Typhoid fever: clinical features

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Treatment of breast cancer stem cells with oncolytic herpes simplex virus

Cancer stem cells have recently been isolated from several different solid tumors. In breast cancer, the $CD44^{+} CD24^{−/low}$ population is considered to comprise stem-like cells. The identification of cancer stem cells has provided new targets for the development of therapeutics. Oncolytic herpes simplex viruses (oHSVs) are an effective strategy for killing breast cancer cells and treating breast tumors in preclinical models. Here, we examined the efficacy of the oHSV G47Δ in killing breast cancer stem cells. Human breast cancer cell line SK-BR-3 and human primary breast cancer cells were cultured in suspension under conditions conducive to the growth of stem cells. They generated mammospheres, which had cancer stem cell properties. The proportion of $CD44^{+} CD24^{−/low}$ cells in these mammospheres exceeded 95%, as determined by flow cytometry. The mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. G47Δ contains the LacZ gene, and X-gal staining of infected cells in vitro and in vivo showed the replication and spread of the virus. G47Δ was found to be highly cytotoxic to the $CD44^{+} CD24^{−/low}$ population in vitro, even when injected at low multiplicities of infection, and G47Δ treatment in vivo significantly inhibited tumor growth compared with mock treatment. This study demonstrates that oHSV is effective against breast cancer stem cells and could be a beneficial strategy for treating breast cancer patients

Thermal Stability of Thin Au Films Deposited on Salt Whiskers

Thin metal films deposited on patterned or rough substrates play an increasing role in microelectronics, sensing, catalysis, and other areas of nanotechnology. However, the thermal stability and solid state dewetting of thin metal films with complex three-dimensional architecture is still poorly understood. In this work we employed a model system of nanocrystalline Au thin films deposited on prismatic single crystalline KCl whiskers to study the solid state dewetting of thin films in a three-dimensional setting. The arrays of KCl whiskers were grown on porous substrates under well-defined humidity and temperature conditions. Single crystalline prismatic KCl whiskers with a very high aspect ratio, [001] axis and {100} side facets were obtained. The whiskers were coated with thin conformal Au films of 20-30 nm in thickness. The annealing of these core-shell whiskers at the temperature of 350oC resulted in solid state dewetting of the Au film, with the dewetting processes occurring much faster along the whisker edges than on the side facets. The orientation relationships between Au and KCl were determined by employing similarly prepared thin Au films deposited on the flat KCl (100) substrates. Inspired by our experimental results, we developed a numerical model describing the curvature-gradient driven and surface diffusion-controlled growth of a hole in the thin film deposited on a curved substrate. The model predicted the growth of anisotropic elliptical holes elongated along the whisker axis. We discuss the experimental results in terms of the proposed model, indicating the importance of the change in orientation relationship between the Au grains and KCl whisker along the whisker edges

Thermal Stability of Thin Au Films Deposited on Salt Whiskers

Thin metal films deposited on patterned or rough substrates play an increasing role in microelectronics, sensing, catalysis, and other areas of nanotechnology. However, the thermal stability and solid state dewetting of thin metal films with complex three-dimensional architecture is still poorly understood. In this work we employed a model system of nanocrystalline Au thin films deposited on prismatic single crystalline KCl whiskers to study the solid state dewetting of thin films in a three-dimensional setting. The arrays of KCl whiskers were grown on porous substrates under well-defined humidity and temperature conditions. Single crystalline prismatic KCl whiskers with a very high aspect ratio, [001] axis and {100} side facets were obtained. The whiskers were coated with thin conformal Au films of 20-30 nm in thickness. The annealing of these core-shell whiskers at the temperature of 350oC resulted in solid state dewetting of the Au film, with the dewetting processes occurring much faster along the whisker edges than on the side facets. The orientation relationships between Au and KCl were determined by employing similarly prepared thin Au films deposited on the flat KCl (100) substrates. Inspired by our experimental results, we developed a numerical model describing the curvature-gradient driven and surface diffusion-controlled growth of a hole in the thin film deposited on a curved substrate. The model predicted the growth of anisotropic elliptical holes elongated along the whisker axis. We discuss the experimental results in terms of the proposed model, indicating the importance of the change in orientation relationship between the Au grains and KCl whisker along the whisker edges

Gradient bandgap narrowing in severely deformed ZnO nanoparticles

Gradient nanostructured metallic materials with a gradual change of grain boundary and dislocation density display unprecedent mechanical properties. Herein, we uncover a gradient of point defects concentration and concomitant gradient bandgap (E g) narrowing in metal oxide nanoparticles processed by a combination of severe shearing and frictional sliding deformation. Using the valence electron-energy loss spectroscopy technique, we find a gradual decrease of E g from 2.93 eV in the interior to 2.43 eV at the edge of the high-pressure torsion processed ZnO flake-shaped particle. This work paves the way to strain engineering of gradient-structured metal oxide semiconductors for unique functional properties

Experience with chronic haemodialysis in Johannesburg

Since 1966 the treatment for patients with end-stage renal disease in Johannesburg has primarily been renal transplantation. This has required an adequate programme of regular dialysis. All patients were treated at the central hospital or at two small satellite units. A total of 158 patients, mean age 34,2 years (88 males) have been dialysed. The mean duration on dialysis prior to transplantation was 5,6 months (range 1 week - 23 months). The commonest cause of renal failure in males was chronic glomerulonephritis (63%), whereas in females it was analgesic nephropathy (39%). Twenty-seven patients (17%) died while on dialysis, including 6 who had had unsuccessful transplantations. Renal osteodystrophy was diagnosed in 30% of the patients. Hepatitis has been endemic among both patients and staff. Nephrectomies were done in 106 patients. Ten patients had operations for peptic ulcer and 5 parathyroidectomies were performed. The number of patients unsuccessfully transplanted, or who died, was less than the number of new patients requiring treatment. In addition, an increasing proportion of patients have become 'relatively untransplaotable'. This has led to overloading of facilities.S. Afr. Med. J., 48, 1821 (1974

Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada.

IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration

Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base

Life-Expectancy Disparities Among Adults With HIV in the United States and Canada: The Impact of a Reduction in Drug- and Alcohol-Related Deaths Using the Lives Saved Simulation Model.

Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004-2007, 2008-2011, and 2012-2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004-2007 to 2012-2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities

A systematic review of primary care models for non-communicable disease interventions in Sub-Saharan Africa

Background Chronic diseases, primarily cardiovascular disease, respiratory disease, diabetes and cancer, are the leading cause of death and disability worldwide. In sub-Saharan Africa (SSA), where communicable disease prevalence still outweighs that of non-communicable disease (NCDs), rates of NCDs are rapidly rising and evidence for primary healthcare approaches for these emerging NCDs is needed. Methods A systematic review and evidence synthesis of primary care approaches for chronic disease in SSA. Quantitative and qualitative primary research studies were included that focused on priority NCDs interventions. The method used was best-fit framework synthesis. Results Three conceptual models of care for NCDs in low- and middle-income countries were identified and used to develop an a priori framework for the synthesis. The literature search for relevant primary research studies generated 3759 unique citations of which 12 satisfied the inclusion criteria. Eleven studies were quantitative and one used mixed methods. Three higher-level themes of screening, prevention and management of disease were derived. This synthesis permitted the development of a new evidence-based conceptual model of care for priority NCDs in SSA. Conclusions For this review there was a near-consensus that passive rather than active case-finding approaches are suitable in resource-poor settings. Modifying risk factors among existing patients through advice on diet and lifestyle was a common element of healthcare approaches. The priorities for disease management in primary care were identified as: availability of essential diagnostic tools and medications at local primary healthcare clinics and the use of standardized protocols for diagnosis, treatment, monitoring and referral to specialist care