7-day Period Research Articles

Potential of dip treatments to disinfest cuttings of the invasive Thrips parvispinus (Thysanoptera: Thripidae).

Thrips parvispinus (Karny) (Thysanoptera: Thripidae), an invasive thrips species, poses a significant threat to global agriculture due to its polyphagous nature and rapid spread. Its recent arrival in the continental United States raises concerns about potential impacts on ornamental and vegetable crops. Dip treatments might serve as a phytosanitary practice for growers to start with plants free of visible pests. This study aimed to assess the efficacy of dip treatments using 4 biorational and microbial insecticides (mineral oil and Beauveria bassiana-based) in controlling T. parvispinus on bean seedlings. Following gentle agitation of cuttings, artificially infested with 10 second-instar (L2) larvae, for 15s in each solution, thrips infestation was evaluated at 1, and 24h postdipping, scoring the numbers of dislodged and dead larvae. Additionally, we tested whether dipping could cause phytotoxicity on bean (Phaseolus vulgaris L.), gardenia (Gardenia jasminoides Ellis), and mandevilla (Mandevilla splendens (Hook.f.) Woodson) cuttings during a 7-day period. Our results demonstrated that dip treatments effectively dislodged and killed T. parvispinus L2 larvae from infested cuttings, with BotaniGard-ES and Suffoil-X exhibiting the highest efficacy and a dislodgment rate of 80%-100%. BotaniGard-ES was the only product causing phytotoxicity on bean seedlings, but not on mandevilla and gardenia. Overall, we demonstrated that dip treatment using biorational insecticides is an additional tool that can be incorporated in the integrated pest management of T. parvispinus. These results hold implications for the broader application in the management of thrips across various plants propagated from cuttings.

P-533. CD4 T-cell, CD4/CD8 Ratio Improvement and a General Reduction in Inflammatory Biomarkers with Low-Level Viremia (LLV) up to Week 192 with Fostemsavir (FTR)-Based Regimens in Individuals with Multidrug-Resistant (MDR) HIV-1

Abstract Background Persistent LLV (40-1000 c/mL) is associated with virologic failure, drug resistance and increased risk of inflammation and may impact morbidity and mortality. FTR (prodrug of the first-in-class attachment inhibitor temsavir) is indicated with other antiretrovirals (ARVs) for heavily treatment-experienced individuals with MDR HIV-1 unable to construct suppressive regimens. BRIGHTE participants (pts) did not have to stop FTR due to LLV. We describe outcomes and inflammatory biomarkers through Week 192 in pts with LLV (< 40, 40-400, 400-1000 and > 1000 c/mL) on FTR-based regimens from the Randomized Cohort (RC) in the BRIGHTE study. Methods BRIGHTE was a phase 3 study (N=371; RC, n=272; Non-randomized Cohort, n=99) in adults failing their current ARV regimen (HIV-1 RNA > 400 c/mL) with ≤ 2 fully active approved ARVs. Pts with 1 or 2 active ARVs entered the RC and received open-label FTR + optimized background therapy after an 8-day blinded placebo-controlled period. Virologic and immunologic responses were analyzed by baseline (BL) demographics and disease characteristics. Results At BL in the RC, 89% of pts had CD4 T-cell count < 350 cells/mm3, with 5% between 350 and < 500 cells/mm3 and 6% ≥ 500 cells/mm3. Mean CD4 T-cell increase observed in the < 40 c/mL (n=142) group was 331 cells/mm3, 40-400 c/mL (n=25) was 263 cells/mm3, 400-1000 c/mL (n=2) was 218 cells/mm3, and in pts with > 1000 c/mL (n=10) was 107 cells/mm3. Similar mean increase in CD4/CD8 ratio was observed in pts with LLV; ratio in the < 40 c/mL (n= 142) group was 0.38, 40-400 c/mL (n=25) was 0.31, 400-1000 c/mL (n=2) was 0.32, and in pts with > 1000 c/mL (n=10) was 0.09. Biomarkers showed a mean general reduction; < 40 c/mL (sCD14: −371 µg/L, n=133; sCD163: −134 µg/L, n=40; D-dimer: 0.16 mg/L, n=139), 40-400 c/mL (sCD14: −428 µg/L, n=21; sCD163: −80 µg/L, n=5; D-dimer: −0.14 mg/L, n=22), 400-1000 c/mL (sCD14: 1174 µg/L, n=2; sCD163: no data; D-dimer: 0.04 mg/L, n=2), > 1000 c/mL (sCD14: 271 µg/L, n=10; sCD163: 107 µg/L, n=3; D-dimer: 0.08 mg/L, n=10). Conclusion In pts with LLV, there is a persistent increase in CD4 T-cell count and improvement in CD4/CD8 ratio, with a general reduction in inflammatory markers up to Week 192. Results highlight the value of FTR-based regimens for sustained improvement where there is incomplete virologic suppression. Disclosures Vincenzo Spagnuolo, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|MSD: Honoraria|ViiV Healthcare: Honoraria Natalia Gregori, MD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Iacopo Marcon, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Fangfang Du, MS in Statistics, GSK: Employee|GSK: Stocks/Bonds (Public Company) Bo Li, PhD, GSK: Employee Marcia Wang, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Alftan Dyson, PharmD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Manyu Prakash, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Andrew Clark, MD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee

P-534. Similar Efficacy, Safety and CD4 T-cell Increase up to Week 96 Observed with Fostemsavir (FTR)-Based Regimens in the BRIGHTE Study and Dolutegravir (DTG)-Based Regimens in the VIKING-3 Study in Individuals with Multidrug-Resistant (MDR) HIV-1

Abstract Background Constructing suppressive regimens in individuals with MDR HIV-1 can be challenging. We assessed populations with limited ART options in the BRIGHTE study using FTR-based regimens and the VIKING-3 study using DTG-based regimens. Methods BRIGHTE was a phase 3 study (N=371; Randomized Cohort [RC], n=272; Non-randomized Cohort, n=99) in adults failing current ART (HIV-1 RNA > 400 c/mL) with ≤ 2 fully active approved ARVs. Participants (pts) with 1 or 2 active ARVs entered the RC and received open-label FTR + optimized background therapy (OBT) after an 8-day blinded placebo-controlled period. In the RC, the most common agent in initial OBT was DTG (84%), with 64% taking it twice daily (BID). VIKING-3 (n=183) was a single-arm open-label phase 3 study in adults with INI-resistant virus receiving DTG 50 mg BID + failing regimen (without raltegravir or elvitegravir) through Day 7, then the regimen was optimized with ≥ 1 fully active ARV and DTG continued. Virologic and immunologic response was analyzed by baseline (BL) demographics and characteristics. Results BRIGHTE pts were male (n=290, 78%), median age 48 years and White (n=259, 70%). Observed antiviral response in the RC was 81% (< 40 c/mL, n=128) and 88% (< 400 c/mL, n=140). Mean CD4 increase from BL was 204.7 cells/mm3, with BL mean CD4 count 152.5 cells/mm3. VIKING-3 pts were male (n=141, 77%), median age 48 years and 71% (n=130) White. Antiviral response observed in VIKING-3 was 84% (< 50 c/mL, n=101) and 93% (< 400 c/mL, n=111). Mean CD4 increase was 192 cells/mm3, with BL mean CD4 count 202 cells/mm3. Safety across study populations was as follows: BRIGHTE (RC), n=92 (34%) serious adverse events (AEs), n=57 (21%) drug-related AEs and n=7 (3%) AEs leading to withdrawal; VIKING-3, n=60 (33%) serious AEs, n=52 (28%) drug-related AEs and n=8 (4%) AEs leading to withdrawal. Conclusion Despite limited ARV options in individuals with MDR HIV-1, data demonstrate that over 96 weeks both DTG (BID) and FTR-based regimens provide robust viral suppression and CD4 T-cell improvement. Although differences in BL characteristics exist, immunosuppression was more profound in BRIGHTE pts. FTR and DTG were commonly used together in BRIGHTE, engaging different mechanisms of action. Data provide further support for effective ARVs for individuals living with MDR HIV-1. Disclosures Antonella Castagna, MD, Bristol-Myers Squibb: Advisor/Consultant|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck Sharp & Dohme: Advisor/Consultant|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Natalia Gregori, MD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Iacopo Marcon, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Fangfang Du, MS in Statistics, GSK: Employee|GSK: Stocks/Bonds (Public Company) Bo Li, PhD, GSK: Employee Marcia Wang, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Alftan Dyson, PharmD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Clifford B. Jones, BSc MSc MB ChB, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: Employee Manyu Prakash, PhD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee Andrew Clark, MD, GSK: Stocks/Bonds (Public Company)|ViiV Healthcare: employee

P-784. Early Prediction of Inducible Macrolide Resistance For Mycobacterium abscessus –Minimum Inhibitory Concentrations at Day 7 Versus Day 14

Abstract Background Mycobacterium abscessus is notoriously difficult to treat. Current guidelines suggest a 14-day long incubation period and/or sequencing of erm41 to detect inducible macrolide resistance when treating pulmonary disease. However, the lengthy incubation is inconvenient, and genotyping is not routinely available nor correlated with treatment outcomes in extrapulmonary infections. We aimed to assess whether a more than two-fold change in minimum inhibitory concentrations (MICs) at D7 can reliably predict inducible macrolide resistance at D14.Table 1.MICs of the included M. abscessus isolates against selected antibiotics and breakpoints interpretationThe only M abscessus sub bolletei had macrolide MIC of 2 (S), 32 (R), 32 (R) on D3, 7, 14, and amikacin MIC of 8 (S), cefoxitin 32 (S), ciprofloxacin 8 (R), doxycycline 32 (R), imipenem 8 (I), linezolid 8 (S), moxifloxacin 8 (R), TMP/SFX > 8/152 (R), tobramycin 16 (I), amoxicillin/clavulanic acid >64/32 (R), ceftriaxone 128 (R), cefepime 64 (R), tigecycline 0.5 (S) Methods Between 2013-2015, 35 M. abscessus isolates were identified from non-pulmonary sites at a medical center in Taiwan. The species were identified using mass spectrometry and sequencing of erm41, and rrl were done. Testing for MIC was done with broth microdilution, with results read on D3, D7, and D14 for macrolides, and all other antibiotics on D3. The isolate is predicted to have inducible macrolide resistance if there is a twofold or more increase in MIC between D3 and D7. The clinical information was obtained from chart review.Table 2.Application of macrolide prediction rule and the correlation with phenotypic and genotypic resistance (N=35) Results There were a total of 35 unique M. abscessus isolates comprising 16 subsp. abscessus, 18 subsp. massiliense and 1 subsp. bolletii. The overall inducible macrolide resistance was 45.7% and 2 of the 5 sequevar C28 M abscessus exhibited inducible macrolides resistance. Using proposed prediction rule, the sensitivity and specificity was 87.5% and 73.7%, respectively; resulting in 2 very major errors (failure to identify inducible macrolide resistance), and comparatively superior to genotypic prediction, resulting in 4 very major errors. From chart review, 80% of the patients received combinatorial treatment, and macrolides were the most widely used antibiotics. 67.9% of them received surgery, or debridement. The overall clinical cure rate was 75%, after a median treatment duration of 6 months.Table 3.Patient characteristicsa: One subject with ESKD under peritoneal dialysis had isolated culture within ascites, one man had MAB growth in pleural effusion.b: One subject had MAB growth in liver abscess, and the other had positive culture in gastric juice.c: 14 (50%) patients got moxifloxacin, 13 (46.4%) patients got levofloxacin and 5 (17.9%) got ciprofloxacin. Conclusion The study highlighted that susceptibility testing read within one week can give meaningful information on inducible macrolide resistance that was not inferior to genotypic information. Further validation of early MIC changes to guide treatment selection is warranted. Disclosures All Authors: No reported disclosures

P-1088. Safety Study of Rifaquizinone in Dogs Following Intra-articular Administration

Abstract Background Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of prosthetic joint infections (PJIs). RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. This study sought to investigate the safety/tolerability of RFQ following intra-articular (IA) administration in Beagle dogs. Methods Forty Beagle dogs (20/sex) were randomly assigned to 4 groups (5/sex/group) to receive 0, 1, 2.5, and 5 mg/kg/day RFQ in 5% (w/v) glucose once daily for 14 days by IA administration into the right knee joint. All the dogs had a 14-day recovery period to assess the reversibility, persistence, or delayed occurrence of adverse effects. Blood and synovial fluid samples were collected and concentrations of RFQ in each matrix were determined by liquid chromatography tandem mass spectrometry. Results No test article-related adverse effects in body weight, food consumption, temperature, clinical pathology, or organ weight were observed in any of the study groups. In 2.5 and 5 mg/kg/day groups, lameness, swelling and ulceration of right knee joint during treatment were observed. The 5 mg/kg group dosing was terminated prematurely due to marked arthritis on right knee joint. The no observed adverse effect level (NOAEL) was 1 mg/kg/day. At this dose level the steady state of RFQ concentrations in synovial fluid was achieved in 4 days and maintained until Day 14 (Figure 1). The mean RFQ concentrations on Day 14 in synovial fluids for male and female dogs were 35,900 and 19,200 ng/mL, respectively, as compared to the plasma Cmax 411 and 303 ng/mL for male and female dogs, respectively. Plasma toxicokinetics (TK) analysis indicated no apparent sex differences in systemic exposure at any dose level. Conclusion The NOAEL of RFQ in dogs was 1 mg/kg/day via IA administration. The synovial fluid concentration at this dose level exceeded minimum biofilm bactericidal concentration inhibit 90% bacterial growth (MBBC90) levels for both S. aures and S. epidermidis. IA administration of RFQ is a promising option for the treatment of PJIs. Disclosures Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Qin Cheng, Master, TenNor Therapeutics (Suzhou) Ltd: Employee Weijian Ke, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee

Sedentary lifestyle induces oxidative stress and atrophy in rat skeletal muscle.

Abundant evidence indicates that skeletal muscle plays a key role in regulating metabolic homeostasis. Therefore, maintaining healthy skeletal muscles is essential to good health. While prolonged muscle inactivity is known to cause oxidative stress and muscle loss, it remains unclear whether a shift from an active to a sedentary lifestyle induces similar effects. This study tested the hypothesis that transitioning to a sedentary lifestyle rapidly leads to oxidative stress and muscle loss in the load-bearing soleus muscle. Adult Wistar rats were randomly divided into control (CON; n=8) and sedentary (SED; n=8) groups. During a 7-day experimental period, CON rats were housed in standard cages allowing free movement, while SED rats were confined to smaller cages promoting sedentary behaviour. Soleus muscles were analysed for antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX)), as well as two oxidative stress biomarkers (advanced protein oxidation products (AOPPs) and 4-hydroxynonenal (4-HNE)). Sedentary behaviour caused a 17.2% reduction in the soleus-to-body weight ratio (P<0.001). Moreover, the activities of SOD, CAT and GPX were significantly lower in the soleus muscle of SED animals (P<0.05), while AOPPs and 4-HNE levels were higher (P<0.001 and P<0.05) compared to CON animals. These findings provide the first evidence that transitioning from an active to a sedentary lifestyle leads to the rapid onset of oxidative stress and atrophy in the soleus muscle. Importantly, the results suggest that impaired antioxidant defences contribute to sedentary behaviour-induced oxidative stress in load-bearing muscles.

P-2341. Was Viral Interference Responsible for the Unusual 2021-22 Influenza Season?

Abstract Background Viral interference is a short-term, non-specific immunity that limits infection by a second virus when a person has been infected by a first virus. Epidemiological and biological data supports the existence of viral interference, most likely caused by interferon production in response to an infection. The 2021-22 influenza season in the US displayed a highly unusual pattern in which a single influenza variant displaying a bimodal pattern, with a fall rise in transmission followed by a winter decrease and subsequent increase. The addition of a refractory period to a simulation of co-circulation of an Omicron-variant COVID-19 like virus and an H3N2-like influenza virus produced similar transmission dynamics to that observed in the 2021-22 influenza season.Figure 1. Covid-19 Omicron variant and influenza cases in the US population and in the simulation.A: Reported Covid-19 Omicron variant and influenza cases in US in the 2021-22 season. B: Simulated COVID-19 and influenza cases with and without refractory period with varied prior immunity to COVID-19. Left Y-axis, influenza cases; right Y-axis, Covid-19 cases. Methods We used the Agent-based modeling platform FRED (Framework for Reproducing Epidemiological Dynamics), with inclusion of a model of Omicron-variant COVID-19 like virus and an H3N2-like influenza virus. Results In a simulation including a 7-day refractory period, the introduction of an Omicron-like variant in December of the season after influenza transmission was already widespread caused influenza transmission to subside while the Omicron-like variant was circulating at high rates. Influenza still circulated at lower levels and rebounded after the Omicron-like variant surge decreased since there was no cross-immunity between the 2 viruses and a large pool of influenza susceptible agents remained. The epidemic curve from this simulation resembled in shape the epidemic curve of H3N2 influenza in 2021-22 (Figure). This effect was not present in similar simulations without a refractory period and was similar over the values of prior population immunity included in the simulation set. Conclusion Viral interference caused by widespread COVID-19 Omicron variant transmission is a plausible explanation for the unusual influenza infection pattern seen in the 2021-22 season. It is likely that viral interference is often influential in the interactions of a number of respiratory pathogens and should therefore be included in simulations that include multiple co-circulating respiratory pathogens. Disclosures All Authors: No reported disclosures

P-682. The Risk of Cardiorespiratory Events for up to 180 days Following Respiratory Syncytial Virus (RSV) Infection Hospitalization: A Self-controlled Case Series Analysis

Abstract Background Beyond the burden of acute respiratory infection, RSV can cause cardiorespiratory disease exacerbations and trigger cardiovascular events in adults. Information on these associations is limited, particularly following the acute illness phase. We evaluated the risk of common cardiorespiratory events during and following RSV hospitalization in adults. Methods We conducted a self-controlled case series analysis using data from administrative claims and electronic health records from Optum’s de-identified Market Clarity database. Adults (≥18 years) with 6 months of baseline continuous enrollment and an RSV-related hospitalization (RSV diagnosis or RSV+ test in the inpatient setting) from 01Jan17–30Jun23 (observation period) were included. Patients with the first admission for chronic obstructive pulmonary disease exacerbations (COPD-E), myocardial infarction (MI), stroke, congestive heart failure exacerbations (CHF-E), and arrhythmias during this period were identified using diagnosis codes. The risk period was defined as 0–180 days after RSV infection, including subintervals of risk periods and pre-risk periods. The remaining time outside of the 180-day risk period and the 21-day pre-risk period during the observation period formed the control period. Conditional Poisson regression adjusting for time-varying age (5-year intervals) was performed to determine the incidence rate ratio (IRR) for each event following RSV infection. Results Among 8,181 adults hospitalized with RSV, 3,494 had COPD-E 1,601 MI, 1,175 stoke, 2,879 CHF-E, and 4,083 arrhythmias during the entire observation period. The IRR during days 1–21 compared to the control period following RSV infection was 16.0 (95% CI 13.9, 18.4), 8.8 (95% CI 7.1,11.0), 9.9 (95% CI 7.9, 12.4), 9.5 (95% CI 8.1, 11.2), and 12.8 (95% CI 11.3, 14.4), respectively, for COPD-E, MI, stroke, CHF-E, and arrhythmias. IRRs were elevated for all outcomes for 42 days and attenuated over time but remained elevated for up to 180 days for stroke and CHF-E. Conclusion There is an increased risk of acute cardiorespiratory events and exacerbations following RSV infection. These cardiorespiratory events should be considered as part of the burden of RSV infection when evaluating RSV preventive interventions. Disclosures Caihua Liang, MD, PhD, Pfizer: Stocks/Bonds (Private Company) Jennifer Judy, MS, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Negar Aliabadi, MD, MS, Pfizer Inc: employment|Pfizer Inc: Stocks/Bonds (Public Company) Reiko Sato, PhD, Pfizer Inc: employee|Pfizer Inc: Stocks/Bonds (Private Company) Erica Chilson, PharmD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds (Public Company) Xin Zhao, MS, Pfizer: Xin Zhao is an employee of Genesis Research Group which received compensation from Pfizer for conducting this study. Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Elizabeth Begier, MD, M.P.H., Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds (Private Company)

P-718. Getting to the Heart of Respiratory Syncytial Virus Disease Burden

Abstract Background There is increasing evidence that viral respiratory infections are associated with acute cardiovascular events. The majority of studies to date involve SARS-CoV-2 and influenza, whereas data for RSV are limited. Methods We performed an analysis of electronic records from patients with documented RSV hospitalization from a prospective incidence study conducted in Rochester, NY from 2017-2020. Clinical, demographic, medical history, and cardiac risk factor data were collected. Outpatient and hospital encounters were reviewed for cardiovascular events (CVE) 6 months before RSV infection and during “high-risk” and “late-risk” periods, 28 days and 1-5 months, respectively, after RSV for a total of one year of observation. Events of interest were myocardial infarction (MI), new or exacerbation of congestive heart failure (CHF), new atrial fibrillation (Afib) or with rapid ventricular response (RVR), arrhythmias, stroke, and others. Peak cardiac biomarkers (troponin and brain natriuretic peptide [BNP]) were collected. Chart review was conducted by 2 physicians independently and consensus achieved. Cardiac Risk Factors Cardiac Risk factors: HTN, hyperlipidemia, diabetes mellitus, family history of CAD in a first-degree relative, current smoking, BMI&amp;gt;30. Results RSV was diagnosed in 471 hospitalized adults. The median age was 69 years, 59% were female and nearly all had underlying medical conditions (92%) with hypertension and diabetes mellitus most common (Figure 1). Cardiac risk factors are summarized in Table 1. During a high-risk period, 167 patients had 270 CVE (89% within 1 week) and 29 patients died. The most common complications were new or exacerbated CHF (27.5%) and Afib with RVR (12.9%), Figure 2. The rates of CVE during pre-RSV, high-risk, and late-risk periods were 0.34, 6.9, and 0.45 per person-years, respectively. Notably, the Incidence Rate Ratio (IRR) of CVE during the high-risk period was 19.9 (CI 15.5-25.9) compared to the pre-RSV period, p&amp;lt; 0.0001. IRR of CVE during late-risk period was 1.55 (CI 1.1-2.1) compared to pre-RSV period, p=0.003. Increased troponins occurred in 34% and high BNP in 62% of those tested. Total number of Cardiovascular Events (CE) was 270 events in 167 patients. CHF – congestive heart failure new onset or decompensation requiring intervention; STEMI/NSTEMI – ST-Elevation Myocardial Infarction, Non-ST Elevation Myocardial Infarction; Afib/Aflutter – Atrial Fibrillation or Atrial Flutter new onset or with rapid ventricular response requiring intervention; SVT – supraventricular tachycardia requiring intervention; VT/NSVT/PEA – Ventricular Tachycardia, Non-sustained Ventricular Tachycardia, Pulseless Electrical Activity; PE/DVT – Pulmonary embolism, Deep Venous Thrombosis; CVA – Cerebrovascular Accident. Conclusion RSV infection is associated with decompensation of chronic cardiac conditions as well as new CVEs with effects persisting past a traditional 28-day risk period. Prevented CVEs should be assessed in upcoming adult RSV vaccine effectiveness studies. Disclosures Edward E. Walsh, MD, Enanta: Advisor/Consultant|Enanta: Honoraria|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Angela R. Branche, MD, Cyanvac: Grant/Research Support|GSK: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Grant/Research Support|Moderna: Honoraria|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi: Honoraria|VaxCo: Grant/Research Support Ann R. Falsey, MD, ADMA: Board Member|BioFire Diagnostics: Grant/Research Support|CyanVac: Grant/Research Support|GSK: Advisor/Consultant|GSK: Travel support|Janssen: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Travel support|VaxCo: Grant/Research Support

Safety of Mechanically Fibrillated Cellulose Nanofibers (CNFs) by Inhalation Exposure Based on TG412

An investigation into the acute toxicity of mechanically fibrillated cellulose nanofibers (fib-CNFs), with a fiber length ranging from 500 to 600 nm, was conducted in accordance with the OECD TG412 guidelines. In this study, rats were exposed to fib-CNFs via nasal inhalation for 6 h daily over a 28-day period. The highest exposure concentration was set at 35 mg/m3, with intermediate and low concentrations at 7.0 mg/m3 and 1.5 mg/m3, respectively. No significant differences were observed in body weight, hematological parameters, or biochemical profiles between the fib-CNF-exposed groups and the control group. However, the histopathological examination of lung tissue revealed elevated macrophage counts in both the alveolar spaces and lymph nodes, accompanied by a significant increase in lung weight. The most severe effects were observed in the high-concentration group, while the low-concentration group exhibited only mild inflammatory changes. Based on these findings, the no observable adverse effect level (NOAEL) for the acute toxicity of fib-CNFs is estimated to be below 1.5 mg/m3.

Effect of one-week New Zealand blackcurrant extract on rowing performance and cognitive function in National team male rowers

ABSTRACT This research investigated the impact of New Zealand blackcurrant (NZBC) on 2000-meter rowing ergometer performance and cognitive abilities. Nine trained male rowers from Iran’s national team participated in a double-blind, placebo-controlled crossover study, undergoing three sessions with NZBC (600 mg∙day−1), placebo (PL), and control (CL) treatments over seven days, followed by a 14-day washout period. Participants completed a 2000-meter ergometer test provided self-reported ratings of perceived exertion (RPE) and completed a cognitive function assessment five minutes following the rowing exercise. Findings indicated no significant ergogenic benefits from NZBC supplementation (420 ± 12 s) compared to PL (424 ± 15 s) and CL (423 ± 14 s), despite showing a minimal effect size (Cohen’s d = 0.23). Six subjects had negligible enhancements in performance. No changes were seen in cognitive function or RPE (p > 0.05). A seven-day regimen of NZBC did not enhance rowing performance, cognitive function, or RPE.

Lactiplantibacillus plantarum improves the growth performance and meat quality of broilers by regulating the cecal microbiota and metabolites

Gut microbiota can digest and ferment feed into metabolites to influence the meat quality. Probiotics are used to regulate the gut microbiota. In this study, a total of 360 broilers were assigned to 4 treatments (10 broilers per cage): control (Con), low dose of Lactiplantibacillus plantarum HW1 (Lp_L), medium dose of Lp (Lp_M) and high dose of Lp (Lp_H) for a 42-day experimental period. Results showed that the Lp treatments improved the growth performance, carcass traits, breast meat quality, and also influenced the fatty acids composition, including the decrease of n-6PUFA/n-3PUFA, and the increase of C18:3n3, ∑n-3PUFA and PUFA/SFA. The lipid metabolism-related gene expressions in the liver showed that Lp treatments increased the expression of AMPK, CPT-1α, PPARα, ATGL and also decreased the expression of PPARγ, SREBP-1c, ACC, FAS, LPL, and SCD. Moreover, the abundances of gut microbiota, such as Synergistaceae and Synergistes were influenced by the Lp treatments. Functional prediction of the gut microbiota indicated that pathways, including pancreatic secretion and spliceosome were enriched by the Lp treatments. Untargeted metabolomics revealed that the Lp treatments altered the content of metabolites, such as 6-ketomyristic acid and indole-3-acetamide. These metabolites were enriched in pathways including fatty acid metabolism. Correlation analyses revealed potential interactions between growth performance and meat quality, as well as gut microbiota (Synergistes, etc.) and metabolites (6-ketomyristic acid, etc.). Overall, our data show that the Lp treatments significantly improved the growth performance, carcass traits and meat quality of broilers by regulating fatty acids, gut microbiota and metabolites.

Advanced Platelet-Rich Fibrin (A-PRF) as Antibiotics Delivery System: In-Vitro Proof-of-Concept Study

Autologous blood centrifugation produces various forms of platelet concentrates widely used in tissue regenerative therapies due to their high concentrations of growth factors and abundance of autologous cells. Advanced Platelet-Rich Fibrin (A-PRF), introduced as a low-speed centrifugation product, contains an even higher concentration of growth factors, a greater number of cells, and a looser fibrin clot structure compared to previous Leukocyte and Platelet-Rich Fibrin (L-PRF). This study aims to assess the potential of A-PRF as a local delivery system for antibiotics. Different concentrations (0.5 mg/mL, 0.25 mg/mL, and 0.125 mg/mL) of injectable amoxicillin (AMX) and metronidazole (MTZ) were preliminarily tested for their impact on A-PRF clot formation, with 0.5 mg/mL selected for subsequent experiments. Blood samples from healthy volunteers were supplemented with antibiotics and centrifuged to form clots. Antibiotic-enriched A-PRF clots were immersed in phosphate-buffered saline (1x PBS) and analyzed at 24 h, 72 h, 7 days, and 14 days. AMX showed a consistent release (mean: 19.9 ± 4.8 ng/mL at 24 h) over 14 days, while MTZ demonstrated greater variability (mean: 12.8 ± 4.5 ng/mL at 24 h). AMX release remained constant over the 14-day period, with no significant variations among patients. In contrast, MTZ displayed a progressively lower release over time. Microbiological analysis revealed bacterial growth inhibition zones for Fusobacterium nucleatum (AMX: 23 mm, MTZ: 28 mm) and Prevotella intermedia (AMX: 34 mm, MTZ: 30 mm) at 24 h. These findings suggest that A-PRF can act as an effective local antibiotic delivery system, maintaining sustained antimicrobial activity and potentially reducing the need for systemic antibiotics.

Alleviating symptoms of paediatric acute rhinosinusitis and acute otitis media with otorrhea using nasal-spraying Bacillus probiotics: a randomized controlled trial

Acute rhinosinusitis (ARS) in children may be accompanied by acute otitis media (AOM) which is often associated with bacterial co-infections. These conditions are among the primary reasons that children visit hospitals and require antibiotic treatment. This study evaluated the efficacy of the nasal-spraying probiotics (LiveSpo Navax containing 5 billion Bacillus subtilis and B. clausii spores/5 mL) as a supportive treatment for dual ARS and AOM with otorrhea in a randomized, single-blind, controlled clinical trial. Eighty-two patients (41 per group), aged 1 month to 12 years, received standard care along with nasal spraying of either physiological saline (Control group) or LiveSpo Navax (Navax group), administered three times daily over a 7-day follow-up period. A total of sixty-one patients (30–31 per group) completed the trial. The Navax group experienced 68.00% and 96.77% reductions in nasal congestion (by day 3) and rhinorrhea (by day 7), respectively, which were 2.04 and 1.94-fold higher than the Control group, with odds ratios (OR) of 4.31 and 30.00 (p < 0.05). Endoscopic results indicated 8% and 11% higher reductions in nasal mucopurulent discharge and tympanic membrane hyperemia in the Navax group compared to the Control group. By day 3, compared to day 0, the Navax group exhibited > 1200-fold reduction in Streptococcus pneumoniae and ≥ 4-fold reduction in Haemophilus influenzae concentrations (p < 0.05) in both nasopharyngeal and middle ear fluid samples, whereas the Control group showed no significant reductions. Navax treatment reduced IL-6 by 1.35- to 1.74-fold and TNF-α by 1.17- to 1.45-fold, more effectively than the Control group (p < 0.05). These results suggest that nasal-spray Bacillus spore probiotics, with their ability to reduce bacterial load and modulate immune responses, provide a cost-effective and safe solution for alleviating symptoms of both ARS and AOM in children.Trial registration: ClinicalTrials.gov, Identifier NCT05804123 on April 7, 2023.

Effect of enhanced recovery after surgery on older patients undergoing transvaginal pelvic floor reconstruction surgery: a randomised controlled trial

BackgroundProspective trial evidence is lacking regarding the application of enhanced recovery after surgery (ERAS) in transvaginal pelvic floor reconstruction surgery among older patients. Our study aimed to investigate whether implementing the ERAS protocol could enhance post-operative recovery in this patient population.MethodsOlder patients undergoing elective transvaginal pelvic floor reconstruction surgery were randomly assigned to either the ERAS group or the conventional group. The primary outcome was post-operative length of stay (LOS). The secondary outcomes encompassed other post-operative recovery metrics, post-operative pain within 30 days, the occurrence of complications, the peri-operative blood test and cognitive function.ResultsA cohort of 100 patients was enrolled. Implementation of the ERAS protocol significantly reduced the duration of post-operative LOS (74.00 (69.00, 96.00) vs. 65.00 (59.00, 78.25) h, P < 0.01). Additionally, the ERAS protocol significantly reduced the duration of the first oral intake post-operatively (5.00 (2.50, 7.00) vs. 3.00 (2.00, 4.00) h, P = 0.01), and reduced rest and movement-related pain within 48 h post-operatively, effects that persisted through the 7-day follow-up period. It also shortened the duration of post-operative laryngeal mask airway support and promoted opioid-sparing. Moreover, the incidence and severity of post-operative nausea and vomiting (PONV) were significantly lower in the ERAS group compared to the conventional group at 12 h post-operatively.ConclusionsImplementation of the ERAS protocol can expedite post-operative recovery in older patients undergoing transvaginal pelvic floor reconstruction surgery, achieve opioid-sparing, alleviate pain post-operatively, and decrease the incidence of complications.Trial registrationThis study was retrospectively registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2400084608). The date of first registration was 21/05/2024.

Autogenous Tooth Transplantation of Canines—A Prospective Clinical Study on the Influence of Adjunctive Antibiosis and Patient-Related Risk Factors during Initial Healing

Abstract: Objectives: This prospective clinical study investigated the efficacy of adjunctive antibiotic therapy (doxycycline) and the patient’s risk factors during initial healing of autogenous canine tooth transplantations. Methods: Sixty-seven patients (ranging from 11 to 37 years of age) treated with tooth transplantations were allocated to three parallel groups based on the tooth’s intraoperative extraoral storage time (EST 0–3, 4–6, and 7–15 min) receiving different antibiotic regimens: (1) no antibiotics; (2) intraoperative intravenous (i.v.) single-shot antibiotics; and (3) intraoperative i.v. single-shot plus postoperative oral antibiotics for five days. Initial healing was rated according to pain intensity and clinical signs of pathology over a 21-day period. The influence of the following parameters was investigated using RStudio (linear regression and partial eta squared statistics): group, sex, age, nicotine abuse, tooth apex condition, preoperative ankylosis, displacement severity, jaw location, the number of simultaneous transplantations and other interventions, preoperative orthodontic extrusion, EST, and intraoperative complications. Results: No significant influence for sex (43 females, 24 males), tooth apex condition (19 open, 48 closed), displacement severity, jaw location (51 upper, 16 lower jaw), EST (mean 4.99 min), intraoperative complications (n = 13), or antibiotic regimen on pathology signs or pain intensity were found. Six patients reported medication side effects. Preoperative ankylosis (n = 15) and unsuccessful orthodontic extrusion (n = 16) increased postoperative pain (p = 0.020, ηP2 = 0.08; p = 0.035, ηP2 = 0.07). Multiple transplants (n = 14) and interventions in multiple regions (n = 27) affected pain and pathology (p = 0.002, ηP2 = 0.14; p = 0.001, ηP2 = 0.17). Increased age and nicotine abuse (n = 6) were associated with increased pathology signs (p = 0.024, ηP2 = 0.08; p = 0.029, ηP2 = 0.07). Conclusions: The results suggest that personalized rather than routine antibiotic therapy might be sufficient for initial healing in canine tooth transplantation. Deteriorating factors include preoperative ankylosis, orthodontic extrusion, an increased number of surgical sites, age, and nicotine abuse. Clinical Significance: Routine antibiotic prevention regimes may not be mandatory for initial healing in autogenous tooth transplantation, but a nuanced antibiotic strategy tailored to each patient’s specific risk factors, which is in line with the principle of antibiotic stewardship, is needed.

A Seasonal Fresh Tea Yield Estimation Method with Machine Learning Algorithms at Field Scale Integrating UAV RGB and Sentinel-2 Imagery

Traditional methods for estimating tea yield mainly rely on manual sampling surveys and empirical estimation, which are labor-intensive and time-consuming. Accurately estimating fresh tea production in different seasons has become a challenging task. It is possible to estimate the seasonal yield of tea at the field scale by using the spatial resolution of 10 m, 5-day revisit period and rich spectral information of Sentinel-2 imagery. This study integrated Sentinel-2 images and uncrewed aerial vehicle (UAV) RGB imagery to develop six regression models at the field scale, which were employed for the estimation of seasonal and annual fresh tea yields of the Yunlong Tea Cooperatives in Yixiang Town, Pu’er City, China. Firstly, we gathered fresh tea production data from 133 farmers in the cooperative over the past five years and obtained UAV RGB and Sentinel-2 imagery. Secondly, 23 spectral features were extracted from Sentinel-2 images. Based on the UAV images, the parcel of each farmer was positioned and three topographic features of slope, aspect, and elevation were extracted. Subsequently, these 26 features were screened using the random forest algorithm and Pearson correlation analysis. Thirdly, we applied six different regression algorithms to establish fresh tea yield models for each season and evaluated their estimation accuracy. The results showed that random forest regression models were the optimal choice for estimating spring and summer yields, with the spring model achieving an R2 value of 0.45, an RMSE of 40.38 kg/acre, and an rRMSE of 40.79%. Similarly, the summer model achieved an R2 value of 0.5, an RMSE of 78.46 kg/acre, and an rRMSE of 39.81%. For autumn and annual yield estimation, voting regression models demonstrated superior performance, with the autumn model achieving an R2 value of 0.42, an RMSE of 70.6 kg/acre, and an rRMSE of 39.77%, and the annual model attained an R2 value of 0.47, an RMSE of 168.7 kg/acre, and an rRMSE of 34.62%. This study provides a promising new method for estimating fresh tea yield in different seasons at the field scale.

Correlates of Inaccuracy in Reporting of Energy Intake Among Persons with Multiple Sclerosis

Background/Objectives: Persons with multiple sclerosis (MS) are interested in diet as a second-line approach for disease management. This study examined potential variables that correlate with inaccuracy of self-reported energy intake (EI) in adults with MS. Methods: Twenty-eight participants completed two assessment appointments within a 14-day period that included a standard doubly labeled water (DLW) protocol for estimating total energy expenditure (TEE). The participants reported their EI using the Automated Self-Administered 24 h (ASA24) Dietary Assessment Tool. The primary variables of interest for explaining the discrepancy between TEE and ASA24 EI (i.e., inaccuracy) included cognition (processing speed, visuospatial memory, and verbal memory), hydration status (total body water), and device-measured physical activity. Pearson’s correlations assessed the association between absolute and percent inaccuracy in reporting of EI with outcomes of interest, followed by linear regression analyses for identifying independent correlates. Results: California Verbal Learning Test—Second Edition (CVLT-II) z-scores and light physical activity (LPA) were significantly associated with mean absolute difference in EI (r = –0.53 and r = 0.46, respectively). CVLT-II z-scores and LPA were the only variables significantly associated with mean percent difference in EI (r = –0.48 and r = 0.42, respectively). The regression analyses indicated that both CVLT-II and LPA significantly explained variance in mean absolute difference in EI, and only CVLT-II explained variance for percent difference in EI. Conclusions: The results from this study indicate that verbal learning and memory and LPA are associated with inaccuracy of self-reported EI in adults with MS. This may guide timely research identifying appropriate protocols for assessment of diet in MS.

Synergistic Effects of Cyanus depressus and Schizochytrium sp. Extracts on Growth Indices and The Expression Levels of Antioxidant and Immunity-Related Genes in Common Carp (Cyprinus carpio)

This study aimed to assess the combined effects of Cyanus depressus and Schizochytrium sp. extracts on growth indices and the expression of genes linked to antioxidant activity and immunity in carp (Cyprinus carpio). Fish, averaging 3.71 ± 0.16 g in weight, were assigned to three dietary groups over a 60-day period: a control group (0 g/kg extract) and two test groups receiving extract mixtures at 0.5 g/kg (CS05) and 1 g/kg (CS1). The supplemented groups, particularly those at 0.5 and 1 g/kg, showed significant increases in final body weight, weight gain, and specific growth rate. The highest superoxide dismutase (SOD) and catalase (CAT) gene expression levels were seen in fish on the 0.5 g/kg CS-supplemented diet, and CS-fed groups displayed the greatest expression of the immune-related gene interleukin-1 beta (IL-1β) relative to the control. Collectively, these findings indicate that Cyanus depressus and Schizochytrium sp. extracts, especially at a dosage of 0.5 g/kg, have promising potential as dietary supplements for enhancing the physiological health and growth of carp.

Cholecalciferol and Ergocalciferol Replacement in Critically Injured Burn Patients: An Observational Cohort Study.

Vitamin D deficiency appears to be more prevalent than previously considered in the adult critically ill population, specifically burn-injured patients. No definitive regimen has been shown to restore vitamin D (25(OH)D) levels more effectively to therapeutic levels in the burn-injured population. The purpose of this study was to investigate the effects of either ergocalciferol (D2, 50 000 IU weekly) or cholecalciferol (D3, 6000 IU daily) in adults with burns ≥10% TBSA. This retrospective, observational study (2020-2022) included patients with vitamin D insufficiency (<30 ng/mL) who received replacement and monitoring with weekly vitamin D levels. Patients on dialysis or those with a hospital length of stay less than 2 weeks were excluded. Forty-five patients treated with ergocalciferol and 99 patients with cholecalciferol were included in the study. Patients treated with cholecalciferol were more likely to achieve 25(OH)D levels greater than 30 ng/mL compared to ergocalciferol over a 42-day period (HR 23.56, [95% CI, 12.57-44.16], P < .0001). A higher proportion of patients in the cholecalciferol group achieved vitamin D greater than 20 ng/mL (HR 6.37, [95% CI, 4.20-9.66], P < .0001). The adjusted hazard ratios (D3 vs D2) for achieving 25(OH)D levels > 30 ng/mL and > 20 ng/mL were and 23.94 (95% CI 5.09-427.6, P = .0019) and 7.32 (95% CI, 3.83-15.52, P < .0001) respectively, after controlling for TBSA and initial 25(OH)D. Cholecalciferol appears to be a more effective agent than ergocalciferol for correcting vitamin D deficiency and insufficiency in patients with burn injuries.