Sucralose inhibited cell survival through the activation of ER stress in human endothelial progenitor cells

by Chia-Ying Li, Hung-Yu Lin, En-Pei Isabel Chiang, Hung-Chang Hung, Feng-Yao Tang

Sucralose, a widely utilized non-caloric sweetener, is frequently added to food and beverage products as a sugar substitute aimed at lowering energy consumption and reducing obesity-related health risks. However, epidemiological studies have indicated a possible association between high intake of sucralose and increased prevalence of coronary artery disease (CAD). Prior research has demonstrated that diminished levels of circulating human endothelial progenitor cells (hEPCs) are linked to a higher risk of CAD. Although sucralose is broadly consumed, its direct biological impact on hEPCs has not been comprehensively characterized. In this study, we investigated the cellular effects of sucralose on hEPCs using a variety of in vitro techniques, including assays for viability, migration, capillary-like tube formation, lactate dehydrogenase (LDH) release-cytotoxicity assay, and protein expression profiling by Western blotting. Our results revealed that increased concentrations of sucralose significantly impaired hEPCs viability, motility, and neovasculogenic function, accompanied by increased expression of markers associated with apoptosis, inflammasome activation, and pyroptosis. Mechanistic analysis further demonstrated that sucralose strongly activated endoplasmic reticulum (ER) stress/PERK pathways in these cells. Inhibition of ER stress via 4-phenylbutyric acid (4-PBA) substantially attenuated sucralose-induced cell death and reduced the expression of pyroptosis-related proteins and inflammasome markers. Taken together, these findings suggest that sucralose disrupts hEPCs function in part by triggering ER stress, which promotes both apoptotic and pyroptotic cell death programs.

The effects of increasing dosages of narasin on ruminal fermentation patterns, bacterial community composition, and nutrient digestibility in beef cattle receiving feedlot diets

by Ana Laura Januário Lelis, Leandro Aparecido Ferreira da Silva, Daniel Moretto Casali, Tiago Leiva, Murilo Chuba Rodrigues, José Paulo Roman Barroso, Pedro Veloso Facury Lasmar, Camila Lisboa Tomaz, Anabelle Jorge Barbosa, Camila Cesario Fernandes Sartini, Johnny Maciel de Souza, Danilo Domingues Millen

This study evaluated the effects of increasing narasin doses on ruminal fermentation, nutrient digestibility, ruminal pH stability, papillae histology, and microbial composition in Angus cattle fed feedlot diets. Three rumen-cannulated Angus steers (average body weight: 680 kg) were assigned to a 3 × 3 Latin square design and received diets containing 13, 20, or 27-ppm of narasin. Each experimental period consisted of 14 days of adaptation followed by seven days of sampling. Ruminal degradability was assessed on days 15–17, apparent digestibility on days 15–19, continuous ruminal pH on days 19–20, and samples for short-chain fatty acids (SCFA), microbiota, and ruminal histology were collected on days 20 and 21. Ruminal degradability was not affected by narasin dose. Digestibility of acid detergent fiber (ADF) was significantly influenced, with the greatest values observed at 27-ppm (P = 0.01). Increasing narasin doses improved ruminal pH stability, as indicated by a linear increase in minimum pH (P = 0.01) and a reduction in the duration of pH below 5.6 (P = 0.10). At 13 ppm, SCFA production, particularly acetate and propionate, increased (P P P = 0.02), and butyrate (P P P = 0.03). Narasin supplementation altered ruminal microbial composition, increasing the relative abundance of Lachnospiraceae and Isotricha while reducing lactic acid–producing bacteria. In terms of ruminal morphology, supplementation with 20-ppm of narasin increased the keratin layer thickness of ruminal papillae (P = 0.02), suggesting enhanced epithelial development. Overall, narasin supplementation modulated ruminal function and microbial ecology, with doses between 13 and 20-ppm providing the most favorable balance between fermentative efficiency and ruminal health in feedlot cattle.

Integrating sequence-based GWAS and comparative genomic analysis reveals conservation and species-specificity of putative functional variants influencing tail length and tail abnormalities in pigs and sheep

by Xuying Zhang, Johanna Mainzer, Isabella Giambra, Tong Yin, Petra Engel, Hannah Hümmelchen, Henrik Wagner, Axel Wehrend, Christiane Egerer, Katharina Gerhards, Gerald Reiner, Sven König

Long tails trigger tail biting in pigs and increase the risk of flystrike infections in sheep. Tail docking has been a common management practice in both species for decades, but increasingly conflicts with legal animal welfare guidelines. Sustainable solutions require breeding strategies targeting shorter tails. In consequence, the aims were to conduct whole-genome sequencing (WGS)-based genome-wide association studies (GWAS) and comparative genomic analyses (CGA) to explore functional elements influencing tail traits. Phenotypically divergent experimental populations of pigs and sheep were established through unified selection and mating experiments. Tail traits included tail length (TL) measured at birth, and tail abnormalities (TA) assessed radiographically at 14 weeks of age. WGS-based GWAS identified a significant locus on SSC18 in pigs and suggestive loci for TL in both species, which, together with previously reported loci for TA, were further analyzed by CGA. The genomic windows of the significant locus on SSC18 in pigs and the TL GWAS locus on OAR4 in sheep were found to be conserved, harboring six common genes with predicted functional variants. These variants were jointly associated with TL (P_lm ) in both species in linear regression models adjusted for sex, age of the dam, body length, and body weight. In other GWAS locus windows (±1 Mb), species-specific TL candidate genes were identified in sheep (HOXB13, MUC5B, EPB41L3, MTCL1, PIEZO2, MPPE1, and LOXHD1) and in pigs (KNL1, DISP2, SPRED1, TGFB2, and HAND1), each harboring associated putative functional variants. For TA, sheep-specific candidates (PGM2, LRRC66, CRACD, LOC105601916, and SH2D4B) and pig-specific candidates (MYOT, TMCO6, and PCDHAC2) were revealed using logistic regression models (P_glm ). GO analyses of candidate genes predicted shared biological processes between sheep and pigs, whereas pathway analyses indicated that common carbohydrate metabolism pathways, along with species-specific immune and inflammatory signaling, and pig-specific TGF-β signaling and endochondral ossification, may contribute to tail length variation and abnormalities. These findings provided deeper insights into the genetic basis of differential embryonic tail morphogenesis and perinatal tail development across species.

Factors associated with unmet healthcare needs in patients using Primary Care Access Points for unattached patients in Quebec (Canada)

by Mylaine Breton, Catherine Lamoureux-Lamarche, Véronique Deslauriers, Djamal Berbiche, Maude Laberge, Annie Talbot, Aude Motulsky, Marie-Pascale Pomey, Isabelle Gaboury

Background

Access to primary care is an important component of health systems. Given the barriers experienced by unattached patients to accessing primary care in Quebec (Canada), the Ministry of Health mandated the province-wide implementation of Primary care access points for unattached patients (Guichet d’accès première ligne; GAP), an organizational innovation designed to orient patients to the most appropriate professional or service. This study aims to 1) document the factors associated with unmet healthcare needs after receiving GAP services and 2) assess whether those factors vary by GAP orientation.

Methods

This cross-sectional study builds on data collected between April and July 2024 using an online patient questionnaire. All patients with a valid email address registered on the centralized waiting list for unattached patients in three local health territories (LHTs) received an email invitation to participate in the survey. The total sample included 20,282 participants who responded to the questionnaire and used the GAP.

Results

The findings showed that younger age, self-reporting poor/fair physical and mental health, receiving services in LHT 3 and reporting an emergency room visit were associated with increased likelihood of reporting unmet needs. Stratified analyses suggested that some characteristics (age, use of emergency room) were associated with unmet needs across orientations, while others (self-reported physical and mental health) were associated with specific orientations.

Conclusion

This study serves as a first step in deepening our understanding from a patient perspective of how to better plan primary care services and improve unattached patients’ experiences using the GAP. The findings showed that patients oriented to other professionals than a medical appointment with a family physician had the highest percentage of unmet needs. The next step involves an in-depth exploration of the reasons for patients’ unmet needs, enabling the development of more precise and effective strategies to address them.

Extended-spectrum β-lactamase and carbapenemase-producing <i>Enterobacterales</i> among adult patients and their family members at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

by Dessie Abera, Adane Mihret, Surafel Fentaw, Eyob Beyene, Abel Abera Negash, Woldaregay Erku Abegaz

Background

Extended-spectrum β-Lactamase and Carbapenemase-producing Enterobacterales cause severe infections and currently, they are spreading beyond hospitals and becoming a serious global health concern. They often colonize the gut silently, facilitating the transmission of resistant bacteria between patients and family members.

Objective

We sought investigate the prevalence and molecular characteristics of Extended-spectrum β-Lactamases-producing Enterobacterales (ESBL-PE), Carbapenem-resistant Enterobacterales (CRE), and factors associated there in among admitted adult patients and their family members at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

Methods

A case-control study was conducted among 100 patients and their respective 100 family members from February 2023 to October 2023. Stool specimens were collected and processed using standard microbiological techniques. Antimicrobial susceptibility testing and ESBL production were determined using VITEK 2 system. Carbapenemase production was tested using modified carbapenem Inactivation method, and detection of resistance genes was performed by PCR.

Result

Intestinal colonization with ESBL-PE was higher in patients (39.0%) than their respective family members (24.0%) (P = 0.028). Among patients, ESBL production was common in E. coli, 40.3% and K. pneumoniae, 34.7% than their family members 24.2% and 22.2%, respectively. Of the ESBL-PE isolates, 84.6% from patients and 100% from family members carried at least one ESBL encoding gene, with bla_CTX-M being the predominant. Colonization with CRE and Carbapenemase-Producing Carbapenem-Resistant Enterobacterales was found to be 19.0% and 10.0%, respectively. These were identified only among patients, with bla_NDM and bla_OXA-48 are the most prevalent genes. Older age (>53 years) (P = 0.02) and previous ICU admission (P  Conclusion

ESBL-PE colonization was more prevalent in patients compared to their family members, with bla_CTX-M identified as the most common gene. Exclusive detection of carbapenemase genes among patients, and the association of previous ICU admission with ESBL-PE colonization, highlights the need for targeted screening and strengthened infection prevention.

Custom foot orthoses for chronic metatarsalgia: Study protocol for a participant- and assessor-blinded superiority randomized controlled trial

by Eléna Payen Schalkens, Maxime Acien, Andrée-Anne Marchand, Pier-Luc Isabelle, Jacques Abboud, Gabriel Moisan

Background

Chronic metatarsalgia (CM) causes significant pain and disability, affecting quality of life. Foot orthoses (FOs) including medially wedged designs with a metatarsal pad decrease excessive plantar pressure under the metatarsal heads, which is a suggested risk factor for developing CM. This FOs model may be effective in diminishing pain and improving function in these individuals. Thus, the objective of this trial will be to compare the effects of medially wedged FOs with a metatarsal pad and sham FOs on pain and foot function in individuals with CM.

Methods/design

This participant- and assessor-blinded superiority randomized controlled trial (RCT) with two parallel groups will be conducted in Trois-Rivières, Canada. Sixty-four participants with CM will be recruited from the Université du Québec à Trois-Rivières outpatient podiatry clinic and via social media invitations. They will be randomized into intervention (customized FOs) or control (sham FOs) groups and will be evaluated at baseline and after 6 and 12 weeks. The primary outcome will be: (1) mean pain during walking for the most painful foot during the past week. The secondary outcomes will be: (1) Foot Function Index, (2) Global rating of change and (3) the 5-level EQ-5D.

Discussion

Medially wedged FOs with a metatarsal pad are expected to provide a greater reduction in pain and improvement in foot function compared to sham FOs. This trial will help guide FOs prescription recommendations for managing foot pain in individuals with CM in the future.

Trial registration

ClinicalTrials.gov NCT06962475

Placebo and nocebo in clinical practice: An online cross-sectional survey of healthcare professionals from European countries on views, practices and training needs

by Mary O’Keeffe, Nathan Skidmore, Arianna Bagnis, Przemysław Bąbel, Elżbieta A. Bajcar, Alessandra De Palma, Andrea W.M. Evers, Eveliina Glogan, Julia W. Haas, Stefanie H. Meeuwis, Marek Oleszczyk, Antonio Portolés, Johan W.S. Vlaeyen, Katia Mattarozzi, on behalf of PANACEA Consortium

Background

Placebo and nocebo effects significantly influence health outcomes, yet healthcare professionals receive limited training and guidance on their mechanisms and clinical application, creating a gap in education and practical understanding. Conducted within the European PANACEA Consortium, this study evaluated healthcare professionals’ knowledge, attitudes, and practices regarding placebo and nocebo effects, and assessed their needs in further education.

Methods

An online cross-sectional survey among a European multi-country convenience sample of healthcare professionals collected data assessing participants’ knowledge, perceptions, and experiences regarding placebo and nocebo effects; their application and ethical considerations in clinical practice; and investigated educational needs and interest in further training. Quantitative data were analyzed using descriptive statistics, and thematic analysis was applied to the free-text responses.

Results

Amongst 807 participants, 71.7% reported taking advantage of placebo effects in their practice, and over half of participants (55.8%) observing nocebo effects. Participants reported feeling somewhat confident (53.3%) in harnessing placebo effects with 47.5% feeling confident in preventing nocebo effects. The majority of respondents had not received formal training on placebo and nocebo effects, with most expressing an interest in further training in areas such as healthcare education, emphasizing communication skills to enhance placebo effects, and knowledge to recognize and reduce nocebo effects.

Conclusions

There is a significant need for more comprehensive training on placebo and nocebo effects, particularly in early health professional education. These findings informed the development of educational resources and best practice recommendations developed as part of the outcomes from the PANACEA Consortium, improving the understanding and application of these effects among healthcare professionals across Europe.

Predictive effects of diabetes-related risk factors for falls in community-dwelling people with diabetic peripheral neuropathy based on a logistic regression model

by Eneida Yuri Suda, Cristina Dallemole Sartor, Anice de Campos Passaro, Ricky Watari, Eunice Young Docko, Isabel C. N. Sacco

Background

This study aimed to identify the predictive effects of different aspects of diabetic peripheral neuropathy (DPN) and other already known risk factors for falls through a comprehensive logistic model within community-dwelling older adults with diabetes and DPN. This paper also provides a model that estimates the probability of a fall occurring in a real-world clinical scenario.

Methods

This cross-sectional retrospective study analyzed data from subjects that had never fallen (non-fallers, n = 534) and that had fallen at least twice in the previous year (fallers, n = 101). The logistic regression analysis was performed on a training sample randomly extracted from the original sample (non-fallers: n = 85; fallers: n = 81). The model was validated by checking the performance parameters using a test sample comprised of 10% of fallers (n = 16) and a proportionate subsample of non-fallers (n = 85) from the original dataset.

Results

Three predictive models were developed. The best model (0.762 receiver operating characteristic[ROC] curve area, 60.4% accuracy, 68.8% sensitivity, 58.8% specificity) identified age (odds ratio[OR]=1.06[95%CI: 1.02, 1.10], P = 0.002), Michigan Neuropathy Screening Instrument score (OR=1.23[95%CI: 1.08, 1.40], P = 0.001), and self-reported balance problems (OR=2.65[95%CI: 1.29, 5.45], P = 0.008) as predictors of falls. A second model with good performance parameters (0.750 ROC curve area, 62.4% accuracy, 62.5% sensitivity, 62.4% specificity) showed that age (OR=1.04[95%CI: 1.01, 1.07], P = 0.015), balance problems (OR=3.29[95%CI: 1.64, 6.59], P = 0.001), and DPN severity (OR=1.18[95%CI: 1.03, 1.34], P = 0.018) were predictors of falls.

Conclusions

We showed the potential of a predictive model for recurrent falls based on commonly evaluated variables in community-dwelling individuals with diabetes for use in clinical practice. Even for individuals who are not at a high risk for falls, it is crucial to assess the combination of DPN signs, symptoms, and severity and the perception of balance problems, as these are more relevant in people with diabetes than the traditional physical impairments associated to aging.

Knowledge, attitudes, and barriers to HIV testing among youth in Kumba, Cameroon: A cross-sectional qualitative community-based focus group study

by Frederick Nchang Cho, Marie Clarie Fien Ndim, Diane Zinkeng Tongwa, Christabel Afor Tatah, Franklin Ngwesse Ngome, Eugine Mbuh Nyanjoh, Andrew N Tassang

Background

Human Immunodeficiency Virus (HIV) remains a major public health concern in sub-Saharan Africa. In Cameroon, young people are disproportionately affected but underrepresented in HIV testing statistics.

Objective

To explore knowledge, attitudes, and behaviours related to HIV testing among youth in Kumba, Cameroon, and to identify barriers to inform community-based interventions.

Methods

A cross-sectional qualitative study was conducted using nine focus group discussions (FGDs) with 75 youth (52 females and 23 males) aged 18 - 35 years across four quarters in the Kumba II municipality. Participants were purposively sampled to reflect diverse educational and occupational backgrounds. Data were thematically analysed using Braun and Clarke’s framework with NVivo Version 14.

Results

Participants demonstrated high awareness of HIV testing services (90.7%) and transmission via sexual contact (96.0%), though knowledge gaps remained regarding non-sexual transmission and testing procedures. While 93.3% had previously undergone HIV testing, 57.3% reported stigma and 46.7% raised confidentiality concerns as ongoing barriers. Female participants feared being labelled as promiscuous, while males cited social norms that discourage help-seeking. Most participants supported school-based or youth-centred community testing, emphasising the need for privacy and youth-friendly environments. Key motivators for testing included the desire to know one’s status (82.7%), symptom appearance (28.0%), and unprotected sex (17.3%).

Conclusions

Despite strong awareness and high testing uptake, stigma and confidentiality concerns persist among youth in Kumba. To enhance HIV testing rates, community-based strategies should prioritise mobile clinics, peer outreach, and confidential youth-centred services. Strengthening education about HIV transmission and demystifying the testing process may further reduce barriers.