bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association of Sodium or Potassium Intake Timing with Athens Insomnia Scale Scores: A Cross-Sectional Study
Authors: Okamoto Taiki , Lo Yun-Peng , Khaing Inn-Kynn , Inoue Shoko , Tada Ayako , Michie Mikiko , Kubo Tatsuhiko , Shibata Shigenobu , Tahara Yu
Published: December 2024

Background/Objectives: Insomnia is a significant public health problem affecting a large population. Although previous research has explored the relationship between specific nutrients and insomnia, comprehensive analyses of daily eating patterns of macro- and micronutrients remain limited. Since nocturnal hypertension is related to sodium/potassium intake and sleep disturbances, the present cross-sectional study hypothesized that daily eating patterns of potassium and sodium would be associated with Athens Insomnia Scale (AIS) scores. Methods: Dietary data (breakfast, lunch, dinner, and snack intake) and additional online questionnaire responses were obtained from users (N = 4568; age: 43.5 ± 11.2 years) of Asken, a Japanese food-logging mobile health application. AIS scores were divided into three groups according to symptom classification. Results: Multiple regression analyses revealed that individuals with higher AIS scores had lower daily potassium intake; potassium at dinner was especially crucial. Conclusions: These results underscore the potential importance of potassium intake in relation to sleep and highlight a novel association between sleep disturbances and the timing of sodium and potassium consumption.
DAG-MAG-ΒHB: A Novel Ketone Diester Modulates NLRP3 Inflammasome Activation in Microglial Cells in Response to Beta-Amyloid and Low Glucose AD-like Conditions
Authors: Gentili Valentina , Schiuma Giovanna , Dilliraj Latha Nagamani , Beltrami Silvia , Rizzo Sabrina , Lara Djidjell , Giovannini Pier Paolo , Marti Matteo , Bortolotti Daria , Trapella Claudio , Narducci Marco , Rizzo Roberta
Published: December 2024

Background: A neuroinflammatory disease such as Alzheimer’s disease, presents a significant challenge in neurotherapeutics, particularly due to the complex etiology and allostatic factors, referred to as CNS stressors, that accelerate the development and progression of the disease. These CNS stressors include cerebral hypo-glucose metabolism, hyperinsulinemia, mitochondrial dysfunction, oxidative stress, impairment of neuronal autophagy, hypoxic insults and neuroinflammation. This study aims to explore the efficacy and safety of DAG-MAG-ΒHB, a novel ketone diester, in mitigating these risk factors by sustaining therapeutic ketosis, independent of conventional metabolic pathways. Methods: We evaluated the intestinal absorption of DAG-MAG-ΒHB and the metabolic impact in human microglial cells. Utilizing the HMC3 human microglia cell line, we examined the compound’s effect on cellular viability, Acetyl-CoA and ATP levels, and key metabolic enzymes under hypoglycemia. Additionally, we assessed the impact of DAG-AG-ΒHB on inflammasome activation, mitochondrial activity, ROS levels, inflammation and phagocytic rates. Results: DAG-MAG-ΒHB showed a high rate of intestinal absorption and no cytotoxic effect. In vitro, DAG-MAG-ΒHB enhanced cell viability, preserved morphological integrity, and maintained elevated Acetyl-CoA and ATP levels under hypoglycemic conditions. DAG-MAG-ΒHB increased the activity of BDH1 and SCOT, indicating ATP production via a ketolytic pathway. DAG-MAG-ΒHB showed remarkable resilience against low glucose condition by inhibiting NLRP3 inflammasome activation. Conclusions: In summary, DAG-MAG-ΒHB emerges as a promising treatment for neuroinflammatory conditions. It enhances cellular health under varying metabolic states and exhibits neuroprotective properties against low glucose conditions. These attributes indicate its potential as an effective component in managing neuroinflammatory diseases, addressing their complex progression.
The Bifidogenic Effect of 2’Fucosyllactose Is Driven by Age-Specific Bifidobacterium Species, Demonstrating Age as an Important Factor for Gut Microbiome Targeted Precision Medicine
Authors: Firrman Jenni , Deyaert Stef , Mahalak Karley K. , Liu LinShu , Baudot Aurélien , Joossens Marie , Poppe Jonas , Cameron Simon J. S. , Van den Abbeele Pieter
Published: December 2024

Background: The human gut microbiota develops in concordance with its host over a lifetime, resulting in age-related shifts in community structure and metabolic function. Little is known about whether these changes impact the community’s response to microbiome-targeted therapeutics. Providing critical information on this subject, faecal microbiomes of subjects from six age groups, spanning from infancy to 70-year-old adults (n = six per age group) were harvested. The responses of these divergent communities to treatment with the human milk oligosaccharide 2’-fucosyllactose (2’FL), fructo-oligosaccharides (FOS), and lactose was investigated using the Ex vivo SIFR® technology that employs bioreactor fermentation and is validated to be predictive of clinical findings. Additionally, it was evaluated whether combining faecal microbiomes of a given age group into a single pooled microbiome produced similar results as the individual microbiomes. Results: First, marked age-dependent changes in community structure were identified. Bifidobacterium levels strongly declined as age increased, and Bifidobacterium species composition was age-dependent: B. longum, B. catenulatum/pseudocatenulatum, and B. adolescentis were most prevalent for breastfed infants, toddlers/children, and adults, respectively. Metabolomic analyses (LA-REIMS) demonstrated that these age-dependent differences particularly impacted treatment effects of 2’FL (more than FOS/lactose). Further analysis revealed that while 2’FL enhanced production of short-chain fatty acids (SCFAs) and exerted potent bifidogenic effects, regardless of age, the specific Bifidobacterium species enhanced by 2’FL, as well as subsequent cross-feeding interactions, were highly age-dependent. Furthermore, single-pooled microbiomes produced results that were indicative of the average treatment response for each age group. Nevertheless, pooled microbiomes had an artificially high diversity, thus overestimating treatment responses (especially for infants), did not recapitulate interindividual variation, and disallowed for the correlative analysis required to unravel mechanistic actions. Conclusions: Age is an important factor in shaping the gut microbiome, with the dominant taxa and their metabolites changing over a lifetime. This divergence affects the response of the microbiota to therapeutics, demonstrated in this study using 2’FL. These results evidence the importance of screening across multiple age groups separately to provide granularity of how therapeutics impact the microbiome and, consequently, human health.
Comparisons of Post-Load Glucose at Different Time Points for Identifying High Risks of MASLD Progression
Authors: Teng Long , Luo Ling , Sun Yanhong , Wang Wei , Dong Zhi , Cao Xiaopei , Ye Junzhao , Zhong Bihui
Published: December 2024

Background: The 1-h post-load plasma glucose was proposed to replace the current OGTT criteria for diagnosing prediabetes/diabetes. However, it remains unclear whether it is superior in identifying progressive metabolic dysfunction-associated steatotic liver disease (MASLD), and thus we aimed to clarify this issue. Methods: Consecutive Asian participants (non-MASLD, n = 1049; MASLD, n = 1165) were retrospectively enrolled between June 2012 and June 2024. CT was used to quantify liver steatosis, while the serum liver fibrotic marker was used to evaluate liver fibrosis. Results: Compared with those with normal levels of both 1-h post-glucose (1hPG) and 2-h post-glucose (2hPG), patients with MASLD showed a significant positive association between elevated 1hPG levels and moderate to severe liver steatosis (odds ratio [OR] = 2.19, 95% confidence interval [CI]: 1.13–4.25, p = 0.02]. Elevated levels of both 1hPG and 2hPG were associated with an increased risk of liver injury (OR = 2.03, 95% CI: 1.44–2.86, p < 0.001). Elevated 2hPG levels with or without elevated 1hPG levels were associated with liver fibrosis (OR = 1.99, 95% CI: 1.15–3.45, p < 0.001; OR = 2.72, 95% CI: 1.79–4.11, p < 0.001, respectively). Additionally, either 1hPG or 2hPG levels were associated with atherosclerosis, revealing significant dose-dependent associations between glucose status and atherosclerosis risk (OR = 2.77, 95% CI: 1.55–4.96, p < 0.001 for elevated 1hPG; OR = 2.98, 95% CI = 1.54–5.78, p = 0.001 for elevated 2hPG; OR = 2.41, 95% CI = 1.38–4.21, p = 0.001 for elevated levels of both 1hPG and 2hPG). The areas under the ROC for predicting steatosis, liver injury, liver fibrosis, and atherosclerosis were 0.64, 0.58, 0.58, and 0.64 for elevated 1hPG (all p < 0.05) and 0.50, 0.60, 0.56, and 0.62 for elevated 2hPG (all p < 0.05), respectively. Conclusions: These findings underscore the necessity for clinicians to acknowledge that the screening and management of MALSD requires the monitoring of 1hPG levels.
Association of Serum Polyunsaturated Fatty Acids (PUFAs) and Children’s Dietary Inflammatory Index (C-DIITM) with Recurrent Respiratory Infections in Children: A Cross-Sectional Study
Authors: Gorczyca Daiva , Szeremeta Karolina , Paściak Mariola , Szponar Bogumiła , Zhao Longgang , Wirth Michael D. , Hebert James R. , Związek Natalia , Prescha Anna
Published: December 2024

To assess the associations between serum and dietary polyunsaturated fatty acids (PUFAs), as well as the inflammatory potential of diet measured by the Children’s Dietary Inflammatory Index (C-DIITM), and recurrent respiratory infections (RRIs) in children. We enrolled 44 children aged 3–16 years with RRIs and 44 healthy controls. Dietary intake was assessed using a 7-day food record from which PUFA intake and C-DIITM were calculated. Serum PUFA levels were determined using gas–liquid chromatography–mass spectrometry. The dietary assessment showed a significantly lower fiber intake in children with RRIs. The RRI group had a higher inflammatory potential in the diet than healthy controls. Children with RRIs have higher serum levels of linoleic, arachidonic, and eicosapentaenoic acids than healthy subjects. A pro-inflammatory diet was positively associated with serum n-6 PUFA levels in both the groups. A high inflammatory potential of diet, body mass index over 75 percentile, and short breastfeeding duration were identified as risk factors for RRIs. The inflammatory potential of diet is strongly associated with RRIs in children and related to their PUFA status. Promoting breastfeeding and healthy dietary habits during childhood are crucial for implementing effective preventive management strategies.
Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential Therapeutic Effects of Probiotics and Their Metabolites
Authors: García Mansilla María José , Rodríguez Sojo María Jesús , Lista Andrea Roxana , Ayala Mosqueda Ciskey Vanessa , Ruiz Malagón Antonio Jesús , Gálvez Julio , Rodríguez Nogales Alba , Rodríguez Sánchez María José
Published: December 2024

Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
Vitamin D Supplementation in Critically Ill—Narrative Review
Authors: Saric Lenko , Domazet Bugarin Josipa , Dosenovic Svjetlana
Published: December 2024

Background: Studies have shown a high prevalence of vitamin D deficiency in critically ill patients, and these patients are at higher risk for pneumonia and have increased incidence of sepsis and mortality. In this study, we reviewed available literature from randomized controlled trials (RCTs) on vitamin D supplementation in critically ill patients and summarized the evidence in this narrative review. Methods: Randomized controlled trials that included vitamin D supplementation as an intervention were eligible for inclusion. No limits were set regarding vitamin D dosage or route of administration, as well as for primary and secondary outcomes. A search was conducted in MEDLINE via PubMed for eligible RCTs. References from systematic reviews (SRs) and meta-analyses (MAs) were screened, and Clinicaltrials.gov was searched for ongoing studies. Results: A total of 21 RCTs involving 3166 patients were analyzed. There was a large heterogeneity in terms of patients’ characteristics and inclusion criteria. Only six studies included patients with vitamin D levels < 50 nmol/L. Regarding clinically important outcomes, most of the studies did not show differences between the intervention and control group in terms of mortality, intensive care unit (ICU) or hospital length of stay (LoS). Conclusions: There is great variability in trial designs regarding the selection of patients, dosage, dosing intervals and routes of administration of vitamin D supplements. Better study designs are mandatory for future clinical research, with measuring and reporting basal vitamin D levels before randomization. Since variability in supplementation regimes limits the possibility of data synthesis, standardized protocols for vitamin D supplementation should be used in clinical trial settings.
Chronobiological Factors Influencing Glycemic Control and Birth Outcomes in Gestational Diabetes Mellitus
Authors: Messika Amalia , Toledano Yoel , Hadar Eran , Tauman Riva , Froy Oren , Shamir Raanan
Published: December 2024

Background/Objectives: Studies have shown that chronobiological factors may adversely affect glycemic control in patients with type 2 diabetes mellitus. We assessed the association of chronobiological factors with glycemic control and neonatal birth weight in women with GDM. Methods: A prospective cohort study included 208 women aged 18–45 years with a singleton pregnancy who were randomly selected from among women undergoing follow-up for GDM at the Maternal-Fetal Medicine Unit of a tertiary medical center. Nutrition, sleep, and lifestyle patterns were assessed from onset of GDM until birth along with glycemic control and birth outcomes. Results: Multivariate analyses on a cohort of 208 women revealed that suboptimal glycemic control was associated with a late breakfast (RR = 2.26; 95% CI 1.09–4.67), increased carbohydrate intake in the evening (RR = 1.19; 95% CI 1.003–1.42), and poor sleep quality (RR = 2.14; 95% CI 1.04–4.41). The adjusted relative risk for neonatal birth weight above the 85th percentile was associated with increased carbohydrate intake in the morning (RR = 1.70; 95% CI 1.30–2.23) and increased carbohydrate intake in the evening (RR = 1.39; 95% CI 1.16–1.67). Conclusions: Chronobiological factors are associated with suboptimal glycemic control and birth weight above the 85th percentile in women with GDM. The study was registered under ClinicalTrials.gov.org, identifier: NCT02916667.
Effects of a Rosmarinus officinalis L. Extract and Rosmarinic Acid in Improving Streptozotocin-Induced Aortic Tissue Damages in Rats
Authors: Ielciu Irina , Filip Gabriela Adriana , Sevastre-Berghian Alexandra C. , Bâldea Ioana , Olah Neli-Kinga , Burtescu Ramona Flavia , Toma Vlad Alexandru , Moldovan Remus , Oniga Ilioara , Hanganu Daniela
Published: December 2024

Background/Aim: Rosmarinus officinalis L. (R. officinalis) is an aromatic medicinal species with important nutraceutical potential, having rosmarinic acid (RA) as one of its main metabolites. The present study aims to evaluate the effects of an extract obtained from the leaves of this species and of its main metabolite in improving the streptozotocin-induced damage of hearts and aorta of diabetic rats. Methods: The leaves of the species were used to obtain a hydroethanolic extract, which was analyzed using the LC/MS method. Diabetes mellitus was induced by intraperitoneal streptozotocin administration in rats. After two weeks, oxidative stress parameters were evaluated from the heart and aorta homogenates. NOS3, AMPK, and adiponectin levels were quantified using ELISA tests, and thoracic aorta rings were isolated for contractility evaluation in the organ bath. Phospho-NF-κB, NRF2, HIF1 alfa, iNOS, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) quantification were performed using the Western blot technique. Results: Carnosic acid, together with rosmarinic acid, were proven to be the main metabolites identified in the composition of the tested extract. Administration of the extract and of RA improved the relaxation response to acetylcholine and the redox status, with the reduction in malondialdehyde (MDA), nitric oxide synthase 3 (NOS 3), AMP-activated protein kinase (AMPK), adiponectin, reduced (GSH) and oxidized glutathione (GSSG) levels, and superoxide dismutase (SOD) activity. RA significantly enhanced the expression of HIF 1α, NRF2, and pNFkB in the heart. Conclusions: Administration of the R. officinalis extract and of RA-alleviated oxidative stress, proving vascular and cardiac antioxidant properties in the hearts and aorta of diabetic rats.
Association Between Serum Folate Concentrations and 10-Year Stroke Risk in a Prospective Community Cohort: Mediation and Interaction Analyses
Authors: Liang Zhe , Fan Fangfang , Liu Bo , Li Kaiyin , Chen Hongyu , Jia Jia , Huo Yong , Li Jianping , Zhang Yan
Published: December 2024

The relationship between folate concentrations and stroke risk remains unestablished, and the mediation effect of homocysteine (Hcy) and interaction effect of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism has yet to be investigated. This cohort study involved 4903 subjects derived from a Chinese community population. The association between folate and first stroke was examined in Cox proportional hazard regression models. The mediation analyses involving Hcy and the undiscovered modification of the MTHFR C677T genotype were assessed. The mean (SD) age of subjects was 56.7 (8.8) years old, and 37.0% were male. A total of 407 strokes, 375 ischemic strokes and 47 hemorrhagic strokes occurred during the mean (SD) follow-up of 9.3 (1.8) years. The participants in the highest folate quartile (≥8.2 ng/mL) exhibited a lower stroke risk compared to those in the lowest quartile (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.50–0.93, p = 0.017; p for trend = 0.009). Hcy significantly mediated 14.51% of the relationship between folate and stroke in the fully adjusted model. Only in individuals with the MTHFR 677CC genotype but not CT/TT genotype was folate adversely correlated with stroke (HR: 0.88, 95% CI: 0.79–0.97, p for interaction = 0.026) and ischemic stroke (HR: 0.88, 95% CI: 0.80–0.98, p for interaction = 0.035). Insufficient folate concentrations were associated with a heightened 10-year stroke risk, in which Hcy concentrations played a crucial mediating role. MTHFR C677T gene polymorphism could potentially modify the folate–stroke relationship.
Tremella fuciformis Berk Alleviated Atherosclerosis Symptoms via Nuclear Factor-Kappa B-Mediated Inflammatory Response in ApoE−/− Mice
Authors: Dong Yihao , Zhang Qinchun , Xie Rui , Zhao Jundi , Han Zhihua , Li Yu , Yu Han , Zhang Yongfeng
Published: December 2024

Background: Atherosclerosis, a persistent inflammatory disease marked by the presence of atherosclerotic plaques or fibrous plaques, is a significant contributor to the onset of the development of cardiovascular disease. Tremella fuciformis Berk contains various active ingredients that have anti-inflammatory, antioxidant, and hypolipidemic properties. Nevertheless, the potential effects of T. fuciformis on atherosclerosis have not been systematically reported. Method: In this study, ApoE−/− mice were employed as models of atherosclerosis caused by a high-fat diet (HFD) to investigate the effect of T. fuciformis. Gut microbiota and serum metabolism analysis were performed to elucidate the potential mechanism of T. fuciformis for its anti-atherosclerosis effects. Results: T. fuciformis significantly decreased the aortic root wall thickness and the area of lipid droplets, regulated lipid levels, and inhibited fat accumulation to improve aortic root lesions. Furthermore, T. fuciformis significantly altered serum metabolite (including diethyl phthalate and succinate) levels, regulated the abundance of microbiota, such as Coriobacteriaceae_UCG-002 and Alistipes, and suppressed the inflammatory response to ameliorate atherosclerosis via the nuclear factor-kappa B (NF-κB)-mediated inflammatory response in HFD-induced ApoE−/− mice. Conclusions: These results offer a theoretical basis and data to support T. fuciformis as a potential strategy for treating atherosclerosis.
A Risk Score to Identify Low Bone Mineral Density for Age in Young Patients with Anorexia Nervosa
Authors: Maimoun Laurent , Huguet Helena , Renard Eric , Lefebvre Patrick , Seneque Maude , Gaspari Laura , Boudousq Vincent , Maimoun Nande Lisa , Courtet Philippe , Sultan Charles , Mariano-Goulart Denis , Picot Marie-Christine , Guillaume Sebastien
Published: December 2024

Objective: Developing a scoring assessment tools for the determination of low bone mass for age at lumbar spine and hip in patients with anorexia nervosa (AN). Methods: The areal bone mineral density (aBMD) was determined with dual-energy X-ray absorptiometry (DXA). In 331 women with AN and 121 controls, aged from 14.5 to 34.9 years, univariate and multivariate logistic regression analyses were performed to address the association of Z-score aBMD evaluated at lumbar spine and hip with several parameters. Results: For the lumbar spine and hip, the three risk factors significantly and independently associated with Z-score aBMD were age of patients (variable in class ≥20 year vs. <20 year), minimal disease-related BMI (continuous variable), and duration of amenorrhea without contraceptive use (variable in class ≥18 months vs. <18 months), with close values for the odds ratio for the two bone sites. A simple risk score equation was developed and tested combining only these three parameters. The AUC’s measuring the score’s performance were, respectively, 0.85 [95% CI: 0.79–0.90] with a sensitivity of 83% and specificity of 71%, and 0.82 [95% CI: 0.76–0.86] with a sensitivity of 92% and specificity of 55% to detect low aBMD in lumbar spine and hip. The cut-off values for low bone mass for age were 0.9 and 1.33 for the two bone sites. The prediction model revealed that a minimum of 83% of the patients presenting low bone mass for age were correctly identified. Conclusions: the study presents for the first time a risk score for diagnosing low bone mass for age in young patients with AN. Considering its excellent sensitivity, and its ease of use, requiring only three parameters that are well identified in this disease, this new score may be useful in clinical settings when DXA scans are not feasible.
Effect of Cashew Nut Consumption on Biomarkers of Copper and Zinc Status in Adolescents with Obesity: A Randomized Controlled Trial
Authors: Dias Thaynan dos Santos , Almondes Kaluce G. de S. , Firmino Matheus A. D. , Oliveira Luis Felipe N. de , Freire Walter B. de S. , Barbosa Fernando , Nogueira Maria Dinara de A. , Pires Liliane V. , Martínez-Vizcaíno Vicente , Mesas Arthur E. , Moreno Luis A. , Maia Carla S. C.
Published: December 2024

Background: Children and adolescents with obesity have altered serum copper (Cu) and zinc (Zn) levels, which are associated with oxidative stress, inflammation, and health outcomes. The inclusion of cashew nuts in an adequate diet may provide health benefits and help improve the mineral status of individuals with obesity. Objective: To evaluate the effects of cashew nut consumption on biomarkers of Cu and Zn status in adolescents with obesity. Methods: This was a randomized controlled trial conducted in adolescents. The participants were divided into a control group (CON) and a cashew nut group (CASN). The CASN group received 30 g/day of roasted cashew nuts for 12 weeks, and both groups received nutritional counseling during the study. Anthropometric, dietary, and biochemical parameters (Zn, Cu, and superoxide dismutase (SOD)) were assessed at the baseline and at the end of the study. Association tests, within-group and between-group mean comparisons, and analyses of variation between study periods (Δ T12-T0) were performed. Results: The sample consisted of 81 adolescents who completed the intervention period, resulting in 54 in the CASN group and 27 in the CON group. After the intervention, the CASN group presented a decrease in plasma Cu (p = 0.004) and an increase in SOD (p = 0.030). Both groups showed an increase in plasma Zn (p < 0.050) and a decrease in the Cu/Zn ratio (p < 0.001). CASN had a negative effect on the Cu concentration, which was significantly different from that of CON (p = 0.004). Conclusions: The consumption of cashew nuts for 12 weeks reduced plasma Cu levels in adolescents with obesity. Nutritional counseling may have contributed to the increase in plasma Zn levels in all the study participants.
Understanding Health Literacy Among Migrants in Portugal: The Impact of Environmental Issues
Authors: Machado Rosa , Garcia Madalena , Serra Isaura , João Ana Lúcia
Published: December 2024

Background/Objectives: The health of migrant populations is strongly influenced by social, cultural, and environmental factors. Promoting health literacy (HL) is essential to empower these populations and reduce health inequalities. We aimed to assess the perceptions and behaviors of migrants residing in a neighborhood within a municipality in the Metropolitan Area of Lisbon regarding health risks arising from environmental conditions, as well as to determine their level of health literacy. Methods: Our cross-sectional, descriptive, exploratory study used the Health Literacy Questionnaire. This study was conducted with ethical approval including a sample of 101 participants. We performed descriptive and inferential statistical analyses using the Statistical Package for the Social Sciences (SPSS) version 29. Results: Most participants were from Portuguese-speaking countries and reported issues with indoor humidity and inadequate thermal comfort in both hot and cold conditions. The primary environmental issues identified included stagnant water, organic waste, and deficient electrical networks. Conclusions: The results revealed precarious housing conditions and inadequate support infrastructure, posing significant environmental health risks. Data revealed low levels of health literacy across most domains assessed.
Checklist of Medico-Veterinary Important Biting Flies (Ceratopogonidae, Hippoboscidae, Phlebotominae, Simuliidae, Stomoxyini, and Tabanidae) and Their Associated Pathogens and Hosts in Maghreb
Authors: Azzouzi Chaimaa , Rabah-Sidhoum Noureddine , Boucheikhchoukh Mehdi , Mechouk Noureddine , Sedraoui Scherazad , Benakhla Ahmed
Published: December 2024

Biting flies are hematophagous dipterans belonging to various taxonomic groups, such as the Hippoboscidae, Ceratopogonidae, Simuliidae, Tabanidae, Muscidae, and Psychodidae families, some of which have significant medical and veterinary importance. They can host and spread various infections to humans and livestock and cause allergic reactions with their saliva. Several species of different families are present in the western Mediterranean region, with new species gradually being discovered. This study focuses on the brachyceran and the nematoceran species; it provides a systematic review listing all reported taxa of biting flies in the Maghreb countries (Algeria, Morocco, and Tunisia). Additionally, the study includes a geo-historical reconstruction of distribution maps for species of epidemiological importance. The associated pathogens and hosts are also included in the checklists, alongside information on the biology and ecology of these parasitic arthropods, to offer a comprehensive overview of the state of dipteran-borne disease surveillance in North African countries. Overall, this work could serve as an exhaustive reference for entomologists and breeders participating in controlling biting fly and midge populations, whether from a technical or research perspective.
Cold Plasma Activity Against Biofilm Formation of Prosthetic Joint Infection Pathogens
Authors: Spiegel Christopher , Coraça-Huber Débora C. , Nogler Michael , Arora Rohit , Putzer David
Published: December 2024

Periprosthetic joint infections occur in 1–2% of all patients undergoing prosthetic joint surgeries. Although strong efforts have been made to reduce infection rates, conventional therapies like one- or two-stage revisions have failed to lower the infection rates. Cold atmospheric plasma (CAP) has shown promising results in reducing bacterial loads on surfaces. In this study, we aimed to investigate the ability of CAP to reduce the bacterial load on metal surfaces with varying distances and different plasma compositions below a temperature suitable for in vivo applications. Methods: Biofilm was formed with Staphylococcus aureus ATCC 29213 and Staphylococcus epidermidis ATCC 12228 cultures on TMZF discs. Plasma treatments using air plasma and argon plasma were conducted on discs containing the established biofilm while the temperature was measured. During the experiments, the duration and the distance of plasma application varied. Afterwards, colony-forming units were counted. Results: The results of this study showed that air and argon plasma could be considered for applications during surgeries at a 1 cm distance. While air plasma showed the highest efficiency in CFU reduction, the temperature generation due to the presence of oxygen poses a limitation concerning the duration of application. The use of argon as a plasma generator does not show the temperature limitation in correlation to exposure time. The use of air plasma with a distance of 1 cm to the application site and an exposure time of 5 s showed the most effective bacterial reduction while not exceeding tissue-damaging temperatures.
Microbial Dynamics in Endodontic Pathology—From Bacterial Infection to Therapeutic Interventions—A Narrative Review
Authors: Wieczorkiewicz Klara , Jarząbek Anna , Bakinowska Estera , Kiełbowski Kajetan , Pawlik Andrzej
Published: December 2024

Endodontic infection is a penetration of microorganisms into the dental pulp. Bacteria are the most common entities that induce an infection. This state is associated with significant pain and discomfort. Therapeutic intervention involves removal of infected pulp from the tooth and roots, which eliminates viable tissue, thus creating a tooth less resistant to mechanical pressure. Studies suggest that there are several types of bacteria most commonly associated with endodontic infections. Furthermore, it is considered that different types of pathogens could play a major role in primary and secondary endodontic infections. The aim of this review is to summarize major bacteria involved in the process of endodontic infection. Furthermore, we discuss the bacterial properties that allow them to penetrate dental pulp and hypothesize about possible future treatment strategies.
The Proviral Reservoirs of Human Immunodeficiency Virus (HIV) Infection
Authors: Murzin Andrey I. , Elfimov Kirill A. , Gashnikova Natalia M.
Published: December 2024

Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction. If treatment is not effective enough or is interrupted, the proviral reservoir can reactivate. Early initiation of ART improves the prognosis of the course of HIV infection, which is explained by the reduction in the proviral reservoir pool observed in the early stages of the disease. Different HIV subtypes present differences in the number of latent reservoirs, as determined by structural and functional differences. Unique signatures of patients with HIV, such as elite controllers, have control over viral replication and can be said to have achieved a functional cure for HIV infection. Uncovering the causes of this phenomenon will bring humanity closer to curing HIV infection, potential approaches to which include stem cell transplantation, clustered regularly interspaced short palindromic repeats (CRISPR)/cas9, “Shock and kill”, “Block and lock”, and the application of broad-spectrum neutralizing antibodies (bNAbs).
The Prevalence of Enteric Viruses in Bivalve Molluscs in a Farming Area in Liguria, Northwest Italy
Authors: Masotti Chiara , Serracca Laura , Costa Erica , Betti Barbara , Garcia-Vozmediano Aitor , Suffredini Elisabetta , Battistini Roberta
Published: December 2024

Bivalve molluscs are filter-feeding organisms, capable of concentrating pathogenic microorganisms from the surrounding environment, thus contributing to the spread of viral pathogens, which they can transmit to humans, especially if eaten raw or undercooked. Although norovirus (NoV) and the hepatitis A virus (HAV) are considered the most common causes of foodborne infections, in recent years, other viruses with a zoonotic potential have been identified in shellfish, such as the hepatitis E virus (HEV), astrovirus (AsV), and aichi virus (AiV). The aim of the study was to investigate the presence of classical and emerging pathogenic enteric viruses in oysters (Crassostrea gigas) and mussels (Mytilus galloprovincialis) from a mollusc farming area in the northwest of Italy, between April 2022 and March 2023. In the period considered, a total of 168 samples (84 oysters and 84 mussels) were analysed. The prevalence of NoV was highest, with 32.7% (55/168) positive samples, followed by 18.4% (31/168) for AsV and 19.6% (33/168) for AiV. This study revealed, for the first time, the presence of AsV and AiV in molluscs farmed in this sea area. All the samples tested were negative for HAV and HEV. The emergence of new enteric viruses like AiV and AsV in bivalve molluscs underscores the importance of improving surveillance and environmental monitoring methods, particularly in shellfish production areas.
Exploring the Chemopreventive Potential of Artemisia annua Methanolic Extract in Colorectal Cancer Induced by Azoxymethane in Mice
Authors: Alrumaihi Faris
Published: December 2024

Background/Objectives: Colorectal cancer (CRC) remains a major global health burden, necessitating innovative preventive approaches. Artemisia annua (A. annua), known for its extensive pharmacological properties, has shown potential in cancer therapy. This study investigates the chemopreventive efficacy of methanolic extract of A. annua (MEA) in an azoxymethane (AOM)-induced murine model of CRC, with a focus on its antioxidant, biomarker modulation, and pro-apoptotic activities. Methods: MEA was obtained via cold solvent extraction, yielding 39%, and demonstrated potent in vitro cytotoxicity against HCT116 and RKO colon cancer cell lines, with IC50 values of 20 µg/mL and 15 µg/mL, respectively. Swiss albino mice were treated with MEA beginning two weeks before AOM induction, with treatment continuing for 21 weeks. Survival was monitored for 40 weeks. Key outcomes included serum biomarker levels (ADA, GGT, CD73, LDH), antioxidant enzyme activities (SOD, CAT, GPx1, MDA), reactive oxygen species (ROS) modulation, apoptosis induction, and histopathological evaluation. Results: MEA significantly improved survival rates, reduced AOM-induced weight loss, and modulated cancer biomarkers, with marked reductions in ADA, GGT, CD73, and LDH levels. Antioxidant defenses were restored, as evidenced by increased SOD, CAT, and GPx1 activities and decreased MDA levels. ROS levels were significantly reduced, and apoptosis in colonic cells was effectively induced. Histopathological analysis revealed substantial mitigation of CRC-associated morphological abnormalities. Conclusions: MEA exhibits robust chemopreventive properties, demonstrating its potential to reduce oxidative stress, modulate key biomarkers, and induce apoptosis in CRC. These findings position MEA as a promising natural candidate for CRC prevention and therapy, warranting further exploration for clinical application.
GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy
Authors: Patel Shikha , Saxena Bhagawati , Mehta Priti , Niazi Sarfaraz K.
Published: December 2024

Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists’ clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.
Microbial Pattern in Amniotic Fluid from Women with Premature Rupture of Membranes and Meconium-Stained Fluid
Authors: Herawati Fauna , Rahaded Patricia Valery , Hartono Ruddy , Yulia Rika
Published: December 2024

Intra-amniotic infection (IAI), also known as chorioamnionitis, is a major cause of maternal and neonatal infection that occurs during pregnancy, labor and delivery, or in the postpartum period. Conditions such as meconium-stained amniotic fluid (MSAF) and premature rupture of membranes (PROMs) are recognized risk factors for amniotic fluid infection. This study identifies the microbial patterns in the amniotic fluid of women with PROMs and MSAF to determine the presence and types of bacterial growth. It also identifies trends in antibiotic use through descriptive statistics. Conducted as a descriptive observational study with prospective data collection, this research included maternal patients with PROMs lasting more than 12 h and those with MSAF, along with their infants. Of 30 cultured amniotic fluid samples, bacterial growth was observed in 13 cases, with Escherichia coli being the most prevalent (40%). Infants born with PROMs accompanied by MSAF were 5.5 days, significantly longer than those born with PROMs alone (3.19 days) or MSAF alone (3.91 days), with a significant difference between groups (p = 0.003). In addition, Escherichia coli isolates in this study are resistant to ceftriaxone, a third-generation cephalosporin antibiotic. Understanding these microbial patterns is critical for guiding clinical decisions, particularly in managing the risk of infection in pregnant women with PROMs and MSAF and ensuring better outcomes for both mothers and newborns.
Development of Novel Oral Delivery Systems Using Additive Manufacturing Technologies to Overcome Biopharmaceutical Challenges for Future Targeted Drug Delivery
Authors: Cirilli Micol , Krause Julius , Gazzaniga Andrea , Weitschies Werner , Cerea Matteo , Rosenbaum Christoph
Published: December 2024

Background/Objectives: The development of targeted drug delivery systems for active pharmaceutical ingredients with narrow absorption windows is crucial for improving their bioavailability. This study proposes a novel 3D-printed expandable drug delivery system designed to precisely administer drugs to the upper small intestine, where absorption is most efficient. The aim was to design, prototype, and evaluate the system’s functionality for organ retention and targeted drug release. Methods: The system was created using 3D printing technologies, specifically FDM and SLA, with materials such as PLA and HPMC. The device was composed of matrices and springs, with different spring geometries (diameter, coil number, and cross-sectional shape) being tested for strength and flexibility. A gastro-resistant string was used to maintain the device in a compact configuration until it reached the neutral pH environment of the small intestine, where the string dissolved. The mechanical performance of the springs was evaluated using a texture analyzer, and the ability of the system to expand upon pH change was tested in simulated gastrointestinal conditions. Results: The results demonstrated that the system remained in the space-saving configuration for two hours under acidic conditions. Upon a pH change to 6.8, the system expanded as expected, with opening times of 5.5 ± 1.2 min for smaller springs and 2.5 ± 0.3 min for larger springs. The device was able to regain its expanded state, suggesting its potential for controlled drug release in the small intestine. Conclusions: This prototype represents a promising approach for targeted drug delivery to the upper small intestine, offering a potential alternative for drugs with narrow absorption windows. While the results are promising, further in vivo studies are necessary to assess the system’s clinical potential and mechanical stability in real gastrointestinal conditions.
Peptide Aptamer–Paclitaxel Conjugates for Tumor Targeted Therapy
Authors: Shen Xinyang , Ma Yuan , Luo Hang , Abdullah Razack , Pan Yufei , Zhang Yihao , Zhong Chuanxin , Zhang Baoting , Zhang Ge
Published: December 2024

Background/Objectives: Traditional paclitaxel therapy often results in significant side effects due to its non-specific targeting of cancer cells. Peptide aptamer–paclitaxel conjugates present a promising alternative by covalently attaching paclitaxel to a versatile peptide aptamer via a linker. Compared to antibody–paclitaxel conjugates, peptide aptamer–paclitaxel conjugates offer several advantages, including a smaller size, lower immunogenicity, improved tissue penetration, and easier engineering. Methods: This review provides an in-depth analysis of the multifunctional peptide aptamers in these conjugates, emphasizing their structural features, therapeutic efficacy, and challenges in clinical applications. Results: This analysis highlights the potential of peptide aptamer–paclitaxel conjugates as a novel and effective approach for targeted cancer therapy. By harnessing the unique properties of peptide aptamers, these conjugates demonstrate significant promise in improving drug delivery efficiency while reducing the adverse effects associated with traditional paclitaxel therapy. Conclusions: The incorporation of peptide aptamers into paclitaxel conjugates offers a promising pathway for developing more efficient and targeted cancer therapies. However, further research and clinical studies are essential to fully unlock the therapeutic potential of these innovative conjugates and enhance patient outcomes.
Enhanced Drug Skin Permeation by Azone-Mimicking Ionic Liquids: Effects of Fatty Acids Forming Ionic Liquids
Authors: Oshizaka Takeshi , Kodera Shunsuke , Kawakubo Rika , Takeuchi Issei , Mori Kenji , Sugibayashi Kenji
Published: December 2024

Background/Objectives: Laurocapram (Azone) attracted attention 40 years ago as a compound with the highest skin-penetration-enhancing effect at that time; however, its development was shelved due to strong skin irritation. We had already prepared and tested an ante-enhancer (IL-Azone), an ionic liquid (IL) with a similar structure to Azone, consisting of ε-caprolactam and myristic acid, as an enhancer candidate that maintains the high skin-penetration-enhancing effect of Azone with low skin irritation. In the present study, fatty acids with different carbon numbers (caprylic acid: C8, capric acid: C10, lauric acid: C12, myristic acid: C14, and oleic acid: C18:1) were selected and used with ε-caprolactam to prepare various IL-Azones in the search for a more effective IL-Azone. Methods: Excised porcine skin was pretreated with each IL-Azone to assess the in vitro skin permeability of antipyrine (ANP) as a model penetrant. In addition, 1,3-butanediol was selected for the skin permeation test to confirm whether the effect of IL-Azone was due to fatty acids and if this effect differed depending on the concentration of IL-Azone applied. Results: The results obtained showed that C12 IL-Azone exerted the highest skin-penetration-enhancing effect, which was higher than Azone. On the other hand, many of the IL-Azones tested had a lower skin-penetration-enhancing effect. Conclusions: These results suggest the potential of C12 IL-Azone as a strong and useful penetration enhancer.
Empowering Patient Safety: Assessment of Adverse Drug Reaction Knowledge and Practice Among Pharmacy Professionals
Authors: Bukić Josipa , Leskur Dario , Durdov Toni , Božić Joško , Modun Darko , Šešelja Perišin Ana , Ančić Daniela , Šepetavc Martina , Mihanović Ante , Rušić Doris
Published: December 2024

Despite technological advancements, healthcare professionals must actively prioritize patient safety. Reporting adverse drug reactions is a critical aspect of this responsibility, and the most accessible healthcare providers, community pharmacists, and pharmacy technicians play a key role. Therefore, this study assessed their knowledge and practices regarding adverse drug reaction reporting in Croatia. A total of 180 participants were included. Pharmacists demonstrated significantly better knowledge than technicians (94.78 vs. 73.97, p = 0.024). Chronic medication users also showed greater understanding compared to non-users (104.96 vs. 85.39, p = 0.021). Knowledge improved with the number of adverse drug reactions reported, and most participants (72.78%) had reported adverse drug reactions. Pharmacists were 83.60% more likely to report adverse drug reactions than technicians (p < 0.001). These findings reveal a gap in pharmacy technicians’ integration into pharmacovigilance, underscoring a need to strengthen their role in adverse drug reaction reporting and patient safety.