little evidence that risk attitude and age are systematically related. Our results shed some light on the previous contradictory empirical findings in the literature and suggest that past risk attitude is potentially of greater relevance than chronological age in determining current risk attitude. [ABSTRACT FROM AUTHOR]

Summary: Objective: To determine the incidence of post‐stroke seizures and the associated risk factors in a government‐restructured hospital in Singapore. Methods: This retrospective study included consecutive patients (age ≥21 years) admitted to the stroke rehabilitation facility at Changi General Hospital, Singapore, between June 2008 and May 2017, with a minimum post‐discharge follow‐up of 6 months. Patients with known epilepsy central nervous system infection or tumor, a history of neurosurgery and or missing data were excluded from study. To determine the incidence of seizures, the patients’ hospital records, including those for all initial and subsequent admissions and outpatient follow‐ups, were reviewed. All prescribed medications were checked and documented. Seizures were diagnosed on the basis of clinical examination with or without electroencephalography. Results: In total, 722 patients (women, 38%) with a mean age of 64 years were included. Of these, 48 (6.64%) experienced post‐stroke seizures during a follow‐up period of 6–108 months. The incidence of seizures was significantly higher in patients with hemorrhagic stroke (42%, p = 0.010), those with ischemic partial anterior circulation stroke (PACS) (27%, p = 0.025), those who underwent a neurosurgical procedure after stroke (p < 0.001), those with a low activated partial thromboplastin time (APTT) at admission (mean, 25.6; p = 0.015), and those using levodopa (21%, p < 0.001). Neurosurgical intervention after stroke (odds ratio [OR] 6.2, 95% confidence interval [CI] 2.9–13.1; p < 0.001), APTT (per‐unit increase; OR 0.86, 95% CI 0.76–0.98; p = 0.028), and underlying ischemic heart disease (IHD; OR 2.2, 95% CI 1.08–4.60; p = 0.029) were found to be independent predictors of seizure occurrence after stroke. Significance: Post‐stroke seizure incidence from our study is 6.64%, with a median follow‐up of 49 months. Among patients with stroke, those with underlying IHD, those who undergo a neurosurgical procedure, and those with a low APTT at admission need careful monitoring. Levodopa should be used with caution and withdrawn as soon as possible. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of the present study was to investigate the effects of oral health education on preschool children’s oral health status and habits, and their guardian’s oral health knowledge. Methods: A 1‐year interventional study was conducted for 201 preschool children from January 2016 to January 2017. A questionnaire survey and clinical oral examination were performed at baseline and at 1‐year follow up. A 30‐min oral health education session was given to children and their teachers and guardians separately by a dentist every 6 months. The impact of health education was evaluated by assessing the changes in guardians’ questionnaires and children’s oral health status during the 1‐year period. Results: The mean oral health knowledge scores of guardians significantly increased from 8.0 ± 2.0 at baseline to 9.0 ± 2.5 at 1‐year follow up (P < .001). Most oral health habits, except drinking water after eating, significantly improved at 1‐year follow up. Significant decreases in debris score (P = .008) and gingival score (P < .001) were found. Conclusion: Comprehensive oral health education was shown to improve guardians’ knowledge of oral hygiene, and oral health habits and status of their children. It is necessary to adopt a comprehensive oral health‐promotion program involving oral health‐care professionals, parents, and teachers. [ABSTRACT FROM AUTHOR]

Introduction: Global effort to increase early diagnosis and engagement in HIV care emphasize the importance of developing novel approaches to reaching those missed by traditional methods. Such needs are particularly great for men who have sex with men (MSM), transgender women (TW), and other populations who face stigma. Myanmar's HIV epidemic is concentrated among key populations and the revised National Strategy aims to reduce late diagnosis and barriers to care to curb HIV incidence among these groups. HIV self-testing (HIVST) may be one method to improve testing and diagnosis among key populations, by placing HIV testing and disclosure within the individual's control. Methods: Formative, qualitative research including in-depth interviews with adult MSM (N = 12) and TW (N = 13) and focus group discussions with MSM, TW, and community key informants (N = 35) were conducted in June-September 2015 in Yangon, Myanmar. To inform a subsequent HIV care continuum intervention, including HIVST, participants' opinions and perceptions about HIVST were elicited. Results: The confidentiality and privacy of HIVST, particularly as it related to disclosure of HIV status and sexual behaviour, was widely recognized among participants. These major advantages were further supported by the opportunity to avoid stigma, convenience of self-testing (reduced need for transportation and time to go to clinics), and the availability of a painfree testing option. Participants weighed these benefits against perceived disadvantages of HIVST, the majority of which centred on the perception that HIVST does not include counselling. Participants were concerned that potential lack of counselling would result in poor mental health outcomes, inadequate linkage to HIV care and surveillance, and reductions in disclosure of HIV status. Participants did not view these disadvantages as an impediment, but provided suggestions for future implementation of HIVST in Myanmar. Conclusions: MSM and TW are optimistic about the confidentiality and privacy afforded by HIVST but wanted HIV counselling and linkage to appropriate services. The domestic reprioritization of HIV and opening of the country to international support has substantially increased the availability of HIV treatment and provides new opportunities, like HIVST, to potentially improve the HIV response for key populations who are at risk for HIV acquisition. [ABSTRACT FROM AUTHOR]

The transporter associated with antigen processing 2 (TAP2) gene is involved in the immunological response to tuberculosis (TB) infection. Variations in the TAP2 gene have been associated with TB infection in small population studies in India, Columbia, and Korea. We investigated the association of TAP2 polymorphisms with TB susceptibility in an elderly Japanese population. We analyzed samples from consecutive autopsy cases (n = 1850) registered in the Japanese Geriatric SNP Research database. TB was diagnosed pathologically by TB granuloma on autopsy samples. There were 289 cases and 1529 controls. Twenty-four single nucleotide variations (SNVs), including four missense variations in the TAP2 region, were genotyped using the Illumina Infinium Human Exome BeadChip array. Of the 24 SNVs in the TAP2 gene, rs4148871, rs4148876 (R651C), and rs2857103 showed statistically significant associations with TB susceptibility, and rs4148871 and rs2857103 also showed significant genotypic associations in a dominant allele model adjusted for age, sex, and smoking. Haplotype analysis showed that TAP2 allele *0103 conferred an increased TB risk (OR = 1.48, p = 0.0008), while the TAP2 *0201 allele was protective against TB (OR = 0.73, p = 0.0007). Our results suggest that TAP2 polymorphisms influence TB susceptibility in a Japanese population. [ABSTRACT FROM AUTHOR]

Background Infection is the most common cause of mortality in end-stage liver disease ( ESLD). The impact of obesity on infection risk in ESLD is not established. Aim To characterise the impact of obesity on infection risk in ESLD. Methods We evaluated the association between infection and obesity in patients with ESLD. Patients grouped as non-obese, obesity class I- II and obesity class III were studied using the Nationwide Inpatient Sample. Validated diagnostic code based algorithms were utilised to determine weight category and infections, including bacteraemia, skin/soft tissue infection, urinary tract infection ( UTI), pneumonia/respiratory infection, Clostridium difficile infection ( CDI) and spontaneous bacterial peritonitis ( SBP). Risk factors for infection and mortality were assessed using multivariable logistic regression analysis. Results Of 115 465 patients identified, 100 957 (87.5%) were non-obese and 14 508 (12.5%) were obese, with 9489 (8.2%) as obesity class I- II and 5019 (4.3%) as obesity class III. 37 117 patients (32.1%) had an infection diagnosis. Infection was most prevalent among obesity class III (44.0%), followed by obesity class I- II (38.9%) and then non-obese (31.9%). In multivariable modelling, class III obesity ( OR = 1.41; 95% CI 1.32-1.51; P < 0.001), and class I- II obesity ( OR = 1.08; 95% CI 1.01-1.15; P = 0.026) were associated with infection. Compared to non-obese patients, obese individuals had greater prevalence of bacteraemia, UTI, and skin/soft tissue infection as compared to non-obese patients. Conclusions Obesity is newly identified to be independently associated with infection in end-stage liver disease. The distribution of infection sites varies based on weight category. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with the case of an 81 year old man with hypertension and dementia who presented to an emergency department with gastric ulcer bleeding caused by press through medication packaging which had been mis-swallowed.

Spatial suppression of peripheral lipid-containing regions in volumetric MR spectroscopic imaging of the human brain requires placing large numbers of outer volume suppression (OVS) slices, which is time-consuming, prone to operator error and may introduce subject-dependent variability in volume coverage. We developed a novel, computationally efficient atlas-based approach for automated positioning of up to 16 OVS slices and the MR spectroscopic imaging slab. Standardized positions in Montreal Neurological Institute atlas space were established offline using a recently developed iterative optimization procedure. During the scanning session, positions in subject space were computed using affine transformation of standardized positions in Montreal Neurological Institute space. Offline analysis using magnetization prepared rapid gradient echo scans from 11 subjects demonstrated reliable OVS placement, comparable with but faster than iterative placement in subject space. This atlas-based method was further validated in 14 subjects using 3D short-echo time proton-echo-planar-spectroscopic-imaging at 3 T. Comparison of manual and automatic placement using 8 OVS slices demonstrated consistent MR spectroscopic imaging volume selection and comparable spectral quality with similar degree of lipid suppression and number of usable voxels. Automated positioning of 16 OVS slices enabled larger volume coverage, while maintaining similar spectral quality and lipid suppression. Atlas-based automatic prescription of short echo time MR spectroscopic imaging is expected to be advantageous for longitudinal and cross-sectional studies. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A safe and efficient method was developed for the dibromination of pyrazolones and 5-hydroxypyrazoles by use of dibromoisocyanuric acid (DBI). The reaction gave the corresponding dibrominated pyrazolones in excellent yields (≥91%). J. Heterocyclic Chem., (2010). [ABSTRACT FROM AUTHOR]

A “one-pot” method for the synthesis of N-(1,3-diphenyl-1H-pyrazol-5-yl)amides was developed by cyclization of benzoylacetonitrile (1) and phenylhydrazine in neat condition followed by acylation. The corresponding N-(1,3-diphenyl-1H-pyrazol-5-yl)amides were provided in good to excellent yields (70–90%). The significant advantages of the new synthetic method are excellent yields and simple work-up procedure without isolation and purification of intermediary 5-amino-1,3-diphenyl pyrazol (2). J. Heterocyclic Chem., (2010). [ABSTRACT FROM AUTHOR]

Spatial suppression of peripheral regions (outer volume suppression) is used in MR spectroscopic imaging to reduce contamination from strong lipid and water signals. The manual placement of outer volume suppression slices requires significant operator interaction, which is time consuming and introduces variability in volume coverage. Placing a large number of outer volume saturation bands for volumetric MR spectroscopic imaging studies is particularly challenging and time consuming and becomes unmanageable as the number of suppression bands increases. In this study, a method is presented that automatically segments a high-resolution MR image in order to identify the peripheral lipid-containing regions. This method computes an optimized placement of suppression bands in three dimensions and is based on the maximization of a criterion function. This criterion function maximizes coverage of peripheral lipid-containing areas and minimizes suppression of cortical brain regions and regions outside of the head. Computer simulation demonstrates automatic placement of 16 suppression slices to form a convex hull that covers peripheral lipid-containing regions above the base of the brain. In vivo metabolite mapping obtained with short echo time proton-echo-planar spectroscopic imaging shows that the automatic method yields a placement of suppression slices that is very similar to that of a skilled human operator in terms of lipid suppression and usable brain voxels. Magn Reson Med 63:592-600, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Chromoblastomycosis is one of several chronic infectious skin diseases caused by various species of dematiaceous fungi. It is clinically characterized by verrucous skin eruptions and occurs most commonly in tropical and subtropical regions. In Okinawa, a subtropical area, there have been only three reported cases of chromoblastomycosis including the present one. Direct microscopic examination of crust specimens and findings of sclerotic cells in histopathology can confirm the diagnosis, and cultures of crust and/or tissue specimens can identify the causative fungi. We herein report the third case of chromoblastomycosis in Okinawa; it arose in an 87-year-old Japanese woman with a history of Hansen's disease, who lived in a leprosarium in Miyako Island. To identify the causative agent as Fonsecaea pedrosoi, we used the polymerase chain reaction and direct sequencing analysis in addition to the usual methods, which include 20% potassium hydroxide microscopy, histopathological confirmation of sclerotic cells by periodic acid-Schiff stain, culture by Sabouraud's glucose agar, slide culture method, and observation of conidia by scanning electron microscopic examination. [ABSTRACT FROM AUTHOR]

The exact species and/or strains of Leishmania parasites involved strongly influence the clinical and epidemiological features of leishmaniasis, and current knowledge of those influences and relationships is inadequate. We report that cytochrome b ( cyt b) gene sequencing identified causal Leishmania parasites of 69 cutaneous leishmaniasis cases in Pakistan over a 3-year period. Of 21 cases in highland areas (Quetta city, Balochistan province), 16 (76.2%) were identified as Leishmania (L.) tropica and five (23.8%) as Leishmania (L.) major. Of 48 cases from lowland areas, cities/villages in Indus valley in Sindh and Balochistan provinces, 47 (97.9%) were identified as L. (L.)  major and one (2.1%) as L. (L.)  tropica. Statistical analysis (Fisher's exact test) revealed a significant difference ( P < 0.0001) in the distribution of the two species by altitude; L. (L.) major is predominant in lowland and L. (L.)  tropica at highland areas. The present result enriched our earlier finding, based on the first year's cultured parasite data, that only L. (L.)  tropica was found in highland areas and only L. (L.)  major in lowland areas. Among Leishmania samples analyzed, three types of cyt b polymorphism of L. (L.)  major were found, including 45 (86.5%) cases of type I, six (11.5%) of type II and one (2%) of type III. We report for the first time on the presence of polymorphisms in L. (L.)  major (types I, II and III) based on species identification using cyt b gene sequencing from clinical samples. Moreover, we found no correlation between clinical presentation (wet-, dry- and/or mixed-types of cutaneous lesions) and causal Leishmania parasites. [ABSTRACT FROM AUTHOR]

To investigate, in an initial study, the use of microarray analysis (MA) to develop an information base for urolithiasis. MA enables the screening of thousands of genes simultaneously making it the technique of choice for situations where the results are known, but the underlying mechanisms are not. Little is known about the pathological changes occurring in the kidney during urolithiasis and this has severely hampered efforts to develop effective therapeutics. Male rats were treated with 0.75% ethylene glycol for 2, 4 or 8 weeks; after death the kidneys were processed for RNA isolation and MA, conducted using a rat-based chip (one kidney/chip) and the results confirmed by reverse transcription-polymerase chain reaction (RT-PCR, 21 probe sets; control, four rats; treated, five rats). Targets were defined as different by the software if the fold change (FC) was ≥ 2, and sorted into functional categories using a data-mining tool. The repeatability of MA was investigated by subjecting the 4-week samples to MA in two independent runs. The results for targets with a FC of ≥ 2 were plotted ( y = 1.01 x − 0.75; r2 0.84). Comparing the results obtained by RT-PCR and MA showed a good qualitative correlation for those targets having a FC of ≥ 5 as determined by MA. Changes in the expression of genes associated with tubule function and regulation, oxidative damage, and inflammation were the most common in the functional categories. Changes in the expression of tubule-specific markers indicated that there was damage to the proximal (γ-adducin, organic anion and cation transporters, sodium-hydrogen exchange protein-isoform 3) and distal tubules (γ-adducin, kallikrein) at 2 and 4 weeks. Increased expression of mitochondrial uncoupling protein indicated that there were changes to the mitochondria and oxidative stress at 2 and 4 weeks. This study shows the power of MA as an exploratory technique, and changes in the expression of several physiologically important genes whose expression has not previously been reported to be affected by hyperoxaluria or calcium oxalate crystalluria. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the airway dimension of simple snorers and subjects with obstructive sleep apnea (OSA) in a Far-East Asian population (Chinese). Study Design: Prospective study of 117 near-consecutive patients evaluated for snoring and possible OSA from January 1998 to December 1998 in a sleep laboratory. Overnight polysomnography (PSG) was performed on all patients and the sleep parameters, including respiratory disturbance index (RDI), snoring index, minimal oxygen saturation (min O2), percentage of slow wave sleep (SWS), and rapid eye movement (REM) were recorded. Three-dimensional computerized tomography (CT) during awake periods was performed. The anteroposterior (AP) and the lateral distance of the retropalatal (RP) region in the oropharynx, the smallest area of RP, and retroglossal (RG) regions, and the total volume of the oropharynx were measured. Result: Ninety-eight patients were diagnosed with OSA (mean RDI, 41.48 +/- 26.45 events per hour; min O2, 72.82 +/- 12.86%), whereas 19 were simple snorers. The AP and the lateral distance of the RP region, as well as the smallest area of the RP region, are significantly smaller in subjects with OSA. However, no differences in the RG region and the total volume of the oropharynx were found between the two groups. Linear regression analysis demonstrated that the lateral dimension and the smallest RP area in overweight subjects inversely correlated with the RDI, but only the AP dimension of the RP area was found to have an inverse correlation with the RDI in the underweight subjects. Conclusion: In Far-East Asians (Chinese), the RP airway was found to be the primary site of narrowing in subjects with OSA, and the narrowest RP area was inversely correlated with RDI. Furthermore, weight may influence the pattern of RP narrowing by contributing to lateral collapse. [ABSTRACT FROM AUTHOR]

The effects of 5 μg/ml of 25-hydroxycholesterol; cholestane-3β, 5α,6β-triol; and cholesterol on acyl CoA cholesterol acyltransferase, acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase was studied in cultured rabbit aortic smooth muscle cells. After 1 hour incubation, 25-hydroxycholesterol resulted in a fourfold stimulation of acyl CoA cholesterol acyltrans-ferase activity. No stimulation by 25-hydroxycholesterol was noted before 15 minutes or after 5 hours of incubation. Neither cholestane-3β,5α,6β-triol nor cholesterol influenced acyl CoA cholesterol acyltransferase activity at any time interval. No significant effects of any of the sterols were noted on acid cholesteryl ester hydrolase or neutral cholesteryl ester hydrolase activity. The imbalance between acyl CoA cholesterol acyl trans-ferase and hydrolase activities induced by 25-hydroxycholesterol could result in cholesteryl ester accumulation by arterial smooth muscle cells, which may be associated with atherosclerosis. [ABSTRACT FROM AUTHOR]