Search

Background: Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration., Purpose: To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS., Study Type: Retrospective., Population: A total of 31 AS patients with reduced and preserved ejection fraction (14 AS&#95;rEF: 7 male, 66.5 [7.8] years old; 17 AS&#95;pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old)., Field Strength/sequence: 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences., Assessment: Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling., Statistical Tests: Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P < 0.05); ICC and CV: variability; Mann-Whitney: effect size., Results: AS&#95;rEF group shows distinct deterioration of cardiac motions compared to AS&#95;pEF and healthy groups (TI AS&#95;rEF : 0.92 [0.85] mm, TI AS&#95;pEF : 5.13 [1.99] mm, TI healthy : 3.61 [1.09] mm, ES: 0.48-0.83; DI AS&#95;rEF : 17.11 [7.89]%, DI AS&#95;pEF : 6.39 [4.04]%, DI healthy : 5.71 [1.87]%, ES: 0.32-0.85; CR AS&#95;rEF : 8.69 [6.11] mm/second, CR AS&#95;pEF : 16.48 [6.70] mm/second, CR healthy : 10.82 [4.57] mm/second, ES: 0.29-0.60; RR AS&#95;rEF : 8.45 [4.84] mm/second; RR AS&#95;pEF : 13.49 [8.56] mm/second, RR healthy : 9.31 [2.48] mm/second, ES: 0.14-0.43). The difference in the motion metrics between healthy and AS&#95;pEF groups were insignificant (P-value = 0.16-0.72). AS&#95;rEF group was dominated by eccentric hypertrophy (47.1%) with concomitant scarring. Conversely, AS&#95;pEF group was dominated by concentric remodeling and hypertrophy (71.4%), which could demonstrate hyperkinesia with slight wall dyssynchrony than healthy. Dysfunction of LV mechanics corresponded to the presence of myocardial scarring (54.9% in AS), which reverted the compensatory mechanisms initiated and performed by LV remodeling., Data Conclusion: The proposed 3D + time modeling technique may distinguish regional motion abnormalities between AS&#95;pEF, AS&#95;rEF, and healthy cohorts, aiding clinical diagnosis and monitoring of AS progression. Subclinical myocardial dysfunction is evident in early AS despite of normal EF., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers., (© 2024. The Author(s).)

Left ventricular adaptations can be a complex process under the influence of aortic stenosis (AS) and comorbidities. This study proposed and assessed the feasibility of using a motion-corrected personalized 3D + time LV modeling technique to evaluate the adaptive and maladaptive LV response to aid treatment decision-making. A total of 22 AS patients were analyzed and compared against 10 healthy subjects. The 3D + time analysis showed a highly distinct and personalized pattern of remodeling in individual AS patients which is associated with comorbidities and fibrosis. Patients with AS alone showed better wall thickening and synchrony than those comorbid with hypertension. Ischemic heart disease in AS caused impaired wall thickening and synchrony and systolic function. Apart from showing significant correlations to echocardiography and clinical MRI measurements (r: 0.70-0.95; p < 0.01), the proposed technique helped in detecting subclinical and subtle LV dysfunction, providing a better approach to evaluate AS patients for specific treatment, surgical planning, and follow-up recovery., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs., Methods: The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability; 2) potential for burden reduction; 3) potential for a paradigm shift; 4) potential for translation and implementation; and 5) impact on equity., Results: Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients' needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts., Interpretation: Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs., Competing Interests: Competing interests: Ana Marušić, Harry Campbell and Igor Rudan are the Co-Editors in Chief of the Journal of Global Health. To ensure that any possible conflict of interest relevant to the journal has been addressed, this article was reviewed according to best practice guidelines of international editorial organisations. The authors completed the ICMJE Unified Competing Interests Form (available upon request from the corresponding author) and declare no further conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: The study aims to analyze the correlation between the maximal diameter (both axial and orthogonal) and volume changes in the true (TL) and false lumens (FL) after stent-grafting for Stanford type B aortic dissection., Method: Computed tomography angiography was performed on 13 type B aortic dissection patients before and after procedure, and at 6 and 12 months follow-up. The lumens were divided into three regions: the stented area (Region 1), distal to the stent graft to the celiac artery (Region 2), and between the celiac artery and the iliac bifurcation (Region 3). Changes in aortic morphology were quantified by the increase or decrease of diametric and volumetric percentages from baseline measurements., Results: At Region 1, the TL diameter and volume increased (pre-treatment: volume =51.4±41.9 mL, maximal axial diameter =22.4±6.8 mm, maximal orthogonal diameter =21.6±7.2 mm; follow-up: volume =130.7±69.2 mL, maximal axial diameter =40.1±8.1 mm, maximal orthogonal diameter =31.9+2.6 mm, P<0.05 for all comparisons), while FL decreased (pre-treatment: volume =129.6±150.5 mL; maximal axial diameter =43.0±15.8 mm; maximal orthogonal diameter =28.3±12.6 mm; follow-up: volume =66.6±95.0 mL, maximal axial diameter =24.5±19.9 mm, maximal orthogonal diameter =16.9±13.7, P<0.05 for all comparisons). Due to the uniformity in size throughout the vessel, high concordance was observed between diametric and volumetric measurements in the stented region with 93% and 92% between maximal axial diameter and volume for the true/false lumens, and 90% and 92% between maximal orthogonal diameter and volume for the true/false lumens. Large discrepancies were observed between the different measurement methods at regions distal to the stent graft, with up to 46% differences between maximal orthogonal diameter and volume., Conclusions: Volume measurement was shown to be a much more sensitive indicator in identifying lumen expansion/shrinkage at the distal stented region., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-814). ZS serves as an unpaid associate editor of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

In India, many people living with HIV (PLHIV) do not successfully initiate antiretroviral therapy (ART) after diagnosis. We conducted a clinic-based qualitative study at the Y.R. Gaitonde Centre for AIDS Research in Chennai, Tamil Nadu to explore factors that influence ART non-initiation. We interviewed 22 men and 15 women; median age was 42 (IQR, 36-48) and median CD4+ was 395 (IQR, 227-601). Participants were distrustful of HIV care freely available at nearby government facilities. Faced with the perceived need to access the private sector and therefore pay for medications and transportation costs, non-initiators with high CD4+ counts often decided to postpone ART until they experienced symptoms whereas non-initiators with low CD4+ counts often started ART but defaulted quickly after experiencing financial stressors or side effects. Improving perceptions of quality of care in the public sector, encouraging safe serostatus disclosure to facilitate stronger social support, and alleviating economic hardship may be important in encouraging ART initiation in India.

Reperfusion of the blood flow to ischemic myocardium is the standard treatment for patients suffering myocardial infarction. However, the reperfusion itself can also induce myocardial injury, in which the actual mechanism and its risk factors remain unclear. This work aims to study the mechanism of ischemia-reperfusion treatment using a three-dimensional (3D) oxygen diffusion model. An electrical model is then coupled to an oxygen model to identify the possible region of myocardial damage. Our findings show that the value of oxygen exceeds its optimum (>1.0) at the ischemic area during early reperfusion period. This complication was exacerbated in a longer ischemic period. While a longer reperfusion time causes a continuous excessive oxygen supply to the ischemic area throughout the reperfusion time. This work also suggests the use of less than 0.8 of initial oxygen concentration in the reperfusion treatment to prevent undesired upsurge at the early reperfusion period and further myocardial injury. We also found the region at risk for myocardial injury is confined in the ischemic vicinity revealed by its electrical conductivity impairment. Although there is a risk that reperfusion leads to myocardial injury for excessive oxygen accumulation, the reperfusion treatment is helpful in reducing the infarct size., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A monolithic, fully coupled fluid-structure interaction (FSI) computational framework was developed to account for dissection flap motion in acute type B aortic dissection (TBAD). Analysis of results included wall deformation, pressure, flow, wall shear stress (WSS), von Mises stress and comparison of hemodynamics between rigid wall and FSI models. Our FSI model mimicked realistic wall deformation that resulted in maximum compression of the distal true lumen (TL) by 21.4%. The substantial movement of intimal flap mostly affected flow conditions in the false lumen (FL). Flap motion facilitated more flow entering the FL at peak systole, with the TL to FL flow split changing from 88:12 in the rigid model to 83:17 in the FSI model. There was more disturbed flow in the FL during systole (5.8% FSI vs 5.2% rigid) and diastole (13.5% FSI vs 9.8% rigid), via a λ 2 -criterion. The flap-induced disturbed flow near the tears in the FSI model caused an increase of local WSS by up to 70.0% during diastole. This resulted in a significant reduction in the size of low time-averaged WSS (TAWSS) regions in the FL (113.11 cm 2 FSI vs 177.44 cm 2 rigid). Moreover, the FSI model predicted lower systolic pressure, higher diastolic pressure, and hence lower pulse pressure. Our results provided new insights into the possible impact of flap motion on flow in aortic dissections, which are particularly important when evaluating hemodynamics of acute TBAD. NOVELTY STATEMENT: Our monolithic fully coupled FSI computational framework is able to reproduce experimentally measured range of flap deformation in aortic dissection, thereby providing novel insights into the influence of physiological flap motion on the flow and pressure distributions. The drastic flap movement increases the flow resistance in the true lumen and causes more disturbed flow in the false lumen, as visualized through the λ 2 criterion. The flap-induced luminal pressure is dampened, thereby affecting pressure measures, which may serve as potential prognostic indicators for late complications in acute uncomplicated TBAD patients., (© 2020 John Wiley & Sons Ltd.)

Background: In India, which has the world's third-largest HIV epidemic, the extent to which levels of HIV-related stigma have changed during an era of ART scale-up is unknown., Methods: We analyzed data from the 2005-06 and 2015-16 National Family Health Surveys (NFHS) to estimate trends in two stigma domains among people in the general population: desires for social distance from people living with HIV (ie, unwillingness to interact) and fear of serostatus disclosure in the case of a hypothetical HIV infection. We fitted multivariable linear probability models to the data with year of NFHS as the explanatory variable and alternately specifying fear of disclosure or desires for social distance as the dependent variable. Analyses were stratified by sex, state, and high vs low HIV prevalence states., Results: We included data on 172 795 women and 159 194 men. Desires for social distance declined in 2015-16 compared with 2005-06 (38% in 2015-16 vs 43% in 2005-06; adjusted b =  -0.046; 95% confidence interval (CI = -0.049 to -0.043; P  < 0.001) but fear of serostatus disclosure increased (31% in 2005-06 vs 37% in 2015-16; adjusted b  = 0.058; 95% CI = 0.055-0.062; P  < 0.001). Declines in social distancing were more pronounced among men and in high HIV prevalence states. Increased fear of serostatus disclosure was greater among women and in high HIV prevalence states. There was significant variability in trends disaggregated by state., Conclusions: During the first decade of ART scale-up in India, fear of HIV serostatus disclosure in the general population increased despite a decline in desires for social distance., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

Myocardial infarction (MI) is the most common cause of a heart failure, which occurs due to myocardial ischemia leading to left ventricular (LV) remodeling. LV remodeling particularly occurs at the ischemic area and the region surrounds it, known as the border zone. The role of the border zone in initiating LV remodeling process urges the investigation on the correlation between early border zone changes and remodeling outcome. Thus, this study aims to simulate a preliminary conceptual work of the border zone formation and evolution during onset of MI and its effect towards early LV remodeling processes by incorporating the oxygen concentration effect on the electrophysiology of an idealized three-dimensional LV through electro-chemical coupled mathematical model. The simulation result shows that the region of border zone, represented by the distribution of electrical conductivities, keeps expanding over time. Based on this result, the border zone is also proposed to consist of three sub-regions, namely mildly, moderately, and seriously impaired conductivity regions, which each region categorized depending on its electrical conductivities. This division could be used as a biomarker for classification of reversible and irreversible myocardial injury and will help to identify the different risks for the survival of patient. Larger ischemic size and complete occlusion of the coronary artery can be associated with an increased risk of developing irreversible injury, in particular if the reperfusion treatment is delayed. Increased irreversible injury area can be related with cardiovascular events and will further deteriorate the LV function over time., (© 2020 John Wiley & Sons Ltd.)

Differential diagnosis of hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) is clinically challenging but important for treatment management. This study aims to phenotype HHD and HCM in 3D + time domain by using a multiparametric motion-corrected personalized modeling algorithm and cardiac magnetic resonance (CMR). 44 CMR data, including 12 healthy, 16 HHD and 16 HCM cases, were examined. Multiple CMR phenotype data consisting of geometric and dynamic variables were extracted globally and regionally from the models over a full cardiac cycle for comparison against healthy models and clinical reports. Statistical classifications were used to identify the distinctive characteristics and disease subtypes with overlapping functional data, providing insights into the challenges for differential diagnosis of both types of disease. While HCM is characterized by localized extreme hypertrophy of the LV, wall thickening/contraction/strain was found to be normal and in sync, though it was occasionally exaggerated at normotrophic/less severely hypertrophic regions during systole to preserve the overall ejection fraction (EF) and systolic functionality. Additionally, we observed that hypertrophy in HHD could also be localized, although at less extreme conditions (i.e. more concentric). While fibrosis occurs mostly in those HCM cases with aortic obstruction, only minority of HHD patients were found affected by fibrosis. We demonstrate that subgroups of HHD (i.e. preserved and reduced EF: HHDpEF & HHDrEF) have different 3D + time CMR characteristics. While HHDpEF has cardiac functions in normal range, dilation and heart failure are indicated in HHDrEF as reflected by low LV wall thickening/contraction/strain and synchrony, as well as much reduced EF., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Biliary cystadenoma is a rare benign tumour with the potential to transform into malignant carcinoma of the biliary ductal system. There is difficulty in differentiating a benign one from a malignant biliary cystadenoma, and therefore these lesions should always be completely resected. We report a case of biliary cystadenoma which underwent a complete resection.

Electronic Patient Reported Outcomes (PROs), which consist of questionnaires administered directly to patients via handheld device or computer, allow for the routine and systematic capture of sensitive domains as well as longitudinal data on functional status, symptom severity, and physical and psychological well-being. There have been few examples of PROs in HIV care in low- and middle-income countries (LMICs) and none in India. We conducted a study to assess the feasibility and acceptability of PROs at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, Tamil Nadu. We adapted an adherence and psychosocial questionnaire into an electronic PRO format and administered it to a convenience sample of 50 participants. Almost all participants indicated that the PRO questionnaire was easy to complete and understand (96%). The percentage who needed any staff help was 83% among illiterate participants but only 13% among literate participants ( p <0.001). In summary, an electronic PRO questionnaire was feasible and acceptable in an HIV care center in southern India. Further study, with special attention towards optimizing PROs for persons with low literacy and limited technology experience, is needed to maximize the potential of PROs within HIV care in India.

Objective: To evaluate the effect of a disease management programme in Kazakhstan on quality indicators for patients with hypertension, diabetes and chronic heart failure., Methods: A supportive, interdisciplinary, quality improvement programme was implemented between November 2014 and November 2015 at seven polyclinics in Pavlodar and Petropavlovsk. Quality improvement teams were established at each clinic and quality improvement tools were introduced, including patient flowsheets, decision support tools, patient registries, a patient recall process, support for patient self-management and patient follow-up with intensity adjusted for level of disease control. Clinic teams met for four 3-day interactive learning sessions within 1 year, with additional coaching visits. Implementation was managed by five local coordinators and consultants trained by international consultants. National and regional steering committees monitored progress., Findings: Between July and October 2015, the proportion of hypertensive patients with the recommended blood pressure increased from 24% (101/424) to 56% (228/409). Among patients with diabetes, the proportion who recently underwent eye examinations increased from 26% (101/391) to 71% (308/433); the proportion who had their low-density lipoprotein cholesterol measured increased from 57% (221/391) to 85% (369/433); and the proportion who had their albumin : creatinine ratio measured increased from 11% (44/391) to 49% (212/433). The proportion of chronic heart failure patients who underwent echocardiography rose from 91% (128/140) to 99% (157/158). All patients set themselves self-management goals., Conclusion: This intensive, supportive, multifaceted programme was associated with significant improvements in quality of care for patients with chronic disease. Further investment in coaching capacity is needed to extend the programme nationally., ((c) 2020 The authors; licensee World Health Organization.)

In India, there is little evidence on reasons for high rates of loss to HIV care. We conducted a clinic-based qualitative study at the YR Gaitonde Centre for AIDS Research and Education to explore factors that influence loss to care. In all, 17 men and 14 women were interviewed; median age was 42 (interquartile range [IQR], 36-48) and median CD4 count was 448 (IQR, 163-609). A majority reported avoiding treatment freely available at nearby government facilities because of disclosure concerns and perceptions of poor quality. As a result, participants sought care in the private sector where they were subjected to medication and transport costs. Life circumstances causing lost wages or unexpected expenditures therefore prevented participants from attending clinic, resulting in loss to care. Improving perceptions of quality of care in the public sector, addressing disclosure concerns, and reducing economic hardships among people living with HIV may be important in reducing loss to HIV care in India.

Myocardial infarct extension, a process involving the enlargement of infarct and border zone, leads to progressive degeneration of left ventricular (LV) function and eventually gives rise to heart failure. Despite carrying a high risk, the causation of infarct extension is still a subject of much speculation. In this study, patient-specific LV models were developed to investigate the correlation between infarct extension and impaired regional mechanics. Subsequently, sensitivity analysis was performed to examine the causal factors responsible for the impaired regional mechanics observed in regions surrounding the infarct and border zone. From our simulations, fibre strain, fibre stress and fibre stress-strain loop (FSSL) were the key biomechanical variables affected in these regions. Among these variables, only FSSL was correlated with infarct extension, as reflected in its work density dissipation (WDD) index value, with high WDD indices recorded at regions with infarct extension. Impaired FSSL is caused by inadequate contraction force generation during the isovolumic contraction and ejection phases. Our further analysis revealed that the inadequacy in contraction force generation is not necessarily due to impaired myocardial intrinsic contractility, but at least in part, due to inadequate muscle fibre stretch at end-diastole, which depresses the ability of myocardium to generate adequate contraction force in the subsequent systole (according to the Frank-Starling law). Moreover, an excessively stiff infarct may cause its neighbouring myocardium to be understretched at end-diastole, subsequently depressing the systolic contractile force of the neighbouring myocardium, which was found to be correlated with infarct extension., (© 2019 John Wiley & Sons, Ltd.)

Background: HIV-related stigma among people living with HIV (PLHIV) is associated with worse health outcomes. We used longitudinal data from a multi-site cohort in South Africa to assess changes over time in stigma after HIV diagnosis and determine whether antiretroviral therapy (ART) initiation is associated with stigma reduction., Methods: We administered the Internalized AIDS-Related Stigma Scale (IARSS, a six-item dichotomous scale questionnaire) at baseline, three months, and six months to newly diagnosed ART-eligible participants between 2014-2015. A confirmatory factor analysis indicated that the IARSS contained a four-item internalized stigma factor (α=0.80) and a two-item disclosure concerns factor (α=0.75). We fitted multiple logistic regression models specifying internalized stigma/disclosure concerns at six months as the outcome and ART initiation as the predictor of interest., Results: Of the 500 participants (187 men and 313 women) enrolled, 308 (62%) initiated ART. Internalized stigma declined among people entering care (mean score, 1.0 to 0.7, p<0.01); however, disclosure concerns remained unchanged (percentage endorsing either disclosure concern item, 78% to 77%, p=0.23). These findings were similar between ART initiators and non-initiators. We estimated a statistically significant positive association between ART initiation and disclosure concerns at six months (OR=1.88; 95% CI, 1.20-2.94) but not between ART initiation and internalized stigma at six months (OR=1.15; 95% CI, 0.75-1.78)., Conclusions: Among ART-eligible South African PLHIV entering into HIV care, internalized stigma modestly declined over time but disclosure concerns persisted. PLHIV who initiated ART were more likely to have persistent disclosure concerns over time as compared with those who did not start ART.

Flow energetics have been proposed as early indicators of progressive left ventricular (LV) functional impairment in patients with myocardial infarction (MI), but its correlation with individual MI parameters has not been fully explored. Using electro-fluid-structure interaction LV models, this study investigated the correlation between four MI parameters: infarct size, infarct multiplicity, regional enhancement of contractility at the viable myocardium area (RECVM), and LV mechanical dyssynchrony (LVMD) with intraventricular vortex and flow energetics. In LV with small infarcts, our results showed that infarct appearance amplified the energy dissipation index (DI), where substantial viscous energy loss was observed in areas with high flow velocity and near the infarct-vortex interface. The LV with small multiple infarcts and RECVM showed remarkable DI increment during systole and diastole. In correlation analysis, the systolic kinetic energy fluctuation index (E') was positively related to ejection fraction (EF) (R 2  = 0.982) but negatively correlated with diastolic E' (R 2  = 0.970). Diastolic E' was inversely correlated with vortex kinetic energy (R 2  = 0.960) and vortex depth (R 2  = 0.876). We showed an excessive systolic DI could differentiate infarcted LV with normal EF from healthy LV. Strong flow acceleration, LVMD, and vortex-infarct interactions were predominant factors that induced excessive DI in infarcted LVs. Instead of causing undesired flow turbulence, high systolic E' suggested the existence of energetic flow acceleration, while high diastolic E' implied an inefficient diastolic filling. Thus, systolic E' is not a suitable early indicator for progressive LV dysfunction in MI patients, while diastolic E' may be a useful index to indicate diastolic impairment in these patients., (© 2019 John Wiley & Sons, Ltd.)

Helminths are highly prevalent metazoan parasites that infect over a billion of the world's population. Hosts have evolved numerous mechanisms to drive the expulsion of these parasites via Th2-driven immunity, but these responses must be tightly controlled to prevent equally devastating immunopathology. However, mechanisms that regulate this balance are still unclear. Here we show that the vigorous Th2 immune response driven by the small intestinal helminth Trichinella spiralis, is associated with increased TGFβ signalling responses in CD4+ T-cells. Mechanistically, enhanced TGFβ signalling in CD4+ T-cells is dependent on dendritic cell-mediated TGFβ activation which requires expression of the integrin αvβ8. Importantly, mice lacking integrin αvβ8 on DCs had a delayed ability to expel a T. spiralis infection, indicating an important functional role for integrin αvβ8-mediated TGFβ activation in promoting parasite expulsion. In addition to maintaining regulatory T-cell responses, the CD4+ T-cell signalling of this pleiotropic cytokine induces a Th17 response which is crucial in promoting the intestinal muscle hypercontractility that drives worm expulsion. Collectively, these results provide novel insights into intestinal helminth expulsion beyond that of classical Th2 driven immunity, and highlight the importance of IL-17 in intestinal contraction which may aid therapeutics to numerous diseases of the intestine., Competing Interests: The authors have declared that no competing interests exist.

Background: Existing clinical diagnostic and assessment methods could be improved to facilitate early detection and treatment of cardiac dysfunction associated with acute myocardial infarction (AMI) to reduce morbidity and mortality., Purpose: To develop 3D personalized left ventricular (LV) models and thickening assessment framework for assessing regional wall thickening dysfunction and dyssynchrony in AMI patients., Study Type: Retrospective study, diagnostic accuracy., Subjects: Forty-four subjects consisting of 15 healthy subjects and 29 AMI patients., Field Strength/sequence: 1.5T/steady-state free precession cine MRI scans; LGE MRI scans., Assessment: Quantitative thickening measurements across all cardiac phases were correlated and validated against clinical evaluation of infarct transmurality by an experienced cardiac radiologist based on the American Heart Association (AHA) 17-segment model., Statistical Test: Nonparametric 2-k related sample-based Kruskal-Wallis test; Mann-Whitney U-test; Pearson's correlation coefficient., Results: Healthy LV wall segments undergo significant wall thickening (P < 0.05) during ejection and have on average a thicker wall (8.73 ± 1.01 mm) compared with infarcted wall segments (2.86 ± 1.11 mm). Myocardium with thick infarct (ie, >50% transmurality) underwent remarkable wall thinning during contraction (thickening index [TI] = 1.46 ± 0.26 mm) as opposed to healthy myocardium (TI = 4.01 ± 1.04 mm). For AMI patients, LV that showed signs of thinning were found to be associated with a significantly higher percentage of dyssynchrony as compared with healthy subjects (dyssynchrony index [DI] = 15.0 ± 5.0% vs. 7.5 ± 2.0%, P < 0.01). Also, a strong correlation was found between our TI and left ventricular ejection fraction (LVEF) (r = 0.892, P < 0.01), and moderate correlation between DI and LVEF (r = 0.494, P < 0.01)., Data Conclusion: The extracted regional wall thickening and DIs are shown to be strongly correlated with infarct severity, therefore suggestive of possible practical clinical utility., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1006-1019., (© 2018 International Society for Magnetic Resonance in Medicine.)

We used data from 660 people living with HIV in southern India to evaluate the reliability, validity, and factor structure of the Internalized AIDS-Related Stigma Scale. Exploratory factor analysis revealed the presence of 2 factors: a 2-item factor related to disclosure concerns and a 4-item factor related to self-hatred. The self-hatred factor demonstrated acceptable internal consistency (Cronbach α = .80). As evidence of construct validity, both factors were correlated with depression symptom severity as measured by the Patient Health Questionnaire-9. Further study is needed to understand the correlates of these factors and their impact on the Indian HIV care continuum.

Polyphthalaldehyde is a self-developing resist material for electron beam and thermal scanning probe lithography (t-SPL). Removing the resist in situ (during the lithography process itself) simplifies processing and enables direct pattern inspection, however, at the price of a low etch resistance of the resist. To convert the material into a etch resistant hard mask, we study the selective cyclic infiltration of trimethyl-aluminum (TMA)/water into polyphthalaldehyde. It is found that TMA diffuses homogeneously through the resist, leading to material expansion and formation of aluminum oxide concurrent to the exposure to water and the degradation of the polyphthalaldehyde polymer. The plasma etch resistance of the infiltrated resist is significantly improved, as well as its stability. Using a silicon substrate coated with 13 nm silicon nitride and 7 nm cross-linked polystyrene, high resolution polyphthalaldehyde patterning is performed using t-SPL. After TMA/H 2 O infiltration, it is demonstrated that pattern transfer into silicon can be achieved with good fidelity for structures as small as 10 nm, enabling >10× amplification and low surface roughness. The presented results demonstrate a simplified use of polyphthalaldehyde resist, targeting feature scales at nanometer range, and suggest that trimethyl-aluminum infiltration can be applied to other resist-based lithography techniques.

Introduction: Cross-sectional evidence suggests that internalized HIV stigma is associated with lower likelihoods of antiretroviral therapy (ART) initiation and HIV-1 RNA suppression among people living with HIV (PLWH). This study examined these associations with longitudinal data spanning the first nine months following HIV diagnosis and explored whether avoidant coping mediates these associations., Methods: Longitudinal data were collected from 398 South African PLWH recruited from testing centres in 2014 to 2015. Self-report data, including internalized stigma and avoidant coping (denying and distracting oneself from stressors), were collected one week and three months following HIV diagnosis. ART initiation at six months and HIV-1 RNA at nine months were extracted from the South Africa National Health Laboratory Service database. Two path analyses were estimated, one testing associations between internalized stigma, avoidant coping and ART initiation, and the other testing associations between internalized stigma, avoidant coping and HIV-1 RNA suppression., Results: Participants were 36 years old, on average, and 63% identified as female, 18% as Zulu and 65% as Xhosa. The two path models fit the data well (ART initiation outcome: X 2 (7) = 8.14, p = 0.32; root mean square error of approximation (RMSEA) = 0.02; comparative fit index (CFI) = 0.92; HIV-1 RNA suppression outcome: X 2 (7)  = 6.58, p = 0.47; RMSEA = 0.00; CFI = 1.00). In both models, internalized stigma one week after diagnosis was associated with avoidant coping at three months, controlling for avoidant coping at one week. In turn, avoidant coping at three months was associated with lower likelihood of ART initiation at six months in the first model and lower likelihood of HIV-1 RNA suppression at nine months in the second model. Significant indirect effects were observed between internalized stigma with ART non-initiation and unsuppressed HIV-1 RNA via the mediator of avoidant coping., Conclusions: Internalized stigma experienced soon after HIV diagnosis predicted lower likelihood of ART initiation and HIV-1 RNA suppression over the first year following HIV diagnosis. Avoidant coping played a role in these associations, suggesting that PLWH who internalize stigma engage in greater avoidant coping, which in turn worsens medication- and health-related outcomes. Interventions are needed to address internalized stigma and avoidant coping soon after HIV diagnosis to enhance treatment efforts during the first year after HIV diagnosis., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Population-level improvements in knowledge about HIV may reduce the stigma attached to HIV and ensure maximal uptake of HIV prevention initiatives. The extent to which levels of HIV knowledge in the general population of sub-Saharan Africa have changed in the current era of antiretroviral therapy (ART) scale-up remains unknown., Methods: Data on HIV knowledge in the general population were drawn from the 2003 to 2015 Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) of 33 countries in sub-Saharan Africa. The DHS/AIS contain five questions on HIV prevention and transmission that have been used by the Joint United Nations Programme on HIV/AIDS (UNAIDS) as a core indicator of HIV knowledge. We created a composite HIV knowledge variable equal to the number of correct responses to these five questions; a participant was considered to have comprehensive knowledge of HIV (yes/no) if he/she answered all five questions correctly. We fitted negative binomial regression models with cluster-correlated robust standard errors and country fixed effects, adjusted for socio-demographic variables, specifying HIV knowledge as the dependent variable and year as the explanatory variable. As an alternative parameterization, we also fitted a multivariable linear probability model with cluster-correlated robust standard errors and country fixed effects specifying comprehensive knowledge of HIV as the dependent variable., Results: A total of 791,186 women and 395,891 men participating in 75 DHS/AIS were included in the analyses. The mean HIV knowledge score was 3.7 among women and 3.9 among men (p < 0.001). Only 35% of women and 41% of men (p < 0.001) had a comprehensive knowledge of HIV. We estimated a modest but statistically significant positive association between year of DHS/AIS and HIV knowledge (adjusted b = 0.005; 95% confidence interval (CI), 0.001 to 0.009). Similarly, we estimated a statistically significant positive association between year of DHS/AIS and comprehensive knowledge of HIV (adjusted b = 0.011; 95% CI, 0.005 to 0.017), suggesting an approximately 1% relative increase per year in the percentage of the general population who possess a comprehensive knowledge of HIV., Conclusions: There have been minimal improvements over time in HIV knowledge across sub-Saharan Africa., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Objective: This study investigated the intraventricular flow dynamics in ischaemic heart disease patients., Patients and Methods: Fourteen patients with normal ejection fraction and 16 patients with reduced ejection fraction were compared with 20 healthy individuals. Phase-contrast MRI was used to assess intraventricular flow variables and speckle-tracking echocardiography to assess myocardial strain and left ventricular (LV) dyssynchrony. Infarct size was acquired using delayed-enhancement MRI., Results: The results obtained showed no significant differences in intraventricular flow variables between the healthy group and the patients with normal ejection fraction group, whereas considerable reductions in kinetic energy (KE) fluctuation index, E' (P<0.001) and vortex KE (P=0.003) were found in the patients with reduced ejection fraction group. In multivariate analysis, only vortex KE and infarct size were significantly related to LV ejection fraction (P<0.001); furthermore, vortex KE was correlated negatively with energy dissipation, energy dissipation index (r=-0.44, P=0.021)., Conclusion: This study highlights that flow energetic indices have limited applicability as early predictors of LV progressive dysfunction, whereas vortex KE could be an alternative to LV performance.

Background: Low frequency sound wave stimulation therapy has become increasingly popular in the rehabilitation fields, due to its ease, less fatiguing and time efficient application., Objective: This 12-week pilot study examines the efficacy of applying low frequency sound wave stimulation (between 16-160 Hz) through both hands and feet on relieving pain and improving functional ability in patients with chronic back pain., Methods: Twenty-three participants with chronic shoulder (eleven participants) or low back pain (twelve participants) underwent a 12-week vibration therapy program of three sessions per week. A low frequency sound wave device comprising four piezoelectric vibration-type tactile tranducers enclosed in separate 5-cm diameter circular plates, which generate sinusoidal vibratory stimuli at a frequency of 16-160 Hz, was used in this study. Primary outcome measure was pain sensation measured using the Visual Analogue Scale (P-VAS). The secondary outcome measures were pain-related disability measured using the pain disability index (PDI) and quality of life measured using the SF-12., Results: At week 12, significant reductions in pain sensation and pain-related disability were observed, with mean reductions of 3.5 points in P-VAS and 13.5 points in the PDI scores. Sixty-five percent of the participants had a reduction of at least 3 points on the P-VAS score, while 52% participants showed a decrease of at least 10 points in the PDI score. Significant improvement was observed in the SF-12 physical composite score but not the mental composite score., Conclusions: The preliminary findings showed that passive application of low frequency sound wave stimulation therapy through both hands and feet was effective in alleviating pain and improving functional ability in patients with chronic back pain.

This study aims to investigate the measurement of left ventricular flow propagation velocity, V p , using phase contrast magnetic resonance imaging and to assess the discrepancies resulting from inflow jet direction and individual left ventricular size. Three V p measuring techniques, namely non-adaptive (NA), adaptive positions (AP) and adaptive vectors (AV) method, were suggested and compared. We performed the comparison on nine healthy volunteers and nine post-infarct patients at four measurement positions, respectively, at one-third, one-half, two-thirds and the conventional 4 cm distances from the mitral valve leaflet into the left ventricle. We found that the V p measurement was affected by both the inflow jet direction and measurement positions. Both NA and AP methods overestimated V p , especially in dilated left ventricles, while the AV method showed the strongest correlation with the isovolumic relaxation myocardial strain rate (r = 0.53, p < 0.05). Using the AV method, notable difference in mean V p was also observed between healthy volunteers and post-infarct patients at positions of: one-half (81 ± 31 vs. 58 ± 25 cm/s), two-thirds (89 ± 32 vs. 45 ± 15 cm/s) and 4 cm (98 ± 23 vs. 47 ± 13 cm/s) distances. The use of AV method and measurement position at one-half distance was found to be the most suitable method for assessing diastolic dysfunction given varying left ventricular sizes and inflow jet directions.

Psychosocial conditions such as depression, intimate partner violence (IPV), and history of childhood sexual abuse (CSA) have been associated with poor HIV-related outcomes. In India, which has the third largest HIV epidemic in the world, little is understood about the impact of psychosocial conditions on people living with HIV (PLHIV). We aimed to understand the prevalence and correlates of psychosocial conditions among PLHIV entering into HIV care at the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India. Thirteen questions were added to the standard voluntary counseling and testing questionnaire, including the Patient Health Questionnaire-9 (a depression scale) and questions assessing for CSA and IPV. We fitted logistic regression models, stratified by gender, with psychosocial condition as the outcome of interest and substance use variables and socio-demographic variables as the correlates of interest. Three hundred and eighty-three persons were enrolled into the study; of these, 253 (66%) tested positive for HIV, including 149 men and 104 women, and were included in the models. More than one-quarter (28%) of the men and 19% of the women reported at least one psychosocial condition (probable depression, CSA, or IPV). In adjusted analysis, current alcohol use was associated with greater than two times higher odds of a psychosocial condition (Adjusted Odds Ratio = 2.24, 95% CI, 1.04-4.85) among men. In conclusion, we estimated the prevalence of probable depression, CSA, and IPV among PLHIV presenting for HIV care in southern India and found that, among male PLHIV, alcohol use was associated with a markedly higher odds of reporting a psychosocial condition. Further study is needed to characterize alcohol use among male PLHIV and the possible deleterious impact of psychosocial conditions and alcohol use on HIV-related outcomes in India.

Introduction: HIV-related stigma hampers treatment and prevention efforts worldwide. Effective interventions to counter HIV-related stigma are greatly needed. Although the "contact hypothesis" suggests that personal contact with persons living with HIV (PLHIV) may reduce stigmatizing attitudes in the general population, empirical evidence in support of this hypothesis is lacking. Our aim was to estimate the association between personal contact with PLHIV and HIV-related stigma among the general population of sub-Saharan Africa., Methods: Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 26 African countries between 2003 and 2008. We fitted multivariable logistic regression models with country-level fixed effects, specifying social distance as the dependent variable and personal contact with PLHIV as the primary explanatory variable of interest., Results: We analyzed data from 206,717 women and 91,549 men living in 26 sub-Saharan African countries. We estimated a statistically significant negative association between personal contact with PLHIV and desires for social distance (adjusted odds ratio [AOR] = 0.80; p  < 0.001; 95% Confidence Interval [CI], 0.73-0.88). In a sensitivity analysis, a similar finding was obtained with a model that used a community-level variable for personal contact with PLHIV (AOR = 0.92; p  < 0.001; 95% CI, 0.89-0.95)., Conclusion: Personal contact with PLHIV was associated with reduced desires for social distance among the general population of sub-Saharan Africa. More contact interventions should be developed and tested to reduce the stigma of HIV., Competing Interests: The authors declare that they have no competing interests.

Background: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer. Herein, we examined crosstalk between ErbB2 and IRSs using cancer cell lines and transgenic mouse models., Methods: MMTV-ErbB2 and MMTV-IRS2 transgenic mice were crossed to create hemizygous MMTV-ErbB2/MMTV-IRS2 bigenic mice. Signaling crosstalk between ErbB2 and IRSs was examined in vitro by knockdown or overexpression followed by western blot analysis for downstream signaling intermediates and growth assays., Results: A cross between MMTV-ErbB2 and MMTV-IRS2 mice demonstrated no enhancement of ErbB2 mediated mammary tumorigenesis or metastasis by elevated IRS2. Substantiating this, overexpression or knockdown of IRS1 or IRS2 in MMTV-ErbB2 mammary cancer cell lines had little effect upon ErbB2 signaling. Similar results were obtained in human mammary epithelial cells (MCF10A) and breast cancer cell lines., Conclusion: Despite previous evidence suggesting that ErbB receptors can bind and activate IRSs, our findings indicate that ErbB2 does not cooperate with the IRS pathway in these models to promote mammary tumorigenesis.

Background: Depression is highly prevalent in people living with HIV (PLHIV) and is associated with increased morbidity and mortality. In India, where access to mental health specialists is limited, little is known about the attitude of HIV clinicians toward depression in PLHIV., Methods: We administered a questionnaire to HIV clinicians attending the 2015 Chennai Antiretroviral Therapy Symposium that assessed respondents' level of agreement with 29 statements regarding the etiology, importance, and management of depression and whether they felt capable and willing to manage depression in PLHIV., Results: The 69 respondents were from 9 Indian states. Most respondents agreed that depression in PLHIV is a serious problem (91%) and is associated with poorer HIV-related outcomes (62%-81%). Although most respondents (76%) reported feeling comfortable discussing mental health problems with PLHIV, almost half (48%) admitted that lack of knowledge and training about mental health issues hindered the diagnosis and treatment of depression in PLHIV. With few exceptions, there were no significant differences in responses by gender, urban/rural practice location, or government versus private practice., Conclusions: Indian HIV clinicians believe that depression in PLHIV is important and are willing to manage depression in the HIV primary care setting. These findings suggest that HIV clinicians require further training to deliver evidence-based interventions to treat PLHIV with depression., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: HIV-related stigma is associated with increased risk-taking behavior, reduced uptake of HIV testing, and decreased adherence to antiretroviral therapy (ART). Although ART scale-up may reduce HIV-related stigma, the extent to which levels of stigma in the general population have changed during the era of ART scale-up in sub-Saharan Africa is unknown., Methods: Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 31 African countries between 2003 and 2013. We fitted multivariable linear regression models with cluster-correlated robust standard errors and country fixed effects, specifying social distance or anticipated stigma as the dependent variable and year as the primary explanatory variable of interest., Results: We estimated a statistically significant negative association between year and desires for social distance (b = -0.020; P < 0.001; 95% confidence interval: -0.026 to -0.015) but a statistically significant positive association between year and anticipated stigma (b = 0.023; P < 0.001; 95% confidence interval: 0.018 to 0.027). In analyses stratified by HIV prevalence above or below the sample median, declines in social distancing over time were more pronounced among countries with a higher HIV prevalence., Conclusions: Concomitant with ART scale-up in sub-Saharan Africa, anticipated stigma in the general population increased despite a decrease in social distancing toward people living with HIV. Although ART scale-up may help reduce social distancing toward people living with HIV, particularly in high-prevalence countries, other interventions targeting symbolic or instrumental concerns about HIV may be needed.

Objectives: We estimated the association between antiretroviral therapy (ART) uptake and HIV-related stigma at the population level in sub-Saharan Africa., Methods: We examined trends in HIV-related stigma and ART coverage in sub-Saharan Africa during 2003 to 2013 using longitudinal, population-based data on ART coverage from the Joint United Nations Program on HIV/AIDS and on HIV-related stigma from the Demographic and Health Surveys and AIDS Indicator Surveys. We fitted 2 linear regression models with country fixed effects, with the percentage of men or women reporting HIV-related stigma as the dependent variable and the percentage of people living with HIV on ART as the explanatory variable., Results: Eighteen countries in sub-Saharan Africa were included in our analysis. For each 1% increase in ART coverage, we observed a statistically significant decrease in the percentage of women (b = -0.226; P = .007; 95% confidence interval [CI] = -0.383, -0.070) and men (b = -0.281; P = .009; 95% CI = -0.480, -0.082) in the general population reporting HIV-related stigma., Conclusions: An important benefit of ART scale-up may be the diminution of HIV-related stigma in the general population.

Cine MRI is a clinical reference standard for the quantitative assessment of cardiac function, but reproducibility is confounded by motion artefacts. We explore the feasibility of a motion corrected 3D left ventricle (LV) quantification method, incorporating multislice image registration into the 3D model reconstruction, to improve reproducibility of 3D LV functional quantification. Multi-breath-hold short-axis and radial long-axis images were acquired from 10 patients and 10 healthy subjects. The proposed framework reduced misalignment between slices to subpixel accuracy (2.88 to 1.21 mm), and improved interstudy reproducibility for 5 important clinical functional measures, i.e. end-diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D-sphericity index, as reflected in a reduction in the sample size required to detect statistically significant cardiac changes: a reduction of 21-66%. Our investigation on the optimum registration parameters, including both cardiac time frames and number of long-axis (LA) slices, suggested that a single time frame is adequate for motion correction whereas integrating more LA slices can improve registration and model reconstruction accuracy for improved functional quantification especially on datasets with severe motion artefacts.