Cytogenetic Analysis After Temporary Residence in the Area of the Uncontrolled Ruthenium-106 Release in Russia in September 2017.

In September and October 2017, elevated atmospheric ruthenium contamination was measured in several European countries. The most probable origin of this release of radionuclides was reconstructed to be the Southern Ural region. During that time, five workers from a German company stayed up to 2 wk about 120 km from the Chelyabinsk region in Ekaterinburg, Russia. No clinical symptoms were reported during or after the suspected radiation exposure, and no internal contamination was found in whole-body measurements. However, to investigate radiation protection issues and to clarify the workers' situation in order to reassure them, as they planned to continue working in Ekaterinburg, our laboratory was urgently requested by the company's occupational physician to perform biodosimetry using dicentric analysis to determine if the workers have been exposed to radiation by incorporation of radionuclides. The workers' dicentric yields have been compared to reference data of background frequencies in unexposed individuals, but, as it is not reasonable to quantify individual absorbed radiation doses from internalized beta emitters due to various confounding factors, individual dose estimation has not been performed. Dicentric frequencies for two workers differed significantly from the mean laboratory background level, which could have been induced by an exposure to incorporated radionuclides due to beta emissions by Ru or to gamma irradiation by the decay nuclide of Ru. However, the maximum absorbed radiation doses calculated for a resident in the Ru-contaminated area during that time does not correspond to the observed dicentric frequencies. It cannot be excluded that their dicentric frequencies were already elevated before September 2017, potentially induced by an earlier radiation exposure to diagnostic x rays or even by chance.

How does dietary particle size affect carnivore gastrointestinal transit: A dog model.

The effect of dietary particle size on gastrointestinal transit in carnivores has not been studied and might offer more insight into their digestive physiology. This study evaluated the effect of two dietary particle sizes (fine = 7.8 mm vs. coarse = 13 mm) of chunked day-old chicks on transit parameters in dogs. Six beagle dogs were fed both dietary treatments in a crossover design of 7 days with transit testing on the fifth day. Transit parameters were assessed using two markers, that is a wireless motility capsule (IntelliCap® ) and titanium oxide (TiO2 ). Dietary particle size did not affect gastric emptying time (GRT), small bowel transit time (SBTT), colonic transit time (CTT) and total transit time (aTTT) of the capsule (p > .05). There was no effect of dietary particle size on TiO2 mean retention time (MRT) (p > .05). The time of last TiO2 excretion (MaxRT) differed (p = .013) between diets, being later for the coarse diet. Both MRT (R = 0.617, p = .032) and MaxRT (R = 0.814; p = .001) were positively correlated to aTTT. The ratio MRT/aTTT tended towards a difference between diets (p = .059) with the coarse diet exceeding fine diet values. Results show that the difference between capsule measurements and TiO2 is larger for the fine than the coarse diet suggesting that the capsule becomes more accurate when dietary particle size approaches marker size. Dietary particle size might have affected transit parameters but differences are too small to claim major physiological consequences.

FRAILTY, FOOD INSECURITY, AND NUTRITIONAL STATUS IN PEOPLE LIVING WITH HIV.

BACKGROUND: Nutritional status and food insecurity are associated with frailty in the general U.S. population, yet little is known about this in the aging population of people living with HIV (PLWH). OBJECTIVES: Given the potential importance of nutrition and the amenability to intervention, we examined the association between nutritional status, food insecurity, and frailty in PLWH. DESIGN: Cross sectional study. SETTING: Boston, Massachusetts, U.S.A. PARTICIPANTS: 50 PLWH, age ≥45 years, recruited from a cohort study examining risk factors for cardiovascular disease. MEASUREMENTS: Frailty, duration of HIV, use of antiretroviral therapy, disease history, food insecurity, physical function, and physical activity were assessed by questionnaire. Dietary intake was assessed using 3-day food records. Blood was drawn for CD4+ cell count, hemoglobin, hematocrit, and lipid levels. Physical measurements included height, weight, and skinfold thickness. RESULTS: The prevalence of frailty was 16% (n=8), 44% were pre-frail (n=22) and 40% were not frail (n=20). The number of reported difficulties with 20 activities of daily living was highest in frail (mean 10.4±3.9 SD), followed by pre-frail (6.5±4.6), and lowest in not frail participants (2.0±2.3). Seven (88%) of the frail PLWH lost weight with an average weight loss of 22.9 pounds; 6 (75%) reported unintentional weight loss, and all 6 of these met the frailty criteria for weight loss of 10 or more pounds. Nine (45%) of the not frail PLWH reported losing weight with an average weight loss of 6.2 pounds; 5 (23%) reported unintentional weight loss of <10 pounds. Frail PLWH were more likely to report being food insecure than not frail PLWH (63% vs. 10%, p=0.02), and tended to have lower energy intake than not frail PLWH. CONCLUSION: Research is needed on targeted interventions to improve food security and activities of daily living in PLWH for both the prevention and improvement of frailty.

Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.

OBJECTIVES: Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI). METHODS: HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma. RESULTS: Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m(2) and the median CD4 count was 558 cells/µL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [-21% (P < 0.001) vs. PI/NNRTI -5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (-10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant. CONCLUSIONS: In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.

Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.

Standardization, decay data measurements and evaluation of 64Cu.

The purposes of this study were to create national activity standards of (64)Cu, to make possible the definition of an international key comparison reference value and to determine the decay data in order to improve the decay scheme. Four laboratories measured the activity of a (64)Cu solution; these results were compared through the International Reference System. Moreover, the laboratories carried out new measurements of the photon emission intensities and of the half-life. A new decay scheme was derived from these new values and the previously published ones.

Gene expression is differently affected by pimecrolimus and betamethasone in lesional skin of atopic dermatitis.

BACKGROUND: Topical corticosteroids and calcineurin inhibitors are well-known treatments of atopic dermatitis (AD) but differ in their efficacy and side effects. We recently showed that betamethasone valerate (BM) although clinically more efficient impaired skin barrier repair in contrast to pimecrolimus in AD. OBJECTIVE: This study elucidates the mode of action of topical BM and pimecrolimus cream in AD. METHODS: Lesional AD skin samples after topical treatment with either BM or pimecrolimus were subjected to gene expression profile analysis. RESULTS: Betamethasone valerate resulted in a significant reduction in mRNA levels of genes encoding markers of immune cells and inflammation, dendritic cells, T cells, cytokines, chemokines, and serine proteases, whereas pimecrolimus exerted minor effects only. This corroborates the clinical finding that BM reduces inflammation more effectively than pimecrolimus. Genes encoding molecules important for skin barrier function were differently affected. Both BM and pimecrolimus normalized the expression of filaggrin and loricrin. BM, but not pimecrolimus, significantly reduced the expression of rate-limiting enzymes for lipid synthesis and the expression of involucrin and small proline-rich proteins, which covalently bind ceramides. This may explain the lack of restoration of functional stratum corneum layers observed after BM treatment. CONCLUSION: The gene expression profiles are consistent with our previous findings that corticosteroids may exert a more potent anti-inflammatory effect but may impair the restoration of the skin barrier. Corticosteroids are still the main treatment for severe and acutely exacerbated AD; pimecrolimus may be preferable for long-term treatment and stabilization.

Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV-tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis.

OBJECTIVE: To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis (TB) with and without human immunodeficiency virus (HIV) coinfection on anti-tuberculous therapy. METHOD: Randomized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients, among whom 51 received and 52 did not receive the supplement. The primary outcome evaluated at completion of TB therapy was outcome of TB treatment, as classified by the national programme. Secondary outcomes were body composition, compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation. RESULTS: There was no significant difference in TB outcomes at the end of treatment, but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone. Among patients with TB, 1/35 (2.9%) supplemented and 5/42(12%) of those not supplemented had poor outcomes, while among TB-HIV-coinfected individuals, 4/13 (31%) supplemented and 3/7 (42.8%) non-supplemented patients had poor outcomes at the end of treatment, and the differences were more marked after 1 year of follow-up. Although there was some trend of benefit for both TB alone and TB-HIV coinfection, the results were not statistically significant at the end of TB treatment, possibly because of limited sample size. CONCLUSION: Nutritional supplements in patients are a potentially feasible, low-cost intervention, which could impact patients with TB and TB-HIV. The public health importance of these diseases in resource-limited settings suggests the need for large, multi-centre randomized control trials on nutritional supplementation.

Nutritional supplementation in HIV-infected individuals in South India: a prospective interventional study.

BACKGROUND: Malnutrition in human immunodeficiency virus (HIV)-infected individuals is associated with faster disease progression, higher mortality rates, and suboptimal response to antiretroviral therapy (ART). METHODS: We conducted a prospective interventional study to evaluate the effects of an oral macronutrient supplement among HIV-infected adults in South India. Patients attending Tuberculosis Research Centre clinics from June 2005 through December 2007 had baseline nutritional assessment and laboratory investigations performed. Patients at 1 center received nutritional counseling and standard care, whereas patients at 2 centers additionally received a macronutrient providing 400 cal and 15 g of protein daily. Study outcomes were changes in anthropometry, body composition, blood chemistry, and immune status at 6 months. RESULTS: In total, 636 ART-naive patients were enrolled in the study; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care). Mean age +/- standard deviation (SD) was 31 +/- 7 years, mean weight +/- SD was 50 +/- 10 kg, and 42% were male. Significant increases in body weight, body mass index, midarm circumference, fat-free mass, and body cell mass were observed in the supplement group but not in the control group at 6 months; gains were greater in patients with CD4 cell counts <200 cells/microL. No changes were observed in lipid levels, whereas the CD4 cell count decreased in the control group. However, after adjusting for baseline differences, these changes were not statistically significantly different between the groups. CONCLUSIONS: Macronutrient supplementation did not result in significantly increased weight gain compared with standard care (including nutritional counseling) among patients with moderately advanced HIV disease. The effect of supplementation on specific subsets of patients and on preserving immune function needs further research.

The HIV-1/HAART associated metabolic syndrome - novel adipokines, molecular associations and therapeutic implications.

The use of highly active anti-retroviral therapy has been associated with effects on various metabolic and morphological parameters that are underlied by significant hormonal and cytokine changes. Novel adipokines may have a role in the pathogenesis of these changes. In fact, leptin deficiency and hypoadiponectinemia correlate with lipoatrophy and central fat accumulation respectively whereas hypoadiponectinemia also appears to be associated with insulin resistance and lipid disorders. Preliminary evidence from proof-of-concept studies suggests that administration of recombinant leptin in replacement doses and/or administration of medications that increase adiponectin levels may improve the HIV-1/HAART associated metabolic syndrome (HAMS). Immune effects of hypoleptinemia and hypoadiponectinemia might have a role in the evolution of the HAMS that need to be further elucidated. The role for resistin in relation to HAMS is controversial and further investigation is necessary. A potential role of other novel cytokines like visfatin, retinol-binding protein-4, apelin, acylation stimulating protein, omentin and vaspin needs to be further elucidated.

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programmes. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1-infected drug users receiving antiretroviral therapy (ART) for at least six months in Hanoi, Vietnam. The mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA <1000 copies/mL). Correlates of viral suppression include self-reported > or = 95% adherence (P < 0.01) and current use of trimethoprim/sulphamethoxazole (P < 0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (P = 0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlight the need for adherence promotion, risk reduction programmes, and population-based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited.

Predictors of insulin resistance among Hispanic adults infected with or at risk of infection with the human immunodeficiency virus and hepatitis C virus.

Both the human immunodeficiency (HIV) and hepatitis C (HCV) viruses have been associated with insulin resistance (IR). However, our understanding of the prevalence of IR, the underlying mechanisms and predisposing factors is limited, particularly among minority populations. We conducted a study of 333 Hispanic adults including: 76 HIV monoinfected, 62 HCV monoinfected, 97 HIV/HCV co-infected and 98 uninfected controls with a specific focus on HCV infection and liver injury as possible predictors of IR. IR was measured using the Quantitative Insulin Sensitivity Check Index (QUICKI). The majority (55-69%) of participants in all groups had QUICKI values <0.350. Body mass index was associated with IR in all groups. Triglycerides were associated with IR in the uninfected control group only (-1.83, SE = 0.58, P = 0.0022). HCV was associated with IR in participants infected with HIV (-0.012, SE = 0.0046, P = 0.010). Liver injury, as measured by score to assess liver injury (FIB-4) score, was significantly associated with IR independently of HCV infection (-0.0035, SE = 0.0016, P = 0.027). In the HIV/HCV co-infected group, treatment with nucleoside reverse-transcriptase (RT) inhibitors plus non-nucleoside RT inhibitors (-0.021, SE = 0.080, P = 0.048), but not protease inhibitors (-0.000042, SE = 0.0082, P = 0.96) was associated with IR. HCV infection and antiretroviral agents, including nucleoside RT inhibitor plus non-nucleoside RT inhibitor treatment are contributors to IR in HIV infection. Liver injury, as measured by the FIB-4 score, is a predictor of IR independently of HCV infection.

Viral and host correlates of serum resistin in simian AIDS.

Resistin is an adipocytokine with a proposed dual role in metabolism and inflammation. In light of the ability to promote inflammatory responses, adipocytokines may prove key factors in modulating the host response to HIV. This study utilizes the simian immunodeficiency virus (SIV) model of HIV/AIDS to investigate changes in serum resistin levels following dietary intervention and SIV infection and determine associations with measures of body composition and disease severity. Resistin levels, body composition (n = 34), and insulin resistance (n = 16) were determined in healthy rhesus macaques. A subset of animals (n = 8) was placed on an atherogenic diet (AD) and subsequently inoculated with SIVmac239. Longitudinal measures of serum resistin, cytokines, viral load, lymphocyte subsets, and body composition were obtained. In healthy macaques consuming a standard diet, resistin levels correlated positively with total fat mass (r = 0.49; p < 0.01) and tissue fat percent (r = 0.53; p < 0.01) but failed to associate with measures of insulin resistance. In contrast, a negative correlation was noted between these measures of adiposity and resistin following SIV inoculation (r = -0.27; p < 0.05 and r = -0.24; p < 0.05, respectively). Viral load correlated positively with serum resistin (r = 0.32; p < 0.01). Serum levels of MCP-1 and sTNF RII demonstrated no correlation with resistin in normal animals on a standard diet, while a significant positive correlation was observed following SIV infection (r = 0.52; p < 0.0001 and r = 0.59; p < 0.0001, respectively). Findings indicate a fundamental difference in the relationship between resistin and body composition following SIV infection and suggest that elevations in resistin parallel measures of disease severity including loss of body fat and viral replication.

A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy.

OBJECTIVE: We conducted a randomized placebo-controlled trial to examine the effects of metformin on visceral adipose tissue (VAT), appendicular fat, lipid profile and insulin sensitivity in HIV-infected persons with central adiposity and mild insulin resistance. METHODS: Forty-eight HIV-infected men and women with a self-reported increase in abdominal girth and an abnormal waist-to-hip ratio were randomly assigned in double-blind fashion to receive metformin 1500 mg or placebo daily for 24 weeks. Persons with diabetes were excluded. The following measures were obtained at baseline and 24 weeks: single-slice computed tomography (CT) scan, dual-energy X-ray absorptiometry (DEXA), lipid profile and oral glucose tolerance test. RESULTS: The median fasting insulin concentration of all participants was 12.3 microU/mL. The percentage change in VAT was not significantly different between the metformin and placebo groups in univariate analysis and linear regression analysis adjusting for age, height, baseline VAT and insulin area under the curve (10.1% vs 3.2%; P=0.58). Metformin was associated with a significant decrease in appendicular fat mass compared with placebo (-686.0 vs 161.0 g; P=0.03). There was no significant change in lipid profile or insulin sensitivity between the two groups at 24 weeks. CONCLUSION: Metformin should be used with caution in the treatment of HIV lipodystrophy, and, if used, should be reserved for persons with adequate peripheral fat and marked insulin resistance.

Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy.

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort.

Despite major advances in the treatment and survival of patients infected with human immunodeficiency virus (HIV), weight loss and wasting remain common problems. In the HIV-infected population, weight loss is associated with lower CD4+ cell counts and is an independent predictor of mortality. The etiology of weight loss and wasting is complex and multifactorial. We discuss, on the basis of a large longitudinal cohort that examined nutritional status in HIV infection, data on weight loss and wasting from the present clinical era. The definition, prevalence, and significance of HIV-associated weight loss and wasting are summarized. The etiology of weight loss is discussed for 2 main categories: inadequate nutrient intake and altered metabolism. Finally, studies of interventions to treat HIV-associated weight loss and wasting are discussed. This information is intended to raise awareness among health care providers of HIV-infected patients that weight loss and wasting remain important acquired immunodeficiency syndrome-defining conditions, despite the advent of HAART.

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

The fat redistribution syndrome in patients infected with HIV: measurements of body shape abnormalities.

OBJECTIVE: To describe the body shape changes in the syndrome of fat redistribution or lipodystrophy seen in patients infected with HIV. DESIGN: An objective description of patients with HIV with fat redistribution syndrome. Body-height, weight, shape, and composition were measured by anthropometrics and biolectrical impedance analysis by a single observer. Clinical data were collected by chart review. SUBJECTS/SETTING: Thirty-nine patients with HIV receiving primary HIV care at a university hospital-affiliated infectious disease clinic who presented with complaints of body shape changes or who were referred by their primary care providers for body shape changes. ANALYSIS: Descriptive statistics were performed. RESULTS: Four of the 39 patients (10%) had not used protease inhibitor therapy. HIV status (by clinical presentation, CD4 and VL) varied widely. Laboratory abnormalities were moderate. Percent body fat differed widely when measured by bioelectrical impedance analysis and anthropometry (23% vs 13%). The mean body mass index was 25.6 kg/m2 for men and 25.8 kg/m2 for women. The mean waist/hip ratio was above normal, at 1.02. The mean mid-arm circumference and triceps skinfolds were below national standards for both men (30.4 cm and 8.1 mm, respectively) and women (26.7 cm and 7.5 mm, respectively). Nine patients (23%) had an increased dorso-cervical pad. Seventeen patients returned for follow-up measurements at 3 months; no significant differences were found between baseline and follow-up measurements. CONCLUSIONS: The waist/hip ratio, mid-arm and mid-thigh circumference, and triceps skinfolds were useful measures to define and follow the fat redistribution syndrome in patients with HIV. These body composition changes were not transitory in this short follow-up period.