Mutation Screening of the HGD Gene Identifies a Novel Alkaptonuria Mutation with Significant Founder Effect and High Prevalence

Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2‐dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU‐causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin.     

Health expenditure and catastrophic spending among older adults living with HIV

Introduction: The burden of HIV is increasing among adults aged over 50, who generally experience increased risk of cormorbid illnesses and poorer financial protection. We compared patterns of health utilisation and expenditure among HIV-positive and HIV-negative adults over 50. Methods: Data were drawn from the Study on global AGEing and adult health in South Africa with analysis focusing on individual and household-level data of 147 HIV-positive and 2725 HIV-negative respondents. Results: HIV-positive respondents reported lower utilisation of private health-care facilities (11.8%) than HIV-negative respondents (25.0%) (p?=?.03) and generally had more negative attitudes towards health system responsiveness than HIV-negative counterparts. Less than 10% of HIV-positive and HIV-negative respondents experienced catastrophic health expenditure (CHE). Women (OR 1.8; p?p?Conclusions: These findings suggest that although HIV-positive and HIV-negative older adults in South Africa are protected to some extent from CHE, inequalities still exist in access to and quality of care available at health-care services – which can inform South Africa’s development of a national health insurance scheme.     

Reciprocity and burnout in direct care staff

Understanding the perceptions of direct care staff of their reciprocal relationships at work and levels of burnout may help us improve not only their psychological health but also the service they provide. A cross-sectional survey was undertaken with direct care staff who worked with children, older people and people with intellectual disabilities in residential settings. Staffs were asked to report their levels of burnout and perceived reciprocity in the relationship they had with service users, other staff and the organisation they worked for. Significant relationships were found between some burnout and reciprocity measures. 'Under benefit' in relationships with service users, colleagues and the organization was related to emotional exhaustion. 'Under benefit' in organizational and staff relationships was related to increased depersonalization. Reciprocity is a potentially useful concept for understanding differences in relationships across a broad range of staff and use of the reciprocity questionnaire in this study allows for comparison between diverse groups. The importance of relationships with the employing organization is highlighted in this sample and suggests that burnout is not solely linked with lack of reciprocity in the caregiving relationship per se.     

Spectrum of myelopathies in HIV seropositive South African patients

The authors determined the cause of myelopathies in 33 HIV seropositive individuals in KwaZulu/Natal, South Africa. The main associations were with human T-cell lymphotrophic virus-I, tuberculosis, herpes zoster, and syphilis. A novel association with probable bilharziasis was noted. Only one case of vacuolar myelopathy was identified. Opportunistic infections will probably persist until routine antiretroviral therapy becomes widely available in South Africa.     

Quality of home-based rapid HIV testing by community lay counsellors in a rural district of South Africa

Introduction

Lack of universal, annual testing for human immunodeficiency virus (HIV) in health facilities suggests that expansion of HIV testing and counselling (HTC) to non-clinical settings is critical to the achievement of national goals for prevention, care and treatment. Consideration should be given to the ability of lay counsellors to perform home-based HTC in community settings.

Methods

We implemented a community cluster randomized controlled trial of home-based HTC in Sisonke District, South Africa. Trained lay counsellors conducted door-to-door HIV testing using the same rapid tests used by the local health department at the time of the study (SD Bioline and Sensa). To monitor testing quality and counsellor skill, additional dry blood spots were taken and sent for laboratory-based enzyme-linked immunosorbent assay (ELISA) testing. Sensitivity and specificity were calculated using the laboratory result as the gold standard.

Results and discussion

From 3986 samples, the counsellor and laboratory results matched in all but 23 cases. In 18 cases, the counsellor judged the result as indeterminate, whereas the laboratory judged 10 positive, eight negative and three indeterminate, indicating that the counsellor may have erred on the side of caution. Sensitivity was 98.0% (95% CI: 96.3–98.9%), and specificity 99.6% (95% CI: 99.4–99.7%), for the lay counsellor field-based rapid tests. Both measures are high, and the lower confidence bound for specificity meets the international standard for assessing HIV rapid tests.

Conclusions

These findings indicate that adequately trained lay counsellors are capable of safely conducting high-quality rapid HIV tests and interpreting the results as per the kit guidelines. These findings are important given the likely expansion of community and home-based testing models and the shortage of clinically trained professional staff.     

Carraguard Vaginal Gel Safety in HIV-Positive Women and Men in South Africa

OBJECTIVE: To assess the safety of the candidate microbicide Carraguard gel in HIV-positive women and men. DESIGN: A randomized, placebo-controlled, triple-blinded clinical trial of Carraguard gel when applied vaginally once per day for 14 intermenstrual days by sexually abstinent and sexually active HIV-positive women; and when applied directly to the penis once per day for 7 days by sexually abstinent HIV-positive men. METHODS: In each cohort (n = 20 per cohort), participants were randomized to Carraguard, methylcellulose placebo, or no product (1:1:1). In addition to traditional microbicide trial safety endpoints, the effects of microbicide use on vaginal shedding of HIV-1 RNA and markers of genital inflammation, epithelial sloughing, and microhemorrhage were also explored. RESULTS: Gel compliance was high in both gel-use groups in the 3 cohorts. Carraguard use was not associated with abnormal genital findings, other abnormal clinical findings, markers of genital inflammation, epithelial sloughing or microhemorrhage, or self-reported symptoms in women and men, or with abnormal vaginal flora or genital shedding of HIV-1 RNA in women. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. CONCLUSIONS: Once-daily use of Carraguard for 7 to 14 days appeared to be safe in HIV-positive women and men.     

First-principles study of coadsorption of Cu2+ and Cl− ions on the Cu (110) surface

Motivated by the importance of Cl⁻ in the industrial electrolytic Cu plating process, we study the coadsorption of Cl⁻ and Cu²⁺ on the Cu (110) surface using first-principles density functional theory (DFT) calculations. We treat the solvent implicitly by solving the linearized Poisson–Boltzmann equation and evaluate the electrochemical potential and energetics of ions with the computational hydrogen electrode approach. We find that Cl⁻ alone is hardly adsorbed at sufficiently negative electrochemical potentials μ_Cl but stable phases with half and full Cl⁻ coverage was observed as μ_Cl is made more positive. For Cl⁻ and Cu²⁺ coadsorption, we identified five stable phases for electrode biases between −2V < U_SHE < 2V, with two being Cl⁻ adsorption phases, two being Cl⁻ + Cu²⁺ coadsorption phases and one being a pure Cu²⁺ adsorption phase. In general, the free energy of adsorption for the most stable phases at larger |U_SHE| are dominated by the energy required to move electrons between the system and the Fermi level of the electrode, while that at smaller |U_SHE| are largely dictated by the binding strength between Cl⁻ and Cu²⁺ adsorbates on the Cu (110) substrate. In addition, by studying the free energy of adsorption of Cu²⁺ onto pristine and Cl⁻ covered Cu (110), we conclude that the introduction of Cl⁻ ion does not improve the energetics of Cu²⁺ adsorption onto Cu (110).

Free energy of adsorption for the most stable phases predicted by DFT calculations as a function of electrode potential.