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OBJECTIVE: We assessed the cost-effectiveness of determining new human immunodeficiency virus (HIV) diagnoses using rapid HIV testing performed by community-based organizations (CBOs) in Kansas City, Missouri, and Detroit, Michigan. METHODS: The CBOs performed rapid HIV testing during April 2004 through March 2006. In Kansas City, testing was performed in a clinic and in outreach settings. In Detroit, testing was performed in outreach settings only. Both CBOs used mobile testing vans. Measures of effectiveness were the number of HIV tests performed and the number of people notified of new HIV diagnoses, based on rapid tests. We retrospectively collected program costs, including those for personnel, test kits, mobile vans, and facility space. RESULTS: The CBO in Kansas City tested a mean of 855 people a year in its clinic and 703 people a year in outreach settings. The number of people notified of new HIV diagnoses was 19 (2.2%) in the clinic and five (0.7%) in outreach settings. The CBO in Detroit tested 976 people a year in outreach settings, and the number notified of new HIV diagnoses was 15 (1.5%). In Kansas City, the cost per person notified of a new HIV diagnosis was $3,637 in the clinic and $16,985 in outreach settings. In the Detroit outreach settings, the cost per notification was $13,448. CONCLUSIONS: The cost of providing a new HIV diagnosis was considerably higher in the outreach settings than in the clinic. The variation can be largely explained by differences in the number of undiagnosed infections among the people tested and by the costs of purchasing and operating a mobile van. [ABSTRACT FROM AUTHOR]

Objective: To assess the costs of rapid human immunodeficiency virus (HIV) testing and counseling to identify new diagnoses of HIV infection among jail inmates.Study Design: We obtained program costs and testing outcomes from rapid HIV testing and counseling services provided in jails from March 1, 2004, through February 28, 2005, in Florida, Louisiana, New York, and Wisconsin. We obtained annual program delivery costs-fixed and variable costs-from each project area. We estimated the average cost of providing counseling and testing to HIV-negative and HIV-infected inmates and estimated the cost per newly diagnosed HIV infection.Results: In the 4 project areas, 17,433 inmates (range, 2185-6463) were tested: HIV infection was diagnosed for 152 inmates (range, 4-81). The average cost of testing ranged from $29.46 to $44.98 for an HIV-negative inmate and from $71.37 to $137.72 for an HIV-infected inmate. The average cost per newly diagnosed HIV infection ranged from $2,451 to $25,288. Variable costs were 61% to 86% of total costs.Conclusion: The cost of identifying jail inmates with newly diagnosed HIV infection by using rapid HIV testing varied according to the prevalence of undiagnosed HIV infection among inmates tested in project areas. Variations in the cost of testing HIV-negative and HIV-infected inmates were because of the differences in wages, travel to the jails, and the amount of time spent on counseling and testing. Program managers can use these data to gauge the cost of initiating counseling and testing programs in jails or to streamline current programs. [ABSTRACT FROM AUTHOR]

Nitrogen oxides (NO x ) emissions can cause air pollution that is harmful to human health, even producing serious ecological problems. Whether it is diluted in the air or not, the management and valorization of NO x from industrial emissions have been constrained by technology and finance. This study shows that red soil can be used as a photocatalyst to convert NO x into soil nitrate nitrogen (NO 3 - -N) in the soil. The addition of zinc oxide (ZnO) and titanium dioxide (TiO 2 ) onto the soil surface improves the photocatalytic precipitation efficiency of 1 ppm NO, approaching a removal efficiency of 77 % under ultraviolet (UV) light. The efficiency of red soil in precipitating NO x through adsorption exceeded that of photocatalysis at 100 ppm NO x (e.g. 16.02 % versus 7.70 % in 0.1-mm soil). Pot experiment reveals that the precipitated NO 3 - -N promoted biomass of water spinach (Ipomoea aquatica Forsk). Additionally, adding ZnO or TiO 2 also affects mineral nutrition. This demonstration of converting air pollutants into available nitrogen (N) for plant growth not only provides a new perspective on treatment and valorization for NO x but also sheds light on the transport of N in the air-soil-plant path., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plants have powerful defense mechanisms and extensive immune receptor repertoires, yet crop monocultures are prone to epidemic diseases. Rice (Oryza sativa) is susceptible to many diseases, such as rice blast caused by Magnaporthe oryzae. Varietal resistance of rice to blast relies on intracellular nucleotide binding, leucine-rich repeat (NLR) receptors that recognize specific pathogen molecules and trigger immune responses. In the Yuanyang terraces in southwest China, rice landraces rarely show severe losses to disease whereas commercial inbred lines show pronounced field susceptibility. Here, we investigate within-landrace NLR sequence diversity of nine rice landraces and eleven modern varieties using complexity reduction techniques. We find that NLRs display high sequence diversity in landraces, consistent with balancing selection, and that balancing selection at NLRs is more pervasive in landraces than modern varieties. Notably, modern varieties lack many ancient NLR haplotypes that are retained in some landraces. Our study emphasizes the value of standing genetic variation that is maintained in farmer landraces as a resource to make modern crops and agroecosystems less prone to disease. The conservation of landraces is, therefore, crucial for ensuring food security in the face of dynamic biotic and abiotic threats., Competing Interests: Declaration of interests The authors declare no competing interests, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Solid tumors are highly reliant on lipids for energy, growth, and survival. In prostate cancer, the activity of the androgen receptor (AR) is associated with reprogramming of lipid metabolic processes. Here, we identified acyl-CoA synthetase medium chain family members 1 and 3 (ACSM1 and ACSM3) as AR-regulated mediators of prostate cancer metabolism and growth. ACSM1 and ACSM3 were upregulated in prostate tumors compared with nonmalignant tissues and other cancer types. Both enzymes enhanced proliferation and protected prostate cancer cells from death in vitro, whereas silencing ACSM3 led to reduced tumor growth in an orthotopic xenograft model. ACSM1 and ACSM3 were major regulators of the prostate cancer lipidome and enhanced energy production via fatty acid oxidation. Metabolic dysregulation caused by loss of ACSM1/3 led to mitochondrial oxidative stress, lipid peroxidation, and cell death by ferroptosis. Conversely, elevated ACSM1/3 activity enabled prostate cancer cells to survive toxic levels of medium chain fatty acids and promoted resistance to ferroptosis-inducing drugs and AR antagonists. Collectively, this study reveals a tumor-promoting function of medium chain acyl-CoA synthetases and positions ACSM1 and ACSM3 as key players in prostate cancer progression and therapy resistance. Significance: Androgen receptor-induced ACSM1 and ACSM3 mediate a metabolic pathway in prostate cancer that enables the utilization of medium chain fatty acids for energy production, blocks ferroptosis, and drives resistance to clinically approved antiandrogens., (©2024 American Association for Cancer Research.)

Background: There is a lack of data on the characteristics of overlap between acquired antimicrobial resistance and virulence factors in Klebsiella pneumoniae in high-risk settings, especially with the inclusion of surveillance isolates along with the clinical. We investigated K. pneumoniae isolates, from a neonatal intensive care unit (NICU) in Nepal, for the presence of both accessory virulence factors and acquired antimicrobial resistance., Methods: Thirty-eight clinical and nineteen surveillance K. pneumoniae isolates obtained between January 2017 and August 2022 in the NICU of Siddhi Memorial Hospital, Bhaktapur, Nepal were investigated with antimicrobial susceptibility testing, PCR-based detection of β-lactamases and virulence factors, and genetic similarity by ERIC-PCR., Results: K. pneumoniae was found positive in 37/85 (43.5%) blood culture-positive neonatal bloodstream infections, 34/954 (3.6%) patient surveillance cultures, and 15/451 (3.3%) environmental surveillance samples. Among 57 isolates analyzed in this study, we detected multidrug resistance in 37/57 (64.9%), which was combined with at least one accessory virulence factor in 21/37 (56.8%). This overlap was mostly among β-lactamase producing isolates with accessory mechanisms of iron acquisition. These isolates displayed heterogenous ERIC-PCR patterns suggesting genetic diversity., Conclusions: The clinical significance of this overlap between acquired antimicrobial resistance and accessory virulence genes in K. pneumoniae needs further investigation. Better resource allocation is necessary to strengthen infection prevention and control interventions in resource-limited settings., (© 2024. The Author(s).)

Introduction : Osteomyelitis is a challenging bone infection associated with ischemia, trauma, or various surgical procedures (e.g., joint reconstruction). Treatment involves eradicating infected bone and soft tissue, local antibiotic delivery, and a 6-week course of antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) infections are common, and vancomycin is the standard treatment, but alternatives like linezolid are needed in vancomycin-resistant and vancomycin-allergic patients. Methods : A retrospective chart review was conducted on patients treated by the senior author between 2013 and 2021. The study included patients who received local delivery of linezolid for bone and/or joint infection with documented evidence of vancomycin allergy. Patient demographics, surgical details, linezolid delivery method, and outcomes were recorded. Clinical outcomes and subsequent procedures leading to infection eradication were documented. Results : A total of 13 patients were treated with linezolid-antibiotic-laden spacers with polymethyl methacrylate (PMMA) carrier. Nine patients were successfully treated using limb-salvage techniques and were still infection-free after a mean follow-up of 55.5 months. Conclusions : Linezolid-loaded bone cement is an option for managing chronic bone and joint infections, particularly MRSA, in patients with vancomycin allergy., Competing Interests: Janet D. Conway is a consultant for Bonesupport, Johnson and Johnson, Orthofix, and Smith and Nephew; receives fellowship support from Biocomposites; and is on the MicroGenDX advisory board. The remaining authors have no competing interests to declare., (Copyright: © 2024 Abhijith Annasamudram et al.)

Background: Studies show that more than 5.1 million deaths annually are attributed to nonoptimal temperatures, including extreme cold and extreme heat. However, those studies mostly report average estimates across large geographical areas. The health risks attributed to nonoptimal temperatures in British Columbia (BC) are reported incompletely or limit the study area to urban centers. In this study, we aim to estimate the attributable deaths linked to nonoptimal temperatures in all five regional health authorities (RHAs) of BC from 2001 to 2021., Methods: We applied the widely used distributed lag nonlinear modeling approach to estimate temperature-mortality association in the RHAs of BC, using daily all-cause deaths and 1 × 1 km gridded daily mean temperature. We evaluated the model by comparing the model-estimated attributable number of deaths during the 2021 heat dome to the number of heat-related deaths confirmed by the British Columbia Coroners Service., Results: Overall, between 2001 and 2021, we estimate that 7.17% (95% empirical confidence interval = 3.15, 10.32) of deaths in BC were attributed to nonoptimal temperatures, the majority of which are attributed to cold. On average, the mortality rates attributable to moderate cold, moderate heat, extreme cold, and extreme heat were 47.04 (95% confidence interval [CI] = 45.83, 48.26), 0.94 (95% CI = 0.81, 1.08), 2.88 (95% CI = 2.05, 3.71), and 3.10 (95% CI = 1.79, 4.4) per 100,000 population per year, respectively., Conclusions: Our results show significant spatial variability in deaths attributable to nonoptimal temperatures across BC. We find that the effect of extreme temperatures is significantly less compared to milder nonoptimal temperatures between 2001 and 2021. However, the increased contribution of extreme heat cannot be ruled out in the near future., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Objectives: Data on antimicrobial resistance (AMR) among children in Nepal are limited. Here we have characterized the causes of bacterial bloodstream infections (BSIs), antimicrobial resistance patterns and the mechanisms of β-lactamase production in Enterobacterales among children attending outpatient and inpatient departments of a secondary care paediatric hospital in Nepal., Methods: We retrospectively collected demographic and clinical data of culture-proven bacterial BSIs between January 2017 and December 2022 among children <18 years attending a 50-bedded paediatric hospital. Stored isolates were subcultured for antimicrobial susceptibility testing against commonly used antimicrobials. Enterobacterales displaying non-susceptibility to β-lactams were phenotypically and genotypically investigated for ESBLs, plasmid-mediated AmpC (pAmpC) β-lactamases and carbapenemases., Results: A total of 377 significant bacteria were isolated from 27 366 blood cultures. Among 91 neonates with a BSI, Klebsiella pneumoniae ( n  = 39, 42.4 % ), Pseudomonas aeruginosa ( n  = 15, 16.3%) and Acinetobacter baumannii complex ( n  = 13, 14.1%) were most common. In the non-neonates, 275/285 (96.5%) infections were community-acquired including Staphylococcus aureus ( n  = 89, 32.4%), Salmonella Typhi ( n  = 54, 19.6%) and Streptococcus pneumoniae ( n  = 32, 11.6%). Among the 98 S. aureus , 29 (29.6%) were methicillin-resistant Staphylococcus aureus . K. pneumoniae and Escherichia coli demonstrated non-susceptibility to extended-spectrum cephalosporins and carbapenems in both community and hospital-acquired cases. For E. coli and K. pneumoniae , bla CTX-M (45/46), bla EBC (7/10) and bla OXA-48 (5/6) were common among their respective groups., Conclusions: We determined significant levels of AMR among children attending a secondary care paediatric hospital with BSI in Nepal. Nationwide surveillance and implementation of antimicrobial stewardship policies are needed to combat the challenge imposed by AMR., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: Cost-effectiveness analysis of HIV self-testing using patient-level data from a randomized clinical trial can inform HIV prevention funding decisions. Cost-effectiveness analysis using net-benefit regression addresses the sampling uncertainty in the trial data and the variability of policymakers' willingness to pay (WTP)., Methods: We used published data from a 12-month longitudinal randomized clinical trial that enrolled 2665 men who had sex with men randomly assigned to the self-testing arm (participants receiving self-test kits) and control arm (participants receiving standard-of-care), and the self-testing arm identified 48 additional new HIV cases. We used net-benefit regression to investigate the cost-effectiveness of an HIV self-testing intervention, which compared the incremental cost per new HIV diagnosis with policymakers' WTP thresholds. We addressed the uncertainties in estimating the incremental cost and the policymakers' WTP per new diagnosis through the incremental net-benefit (INB) regression and cost-effectiveness acceptability curve (CEAC) analyses., Results: From the health care provider's perspective, the INB analysis showed a positive net benefit of HIV self-testing compared with standard-of-care when policymakers' WTP per new HIV diagnosis was $9365 (95% confidence interval: $5700 to $25,500) or higher. The CEAC showed that the probability of HIV self-testing being cost-effective compared with standard-of-care was 58% and >99% at a WTP of $10 000 and $50 000 per new HIV diagnosis, respectively., Conclusion: The INB and CEAC analyses suggest that HIV self-testing has the potential to be cost-effective for relatively low values of policymakers' WTP., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: HIV testing is an entry point to access HIV care and prevention services. Building Healthy Online Communities developed a website ( TakeMeHome.org ) where participants can order HIV home test kits. The purpose of this study was to analyze the costs and impact of the TakeMeHome program., Methods: We estimated the costs of TakeMeHome across all participating jurisdictions for the first year of the program. We estimated program costs using purchase orders and invoices, contracts, and allocation of staff time, and the costs included website design, participant recruitment, administration and overhead, HIV self-test kits, and shipping and handling. Primary outcomes of the analysis were total program cost, cost per HIV test, and cost per new HIV diagnosis., Results: The TakeMeHome program distributed 5323 HIV self-tests to 4859 participants over a 12-month period. The total program cost over this period was $314,870. The cost per HIV test delivered was estimated at $59, and the cost per person tested was $65. The program identified 18 confirmed new HIV diagnoses (0.6% positivity) verified with surveillance data in 7 health jurisdictions at $169,890. The cost per confirmed new HIV diagnosis was estimated at $9440., Conclusions: The TakeMeHome program delivered HIV self-testing at a reasonable cost, and the program may be a cost-effective use of HIV prevention resources. The public-private partnership can be an effective mechanism to validate HIV diagnoses identified with self-testing and provide HIV prevention and linkage to care services., Competing Interests: J.H. reports institutional funding from Gilead Sciences, and no other potential conflicts of interests were disclosed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI enzalutamide inhibits only a subset of all AR-regulated genes, and hypothesise that the unaffected gene networks represent potential targets for therapeutic intervention. This study identified the hyaluronan-mediated motility receptor (HMMR) as a survival factor in prostate cancer and investigated its potential as a co-target for overcoming resistance to ARSIs., Methods: RNA-seq, RT-qPCR and Western Blot were used to evaluate the regulation of HMMR by AR and ARSIs. HMMR inhibition was achieved via siRNA knockdown or pharmacological inhibition using 4-methylumbelliferone (4-MU) in prostate cancer cell lines, a mouse xenograft model and patient-derived explants (PDEs)., Results: HMMR was an AR-regulated factor that was unaffected by ARSIs. Genetic (siRNA) or pharmacological (4-MU) inhibition of HMMR significantly suppressed growth and induced apoptosis in hormone-sensitive and enzalutamide-resistant models of prostate cancer. Mechanistically, 4-MU inhibited AR nuclear translocation, AR protein expression and subsequent downstream AR signalling. 4-MU enhanced the growth-suppressive effects of 3 different ARSIs in vitro and, in combination with enzalutamide, restricted proliferation of prostate cancer cells in vivo and in PDEs., Conclusion: Co-targeting HMMR and AR represents an effective strategy for improving response to ARSIs., (© 2023. The Author(s).)

Background: Transferrable mechanisms of quinolone resistance (TMQR) can lead to fluoroquinolone non-susceptibility in addition to chromosomal mechanisms. Some evidence suggests that fluoroquinolone resistance is increasing among the pediatric population. We sought to determine the occurrence of TMQR genes among quinolone-resistant E. coli and K. pneumoniae causing urinary tract infections among Nepalese outpatient children (< 18 years) and identify molecular characteristics of TMQR-harboring isolates., Methods: We performed antimicrobial susceptibility testing, phenotypic extended-spectrum β-lactamase (ESBL) and modified carbapenem inactivation method tests, and investigated the presence of six TMQR genes (qnrA, qnrB, qnrS, aac(6')-Ib-cr, oqxAB, qepA), three ESBL genes (bla CTX-M , bla TEM , bla SHV ), and five carbapenemase genes (bla NDM , bla OXA-48 , bla KPC , bla IMP , bla VIM ). The quinolone resistance-determining region (QRDR) of gyrA and parC were sequenced for 35 TMQR-positive isolates., Results: A total of 74/147 (50.3%) isolates were TMQR positive by multiplex PCR [aac(6')-Ib-cr in 48 (32.7%), qnrB in 23 (15.7%), qnrS in 18 (12.3%), qnrA in 1 (0.7%), and oqxAB in 1 (0.7%) isolate]. The median ciprofloxacin minimum inhibitory concentration of TMQR-positive isolates (64 µg/mL) was two-fold higher than those without TMQR (32 µg/mL) (p = 0.004). Ser-83→Leu and Asp-87→Asn in GyrA and Ser-80→Ile in ParC were the most common QRDR mutations (23 of 35). In addition, there was a statistically significant association between TMQR and two β-lactamase genes; bla CTX-M (p = 0.037) and bla TEM (p = 0.000)., Conclusion: This study suggests a high prevalence of TMQR among the quinolone-resistant E. coli and K. pneumoniae isolates causing urinary tract infection in children in this area of Nepal and an association with the carriage of ESBL gene. This is a challenge for the management of urinary infections in children. Comprehensive prospective surveillance of antimicrobial resistance in these common pathogens will be necessary to devise strategies to mitigate the emergence of further resistance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Preexposure prophylaxis (PrEP) is recommended for people at risk of acquiring HIV. We assessed billable costs associated with PrEP delivery at community health centers., Methods: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) study is an observational cohort of people receiving daily oral PrEP at participating federally qualified health centers and other community health centers. We assessed health care utilization and billable costs of providing PrEP at 2 health centers, 1 in Chicago, Illinois, and 1 in Washington, DC, from 2014 to 2018. The health centers followed the clinical practice guidelines for PrEP provision, including regular visits with health care providers and ongoing laboratory monitoring. Using clinic billing records and Current Procedural Terminology (CPT) coding, we retrospectively extracted data on the frequency and costs (in 2017 US dollars) of PrEP clinic visits and laboratory screening, for each patient, for 12 months since first PrEP prescription., Results: The average annual number of PrEP clinic visits and associated laboratory screens per patient was 5.1 visits and 25.2 screens in Chicago (n = 482 patients) and 5.4 visits and 24.8 screens in Washington, DC (n = 56 patients). The average annual PrEP billable cost per patient was $583 for clinic visits and $1070 for laboratory screens in Chicago and $923 for clinic visits and $1018 for laboratory screens in Washington, DC. The average annual total cost per patient was $1653 (95% CI, $1639-$1668) in Chicago and $1941 (95% CI, $1811-$2071) in Washington, DC., Conclusions: Our analysis, which provides PrEP billable cost estimates based on empirical data, may help inform health care providers who are considering implementing this HIV prevention strategy.

Potato (Solanum tuberosum) and tomato (Solanum lycopersicon) crops suffer severe losses to late blight caused by the oomycete pathogen Phytophthora infestans. Solanum americanum, a relative of potato and tomato, is globally distributed and most accessions are highly blight resistant. We generated high-quality reference genomes of four S. americanum accessions, resequenced 52 accessions, and defined a pan-NLRome of S. americanum immune receptor genes. We further screened for variation in recognition of 315P. infestans RXLR effectors in 52 S. americanum accessions. Using these genomic and phenotypic data, we cloned three NLR-encoding genes, Rpi-amr4, R02860 and R04373, that recognize cognate P. infestans RXLR effectors PITG&#95;22825 (AVRamr4), PITG&#95;02860 and PITG&#95;04373. These genomic resources and methodologies will support efforts to engineer potatoes with durable late blight resistance and can be applied to diseases of other crops., (© 2023. The Author(s).)

Background: Acute respiratory infections (ARIs) are one of the most common causes of mortality and morbidity worldwide. Every year millions of children suffer from viral respiratory tract infections (RTIs) ranging from mild to severe illnesses. Human Metapneumovirus (HMPV) is among the most frequent viruses responsible for RTIs. However, HMPV infections and their severity among children have not been explored yet in Nepal., Purpose: Therefore, the study was focused on HMPV infections and other potential viral etiologies or co-infections using multiplex PCR among children attending Kanti Children's Hospital and assessed the clinical characteristics of the infections as well as found the co-infections. A hospital-based cross-sectional study was designed and a convenience sampling method was used to enroll children of less than 15 years with flu-like symptoms from both outpatients and inpatients departments over three months of the study period., Results: HMPV infection (13.3%) was the most predominant infection among the different viral infections in children with ARIs in Kanti Children's Hospital. The HMPV was more prevalent in the age group less than three years (21.8%). Cough and fever were the most common clinical features present in all children infected with HMPV followed by rhinorrhea, sore throat, and wheezing. HMPV-positive children were diagnosed with pneumonia (42.9%), bronchiolitis (28.5%), upper respiratory tract infections (14.3%), and asthma (14.3%). The prevalence of HMPV was high in late winter (14.3%) followed by early spring (13.5%)., Conclusions: This study provides the baseline information on HMPV and associated co-infection with other respiratory viruses for the differential diagnosis based on molecular methods and also the comparison of clinical presentations among the different respiratory syndromes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Biochar is one of the few nature-based technologies with potential to help achieve net-zero emissions agriculture. Such an outcome would involve the mitigation of greenhouse gas (GHG) emission from agroecosystems and optimization of soil organic carbon sequestration. Interest in biochar application is heightened by its several co-benefits. Several reviews summarized past investigations on biochar, but these reviews mostly included laboratory, greenhouse, and mesocosm experiments. A synthesis of field studies is lacking, especially from a climate change mitigation standpoint. Our objectives are to (1) synthesize advances in field-based studies that have examined the GHG mitigation capacity of soil application of biochar and (2) identify limitations of the technology and research priorities. Field studies, published before 2022, were reviewed. Biochar has variable effects on GHG emissions, ranging from decrease, increase, to no change. Across studies, biochar reduced emissions of nitrous oxide (N 2 O) by 18% and methane (CH 4 ) by 3% but increased carbon dioxide (CO 2 ) by 1.9%. When biochar was combined with N-fertilizer, it reduced CO 2 , CH 4 , and N 2 O emissions in 61%, 64%, and 84% of the observations, and biochar plus other amendments reduced emissions in 78%, 92%, and 85% of the observations, respectively. Biochar has shown potential to reduce GHG emissions from soils, but long-term studies are needed to address discrepancies in emissions and identify best practices (rate, depth, and frequency) of biochar application to agricultural soils., (© 2023 The Authors. Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Introduction: Good nutrition knowledge and nutrient intake have been regarded as significant determinants in enhancing athletes' performance and overall health status. This study aimed to assess knowledge, attitude, and practices of nutrition and dietary intake among athletes., Methods: A cross-sectional study was conducted from January to April 2022 among national athletes from two sports clubs in Kathmandu Metropolitan City, Nepal. A semi-structured questionnaire was used to collect the data. Anthropometric measurements and dietary intake were recorded. Bivariate and multivariate binary logistic regression was used to estimate the crude odds ratios (cOR), and adjusted odds ratios (aOR) with 95% confidence intervals (CIs)., Results: A total of 270 players were included in this study (mean age, 25 years; 49.6% male, 50.4% female). Almost half of the athletes had good nutrition knowledge [54.1% (146/270)], attitude [56.7% (153/270)], and practices [50% (135/270)] scores. The mean energy, carbohydrate, protein, and fat intake were 35.0 kcal/kg/day, 5.6, 0.9, and 0.9 g/kg/day, respectively. Likewise, mean calcium and iron intake were 370, and 12.5 mg, respectively. In the multivariate model, families with monthly household income less than 50,000 Nepalese rupees ($400) (adjusted Odds Ratio/aOR = 2.58; 95% CI: 1.12 to 5.96), and those who did not receive diet plan (aOR = 3.14; 95% CI: 1.25 to 7.84) were more likely to have poor nutrition knowledge. Players who did not check food labelling (aOR = 1.44; 95% CI: 0.78 to 2.63) were more likely to have negative attitude towards nutrition. Players who did not ever attend nutrition class (aOR = 3.54; 95% CI: 1.46 to 8.54) and those who did not consume different food during off and on the season of sports (aOR = 2.36; 95% CI: 1.39 to 4.01) were more likely to have poor nutrition practice., Conclusions: Half of the athletes' nutritional knowledge, attitudes, and practices score were satisfactory. Nutrient intake among athletes was suboptimal. Nutrition intervention programs are critical to improve nutritional knowledge, attitude and practice related to dietary intake among national athletes in Nepal., (© 2023. The Author(s).)

Context: Digital video-based behavioral interventions are effective tools for improving HIV care and treatment outcomes., Objective: To assess the costs of the Positive Health Check (PHC) intervention delivered in HIV primary care settings., Design, Setting, and Intervention: The PHC study was a randomized trial evaluating the effectiveness of a highly tailored, interactive video-counseling intervention delivered in 4 HIV care clinics in the United States in improving viral suppression and retention in care. Eligible patients were randomized to either the PHC intervention or the control arm. Control arm participants received standard of care (SOC), and intervention arm participants received SOC plus PHC. The intervention was delivered on computer tablets in the clinic waiting rooms. The PHC intervention improved viral suppression among male participants. A microcosting approach was used to assess the program costs, including labor hours, materials and supplies, equipment, and office overhead., Participants: Persons with HIV infection, receiving care in participating clinics., Main Outcome Measures: The primary outcome was the number of patients virally suppressed, defined as having fewer than 200 copies/mL by the end of their 12-month follow-up., Results: A total of 397 (range across sites [range], 95-102) participants were enrolled in the PHC intervention arm, of whom 368 participants (range, 82-98) had viral load data at baseline and were included in the viral load analyses. Of those, 210 (range, 41-63) patients were virally suppressed at the end of their 12-month follow-up visit. The overall annual program cost was $402 274 (range, $65 581-$124 629). We estimated the average program cost per patient at $1013 (range, $649-$1259) and the cost per patient virally suppressed at $1916 (range, $1041-$3040). Recruitment and outreach costs accounted for 30% of PHC program costs., Conclusions: The costs of this interactive video-counseling intervention are comparable with other retention in care or reengagement interventions., Competing Interests: V.C.M. has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. All other authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: KL is a founder of Floodlight Genomics, TI receives funding from Krishi Gobeshona Foundation of Bangladesh, and SK receives funding from industry and has filed patents on plant disease resistance., (Copyright: © 2023 Latorre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

F 1 F o ATP synthase is a ubiquitous molecular motor that utilizes a rotary mechanism to synthesize adenosine triphosphate (ATP), the fundamental energy currency of life. The membrane-embedded F o motor converts the electrochemical gradient of protons into rotation, which is then used to drive the conformational changes in the soluble F 1 motor that catalyze ATP synthesis. In E. coli, the F o motor is composed of a c 10 ring (rotor) alongside subunit a (stator), which together provide two aqueous half channels that facilitate proton translocation. Previous work has suggested that Arg50 and Thr51 on the cytoplasmic side of each subunit c are involved in the proton translocation process, and positive charge is conserved in this region of subunit c. To further investigate the role of these residues and the chemical requirements for activity at these positions, we generated 13 substitution mutants and assayed their in vitro ATP synthesis, H + pumping, and passive H + permeability activities, as well as the ability of mutants to carry out oxidative phosphorylation in vivo. While polar and hydrophobic mutations were generally tolerated in either position, introduction of negative charge or removal of polarity caused a substantial defect. We discuss the possible effects of altered electrostatics on the interaction between the rotor and stator, water structure in the aqueous channel, and interaction of the rotor with cardiolipin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States., Methods: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective., Results: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL)., Conclusions: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Men who have sex with men (MSM) often change sexual behaviors following HIV diagnosis. This systematic review examined such changes, including sero-adaptive behaviors (i.e., deliberate safer-sex practices to reduce transmission risk) to better understand the magnitude of their association with HIV diagnosis. We searched four databases (1996-2017) and reviewed references from other systematic reviews. We included studies conducted in the United States that compared sexual behavior among HIV-infected "aware" versus "unaware" MSM. We meta-analytically pooled RRs and associated 95% confidence intervals (CI) using random-effects models, and assessed risk of bias and evidence quality. Twenty studies reported k = 131 effect sizes on sexual practices outcomes, most of which reported changes in unprotected sex (k = 85), and on sex with at-risk partners (k = 76); 11 reported sero-adaptive behaviors. Unprotected anal intercourse with an HIV-uninfected/unknown-status partner was less likely among aware MSM (insertive position: k = 2, RR 0.26, 95% CI 0.17, 0.41; receptive position: k = 2, RR 0.53, 95% CI 0.37, 0.77). Risk of not always serosorting among aware MSM (k = 3) was RR = 0.92 (0.83, 1.02). Existing evidence, although low-quality, suggests that HIV-infected MSM tend to adopt safer sexual practices once aware of their diagnosis. Variation in reporting of outcomes limits their comparability. Sero-adaptive behavior data are sparse., (© 2022. The Author(s).)

Background: Nepal has progressed gradually in reducing under-5 mortality and neonatal mortality; however, they are still high at 30.8 and 19.8 per 1000 live births, respectively. Neonatal mortality constituted about 64% of the under-5 mortality in 2019, higher than the global average of 47%., Methods: This is a prospective study among pregnant women and their newborn babies in Siddhi Memorial Hospital, Bhaktapur, Nepal, from October 2017 to April 2018. Demographic and clinical data, high vaginal swabs of pregnant mothers, and umbilical cord blood were collected. High vaginal swabs were cultured, and umbilical cord blood samples were cultured and tested for inflammatory markers. After discharge to home, neonates were followed for 28 days of life by weekly phone calls., Results: Total number of pregnant mothers enrolled was 151. The median age was 26 years (IQR: 18-40), and the proportion of adolescent mothers was 4.7%. Half of the deliveries were done by the caesarian section, and 8.6% had gestational age <37 weeks. High vaginal swab cultures were positive in 8.2% of the samples (n=135), and Escherichia coli was the most common bacteria. Out of 153 newborn babies (2 were twins), 8 (5.2%) were admitted to the neonatal intensive care unit. The proportion of low birth weight was 13%, and it was independently associated with neonatal intensive care unit admission (adjusted OR=9.4, 95%CI 1.8-50.1; P value= 0.009)., Conclusions: Adolescent pregnancies and Low Birth Weight babies were commonly observed. Both of these issues need to be addressed by effective measures that would improve the current situation of maternal and child health in Nepal.

Main Conclusion: Consequences of air pollutants on physiology, biology, yield and quality in the crops are evident. Crop and soil management can play significant roles in attenuating the impacts of air pollutants. With rapid urbanization and industrialization, air pollution has emerged as a serious threat to quality crop production. Assessing the effect of the elevated level of pollutants on the performance of the crops is crucial. Compared to the soil and water pollutants, the air pollutants spread more rapidly to the extensive area. This paper has reviewed and highlighted the major findings of the previous research works on the morphological, physiological and biochemical changes in some important crops and fruits exposed to the increasing levels of air pollutants. The crop, soil and environmental factors governing the effect of air pollutants have been discussed. The majority of the observations suggest that the air pollutants alter the physiology and biochemical in the plants, i.e., while some pollutants are beneficial to the growth and yields and modify physiological and morphological processes, most of them appeared to be detrimental to the crop yields and their quality. A better understanding of the mechanisms of the uptake of air pollutants and crop responses is quite important for devising the measures ‒ at both policy and program levels ‒ to minimize their possible negative impacts on crops. Further research directions in this field have also been presented., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death, with 80% of the total death occurring in low- to middle-income countries (LMICs). Nepal is one of the LMIC; COPD is a highly prevalent and significant public health issue often underdiagnosed. Medical physicians' good knowledge and practice to diagnose and treat COPD can help reduce the disease burden., Objectives: To determine the level of knowledge, practice and factors influencing the practice of physicians regarding COPD management based on GOLD guidelines., Design: A cross-sectional descriptive study using a structured questionnaire was conducted among medical physicians working in Bagmati and Gandaki province of Nepal. Out of total scores, physicians knowledge and practice were graded according to Bloom's original cut-off point for good (≥80%), satisfactory (60%-78%) and poor (<60%)., Result: A total of 152 medical physicians participated in this study. Out of the possible total score 20, the mean score on knowledge was 17.8 ± 2.4, and out of possible total score eight, the mean score on practice was 5.3 ± 1.3. The correlation test between total knowledge and practice scores showed r = 0.18 and p value <0.02. The most selected factors hindering the appropriate management of COPD was lack of patient follow up and lack of professional training in COPD. Other factors included patient unwillingness to discuss smoking quit plan, lack of screening tool, unavailability of spirometry and physician unawareness of available medicine to treat COPD., Conclusion: Despite physicians having good knowledge in COPD, the practice in COPD management is below guideline-recommended. There is a significant, very low positive correlation between total knowledge score and practice score. Proper COPD training to physicians, disease awareness among patients, easy availability of diagnostic equipment and medication can help improve physicians' practice and appropriately manage COPD patients., (© 2022 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Group B streptococcus (GBS) or Streptococcus agalactiae is an opportunistic pathogen that causes serious illness in newborns, pregnant women, and adults. However, insufficient detection methods and disease prevention programs have contributed to an increase in the incidence and fatality rates associated with this pathogen in non-neonatal patients. This study aimed to investigate factors of the observed increased incidence by investigation of serotype distribution, virulence factors, and antimicrobial susceptibility patterns from invasive GBS disease among non-neonatal patients in Thailand. During 2017-2018, a total of 109 S. agalactiae isolates were collected from non-pregnant patients. There were 62 males and 47 females, with an average age of 63.5 years (range: 20 - 96). Serotypes were determined by latex agglutination assay and multiplex polymerase chain reaction (PCR)-based assay. Among those isolates, seven virulence genes ( rib , bca , pavA , lmb , scpB , cylE , and cfb ) were detected by PCR amplification, and were determined for their susceptibility to 20 antimicrobial agents using a Sensititre TM Streptococcus species STP6F AST plate. Among the study isolates, serotype III was predominant (52.3%), followed by serotype V and serotype VI (13.8% for each), serotype Ib (11.9%), and other serotypes (8.2%). Of the seven virulence genes, pavA was found in 67.0%. Except for one, there were no significant differences in virulence genes between serotype III and non-serotype III. Study isolates showed an overall rate of non-susceptibility to penicillin, the first-line antibiotic, of only 0.9%, whereas the resistance rates measured in tetracycline, clindamycin, azithromycin, and erythromycin were 41.3, 22.0, 22.0, and 22.0%, respectively. Strains that were resistant to all four of those drugs were significantly associated with non-serotype III ( p < 0.001). Using multi-locus sequence typing (MLST), 40.0% of the four-drug-resistant isolates belonged to serotype VI/ST1, followed by serotype Ib/ST1 (35.0%). Cluster analysis with global GBS isolates suggested that the multiple drug-resistant isolates to be strongly associated with the clonal complex (CC) 1 ( p < 0.001). Compared to the 2014 study of 210 invasive GBS isolates conducted in 12 tertiary hospitals in Thailand, the proportion of serotype III has dramatically dropped from nearly 90% to about 50%. This suggests that resistances to the second-line antibiotics for GBS might be the selective pressure causing the high prevalence of non-serotype III isolates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tulyaprawat, Pharkjaksu, Shrestha and Ngamskulrungroj.)

Alterations to the androgen receptor (AR) signalling axis and cellular metabolism are hallmarks of prostate cancer. This study provides insight into both hallmarks by uncovering a novel link between AR and the pentose phosphate pathway (PPP). Specifically, we identify 6-phosphogluoconate dehydrogenase ( 6PGD ) as an androgen-regulated gene that is upregulated in prostate cancer. AR increased the expression of 6PGD indirectly via activation of sterol regulatory element binding protein 1 (SREBP1). Accordingly, loss of 6PGD, AR or SREBP1 resulted in suppression of PPP activity as revealed by 1,2- 13 C 2 glucose metabolic flux analysis. Knockdown of 6PGD also impaired growth and elicited death of prostate cancer cells, at least in part due to increased oxidative stress. We investigated the therapeutic potential of targeting 6PGD using two specific inhibitors, physcion and S3, and observed substantial anti-cancer activity in multiple models of prostate cancer, including aggressive, therapy-resistant models of castration-resistant disease as well as prospectively collected patient-derived tumour explants. Targeting of 6PGD was associated with two important tumour-suppressive mechanisms: first, increased activity of the AMP-activated protein kinase (AMPK), which repressed anabolic growth-promoting pathways regulated by acetyl-CoA carboxylase 1 (ACC1) and mammalian target of rapamycin complex 1 (mTORC1); and second, enhanced AR ubiquitylation, associated with a reduction in AR protein levels and activity. Supporting the biological relevance of positive feedback between AR and 6PGD, pharmacological co-targeting of both factors was more effective in suppressing the growth of prostate cancer cells than single-agent therapies. Collectively, this work provides new insight into the dysregulated metabolism of prostate cancer and provides impetus for further investigation of co-targeting AR and the PPP as a novel therapeutic strategy., Competing Interests: JG, JH, NR, MM, LQ, RS, AH, JX, AH, JH, MC, IM, DL, LS, LB None, SI none, (© 2021, Gillis et al.)

Nonpoint source pollution (NPS) has become the leading factor of global water quality problems, attracting great attention from governments and researchers in various countries. Based on this situation, understanding the current research status of NPS can help guide future research. However, most of the current reviews only describe the research status of some specific aspects but fail to quantify the research hotspots and development trends on the whole, which limits the overall understanding of NPS. In this paper, bibliometrics was used to study the current status, hotspots, and frontiers of NPS research during 1991-2015, and the future research development was predicted. Over the past 15 years, there has been a remarkable growth trend in publication output, and the participation of countries/territories has also increased. Journal of Environmental Quality , Journal of Hydrology , and Total Environmental Science were the top three journals. Sharpley AN and Arnold JG from the USA were the most productive authors with the best quality articles. The major author clusters and research regions are located in North America and Europe, followed by East Asia. The United States dominates this research field, with the largest number of independent and collaborative articles. Chinese authors gained more attention through international cooperation. Keyword analysis confirmed that water quality and nutrients were the main concerns of NPS pollution research, which mainly involved a number of research topics, such as pollutant emission reduction research and the evaluation and simulation of pollutants' migration and their transformation under different situations, while pesticides were less of a concern, which suggests that the abuse of pesticides has come under control. Meanwhile, SWAT was the dominating model in the last decade partly because it satisfied the growing needs of watershed-scale management.

Flavonoids have achieved widespread importance in pharmaceutical, food, and cosmetics industries. Furthermore, modification of these naturally occurring flavonoids to structurally diverse compounds through whole cell biotransformation with enhanced biological activities has numerous biotechnological applications. The present study investigated the biotransformation potential of Streptomyces species isolated from a high-altitude-soil sample towards selected flavonoid molecules. The biotransformed metabolites were confirmed by comparing the HPLC chromatogram with authentic compounds and LC-MS/MS analysis. Of these isolates, Streptomyces species G-18 (Accession number: MW663767.1) catalyzed isoflavone molecules daidzein and genistein to produce hydroxylated products at 24 h of reaction condition in a whole cell system. The hydroxylation of daidzein (4',7-dihydroxyisoflavone) was confirmed at 3'-position of the B ring to produce 3',4',7-trihydroxyisoflavone. In addition, Streptomyces species G-14 (Accession number: MW663770.1) and Streptomyces species S4L (Accession number: MW663769.1) also revealed the transformation of daidzein (4',7-dihydroxyisoflavone) to hydroxy daidzein at a distinct position than that of G-18 isolates, whereas thee Streptomyces species S4L reaction mixture with naringenin as a substrate also revealed the hydroxylated product. Our results demonstrated that microorganisms isolated from different ecological niches have broad application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Lasata Shrestha et al.)

HIV-infected individuals "aware" of their infection are more likely to use condoms, compared to HIV-infected "unaware" persons. To quantify this likelihood, we undertook a systematic review and meta-analysis of U.S. and Canadian studies. Twenty-one eligible studies included men who have sex with men (MSM; k = 15), persons who inject drugs (PWID; k = 2), and mixed populations of high-risk heterosexuals (HRH; k = 4). Risk ratios (RR) of "not always using condoms" with partners of any serostatus were lower among aware MSM (RR 0.44 [not significant]), PWID (RR 0.70) and HRH (RR 0.27); and, in aware MSM, with partners of HIV-uninfected or unknown status (RR 0.46). Aware individuals had lower "condomless sex likelihood" with HIV-uninfected or unknown status partners (MSM: RR 0.58; male PWID: RR 0.44; female PWID: RR 0.65; HRH: RR 0.35) and with partners of any serostatus (MSM only, RR 0.72). The association diminished over time. High risk of bias compromised evidence quality.

Background: Lifetime cost estimates are a useful tool in measuring the economic burden of HIV in the United States. Previous estimation methods need to be updated, given improving antiretroviral therapy regimens and updated costs., Methods: We used an updated version of the agent-based model progression and transmission of HIV (PATH) 3.0 to reflect current regimens and costs. We simulated a cohort of those infected in 2015 until the last person had died to track the lifetime costs for treatment of HIV, including HIV health care utilization costs (inpatient, outpatient, opportunistic infection prophylaxis, non-HIV medication, and emergency department), opportunistic infection treatment costs, and testing costs. We assumed a median per-person diagnosis delay of 3 years and a 3% base monthly probability of dropout from care for a base-case scenario. Additionally, we modeled a most favorable scenario (median diagnosis delay of 1 year and 1% base dropout rate) and a least favorable scenario (median diagnosis delay of 5 years and 5% base dropout rate)., Results: We estimated an average lifetime HIV-related medical cost for a person with HIV of $420,285 (2019 US$) discounted (3%) and $1,079,999 undiscounted for a median 3-year diagnosis delay and 3% base dropout rate. Our discounted cost estimate was $490,045 in our most favorable scenario and $326,411 in our least favorable scenario., Conclusions: Lifetime per-person HIV-related medical costs depend on the time from infection to diagnosis and the likelihood of dropping out of care. Our results, which are similar to previous studies, reflect updated antiretroviral therapy regimens and costs for HIV treatment., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Supernumerary mini-chromosomes-a unique type of genomic structural variation-have been implicated in the emergence of virulence traits in plant pathogenic fungi. However, the mechanisms that facilitate the emergence and maintenance of mini-chromosomes across fungi remain poorly understood. In the blast fungus Magnaporthe oryzae (Syn. Pyricularia oryzae), mini-chromosomes have been first described in the early 1990s but, until very recently, have been overlooked in genomic studies. Here we investigated structural variation in four isolates of the blast fungus M. oryzae from different grass hosts and analyzed the sequences of mini-chromosomes in the rice, foxtail millet and goosegrass isolates. The mini-chromosomes of these isolates turned out to be highly diverse with distinct sequence composition. They are enriched in repetitive elements and have lower gene density than core-chromosomes. We identified several virulence-related genes in the mini-chromosome of the rice isolate, including the virulence-related polyketide synthase Ace1 and two variants of the effector gene AVR-Pik. Macrosynteny analyses around these loci revealed structural rearrangements, including inter-chromosomal translocations between core- and mini-chromosomes. Our findings provide evidence that mini-chromosomes emerge from structural rearrangements and segmental duplication of core-chromosomes and might contribute to adaptive evolution of the blast fungus., Competing Interests: The authors have declared that no competing interests exist.

Objectives. To optimize combined public and private spending on HIV prevention to achieve maximum reductions in incidence. Methods. We used a national HIV model to estimate new infections from 2018 to 2027 in the United States. We estimated current spending on HIV screening, interventions that move persons with diagnosed HIV along the HIV care continuum, pre-exposure prophylaxis, and syringe services programs. We compared the current funding allocation with 2 optimal scenarios: (1) a limited-reach scenario with expanded efforts to serve eligible persons and (2) an ideal, unlimited-reach scenario in which all eligible persons could be served. Results. A continuation of the current allocation projects 331 000 new HIV cases over the next 10 years. The limited-reach scenario reduces that number by 69%, and the unlimited reach scenario by 94%. The most efficient funding allocations resulted in prompt diagnosis and sustained viral suppression through improved screening of high-risk persons and treatment adherence support for those infected. Conclusions. Optimal allocations of public and private funds for HIV prevention can achieve substantial reductions in new infections. Achieving reductions of more than 90% under current funding will require that virtually all infected receive sustained treatment.

Background: A lower respiratory tract infection caused by novel coronavirus termed as Corona Virus Disease (COVID-19) was first identified in China and subsequently took the form of pandemic. Studies on disease outbreak in the past and recent COVID-19 outbreak have demonstrated increased psychological distress and adverse impacts on mental health and psychological wellbeing of people. However, the impact of COVID-19 on psychological wellbeing of people in Nepal hasn't been studied adequately. So, this paper aims to report the findings from a social media survey on psychological impacts of COVID-19 in Nepal., Methods: Data were collected through social media from 2082 Nepalese respondents between 23rd April, 2020 and 3rd May, 2020. A total of 2014 respondents who were currently residing in Nepal were included in the analysis., Results: The study suggested that half of the respondents suffered from at least one symptom of psychological distress whereas 32% suffered from two or more symptoms of psychological distress such as restlessness, fearfulness, anxiety and worry and sadness in the past 2 weeks preceding the survey date. The findings further suggested that respondents having lower family income, residing in rented room, and participants from province 2 were more likely to suffer from both single and multiple symptoms of psychological distress., Conclusion: The study has shown high prevalence of psychological distress amongst the Nepalese respondents following COVID-19 outbreak. Appropriate mental health and psychosocial support response needs to be instituted to adequately respond to psychological impacts of the epidemic.

Background: Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown., Objective: To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database., Design: Retrospective cohort study., Setting: Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions., Measurements: Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments., Results: Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance., Limitation: The IQVIA database does not capture every prescription nationwide., Conclusion: Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion., Primary Funding Source: Centers for Disease Control and Prevention.