Prevalence of monoclonal gammopathy of undetermined significance in eswatini: a Population-Based study in africa.

PURPOSE: Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiologic studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, USA study. METHODS: Between 2016 and 2017, 13,339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally-representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared to that of Olmsted County. Additionally, demographic and HIV-related associations with MGUS were assessed. RESULTS: Of the 515 samples randomly selected, the median age was 50 years (range 35-80) and 60% were female; 38.6% were HIV-positive, of whom 82.4% were on antiretroviral therapy. We found that 68 had evidence of MGUS for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (OR, 1.05; 95%CI, 0.62-1.77), but among HIV-positive individuals, MGUS was less frequent for those on antiretroviral therapy (adjusted OR, 0.31; 95%CI, 0.11-0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2-3.4%), while light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%). CONCLUSION: Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.

Impact of trivalent Yttrium on the structural and optical properties of CaAl2O4: New frontier in supercapacitor positive electrode.

In this work, trivalent Yttrium doped calcium aluminate (CaAl2O4:x% Y3+) were synthesized for the first time. Through Photoluminescence (PL) spectroscopy and Commission Internationale de l'Eclairage (CIE), CaAl2O4:0.1 % Y3+ has demonstrated to be a potential high emitting phosphor material amongst other high concentration Y3+ doped samples, emitting a vibrant blue - pink hue where others are emitting a transiting hue from blue to green within a white vertex region. FTIR and UV-Vis have confirmed the prepared material and the presence of Y dopant. The SEM showed insignificant morphological change and the presence of pores, which were quantified using BJH and DFT methods to be micro - and meso-pores. Moreover, CaAl2O4 is also being reported as a positive electrode in supercapacitors for the first time. The analysis shows that it has superior performance within 1 M KOH electrolyte, with a specific capacity of 47.71 mA h g-1 at 1 A g-1 and a maximum power of 39.68 kW kg-1. Trasatti's method showed a surface (138 Fg-1) and diffusion (695 Fg-1) contribution ratio of 17:83 (%) of the total stored energy. It has a capacity retention and columbic efficiency of 100 % at the end of 10 000 cycles, which was achieved via utilization of all micropores reaction sites. The EIS showed a small solution resistance of 0.75 Ω, indicating high ionic conductivity and a phase angle of - 50 ° . Thus, these results show that CaAl2O4 is a potential candidate for photoluminescence and energy storage application.

Isolation, identification and biological characterization of bacterial endophytes isolated from Gunnera Perpensa L.

In the present study, eleven endophytic bacterial strains, Herbaspirillum sp. (GP-SGM1, GP-SGM2, GP-SGM3, GP-SGM11), Pseudomonas sp. (GP-SGM4, GP-SGM5), Novosphingobium sp. GP-SGM6, Chryseobacterium sp. GP-SGM7, Labedella sp. GP-SGM8, Brevibacterium sp. GP-SGM9, and Pseudomonas sp. GP-SGM10, were isolated from the rhizomes of Gunnera perpensa L. The growth kinetics, assessed through maximum growth rates (µmax) and optical density (OD) values, revealed that GP-SGM7 exhibited highest µmax values of 0.33 ± 0.01 hr-1 with an OD of 4.20 ± 0.04. In contrast, GP-SGM11 exhibited the lowest µmax of 0.12 ± 0.05 hr-1 and the smallest OD of 1.50 ± 0.00. In addition, the endophyte crude extracts were tested for antibacterial activity against five pathogenic strains using the disk diffusion method, with GP-SGM7 crude extracts exhibiting promising antibacterial activity against Klebsiella pneumoniae, and Staphylococcus aureus. Antioxidant activity was determined by DPPH (2, 2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays. The crude extracts of GP-SGM1, GP-SGM7, GP-SGM9, and GP-SGM10 were the most effective at scavenging DPPH radicals, with GP-SGM7 also exhibiting high FRAP value of 0.54 ± 0.01. These findings emphasize the therapeutic potential of endophytic bacteria from Gunnera perpensa L. in addressing skin-related issues, including bacterial infections and free radicals.

The effect of teamwork, communication skills, and structural empowerment on the provision of patient-centered care among nurses in Eswatini: A cross-sectional study.

AIMS: To identify the influence of teamwork, communication skills, and structural empowerment on providing patient-centered care among nurses in Eswatini. DESIGN: A quantitative, cross-sectional survey was used. METHODS: This survey conducted in Eswatini selected registered nurses working as full-time nurses with more than 3 months of working experience using convenience sampling. Different measures were adopted and used to collect data among 130 eligible nurses from February to March 2022. Data were analyzed using Statistical Program for Social Sciences version 26.0. RESULTS: A total of 123 nurses responded in the study and the mean age was 31.05 years with a standard deviation of 5.49. The overall response rate was 94.6% in this study. Hierarchical multiple regression analysis revealed that teamwork (ß = 0.236, p < 0.05) and communication skills (ß = 0.328, p < 0.05) were significant predictors of the provision of patient-centered care among nurses. CONCLUSION: Team-building exercises and management interventions to empower nurses should be established to improve the provision of patient-centered care among nurses. Nurses should be empowered to provide patient-centered care in health facilities by encouraging them to provide their input in management procedures and planning programs. IMPACT: Clinical practice requires nurses to use effective communication skills and work as a team. Nursing care established on teamwork, respect, empathy, and communication skills allows patients to express their concerns and views in health facilities as they feel involved in care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution in this paper. This study only involved registered nurses as health professionals.

Effect of preoperative biliary drainage on intraoperative biliary cultures and surgical outcomes after pancreatic resection.

BACKGROUND: Prolonged obstructive jaundice (OJ), associated with resectable pancreatic pathology, has many deleterious effects that are potentially rectifiable by preoperative biliary drainage (POBD) at the cost of increased postoperative infective complications. The aim of this study is to assess the impact of POBD on intraoperative biliary cultures (IBCs) and surgical outcomes in patients undergoing pancreatic resection. METHODS: Data from patients at Groote Schuur Hospital, Cape Town, between October 2008 and May 2019 were analysed. Demographic, clinical, and outcome variables were evaluated, including perioperative morbidity, mortality, and 5-year survival. RESULTS: Among 128 patients, 69.5% underwent POBD. The overall perioperative mortality in this study was 8.8%. The POBD group had a significantly lower perioperative mortality rate compared to the non-drainage group (5.6% vs. 25.6%). POBD patients had a higher incidence of surgical site infections (55.1% vs. 23.1%), polymicrobial growth from IBCs and were more likely to culture resistant organisms. Five-year survival was similar in the two groups. CONCLUSION: POBD was associated with a high incidence of resistant organisms on the IBCs, a high incidence of surgical site infections and a high correlation between cultures from the surgical site infection and the IBCs.

The effect of mobile marketing antecedents on the purchase intention of staple products: A case of the bottom of the pyramid (BoP) market segment in Khayelitsha, South Africa.

Purpose: This research seeks to ascertain the impact of mobile marketing antecedents on the purchase intention of staple products among BoP consumers to create a viable digital-commerce channel that serves this segment. To achieve this, the paper proposes that mobile marketing antecedents, such as service quality and price sensitivity, influence trust and satisfaction, which, in turn, influence the purchase intention of staple products. Design/methodology/approach: A questionnaire was collected from 385 BoP consumers. Smart PLS 4 was used to analyse data using Structural equation modelling (SEM). Findings: Service quality positively influences trust towards mobile marketing. In contrast, a similar positive trend was observed for satisfaction, price sensitivity, service quality, and purchase intentions. Surprisingly, satisfaction and trust did not influence purchase intentions. Originality/value: Through the Value-Based Adoption Model (VAM), original contributions to the literature have been established, which have received little attention from consumer behaviour researchers, particularly in the context of emerging economies, to explore several mobile marketing antecedents that motivate or demotivate BoP consumers, who are mainly untapped, to make online purchases.

Evidence of varicella zoster virus (VZV) reactivation in children with arterial ischemic stroke: Results of the VIPS II Study.

Background: Varicella zoster virus (VZV) has been associated with focal cerebral arteriopathy (FCA) and arterial ischemic stroke (AIS) in childhood. The Vascular effects of Infection in Pediatric Stroke (VIPS) II study aimed to examine this relationship in the modern era when most children in North America and Australia receive VZV vaccination with live, attenuated virus. Methods: This 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022), collected baseline [hyperacute (≤72 hours; n=194) and acute (4-6 days; n=181)] and convalescent (1-6 weeks; n=74) serum samples. Sites enrolled 95 stroke-free controls with single serum samples. A virology research laboratory measured VZV IgM and IgG titers by an in-house enzyme-linked immunosorbent assay (ELISA). Baseline IgG seropositivity indicated prior exposure (vaccination/infection) and elevated IgM titers indicated recent reactivation. Results: Median (IQR) age was 11.6 (5.5-15.6) years for cases and 11.8 (6.8-15.3) years for controls. Baseline serologies indicated prior VZV exposure in 198 cases (97%) and all controls. Parents of cases reported VZV vaccination in 160 (78%) and remote chicken pox in three (1.4%). Twenty cases (9.8%) and three controls (3.1%) had serologic evidence of recent VZV reactivation (p=0.06); all had remote VZV exposure (vaccination in 19 cases and all controls) and all were asymptomatic. Recent VZV reactivation was seen in similar proportions in arteriopathic, cardioembolic, and idiopathic stroke. Of 32 cases of FCA, 4 (12.5%) had recent VZV reactivation, versus no cases of arterial dissection (n=10) or moyamoya (n=16). Conclusions: Serologic evidence of recent VZV reactivation (≈1-6 weeks prior to stroke) was present in one in 10 cases of childhood AIS, including those without arteriopathy. Clinically silent VZV reactivation may be a childhood stroke trigger despite widespread vaccination. These cases could represent waning immunity with reactivation of either vaccine virus or wild-type virus after an unrecognized secondary VZV infection.

HIV Stigma, Health, and Violence: A Longitudinal Study among Adolescent Boys with HIV in Soweto, South Africa.

There are over 1.4 million adolescents living with HIV in sub-Saharan Africa, the majority of whom acquired the virus through perinatal transmission (PHIV). HIV stigma is particularly high among adolescents living with HIV and is associated with several outcomes that worsen health and increase the risk of onward HIV transmission. We tested associations between internalized HIV stigma and four of these outcomes over a one-year period among a sample of adolescent boys living with PHIV in Soweto, South Africa. Participants (N = 241) answered questions about internalized HIV stigma at baseline. They completed weekly mobile surveys over the following year to answer questions about their experiences with depression, binge drinking, medication adherence, and violence victimization. Using generalized linear mixed models, we found that baseline internalized HIV stigma was associated with increased odds of depression (OR 1.74), alcohol misuse (OR 2.09), and violence victimization (OR 1.44) and decreased odds of medication adherence (OR 0.60) over the course of a year. These outcomes negatively impact the health and wellbeing of adolescents living with PHIV and increase their risk of transmitting HIV to their partners in the future. Our findings provide novel, longitudinal evidence for the deleterious effects of HIV stigma. To improve health outcomes for adolescents with PHIV, it will be crucial to develop effective HIV stigma reduction interventions that address specific developmental, gendered, and cultural experiences.

Feasibility and acceptability of point of care testing for sexually transmitted infections in outpatient clinics offering integrated services in Eswatini.

BACKGROUND: Lack of point of care testing (POCT) for sexually transmitted infections (STIs) is a continuing missed opportunity in Sub-Saharan Africa. We assessed feasibility and acceptability of STI POCT in Eswatini. METHODS: STI POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) was piloted among sexually active adults 18-45 years attending two urban outpatient clinics offering HIV services. Females were randomized 1:1 to provide urine or vaginal swab and all males provided urine samples for CT/NG testing using Cepheid CT/NG cartridges on existing GeneXpert platforms. Results were returned in-person or by telephone call. We assessed duration of procedures and participant and healthcare worker acceptability of services (5-point Likert scale), time spent on STI POCT services, and correlates of CT/NG infection. RESULTS: Of 250 adults triaged, 99% (248/250) accepted STI POCT, including 44% (109/248) people living with HIV. STI POCT procedures took a median of 3:22 hours. Most adults (90%, 224/248), received results within a day (61% same day, 29% next day). CT/NG was detected among 22% (55/248): 31/55 CT, 21/55 NG and 3/55 coinfections. Youth 18-25 years, history of any sexual intercourse, and condom-less sex within the previous 7 days were significantly associated with CT/NG detected (p < 0.05). Most adults with CT/NG were treated (51/55, 93%). Most participants were satisfied with STI POCT (217/241, 90%), and would accept again/recommend it. All 32 healthcare workers who participated were satisfied with STI POCT. CONCLUSION: STI POCT was feasible, acceptable, and identified a high prevalence of STIs, highlighting the urgent need for this testing.

First-line anti-tuberculosis drug challenge reactions in DRESS in an HIV endemic setting.

BACKGROUND: In high HIV prevalence settings, first line anti-tuberculosis drug (FLTD)-associated DRESS poses therapeutic challenges. Sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimises re-initiation of non-offending drugs. However, SADC-associated reaction complexities limit its utility. OBJECTIVE: We aimed to describe characteristics of FLTD-associated DRESS patients, their treatment-limiting SADC reactions and related outcomes. METHODS: Patients hospitalized with FLTD-associated DRESS from 2013-2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible. RESULTS: SADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred, 34/47(72%) in 29/41(71%) patients, were treatment-limiting and 12/41(29%) reinitiated FLTDs uneventfully. Fifteen single and eight multiple drug-reactors were identified. Rifampicin, in 13/23(57%) reactors was the commonest individual offender. Ethambutol was most frequently involved in multiple drug-reactors. Median(IQR) time to a detectable reaction was 24(12-120) hours, 6/34(18%) being immediate (<6hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%) and facial oedema (18%), singly or in combination were commonest features. Three reactions, one epidermal necrolysis and two liver derangements, were CTCAE grade 4 (life-threatening) events. No predictors of multiple drug-reactivity were identified, but multiple reactors were hospitalised significantly longer, 125(100-134) versus 60(45-80) days. CONCLUSIONS: SADC optimises FLTD reinitiation. However, timing, clinical presentation and severity of SADC-associated reactions following FLTD-associated DRESS is markedly heterogenous. Additionally, multiple drug-reactors are a complex group requiring longer hospitalisation, and without routine biomarkers to differentiate true multiple drug hypersensitivity from non-specific flare-ups and guide long-term drug avoidance strategies.

The introduction of video-enabled directly observed therapy (video-DOT) for patients with drug-resistant TB disease in Eswatini amid the COVID-19 pandemic - a retrospective cohort study.

BACKGROUND: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic. METHODS: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis. RESULTS: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis. CONCLUSIONS: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

Editorial: The RNA revolution and cancer.

RNA biology has revolutionized cancer understanding and treatment, especially in endocrine-related malignancies. This editorial highlights RNA's crucial role in cancer progression, emphasizing its influence on tumor heterogeneity and behavior. Processes like alternative splicing and noncoding RNA regulation shape cancer biology, with microRNAs, long noncoding RNAs, and circular RNAs orchestrating gene expression dynamics. Aberrant RNA signatures hold promise as diagnostic and prognostic biomarkers in endocrine-related cancers. Recent findings, such as aberrant PI3Kδ splice isoforms and epithelial-mesenchymal transition-related lncRNA signatures, unveil potential therapeutic targets for personalized treatments. Insights into m6A-associated lncRNA prognostic models and the function of lncRNA LINC00659 in gastric cancer represents ongoing research in this field. As understanding of RNA's role in cancer expands, personalized therapies offer transformative potential in managing endocrine-related malignancies. This signifies a significant stride towards precision oncology, fostering innovation for more effective cancer care.

Comparison of the effect of bacterial stimulation on the global epigenetic landscape and transcription of immune genes in primarily zoophilic members of the Anopheles gambiae complex (Diptera: Culicidae).

Members of the Anopheles gambiae complex vary in their vector competence, and this is often attributed to behavioural differences. Similarly, there are differences in transmission capabilities of the zoophilic members of this complex despite exhibiting similar behaviours. Therefore, behavioural differences alone cannot fully explain vector competence variation within members of the An. gambiae complex. The immune system of mosquitoes plays a key role in determining susceptibility to parasite infection and consequently transmission capacity. This study aimed to examine variations in the immune response of An. arabiensis, An. merus and An. quadriannulatus, a major, minor, and non-vector respectively. The global epigenetic landscape was characterised and the expression of Defensin-1 and Gambicin was assessed in response to Gram-positive (Streptococcus pyogenes) and Gram-negative (Escherichia coli) bacterial infections. The effect of insecticide resistance in An. arabiensis on these aspects was also assessed. The immune system was stimulated by a blood-borne bacterial supplementation. The 5mC, 5hmC, m6A methylation levels and Histone Acetyl Transferase activity were assessed with commercial ELISA kits. The transcript levels of Defensin-1 and Gambicin were assessed by quantitative Real-Time Polymerase Chain Reaction. Species-specific differences in 5mC and m6A methylation existed both constitutively as well as post immune stimulation. The epigenetic patterns observed in the laboratory strains were largely conserved in F1 offspring of wild-caught adults. The methylation patterns in the major vector typically differed from that of the minor/non-vectors. The differences between insecticide susceptible and resistant An. arabiensis were more reflected in the expression of Defensin-1 and Gambicin. The expression of these peptides differed in the strains only after bacterial stimulation. Anopheles merus and An. quadriannulatus expressed significantly higher levels of antimicrobial peptides, both constitutively and after immune stimulation. These findings suggest molecular variations in the immune response of members of the An. gambiae complex.

Next generation sequencing-aided screening, isolation, molecular identification, and antimicrobial potential for bacterial endophytes from the medicinal plant, Elephantorrhiza elephantina.

Elephantorrhiza elephantina, a wild plant in southern Africa, is utilized in traditional medicine for various ailments, leading to its endangerment and listing on the Red List of South African Plants. To date, there have been no reports on bacterial endophytes from this plant, their classes of secondary metabolites, and potential medicinal properties. This study presents (i) taxonomic characterization of bacterial endophytes in leaf and root tissues using 16S rRNA, (ii) bacterial isolation, morphological, and phylogenetic characterization, (iii) bacterial growth, metabolite extraction, and LC-MS-based metabolite fingerprinting, and (iv) antimicrobial testing of bacterial crude extracts. Next-generation sequencing yielded 693 and 2,459 DNA read counts for the rhizomes and leaves, respectively, detecting phyla including Proteobacteria, Bacteroidota, Gemmatimonadota, Actinobacteriota, Verrucomicrobiota, Dependentiae, Firmicutes, and Armatimonodata. At the genus level, Novosphingobium, Mesorhizobium, Methylobacterium, and Ralstonia were the most dominant in both leaves and rhizomes. From root tissues, four bacterial isolates were selected, and 16S rRNA-based phylogenetic characterization identified two closely related Pseudomonas sp. (strain BNWU4 and 5), Microbacterium oxydans BNWU2, and Stenotrophomonas maltophilia BNWU1. The ethyl acetate:chloroform (1:1 v/v) organic extract from each isolate exhibited antimicrobial activity against all selected bacterial pathogens. Strain BNWU5 displayed the highest activity, with minimum inhibitory concentrations ranging from 62.5 µg/mL to 250 µg/mL against diarrhoeagenic Escherichia coli, Escherichia coli O157:H7, Salmonella enterica, antibiotic-resistant Vibrio cholerae, Staphylococcus aureus, Bacillus cereus, and Enterococcus durans. LC-MS analysis of the crude extract revealed common antimicrobial metabolites produced by all isolates, including Phenoxomethylpenicilloyl (penicilloyl V), cis-11-Eicosenamide, 3-Hydroxy-3-phenacyloxindole, and 9-Octadecenamide.

Cerebral arteriopathies of childhood and stroke - A focus on systemic arteriopathies and pediatric fibromuscular dysplasia (FMD).

Systemic vascular involvement in children with cerebral arteriopathies is increasingly recognized and often highly morbid. Fibromuscular dysplasia (FMD) represents a cerebral arteriopathy with systemic involvement, commonly affecting the renal and carotid arteries. In adults, FMD diagnosis and classification typically relies on angiographic features, like the 'string-of-beads' appearance, following exclusion of other diseases. Pediatric FMD (pFMD) is considered equivalent to adult FMD although robust evidence for similarities is lacking. We conducted a comprehensive literature review on pFMD and revealed inherent differences between pediatric and adult-onset FMD across various domains including epidemiology, natural history, histopathophysiology, clinical, and radiological features. Although focal arterial lesions are often described in children with FMD, the radiological appearance of 'string-of-beads' is highly nonspecific in children. Furthermore, children predominantly exhibit intimal-type fibroplasia, common in other childhood monogenic arteriopathies. Our findings lend support to the notion that pFMD broadly reflects an undefined heterogenous group of monogenic systemic medium-or-large vessel steno-occlusive arteriopathies rather than a single entity. Recognizing the challenges in categorizing complex morphologies of cerebral arteriopathy using current classifications, we propose a novel term for describing children with cerebral and systemic vascular involvement: 'cerebral and systemic arteriopathy of childhood' (CSA-c). This term aims to streamline patient categorization and, when coupled with advanced vascular imaging and high-throughput genomics, will enhance our comprehension of etiology, and accelerate mechanism-targeted therapeutic developments. Lastly, in light of the high morbidity in children with cerebral and systemic arteriopathies, we suggest that investigating for systemic vascular involvement is important in children with cerebral arteriopathies.

Mutant p53 reactivators protect breast cancer cells from ferroptosis.

Ferroptosis is a novel nonapoptotic form of cell death characterized by iron-dependent reactive oxygen species-mediated lipid peroxidation. In several different cell systems, the tumor suppressor p53 can enhance sensitivity to ferroptotic inducers. At least half of all human cancers show loss of function of p53. Furthermore, many of those tumors express mutant forms of p53 that has lost its wild-type function. Several groups have designed small molecules that can reactivate the wild-type function of these missense p53 mutants. We reasoned that p53 reactivators may also enhance sensitivity of certain cancer cells to ferroptosis stimuli. To test this idea we combined a number of different p53 reactivators with small molecule inducers of ferroptosis. In contrast, we observed that several p53 reactivators protected cells from cell death induced by ferroptotic inducers. Surprisingly, this protection still occurred in p53-null cell lines. We observed that these reactivators were neither free radical scavengers nor ion chelators. One of these p53 reactivator molecules, NSC 59984, reduced expression of GPX4, which is unlikely to explain its ability to reduce sensitivity to ferroptosis. We suggest that these p53 reactivators function via an unknown, p53-independent manner to suppress ferroptosis.

Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study.

BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. FINDINGS: The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). INTERPRETATION: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. FUNDING: National Institute of Health Fogarty International Center.

Whispers in the wind: Face mask sampling for Mycobacterium tuberculosis detection in children with pulmonary tuberculosis.

BACKGROUND: Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with TB. To date, no study has evaluated the use of FMS to detect pulmonary Tuberculosis (TB) in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children. METHODS: Face masks were spiked, analysed on GeneXpert-Ultra, qPCR, and tNGS. Children with pulmonary TB were asked to wear three modified FFP2 masks for 30 minutes as part of an exploratory clinical study. RESULTS: Experiments with H37Ra M. tuberculosis strain showed a limit of 95% detection of 3.75 CFU (4.85-3.11; 95%CI) on GeneXpert-Ultra. Ten children with pulmonary TB participated in the clinical study. M. tuberculosis-specific DNA was detected on none of the face masks. CONCLUSIONS: Paediatric FMS has a low limit of detection for M. tuberculosis-specific DNA in vitro. However, M. tuberculosis DNA was not detected in any of thirty masks worn by children with pulmonary TB. This suggests that FMS in this form may not be more effective for detecting M. tuberculosis in children with TB than existing methods.

"I find it hard to change poor food habits": Measuring food choice motives in an emerging economy.

Food choices are driven by an array of motives that have been approached, determined and quantified in a number of ways, mainly in developed countries. The objective of this study was to better understand the motives behind food choices in an emerging economy by collecting information from urban people in South Africa in a series of four studies. (1) Items generated through focus group discussions with low, middle and high income participants by Magano et al. (2023) were checked for content and face validity and (2) 123 statements derived from them were evaluated by 621 respondents. After exploratory factor analysis (EFA), 46 statements best representing the motivational space were (3) presented to another group of respondents (n = 259). Here, the EFA resulted in a 31-item, 7-factor food choice questionnaire for emerging economies (FCQ-EE) which was (4) confirmed by a nationwide sample (n = 814) and further refined to an alternative 19-item, 7-factor solution. The emerging factors were: Healthy eating constraints (HEC), Frugality (FR), Emotional eating (EE), Meat appeal (MA), Weather (WE), Quality seeking (QS) and Cooking constraints (CC). Whether used in the 31-item or 19-item format, this set of statements highlights factors underlying food choice in an emerging economy and offers a way to study their importance in similar contexts. Further research is needed to show the extent to which these factors can predict actual food choices.