Primary drug resistance in South Africa: data from 10 years of surveys

HIV-1 transmitted drug resistance (TDR) could reverse the gains of antiretroviral rollout. To ensure that current first-line therapies remain effective, TDR levels in recently infected treatment-naive patients need to be monitored. A literature review and data mining exercise was carried out to determine the temporal trends in TDR in South Africa. In addition, 72 sequences from seroconvertors identified from Africa Centre's 2010 HIV surveillance round were also examined for TDR. Publicly available data on TDR were retrieved from GenBank, curated in RegaDB, and analyzed using the Calibrated Population Resistance Program. There was no evidence of TDR from the 2010 rural KwaZulu Natal samples. Ten datasets with a total of 1618 sequences collected between 2000 and 2010 were pooled to provide a temporal analysis of TDR. The year with the highest TDR rate was 2002 [6.67%, 95% confidence interval (CI): 3.09-13.79%; n=6/90]. After 2002, TDR levels returned to <5% (WHO low-level threshold) and showed no statistically significant increase in the interval between 2002 and 2010. The most common mutations were associated with NNRTI resistance, K103N, followed by Y181C and Y188C/L. Five sequences had multiple resistance mutations associated with NNRTI resistance. There is no evidence of TDR in rural KwaZulu-Natal. TDR levels in South Africa have remained low following a downward trend since 2003. Continuous vigilance in monitoring of TDR is needed as more patients are initiated and maintained onto antiretroviral therapy.     

Accuracy of four dental age estimation methods in determining the legal age threshold of 18 years among South Indian adolescents and young

The aim of this study was to compare the accuracy, specificity and sensitivity of four commonly used methods of dental age estimation in a sample of south Indian adolescents and young adults aged between 14 and 30 years, with an age threshold of 18 years, using receiver operating characteristic curves (ROC) and the area under the curve (AUC). A total of 1070 orthopantomograms (535 males and 535 females) of adolescents and young adults of south Indian origin were collected retrospectively and interpreted. The effectiveness of each method was evaluated by using sensitivity (Se), specificity (Sp), likelihood ratios (LR+ and LR-) and AUC. Among all methods, I3M< 0.08 resulted in better values of AUC, Se and Sp which were 0.950, 91.5%, 97.8% and 0.950, 88.5% and 98.6% in males and females, respectively. For “stage H” of Demirjian’s system, the AUC, Se and Sp were 0.940, 84.9%, 97.7% and 0.930, 79.9% and 98.5% in males and females, respectively. The use of the Olze et al “stage 1 (or higher)” root pulp visibility and “stage D” of third molar eruption were not recommended in the studied population due to the greater percentage of third molars with incomplete mineralization in younger age groups and impaction. Taking into account the values of Se, Sp, both positive and negative LRs, we recommend the use of the cut-off value of I3M< 0.08 to discriminate adults and minors in south Indian adolescents and young adults.     

Waste to white light: a sustainable method for converting biohazardous waste to broadband white LEDs

The Covid-19 pandemic has generated a lot of non-degradable biohazardous plastic waste across the globe in the form of disposable surgical and N95 masks, gloves, face shields, syringes, bottles and plastic storage containers. In the present work we address this problem by recycling plastic waste to single system white light emitting carbon dots (CDs) using a pyrolytic method. The synthesized CDs have been embedded into a transparent polymer to form a carbon dot phosphor. This CD phosphor has a broad emission bandwidth of 205 nm and is stable against photo degradation for about a year. A white LED with CRI ∼70 and CIE co-ordinates of (0.25, 0.32) using the fabricated CD phosphor is reported. Further our phosphor is scalable and is environmentally sustainable, and will find wide application in next generation artificial lighting systems.

Recycling of plastic waste to white LEDs.     

Riding with the sharks: Serious leisure cyclist's perceptions of sharing the road with motorists

As serious leisure cyclists increase their presence on Australian public roads, there have been reports within the popular and mainstream literature of a growing tension between these cyclists and other road users. Until now, there has been limited research exploring the relationship between serious leisure cyclists and other road users as it pertains to issues of safety and motivations to cycle for leisure. This mixed methods research provides insights into a particular cohort of serious leisure cyclists and their experiences of sharing the roads with motorists. Analysis reveals a range of concerns amongst this sub-group, mediated by factors such as age, experience and environment. The paper calls for a differential focus on sub-groups of cyclists when considering policy formation, regulation and safe provision for cyclists on roads.     

Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

Chromodomain, helicase, DNA binding 5 (CHD5) is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04). The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.     

Human polymorphonuclear neutrophil activation with arachidonic acid.

The capacity of arachidonic acid (AA) to stimulate granule exocytosis from human polymorphonuclear neutrophils (PMNs) was investigated. AA induced the selected extracellular release of azurophil (myeloperoxidase, lysozyme) and specific (lysozyme, vitamin B12 binding protein) granule constituents from human PMNs in a time- and concentration-dependent manner. Cytochalasin B (CB) enhanced but was not required for PMN activation with AA. Although extracellular calcium had no effect on granule exocytosis, AA did stimulate the mobilization of intracellular sequestered Ca2+ which resulted in an increase in cytosolic-free Ca2+ ([Ca2+]i) as reflected by increased fluorescence of Fura-2-treated cells. AA stimulated Ca2+/phospholipid-dependent protein kinase C (PK-C) activity in PMNs. 4,4'-Diisothiocyano-2,2'-disulphonic acid stilbene (DIDS), an anion channel blocker, caused a concentration-dependent inhibition of granule enzyme release. Activation of PMNs with AA was unaffected by the lipoxygenase/cycle-oxygenase inhibitors, 5,8,11, 14-eicosatetraynoic acid (ETYA) and benoxaprofen, a lipoxygenase inhibitor, 6, 9, deepoxy-6,9-(phenylimino) delta 6,8-prostaglandin 1(1) (piriprost potassium) or a pure cyclo-oxygenase inhibitor, flurbiprofen. These data define the properties of AA as a secretory stimulus for human PMNs.     

Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution,migration, and differentiation

Amyotrophic lateral sclerosis (ALS), a multifactorial disease characterized by diffuse motor neuron degeneration, has proven to be a difficult target for stem cell therapy. The primary aim of this study was to determine the long-term effects of intravenous mononuclear human umbilical cord blood cells on disease progression in a well-defined mouse model of ALS. In addition, we rigorously examined the distribution of transplanted cells inside and outside the central nervous system (CNS), migration of transplanted cells to degenerating areas in the brain and spinal cord, and their immunophenotype. Human umbilical cord blood (hUCB) cells (10(6)) were delivered intravenously into presymptomatic G93A mice. The major findings in our study were that cord blood transfusion into the systemic circulation of G93A mice delayed disease progression at least 2-3 weeks and increased lifespan of diseased mice. In addition, transplanted cells survived 10-12 weeks after infusion while they entered regions of motor neuron degeneration in the brain and spinal cord. There, the cells migrated into the parenchyma of the brain and spinal cord and expressed neural markers [Nestin, III Beta-Tubulin (TuJ1), and glial fibrillary acidic protein (GFAP)]. Infused cord blood cells were also widely distributed in peripheral organs, mainly the spleen. Transplanted cells also were recovered in the peripheral circulation, possibly providing an additional cell supply. Our results indicate that cord blood may have therapeutic potential in this noninvasive cell-based treatment of ALS by providing cell replacement and protection of motor neurons. Replacement of damaged neurons by progeny of cord blood stem cells is probably not the only mechanism by which hUCB exert their effect, since low numbers of cells expressed neural antigens. Most likely, cord blood efficacy is partially due to neuroprotection by modulation of the autoimmune process.