A Comprehensive Review on Phage Therapy and Phage-Based Drug Development.

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.

Ecotoxicological assessment of sanitary sewer overflows and rainfall dynamics offers insights into conditions for potential adverse ecological outcomes.

Sewer overflows are an environmental concern due to their potential to introduce contaminants that can adversely affect downstream aquatic ecosystems. As these overflows can occur during rainfall events, the influence of rainwater ingress from inflow and infiltration on raw untreated wastewater (influent) within the sewer is a critical factor influencing the dilution and toxicity of the contaminants. The Vineyard sewer carrier in the greater city of Sydney, Australia, was selected for an ecotoxicological investigation of a sanitary (separate from stormwater) sewerage system and a wet-weather overflow (WWO). Three influent samples were collected representing dry-weather (DW), intermediate wet-weather (IWW) and wet-weather (WW). In addition, a receiving water sample was also collected downstream in Vineyard Creek (WW-DS) coinciding with a WWO. We employed direct toxicity assessment (DTA) and toxicity identification evaluation (TIE) approaches to gain comprehensive insights into the nature and magnitude of the impact on influent from rainwater ingress into the sewer. Three standard ecotoxicological model species, a microalga, Chlorella vulgaris, the water flea, Ceriodaphnia dubia and the midge larva, Chironomus tepperi were used for both acute and chronic tests. The study revealed variable toxicity responses, with the sample of influent collected in wet-weather displaying lower toxicity compared to the dry-weather sample of influent. Ammonia, and metals, were identified in dry weather as contributors to the observed toxicity, however, this risk was alleviated through rainwater ingress in wet-weather with further dilution within the receiving water. Based on toxicity data, dilutions of influent to minimise effects on C. vulgaris and C. dubia ranged from 1 in 12 in DW to 1 in 2.8 in WW, and further diminished in the receiving water to 1 in 1.8. The successful application of ecotoxicological approaches enabled the assessment of cumulative effects of contaminants in influent, offering valuable insights into the sanitary sewer system under rainwater ingress.

Oral toxicity evaluation of Bacillus clausii M31 isolated from the children's feces in the northern province of Vietnam.

This study investigated the acute and repeated 28-day dose toxicity profiles of Bacillus clausii M31, isolated from children's feces, in Swiss rats and New Zealand rabbits. To investigate acute toxicity, rats were given varied doses of B. clausii M31 (1 × 1011 CFU/mL, 3 × 1011 CFU/mL, and 5 × 1011 CFU/mL) orally once daily for 14 days, in accordance with OECD recommendations No. 423. To evaluate toxicity, rabbits were given either a low dosage (1 × 1011 CFU/mL) or a high dose (5 × 1011 CFU/mL) during a 28-day period using the OECD Test Guideline 407 protocol. Neither death nor significant abnormalities were observed in the rats during the experiment. The microscopic examination of key organs revealed no substantial changes in organ morphology. Furthermore, analyses of serum biochemistry and hematological parameters did not reveal any treatment-associated variations. In sum, these findings suggest that the oral intake of B. clausii M31 at concentrations up to 5 × 1011 CFU/mL for 28 days poses no discernible risks.

Elevated body mass index is not significantly associated with reduced influenza vaccine effectiveness.

Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011-12 through 2017-18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m2), overweight (25-29 kg/m2), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1-adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16-31, 46-54, and 44-57%, and in children from 29-34, 57-65, and 50-55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness.

Phagemid-based capsid system for CRISPR-Cas13a antimicrobials targeting methicillin-resistant Staphylococcus aureus.

In response to the escalating antibiotic resistance in multidrug-resistant pathogens, we propose an innovative phagemid-based capsid system to generate CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) for targeted therapy against multidrug-resistant Staphylococcus aureus. Our optimized phagemid system maximizes AB-capsid yield and purity, showing a positive correlation with phagemid copy number. Notably, an 8.65-fold increase in copy number results in a 2.54-fold rise in AB-capsid generation. Phagemids carrying terL-terS-rinA-rinB (prophage-encoded packaging site genes) consistently exhibit high packaging efficiency, and the generation of AB-capsids using lysogenized hosts with terL-terS deletion resulted in comparatively lower level of wild-type phage contamination, with minimal compromise on AB-capsid yield. These generated AB-capsids selectively eliminate S. aureus strains carrying the target gene while sparing non-target strains. In conclusion, our phagemid-based capsid system stands as a promising avenue for developing sequence-specific bactericidal agents, offering a streamlined approach to combat antibiotic-resistant pathogens within the constraints of efficient production and targeted efficacy.

Estimating the generation time for influenza transmission using household data in the United States.

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially post the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days completing daily symptom diaries and collecting nasal swabs, which were tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission before symptomatic onset, infectious period, and latent period. We estimated a mean intrinsic generation time of 3.2 (95% credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95% CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variation in incubation periods. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts.

Real-world Efficacy and Safety of Low-Dose Abiraterone With Food and Standard-Dose Abiraterone in De Novo Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Analysis.

BACKGROUND: The standard treatment for de novo metastatic hormone-sensitive prostate cancer (mHSPC) involves androgen deprivation therapy (ADT) combined with next-generation hormonal agents and/or docetaxel. While the standard dose (STD) of abiraterone is 1,000 mg administered while fasting, recent evidence suggests that a low dose (LOW) of 250 mg taken with a low-fat meal may achieve comparable pharmacokinetic outcomes. OBJECTIVES: This study aimed to evaluate the failure-free survival (FFS) and safety of LOW and STD in de novo high-risk mHSPC patients. MATERIALS AND METHODS: We conducted a retrospective analysis of males with de novo high-risk mHSPC treated with ADT plus abiraterone (250 mg with a low-fat meal or 1000 mg fasting) at the Vietnam National Cancer Hospital from January 2019 to May 2024. The primary endpoint was FFS, assessed using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: The study included 183 patients, with 91 in the LOW group and 92 in the STD group. The rates of patients who achieved undetectable PSA (PSA < 0.2 ng/ml) were 52.7% in the LOW group and 47.8% in the STD group. The median time to undetectable PSA was 6.9 months in the LOW group and 6.4 months in the STD group. The median overall FFS was 28.1 months (95% CI: 21.1 to 35.0) in the LOW group and 25.4 months (95% CI: 15.5 to 35.3) in the STD group (P = .286). Multivariate analysis indicated that visceral metastases and detectable PSA (PSA ≥ 0.2 ng/ml) were significant negative predictors of FFS in both groups. The incidence of grade 3 and grade 4 adverse events was similar between the LOW group and the STD group. CONCLUSIONS: The LOW group and STD group showed effectiveness and safety in de novo high-risk mHSPC. The use of low-dose abiraterone in de novo mHSPC can significantly reduce treatment costs.

Influenza virus shedding and symptoms: Dynamics and implications from a multiseason household transmission study.

Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.

Optimization of donor cell production for somatic cell nuclear transfer in the critically endangered Vietnamese I pig.

We aimed to establish efficient donor cells to produce piglets by somatic cell nuclear transfer (SCNT) of the endangered Vietnamese I pig. In Experiment 1, we assessed the effects of cell passages on the in vitro development of SCNT embryos. Cells with five and six passages showed significantly cleaved and blastocyst formation rates (86.72 and 86.64; 35.68 and 35.51, respectively, P < 0.05). The highest average total cell number per blastocyst was observed in groups of cells with five and six passages (50.45 and 50.18, respectively). Experiment 2 was performed to assess the sex of donor cells on the subsequent development of SCNT embryos. There was no significant difference in the cleaved and blastocyst formation rates, and the average total cell between female and male groups (86.51 % vs 86.94 % and 35.31 % vs 35.08 %, 50.29 % vs 50.67 %, respectively, P > 0.05). Experiment 3 was performed to assess the effect of cell lines on the development of SCNT embryos. Our results showed no significant difference in the success rate of fibroblast nuclear transfer into recipient oocytes, the cleaved and blastocyst formation rates, and the average total cell number per blastocyst among the cell lines 6004, 9154, 9155, 9156 and 9157 (P > 0.05). Experiment 4 was performed to assess the ability of SCNT embryos to induce pregnancy and to develop term. SCNT embryos were produced from I fibroblast cells established based on the results of Experiments 1, 2 and 3. Transfer of blastocyst stage embryos into 19 recipients (100-120 embryos in each) resulted in 14 pregnancies, in which 8 pregnant females terminated on Day 22-42 and 6 others produced 20 cloned piglets from donor cells of a female pig but 5 piglets died before birth and 15 healthy cloned piglets. However, 3 out of 15 healthy piglets died of unknown causes within 24h of birth and 3 out of 15 healthy piglets died at 3-5 days of age due to diarrhoea, 9 out of 15 healthy piglets are now 3 months of age. Finally, we established a protocol for the donor cell production which enabled the production of the endangered I pig embryos by SCNT and maximized blastocyst production rate by more than 35 % and pregnant rate after the transfer of cloned I pig embryos to recipients at 73.68 % for the first time in Vietnam.

A Research Agenda to Improve Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Cardiovascular Disease: An Official American Thoracic Society Research Statement.

Background: Individuals with chronic obstructive pulmonary disease (COPD) are often at risk for or have comorbid cardiovascular disease and are likely to die of cardiovascular-related causes. Objectives: To prioritize a list of research topics related to the diagnosis and management of patients with COPD and comorbid cardiovascular diseases (heart failure, atherosclerotic vascular disease, and atrial fibrillation) by summarizing existing evidence and using consensus-based methods. Methods: A literature search was performed. References were reviewed by committee co-chairs. An international, multidisciplinary committee, including a patient advocate, met virtually to review evidence and identify research topics. A modified Delphi approach was used to prioritize topics in real time on the basis of their potential for advancing the field. Results: Gaps spanned the translational science spectrum from basic science to implementation: 1) disease mechanisms; 2) epidemiology; 3) subphenotyping; 4) diagnosis and management; 5) clinical trials; 6) care delivery; 7) medication access, adherence, and side effects; 8) risk factor mitigation; 9) cardiac and pulmonary rehabilitation; and 10) health equity. Seventeen experts participated, and quorum was achieved for all votes (>80%). Of 17 topics, ≥70% agreement was achieved for 12 topics after two rounds of voting. The range of summative Likert scores was -15 to 25. The highest priority was "Conduct pragmatic clinical trials with patient-centered outcomes that collect both pulmonary and cardiac data elements." Health equity was identified as an important topic that should be embedded within all research. Conclusions: We propose a prioritized research agenda with the purpose of stimulating high-impact research that will hopefully improve outcomes among people with COPD and cardiovascular disease.

Prevalence of depressive symptoms among urban school adolescents in Vietnam: The role of youth, family, and school relationships.

BACKGROUND: Adolescents frequently encounter a spectrum of psychiatric conditions, predominantly depressive and anxiety disorders, along with various behavioral disturbances. OBJECTIVE: This investigation aims to delineate the prevalence of depressive disorders among adolescents in urban Vietnam and to elucidate the interrelationships between familial and school-related dynamics and adolescent depression. MATERIALS AND METHODS: A cross-sectional survey was conducted in 2022, involving 507 students aged 15 to 17 from high schools in Hanoi, Vietnam. Reynolds Adolescent Depression Scale - Second Edition (RADS-2) was used to assess the presence of depressive symptoms. Social-demographic characteristics, adolescent-family and adolescent-school relationships, and academic environment characteristics of high school students were interviewed. Multivariate Tobit regression models were employed to discern contributory factors across four domains of RADS-2. RESULTS: Among the 507 adolescents, the mean scores on the RADS scale were 15.1 ± 4.2 for the dysphoric mood domain, 16.4 ± 4.0 for the anhedonia-negative domain, 13.1 ± 4.4 for the negative self-evaluation domain, and 12.4 ± 3.7 for the somatic complaints domain. The analysis indicated that adolescents with suboptimal parental relationships, absence of confidants, frequent parental conflicts, exposure to parental arguments, substantial exam-related stress, or overwhelming academic demands were more likely to exhibit elevated depressive symptoms. Conversely, adolescents who were satisfied with their friendships at school and received care, support from teachers or friends, and involved in school's extracurricular activities lower exhibited levels of depression. CONCLUSIONS: Findings reveal the significant impact of family and peer relationships, as well as academic stress, on the development of depressive symptoms. These significant results inform the design and development of future interventions aimed at mitigating depression risks among high school students, emphasizing the crucial roles of both educational institutions and family dynamics.

A pre-post evaluation of a digital intervention to improve psychosocial outcomes of caregivers of people living with cancer in Vietnam.

OBJECTIVES: To evaluate a co-designed intervention using digital resources "Vietnam Cancer Caring Coping" (V-CCC) on the health literacy, depression, and quality of life of caregivers supporting a cancer patient in oncology hospitals in Vietnam. METHODS: A pre-post quantitative evaluation with adult cancer caregivers across regional Oncology hospitals in Vietnam (Ho Chi Minh City, Da Nang, Can Tho, and Hue). Participants completed baseline and follow-up measures of health literacy (HLS-SF12) depression (PHQ-9) and Health-related Quality of Life (5Q-5D-5L). Participants accessed and reviewed V-CCC for a 2-week period. RESULTS: Two hundred and thirty-four caregivers completed pre and post-tests. Most participants were female (n = 143, 61%), married (n = 165, 70%), aged 18-44 (n = 155, 66%), lived rurally (n = 157, 67%). All health literacy scores of participants in post-intervention were significantly higher than that in pre-intervention across all domain's healthcare, disease prevention, and health promotion as well as the total score (p < 0.001). A significant reduction in the proportion of caregivers reporting PHQ-9 moderately severe/severe depression post-intervention was demonstrated (10.2 vs. 6.1%, respectively (p ≤ 0.001). No significant differences were observed pre and post-intervention across four 5Q-5D-5L health dimensions: mobility, self-care, usual activities, and pain/discomfort. Regarding anxiety/depression as measured by 5Q-5D-5L the proportion of participants who reported having moderate, severe, and extreme problems in pre- and post-intervention was statistically significant (32 vs. 24%), respectively (p = 0.0028). CONCLUSION: Co-designed digital resources can reduce health literacy inequities and improve psychological outcomes for cancer caregivers.

Effectiveness of a Smartphone-Based Stress Management Program for Depression in Hospital Nurses During COVID-19 in Vietnam and Thailand: 2-Arm Parallel-Group Randomized Controlled Trial.

BACKGROUND: During the COVID-19 pandemic, health care professionals experienced high levels of depression. However, extant research has not highlighted effective internet-based psychological interventions to improve the mental health in this population during the pandemic. It remains unclear whether self-guided, internet-based cognitive behavioral therapy (iCBT) programs are effective in improving the mental health of health care workers during the COVID-19 pandemic. OBJECTIVE: The aim of this study was to evaluate the effectiveness of a smartphone-based iCBT stress management program for reducing the depression experienced by nurses in Vietnam and Thailand. METHODS: From March to April 2022, a 2-arm, parallel-group randomized controlled trial was implemented. One arm offered a 7-week self-guided iCBT program, and the other offered treatment as usual as a control arm. Full-time nurses were recruited from 6 hospitals: 2 hospitals in Vietnam and 4 hospitals in Thailand. The primary outcome of this program was the severity of depression measured by the Depression Anxiety Stress Scale-21 items. Follow-up surveys were conducted to measure the change in depression severity at 3 months (July-August 2022) and at 6 months (October-November 2022) after baseline. Mixed modeling for repeated measures was used to test the effects of the intervention compared with the control for the follow-up. RESULTS: A total of 1203 nurses were included in this study: 602 in the intervention group and 601 in the control group. The follow-up rate at 3 and 6 months ranged from 85.7% (515/601) to 87.5% (527/602). The completion rate for the program was 68.1% (410/602). The group difference in depression was significant at the 3-month follow-up (coefficient=-0.92, 95% CI -1.66 to -0.18; P=.02) and nonsignificant at the 6-month follow-up (coefficient=-0.33, 95% CI -1.11 to 0.45; P=.41). The estimated effect sizes were -0.15 and -0.06 at the 3- and 6-month follow-ups, respectively. CONCLUSIONS: Our study shows that the smartphone-based iCBT program was effective in reducing depression at the 3-month follow-up among hospital nurses in Vietnam and Thailand during the COVID-19 pandemic. However, the effect size was small, and therefore, these results may not be clinically meaningful. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000044145; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050128. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.20944/preprints202303.0450.v1.

Stakeholder-informed pragmatic trial protocol of the TabCAT-BHA for the detection of cognitive impairment in primary care.

BACKGROUND: Cognitive impairment and dementia are frequently under-recognized. Health system strategies anchored in primary care are essential to address gaps in timely, comprehensive diagnosis. The goal of this paper is to describe the adaptation of a tablet-based brain health assessment (TabCAT-BHA) intervention and the study protocol to test its effectiveness in improving the detection of cognitive impairment, including dementia. METHODS: This mixed-methods, pragmatic, cluster randomized, hybrid effectiveness-implementation trial is being conducted in two 18-month waves with 26 Kaiser Permanente Southern California primary care clinics, with 13 serving as intervention clinics and 13 as usual care clinics. Patients 65 years and older with memory concerns (n ~ 180,000) receiving care at the 26 clinics will be included in the analyses. Primary care clinics are provided the following practice supports as part of the TabCAT-BHA intervention: brief education and training on neurocognitive disorders and study workflows; digital tools to assess cognitive function and support clinician decision making and documentation; and registered nurse support during the work-up and post-diagnosis periods for primary care providers, patients, and families. The intervention was adapted based on engagement with multiple levels of clinical and operational leaders in the healthcare system. Effectiveness outcomes include rates of cognitive impairment diagnosis in primary care and rates of completed standardized cognitive assessments and specialist referrals with incident diagnoses. Implementation outcomes include acceptability-appropriateness-feasibility, adoption, and fidelity. RESULTS: We identified seven themes organized by system-, provider-, and patient-level domains that were used to adapt the TabCAT-BHA intervention. Accordingly, changes were made to the provider education, diagnostic work-up, and post-diagnostic support. Results will be reported in fall of 2027. CONCLUSIONS: Our engagement with multiple primary and specialty care clinical and operational leaders to adapt the TabCAT-BHA intervention to these primary care clinics has informed the protocol to evaluate the intervention's effectiveness for improving the detection of cognitive impairment, including dementia, in an integrated healthcare system. TRIAL REGISTATION: Clinicaltrials.gov: NCT06090578 (registered 10/24/23).

α- or ß-Adrenergic blockade does not affect transplanted islet cell responses to hypoglycemia in type 1 diabetes.

Type 1 diabetes recipients of intrahepatic islet transplantation exhibit glucose-dependent suppression of insulin and activation of glucagon secretion in response to insulin-induced hypoglycemia associated with clinical protection from hypoglycemia. Whether sympathetic activation of adrenergic receptors on transplanted islets is required for these responses in defense against hypoglycemia is not known. To evaluate the adrenergic contribution to posttransplant glucose counterregulation, we performed a randomized, double-blind crossover study of responses during a hyperinsulinemic euglycemic-hypoglycemic clamp under phentolamine (α-adrenergic blockage), propranolol (ß-adrenergic blockage), or placebo infusion. Characteristics of participants (5 females/4 males) were as follows: median (range) age 53 (34-63) yr, diabetes duration 29 (18-56) yr, posttransplant 7.0 (1.9-8.4) yr, HbA1c 5.8 (4.5-6.8)%, insulin in-/dependent 5/4, all on tacrolimus-based immunosuppression. During the clamp, blood pressure was lower with phentolamine and heart rate was lower with propranolol versus placebo (P < 0.05). There was no difference in the suppression of endogenous insulin secretion (derived from C-peptide measurements) during the euglycemic or hypoglycemic phases, and although levels of glucagon were similar with phentolamine or propranolol vs. placebo, the increase in glucagon from eu- to hypoglycemia was greater with propranolol vs. placebo (P < 0.05). Pancreatic polypeptide was greater with phentolamine versus placebo during the euglycemic phase (P < 0.05), and free fatty acids were lower and the glucose infusion rate was higher with propranolol versus placebo during the hypoglycemic phase (P < 0.05 for both). These results indicate that neither physiological α- nor ß-adrenergic blockade attenuates transplanted islet responses to hypoglycemia, suggesting sympathetic reinnervation of the islet graft is not necessary for posttransplant glucose counterregulation.NEW & NOTEWORTHY Whether adrenergic input to islets is necessary for glucose homeostasis in humans is debated. Here, the adrenergic contribution to intrahepatically transplanted islet cell responses to hypoglycemia in individuals with type 1 diabetes was investigated through α- or ß-adrenergic receptor blockade during hyperinsulinemic euglycemic-hypoglycemic clamps. Neither α- nor ß-adrenergic blockage affected the suppression of endogenous insulin or activation of glucagon secretion, suggesting that sympathetic reinnervation of islet grafts is not required for posttransplant defense against hypoglycemia.

Asymptomatic and mildly symptomatic influenza virus infections by season -- Case-ascertained household transmission studies, United States, 2017-2023.

Asymptomatic influenza virus infection occurs but may vary by factors such as age, influenza vaccination status, or influenza season. We examined the frequency of influenza virus infection and associated symptoms using data from two case-ascertained household transmission studies (conducted from 2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had non-respiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing the effectiveness of symptom-based surveillance systems.

Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults.

The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.

Peroxisomal cholesterol metabolism regulates yap-signaling, which maintains intestinal epithelial barrier function and is altered in Crohn's disease.

Intestinal epithelial cells line the luminal surface to establish the intestinal barrier, where the cells play essential roles in the digestion of food, absorption of nutrients and water, protection from microbial infections, and maintaining symbiotic interactions with the commensal microbial populations. Maintaining and coordinating all these functions requires tight regulatory signaling, which is essential for intestinal homeostasis and organismal health. Dysfunction of intestinal epithelial cells, indeed, is linked to gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease, and gluten-related enteropathies. Emerging evidence suggests that peroxisome metabolic functions are crucial in maintaining intestinal epithelial cell functions and intestinal epithelium regeneration and, therefore, homeostasis. Here, we investigated the molecular mechanisms by which peroxisome metabolism impacts enteric health using the fruit fly Drosophila melanogaster and murine model organisms and clinical samples. We show that peroxisomes control cellular cholesterol, which in turn regulates the conserved yes-associated protein-signaling and contributes to intestinal epithelial structure and epithelial barrier function. Moreover, analysis of intestinal organoid cultures derived from biopsies of patients affected by Crohn's Disease revealed that the dysregulation of peroxisome number, excessive cellular cholesterol, and inhibition of Yap-signaling are markers of disease and could be novel diagnostic and/or therapeutic targets for treating Crohn's Disease. Our studies provided mechanistic insights on peroxisomal signaling in intestinal epithelial cell functions and identified cholesterol as a novel metabolic regulator of yes-associated protein-signaling in tissue homeostasis.

Effective treatment of 2,4,6-trinitrotoluene from aqueous media using a sono-photo-Fenton-like process with a zero-valent iron nanoparticle (nZVI) catalyst.

In this study, we examine the effectiveness of using a combination of a sono-photo-Fenton-like procedure and nano zero-valent iron catalyst (nZVI) to treat 2,4,6-trinitrotoluene (TNT) in an aquatic environment. Zero-valent iron particles were generated by a chemical reduction technique. nZVI nanoparticles were analyzed using scanning electron microscopy (SEM) and X-ray diffraction (XRD) to characterize the nanocatalyst. The resulting nZVI nanoparticles were used as an addition in a sono-photo-Fenton method to remediate an aqueous solution contaminated with TNT. Furthermore, influences of operational factors such as temperature, catalyst dosage, wavelength, ultraviolet power, ultrasonic frequency and power, pH level, H2O2/nZVI ratio, initial TNT concentration, and reaction duration on the treatment of TNT were investigated. Under the conditions of an ideal pH of 3, temperature range of 40-45 °C, concentration of 50 mg per L TNT, dose of 2 mM of nZVI, and ratio of H2O2/Fe0 of 20, a treatment efficiency of 95.2% was achieved after a duration of 30 minutes. The sono-photo-Fenton process combined with nZVI showed a higher TNT removal efficiency compared to the Fenton, sono-Fenton, and photo-Fenton processes under the same conditions. Moreover, it promises a potential solution to treat TNT at the pilot scale while allowing reuse of the nZVI catalyst and the limitation of sludge.

Nutritional status, dietary quality and eating disturbance issues among people with dementia in Vietnam: evidence of a cross-sectional study.

BACKGROUND: Due to cognitive impairments, people with dementia (PWD) often have difficulties in eating and drinking. This study aimed to assess the nutritional status, dietary quality and eating disturbance issues among PWD in Vietnam. METHODS: We conducted a cross-sectional study at the Vietnamese National Geriatric Hospital from April to December 2022. We used Mini-Mental State Exam (MMSE) to classify the severity levels of dementia. Mini Nutritional Assessment (MNA), 24-hour recall, eating disturbance questionnaires, and anthropometric indicators were used to evaluate the nutritional status, dietary quality, and eating disorders of study subjects. RESULTS: Overall, among 63 study participants, 74.6 per cent of PWD were at risk of or having malnutrition. By dementia classification according to MMSE scale, people with moderate and severe dementia accounted for 53.3 per cent of those who met the recommended energy levels, compared to 42.4 per cent of people with mild dementia and normal people. In the above two groups, around three per cent of participants reached the recommended amount of fibre. Calcium (50-70%), vitamin A (80-90%), and D (90%) were found to be the most severe deficiency forms of minerals and vitamins in both male and female participants. The majority of participants (90.5%) had at least one form of eating disorders with the most frequent issue being appetite changes (76.2%) and swallowing issues (50.8%). CONCLUSIONS: PWD in our sample frequently experienced malnutrition, a lack of essential nutrients, difficulties swallowing, changes in eating habits and appetite. It is neccesary to early screen and assess nutritional status and swallowing disturbance in PWD, and instruct their caregivers to prepare nutritious meals for them.