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Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans

Associations Between Routine Vaccinations and the Risk of New-Onset Idiopathic Uveitis.

OBJECTIVE: To evaluate the association between vaccination and the risk of new-onset idiopathic uveitis (NIU). DESIGN: Retrospective cohort study of aggregated electronic health records from multiple health systems across the United States. SUBJECTS: Subjects who received the coronavirus disease 2019 (COVID-19), human papillomavirus (HPV), varicella, recombinant herpes zoster, or live herpes zoster vaccinations from 2006 to 2025 and propensity-score matched controls. INTERVENTION: Vaccines against COVID-19, HPV, varicella, recombinant herpes zoster, or live herpes zoster. MAIN OUTCOMES AND MEASURES: The main outcome was the incidence of NIU at 3, 6, and 12 months following vaccination. Vaccinated patients were compared with matched controls who did not receive the respective vaccines. Analyses were repeated, excluding patients with previous diagnosis of the respective viral infection. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated for overall NIU and constituent subtypes (anterior, intermediate, posterior, and panuveitis). RESULTS: All tested vaccinations were associated with reduced risk of NIU through 12 months compared with matched controls. Relative risk reductions were 65% for COVID-19 (RR, 0.35; CI, 0.33-0.37), 56% for HPV (RR, 0.44; CI, 0.35-0.54), 71% for varicella (RR, 0.29; CI, 0.25-0.33), 68% for live zoster (RR, 0.32; CI, 0.23-0.43), and 69% for recombinant zoster vaccination (RR, 0.31; CI, 0.26-0.37). Similar reductions were observed after excluding patients with prior diagnoses of the respective viral infections. CONCLUSIONS: Vaccination was associated with a lower risk of idiopathic uveitis, representing the complex interplay between immune modulation and the development of NIU.

Humans

How is goal setting used in interventions for chronic disease prevention and management in sub-Saharan Africa? A systematic review and narrative synthesis.

Non-communicable diseases are increasingly prevalent in sub-Saharan Africa, and goal setting is often used to promote healthy self-management behaviours. In this review, we aimed to synthesise literature around how goal setting is used, for application in future interventions in the region. A systematic search was conducted in six databases and results screened for eligibility. Study characteristics, intervention details, goal setting components, feedback from participants and facilitators were extracted. Data were analysed using narrative synthesis and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality. We included 24 publications describing 18 unique interventions. Included studies were of high to moderate methodological quality. Goal setting intervention components were informed by a variety of frameworks and involved a range of tasks. Interventions were often facilitator-led; many were conducted in group settings. Participants reported goal setting as useful for putting self-management into practice but encountered challenges related to language and literacy levels. Adequate detail on goal setting intervention components was not always present. Through this review, we provide a comprehensive picture of the variability of goal setting approaches in chronic disease prevention and management in sub-Saharan Africa and recommend more standardised use and reporting of goal setting intervention components.

Humans

Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.

Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6 weeks to 12 months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited.

Humans

A hybrid effectiveness-implementation trial to integrate precision skin cancer risk feedback in federally qualified health centers.

BACKGROUND: Skin cancers are the most common type of cancer in the United States, occur in all segments of the population, and are preventable. Our previous research with primary care patients' demonstrated interest in and efficacy of a precision prevention intervention providing feedback on MC1R risk level (higher versus average) in combination with prevention education materials relative to a standard educational intervention. Our current study is a hybrid type 1 effectiveness-implementation trial deployed at six federally-qualified health centers. This paper presents the study protocol. METHODS: A community advisory panel will guide development of study materials and measures. Staff training at each clinic will be completed in-person. Patients will be approached and screened in-person. Those completing genetic testing and the baseline survey will be randomized to the precision versus standard intervention for each risk level with a target sample size of 286 for each combination. Primary outcomes of effectiveness, assessed at 6 and 12 months, include a tanning score (5 items assessing intentional and unintentional tanning), number of sunburns, conduct of a skin self-examination, and electronic health record documentation of clinician-patient communication about skin cancer prevention. Effectiveness comparisons will focus on the precision relative to the standard intervention among higher risk participants. Implementation data will be collected to identify barriers and facilitators. RESULTS: Effectiveness and implementation outcomes will be evaluated following study completion. CONCLUSIONS: Results will guide subsequent scale-up of the precision intervention, including modifications of the intervention as well as methods for implementation. CLINICAL TRIALS IDENTIFIER: NCT07222995.

Humans

Dengue and chikungunya vaccines past, present and future: implications for travelers.

PURPOSE OF REVIEW: Novel vaccines for dengue and chikungunya viruses offer new prevention options against two globally important arboviral diseases. This review summarizes recent developments in vaccine licensure, implementation, real-world experience and research priorities, with emphasis on implications for both endemic populations and travelers. RECENT FINDINGS: Of the three live-attenuated dengue vaccines licensed to date, TAK-003 is authorized in >40 countries and Butantan-DV in Brazil, while manufacturing of CYD-TDV is discontinued. Long-term and postmarketing data continue to refine understanding of serotype-specific protection, waning immunity, and rare adverse events.For chikungunya, two single-dose vaccines are licensed-a live-attenuated vaccine (VLA1553) and virus-like particle vaccine (PXVX0317). Uptake is guided by emerging safety and effectiveness data, with each platform offering potential advantages in different settings.Further data on long-term protection, safety, effectiveness, use in vulnerable populations and integration into outbreak management and immunization systems is anticipated. SUMMARY: Dengue and chikungunya vaccines are increasingly being used in immunization programs and pretravel consultations. Further real-world data are needed-particularly for seronegative dengue vaccine recipients and older, immunocompromised or medically at-risk adults. Research priorities include developing single-dose, nonlive dengue vaccines suitable for high-risk groups, understanding long-term chikungunya vaccine performance, and exploring broader flaviviral or pan-arboviral platforms.

Humans

ScRNA-seq analysis reveals the effects of nitrite stress on the endocrine system of the eyestalk in Litopenaeus vannamei.

Nitrite is a harmful substance generated in Litopenaeus vannamei farming systems, largely originating from the inadequate breakdown of surplus feed and shrimp feces. Its accumulation in the water can affect the growth and physiological functions of shrimp, damage the immune system, and even cause mass mortality, thus becoming a key environmental factor restricting the green development of the industry. Under nitrite stress, the eyestalk, as an important neuroendocrine regulatory center in crustaceans, participates in the stress adaptation of the organism and exerts a protective effect by regulating energy metabolism and immune function. However, the molecular regulatory mechanism of the eyestalk in response to nitrite stress remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) technology was used to analyze the heterogeneity of eyestalk cells in L. vannamei under nitrite stress. A total of 18, 394 high-quality cells were obtained, and six major cell subpopulations, including Neurosecretory cell, Motor neuron, Sensory neuron, Interneuron, Neurogliocyte, and Support cell, were identified. Differential expression analysis identified 839 differentially expressed genes, and different cell types showed distinct specific responses to nitrite stress. Functional enrichment analysis indicated that pathways such as glycolysis, oxidative phosphorylation, ribosome function, and endoplasmic reticulum protein processing were significantly activated, while signal transduction and DNA repair-related pathways were inhibited. Further analysis revealed that nitrite stress could induce mitochondrial function changes and trigger oxidative stress, thereby affecting the neuroendocrine system function of the eyestalk. This study provided insights into transcriptomic responses of the eyestalk to nitrite stress at the single-cell level, laying a theoretical foundation for the management of aquaculture environments.

Animals

Transpulmonary proteomic gradient analysis in women with pulmonary arterial hypertension associated with systemic sclerosis.

This study investigated proteomic alterations in the pulmonary circulation of patients with pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc) by analyzing the transpulmonary protein gradient and comparing the proteomic profiles with systemic sclerosis (SSc) without PAH. Twenty women were included (10 PAH-SSc, 64.6 ± 10.8 years; 10 SSc, 62.8 ± 11.5 years). The transpulmonary gradient was defined as the difference in biomarker concentrations between wedge-position and pulmonary artery blood samples. Peptides were analysed using liquid chromatography-mass spectrometry, and differentially abundant proteins were identified with Proteome Discoverer. Protein-protein interaction networks were generated with STRING and visualized in Cytoscape. A total of 270 proteins were detected, with no significant transpulmonary gradient alterations. However, patients with PAH-SSc showed distinct proteomic profiles compared to SSc. Multivariate analysis identified 48 differentially abundant proteins in pulmonary artery plasma, with 15 overrepresented and 33 downregulated in PAH-SSc. Among these, the downregulation of transforming growth factor-beta-induced protein ig-h3 (TGFβI/ig-h3) points to a potential involvement of the TGF-β-related extracellular matrix remodelling pathway in PAH-SSc. However, further validation in larger and independent cohorts is required before its relevance as a biomarker or therapeutic target can be established. In conclusion, while no transpulmonary proteomic gradient was observed, the proteomic profiles of PAH-SSc and SSc were different. The profile in PAH-SSc was characterized by differences in immune response, lipid metabolism, and hemostatic proteins. SIGNIFICANCE: This study offers the first proteomic characterization of the transpulmonary gradient in PAH-SSc and SSc. Although no differences in the gradient were found, the pulmonary artery plasma proteome of PAH-SSc patients showed a distinct pattern compared to SSc. Several proteins associated with immune function, haemostasis, and cellular processes were altered, which may indicate specific pathophysiological features of PAH-SSc or suggest how lung dysfunction develops in SSc. Targeting dysregulated proteins like TGFβI/ig-h3 or addressing immune-coagulation imbalances may support future research studies. Overall, these findings refine the molecular profile of PAH-SSc and provide a basis for future large-scale studies aimed at clarifying disease mechanisms and identifying clinically relevant molecular signatures.

Humans

Conduction System Pacing Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Anticipated High Pacing Burden.

Right ventricular pacing (RVP) in patients with atrioventricular (AV) block and high anticipated pacing burden is associated with pacing-induced cardiomyopathy (PICM) in approximately 12% to 20% of patients, whereas conduction system pacing (CSP) preserves more physiologic ventricular activation and may mitigate these consequences; the totality of contemporary randomized evidence has not been systematically pooled. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing CSP with RVP in patients with AV block or anticipated high ventricular pacing burden and a minimum 6-month follow-up, with co-primary outcomes of PICM incidence and change in left ventricular ejection fraction (&#x394;LVEF) and secondary outcomes of heart failure hospitalization (HFH), all-cause mortality, composite clinical endpoint, and paced QRS duration (PROSPERO CRD420261400227); random-effects meta-analysis used DerSimonian-Laird estimation. Five RCTs (LBBP-FAVOUR, CSPACE, Prague CSP, PACE-HF, STAY; N = 806) met inclusion criteria. CSP significantly reduced PICM (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.18 to 0.48; p <0.001; I&#xb2; = 0%; k = 4), was associated with greater LVEF preservation (pooled mean difference [MD] +4.41%, 95% CI +1.82 to +6.99; p = 0.001; I&#xb2; = 87%; k = 5), and reduced HFH (HR 0.24, 95% CI 0.12 to 0.48; p <0.001; I&#xb2; = 0%; k = 5). CSP shortened paced QRS duration (MD -27.5 ms, 95% CI -32.6 to -22.5; p <0.001; k = 5). All-cause mortality was numerically lower with CSP but did not reach significance (HR 0.57, 95% CI 0.29 to 1.12; p = 0.10; k = 4). In a prespecified sensitivity analysis restricting to multicenter trials with N &#x2265; 150, all findings were concordant with the primary analysis. In conclusion, CSP substantially reduces PICM, preserves LVEF, and reduces HFH compared with RVP in patients with AV block and anticipated high pacing burden, supporting its consideration as the preferred pacing strategy in appropriately selected patients.

Humans

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans

Mechanisms of impact of mental health peer support in high-, middle- and low-income settings: mediation analysis of the UPSIDES randomised controlled trial.

AIMS: While there is growing evidence for the effectiveness of peer support (PS) in improving psychosocial outcomes among individuals with severe mental health conditions, the mechanisms through which these effects occur remain insufficiently understood. This study examines whether social inclusion, hope and empowerment mediate the relationship between PS, personal recovery and health and social functioning. METHODS: Data were collected from 565 adults with severe mental health conditions who participated in the multicentre UPSIDES randomised controlled trial across six sites in Germany, Uganda, Tanzania, India and Israel. Participants in the intervention group received structured PS from trained peer workers over a 6- to 8-month period. Standardised, self-report measures of social inclusion, hope, empowerment and personal recovery, as well as clinician-rated health and social functioning, were administered at baseline, 4&#xa0;months, end of intervention (8&#xa0;months) and 12-month follow-up. Cross-lagged panel modelling was used to explore longitudinal associations and mediating pathways. RESULTS: The cross-lagged models showed strong autoregressive effects across all variables, indicating high temporal stability. There were no significant direct effects of PS on recovery or health and social functioning. However, mediation analysis identified significant indirect effects of PS on personal recovery via social inclusion (&#x3b2;&#xa0;=&#xa0;0.114, 95% confidence interval [CI] [0.049, 0.194], P&#xa0;<&#xa0;0.05) and hope (&#x3b2;&#xa0;=&#xa0;0.037, 95% CI [0.001, 0.086], P&#xa0;<&#xa0;0.05). Similar indirect effects were observed for health and social functioning (via social inclusion: &#x3b2;&#xa0;=&#xa0;-0.035, 95% CI [-0.064,&#xa0;-0.013]; via hope: &#x3b2;&#xa0;=&#xa0;-0.026, 95% CI [-0.052, -0.006]; both P&#xa0;<&#xa0;0.05). CONCLUSIONS: Findings suggest that PS affects recovery-related outcomes primarily through intermediate mechanisms of enhanced hope and social inclusion. These results support theoretical models positing indirect pathways of change in PS interventions and highlight the value of targeting social and psychological domains when designing and implementing PS in mental health services. Individuals with lower baseline levels of hope and social inclusion may particularly benefit from PS.

Humans

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding

Barriers and Facilitators of Help-Seeking for LGBTQ+ Survivors of Sexual Violence: A Systematic Review.

People who identify as LGBTQ+ (Lesbian, Gay, Bisexual, Transgender, Queer, plus) are known to experience similar or higher levels of sexual violence compared to their heterosexual cisgender counterparts. However, sexual violence research has largely focused on heterosexual female survivors of male perpetrated crime. Thus, the unique support needs and help-seeking patterns of LGBTQ+ survivors are poorly understood. This review addresses this gap by systematically exploring literature on barriers and facilitators to help-seeking for LGBTQ+ survivors of sexual violence. Four databases (PsycINFO, CINAHL, MEDLINE, and Web of Science) were searched to identify relevant material, with 35 articles (30 qualitative, 1 quantitative, and 4 mixed-methods) meeting the inclusion criteria. Data were extracted and analyzed using a narrative synthesis. The topic was investigated almost exclusively cross-sectionally. Barriers included discrimination experiences, myths and stereotypes, feelings of shame and self-blame, and rejection of victim status. Additional barriers were reported by survivors who hold multiple minority identities, in particular LGBTQ+ people of color and sex workers. Facilitators to help-seeking included the intrinsic need to connect with others, social encouragement and empowerment, and positive disclosure experiences. The Power Threat Meaning framework provides insight into these findings by presenting help-seeking behaviors as adaptive responses to increase a sense of safety following a traumatic experience. The analyzed data indicate several implications for the development and improvement services to support LGBTQ+ survivors. They further serve to highlight the need for additional robust research, conducted with an intersectional lens, to explore the needs of sexual and gender minority survivors of sexual violence.

Humans

"Abrazos, no Balazos": Intensity of Risk for Exposure to Violence and Armed Conflict Trajectories for Adolescents and Young Adults in M&#xe9;xico 2018-2024.

PURPOSE: "Abrazos, no balazos" (Hugs, not gunshots) is the approach to violence used by the Federal Mexican government from 2018 to 2024. This study identifies distinct conceptually useful latent class growth trajectories in the annual intensity of risk for exposure to events and fatalities from violence against civilians and battles for adolescents and young adults (AYAs) in M&#xe9;xico from 2018 to 2024. METHODS: Data are from the Armed Conflict Location and Event Data project. Latent class growth analyses were conducted with four longitudinal dependent variables assessed in seven sequential years (2018-2024). RESULTS: In most of the Mexican states, AYAs experienced low intensity-flat trajectories (p >.096) in the annual intensity of risk for exposure to events and fatalities from violence against civilians and battles. AYAs who lived in states with extremely, markedly, or moderately elevated 2018 intensities of risk for exposure to violence experienced decreasing trajectories (p =.000). One latent class with a mildly elevated-increasing trajectory (p =.000) in the annual intensity of risk for exposure to violence was identified for each of the four longitudinal dependent variables. DISCUSSION: During the time that the Federal Mexican government used the "Abrazos, no balazos" approach, AYAs in the majority of the states in M&#xe9;xico had intensity of risk for exposure to violence and armed conflict trajectories that were consistent with the goals of primary and secondary violence prevention. Violence prevention efforts should be augmented in states with unfavorable trajectories.

Humans

An overview of the use of proteomics and peptidomics to characterize alternative protein foods.

The global protein transition is accelerating the development of alternative protein foods, mainly derived from plants, insects, algae, fungi, and cellular agriculture. Ensuring the authenticity, safety, and nutritional adequacy of these emerging protein matrices requires molecular-level characterization beyond traditional compositional analyses. Proteomics and peptidomics have emerged as transformative analytical platforms capable of decoding the molecular signatures that define protein origin, structural integrity, digestibility, functionality, and health potential. The review comprehensively examines the application of proteomics, and peptidomics for profiling alternative protein foods. Further, the source authentication strategies based on species-specific protein and peptide biomarkers, detection of adulteration in complex matrices, and allergenicity assessment is discussed. Special attention is also given to nutritional proteomics with protein digestibility, gastrointestinal peptide release, and identification of bioactive sequences. SIGNIFICANCE: The importance of this review is that proteomics and peptidomics are becoming central in the management of the fast-growing environment of alternative protein foods, such as plant-based, insect, algal, fungal, and cultured meat products. It provides an explanation of the application of mass spectrometry-based processes to decode molecular signatures defining the origin of proteins, their structural integrity, digestibility, allergenicity, and bioactive properties, and thus directly contribute to safety, nutritional analysis, and authenticity of the product. Presentation of the article includes the integration of the knowledge of traditional muscle foods with alternative systems of proteins, where validated protein and peptide biomarkers are used in authentication, fraud detection, and allergy risk assessment in a wide variety of matrices. It also indicates the role of nutritional proteomics and peptidomics in informing the formulation strategy to promote digestibility and release of health-promoting peptides. In general, this review will guide scientists, the food industry, and regulatory bodies to use modern proteomic technologies in quality assurance, and decision-making, for the advancementof sustainable protein-based foods.

Proteomics

Efficacy of the NMIC-150 system in identifying extended-spectrum beta-lactamases in clinical isolates.

Extended-spectrum beta-lactamases (ESBLs) are significant contributors to the growing global crisis of antimicrobial resistance. This study evaluated the performance of the NMIC-150 System for susceptibility testing of third-generation cephalosporins (3GCs) and assessed whether ceftazidime-avibactam and aztreonam-avibactam could identify ESBL-producing carbapenem-resistant Enterobacterales (CREs). A total of 278 non-duplicate clinical isolates (Klebsiella pneumoniae, E. coli, and Proteus mirabilis) were analyzed. Antimicrobial susceptibility was determined using reference broth microdilution (BMD) and the NMIC-150 System. ESBL production was defined as an &#x2265;eight-fold reduction in the minimum inhibitory concentration (MIC) of 3GCs in the presence of clavulanic acid, according to CLSI criteria. Whole-genome sequencing was performed to characterize ESBL and carbapenemase genes among 3GC-resistant isolates. A Random Forest model was used to predict ESBL-producing isolates based on MIC values. The NMIC-150 System demonstrated over 90% categorical and essential agreement with BMD for ceftazidime and ceftriaxone, along with robust predictive performance via Random Forest analysis. These findings suggest that the NMIC-150 System is a reliable platform for 3GC susceptibility testing and that an &#x2265;eight-fold MIC reduction with ceftazidime-avibactam or aztreonam-avibactam may serve as a phenotypic indicator of ESBL production in CRE isolates. In conclusion, the NMIC-150 System shows potential for routine antimicrobial resistance surveillance and may facilitate the rapid identification of ESBL-producing CREs in clinical settings.

Microbial Sensitivity Tests

Optimization of a niosomal formulation for Quercetin delivery: Comparative effects on growth performance, antioxidant and immune responses, and disease resistance against Streptococcus iniae in rainbow trout (Oncorhynchus mykiss).

Quercetin (QUR) is a flavonoid with antibacterial and antioxidant properties that has been studied for its effects on fish health and the immune system. Due to the low bioavailability of QUR, the present study was primarily aimed at developing a niosomal formulation of QUR to enhance its bioavailability and therapeutic properties. The performance of niosomal QUR was then compared with that of its free form by evaluating their effects on the growth and immune system of rainbow trout, Oncorhynchus mykiss. For this purpose, an optimal QUR-containing niosome was formulated by testing different proportions of cholesterol, surfactant, and stabilizer, and the niosomes were then added to the fish diet. A QUR-free diet and a diet containing QUR-free niosomes (QFN) were considered control groups. Niosomes prepared at low hydrophilic-lipophilic balance (HLB) values showed higher QUR entrapment efficiency (QUR-EE%) (P&#x202f;<&#x202f;0.01). An increase in the molar ratio of cholesterol to surfactant significantly reduced QUR-EE% (P&#x202f;<&#x202f;0.05). A surfactant/cholesterol/stabilizer ratio of 1:1:0.1 increased QUR-EE% (P&#x202f;<&#x202f;0.05). The particle size of the niosomes was also affected by HLB and the surfactant/cholesterol/stabilizer ratio. Low HLB values resulted in smaller particle sizes (P&#x202f;<&#x202f;0.01). Furthermore, a surfactant/cholesterol/stabilizer ratio of 1:1:0.1 resulted in the smallest niosomal particle size (P&#x202f;<&#x202f;0.05). The presence of diacetyl phosphate as the stabilizer in the formulation improved the niosomal zeta potential to -40.55&#x202f;mV. The optimal niosomal formulation (HLB&#x202f;=&#x202f;6.6; surfactant/cholesterol/stabilizer ratio of 1:1:0.1) remained stable at 2&#x202f;&#xb0;C over 10 days of storage, as the niosomal QUR content and size did not show significant changes during this period (P&#x202f;>&#x202f;0.01). After preparation of the diets containing the optimal niosomal QUR, fish were fed the experimental diets for two months. QUR, in both niosomal and free forms, resulted in better growth performance than the QUR-free diets (P&#x202f;<&#x202f;0.01). There were no significant differences in growth performance between the free and niosomal forms of QUR; however, 500&#x202f;mg/kg QUR showed significantly better growth performance than 250&#x202f;mg/kg QUR (P&#x202f;<&#x202f;0.01). Although both the niosomal and free forms of QUR enhanced immune and antioxidant components in the fish, the effects of the niosomal form were more significant (P&#x202f;<&#x202f;0.01). In addition, QUR in both free and niosomal forms reduced fish mortality after challenge with Streptococcus iniae. In conclusion, the results of this study suggest that the niosomal form of QUR has strong potential for improving the immune system of fish and increasing resistance to S. iniae infection.

Animals

Boosting kynurenic acid in kombucha via substrate selection: metagenomic and biochemical insights.

Kombucha is gaining global popularity for its health benefits. This study explored the use of chestnut honey, a rich source of kynurenic acid (KYNA), to produce kombucha enriched with this metabolite. Five variants were prepared using different green/black tea blends and carbon sources: white sugar or acacia honey (controls) versus chestnut honey. Samples were analyzed for tryptophan metabolites, physicochemical properties, and microbial diversity. Komagataeibacter and Enterobacter were predominant bacterial genera in SCOBY. Candida and Aspergillus were predominated in the single sample analyzed for fungi. During fermentation, tryptophan decreased, while kynurenine increased. KYNA levels remained largely stable during fermentation and were mainly influenced by the fermentation substrate. No melatonin pathway derivatives were detected. On day 7, chestnut honey yielded kombucha with 381.680-739.915&#xa0;&#x3bc;mol/L KYNA and elevated myricetin. Overall, chestnut honey-based kombucha represents a system in which substrate composition appears to be the main factor influencing KYNA levels in the final beverage.

Kynurenic Acid