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We compared appendiceal visualization on 2-mSv CT vs. conventional-dose CT (median 7 mSv) in adolescents and young adults and analyzed the undesirable clinical and diagnostic outcomes that followed appendiceal nonvisualization.A total of 3074 patients aged 15-44 years (mean ± standard deviation, 28 ± 9 years; 1672 female) from 20 hospitals were randomized to the 2-mSv CT or conventional-dose CT group (1535 vs. 1539) from December 2013 through August 2016. A total of 161 radiologists from 20 institutions prospectively rated appendiceal visualization (grade 0, not identified; grade 1, unsure or partly visualized; and grade 2, clearly and entirely visualized) and the presence of appendicitis in these patients. The final diagnosis was based on CT imaging and surgical, pathologic, and clinical findings. We analyzed undesirable clinical or diagnostic outcomes, such as negative appendectomy, perforated appendicitis, more extensive than simple appendectomy, delay in patient management, or incorrect CT diagnosis, which followed appendiceal nonvisualization (defined as grade 0 or 1) and compared the outcomes between the two groups.In the 2-mSv CT and conventional-dose CT groups, appendiceal visualization was rated as grade 0 in 41 (2.7%) and 18 (1.2%) patients, respectively; grade 1 in 181 (11.8%) and 81 (5.3%) patients, respectively; and grade 2 in 1304 (85.0%) and 1421 (92.3%) patients, respectively (The use of 2-mSv CT instead of conventional-dose CT impairs appendiceal visualization in more patients. However, appendiceal nonvisualization on 2-mSv CT rarely leads to undesirable clinical or diagnostic outcomes.

Superoxide dismutase 3 (SOD3), also known as extracellular superoxide dismutase, is an enzyme that scavenges reactive oxygen species (ROS). It has been reported that SOD3 exerts anti-inflammatory abilities in several immune disorders. However, the effect of SOD3 and the underlying mechanism in inflammatory bowel disease (IBD) have not been uncovered. Therefore, in the present study, we investigated whether SOD3 can protect intestinal cells or organoids from inflammation-mediated epithelial damage. Cells or mice were treated with SOD3 protein or SOD3-transduced mesenchymal stem cells (MSCs). Caco-2 cells or intestinal organoids stimulated with pro-inflammatory cytokines were used to evaluate the protective effect of SOD3 on epithelial junctional integrity. Dextran sulfate sodium (DSS)-induced colitis mice received SOD3 or SOD3-transduced MSCs (SOD3-MSCs), and were assessed for severity of disease and junctional protein expression. The activation of the mitogen-activated protein kinase (MAPK) pathway and elevated expression of cytokine-encoding genes decreased in TNF-α-treated Caco-2 cells or DSS-induced colitis mice when treated with SOD3 or SOD3-MSCs. Moreover, the SOD3 supply preserved the expression of tight junction (ZO-1, occludin) or adherence junction (E-cadherin) proteins when inflammation was induced. SOD3 also exerted a protective effect against cytokine- or ROS-mediated damage to intestinal organoids. These results indicate that SOD3 can effectively alleviate enteritis symptoms by maintaining the integrity of epithelial junctions and regulating inflammatory- and oxidative stress.

The role of geographical disparities of health-related risk factors with anemia are poorly documented for women of reproductive age in sub-Saharan Africa (SSA). We aimed to determine the contribution of potential factors and to identify areas at higher risk of anemia for women in reproductive age in SSA. Our study population comprised 27 nationally representative samples of women of reproductive age (15–49) who were enrolled in the Demographic and Health Surveys and conducted between 2010 and 2019 in SSA. Overall, we found a positive association between being anemic and the ecological exposure to malaria incidence [adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) 1.02–1.02], and HIV prevalence (AOR = 1.01, CI 1.01–1.02). Women currently pregnant or under deworming medication for the last birth had 31% (AOR = 1.31, CI 1.24–1.39) and 5% (AOR = 1.05, CI 1.01–1.10) higher odds of having anemia, respectively. Similarly, women age 25–34 years old with low education, low income and living in urban settings had higher odds of having anemia. In addition, underweight women had 23% higher odds of suffering anemia (AOR = 1.23, CI 1.15–1.31). Females with low levels of education and wealth index were consistently associated with anemia across SSA. Spatial distribution shows increased risk of anemia in Central and Western Africa. Knowledge about the contribution of known major drivers and the spatial distribution of anemia risk can mitigate operational constraints and help to design geographically targeted intervention programs in SSA.

Introduction The Central Africa International epidemiology Database to Evaluate AIDS (CA‐IeDEA) is an open observational cohort study investigating impact, progression and long‐term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We describe trends in demographic, clinical and immunological characteristics as well as antiretroviral therapy (ART) use of patients aged > 15 years entering into HIV care in the participating CA‐IeDEA site. Methods Information on sociodemographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 through 2018 were extracted from clinic records of patients aged > 15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrolment in HIV care including ART initiation within the first 30 days after enrolment in care and calculated proportions, means and medians (interquartile ranges) for the main variables of interest. Results Among 69,176 patients in the CA‐IeDEA cohort, 39% were from Rwanda, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men enrolled in care and subsequently initiated ART. Women were also younger than men (32 vs. 38 years, P

Funder: South African Medical Research Council; funder-id: http://dx.doi.org/10.13039/501100001322; Grant(s): ID:494184, Background: A cost analysis of implementation of interventions informs budgeting and economic evaluations. Objective: To estimate the cost of implementing the integrated chronic disease management (ICDM) model in primary healthcare (PHC) clinics in South Africa. Methods: Cost data from the provider’s perspective were collected in 2019 from four PHC clinics with comparable patient caseloads (except for one). We estimated the costs of implementing the ICDM model current activities for three (facility reorganization, clinical supportive management and assisted self-management) components and additional costs of implementing with enhanced fidelity. Costs were estimated based on budget reviews, interviews with management teams, and other published data. The standard of care activities such as medication were not included in the costing. One-way sensitivity analyses were carried out for key parameters by varying patient caseloads, required infrastructure and staff. Annual ICDM model implementation costs per PHC clinic and per patient per visit are presented in 2019 US dollars. Results: The overall mean annual cost of implementing the ICDM model was $148 446.00 (SD: $65 125.00) per clinic. Current ICDM model activities cost accounted for 84% ($124 345.00) of the annual mean cost, while additional costs for higher fidelity were 16% ($24 102.00). The mean cost per patient per visit was $6.00 (SD:$0.77); $4.94 (SD:0.70) for current cost and $1.06 (SD:0.33) for additional cost to enhance ICDM model fidelity. For the additional cost, 49% was for facility reorganization, 31% for adherence clubs and 20% for training of nursing staff. In the sensitivity analyses, the major cost drivers were the proportion of effort of assisted self-management staff and the number of patients with chronic diseases receiving care at the clinic. Conclusion: Minimal additional cost are required to implement the ICDM model with higher fidelity. Further research on the cost-effectiveness of the ICDM model in middle-income countries is required.

Purpose Transanal single-stage endorectal pull-through (TERPT) procedure for patients with Hirschsprung disease (HD) has favorable outcomes, with a lower complication rate. Nevertheless, various degrees of bowel dysfunction and fecal incontinence can persist for a long time in some patients. The aim of this study was to assess the mid- and long-term outcomes of TERPT performed during the infantile period after the completion of toilet training. Methods We retrospectively reviewed 82 patients aged ≥4 years who underwent TERPT during the infantile period after the pathological diagnosis of HD between 2001 and 2013. Functional outcomes were investigated according to the answers of the Bowel Function Score (BFS) questionnaire, a previously validated 7-item questionnaire about bowel habits. Normal values were obtained in a previous study on BFS for children in Western countries, and a one-sample t-test was used for statistical analysis. Results Overall, BFS was similar in all investigated age groups. On comparing fecal soiling and social problems between the HD and normal populations, a lower score at an early age in patients with HD was noted; however, the scores became similar when the patients were 7 years of age. Stool frequency decreased continuously but was not significantly different between the 2 groups. Conclusion The functional outcomes of TERPT performed during the infantile period, after completing toilet training, were similar to that of the normal population. In most cases, uncomfortable symptoms were diminished and functions improved with age.

Objectives To compare the dose reduction potential (DRP) of a vendor-agnostic deep learning model (DLM, ClariCT.AI) with that of a vendor-specific deep learning–based image reconstruction algorithm (DLR, TrueFidelity™). Methods Computed tomography (CT) images of a multi-sized image quality phantom (Mercury v4.0) were acquired under six radiation dose levels (0.48/0.97/1.93/3.87/7.74/15.47 mGy) and were reconstructed using filtered back projection (FBP) and three strength levels of the DLR (low/medium/high). The FBP images were denoised using the DLM. For all DLM and DLR images, the detectability index (d′) (a task-based detection performance metric) was obtained, under various combinations of three target sizes (10/5/1 mm), five inlets (CT value difference with the background; −895/50/90/335/1000 HU), five phantom diameters (36/31/26/21/16 cm), and six radiation dose levels. Dose reduction potential (DRP) measures the dose reduction made by using DLM or DLR, while yielding d′ equivalent to that of FBP at full dose. Results The DRPs of the DLM, DLR-low, DLR-medium, and DLR-high were 86% (81–88%), 60% (46–67%), 76% (60–81%), and 87% (78–92%), respectively. For 10-mm targets, the DRP of the DLM (87%) was higher than that of all DLR algorithms (58–86%). However, for smaller targets (5 mm/1 mm), the DRPs of the DLR-high (89/88%) were greater than those of the DLM (87/84%). Conclusion The dose reduction potential of the vendor-agnostic DLM was shown to be comparable to that of the vendor-specific DLR at high strength and superior to those of the DLRs at medium and low strengths. Key Points • DRP of the vendor-agnostic model was comparable to that of high-strength vendor-specific model and superior to those of medium- and low-strength models. • Under various radiation dose levels, the deep learning model shows higher detectability indexes compared to FBP. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-021-08199-9.

Background while the HIV epidemic remains a considerable challenge in sub-Saharan Africa, a dramatic reduction in the associated mortality has led to a fundamental shift in the public health priorities aimed at tackling multimorbidity. Against the unprecedented level of urbanisation taking place in Tanzania, the burden of multimorbidity and its consequences among ageing adults, in the form of costly inpatient hospitalisation, remain unquantified. Methods we used data from one of Africa’s largest urban population cohort, the Dar es Salaam Health and the Demographic Surveillance System, to quantity the extent of multimorbidity (occurrence of 2 ≥ health conditions) and discordant multimorbidity (occurrence of conditions in 2 ≥ domains in mental health, non-communicable and communicable health) among 2,299 adults aged ≥40 years in Dar es Salaam, Tanzania. We fitted logistic regression models to investigate the association between multimorbidity and inpatient hospitalisation. Results the prevalence of multimorbidity and discordant multimorbidity were 25.3 and 2.5%, respectively. Although the severe forms of multimorbidity (2.0% with ≥4 health conditions) and discordancy were low, hospitalisation was significantly higher based on the regression analyses. Household food insecurity was the only socio-economic variable that was significantly and consistently associated with a greater hospitalisation. Conclusion we found an alarmingly high degree of multimorbidity among this ageing urban population where hospitalisation was driven by multimorbidity. As public health resources remain scarce, reducing costly inpatient hospitalisation requires multilevel interventions that address clinical- and structural-level challenges (e.g. food insecurity) to mitigate multimorbidity and promote long-term healthy independent living among older adults in Tanzania.

Extensive water loss and melanin hyperproduction can cause various skin disorders. Low-temperature argon plasma (LTAP) has shown the possibility of being used for the treatment of various skin diseases, such as atopic dermatitis and skin cancer. However, the role of LTAP in regulating skin moisturizing and melanogenesis has not been investigated. In this study, we aimed to determine the effect of LTAP on yes-associated protein (YAP), a major transcriptional coactivator in the Hippo signaling pathway that is involved in skin moisturizing and melanogenesis-regulating markers. In normal human epidermal keratinocytes (NHEKs), the human epidermal keratinocyte line HaCaT, and human dermal fibroblasts (HDFs), we found that LTAP exhibited increased expression levels of YAP protein. In addition, the expression levels of filaggrin (FLG), which is involved in natural moisturizing factors (NMFs), and hyaluronic acid synthase (HAS), transglutaminase (TGM), and involucrin (IVL), which regulate skin barrier and moisturizing, were also increased after exposure to LTAP. Furthermore, collagen type I alpha 1 and type III alpha 1 (COL1A1, COL3A1) were increased after LTAP exposure, but the expression level of matrix metalloproteinase-3 (MMP-3) was reduced. Moreover, LTAP was found to suppress alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in murine melanoma B16F10 cells and normal human melanocytes (NHEMs). LTAP regulates melanogenesis of the melanocytes through decreased YAP pathway activation in a melanocortin 1 receptor (MC1R)-dependent manner. Taken together, our data show that LTAP regulates skin moisturizing and melanogenesis through modulation of the YAP pathway, and the effect of LTAP on the expression level of YAP varies from cell to cell. Thus, LTAP might be developed as a treatment method to improve the skin barrier, moisture content, and wrinkle formation, and to reduce melanin generation.

The performance of deep learning algorithm (DLA) to that of radiologists was compared in detecting low contrast objects in CT phantom images under various imaging conditions. For training, 10,000 images were created using American College of Radiology CT phantom as the background. In half of the images, objects of 3–20 mm size and 5–30 HU contrast difference were generated in random locations. Binary responses were used as the ground truth. For testing, 640 images of Catphan® phantom were used, half of which had objects of either 5 or 9 mm size with 10 HU contrast difference. Twelve radiologists evaluated the presence of objects on a five-point scale. The performances of the DLA and radiologists were compared across different imaging conditions in terms of area under receiver operating characteristics curve (AUC). Multi-reader multi-case AUC and Hanley and McNeil tests were used. We performed post-hoc analysis using bootstrapping and verified that the DLA is less affected by the changing imaging conditions. The AUC of DLA was consistently higher than those of the radiologists across different imaging conditions (p &lt, 0.0001), and it was less affected by varying imaging conditions. The DLA outperformed the radiologists and showed more robust performance under varying imaging conditions.

Introduction The uptake of HIV testing and linkage to care remains low among men, contributing to high HIV incidence in women in South Africa. We conducted the “Home-Based Intervention to Test and Start” (HITS) in a 2x2 factorial cluster randomized controlled trial in one of the World’s largest ongoing HIV cohorts in rural South Africa aimed at enhancing both intrinsic and extrinsic motivations for HIV testing. Methods Between February and December 2018, in the uMkhanyakude district of KwaZulu-Natal, we randomly assigned 45 communities (clusters) (n = 13,838 residents) to one of the four arms: (i) financial incentives for home-based HIV testing and linkage to care (R50 [$3] food voucher each); (ii) male-targeted HIV-specific decision support application, called EPIC-HIV; (iii) both financial incentives and male-targeted HIV-specific decision support application and (iv) standard of care (SoC). EPIC-HIV was developed to encourage and serve as an intrinsic motivator for HIV testing and linkage to care, and individually offered to men via a tablet device. Financial incentives were offered to both men and women. Here we report the effect of the interventions on uptake of home-based HIV testing among men. Intention-to-treat (ITT) analysis was performed using modified Poisson regression with adjustment for clustering of standard errors at the cluster levels. Results Among all 13,838 men ≥ 15 years living in the 45 communities, the overall population coverage during a single round of home-based HIV testing was 20.7%. The uptake of HIV testing was 27.5% (683/2481) in the financial incentives arm, 17.1% (433/2534) in the EPIC-HIV arm, 26.8% (568/2120) in the arm receiving both interventions and 17.8% in the SoC arm. The probability of HIV testing increased substantially by 55% in the financial incentives arm (risk ratio (RR)=1.55, 95% CI: 1.31 to 1.82, p < 0.001) and 51% in the arm receiving both interventions (RR = 1.51, 95% CI: 1.21 to 1.87 p < 0.001), compared to men in the SoC arm. The probability of HIV testing did not significantly differ in the EPIC-HIV arm (RR = 0.96, 95% CI: 0.76 to 1.20, p = 0.70). Conclusions The provision of a small financial incentive acted as a powerful extrinsic motivator substantially increasing the uptake of home-based HIV testing among men in rural South Africa. In contrast, the counselling and testing application which was designed to encourage and serve as an intrinsic motivator to test for HIV did not increase the uptake of home-based testing.

IntroductionNew York City (NYC) was a global epicenter of COVID-19. Vaccines against COVID-19 became available in December 2020 with limited supply, resulting in the need for policies regarding prioritization. The next month, SARS-CoV-2 variants were detected that were more transmissible but still vaccine-susceptible, raising scrutiny of these policies. In particular, prioritization of higher-risk people could prevent more deaths per dose of vaccine administered but could also delay herd immunity if the prioritization introduced bottlenecks that lowered vaccination speed (the number of doses that could be delivered per day). We used mathematical modeling to examine the trade-off between prioritization and the vaccination speed.MethodsA stochastic, discrete-time susceptible-exposed-infected-recovered (SEIR) model with age- and comorbidity-adjusted COVID-19 outcomes (infections, hospitalizations, and deaths by July 1, 2021) was used to examine the trade-off between vaccination speed and whether or not vaccination was prioritized to individuals age 65+ and “essential workers,” defined as including first responders and healthcare, transit, education, and public safety workers. The model was calibrated to COVID-19 hospital admissions, hospital census, ICU census, and deaths in NYC. Vaccination speed was assumed to be 10,000 doses per day starting December 15th, 2020 targeting healthcare workers and nursing home populations, and to subsequently expand at alternative starting times and speeds. We compared COVID-outcomes across alternative expansion starting times (January 15th, January 21st, or February 1st) and speeds (20,000, 30,000, 50,000, 100,000, 150,000, or 200,000 doses per day for the first dose), as well as alternative prioritization options (“yes” versus “no” prioritization of essential workers and people age 65+). Model projections were produced with and without considering the emergence of a SARS-COV-2 variant with 56% greater transmissibility over January and February, 2021.ResultsIn the absence of a COVID-19 vaccine, the emergence of the more transmissible variant would triple the peak in infections, hospitalizations, and deaths and more than double cumulative infections, hospitalizations, and deaths. To offset the harm from the more transmissible variant would require reaching a vaccination speed of at least 100,000 doses per day by January 15th or 150,000 per day by January 21st. Prioritizing people ages 65+ and essential workers increased the number of lives saved per vaccine dose delivered: with the emergence of a more transmissible variant, 8,000 deaths could be averted by delivering 115,000 doses per day without prioritization or 71,000 doses per day with prioritization. If prioritization were to cause a bottleneck in vaccination speed, more lives would be saved with prioritization only if the bottleneck reduced vaccination speed by less than one-third of the maximum vaccine delivery capacity. These trade-offs between vaccination speed and prioritization were robust over a wide range of delivery capacity.ConclusionsThe emergence of a more transmissible variant of SARS-CoV-2 has the potential to triple the 2021 epidemic peak and more than double the 2021 COVID-19 burden in NYC. Vaccination could only offset the harm of the more transmissible variant if high speed were achieved in mid-to late January. Prioritization of COVID-19 vaccines to higher-risk populations saves more lives only if it does not create an excessive vaccine delivery bottleneck.

AIM To predict survival time of Korean hepatocellular carcinoma (HCC) patients by analyzing big data using Cox proportional hazards model. METHODS Big data of the patients who underwent treatment for HCC from 2008 to 2015, provided by Korea Central Cancer Registry, National Cancer Center, and Ministry of Health and Welfare, were analyzed. A total of 10 742 patients with HCC were divided into two groups, with Group I (3021 patients) confirmed on biopsy and Group II (5563 patients) diagnosed as HCC according to HCC diagnostic criteria as outlined in Korean Liver Cancer Association guidelines. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of recurrence after treatment and survival status. RESULTS A total of 3021 patients in Group I and 5563 patients in Group II were included in the study and the difference in survival time between the two groups was statistically significant (P < 0.05). Recurrence was only included in intrahepatic cases, and the rates were 21.2 and 19.8% while the periods from the first treatment to recurrence were 15.57 and 14.19 months, respectively. Age, diabetes, BMI, platelet, alpha-fetoprotein, histologic tumor maximum size, imaging T stage, presence of recurrence, and duration of recurrence were included in multivariate analysis. CONCLUSION By using nationwide, multicenter big data, it is possible to predict recurrence rate and survival time which can provide the basis for treatment response to develop a predictive program.

Background The aim of this study was to evaluate the efficacy of deproteinized bovine bone mineral with 10% collagen (DBBM-C) soaked with hyaluronic acid (HA) for ridge preservation in compromised extraction sockets. Methods Bilateral third, fourth premolars and first molar were hemisected, distal roots were extracted, and then combined endodontic periodontal lesion was induced in the remaining mesial roots. After 4 months, the mesial roots were extracted and the following four treatments were randomly performed: Absorbable collagen sponge (ACS), ACS soaked with HA (ACS+HA), Ridge preservation with DBBM-C covered with a collagen membrane (RP), Ridge preservation with DBBM-C mixed with HA and covered with a collagen membrane (RP+HA). Animals were sacrificed at 1 and 3 months following treatment. Ridge dimensional changes and bone formation were examined using microcomputed tomography, histology, and histomorphometry. Results At 1 month, ridge width was significantly higher in the RP and RP+HA groups than in the ACS and ACS+HA groups, while the highest proportion of mineralized bone was observed in ACS+HA group. At 3 months, ridge width remained significantly higher in the RP and RP+HA groups than in the ACS and ACS+HA groups. ACS+HA and RP+HA treatments featured the highest proportion of mineralized bone and bone volume density compared to the other groups. No statistical difference was observed between ACS+HA and RP+HA treatments. Conclusions Ridge preservation with the mixture DBBM-C/HA prevented dimensional shrinkage and improved bone formation in compromised extraction sockets at 1 and 3 months. This article is protected by copyright. All rights reserved, One sentence summary. The mixture of hyaluronic acid and deproteinized bovine bone mineral with 10% collagen in compromised extraction sockets can improve bone formation and prevent dimensional shrinkage.

A vast disparity exists between science and practice for CT radiation dose. Despite high-level evidence supporting the use of low-dose CT (LDCT) in diagnosing appendicitis, a recent survey showed that many care providers were still concerned that the low image quality of LDCT may lead to incorrect diagnoses. For successful implementation of LDCT practice, it is important to inform and educate the care providers not only of the scientific discoveries but also of concrete guidelines on how to overcome more practical matters. Here, we discuss CT imaging techniques and other practical issues for implementing LDCT practice.

Soon Jun Hong,1,* Ki-Chul Sung,2,* Sang-Wook Lim,3 Seok-Yeon Kim,4 Weon Kim,5 Jinho Shin,6 Sungha Park,7 Hae-Young Kim,8 Moo-Yong Rhee9,10 On behalf of MH_APOLLO to read: HM_APOLLO1Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 2Department of Cardiology, Gangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea; 3Cardiology Division, Cardiac Center, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 4Department of Cardiology, Seoul Medical Center, Seoul, Republic of Korea; 5Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea; 6Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea; 7Department of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 8Department of Health Policy and Management, College of Health Science & Department of Health Care Science, Graduate School, Korea University, Seoul, Republic of Korea; 9Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi, Republic of Korea; 10College of Medicine, Dongguk University, Gyeongju-si, Gyeongbuk, Republic of Korea*These authors contributed equally to this workCorrespondence: Moo-Yong RheeCardiovascular Center, Dongguk University Ilsan Hospital, 27 Dongguk-Ro, Ilsandong-Gu, Goyang-si, Gyeonggi-do 10326, Republic of KoreaTel +82 31 961 5775Fax +82 31 961 7786Email mooyong_rhee@dumc.or.krPurpose: We evaluated the dose-responsiveness, efficacy, and safety of low-dose triple antihypertensive combination therapies in patients with mild-to-moderate hypertension.Patients and Methods: After a 1 to 2-week placebo run-in period, 248 patients were randomized to the half-dose triple combination (amlodipine 2.5 mg + losartan 25 mg + chlorthalidone 6.25 mg), third-dose triple combination (amlodipine 1.67 mg + losartan 16.67 mg + chlorthalidone 4.17 mg), quarter-dose triple combination (amlodipine 1.25 mg + losartan 12.5 mg + chlorthalidone 3.13mg), amlodipine 10mg, amlodipine 5mg, losartan 100mg, and placebo groups for 8 weeks. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to week 8.Results: The placebo-corrected SBP reductions of the half-dose, third-dose, quarter-dose combination, amlodipine 10 mg, amlodipine 5 mg and losartan 100 mg treatments were − 17.2, − 19.5, − 14.9, − 18.5, − 11.3 and − 9.9 mmHg, respectively. The BP control and response rates were significantly higher in the half-dose, third-dose, and quarter-dose combination groups than in the placebo group (all p < 0.01). Despite no intergroup differences in study drug-related adverse events, ankle circumference increased significantly in the amlodipine group compared to those in the combination treatment groups. The quarter-dose combination, amlodipine 5 mg, and losartan 100 mg groups showed similar SBP reduction and BP response rates. The SBP reduction and BP response rate in the third-dose and half-dose combination groups were not significantly different from those in the amlodipine 10 mg group but superior to those in the losartan 100 mg group.Conclusion: Low-dose triple combination therapies could be effective as antihypertensive therapies.Trial Registration: ClinicalTrials.gov identifier NCT03897868.Keywords: hypertension, blood pressure, combination therapy, low-dose, amlodipine, losartan, chlorthalidone

Purpose: This retrospective study compared the long-term outcomes of dental implants according to type of connection and surface. Materials and Methods: Multiunit restorations were classified as follows: an external connection with a turned surface, an external connection with an anodized surface, or an internal connection with a fluoride-modified surface. Patients who were followed up for longer than 7 years after implant loading were included in the study. Cumulative implant survival rates and the amounts of marginal bone loss were calculated by reviewing dental records and radiographs. Only implants that survived until the last follow-up visit were included in the analysis of marginal bone loss. Statistical analyses were performed to detect between-group differences at the significance level of .05. Results: Sixty-nine patients with 261 bone-level implants were included. The average follow-up duration was 15.2 years in the external turned group, 10.6 years in the external anodized group, and 9.9 years in the internal fluoride-modified group. There was no significant between-group difference in the cumulative survival rate (P = .439) despite eight implant failures (six in the external turned group and two in the internal fluoride-modified group). The mean (SD) marginal bone loss values at the last follow-up were 0.47 mm (0.67), 0.87 mm (1.07), and 0.23 mm (0.58) in the external turned, external anodized, and internal fluoride-modified groups, respectively. After adjusting for follow-up duration, there was significantly less marginal bone loss in the external turned group than in the external anodized group (P < .001) and in the internal fluoride-modified group than in the external anodized group (P < .001). No significant difference in marginal bone loss was found between the external turned and internal fluoride-modified groups (P = .44). Conclusion: The implant-abutment connection structure is an important contributor to the maintenance of the level of marginal bone surrounding the implant. Implant surface characteristics are another contributor to marginal bone resorption.

To compare 2-mSv CT and conventional-dose CT (CDCT, typically 7-8 mSv) regarding final diagnosis and patient disposition following equivocal CT results in adolescents and young adults with suspected appendicitis.In total, 3074 patients of 15-44 years (28 ± 9 years, 1672 women) from 20 hospitals were randomized to undergo contrast-enhanced 2-mSv CT (n = 1535) or CDCT (n = 1539) from December 2013 through August 2016. One hundred sixty-one radiologists prospectively rated the likelihood of appendicitis in a Likert scale (i.e., grades 1-5). The final diagnosis was based on CT image, surgical, pathologic, and clinical findings. Post hoc analysis was performed for final diagnosis, surgical procedure, and delay in patient management following equivocal results (i.e., grade 3).The 2-mSv CT and CDCT groups were comparable for final diagnosis following equivocal results, including confirmed appendicitis (1.2% [18 patients] vs. 1.2% [19], p0.99), negative appendectomy (0.1% [2] vs. 0.3% [4], p = 0.53), and perforated appendicitis (0.1% [1] vs. 0.2% [3], p = 0.53). More patients were confirmed as not having appendicitis following equivocal results in the CDCT group than in the 2-mSv CT group (2.2% [34] vs. 1.0% [16], p = 0.016). The two groups were comparable for the need of appendectomy (1.4% [22] vs. 1.5% [23], p0.99), need of additional imaging tests (0.7% [11] vs. 1.1% [17], p = 0.35), and delay in patient management following equivocal results.2-mSv CT is comparable to CDCT regarding final diagnosis and patient disposition following equivocal CT results.• Our results strengthen evidence justifying the use of low-dose CT instead of conventional-dose CT (CDCT) in adolescents and young adults with suspected appendicitis. • The 2-mSv CT and CDCT groups were comparable for final diagnosis following equivocal CT results, including confirmed appendicitis (1.2% vs. 1.2%, p0.99), negative appendectomy (0.1% vs. 0.3%, p = 0.53), and perforated appendicitis (0.1% vs. 0.2%, p = 0.53). • The two groups were comparable for the need for appendectomy (1.4% vs. 1.5%, p0.99), need for additional imaging tests (0.7% vs. 1.1%, p = 0.35), and delay in patient management, following equivocal CT results.

IntroductionNew York City (NYC) has the largest public school system in the United States (US). During the SARS-CoV-2 pandemic, NYC was the first major US city to open schools for in-person learning in the 2020-2021 academic year. Several policies were implemented to reduce the risk of in-school transmission, including infection control measures (facemasks, physical distancing, enhanced indoor ventilation, cohorting of small groups, and hand hygiene), option of all-remote instruction, alternative options for how class schedules would rotate in-person and remote instruction, daily symptom screening, and testing 10-20% of students and staff weekly or monthly depending on local case rates. We sought to determine which of these policies had the greatest impact on reducing the risk of in-school transmission.MethodsWe evaluated the impact of each policy by referring to global benchmarks for the secondary attack rate (SAR) of SARS-CoV-2 in school settings and by simulating the potential for transmission in NYC’s rotating cohort schedules, in which teachers could act as “bridges” across rotating cohorts. We estimated the impact of (1) infection control measures, (2) providing an option of all-remote instruction, (3) choice of class scheduling for in-person learners, (4) daily symptom screening, (5) testing to curtail transmission, and (6) testing to identify school outbreaks. Each policy was assessed independently of other policies, with the exception of symptom screening and random testing, which were assessed both independently and jointly.ResultsAmong the policies analyzed, the greatest transmission reduction was associated with the infection control measures, followed by small class cohorts with an option for all-remote instruction, symptom screening, and finally randomly testing 10-20% of school attendees. Assuming adult staff are the primary source of within-school SARS-CoV-2 transmission, weekly testing of staff could be at least as effective as symptom screening, and potentially more so if testing days occur in the beginning of the workweek with results available by the following day. A combination of daily symptom screening and testing on the first workday of each week could reduce transmission by 70%.ConclusionsAdherence to infection control is the highest priority for safe school re-opening. Further transmission reduction can be achieved through small rotating class cohorts with an option for remote learning, widespread testing at the beginning of the work week, and daily symptom screening and self-isolation. Randomly testing 10-20% of attendees weekly or monthly does not meaningfully curtail transmission and may not detect outbreaks before they have spread beyond a handful of individuals. School systems considering re-opening during the SARS-CoV-2 pandemic or similarly virulent respiratory disease outbreaks should consider these relative impacts when setting policy priorities.

Objectives: To provide information on how to teach correct oral health behaviour to youths and to develop programmes to that end, this study examined the oral health behaviour and demographic characteristics of adolescents. Methods: The raw data of ‘The Third 2007 Youth Health Behavior Online Survey’ carried out by the Korea Center for Disease Control and Prevention were analysed. Independent t-test, one-way ANOVA, and chi-squared analyses were used to assess the relationships between oral health behaviours and demographic characteristics. Results: The oral health behaviour of the adolescents who were investigated differed significantly depending on their demographic characteristics (P

With the advent of the Internet of Things, embedded systems have become widely used in various fields. Concurrently, the security of these systems has become a concern for many. However, security features that are already available for high-end systems have not been provided in low-end embedded systems due to its negative impact on cost and power consumption. Thus, to increase security with low overhead, many studies to implement the memory isolation approach to these systems have been conducted. However, existing techniques for this approach have suffered from problems in terms of scalability or performance. To mitigate such problems, we present RIMI, a new instruction extension to provide memory isolation in embedded systems. Thanks to instructions in RIMI, we can implement an instruction-level memory isolation where the access permission is bound to each memory and control transfer instructions. We implemented the RIMI prototype on a RISC-V architecture, which is a prominent open-source instruction set architecture (ISA). Our evaluation results show that existing security solutions, i.e., shadow stacks and in-process isolation, can be efficiently implemented with RIMI.

Background The coronavirus disease 2019 (COVID-19) has escalated to be a global threat to public health. Analysis of the use of radiology resources may render us insight regarding the public health behavior during pandemic. We measured the influence COVID-19 had on the use of radiology resources in terms of the number of examinations performed, and turnaround time for portable radiography. Methods This study was conducted at a tertiary hospital located in area where the prevalence of COVID-19 infection was low (0.01%). We compared the number of radiology examinations 1) before pandemic (in 2019) vs. during peak of pandemic (January to March 2020), and 2) before pandemic vs. after the peak of pandemic (April to June 2020) via t-tests. We repeated similar analyses for subgroups as follows: gender, age, department (outpatient, inpatient, emergency, screening), body parts, and modality. We also performed a survey of radiologic technologists regarding the turnaround time and rate-limiting step of portable radiography for patients with and without suspicion or confirmation of COVID-19. Results Although not statistically significant, the daily number of examinations during the peak of pandemic decreased by 9 percentage points (2,638 vs. 2,413; difference [95% CI], −225 [−489, 38]; P = 0.094). The percentage change was especially notable for children, emergency, and screening department (25, 19, and 44 percentage points, respectively). After the peak of the pandemic, the number of examinations increased back to near the pre-pandemic level (2,638 vs. 2,588; −50 [−317, 218]; P = 0.71). The turnaround time for portable radiography tended to be longer for patients with suspicion or confirmation of COVID-19, with donning personal protective equipment being the major rate-limiting step. Conclusion The number of examinations decreased during the pandemic, reflecting the tendency of the public to refrain from seeking medical care even in a community of low infection risk. Nevertheless, burden of healthcare providers may not have decreased as much, considering longer turnaround time required for COVID-19 related examinations., Graphical Abstract

Purpose We evaluated the efficacy and safety of nebivolol and rosuvastatin combination treatment in patients with hypertension and hyperlipidemia. Patients and Methods Eligible patients, after more than 4 weeks of therapeutic lifestyle change, were randomly assigned to three groups: 5 mg nebivolol plus 20 mg rosuvastatin (NEBI/RSV), 20 mg rosuvastatin (RSV), or 5 mg nebivolol (NEBI). Treatments lasted 8 weeks. Results Efficacy was analyzed using data from 276 patients. Sitting systolic and diastolic blood pressures differed between the NEBI/RSV and RSV groups (LSmean difference = −5.89 and −5.99 mmHg; 95% confidence interval [CI] = −9.88 to −1.90 mmHg and −8.13 to −3.84 mmHg, respectively). Reductions in the two pressures did not differ between the NEB/RSV and NEB groups. The percent reduction in low-density lipoprotein (LDL) cholesterol differed between the NEBI/RSV and NEBI groups (LSmean difference = −47.76%, 95% CI = −52.69 to −42.84%) but not between the NEBI/RSV and RSV groups. The blood pressure (BP) control rate was higher in the NEBI/RSV group than in the RVS group (51.09% vs 29.67%, p = 0.003). The LDL cholesterol goal achievement rate was higher in the NEBI/RSV group than in the NEBI group (85.87% vs 11.83%, p < 0.001). The incidence of adverse drug reactions in the NEBI/RSV, RSV, and NEBI groups was 8.51%, 7.45%, and 8.60%, respectively (p = 0.950). Conclusion Nebivolol plus rosuvastatin treatment is effective in reducing BP and LDL cholesterol levels and is safe in patients with hypertension and hypercholesterolemia without the loss of BP or the LDL cholesterol-lowering effect of each drug. Trial Registration CRIS registration number KCT0002148.

BackgroundTenofovir disoproxil fumarate (TDF) is the antiretroviral drug most commonly associated with renal dysfunction. However, few studies have examined this association in sub-Saharan Africa despite recent scale-up of antiretroviral therapy (ART) to all people living with HIV (Treat All) in this region. We assessed estimated glomerular filtration rate (eGFR) change among HIV infected Rwandan adults following first line TDF-based therapy initiation.MethodsThis prospective, observational study was conducted in 10 Rwandan health centers. Participants were ART-naive adults (≥18 years) living with HIV who initiated TDF-based ART from 1st July 2016 through 30th July 2018. The primary outcome was eGFR change from pre-(within 12 months) to post-TDF initiation (within 6 months).ResultsOf 476 patients with pre- and post-TDF eGFR measurements, 264 (55.5%) were women and mean age was 35.9 years (SD 9.6). Mean pre-TDF eGFR was 92.4 (SD 24.0) and mean post-TDF was 96.0 (SD 21.0) mL/min/1.73m2. Mean pre-to post-TDF change thus increased 3.60 (SD, 26.6) mL/min/1.73m2 (p=0.001).ConclusionWe detected a statistically significant clinically small renal function improvement within 6 months following TDF initiation among 476 ART-naïve patients. This supports continued TDF use for first-line treatment.

OBJECTIVE. The objective of our study was to compare diagnostic performance of 2-mSv CT and standard-dose CT (SDCT) for the diagnosis of perforated appendicitis in adolescents and young adults. MATERIALS AND METHODS. We used the intention-to-treat analysis set of a pragmatic randomized controlled trial involving 3074 patients (age range, 15-44 years) with suspected appendicitis and 161 radiologists from 20 hospitals. The patients were randomized to undergo either 2-mSv CT or SDCT. Predefined endpoints were sensitivity and specificity. Considering potential verification bias caused by the difference in diagnostic interventions (2-mSv CT vs SDCT), we added endpoints of detection rate (DR) and false-referral rate. The reference standards were surgical or pathologic findings. We used Fisher exact tests. Sensitivity analyses included the following: first, a per-protocol analysis; second, an analysis of a surgical reference standard but not a pathologic reference standard; and, third, an analysis to adjust for site clustering. We tested for heterogeneity in DR and false-referral rate across various patient and hospital characteristics. RESULTS. The 2-mSv CT and SDCT groups were comparable regarding DR (5.1% [78/1535] vs 4.9% [76/1539]; 95% CI for the difference, -1.4 to 1.7 percentage points; p = 0.87), false-referral rate (3.1% [48/1535] vs 3.1% [47/1539]; 95% CI for the difference, -1.2 to 1.3 percentage points; p = 0.92), sensitivity (42.9% [78/182] vs 43.2% [76/176]; 95% CI for the difference, -10.6 to 9.9 percentage points; p > 0.99), and specificity (89.2% [305/342] vs 91.2% [354/388]; 95% CI for the difference, -6.4 to 2.3 percentage points; p = 0.38). Sensitivity analyses showed similar results. We found no significant subgroup heterogeneity. CONCLUSION. The performance of 2-mSv CT, with limited sensitivity but high specificity, is comparable to that of SDCT for the diagnosis of appendiceal perforation.

Author(s): Murenzi, Gad; Kim, Hae-Young; Munyaneza, Athanase; Tuyisenge, Patrick; Zawadi, Thierry M; Buteera, Alex M; Adedimeji, Adebola; Mutesa, Leon; Castle, Philip E; Anastos, Kathryn; Palefsky, Joel M | Abstract: BackgroundMen who have sex with men (MSM) have a high prevalence of anal and penile human papillomavirus (HPV) infections with MSM living with HIV (MSMLH) bearing the highest rates. Data on anogenital high-risk HPV (hrHPV) among MSM in Rwanda and the associated risk factors are scant.MethodsWe recruited 350 self-identified MSM aged 18 years living in Kigali, Rwanda, with 300 recruited from the community and 50 from partner clinics. Anal and penile specimens from all participants were analyzed for hrHPV using the AmpFire platform. Logistic regression was used to calculate crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (95% CIs) as a measure of association between various factors and anal and penile hrHPV infection prevalence.ResultsAnal hrHPV prevalence was 20.1%, was positively associated with having receptive anal sex with more partners (aOR: 9.21, 95% CI: 3.66 to 23.14), and was negatively associated with having insertive anal sex with more partners (aOR: 0.28, 95% CI: 0.12 to 0.66). Penile hrHPV prevalence was 35.0%, was negatively associated with having receptive anal sex with more partners (aOR: 0.29, 95% CI: 0.13 to 0.66), and differed significantly by HIV status, with 55.2% and 29.7% for MSMLH and HIV-negative MSM, respectively (P l 0.01).ConclusionPenile hrHPV prevalence was higher than that of anal hrHPV and it was significantly higher in Rwandan MSMLH than in HIV-negative MSM. The prevalence of anal and penile HPV infections is likely variable at different locations in Africa, according to a number of factors including HIV status and sexual practices.

BackgroundThe Central Africa International epidemiology Database to Evaluate AIDS (CA-IeDEA) is a prospective study investigating impact, progression and long-term outcomes of HIV/AIDS among people living with HIV (PLWH) in Burundi, Cameroon, Democratic Republic of Congo (DRC), Republic of Congo (ROC) and Rwanda. We described trends in baseline demographic, clinical and immunological characteristics of patients aged >15 years entering into HIV care in the participating CA-IeDEA site and subsequent ART initiation.Materials and MethodsInformation on socio-demographic characteristics, height, weight, body mass index (BMI), CD4 cell count, WHO staging and ART status at entry into care from 2004 to 2018 were extracted from clinic records of patients aged >15 years enrolling in HIV care at participating clinics in Burundi, Cameroon, DRC, ROC and Rwanda. We assessed trends in patient characteristics at enrollment in HIV care and ART initiation at the participating site and calculated proportions, means and medians (interquartile ranges) for the main variables of interest.ResultsAmong 69,176 participants in the CA-IeDEA cohort, 39% % were from Rwanda,, 24% from ROC, 18% from Cameroon, 14% from Burundi and 5% from DRC. More women (66%) than men were enrolled in care and subsequently initiated ART. Women were also younger (32 years) than men (38 years) (p= ConclusionTrends from 2004-2018 in the characteristics of patients participating in the CA-IeDEA cohort highlight improvements over time at entry into care and subsequent ART in all participating sites.

We conducted a discrete choice experiment (DCE) and quantified preferences for HIV testing among South African youth (Nov 2018 to Mar 2019). Six attributes and levels were identified through qualitative methods: source of HIV information; incentive amount and type; social support; testing method; and location. Each participant chose one of two options that comprised six attributes across 18 questions. Conditional logistic regression estimated the degree of preference [β]. Of 130 participants, median age was 21 years (interquartile range 19–23 years), majority female (58%), and 85% previously tested for HIV. Testing alone over accompanied by a friend (β = 0.22 vs. − 0.35; p

OBJECTIVE To verify whether ridge preservation is effective in the reduction of dimensional loss and in bone formation compared to spontaneous healing in extraction sockets of periodontally compromised teeth. METHODS Twenty-six subjects requiring tooth extraction for stage III/IV periodontitis were randomly assigned to one of two interventions: alveolar ridge preservation using collagenated bovine bone mineral and a resorbable collagen membrane (test, RP) or spontaneous healing (control, SH). Six months later, postoperative cone-beam computed tomography (CBCT) was performed to measure the linear and volumetric changes of the sockets compared to baseline scans. Biopsies were retrieved at the implant site for histomorphometric calculations. Nonparametric tests were applied for statistical analysis. RESULTS Significantly less shrinkage occurred in RP compared to SH, mainly in the crestal zone. The width loss difference between groups was 3.3 mm and 2.2 mm at 1 mm and 3 mm below the crest, respectively (p

A growth scheme at a low processing temperature for high crystalline-quality of ZnO nanostructures can be a prime stepping stone for the future of various optoelectronic devices manufactured on transparent plastic substrates. In this study, ZnO nanorods (NRs) grown by the hydrothermal method at 150 &deg, C through doping of transition metals (TMs), such as Co, Ni, or Co-plus-Ni, on polyethylene terephthalate substrates were investigated by various surface analysis methods. The TM dopants in ZnO NRs suppressed the density of various native defect-states as revealed by our photoluminescence and X-ray photoelectron spectroscopy analysis. Further investigation also showed the doping into ZnO NRs brought about a clear improvement in carrier mobility from 0.81 to 3.95 cm2/V-s as well as significant recovery in stoichiometric contents of oxygen. Ultra-violet photodetectors fabricated with Co-plus-Ni codoped NRs grown on an interdigitated electrode structure exhibited a high spectral response of ~137 A/W, on/off current ratio of ~135, and an improvement in transient response speed with rise-up and fall-down times of ~2.2 and ~3.1 s, respectively.

Ewing sarcoma is a pediatric bone cancer that expresses the chimeric protein EWSR1/FLI1. We previously demonstrated that EWSR1/FLI1 impairs the localization of Aurora B kinase to the midzone (the midline structure located between segregating chromosomes) during anaphase. While localization of Aurora B is essential for faithful cell division, it is unknown whether interference with midzone organization by EWSR1/FLI1 induces aneuploidy. To address this, we generated stable Tet-on inducible cell lines with EWSR1/FLI1, using CRISPR/Cas9 technology to integrate the transgene at the safe-harbor AAVS1 locus in DLD-1 cells. Induced cells expressing EWSR1/FLI1 displayed an increased incidence of aberrant localization of Aurora B, and greater levels of aneuploidy, compared with noninduced cells. Furthermore, the expression of EWSR1/FLI1-T79A, containing a threonine (Thr) to alanine (Ala) substitution at amino acid 79, failed to induce these phenotypes, indicating that Thr 79 is critical for EWSR1/FLI1 interference with mitosis. In contrast, the phosphomimetic mutant EWSR1/FLI1-T79D (Thr to aspartic acid (Asp)) retained the high activity as wild-type EWSR1/FLI1. Together, these findings suggest that phosphorylation of EWSR1/FLI1 at Thr 79 promotes the colocalization of EWSR1/FLI1 and Aurora B on the chromosomes during prophase and metaphase and, in addition, impairs the localization of Aurora B during anaphase, leading to induction of aneuploidy. This is the first demonstration of the mechanism for EWSR1/FLI1-dependent induction of aneuploidy associated with mitotic dysfunction and the identification of the phosphorylation of the Thr 79 of EWSR1/FLI1 as a critical residue required for this induction.

Purpose of Review The ANRS 12249 treatment as prevention (TasP) trial investigated the impact of a universal test and treat (UTT) approach on reducing HIV incidence in one of the regions of the world most severely affected by the HIV epidemic—KwaZulu-Natal, South Africa. We summarize key findings from this trial as well as recent findings from controlled studies conducted in the linked population cohort quantifying the long-term effects of expanding ART on directly measured HIV incidence (2004–2017). Recent Findings The ANRS TasP trial did not—and could not—demonstrate a reduction in HIV incidence, because the offer of UTT in the intervention communities did not increase ART coverage and population viral suppression compared to the standard of care in the control communities. Ten controlled studies from the linked population cohort—including several quasi-experimental study designs—exploit heterogeneity in ART exposure to show a consistent and substantial impact of expanding provision of ART and population viral suppression on reduction in HIV incidence at the couple, household, community, and population levels. Summary In this setting, all of the evidence from large, population-based studies (inclusive of the ANRS TasP trial) is remarkably coherent and consistent—i.e., higher ART coverage and population viral suppression were repeatedly associated with clear, measurable decreases in HIV incidence. Thus, the expanded provision of ART has plausibly contributed in a major way toward the dramatic 43% decline in population-level HIV incidence in this typical rural African population. The outcome of the ANRS TasP trial constitutes a powerful null finding with important insights for overcoming implementation challenges in the population delivery of ART. This finding does not imply lack of ART effectiveness in blocking onward transmission of HIV nor its inability to reduce HIV incidence. Rather, it demonstrates that large increases in ART coverage over current levels will require health systems innovations to attract people living with HIV in early stages of the disease to participate in HIV treatment. Such innovations and new approaches are required for the true potential of UTT to be realized.

BACKGROUND: There has been slow uptake of isoniazid preventive therapy (IPT) among people living with HIV (PLWH).METHODS: We surveyed adults recently diagnosed with HIV in 14 South African primary health clinics. Based on the literature and qualitative interviews, sixteen potential barriers and facilitators related to preventive therapy among PLWH were selected. Best-worst scaling (BWS) was used to quantify the relative importance of the attributes. BWS scores were calculated based on the frequency of participants' selecting each attribute as the best or worst among six options (across multiple choice sets) and rescaled from 0 (always selected as worst) to 100 (always selected as best) and compared by currently receiving IPT or not.RESULTS: Among 342 patients surveyed, 33% (n = 114) were currently taking IPT. Having the same standard of life as someone without HIV was most highly prioritized (BWS score = 67.3, SE = 0.6), followed by trust in healthcare providers (score, 66.3 ± 0.6). Poor standard of care in public clinics (score, 30.6 ± 0.6) and side effects of medications (score, 33.7 ± 0.6) were least prioritized. BWS scores differed by IPT status for few attributes, but overall ranking was similar (spearman's rho = 0.9).CONCLUSION: Perceived benefits of preventive therapy were high among PLWH. IPT prescription by healthcare providers should be encouraged to enhance IPT uptake among PLWH.

Uptake of HIV testing remains low among men in South Africa. As part of a trial, we assessed the acceptability of a theoretically derived and adapted tablet-based-application (EPIC-HIV1) in rural South Africa. We conducted 20 in-depth interviews with men aged ≥18 years and offered a tablet-based survey to all men aged ≥15 years who received EPIC-HIV1 (Sep-Dec 2018). We conducted a descriptive analysis of the survey and used Self-Determination Theory (SDT) to guide our thematic analysis. A total of 232/307 (75%) completed the survey, 55% of whom were aged 15–24 years. 96%[ CI: 92.8–98.2%; n = 223] found EPIC-HIV1 acceptable and 77% [95% CI: 71.8–82.6%; n = 179] found it user-friendly. 222 [96%] reported that EPIC-HIV1 motivated them to test; 83% (192/232) tested for HIV, of which 33% (64/192) were first time testers. Those who did not consent (n = 40) were more likely to have had an HIV-positive test result. Participants reported that the app boosted their confidence to test. However, they were unsure that the app would help them overcome barriers to test in local clinics. Given reach and usability, an adapted SDT male-tailored app was found to be acceptable and could encourage positive health-seeking behavioural change among men.

Differentiating complicated appendicitis has become important, as multiple trials showed that non-operative management of uncomplicated appendicitis is feasible. We developed and validated a diagnostic model to differentiate complicated from uncomplicated appendicitis.This retrospective study included 1153 patients (mean age ± standard deviation, 30 ± 8 years) with appendicitis on CT (804 patients for development, and 349 for validation). Complicated appendicitis was confirmed in 300 and 121 patients in the development and validation datasets, respectively. The reference standard was surgical or pathological report except in 7 patients who underwent percutaneous abscess drainage. We developed a model using multivariable logistic regression and Bayesian information criterion. We assessed calibration and discriminatory performance of the model in the validation dataset via calibration plot and the area under the curve (AUC), respectively. We measured sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and proportion of false- and true-negatives of the model in the validation dataset, targeting 95% sensitivity.Five CT features (contrast-enhancement defect of the appendiceal wall, abscess, moderate or severe periappendiceal fat stranding, appendiceal diameter, and extraluminal air) and percentage of segmented neutrophil were included in our model. The calibration slope was 1.03, and AUC was 0.81 (95% CI 0.77-0.85) in the validation dataset. The sensitivity, specificity, PPV, NPV, and proportion of false- and true-negatives were 93.4% (91.8-99.1), 28.1% (13.6-24.1), 40.8% (35.0-46.8), 88.9% (79.3-95.1), 2.3%, and 18.3%, respectively.Our model may identify patients with unequivocally uncomplicated appendicitis, who may benefit from non-operative management with low risk of failure.

Background Meconium peritonitis is defined as aseptic chemical inflammation caused by intrauterine bowel perforation. The underlying causes of bowel perforation include intestinal atresia, midgut volvulus, intussusception, congenital bands, and meconium ileus. Case presentation Siblings with prenatally diagnosed meconium peritonitis of different etiologies were found. The elder sister was born at 36 + 6 weeks gestation with a birth weight of 3110 g. She was diagnosed with meconium peritonitis caused by ileal atresia. Two years later, the younger brother was born at 34 + 3 weeks gestation with a birth weight of 2850 g. He was diagnosed with meconium peritonitis caused by midgut volvulus. Conclusions Among the previously reported cases of meconium peritonitis, familial occurance of meconium peritonitis is extremely rare. We present a case of prenatally diagnosed meconium peritonitis in siblings to promote further understanding of its etiology and clinical course.

Background South Africa is at the epicentre of the HIV pandemic, with the world's highest number of new infections and the largest treatment programme. Using metrics proposed by the Joint United Nations Programme on AIDS (UNAIDS), we evaluate progress toward epidemic control and highlight areas for intervention in a hyperendemic South African setting. Methods The Africa Health Research Institute (AHRI) maintains a comprehensive population-based surveillance system in the Hlabisa sub-district of KwaZulu-Natal. Between 2005 and 2017, we tested 39 735 participants (aged 15–49 years) for HIV and followed 22 758 HIV-negative and 13 460 HIV-positive participants to identify new infections and all-cause AIDS-related deaths, respectively. Using these data, we estimated the percentage reduction in incidence, the absolute incidence rate, the incidence-mortality ratio and the incidence-prevalence ratio over place and time. Results We observed a 62% reduction in the number of new infections among men between 2012 and 2017 and a 34% reduction among women between 2014 and 2017. Among men, the incidence-mortality ratio peaked at 4.1 in 2013 and declined to 3.1 in 2017, and among women it fell from a high of 6.4 in 2014 to 4.3 in 2017. Between 2012 and 2017, the female-incidence/male-prevalence ratio declined from 0.24 to 0.13 and the male-incidence/female-prevalence ratio from 0.05 to 0.02. Conclusions Using data from a population-based cohort study, we report impressive progress toward HIV epidemic control in a severely affected South African setting. However, overall progress is off track for 2020 targets set by the UNAIDS. Spatial estimates of the metrics, which demonstrate remarkable heterogeneity over place and time, indicate areas that could benefit from additional or optimized HIV prevention services.

Objectives. In this study, a clear aligner was moved at intervals of 0.25 mm and pressure variations were assessed using a sensor. Methods. The model used for producing the clear aligner was created using a 3-dimensional printer. A clear, circular thermoplastic of 0.75 mm thickness was used for making the clear aligner using the vacuum forming method. A pressure sensor was used to assess the pressure in the device, and the variation in the sheet pressure was statistically analyzed tooth movement using the clear aligner, moving at an interval of 0.25 mm, is recommended. Results. The results of pressure sensor assessment showed that the pressure of the devices with 0.25 mm and 1.00 mm movements was identical to that of the device with 0 mm movement. In other words, the pressure sensor could not distinguish the pressure of devices that moved 0.25 mm and 1.00 mm. Conclusions. This experiment demonstrated that a movement of more than 0.50 mm is needed to apply the appropriate pressures needed for orthodontics in a clear polymer sheet.

CT plays a central role in determining the resectability of pancreatic cancer, which directs the use of neoadjuvant therapy. This study aimed to assess the diagnostic accuracy of CT in predicting circumferential resection margin (CRM) involvement in patients with resectable or borderline resectable pancreatic head cancer.Seventy-seven patients who were scheduled for upfront surgery for resectable or borderline resectable pancreatic head cancer were prospectively enrolled, and 75 patients (38 male and 37 female; mean age ± standard deviation, 68 ± 11 years) were finally analyzed. The CRM status was evaluated separately for the superior mesenteric artery (SMA) and posterior and superior mesenteric vein/portal vein (SMV/PV) margins. Three independent radiologists reviewed the preoperative CT images and evaluated the resection margin status. The reference standard for CRM status was pathologic examination of pancreaticoduodenectomy specimens in an axial plane perpendicular to the axis of the second portion of the duodenum. The diagnostic accuracy of CT was assessed for overall CRM involvement, defined as involvement of the SMA or posterior margins (per-patient analysis), and involvement of each of the three resection margins (per-margin analysis). The data were pooled using a crossed random effects model.Forty patients had pathologically confirmed overall CRM involvement in pancreatic cancer, while CRM involvement was not seen in 35 patients. For overall CRM involvement, the pooled sensitivity and specificity were 15% (95% confidence interval: 7%-49%) and 99% (96%-100%), respectively. For each of the resection margins, the pooled sensitivity and specificity were 14% (9%-54%) and 99% (38%-100%) for the SMA margin, 12% (8%-46%) and 99% (97%-100%) for the posterior margin; and 37% (29%-53%) and 96% (31%-100%) for the SMV/PV margin, respectively.CT showed very high specificity but low sensitivity in predicting pathological CRM involvement in pancreatic cancer.

Objective To estimate the incremental cost-effectiveness of universal vs. test-directed treatment of latent tuberculous infection (LTBI) among human immunodeficiency virus (HIV) positive pregnant women in South Africa. Methods We compared tuberculin skin test (TST) directed isoniazid preventive therapy (IPT) (TST placement with delivery of IPT to women with positive results) against QuantiFERON®-TB Gold In-Tube (QGIT) directed IPT and universal IPT using decision analysis. Costs were measured empirically in six primary care public health clinics in Matlosana, South Africa. The primary outcome was the incremental cost-effectiveness ratio, expressed in 2016 US$ per disability-adjusted life-year (DALY) averted. Results We estimated that 29.2 of every 1000 pregnant women would develop TB over the course of 1 year in the absence of IPT. TST-directed IPT reduced this number to 24.5 vs. 22.6 with QGIT-directed IPT and 21.0 with universal IPT. Universal IPT was estimated to cost $640/DALY averted (95% uncertainty range $44-$3146) relative to TST-directed IPT and was less costly and more effective (i.e., dominant) than QGIT-directed IPT. Cost-effectiveness was most sensitive to the probability of developing TB and LTBI prevalence. Conclusion Providing IPT to all eligible women can be a cost-effective strategy to prevent TB among HIV-positive pregnant women in South Africa.

Purpose: The purpose of this study was to examine changes in the self-rated health of adolescents and to identify its predictors using longitudinal data from the KCYPS. Methods: A sample of 2,351 adolescents who were in the first grade of middle school in 2010 was analyzed. The study employed latent growth analysis using data from 2010 to 2016. Results: Results indicated that self-rated health of adolescents increased, following the form of a linear function. The analyses revealed that adolescent self-perception of health were conceptualized not only by their health-related behaviors, but also by personal, socioeconomic and psychological factors. Specifically, physical activity, passive leisure time activities, gender (initial: b=-.060, slope: b=.030), place of residence (initial: b=-.079), self-rated economic condition (b=.098), working status of mother (b=.016), monthly family income (b=-.001), aggression (b=.061), depression (initial: b=-.104, slope: b=.012), stress (initial: b=-.172, slope: b=.014, ego-resiliency (initial: b=.197, slope: b=-.021), and self-esteem (initial: b=.106, slope: b=-.017) had significant effects on the overall linear change of self-rated health (p

Aims Several anti-melanogenic molecules have been developed or identified, but their uses are limited due to either adverse effects or instability during the treatment. We aimed to evaluate the effects of extracellular superoxide dismutase (SOD3), a powerful antioxidant, as a candidate anti-melanogenic molecule. Main methods UVB-induced reactive oxygen species (ROS) production and proliferation in melan-a cells was evaluated by 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate staining and bromodeoxyuridine incorporation assay, respectively. Quantitative real-time polymerase chain reaction and western blot were performed to detect the melanogenesis-related gene expression and downstream signaling. Anti-melanogenic effects of SOD3 were also evaluated using SOD3 transgenic mice under UVB exposure in-vivo condition. Key findings SOD3 inhibited UVB-induced proliferation, ROS production and melanogenesis in melanocytes. Measurement of melanin content and tyrosinase activity assays showed that SOD3 significantly inhibited melanin synthesis. Moreover, these suppressive effects of SOD3 were dependent on the endothelin-1 (ET-1)/endothelin B receptor, protein kinase C, melanocortin 1 receptor/protein kinase A, Wnt7a/β-catenin, and mitogen-activated protein kinase pathways, with concomitant downregulation of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related proteins 1, dopachrome tautomerse. Interestingly, SOD3 was found to inhibit transforming growth factor-beta 1 (TGF-β1) to inactivate the ET-1 signaling pathway, and finally prevents the production of melanin. Significance Our results provide novel insights into the role of SOD3 in melanocyte homeostasis and its uses as a potential biomedicine to treat hyperpigmentary conditions of the skin.