Optimizing and validating a pediatric screening tool to more efficiently test and identify children living with HIV.

OBJECTIVE: To develop and validate a screening tool to improve testing efficiency and increase case finding of children living with HIV. DESIGN: Cross-sectional study. METHODS: Between November 2020 and September 2021, children 18 months to 14 years presenting at outpatient departments in 30 health facilities in Zambia were administered a 14-question pediatric HIV screening tool and then tested for HIV. Data were analyzed using a randomly extracted 'validation' dataset and multivariable logistic regression to determine the highest performing and optimal number of screening questions. The final tool was then evaluated in the 'test' dataset. Sensitivity and specificity were calculated for both datasets. The final tool was then also implemented in 12 additional facilities to determine operational feasibility and uptake. RESULTS: A total of 9902 children were included in the final analysis. HIV prevalence was 1.3%. Six questions were significantly associated with HIV-positivity. The optimal screening cutoff score was to answer 'yes' to one or more of the six questions; using this cutoff sensitivity was 92.5% [95% confidence interval (CI) 85.7-96.7%] and specificity was 62.9% (95% CI 61.9-64%). In the test dataset, the same tool had a sensitivity of 84.6% (95% CI 65.1-95.6%) and specificity of 64.6% (95% CI 62.4-66.7%). Uptake was 89%. CONCLUSION: The results of this study show sensitivity and acceptable specificity in a six-question validated HIV screening tool. Implementing this screening tool in settings where universal testing is not feasible should more efficiently accelerate identification of children living with HIV (CLHIV) and their timely initiation onto life-saving drugs.

Fusing 10-vertex closo-carborane anions with N-heterocyclic carbenes.

Discovered by Knöth in 1964, the 10-vertex closo-carborane anion [HCB9H91-] is a classical bicapped square antiprism that contains an unusual pentacoordinate carbon center. Compared to its larger icosahedral cousin [HCB11H111-], few investigations have been made into its use as a weakly coordinating anion or as a ligand substituent. Here we show that it is possible to prepare both a dianionic N-heterocyclic carbene (NHC) Li+ adduct as well as a trianionic C-2, C-5 dilithio species featuring two 10-vertex carborane anion substituents. All compounds were characterized via multinuclear NMR spectroscopy, single crystal X-ray diffraction, and HRMS when possible.

A 10-year Review of TB Notifications and Mortality Trends Using a Joint Point Analysis in Zambia - a High TB burden country.

BACKGROUND: Zambia is one of the TB high-burden countries. It is important to track the progress being made towards enhancing case finding and reducing mortality. We reviewed routine TB notifications and mortality trends, over a decade from all facilities in Zambia. METHODS: A 10-year retrospective study of TB notifications and mortality trends was performed using a Joint Point Analysis version 4.9.0.0, NCI. We extracted the annual national TB program data for the period under review. RESULTS: There was a decline in annual point average for notification between 2010 and 2020 in both males and females, but the females notification rates had a higher rate of decline (AAPC = -6.7, 95%CI:-8.3 to -5.0), p<0.001) compared to the decline in males notification rate (AAPC = -4.1, 95%CI:-4.1 to -5.1, P<0.001). We found a significant growth rate in the proportion of TB patients that were bacteriologically confirmed (AAPC = 6.1, 95% CI: 3.6 to 8.7, p< 0.001), while the proportion of clinically diagnosed patients declined (AAPC= -0.1, 95%CI: -2.3 to 2.1, p<0.001). Notification of drug-resistant TB increased exponentially (AAPC=27.3, 95% CI: 13 to 41), p< 0.001) while mortality rate declined from 21.3 in 2011 to 12.7 in 2019 per 100,000 population (AAP=-5.6, 95%CI: -9.6 to -1.5, p=0.008). CONCLUSIONS: This study has illustrated the importance of reviewing and analyzing routinely collected TB data by national programs. The study revealed areas of improvement in terms of TB control and underscores the need for increased and sustained investment in case detection and diagnostics.

Curcumin Protects Osteoblasts From Oxidative Stress-Induced Dysfunction via GSK3ß-Nrf2 Signaling Pathway.

Osteoblasts dysfunction, induced by oxidative stress (OS), is one of major pathological mechanisms for osteoporosis. Curcumin (Cur), a bioactive antioxidant compound, isolated from Curcumin longa L, was regarded as a strong reactive oxygen species (ROS) scavenger. However, it remains unveiled whether Cur can prevent osteoblasts from OS-induced dysfunction. To approach this question, we adopted a well-established OS model to investigate the preventive effect of Cur on osteoblasts dysfunction by measuring intracellular ROS production, cell viability, apoptosis rate and osteoblastogenesis markers. We showed that the pretreatment of Cur could significantly antagonize OS so as to suppress endogenous ROS production, maintain osteoblasts viability and promote osteoblastogenesis. Inhibiting Glycogen synthase kinase (GSK3ß) and activating nuclear factor erythroid 2 related factor 2 (Nrf2) could significantly antagonize the destructive effects of OS, which indicated the critical role of GSK3ß-Nrf2 signaling. Furthermore, Cur also abolished the suppressive effects of OS on GSK3ß-Nrf2 signaling pathway. Our findings demonstrated that Cur could protect osteoblasts against OS-induced dysfunction via GSK3ß-Nrf2 signaling and provide a promising way for osteoporosis treatment.

Strongly Coordinating Ligands To Form Weakly Coordinating Yet Functional Organometallic Anions.

Weakly coordinating anions (WCAs) are generally tailored to act as spectators with little or no function. Here we describe the implementation of strongly coordinating dianionic carboranyl N-heterocyclic carbenes (NHCs) to create organometallic -ate complexes of Au(I) that serve both as WCAs and functional catalysts. These organometallic WCAs can be utilized to form both heterobimetallic (Au(I)-/Ag(I)+; Au(I)-/Ir(I)+) and organometallic/main group ion pairs (Au(I)-/(CPh3+ or SiEt3+). Because parent unfunctionalized dianionic carboranyl NHC complex 3 is unstable in most solvents when paired with CPh3+, novel synthesis methodology was devised to create polyhalogenated carboranyl NHCs, which show superior stability toward electrophilic substitution and cyclometalation chemistry. Additionally, the WCAs containing polyhalogenated carboranyl NHCs are among the most active catalysts reported for the hydroamination of alkynes. This investigation has also produced the first examples of a low-coordinate Au(III) center with two cis accessible coordination sites and the first true dianionic carbene. These studies pave the way for the design of functional ion pairs that have the potential to participate in tandem or cooperative small-molecule activation and catalysis.

Multiwell Assay for the Analysis of Sugar Gut Permeability Markers: Discrimination of Sugar Alcohols with a Fluorescent Probe Array Based on Boronic Acid Appended Viologens.

With the aim of discerning between different sugar and sugar alcohols of biomedical relevance, such as gut permeability, arrays of 2-component probes were assembled with up to six boronic acid-appended viologens (BBVs): 4,4'-o-BBV, 3,3'-o-BBV, 3,4'-o-BBV, 4,4'-o,m-BBV, 4,7'-o-PBBV, and pBoB, each coupled to the fluorophore 8-hydroxypyrene, 1,3,6-trisulfonic acid trisodium salt (HPTS). These probes were screened for their ability to discriminate between lactulose, l-rhamnose, 3-O-methyl-d-glucose, and xylose. Binding studies of sugar alcohols mannitol, sorbitol, erythritol, adonitol, arabitol, galactitol, and xylitol revealed that diols containing threo-1,2-diol units have higher affinity for BBVs relative diols containing erythro-1,2 units. Those containing both threo-1,2- and 1,3-syn diol motifs showed high affinity for boronic acid binding. Fluorescence from the arrays were examined by principle component analysis (PCA) and linear discriminant analysis (LDA). Arrays with only three BBVs sufficed to discriminate between sugars (e.g., lactulose) and sugar alcohols (e.g., mannitol), establishing a differential probe. Compared with 4,4'-o-BBV, 2-fold reductions in lower limits of detection (LOD) and quantification (LOQ) were achieved for lactulose with 4,7-o-PBBV (LOD 41 µM, LOQ 72 µM). Using a combination of 4,4'-o-BBV, 4,7-o-PBBV, and pBoB, LDA statistically segregated lactulose/mannitol (L/M) ratios from 0.1 to 0.5, consistent with values encountered in small intestinal permeability tests. Another triad containing 3,3'-o-BBV, 4,4'-o-BBV, and 4,7-o-PBBV also discerned similar L/M ratios. This proof-of-concept demonstrates the potential for BBV arrays as an attractive alternate to HPLC to analyze mixtures of sugars and sugar alcohols in biomedical applications and sheds light on structural motifs that make this possible.