Optical dark-field spectroscopy of single plasmonic nanoparticles for molecular biosciences.

An ideal sensor capable of quantifying analytes in minuscule sample volumes represents a significant technological advancement. Plasmonic nanoparticles integrated with optical dark-field spectroscopy have reached this capability, demonstrating versatility and expanding applicability across in vitro and in vivo subjects. This review underscores the applicability of optical dark-field spectroscopy with single plasmonic nanoparticles to elucidate a wide range of biomolecular characteristics, including binding constants, molecular dynamics, distances, and forces, as well as recording cell communication signals. Perspectives highlight the potential for the development of implantable nanosensors for metabolite detection in animal models, illustrating the technique's efficacy without the need for labeling molecules. In summary, this review aims to consolidate knowledge of this adaptable and robust technique for decoding molecular biological phenomena within the nano- and bio-scientific community.

Cytomegalovirus chronic retinal necrosis with ganciclovir resistance: a case report.

BACKGROUND: Cytomegalovirus (CMV) chronic retinal necrosis (CRN) is a rare viral retinal infection that occurs in mildly immunocompromised people. It shares some features with both acute retinal necrosis and CMV retinitis. It is typically treated with combination intravitreal and systemic ganciclovir. We discuss the management of a case of CMV CRN with ganciclovir resistance. CASE PRESENTATION: An 80-year-old female presented with one month of blurry vision in the left eye. She was being treated with abatacept, methotrexate, and prednisone for rheumatoid arthritis. Examination revealed anterior chamber and vitreous cell along with peripheral retinal whitening. Fluorescein angiogram showed diffuse retinal non-perfusion. Aqueous fluid PCR testing returned positive for CMV. The retinitis was initially controlled with oral and intravitreal ganciclovir, but then recurred and progressed despite these therapies. Ganciclovir resistance was suspected and the patient was switched to intravitreal foscarnet injections, along with oral letermovir and leflunomide, which lead to resolution of the retinitis. The patient has now continued with letermovir and leflunomide for approximately 2.5 years without reactivation of the retinitis or need for further intravitreal anti-viral injections and with adequate control of her rheumatoid arthritis. CONCLUSION: The incidence of CMV CRN may increase in the future as the use of non-cytotoxic immunosuppressive therapies that result in relatively mild immunosuppression also increases. Treatment with ganciclovir is effective but frequently leads to resistance, as in our case. In this situation, combination therapy with letermovir and leflunomide, particularly in the setting of rheumatoid arthritis where leflunomide can also have an anti-inflammatory effect, can be considered.

Hemorrhagic Erucism due to Lonomia spp. in Peru - A Call for Action.

Envenomation due to exposure to caterpillars is an emerging public health problem. A life-threatening bleeding diathesis has been described in South America after exposure to Lonomia obliqua or L. acheolus. Deforestation, forest degradation, and global warming might increase the frequency of human exposure to these insects. Prompt recognition and administration of antivenom are crucial to ensure a favorable outcome.

Active case finding to detect symptomatic and subclinical pulmonary tuberculosis disease: implementation of computer-aided detection for chest radiography in Viet Nam.

Objective: In Viet Nam, tuberculosis (TB) prevalence surveys revealed that approximately 98% of individuals with pulmonary TB have TB-presumptive abnormalities on chest radiographs, while 32% have no TB symptoms. This prompted the adoption of the "Double X" strategy, which combines chest radiographs and computer-aided detection with GeneXpert testing to screen for and diagnose TB among vulnerable populations. The aim of this study was to describe demographic, clinical and radiographic characteristics of symptomatic and asymptomatic Double X participants and to assess multilabel radiographic abnormalities on chest radiographs, interpreted by computer-aided detection software, as a possible tool for detecting TB-presumptive abnormalities, particularly for subclinical TB. Methods: Double X participants with TB-presumptive chest radiographs and/or TB symptoms and known risks were referred for confirmatory GeneXpert testing. The demographic and clinical characteristics of all Double X participants and the subset with confirmed TB were summarized. Univariate and multivariable logistic regression modelling was used to evaluate associations between participant characteristics and subclinical TB and between computer-aided detection multilabel radiographic abnormalities and TB. Results: From 2020 to 2022, 96 631 participants received chest radiographs, with 67 881 (70.2%) reporting no TB symptoms. Among 1144 individuals with Xpert-confirmed TB, 51.0% were subclinical. Subclinical TB prevalence was higher in older age groups, non-smokers, those previously treated for TB and the northern region. Among 11 computer-aided detection multilabel radiographic abnormalities, fibrosis was associated with higher odds of subclinical TB. Discussion: In Viet Nam, Double X community case finding detected pulmonary TB, including subclinical TB. Computer-aided detection software may have the potential to identify subclinical TB on chest radiographs by classifying multilabel radiographic abnormalities, but further research is needed.

Multi-organ clinical manifestations of Mpox: an umbrella review of systematic reviews.

BACKGROUND: Mpox is a severe viral zoonosis that has emerged as a public health concern due to its potential for human-to-human transmission and severe illness. Understanding its clinical manifestations is crucial for effective management and control. Several systematic reviews have assessed various manifestations of Mpox. This umbrella review synthesizes evidence on Mpox's manifestations across different organ systems. METHOD: We conducted an umbrella review, adhering to Joanna Briggs Institute (JBI) methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on systematic reviews of Mpox manifestations. We performed a literature search up to 25th September 2023, in databases like PubMed, Embase, and Web of Science. We included systematic reviews of observational studies, case reports, case series, or RCTs reporting any manifestations of Mpox in humans, focusing on a global scope. AMSTAR 2 was used to evaluate the quality of systematic reviews, and data has been synthesized in narrative and tabular manners. RESULTS: A total of 25 systematic reviews were included, uncovering diverse manifestations of Mpox, such as cutaneous, cardiovascular, oral, ophthalmic, gastrointestinal, respiratory, and pregnancy-related. Cutaneous manifestations (up to 100%) were the most prevalent, featuring lesions and rashes. Constitutional symptoms of viral illness were reported in ~ 60% to > 85% of the cases. Significant respiratory symptoms were present in ~ 50% of cases overall. Headaches were the leading neurological symptom present in > 30%. Symptoms of gastrointestinal involvement ranged from 39% (oral lesions) with decreasing frequency to low diarrhea at ~ 5%, with proctitis percentages ranging from high teens to mid-twenties. Ophthalmic manifestations (6% but with wide variations among studies). Many primary studies included in the systematic reviews consisted of case reports and case series. A wide range of manifestations across different organ systems was observed. Negative outcomes for pregnancies were reported, but evidence is limited. Adverse cardiovascular and neurological outcomes were identified, though only a few studies provided insights into these findings. CONCLUSION: Mpox exhibits diverse manifestations, impacting multiple organ systems, with substantial variations. The findings highlight the importance of ongoing, nuanced, and region-specific research and management strategies for Mpox. The reliance on case reports and series underscores the need for more high-quality, long-term studies to deepen our understanding and management of this significant public health concern.

Suspension electrospinning of decellularized extracellular matrix: A new method to preserve bioactivity.

Decellularized extracellular matrices (dECM) have strong regenerative potential as tissue engineering scaffolds; however, current clinical options for dECM scaffolds are limited to freeze-drying its native form into sheets. Electrospinning is a versatile scaffold fabrication technique that allows control of macro- and microarchitecture. It remains challenging to electrospin dECM, which has led researchers to either blend it with synthetic materials or use enzymatic digestion to fully solubilize the dECM. Both strategies reduce the innate bioactivity of dECM and limit its regenerative potential. Herein, we developed a new suspension electrospinning method to fabricate a pure dECM fibrous mesh that retains its innate bioactivity. Systematic investigation of suspension parameters was used to identify critical rheological properties required to instill "spinnability," including homogenization, concentration, and particle size. Homogenization enhanced particle interaction to impart the requisite elastic behavior to withstand electrostatic drawing without breaking. A direct correlation between concentration and viscosity was observed that altered fiber morphology; whereas, particle size had minimal impact on suspension properties and fiber morphology. The versatility of this new method was demonstrated by electrospinning dECM with three common decellularization techniques (Abraham, Badylak, Luo) and tissue sources (intestinal submucosa, heart, skin). Bioactivity retention after electrospinning was confirmed using cell proliferation, angiogenesis, and macrophage polarization assays. Collectively, these findings provide a framework for researchers to electrospin dECM for diverse tissue engineering applications.

Comprehensive compilation of congener profiles to support health assessment of environmental exposures to polychlorinated biphenyl mixtures.

Exposure to polychlorinated biphenyls (PCBs) remains a potential human health risk due to their persistence in the environment, despite a global ban on their production. Understanding the composition of PCB mixtures is essential for the application of a mixtures-based approach to assessing health risks of PCB exposure. This work represents the most extensive effort to date to compile and make publicly available the PCB congener profiles for mixtures with toxicological data, providing a foundation for understanding toxicological potency of PCB mixtures in the environment. We searched for published congener profiles across 29 commercial and simulated environmental PCB mixtures, including various Aroclors, Phenoclors, Clophens, and Kanechlors, among others. A total of 117 references containing 401 distinct complete or partial tabularized profiles were found. Aroclor 1254 had the most published profiles, with 79 unique datasets characterizing multiple mixture lots. In contrast, no congener-specific composition data were identified for Fenclors, Clophen C, or Pyralenes. Eighty-seven of the most complete and clearly reported profiles underwent a detailed extraction of the congener data, PCB mixture source, and analytical methods. Challenges encountered during data extraction included congener coelutions, incomplete methods reporting, and inconsistencies in PCB nomenclature. These factors complicate data visualization, comparisons across datasets, and use of the data in subsequent analyses. Where possible, we have converted profiles to the same units and congener numbering convention to allow for easier comparison. The extracted data are publicly available online as interactive visuals and as a downloadable Microsoft Excel® workbook. This dataset provides researchers with an overview of the current PCB mixture profile landscape that can serve as a tool to support efforts to minimize the health impacts of environmental PCB exposure, including the exploration of links between mixture composition and toxicity and the identification of the most efficient and effective remediation strategies at contaminated sites.

All-Optical Trapping and Programmable Transport of Gold Nanorods with Simultaneous Orientation and Spinning Control.

Gold nanorods (GNRs) are of special interest in nanotechnology and biomedical applications due to their biocompatibility, anisotropic shape, enhanced surface area, and tunable optical properties. The use of GNRs, for example, as sensors and mechanical actuators, relies on the ability to remotely control their orientation as well as their translational and rotational motion, whether individually or in groups. Achieving such particle control by using optical tools is challenging and exceeds the capabilities of conventional laser tweezers. We present a tool that addresses this complex manipulation problem by using a curve-shaped laser trap, enabling the optical capture and programmable transport of single and multiple GNRs along any trajectory. This type of laser trap combines confinement and propulsion optical forces with optical torque to transport the GNRs while simultaneously controlling their rotation (spinning) and orientation. The proposed system facilitates the light-driven control of GNRs and the quantitative characterization of their motion dynamics including transport speed, spinning frequency, orientation, and confinement strength. We experimentally demonstrate that remote control of the GNRs can be achieved both near a substrate surface (2D trapping) and deep within the sample (3D all-optical trapping). The motion dynamics of two sets of off-resonant GNRs, possessing similar aspect ratios but different resonance wavelengths, are analyzed to highlight the role played by their optical and mechanical properties in the optical manipulation process. The experimental results are supported by a theoretical model describing the observed motion dynamics of the GNRs. This optical manipulation tool can significantly facilitate applications of light-driven nanorods.

Control strategies for emerging infectious diseases: Crimean-Congo hemorrhagic fever management.

Background and Aims: Crimean-Congo Hemorrhagic Fever (CCHF) is a significant public health concern transmitted by ticks. This study seeks to thoroughly grasp the epidemiology and transmission patterns of CCHF, which is caused by the CCHF virus (CCHFV), a member of the Nairovirus genus in the Bunyaviridae family. Methods: The study investigates the global distribution and endemicity of CCHF, its mortality rates, modes of transmission (including tick bites, contact with infected animal blood, and limited person-to-person transmission), and factors influencing its prevalence across different regions. Genetic diversity within CCHFV and its impact on transmission dynamics are explored, along with efforts to control the disease through tick prevention, antiviral treatment, and the development of vaccines and diagnostics. Results: CCHFV exhibits widespread distribution, particularly in the Middle East, Africa, Asia, and Eastern Europe, with an overall mortality rate of approximately 30% and a case fatality rate ranging from 10% to 40%. Transmission occurs primarily through tick bites and contact with infected animal blood, with limited person-to-person transmission. Livestock workers, slaughterhouse employees, and animal herders in endemic areas are most affected by their frequent interaction with sick animals and ticks. Genetic diversity within CCHFV contributes to variations in transmission dynamics, complicating control efforts. Antiviral ribavirin shows efficacy in treating CCHF infection. Conclusion: This study underscores the importance of further research to understand the enzootic environment, transmission routes, and genetic diversity of CCHFV for effective control measures, including the development of vaccines, treatment options, and diagnostics.

Comparative analysis of the quality of the cement mantle in hip hemiarthroplasty after femoral neck fracture between three different surgical approaches: a single-center retrospective observational study.

PURPOSE: Achieving the initial stability of implants is necessary for hip hemiarthroplasty (HHA), especially in elderly patients, and this can be achieved with a cement mantle of quality. The direct anterior approach (DAA) for HHA lately has shown positive results. However, evidence is lacking of HHA in elderly patients with osteoporosis after femoral neck fracture (FNF). This study compares differences in cement mantle quality after HHA, its complications, radiological outcomes and functional status in elderly patients with FNF intervened through different approaches. METHODS: A non-interventional, retrospective case-control study was conducted. 150 cases were selected based on the surgical approach (DAA, DLA and PLA) in a 1:1:1 proportion between 2018 and 2019. Under 75 years old suspicion or confirmation of a pathological fracture were excluded. Antibiotic-loaded cement was utilized. Cement preparation involved vacuum centrifugation and standard instructions for preparation canal and filling, and prosthesis placement were followed. RESULTS: No statistically significant differences in cement mantle quality, radiological outcomes, and the majority of the postoperative complications and functional status considering the surgical approach (p > 0.05). However, the DAA was associated significantly with shorter hospital stays (8.3 days vs 11.3 and 13 days for DLA and PLA) a decrease in postoperative blood transfusion (22% vs 34% and 53%), and lower rate of loss of walking (8% vs 20% and 28.6%). CONCLUSION: The DAA for HHA in patients with FNF provides a high-quality cement mantle, similar to other approaches. Also, the DAA shows advantages like shorter hospital stays and lower transfusion rates in elderly patients.

Self-adaptive integrated photonic receiver for turbulence compensation in free space optical links.

In Free Space Optical (FSO) communication systems, atmospheric turbulence distorts the propagating beams, causing a random fading in the received power. This perturbation can be compensated using a multi-aperture receiver that samples the distorted wavefront on different points and adds the various signals coherently. In this work, we report on an adaptive optical receiver that compensates in real time for scintillation in FSO links. The optical front-end of the receiver is entirely integrated in a silicon photonic chip hosting a 2D Optical Antenna Array and a self-adaptive analog Programmable Optical Processor made of a mesh of tunable Mach-Zehnder interferometers. The photonic chip acts as an adaptive interface to couple turbulent FSO beams to single-mode guided optics, enabling energy and cost-effective operation, scalability to systems with a larger number of apertures, modulation-format and data-protocol transparency, and pluggability with commercial fiber optics transceivers. Experimental results demonstrate the effectiveness of the proposed receiver with optical signals at a data rate of 10 Gbit/s transmitted in indoor FSO links where different turbulent conditions, even stronger than those expected in outdoor links of hundreds of meters, are reproduced.

Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer.

INTRODUCTION: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment. METHODS: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS). RESULTS: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019). CONCLUSION: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

Meta-analysis of Pregnancy Events in Biomedical HIV Prevention Trials in Sub-Saharan Africa: Implications for Gender Transformative Trials.

Historically, pregnant and lactating populations (PLP) have been excluded or disenrolled from biomedical HIV prevention trials, despite being more likely to acquire HIV during pregnancy and the post-partum period. We conducted a meta-analysis of pregnancy events in biomedical HIV prevention trials in sub-Saharan Africa to support trialists moving toward more inclusive clinical and implementation studies. We searched peer-reviewed literature reporting pregnancy events and contraceptive requirements in HIV prevention trials between 2001 and 2022. We hypothesized four variables to explain variation: contraceptive requirements, study start year, study product, and sub-region. We fit a meta-analytic model to estimate individual effect sizes and sampling variances, then conducted sub-group analyses to assess moderating effects. We identified 38 references for inclusion, across which the proportion of pregnancy events was 8% (95% confidence interval [CI]: 6-10%) with high heterogeneity (I2 = 99%). Studies not requiring contraceptives (21%, 95%CI: 7-48%) reported a significantly higher proportion of pregnancy events than studies requiring two methods (5%, 95%CI: 2-10%). Studies launched between 2001 and 2007 (11%, 95%CI: 8-16%), microbicide gel trials (12%, 95%CI: 8-18%), and studies conducted in Western Africa (28%, 95%CI: 13-51%) reported higher proportions of pregnancy events than reference groups. Together, these variables have a moderating effect on pregnancy events (p < 0.0001), explaining 63% of heterogeneity in trials. Results describe how, over time, more stringent contraceptive requirements reduced pregnancy events, which ensured necessary statistical power but limited reproductive choice by participants. With the move toward continuing PLP on experimental products, trialists can utilize estimated pregnancy events reported here to inform strategies that accommodate participants' changing fertility preferences.

Effects of swift heavy ions on metal nanoparticles embedded in silica: Using linearly polarized light to monitor the elongation kinetics.

The elongation of metallic nanoparticles (NPs) embedded in a dielectric matrix after irradiation with swift heavy ions is a phenomenon that has been known for several years. However, the precise mechanism behind this deformation process is still not fully understood, primarily due to the dearth of information during intermediate stages of deformation. In this study, we report the continuation of our previous work [Peña-Rodríguez et al., Sci. Rep. 7(1), 922 (2017)], exploiting the strong dependence of the localized surface plasmon resonance on the aspect ratio of elongated metal NPs to study the elongation kinetics in situ. In situ optical absorption spectra were measured using a polarizing beam splitter to separate the longitudinal and transverse plasmon modes of the anisotropic NPs. Then, the detailed geometrical and compositional parameters were determined from a fit of these spectra. The use of linearly polarized light allowed for a more accurate analysis of the elongation kinetics, particularly useful in the first stages, where longitudinal and transverse modes overlap.

Pneumocystis jirovecii Pneumonia in HIV-Negative, Non-transplant Patients: Epidemiology, Clinical Manifestations, Diagnosis, Treatment, and Prevention.

Purpose of Review: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that is increasingly seen in HIV-negative patients with immune compromise due to other etiologies. We lack comprehensive clinical recommendations for this population. Recent Findings: In non-HIV cases, PJP has a mortality rate of up to 50%, which is unacceptable despite the presence of safe and effective prophylaxis and therapy. Steroid use is one of the most common risk factors for disease development. New data suggests that lower doses of the preferred treatment regimen, TMP-SMX, may be equally effective for treatment while limiting side effects. While commonly used, the benefit of corticosteroids for the treatment of PJP has recently been called into question, with a recent multicenter cohort demonstrating no benefit among solid organ transplant recipients. Summary: A high suspicion of PJP in individuals with pneumonia during immunosuppressant use is crucial. Therapeutic options are evolving to decrease potential side effects while maintaining efficacy in this highly morbid disease.

Epidemiology and Clinical Outcomes of Bacterial Meningitis in Children and Adults in Low- and Middle-Income Countries.

Purpose of Review: Despite the availability of effective vaccines against the three primary pathogens (Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries. Recent Findings: Bacterial meningitis represents a significant public health challenge for national and global health systems. Since vaccine-preventable meningitis remains highly prevalent in low-income and middle-income countries, the World Health Organization (WHO) recently developed a global roadmap to defeating meningitis by 2030 and ameliorating its associated neurological sequelae. Summary: There is a need for a global approach to surveillance and prevention of bacterial meningitis. Increasing vaccination coverage with conjugate vaccines against pneumococcus and meningococcus with optimal immunization schedules are high-value healthcare interventions. Additionally, overcoming diagnostic challenges and the early institution of empirical antibiotic therapy and, when feasible, adjunctive steroid therapy constitutes the pillars of reducing the disease burden of bacterial meningitis in resource-limited settings.

Assessing the effect of COVida orphans and vulnerable children support services on viral load coverage and suppression among children and adolescents living with HIV in four provinces in Mozambique.

Orphans and vulnerable children (OVC) programs focusing on improving HIV outcomes for children and adolescents living with HIV (C&ALHIV) may improve viral load (VL) testing coverage, a critical step toward achieving VL suppression. In Mozambique, we conducted a retrospective medical record review comparing VL testing coverage and suppression between C&ALHIV receiving OVC support and two cohorts of non-participants constructed using propensity score matching. We collected data for 25,783 C&ALHIV in Inhambane, Maputo City, Nampula, and Tete between October 2020-September 2021. Unadjusted rates of VL testing were 62.9% among OVC participants compared with 39.2% and 50.4% of non-participants in OVC support and non-OVC support districts, respectively. In multivariate models, OVC participants were 18 and 10 percentage points more likely to have received a VL test than non-participants in OVC districts (p < 0.01) and non-OVC districts (p < 0.01), respectively. OVC participants under 5 years old were significantly more likely to have received a VL test than their same-age counterparts in both comparison groups. Overall, the OVC program did not demonstrate significant effects on VL suppression. This approach could be replicated in other contexts to improve testing coverage. It is crucial that clinical partners and governments continue to share data to enable timely monitoring through OVC programming.

Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System.

RATIONALE: Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored. OBJECTIVES: To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals. METHODS: Toluene-induced addictive-like response was evaluated with a locomotor sensitization model in mice. Toluene-sensitized animals had access to running wheels 1, 2, 4 or 24 h/day for 4 weeks; thereafter, locomotor sensitization expression was evaluated after a toluene challenge. RAS elements (ACE and ACE2 enzymes; AT1, AT2 and Mas receptors) expression was determined by Western blot in the VTA, NAc and PFCx of toluene-sensitized mice with and without exercise. RESULTS: Individual differences in toluene-induced locomotor sensitization development were observed. Access to wheel running 1 and 2 h/day reduced but 4 and 24 h/day completely blocked locomotor sensitization expression. Repeated toluene exposure changed RAS elements' expression in the VTA, NAc and PFCx, while exercise mainly modified ACE and AT1 in air-exposed and toluene-sensitized mice. CONCLUSIONS: Inhalant-exposed animals show different sensitization phenotypes. Exercise duration determined its efficacy to attenuate the addictive-like response. Toluene exposure and exercise each modified RAS, the latter also modifying toluene-induced changes.

Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.