Addressing mpox at a Frontline Community Health Center: Lessons for the Next Outbreak.

The 2022 mpox (formerly monkeypox) outbreak affected predominantly men who have sex with men (MSM), likely through sexual transmission, which resulted in institutions specializing in sexual health being at the frontlines of the mpox outbreak. Fenway Health in Boston serves close to 10 000 MSM annually, which includes more than 2400 MSM who are living with HIV and 3320 MSM with active HIV preexposure prophylaxis (PrEP) prescriptions. We report on the programs implemented and changes to clinical practice at Fenway Health during the mpox outbreak. Fenway Health diagnosed its first case of mpox in June 2022 and treated this patient with tecovirimat. In early July 2022, Fenway Health administered its first dose of the Jynneos vaccine under the Emergency Use Authorization for protection against mpox. As of October 6, 2022, 69 people had tested positive for the mpox virus at Fenway Health. Among the 69 people who tested positive, 43 (62.3%) self-identified as male, with the remaining not reporting a sex or gender identity, and 40 (58.0%) reported their sexual orientation as gay or bisexual. Twenty-five people (36.2%) were treated with tecovirimat. As of October 30, 2022, Fenway Health had administered 6376 doses of the Jynneos vaccine. The programmatic changes involved in rollout and scale-up of vaccination, treatment, and community outreach services at Fenway Health during the 2022 mpox outbreak that we describe here could inform strategies to address subsequent outbreaks.

Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083. METHODS: HPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094. FINDINGS: HPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use. INTERPRETATION: HIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women. FUNDING: National Institute of Allergy and Infectious Diseases and ViiV Healthcare.

PrEP Echo: A National Interdisciplinary Telementoring Program for HIV Prevention Through Practice Transformation.

HIV pre-exposure prophylaxis (PrEP) is highly effective, but PrEP use has been suboptimal. We describe a telementoring program for clinics in high-HIV burden areas, focusing on systems-level practice transformation and care for populations disproportionately affected by HIV. We developed and delivered a telementoring program for U.S. health centers. We analyzed participants' baseline and post-session surveys to ascertain experiences providing PrEP and caring for people disproportionately affected by HIV, comparing responses between medical and behavioral health clinicians. Forty-eight people from 16 health centers participated. Medical clinicians were more likely than behavioral health clinicians to care for people taking PrEP, but the groups did not differ in self-rated capacity to counsel about PrEP or care for populations disproportionately affected by HIV. Virtual training on practice transformation for PrEP, involving medical and behavioral health clinicians, is feasible and acceptable. PrEP training and delivery efforts should include behavioral health clinicians.

Machine learning-based drug design for identification of thymidylate kinase inhibitors as a potential anti-Mycobacterium tuberculosis.

The rise of antibiotic-resistant Mycobacterium tuberculosis (Mtb) has reduced the availability of medications for tuberculosis therapy, resulting in increased morbidity and mortality globally. Tuberculosis spreads from the lungs to other parts of the body, including the brain and spine. Developing a single drug can take several decades, making drug discovery costly and time-consuming. Machine learning algorithms like support vector machines (SVM), k-nearest neighbor (k-NN), random forest (RF) and Gaussian naive base (GNB) are fast and effective and are commonly used in drug discovery. These algorithms are ideal for the virtual screening of large compound libraries to classify molecules as active or inactive. For the training of the models, a dataset of 307 was downloaded from BindingDB. Among 307 compounds, 85 compounds were labeled as active, having an IC50 below 58 mM, while 222 compounds were labeled inactive against thymidylate kinase, with 87.2% accuracy. The developed models were subjected to an external ZINC dataset of 136,564 compounds. Furthermore, we performed the 100-ns dynamic simulation and post trajectories analysis of compounds having good interaction and score in molecular docking. As compared to the standard reference compound, the top three hits revealed greater stability and compactness. In conclusion, our predicted hits can inhibit thymidylate kinase overexpression to combat Mycobacterium tuberculosis.Communicated by Ramaswamy H. Sarma.

In Silico Identification of Lead Compounds for Pseudomonas Aeruginosa PqsA Enzyme: Computational Study to Block Biofilm Formation.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium implicated in acute and chronic nosocomial infections and a leading cause of patient mortality. Pseudomonas aeruginosa infections are frequently associated with the development of biofilms, which give the bacteria additional drug resistance and increase their virulence. The goal of this study was to find strong compounds that block the Anthranilate-CoA ligase enzyme made by the pqsA gene. This would stop the P. aeruginosa quorum signaling system. This enzyme plays a crucial role in the pathogenicity of P. aeruginosa by producing autoinducers for cell-to-cell communication that lead to the production of biofilms. Pharmacophore-based virtual screening was carried out utilizing a library of commercially accessible enzyme inhibitors. The most promising hits obtained during virtual screening were put through molecular docking with the help of MOE. The virtual screening yielded 7/160 and 10/249 hits (ZINC and Chembridge). Finally, 2/7 ZINC hits and 2/10 ChemBridge hits were selected as potent lead compounds employing diverse scaffolds due to their high pqsA enzyme binding affinity. The results of the pharmacophore-based virtual screening were subsequently verified using a molecular dynamic simulation-based study (MDS). Using MDS and post-MDS, the stability of the complexes was evaluated. The most promising lead compounds exhibited a high binding affinity towards protein-binding pocket and interacted with the catalytic dyad. At least one of the scaffolds selected will possibly prove useful for future research. However, further scientific confirmation in the form of preclinical and clinical research is required before implementation.

Strength enhancement of concrete using incinerated agricultural waste as supplementary cement materials.

The potassium (K) and sodium (Na) elements in banana are needed for hydration reaction that can enhance the strength properties of concrete. This research aims (a) to determine the material engineering properties of banana skin ash (BSA) and concrete containing BSA, (b) to measure the strength enhancement of concrete due to BSA, and (c) to identify optimal application of BSA as supplementary cement materials (SCM) in concrete. The BSA characterization were assessed through X-ray fluorescence (XRF) and Blaine's air permeability. The workability, compressive strength, and microstructures of concrete containing BSA were analysed using slump test, universal testing machine (UTM) and scanning electron microscope (SEM). A total of 15 oxides and 19 non-oxides elements were identified in BSA with K (43.1%) the highest and Na was not detected. At 20 g of mass, the BSA had a higher bulk density (198.43 ± 0.00 cm3) than ordinary Portland cement (OPC) (36.32 ± 0.00 cm3) indicating availability of large surface area for water absorption. The concrete workability was reduced with the presence of BSA (0% BSA: > 100 mm, 1% BSA: 19 ± 1.0 mm, 2%: 15 ± 0.0 mm, 3% BSA: 10 ± 0.0 mm). The compressive strength increased with the number of curing days. The concrete microstructures were improved; interfacial transition zones (ITZ) decreased with an increase of BSA. The optimal percentage of BSA obtained was at 1.25%. The established model showed significant model terms (Sum of Squares = 260.60, F value = 69.84) with probability of 0.01% for the F-value to occur due to noise. The established model is useful for application in construction industries.

Dataset of computed N-value and factual N-value traced for Soil Subsurface Profiling.

Soil requires load bearing impact assessment for stability. Therefore, this study aims to utilize the multi-channel analysis surface wave (MASW) for soil subsurface investigation and profiling around Peninsular Malaysia. The standard penetration test (SPT) was conducted for comparison between factual N-value and computed N-value from shear wave velocity (Vs ) obtained from MASW using the Imai and Tonouchi equation. The correlation coefficient (R) and coefficient of determination, (R2 ), showed strong relationship between factual N-value and computed N-value. The model of Vs and factual N-value data distribution is non-normal but the analyzed relationship shows a significant level of p-value < 0.05. The R2 for each location of Vs -N-value relationship are ranging from 0.5 to 0.9.

Modeling of Cu(II) Adsorption from an Aqueous Solution Using an Artificial Neural Network (ANN).

This research optimized the adsorption performance of rice husk char (RHC4) for copper (Cu(II)) from an aqueous solution. Various physicochemical analyses such as Fourier transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FESEM), carbon, hydrogen, nitrogen, and sulfur (CHNS) analysis, Brunauer-Emmett-Teller (BET) surface area analysis, bulk density (g/mL), ash content (%), pH, and pHZPC were performed to determine the characteristics of RHC4. The effects of operating variables such as the influences of aqueous pH, contact time, Cu(II) concentration, and doses of RHC4 on adsorption were studied. The maximum adsorption was achieved at 120 min of contact time, pH 6, and at 8 g/L of RHC4 dose. The prediction of percentage Cu(II) adsorption was investigated via an artificial neural network (ANN). The Fletcher-Reeves conjugate gradient backpropagation (BP) algorithm was the best fit among all of the tested algorithms (mean squared error (MSE) of 3.84 and R2 of 0.989). The pseudo-second-order kinetic model fitted well with the experimental data, thus indicating chemical adsorption. The intraparticle analysis showed that the adsorption process proceeded by boundary layer adsorption initially and by intraparticle diffusion at the later stage. The Langmuir and Freundlich isotherm models interpreted well the adsorption capacity and intensity. The thermodynamic parameters indicated that the adsorption of Cu(II) by RHC4 was spontaneous. The RHC4 adsorption capacity is comparable to other agricultural material-based adsorbents, making RHC4 competent for Cu(II) removal from wastewater.

Dataset on leaching properties of coal ashes from Malaysian coal power plant.

Coal combustion by-products (CCPs) (i.e. fly (FA) and bottom (BA) ashes) generated by power plants contain heavy metals. This research presents leaching properties of coal ashes (FA and BA) collected from Jimah coal-fired power station, Port Dickson, Negeri Sembilan using USEPA standard methods namely toxicity characteristic leaching procedure (TCLP), and synthetic precipitation leaching procedure (SPLP). Heavy metals like lead (Pb), zinc (Zn), copper (Cu) and arsenic (As) were quantified using atomic absorption spectrometer (AAS). The leached of heavy metals fluxes were Cu < Zn < Pb < As. As leached the most whilst indicating of possible contamination from As. Overall, the ranges of leached concentration were adhered to permissible limits of hazardous waste criteria for metal (Pb and As) and industrial effluent (Zn and Cu). The presented data has potential reuse as reference for the coal ash concrete mixed design application in construction industries.

Dataset on specific UV absorbances (SUVA254) at stretch components of Perak River basin.

Perak River basin is in Perak state of Peninsular Malaysia. In this research, the river stretch serves as water intake for domestic, agricultural and industrial purposes in Perak Tengah, Hilir Perak and Manjung regions. It is located in mixed use area whilst exposing the river to anthropogenic elements. The sampling locations were conducted at selected points of Perak River namely Tanjung Belanja Bridge (TBB), Water Treatment Plant Parit (WTPP), Parit Town discharge (PTD), Water Treatment Plant Senin (WTPS) and Water Treatment Plant Kepayang (WTPK). The existence of aromatic hydrocarbons in freshwater samples was pre-assessed via qualification analysis; specific ultraviolet absorbance (SUVA254) method at 254 nm of wavelength. The SUVA dataset were 48.38 L/mg-m (TBB), 50.54 L/mg-m (WTPP), 8.05 L/mg-m (PTD), 85.75 L/mg-m (WTPS) and 217.39 L/mg-m (WTPK). The SUVA254 values of fresh water at the river basin have exceeded the water quality standards value equivalent to 2.0 L/mg-m permitted by the Environmental Protection Agency of United States. The exceeding values were an indication of a large portion of aromatic compounds in the water. Qualification analyses evident the existence of water pollutants at treacherous concentrations for public health in freshwater samples of Perak River basin. Thus, this research has presented important findings towards further research and countermeasure for a better alternative of water treatment in Malaysia.

Step by step procedures: Degradation of polycyclic aromatic hydrocarbons in potable water using photo-Fenton oxidation process.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds, composed of two or more fused benzene rings and abundantly found in mixed-use areas. Mixed-use areas consist of dense population, urbanization, industrial and agricultural activities. River pollution are common in mixed-use areas and 98% of Malaysia's fresh water supply originates from surface water. The biological degradation, adsorption and advanced oxidation process were documented as the available PAHs treatment for water. To date, the application of the photo-Fenton oxidation process has been reported for the treatment of PAHs from contaminated soil (review paper), landfill leachate, municipal solid waste leachate, sanitary landfill leachate, aniline wastewater, ammunition wastewater and saline aqueous solutions. As for potable water, the application of Fenton reagent was aided with photo treatment or electrolysis not focusing on PAHs removal. •The presented MethodsX was conducted for PAHs degradation analysis in potable water samples using photo-Fenton oxidation process.•The designed reactor for batch experiment is presented.•The batch experiment consists of parameters like concentration of 17 USEPA-PAHs in the prepared aqueous solution (fixed variable), reaction time, pH and molarity ratio of hydrogen peroxide (H2O2): ferrous sulfate (FeSO4).

Application of response surface methodology for the optimization of polycyclic aromatic hydrocarbons degradation from potable water using photo-Fenton oxidation process.

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds, composed of benzene rings. The objective of this research was to identify the optimum condition for the degradation of PAHs contaminated water using photo-Fenton oxidation process via response surface methodology (RSM). Aqueous solution was prepared and potable water samples were collected from water treatment plants in Perak Tengah, Perak, Malaysia in September 2016. The reaction time, pH, molarity of H2O2 and FeSO4 were analyzed followed by RSM using aqueous solution. A five level central composite design with quadratic model was used to evaluate the effects and interactions of these parameters. The response variable was the percentage of total organic carbon (TOC) removal. PAHs quantification was done using gas chromatography mass spectrometry analysis. The regression line fitted well with the data with R2 value of 0.9757. The lack of fit test gives the highest value of Sum of Squares (15,666.64) with probability F value 0.0001 showing significant quadratic model. The optimum conditions were established corresponding to the percentage of TOC removal. The PAHs removal efficiency for potable water samples ranged from 76.4% to 91% following the first order of kinetic rates with R2 values of >0.95. Conventional water treatment techniques are not effective for PAHs removal. Thus, advanced oxidation processes may be considered as an alternative to conventional water treatment techniques in Malaysia and other developing countries.

Medical management of drug-sensitive active thoracic tuberculosis: the work-up, radiographic findings and treatment.

Tuberculosis (TB) infection and disease have plagued human civilization across time and led to immeasurable morbidity and mortality. This review article focuses on the most currently available information regarding the diagnostic workup, radiologic presentation and treatment of drug-sensitive active TB. As discussed, if adequate resources and methods are available to diagnose, evaluate, and treat patients, drug sensitive TB is an imminently curable disease.

Genotoxicity assessment of raw and treated water samples using Allium cepa assay: evidence from Perak River, Malaysia.

Allium cepa assay was carried out in this study to evaluate genotoxic effects of raw and treated water samples from Perak River in Perak state, Malaysia. Samples were collected from three surface water treatment plants along the river, namely WTPP, WTPS, and WTPK. Initially, triplicates of equal size Allium cepa (onions) bulbs, 25-30 mm in diameter and average weight of 20 g, were set up in distilled water for 24 h at 20 ± 2 °C and protected from direct sunlight, to let the roots to grow. After germination of roots (0.5-1.0 cm in length), bulbs were transferred to collected water samples each for a 96-h period of exposure. The root physical deformations were observed. Genotoxicity quantification was based on mitotic index and genotoxicity level. Statistical analysis using cross-correlation function for replicates from treated water showed that root length has inverse correlation with mitotic indices (r = - 0.969) and frequencies of cell aberrations (r = - 0.976) at lag 1. Mitotic indices and cell aberrations of replicates from raw water have shown positive correlation at lag 1 (r = 0.946). Genotoxicity levels obtained were 23.4 ± 1.98 (WTPP), 26.68 ± 0.34 (WTPS), and 30.4 ± 1.13 (WTPK) for treated water and 17.8 ± 0.18 (WTPP), 37.15 ± 0.17 (WTPS), and 47.2 ± 0.48 (WTPK) for raw water. The observed cell aberrations were adherence, chromosome delay, C-metaphase, chromosome loss, chromosome bridge, chromosome breaks, binucleated cell, mini cell, and lobulated nuclei. The morphogenetic deformations obtained were likely due to genotoxic substances presence in collected water samples. Thus, water treatment in Malaysia does not remove genotoxic compounds.

Didactic training vs. computer-based self-learning in the prediction of diminutive colon polyp histology by trainees: a randomized controlled study.

Background and study aim Experts can accurately predict diminutive polyp histology, but the ideal method to train nonexperts is not known. The aim of the study was to compare accuracy in diminutive polyp histology characterization using narrow-band imaging (NBI) between participants undergoing classroom didactic training vs. computer-based self-learning. Participants and methods Trainees at two institutions were randomized to classroom didactic training or computer-based self-learning. In didactic training, experienced endoscopists reviewed a presentation on NBI patterns for adenomatous and hyperplastic polyps and 40 NBI videos, along with interactive discussion. The self-learning group reviewed the same presentation of 40 teaching videos independently, without interactive discussion. A total of 40 testing videos of diminutive polyps under NBI were then evaluated by both groups. Performance characteristics were calculated by comparing predicted and actual histology. Fisher's exact test was used and P < 0.05 was considered significant. Results A total of 17 trainees participated (8 didactic training and 9 self-learning). A larger proportion of polyps were diagnosed with high confidence in the classroom group (66.5 % vs. 50.8 %; P < 0.01), although sensitivity (86.9 % vs. 95.0 %) and accuracy (85.7 % vs. 93.9 %) of high-confidence predictions were higher in the self-learning group. However, there was no difference in overall accuracy of histology characterization (83.4 % vs. 87.2 %; P = 0.19). Similar results were noted when comparing sensitivity and specificity between the groups. Conclusion The self-learning group showed results on a par with or, for high-confidence predictions, even slightly superior to classroom didactic training for predicting diminutive polyp histology. This approach can help in widespread training and clinical implementation of real-time polyp histology characterization.

Effectiveness of simple control measures on methicillin-resistant Staphylococcus aureus infection status and characteristics with susceptibility patterns in a teaching hospital in Peshawar.

OBJECTIVE: To determine the effectiveness of simple control measures on the infection status and characteristics of methicillin-resistant Staphylococcus aureus including susceptibility patterns among health professionals and patients in a teaching hospital. METHODS: The cross-sectional study was conducted from September 2013 to January 2014, and comprised samples collected from healthcare personnel and patients in the various units of Khyber Teaching Hospital, Peshawar. The specimens were collected before and one month after the implementation of simple control measures for outbreak prevention of methicillin-resistant Staphylococcus aureus. These were tested for culture and antimicrobial susceptibility. Data about methicillin-sensitive and methicillin-resistant Staphylococcus aureus infection, wound characteristics and susceptibility patterns was collected and effectiveness of simple control measures was determined. SPSS 20 was used for statistical analysis. RESULTS: Of the total 390 isolates, 180(46.2%) were Staphylococcus aureus; 77(19.7%) from healthcare personnel and 103(26.4%) from patients. Of these, 164(42.1%) were methicillin-sensitive and 16(4.1%) were methicillin-resistant. Among the patients, 38(15.1%) methicillin-sensitive and 8(3.2%) methicillin-resistant isolates were recovered from wounds or skin and soft tissues. Pus with 33(13.1%) and 4(1.6%) cases respectively was the second most common source. Among methicillin-resistant isolates, resistance to Linezolid was 0%, all were resistant to Oxacillin, Cefoxitin, Amoxicillin, Cefotaxime and Cephradine, and resistance to both Co-Amoxiclav and Ciprofloxacin was 87.5%. After one month of implementation of simple control measures, the number of methicillin-resistant cases among healthcare professionals and patients dropped from 4(2.9%) and 7(10.8%) to 1(0.7%) and 5(2.7%), respectively. CONCLUSIONS: Methicillin-resistant and methicillin-sensitive Staphylococcus aureus differed in their anti-microbial susceptibility profiles. Selection of antibiotics based on susceptibility and culture is needed for prevention of resistance and effective treatment. A decrease was observed in methicillin-resistant cases with implementation of control measures.

IL-17 mediates estrogen-deficient osteoporosis in an Act1-dependent manner.

Estrogen-deficient osteoporosis may be an inflammatory disorder and we therefore asked if IL-17 participates in its pathogenesis. Deletion of the principal IL-17 receptor (IL-17RA) protects mice from ovariectomy (OVX)-induced bone loss. Further supporting a central role of IL-17 in its pathogenesis, OVX-induced osteoporosis is prevented by a blocking antibody targeting the cytokine. IL-17 promotes osteoclastogenesis by stimulating RANK ligand (RANKL) expression by osteoblastic cells, mediated by the IL-17RA SEFIR/TILL domain. Estrogen deprivation, however does not enhance IL-17RA mRNA expression by osteoblasts or in bone, but augments that of Act1, an IL-17RA-interacting protein and signaling mediator. Similar to IL-17RA(-/-) mice, those lacking Act1 are protected from OVX-induced bone loss. Also mirroring IL-17RA-deficiency, absence of Act1 in osteoblasts, but not osteoclasts, impairs osteoclastogenesis via dampened RANKL expression. Transduction of WT Act1 into Act1(-/-) osteoblasts substantially rescues their osteoclastogenic capacity. The same construct, however, lacking its E3 ligase U-box or its SEFIR domain, which interacts with its counterpart in IL-17RA, fails to do so. Estrogen deprivation, therefore, promotes RANKL expression and bone resorption in association with upregulation of the IL-17 effector, Act1, supporting the concept that post-menopausal osteoporosis is a disorder of innate immunity.