A homozygous mutation in the human selenocysteine tRNA gene impairs UGA recoding activity and selenoproteome regulation by selenium.

The selenocysteine (Sec) tRNA (tRNA[Ser]Sec) governs Sec insertion into selenoproteins by the recoding of a UGA codon, typically used as a stop codon. A homozygous point mutation (C65G) in the human tRNA[Ser]Sec acceptor arm has been reported by two independent groups and was associated with symptoms such as thyroid dysfunction and low blood selenium levels; however, the extent of altered selenoprotein synthesis resulting from this mutation has yet to be comprehensively investigated. In this study, we used CRISPR/Cas9 technology to engineer homozygous and heterozygous mutant human cells, which we then compared with the parental cell lines. This C65G mutation affected many aspects of tRNA[Ser]Sec integrity and activity. Firstly, the expression level of tRNA[Ser]Sec was significantly reduced due to an altered recruitment of RNA polymerase III at the promoter. Secondly, selenoprotein expression was strongly altered, but, more surprisingly, it was no longer sensitive to selenium supplementation. Mass spectrometry analyses revealed a tRNA isoform with unmodified wobble nucleotide U34 in mutant cells that correlated with reduced UGA recoding activities. Overall, this study demonstrates the pleiotropic effect of a single C65G mutation on both tRNA phenotype and selenoproteome expression.

Role of unsafe medical practices and sexual behaviours in the hepatitis B and C syndemic and HIV co-infection in Rwanda: a cross-sectional study.

OBJECTIVES: This study describes the burden of the hepatitis B, C and HIV co-infections and assesses associated risk factors. SETTING: This analysis used data from a viral hepatitis screening campaign conducted in six districts in Rwanda from April to May 2019. Ten health centres per district were selected according to population size and distance. PARTICIPANTS: The campaign collected information from 156 499 participants (51 496 males and 104 953 females) on sociodemographic, clinical and behavioural characteristics. People who were not Rwandan by nationality or under 15 years old were excluded. PRIMARY AND SECONDARY OUTCOMES: The outcomes of interest included chronic hepatitis C virus (HCV) infection, chronic hepatitis B virus (HBV) infection, HIV infection, co-infection HIV/HBV, co-infection HIV/HCV, co-infection HBV/HCV and co-infection HCV/HBV/HIV. Multivariable logistic regressions were used to assess factors associated with HBV, HCV and HIV, mono and co-infections. RESULTS: Of 156 499 individuals screened, 3465 (2.2%) were hepatitis B surface antigen positive and 83% (2872/3465) of them had detectable HBV desoxy-nucleic acid (HBV DNA). A total of 4382 (2.8%) individuals were positive for antibody-HCV (anti-HCV) and 3163 (72.2%) had detectable HCV ribo-nucleic acid (RNA). Overall, 36 (0.02%) had HBV/HCV co-infection, 153 (0.1%) HBV/HIV co-infection, 238 (0.15%) HCV/HIV co-infection and 3 (0.002%) had triple infection. Scarification or receiving an operation from traditional healer was associated with all infections. Healthcare risk factors-history of surgery or transfusion-were associated with higher likelihood of HIV infection with OR 1.42 (95% CI 1.21 to 1.66) and OR 1.48 (1.29 to 1.70), respectively, while history of physical traumatic assault was associated with a higher likelihood of HIV and HBV/HIV co-infections with OR 1.69 (95% CI 1.51 to 1.88) and OR 1.82 (1.08 to 3.05), respectively. CONCLUSIONS: Overall, mono-infections were common and there were differences in significant risk factors associated with various infections. These findings highlight the magnitude of co-infections and differences in underlying risk factors that are important for designing prevention and care programmes.

Identifying risk factors of anemia among women of reproductive age in Rwanda - a cross-sectional study using secondary data from the Rwanda demographic and health survey 2014/2015.

BACKGROUND: Anemia among Women of Reproductive Age (WRA) continues to be among the major public health problems in many developing countries, including Rwanda, where it increased in prevalence between the 2015 and 2010 Rwanda Demographic and Health Survey (RDHS) reports. A thorough understanding of its risk factors is necessary to design better interventions. However, to the best of our knowledge, no study has been conducted in Rwanda on a nationally representative sample to assess factors associated with anemia among WRA. Accordingly, this study was conducted to address such gap. METHODS: A quantitative, cross-sectional study was conducted using data from the RDHS 2014-2015. The study population consisted of 6680 WRA who were tested for anemia during the survey. Anemia was defined as having a hemoglobin level equal to or below 10.9 g/dl for a pregnant woman, and hemoglobin level equal to or below 11.9 g/dl for a non-pregnant woman. Pearson's chi-squared test and multiple logistic regression were conducted for bivariate and multivariable analysis, respectively. RESULTS: The prevalence of anemia among WRA was 19.2% (95% CI: 18.0-20.5). Four factors were found to be associated with lower odds of anemia, including being obese (OR: 0.61, 95% CI: 0.40-0.91), being in the rich category (OR: 0.74, 95% CI: 0.63-0.87), sleeping under a mosquito net (OR: 0.85, 95% CI: 0.74-0.98), and using hormonal contraceptives (OR: 0.61, 95% CI: 0.50-0.73). Five factors were associated with higher odds of anemia, including being underweight (OR: 1.39, 95% CI: 1.09-1.78), using an intrauterine device (OR: 1.98, 95% CI: 1.05-3.75), being separated or widowed (OR: 1.35, 95% CI: 1.09-1.67), and living in the Southern province (OR: 1.45, 95% CI: 1.11-1.89) or in the Eastern province (OR: 1.41, 95% CI: 1.06-1.88). CONCLUSION: Anemia continues to pose public health challenges; novel public health interventions should consider geographic variations in anemia risk, seek to improve women's economic statuses, and strengthen iron supplementation especially for Intrauterine device users. Additionally, given the association between anemia and malaria, interventions to prevent malaria should be enhanced.

Risk factors for viral hepatitis C infection in Rwanda: results from a nationwide screening program.

BACKGROUND: The epidemiology and risk factors for hepatitis C virus (HCV) infection in Rwanda are not well known; however, this information is crucial to shaping the country's public health approach to hepatitis C control. METHODS: A HCV screening campaign was conducted in the general population in 24 districts previously identified to have a high HCV disease burden. At the time of sample collection, sociodemographic information and self-reported risk factors were collected. Bivariate and multivariate logistic regressions were conducted to assess risk factors independently associated with hepatitis C antibodies (HCVAb) seroprevalence. RESULTS: Out of a total of 326,263 individuals screened for HCVAb, 22,183 (6.8%) were positive. In multivariate analysis, risk factors identified as statistically associated with HCVAb Seroprevalence include history of traditional operation or scarification (OR = 1.09, 95% CI: 1.05-1.14), presence of viral hepatitis in the family (OR = 1.27, 95% CI: 1.15-1.40), widowed or separated/divorced (OR = 1.36, 95% CI: 1.26-1.47), Southern province (OR = 1.98, 95% CI: 1.88-2.08) and aged 65 years and older (OR = 4.86, 95% CI: 4.62-5.11). Ubudehe category 3 (OR = 0.97, 95% CI: 0.93-1.01) and participants using RAMA (Health insurances for employees of public and private sectors) insurance (OR = 0.76, 95% CI: 0.70-0.85) had lower odds of HCV seroprevalence. CONCLUSIONS: Our findings provide important information for Rwanda's strategy on prevention and case-finding. Future prevention interventions should aim to reduce transmission through targeted messaging around traditional healing practices and case-finding targeting individuals with a history of exposure or advanced age.

Making progress towards food security: evidence from an intervention in three rural districts of Rwanda.

OBJECTIVE: Determining interventions to address food insecurity and poverty, as well as setting targets to be achieved in a specific time period have been a persistent challenge for development practitioners and decision makers. The present study aimed to assess the changes in food access and consumption at the household level after one-year implementation of an integrated food security intervention in three rural districts of Rwanda. DESIGN: A before-and-after intervention study comparing Household Food Insecurity Access Scale (HFIAS) scores and household Food Consumption Scores (FCS) at baseline and after one year of programme implementation. SETTING: Three rural districts of Rwanda (Kayonza, Kirehe and Burera) where the Partners In Health Food Security and Livelihoods Program (FSLP) has been implemented since July 2013. SUBJECTS: All 600 households enrolled in the FSLP were included in the study. RESULTS: There were significant improvements (P<0·001) in HFIAS and FCS. The median decrease in HFIAS was 8 units (interquartile range (IQR) -13·0, -3·0) and the median increase for FCS was 4·5 units (IQR -6·0, 18·0). Severe food insecurity decreased from 78% to 49%, while acceptable food consumption improved from 48% to 64%. The change in HFIAS was significantly higher (P=0·019) for the poorest households. CONCLUSIONS: Our study demonstrated that an integrated programme, implemented in a setting of extreme poverty, was associated with considerable improvements towards household food security. Other government and non-government organizations' projects should consider a similar holistic approach when designing structural interventions to address food insecurity and extreme poverty.

L-carnitine treatment in incident hemodialysis patients: the multicenter, randomized, double-blinded, placebo-controlled CARNIDIAL trial.

BACKGROUND: L-carnitine levels decrease rapidly and steadily with duration of hemodialysis, and carnitine depletion can impair response to recombinant human erythropoietin (rHuEPO). The study hypothesis was that L-carnitine supplementation during the first year of hemodialysis would improve this response. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From October 2006 through March 2010, this multicenter, randomized, double-blinded study assigned 92 incident hemodialysis patients to receive placebo or 1 g of intravenous L-carnitine after each dialysis session for 1 year. The primary outcome measure compared the groups for rHuEPO resistance index (EPO-RI), defined as weekly rHuEPO doses (IU/kg body weight divided by hemoglobin level) (g/dl). RESULTS: In the L-carnitine group, carnitine concentration increased from a mean ± SD of 79 ± 51 µmol/L to 258 ± 137 µmol/L; in the placebo group, it declined from 68 ± 25 µmol/L to 53 ± 24 µmol/L (interaction group × time, P<0.001). Carnitine deficiency affected about 30% of the patients in the placebo group during the study period. EPO-RI varied from 15.8 ± 11.3 to 9.5 ± 5.8 IU/kg per g/dl in the placebo group and from 20.6 ± 12.8 to 15.6 ± 15.9 IU/kg per g/dl in the L-carnitine group, for a mean variation of -3.94 ± 12.5 IU/kg per g/dl and -2.98 ± 15.5 IU/kg per g/dl, respectively (P=0.7). After adjustment for baseline characteristics, the EPO-RI course was similar in each group (difference between groups, P=0.10; interaction group × time, P=0.9). CONCLUSIONS: Carnitine levels decrease by about 11% ± 33% during the first year of hemodialysis. Treatment of incident hemodialysis patients with L-carnitine does not improve their response to rHuEPO.

Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis.

PURPOSE OF REVIEW: Several entities have been investigated carefully for the symptomatic and structural management of osteoarthritis. This review reports recent findings suggesting that such compounds may delay the structural progression of osteoarthritis. RECENT FINDINGS: The most compelling evidence of a potential for inhibiting the structural progression of osteoarthritis has been obtained with glucosamine sulfate, whereas preliminary results obtained in patients with osteoarthritis of the hands also suggest that chondroitin sulfate could be used in the same indication. At any rate, these two compounds have clearly demonstrated a symptomatic action, mainly in osteoarthritis of the lower limbs. Patients with the less severe radiographic osteoarthritis will experience, in the long run, the most dramatic disease progression in terms of joint space narrowing. Such patients may be particularly responsive to structure-modifying drugs. SUMMARY: Glucosamine sulfate has demonstrated its ability to reduce the progression of osteoarthritis in the lower limbs. The preliminary results obtained in the hands suggest that chondroitin sulfate could also be of interest in this indication. An important issue is that all the conclusive studies with such chemical entities resulted from the use of prescription medicines, not over-the-counter pills or food supplements.