Suppression Rate Research Articles

Impact of botanical extracts on mungbean pest management and seed storability in the northern highlands of Tanzania

This study assessed the efficacy of plant extracts as alternatives to synthetic pesticides for pest control and seed quality preservation in mungbean cultivation in northern Tanzania, specifically at TARI Selian and Miwaleni. The study employed a randomized complete block design. Four plants’ extracts—Tephrosia vogelii, Clutia abbsynica, Clausena anisata, and Lobelia gibelloa—were evaluated during the 2020 growing season (field) and 2021 storage period (storability). The study focused on their effects on insect pests (leaf beetles, thrips, aphids, whiteflies, and pod borers) and their ability to maintain seed quality during storage. C. anisata emerged as the most effective extract across all pests, demonstrating high suppression rates for thrips (3.4), aphids (3.22), whiteflies (3.4), and pod borers (2.7). In contrast, L. gibelloa was the least effective, with lower suppression rates for thrips (3.1) and aphids (3.1). Furthermore, botanical treatments significantly reduced pest damage in stored seeds, with T. vogelii and C. abbsynica showing superior performance in preserving seed weight and quality during storage. Seeds treated with T. vogelii had significantly fewer holes and lower weight loss compared to other treatments, indicating its effectiveness in both pest management and seed preservation. Conversely, L. gibelloa and C. anisata contributed to greater weight loss, particularly at higher application rates. The study demonstrates that plant extracts can offer a sustainable, eco-friendly alternative to synthetic pesticides, effectively controlling pests and preserving seed quality. These findings are crucial for improving mungbean production and storage, enhancing food security, and reducing reliance on chemical pesticides in diverse agro-ecological contexts. Future research should further explore the long-term ecological impacts and optimal application rates of these botanicals for integrated pest management and seed storage.

Risk Factors for Viral Non-suppression Among Youth Living with HIV in Nigeria: Findings from the iCARE Nigeria Study.

Viral suppression with antiretroviral therapy (ART) is a critical component of UNAIDS objectives to end the HIV epidemic. Youth living with HIV (YLH) have worse viral suppression rates than adults. The aim of this study was to identify risk factors for viral non-suppression among YLH in Nigeria. A secondary analysis of enrollment data from the iCARE Nigeria study, collected April-October 2021 for 541 YLH comprised demographic, psychosocial, behavioral, clinical variables, and viral load quantification. Viral non-suppression was defined as viral load ≥ 200 copies/mL. Generalized linear models using Akaike information criterion for selection of indicator variables in a stepwise approach were used to determine the risk factors for viral non-suppression. The final analytic sample was 491 and the proportion of non-suppressed participants at baseline was 40%. In the final model, substance use (other than alcohol, tobacco and/or cannabis) (aOR = 3.20 [95% CI: 1.05, 10.34]), missed medication doses (aOR = 1.09 [95% CI: 1.04, 1.15]), and a higher number of self-reported medication barriers (e.g., forgot, busy, change in routine) (aOR = 1.08 [95% CI: 1.00, 1.16]) were associated with a higher likelihood of viral non-suppression. Being prescribed a first-line regimen (aOR = 0.28 [95% CI: 0.17, 0.44]), disclosure to at least one brother (aOR = 0.64 [95% CI: 0.42, 0.97]), and higher treatment outcome expectancies (e.g., taking medication will improve health) (aOR = 0.81 [95% CI: 0.66, 0.98]), were all associated with a lower likelihood of viral non-suppression. Viral non-suppression among YLH in Nigeria is associated with psychosocial and behavioral factors, including missed doses, medication barriers, treatment outcome expectancies, and disclosure, that are potential targets for intervention to achieve ART goals.

Role of Dolutegravir/Lamivudine in the Management of Pregnant People Living with HIV-1: A Narrative Review.

Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a guiding principle during pregnancy. Dolutegravir/lamivudine (DTG/3TC) has demonstrated high efficacy, a high barrier to resistance, and a good safety profile in non-pregnant individuals; however, DTG/3TC is not recommended by perinatal HIV treatment guidelines for initial therapy in pregnant people living with HIV-1 because of limited data on use of the 2-drug regimen during pregnancy. Efficacy and pharmacokinetic data from pregnant individuals using DTG and/or 3TC are reviewed and used to extrapolate anticipated DTG/3TC efficacy in pregnancy. There are robust data on the use of DTG- and 3TC-containing combination regimens, which are recommended by perinatal HIV treatment guidelines during pregnancy, supporting their well-established efficacy and safety in pregnant people living with HIV-1. Updated data from the Tsepamo and Eswatini surveillance studies (>14,000 DTG exposures from conception) indicate no increased risk of neural tube defects with DTG. Pharmacokinetic data for DTG and 3TC indicate that exposures in pregnancy are within the therapeutically effective range seen in non-pregnant adults. Two studies evaluated DTG/3TC during pregnancy and both reported high virologic suppression rates [HIV-1 ribonucleic acid (RNA)<50 copies/mL at delivery: 97% (30/31) overall], no events of vertical transmission, and no new safety signals, consistent with the use of DTG-based 3-drug regimens in pregnancy. The use of DTG/3TC during pregnancy is anticipated to be comparably effective and well tolerated for both parental health and prevention of vertical transmission with fetal exposure to fewer antiretrovirals compared with 3- or 4-drug regimens. These considerations are relevant when evaluating use of DTG/3TC in people living with HIV-1 who are pregnant or considering pregnancy in clinical practice and in perinatal HIV treatment guidelines.Video abstract available for this article. Supplementary file1 (MP4 319,147 KB).

Viral load suppression and retention in care among children and adolescents receiving multi-month anti-retroviral therapy refills: a program data review in Uganda

BackgroundIn July 2022, Uganda’s Ministry of Health extended the 2021 WHO guidelines that recommended 3–6 monthly dispensing of antiretroviral therapy (ART) to include all children and adolescents living with HIV (CALHIV). Treatment outcomes following this recommendation have not yet been documented. We compared viral load (VL) suppression and retention in HIV care rates among CALHIV receiving 1, 2–5, and > = 6 monthly ART dispensation in Uganda.MethodsA cross-sectional study of electronic medical records in 118 health facilities was conducted. Data for CALHIV 10–19 years captured at their most recent five clinic visits as of 15th May 2023 were analysed. Most recent two VL < 1000 copies/ml were used as measures for VL suppression and sustained VL suppression. A client was considered retained in care if they visited the clinic within 28 days from their expected return visit date. We used margins plots and a modified poisson model adjusting for facility level clustering to assess VL suppression and retention across multi-month ART categories.ResultsA total of 2864 CALHIV, 1609 (56.2%) being females and with a median age of 12 years (inter quartile range, iqr = 7) were included. Overall suppression and retention rates were 80.4% (2133/2654) and 87.8% (2514/2864) respectively. A significant number had been dispensed ART for ≥ 2 months (50%, 2–5 months and 43.5%, ≥ 6 months). Probability of having a suppressed VL was higher among CALHIV that had received ≥ 6 months and 2–5 months of ART compared to those of 1 month i.e., 83% vs 79% vs 41% respectively. Probability of being retained in care didn’t differ across multi-month ART categories. CALHIV who received ART for 2–5 months and ≥ 6 months compared to 1 month were more likely to have a suppressed VL; (adj.PR = 1.98; 95%CI:1.41, 2.80) and (adj.PR = 2.21; 95% CI:1.59, 3.05) respectively. CALHIV with a Tuberculosis diagnosis history were less likely to have a suppressed VL (adj.PR = 0.73; 95%CI:0.65,0.81), however this was not statistically significantly different between multi-month categories.ConclusionCALHIV receiving multi-month ART including 6 months dispensation had better VL suppression rates. Retention rates however didn’t differ by multi-month dispensing categories as observed among adults in the interval trial. We recommend multi-month ART dispensation including more than 6 months among CALHIV irrespective of their age, clinical stage, and history of prior co-morbidities.

Lactate/Cysteine Dual-Consuming Probiotic-Nanomedicine Biohybrid System for Enhanced Cancer Chemo-Immunotherapy.

Immunotherapy is revolutionizing oncology, but its therapeutic efficiency is still limited by the off-target toxicities and poor antitumor immune responses. By integrating the drug-loaded nanoparticles (DMnSH) with the unique metabolic traits of Veillonella parvula (Vei), a probiotic-nanomedicine conjugate Vei@DMnSH biohybrid is elaborately designed for enhanced cancer chemo-immunotherapy. Specifically, Vei@DMnSH can accumulate in hypoxic tumor sites and simultaneously consume lactate and cysteine to reverse the lactate-associated immunosuppression and impede the biosynthesis of GSH. In addition, the DMnSH nanoparticles will rapidly deplete intracellular GSH and disassemble to release DOX and Mn2+. Accompanied by the two-pronged GSH depletion, the Mn2+-mediated Fenton-like reaction can effectively generate oxidative hydroxyl radicals to induce heavy redox imbalance. Combined with the therapeutic effect of DOX, robust immunogenic cell death is provoked and subsequently activates antitumor adaptive immunity with a tumor suppression rate over 82%, synergistically enhancing the therapeutic outcomes of cancer chemo-immunotherapy.

Preparation and characterization of a low viscosity spray dust suppressant based on xanthan gum grafted sodium α-olefin sulfonate copolymer with proactive coal-adhesive and surface-active properties

To address the problem of the high viscosity of current composite dust suppressants, which results in spray droplet sizes that are not optimal for capturing respirable dust, a low viscosity, proactive coal-adhesive, long-lasting spray dust suppressant, XG-AOS/Tre, has been developed. The suppressant utilizes xanthan gum (XG) from microbial fermentation, with α-olefin sulfonate grafted onto its hydroxyl groups to form a copolymer (XG-AOS), reducing its viscosity while maintaining the surface activity of the hydrocarbon chain and its affinity for coal dust. It has a weighted average molecular weight of 398341, a surface tension of 26.1 mN/m, a viscosity of 1.59 mPa·s, and a contact angle of 48° with coal cake. The suppressant achieves a total dust suppression rate of 85.7 % and a respirable dust suppression rate of 85.9 %. Because of its surface activity and high molecular weight, it efficiently wets and settles coal dust. It retains 47.3 % of the water in its solution 24 h after being sprayed and forms an adhesive film upon complete evaporation, providing the coal dust with resistance to wind erosion. The dust suppressant improves the dust suppression rate for dust control in coal mining. Its properties contribute to the sustainable development and environmental protection of the coal industry.

HIV Support Group Care Utilization and its Effect on Treatment Outcome Among HIV Patients on Antiretroviral Therapy: Evidence from Ethiopia Population-Based HIV Impact Assessment.

In the realm of HIV care, support groups play a pivotal role by bringing together individuals living with HIV to share experiences and receive guidance from healthcare professionals. These groups are renowned for their substantial benefits, including improving emotional well-being, enhancing treatment adherence, and fostering a strong sense of community. However, despite these advantages, there is a notable gap in Ethiopia regarding concrete evidence of their impact on key treatment outcomes. This study aims to bridge this gap by exploring how support group care influences viral suppression rates among HIV patients. The study was conducted among 259 HIV-positive individuals on ART using the EPHIA survey, employing a two-stage, stratified sampling design across urban areas in nine regions and two city administrations. Data analysis was performed using STATA version 17, and multicollinearity was assessed (VIF = 1.07). A multivariate logistic regression model was fitted, with a p-value of ≤ 0.05 considered statistically significant. Results showed that 25.12% of participants utilized HIV support groups. Those who participated in support groups were 3.14 times more likely to achieve viral load suppression compared to non-participants (AOR = 3.14, 95% CI: 1.35-6.30). This study highlights that HIV support groups significantly boost viral suppression rates, underscoring the importance of integrating these groups into standard treatment protocols. These findings underline the need for continued research to assess long-term outcomes and further optimize the effectiveness of support group care in enhancing HIV treatment outcomes.

Magnetostrictive Vibration Suppression via Integration of Current Amplification Negative Capacitor and Current Inversion Semi-Active Control Circuit

When attempting to suppress structural vibrations employing a magnetostrictive transducer, owing to the control force is generated from current, a larger amplification of the current entails superior control performance. The semi-active control theory uses the synchronized switching damping (SSD) technique for structural vibration suppression while requiring a minimal energy supply. However, the absence of external energy input limits the current amplification performance. To address this limitation, this study proposes a novel method that combines semi-active vibration suppression method with negative capacitance to improve the current amplification performance. The proposed circuit switches the circuit status between shunt, inductor-capacitor (LC) electrical oscillation, and negative capacitance circuits. A mathematical model was employed to analyze the current operation, suppression performance, and robustness of the proposed circuit. Further, machine learning and kernel regression model were employed to predict the optimal control force gain. Validation experiments conducted on a 10-bay truss structure identical to the simulation model show that the experimental results align with the simulation predictions. The vibration suppression rates of the proposed method under single-mode and multiple-mode vibrations reached 85.8% and 78.3%, respectively, which are 2.64 and 1.89 times higher than those achieved by conventional methods.

Antagonistic effect of symbiotic bacteria from entomopathogenic nematodes and Bacillus spp. against Panax ginseng root rot pathogens

Ginseng root rot is a destructive disease of Panax ginseng that seriously affects the yield and quality of P. ginseng. Based on the broad-spectrum suppression properties of entomopathogenic nematode (EPN) symbiotic bacteria, four symbiotic bacteria were selected: Xenorhabdus bovienii (Xbf), Xenorhabdus nematophila (Xna), Xenorhabdus nematophila Cxrd (Xnc) and Xenorhabdus budapestensis (Xbc). Meanwhile, six beneficial Bacillus strains (Bacillus velezensis S1A; Bacillus amyloliquefaciens H4C; Bacillus subtilis N5D; and Bacillus albus HYS, K8, and N2A) were tested. Their individual and combined effects (both in vitro and in P. ginseng slices) on fungi pathogenic to P. ginseng, Fusarium solani, Fusarium proliferatum and Fusarium oxysporum were evaluated. Xenorhabdus budapestensis had the highest suppression effects (up to 82%) on F. solani and F. oxysporum, and a 60% inhibition rate on F. proliferatum, significantly higher than Xnc, Xbf and Xna. Bacillus velezensis and B. subtilis had the strongest suppression rates on F. solani (40%). The combined effects of Xbc and B. subtilis K8 on F. solani and F. oxysporum were stronger than their individual effects. The P. ginseng slice experiment further confirmed the enhanced inhibition of Fusarium by mixing Xbc with B. subtilis K8. In conclusion, we used EPN symbiotic bacteria to suppress P. ginseng root rot and screened two EPN symbiotic bacteria that were highly effective against Fusarium spp. The combination of Bacillus strains with EPN symbiotic bacteria enhanced the suppression effect. Our results provide new biological materials and directions for biological control of P. ginseng root rot.

Provider assisted partner notification utilization and associated factors among adolescents living with HIV in Uganda, a cross-sectional study

BackgroundAssisted Partner Notification (APN) is a high yield HIV testing strategy that is recommended by the World Health Organization (WHO) for adults and adolescents aged at least 15 years in sub-Saharan Africa for HIV care and prevention. Although studies among adults have been done, there remains a paucity of data of APN service utilization among adolescents in Uganda, yet Adolescents Girls and Young Women (AGYW) have the highest incidence of HIV in Uganda, and generally, adolescents have the lowest HIV viral suppression rates. Failure to disclose to sexual partners poses a risk of propagating infection. This study aimed to explore utilization of provider APN and associated factors among sexually active adolescents living with HIV (ALWH) aged 15–19 years in routine HIV care.MethodsWe conducted a cross-sectional study at Baylor College of Medicine Children’s Foundation Uganda’s Center of Excellence Clinic located at Mulago Hospital in Kampala, Uganda. We consecutively enrolled sexually active ALWH aged 15 to 19 years in routine HIV care. We collected data on the individual ALWH, partner characteristics, and APN service utilization, using a structured questionnaire. Medical history for the ALWH was abstracted from the electronic database at the facility. Chi square tests and modified poisson regression were used for analysis of associated factors.ResultsFrom February to March 2023, 372 ALWH were enrolled. The median (IQR) age was 17 years [16–19], 52.4% were females, and 82% had completed secondary school. Of the 372 participants, (49%) consented to utilize APN, mostly via the passive-referral approach (41.4%), and as a last resort via a provider referral (12.4%). The factors associated with increased likelihood of provider partner notification utilization included relationship duration ≥ 2years [adjusted prevalence ratio (aPR), 1.3, (1.05 to 1.60)]; being doubly orphaned (aPR 1.54, 1.12 to 2.30); not watching pornography (aPR 2.16, 1.5 to 3.11).ConclusionsThere was low utilization of APN services among sexually active adolescents with HIV. Passive referral was the preferred method. While acceptable, provider APN was not the preferred method for partner notification among adolescents. There is need to develop adolescent-friendly APN strategies to improve utilization of this important intervention.

PH-responsive hydrogel with gambogic acid and calcium nanowires for promoting mitochondrial apoptosis in osteosarcoma

Calcium (Ca2+) overload therapy gained significant attention in oncology. However, its therapeutic efficacy remained limited due to insufficient Ca2+ accumulation at the tumor site and suboptimal intracellular Ca2+ influx. In this study, gambogic acid (GA), a natural phenolic compound known to promote Ca2+ influx, was encapsulated within an enzyme-triggered, pH-responsive hydrogel (GM@Lip@CHP-Gel) containing Ca2+ hydrogen phosphate nanowires (CHP) to achieve a synergistic approach for bone tumor therapy. GM@Lip@CHP-Gel selectively responded to the slightly acidic tumor microenvironment, triggering degradation of its 3D network structure and sustaining the release of GA and Ca2+ into tumor cells. GA subsequently stimulated Ca2+ influx in tumor cells, effectively disrupting Ca2+ homeostasis. CHP nanowires served as a continuous Ca2+ source, enhancing GA-mediated Ca2+ overload and promoting mitochondrial apoptosis in tumor cells. The combined strategy resulted in an in vivo tumor suppression rate of 79 % and a lung metastasis inhibition rate of 89.4 %, with a protective effect on bone tissue. The naturally derived, Ca2+-mediated treatment demonstrated physiochemical stability in physiological environments and minimized side effects on healthy organs, positioning it as a promising approach for clinical bone cancer therapy.

Polymeric Multivalent Fc Binding Peptides-Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA-4.

Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA-4, is successful in clinical use. However, it is associated with a high incidence of adverse events, and its therapeutic efficacy needs improving. In this study, polymeric multivalent Fc-binding peptides (PLG-Fc-III-4C) are employed to fabricate a bispecific antibody (PD1/CTLA-4 BsAb) to potentiate dual immunotherapy targeting PD1 and CTLA-4. The PD1/CTLA-4 BsAb is prepared by mixing PLG-Fc-III-4C with aPD1 and aCTLA-4 in an aqueous solution for 3 h using the clinically optimal 3:1 proportion of aPD1 to aCTLA-4. PD1/CTLA-4 BsAb significantly inhibits tumors in MC38 colon cancer-bearing mice more effectively than the combination of aPD1 and aCTLA-4, with tumor suppression rates of 96.8% and 77.3%, respectively. It also induces a higher percentage of CD8+ T cells and increases the secretion of effector cytokines while reducing Treg levels in tumors compared to phosphate-buffered saline, indicating significant tumor immunity regulation. Mechanistically, a 6.3-fold increase in PD1/CTLA-4 BsAb accumulation in tumors due to the tumor targeting ability of aPD1, and the PD1/CTLA-4 BsAb significantly reduces the adverse colitis event in healthy mice, compared to aPD1 and aCTLA-4. Thus, these findings provide a novel approach to enhance antitumor therapy using aPD1 and aCTLA-4.

HIV-1 viral decay in blood and semen in antiretroviral-naïve adults initiating dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide

While coformulated dolutegravir and lamivudine (DTG/3TC) is recommended as the first-line antiretroviral therapy (ART), the data on the viral decay in seminal plasma (SP) and blood plasma (BP), as well as changes in inflammatory biomarkers in BP, remain limited among antiretroviral-naïve people with HIV (PWH) receiving DTG/3TC. We conducted a prospective observational cohort study to compare the impact of DTG/3TC vs bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) on viral decay kinetics and changes of inflammatory biomarkers in antiretroviral-naïve PWH. Newly diagnosed PWH who initiated BIC/FTC/TAF (n=57) or DTG/3TC (n=43) were enrolled. BP and SP were collected at 0, 4, 12, 24, and 48 weeks after ART initiation. The primary endpoint was viral suppression of HIV-1 in BP and SP at week 48. Secondary endpoints included changes of HIV-1 DNA levels and inflammatory biomarkers over the 48-week follow-up. Overall, 96 (96.0%) completed the 48-week follow-up (DTG/3TC, n=40; BIC/FTC/TAF, n=56). Viral suppression rates in BP and SP were comparable between BIC/FTC/TAF and DTG/3TC group in per-protocol analyses at week 48 (BP, 96.4% vs 100%, p=0.519; SP, 100% vs 100%, p>0.999). Both regimens demonstrated similar effectiveness in reducing HIV-1 RNA levels in BP (3.0 vs 3.1 log10 copies/mL) and SP (0.9 vs 1.2 log10 copies/mL). There were no statistically significant differences in the reductions of HIV-1 DNA levels and changes of inflammatory biomarkers over the 48-week follow-up. These findings suggested comparable effectiveness of DTG/3TC vs BIC/FTC/TAF in achieving viral suppression in BP and SP and similar changes of inflammatory biomarkers in BP.

Effectiveness, safety, and patient-reported outcomes of treatment with bictegravir/emtricitabine/tenofovir alafenamide fixed dose combination in people living with HIV in Argentina: the BICTARG cohort.

Real-world data on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) fixed-dose combination from resource-constrained settings like Latin America are limited. We conducted an observational retrospective cohort study of treatment-naive (TN, n=315) and treatment-experienced (TE, n= 2356) people living with HIV prescribed BIC/FTC/TAF in Argentina from 10/2019 to 12/2021, with 24 and 48-week follow-up data analyzed for virological suppression, persistence, safety, and metabolic parameters. Patient-reported outcomes were assessed via across-sectional online survey. Baseline characteristics: median age 45 years, 72.2% male, 99.6% Hispanic/Latino ethnicity. Treatment per sistence at 48 weeks was 99.3% (TN) and 99.5% (TE). Virological suppression rates (<200/<50 copies/mL) at 24 weeks were 97.4/88% (TN) and 99/97% (TE). At 48 weeks were 100/92% (TN) and 99/97% (TE). In the TE group, triglycerides decreased with no other lipid changes. In TN, mild total/LDL/HDL cholesterol increases occurred. eGFR mildly decreased in both groups. The online survey (n=536) showed 91.5% reported no medication concerns. Median quality of life scores were 90 (TN) and 88 (TE). Most reported no self-care, activity, mobility, pain/discomfort, or anxiety/depression issues. BIC/FTC/TAF demonstrated high persistence, safety, virological efficacy, and favorable metabolic profile over 48 weeks. The cross-sectional survey indicated high treatment satisfaction and good quality of life in this cohort from Argentina.

Effectiveness of interactive voice response-call for life mHealth tool on adherence to anti-retroviral therapy among young people living with HIV: A randomized trial in Uganda.

In people living with HIV, adherence to antiretroviral therapy (ART) is essential for achieving and sustaining viral suppression and reducing mortality. In young people living with HIV, ART adherence and retention remain a challenge with unsatisfactory viral suppression rates despite facility-based intensive adherence counseling that is the standard of care. Few studies have evaluated mHealth adherence interventions among young people living with HIV in resource-limited settings. This was a randomized parallel trial. Young people aged between15-24 living with HIV, initiating ART, or on ART for not more than 6 months at three ART clinics were recruited and randomized to a ratio of 1:1 to either standard of care or the intervention "Call for Life-Interactive Voice Response" with standard of care, between 12th August 2020 and 1st June 2022. The intervention is mobile technology-based software, that has interactive voice response functionalities, with a web-based interface, that allows interaction through the use of voice and tones via a dial pad. The primary outcome was viral suppression defined as HIV RNA below 1,000 copies per mL at 12 months with retention in care and viral suppression at month 6 as a secondary outcome. Descriptive statistics were used for participant characteristics. Primary outcomes and factors associated with viral load failure were assessed using the log-binomial model. All calculations were done using statistical software release 16.0. A total of 206 participants were recruited and randomized; the mean age was 22.5(SD±1.9) years and 81% (167/206) were female. The intervention had 78.6% (81/103), females, while the standard of care had 83.5% (86/103). Viral suppression at 12 months in the intervention arm was 73.6% (67/91) versus 51.9% (40/77) in the standard of care arm, p=0.01. Retention in care was 88.4% (91/103) in the intervention vs. 74.7% (77/103) in the standard of care arm p=0.01. This is the first study in Uganda to demonstrate that mHealth has the potential to improve medication adherence and retention in care among youth living with HIV in Uganda. NCT04718974 Registry: clinical Trials.gov.

Ultrasound-triggered nano delivery of lenvatinib for selective immunotherapy treatment against hepatocellular carcinoma

Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy.

A meta-analytical approach for estimating methane suppression from dietary additives in ruminants

IntroductionMethane production inhibitors included in feed additives are increasingly used to suppress methane production in the rumen. Most products interact with the rumen microbiome and/or component biochemical pathways that scavenge free hydrogen ions (H+) to make methane (CH4 ). The capacity of these agents to inhibit rumen methane production is determined by the ability of the chemical to block methane production pathways, the amount of agent delivered to the rumen (i.e. the dose) and the absorption, distribution, metabolism and excretion (i.e. the pharmacokinetic) characteristics of the chemical that contribute to removal from the site of action (the rumen). The intrinsic inhibitory capacity of an agent determines the maximum rate of methane suppression. This maximal rate may reduce according to pharmacokinetic effects arising from dose rate and frequency. Most studies of additive methane reduction efficacy use total mixed ration (TMR; with the additive included into the ration) feeding systems and estimate methane reduction (absolute or relative) across a 24-hour period. Few studies report critical pharmacokinetic parameters, making it difficult to extrapolate findings into non-TMR systems (such as grazing) where differing doses and dose frequencies apply.MethodsWe consider the likely behaviour of a rumen-acting oral additive to reduce methane production applying basic pharmacokinetic principles to propose an analytical approach to data from multiple field studies employing different dose rates and dose frequencies to estimate methane suppression responses. This is based upon a logistic transformation of relative efficacy (percentage reduction in methane comparing treatment with control groups) as the dependent variable and includes total dose, dose frequency, quadratic and interaction terms between total dose and dose frequency as independent variables that potentially capture any pharmacokinetic effects on performance. The model was tested using simulation and verified against real data (cattle 3-nitrooxypropanol (3-NOP) methane-reduction studies).ResultsGood fit between predicted and observed methane suppression was obtained.DiscussionWe propose use of the general form of this logistic model with dose and dose frequency components included that address basic pharmacological impacts on methane suppression as the standard approach to meta-analysis.

Research on Radial Vibration Model and Low-Frequency Vibration Suppression Method in PMSM by Injecting Multiple Symmetric Harmonic Currents

Driven by frequency conversion, the windings of a three-phase permanent magnet synchronous motor (PMSM) contain both odd and even harmonic currents. Due to the motor’s pole–slot conductance modulation, the interaction between the magnetic fields generated by these harmonic currents and the permanent magnet field results in harmonic radial vibrations of the motor. This paper analyzes the three-phase currents of the prototype and derives the radial magnetomotive force (MMF) spatiotemporal models for symmetric harmonic currents. By integrating Maxwell’s magnetic force formula and vibration response formula, the radial vibration models for symmetric harmonic currents are developed. The characteristics of vibrations caused by odd and even harmonic currents, as well as positive sequence and negative sequence harmonic currents, are analyzed separately. A cyclic sequence, low-frequency vibration suppression control method incorporating multiple harmonic current injections was designed. Experimental results of this method are compared with those obtained using an ideal sinusoidal current. Except for the second harmonic vibration, all other vibrations are significantly suppressed, with a maximum suppression rate of 92.28%. The total vibration level is reduced by 12.7619 dB, and the average torque is reduced by 0.67% with the total harmonic distortion of the current at 2.89%. The experimental results show that the vibration method in this paper has little influence on the average torque of the motor, the current distortion rate is small, and the vibration suppression effect is good.

Human immunodeficiency virus/acquired immune deficiency syndrome antiretroviral therapy initiated on the same day in treatment-naïve people with human immunodeficiency virus: A comparative study of efficacy and regimen.

Rapid initiation of antiretroviral therapy (ART) is recommended by guidelines, however, real-world studies of same-day initiation of ART in China are limited, and an optimal treatment regimen has yet to be identified. The study aims to provide a realistic reference for rapid initiation of ART. We retrospectively analyzed the clinical data of treatment-naïve people with human immunodeficiency virus (PWHs) who were diagnosed and prescribed same-day ART initiation from January 1, 2021 to December 31, 2022 at Chongqing Public Health Medical Center. PWHs voluntarily chose an ART regimen that divided them into two groups: National Free Antiretroviral Treatment Program (NFATP)-recommended regimens group (2 nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors/protease inhibitors) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) group. The primary endpoint was the virological outcome of the two groups for same-day ART initiation at 24weeks and 48weeks. The secondary endpoints included changes in CD4 counts, maintenance of the original ART regimen at 48weeks, and lipid levels and renal function at 48weeks. A total of 255 PWHs were included in the study, including 131 (51.4%) in the NFATP group and 124 (48.6%) in the BIC/FTC/TAF group. The overall virological suppression rates at 24weeks and 48weeks were 78.2% (165/211) and 95.4% (207/217), respectively. At 24weeks, the virologic suppression rate in the NFATP group was lower than that in the BIC/FTC/TAF group (65.3% [66/101] vs . 90.0% [99/110], P <0.001). The median increase in the CD4 count was 198.0 (126.0-300.0) cells/μL at 24weeks, with 182.0 (108.0-245.0) cells/μL in the NFATP group and 219 (132.0-316.0) cells/μL in the BIC/FTC/TAF group ( P =0.035). At 48weeks, there was no significant difference in the virological suppression rate or CD4 count between the groups. The 48-week initial ART regimen retention rates and treatment retention rates were significantly higher in the BIC/FTC/TAF group than in the NFATP group (91.1% (113/124) vs . 71.8% (94/131), 99.2% (118/119) vs . 93.0% (120/129), respectively). In terms of safety, there were no significant changes from baseline in levels of creatinine, estimated glomerular filtration rate (eGFR), or lipids in either group at 48weeks. ART initiation on the day of diagnosis is effective, safe, and feasible, with satisfactory rates of virologic suppression, 48-week initial ART regimen retention rates, and treatment retention rates in treatment-naïve PWHs. In our study, the early virologic suppression rate, CD4 cell counts, and treatment retention of the BIC/FTC/TAF regimens were significantly better than those of the NFATP regimens.

Drug monitoring was conducted for rifapentine among people with HIV receiving dolutegravir containing antiretroviral therapy and latent tuberculosis treatment

The proportion of trough plasma concentration of dolutegravir (DTG) above protein adjusted 90% inhibition concentration (IC90) (0.064mg/L) was 98.1% across all visits during the twelve doses of once-weekly rifapentine and isoniazid (3HP) in people with HIV (PWH). Furthermore, the participants maintained a high rate of HIV viral suppression (98%) within 6 months after completing 3HP.