Screening of essential oils against oxacillin - resistant Staphylococcus aureus strains isolated from bovine mastitis / Screening de aceites esenciales frente a Staphylococcus aureus oxacilino - resistentes extraidos de aislados de mastitis bovina

Bovine mastitis is a disease wi th far - reaching consequences for the dairy industry. Staphylococcus aureus is a pathogen that is especially resistant to antibiotics. The objective of this study was to evaluate the antimicrobial activity of the essential oils Lippia citriodora (Lam.), Thy mus vulgaris (L), and a mixture of the essential oils Lippia citriodora and Thymus vulgaris (50/50 v/v), against isolates of oxacillin - resistant Staphylococcus aureus (n=15) of positive cases of bovine mastitis. For the statistical analysis, the IBM SPSS s tatistical package was used. The mixture of essential oils ( Lippia citriodora and Thymus vulgaris (50/50 v/v)) obtained the most significant antimicrobial activity in relation to pure essential oils. It is therefore concluded that the mixture of these oils boosts their antimicrobial activity ( p <0.05). The minimum inhibitory and bactericidal concentration of this mixture for the total isolations was 12 µL/L and 25 µL/mL, respectively.

La mastitis bovina es una enfermedad de gran impacto para la industria lechera. El Staphylococcus aureus es uno de los principales patógenos, especialmente aquellos resistentes a los antibióticos. El objetivo de este estudio fue evaluar la actividad antimicrobiana de los aceites esenciales de Lippia citriodora (Lam.), Thymus vulgaris (L), y una mezcla de aceites esenciales de Lippia citriodora y Thymus vulgaris (50/50 v/v), frente a aislamientos clínicos de Staph ylococcus aureus oxacilino - resistentes (n=15) de mastitis bovina. Se utilizó p rograma estadístico IBM SPSS y se concluyó la diferencia significativa a un p <0.05. La mezcla de aceites esenciales ( Lippia citriodora y Thymus vulgaris (50/50 v/v)), obtuvo la m ayor actividad antimicrobiana en relación a los aceites esenciales puros, se concluye que la mezcla de estos aceites potencia su actividad antimicrobiana ( p <0.019). La concentración mínima inhibitoria y bactericida de esta mezcla fue del 12 µL/mL y 25 µL/m L, respectivamente, y puede ser una alternativa terapéutica.

How to Assess Oral Narrative Skills of Children and Adolescents with Intellectual Disabilities: A Systematic Review.

Children and adolescents with intellectual disabilities (ID) often encounter difficulties with narrative skills. Yet, there is a lack of research focusing on how to assess these skills in this population. This study offers an overview of the tools used for assessing oral narrative skills in children and adolescents with ID, addressing key questions about common assessment tools, their characteristics, and reported evidence. A systematic review was conducted of the literature published between 2010 and 2023 in the PsycINFO, ERIC, Education, and Psychology databases. An initial 1176 studies were reviewed by abstract, of which 485 were read in full text, leading to the selection and analysis of 22 studies. Most of the identified tools involve analyzing language samples obtained using wordless picture story books. Three common tools are emphasized. Studies have primarily identified inter-rater reliability and test-criterion evidence for validity. The main tools and their characteristics are discussed in depth to aid readers in discerning suitable options for research or practical applications. The importance of reporting diverse sources of evidence for validity and reliability within this population is highlighted.

Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.

Increasing primary care capacity and referral efficiency: A case study of a telehealth centre eConsult service in Brazil.

INTRODUCTION: eConsults are asynchronous digital communications for primary care professionals to seek timely specialist advice. Potential benefits include increased primary healthcare capacity and referral efficiency. Santa Catarina Telehealth Centre in Brazil has offered eConsults for an increasing number of specialties since 2008. This study described the characteristics of this service, including referral efficiency, sustainability, and satisfaction. METHODS: Retrospective longitudinal analysis of eConsults activity data from 2015 to 2022 with three domains of the Model for Assessment of Telemedicine Applications used to structure the analysis. RESULTS: Characteristics of the application: The total number of eConsults performed in 2015 was 4764, reaching 41,178 in 2022. While 30.3% of eConsults were synchronous in 2015, only asynchronous communication remained from 2021. Clinical effectiveness: eConsults requested to refer patients to specialist care resulting in primary care management remaining above 30% of the total for all specialties from 2019 to 2022, with hematology having the highest percentage (>52%). Organizational aspects: Established workflows with local specialists responding to eConsults (cardiology, endocrinology, hematology and orthopaedics) kept a constant or increasing number of eConsults and maintained the proportion of primary care management from 2019 to 2022, once recovered from COVID-19 and funding restrictions-related reductions. Over 90% of primary care professionals are either satisfied or very satisfied with the eConsult service. CONCLUSION: Over 8 years, 223,734 consultations were conducted, with high satisfaction, demonstrating the substantial potential for increased primary care-sensitive conditions management. Hiring local specialists, fostering integrated care, and enabling sustainable workflows are key to eConsults' success.

Antioxidants in Photoaging: From Molecular Insights to Clinical Applications.

Photoaging (PA) is considered a silent disease affecting millions of people globally and is defined as skin damage due to prolonged exposure to ultraviolet radiation (UVR) from the sun. Physiologically, the skin is in a state of renewal and synthesis of components of the extracellular matrix (ECM). However, exposure to UVR affects the production of the ECM, and the functioning and response of skin cells to UVR begins to change, thus expressing clinical and phenotypic characteristics of PA. The primary mechanisms involved in PA are direct damage to the DNA of skin cells, increases in oxidative stress, the activation of cell signaling pathways responsible for the loss of skin integrity, and cytotoxicity. The medical and scientific community has been researching new therapeutic tools that counteract PA, considering that the damage caused by UVR exceeds the antioxidant defense mechanisms of the skin. Thus, in recent years, certain nutraceuticals and phytochemicals have been found to exhibit potential antioxidant and photoprotective effects. Therefore, the main objective of this review is to elucidate the molecular bases of PA and the latest pharmaceutical industry findings on antioxidant treatment against the progression of PA.

Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients: a controlled clinical trial (Alantel Trials).

BACKGROUND: Dermatitis is a skin condition caused by multiple causes, including radiotherapy treatment. Pharmacological treatments can become chronic and are not exempt from side effects. The latest recommendations of the American Academy of Dermatology establish the use of natural, nourishing, and moisturizing cosmetic products as prevention and the first therapeutic step for dermatitis. Alantel® is a cream developed to reduce redness and irritation, promote the local immune system, combat immunosenescence, and promote the healing of epidermal lesions. The objective was to evaluate the effect of a cream (Alantel) based on natural products at high concentrations for the preventive and curative treatment (at early stages) of radiation-induced dermatitis in patients with breast cancer. METHODS: Our protocol is an experimental, prospective, triple-blind, multicenter, controlled clinical trial with two parallel arms. The experimental group will be treated with Alantel, while the control group will receive another moisturizing cream. Radiotherapy oncology professionals will recruit a total of 88 patients (44 per comparison group) with breast cancer who will receive radiotherapy oncology treatment for 15 days, and they will be randomly allocated to the experimental or control group. Selected patients will be followed up for four visits by primary care physicians for up to 1 week after completion of radiotherapy. The main study variable will be the incidence rate of mild post-radiation dermatitis. An intention-to-treat analysis will be performed, applying a comparison test for independent means and proportions. A bivariate and multivariate analysis will also be developed to check the treatment effect, adjusting for predictive sociodemographic and clinical variables. DISCUSSION: By carrying out this clinical trial, it is expected to verify that Alantel cream, based on natural products at high concentrations, has advantages over a moisturizing cream for the preventive and curative treatment of RD in patients with breast cancer. The COVID-19 pandemic has been influenced by delaying the start of the study. One of the main limitations of this study will be the time required to recruit the patients from the planned sample, given that the selection criteria are restrictive and, although the study is multicenter, recruitment will be coordinated through a single service on radiotherapy oncology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04116151 . Registered on 4 October 2019.

Characterization of the invasive macroalgae Rugulopteryx Okamurae for potential biomass valorisation.

This study aimed to examine the composition and properties of the invasive macroalgae R. okamurae and explore potential applications. The results showed that the seaweed biomass is mainly composed of structural carbohydrates, with alginate being the main constituent, accounting for 32 % of its total composition and with a mannuronic and guluronic acid ratio (M/G) ratio of 0.93. It also has a relatively high concentration of fucose, related to the presence of fucoidans that have important biological functions. Among the mineral contents, a high magnesium and calcium (7107 and 5504 mg/kg) concentration, and the presence of heavy metals above legislated thresholds, were notable. R. okamurae also contained a high lipid content of 17 %, mainly composed of saturated fatty acids, but with a significant fraction of n3 polyunsaturated fatty acids (18 %) resulting in a low n6/n3 ratio (0.31), that has health benefits. The protein content of R. okamurae was 12 %, with high-quality proteins, as essential amino acids (mainly leucine, phenylalanine and valine) constitute 32 % of the total amino acids. It also showed a high polyphenol content and outstanding antioxidant properties (106.88 mg TE/g). Based on these findings, R. okamurae has significant potential as a sustainable source of bioactive compounds that can add value to different sectors, including food, feed, pharmaceuticals and cosmetics.

Engineering Proteins for PEDOT Dispersions: A New Horizon for Highly Mixed Ionic-Electronic Biocompatible Conducting Materials.

Poly (3,4-ethylenedioxythiophene) (PEDOT) doped with polystyrene sulfonate (PSS) is the most used conducting polymer from energy to biomedical applications. Despite its exceptional properties, there is a need for developing new materials that can improve some of its inherent limitations, e.g., biocompatibility. In this context, doping PEDOT is propose with a robust recombinant protein with tunable properties, the consensus tetratricopeptide repeated protein (CTPR). The doping consists of an oxidative polymerization, where the PEDOT chains are stabilized by the negative charges of the CTPR protein. CTPR proteins are evaluated with three different lengths (3, 10, and 20 identical CTPR units) and optimized varied synthetic conditions. These findings revealed higher doping rate and oxidized state of the PEDOT chains when doped with the smallest scaffold (CTPR3). These PEDOT:CTPR hybrids possess ionic and electronic conductivity. Notably, PEDOT:CTPR3 displayed an electronic conductivity of 0.016 S cm-1 , higher than any other reported protein-doped PEDOT. This result places PEDOT:CTPR3 at the level of PEDOT-biopolymer hybrids, and brings it closer in performance to PEDOT:PSS gold standard. Furthermore, PEDOT:CTPR3 dispersion is successfully optimized for inkjet printing, preserving its electroactivity properties after printing. This approach opens the door to the use of these novel hybrids for bioelectronics.

Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study.

Early-stage colorectal carcinoma (CRC)-pT1-is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5-2%. Among these cases, approximately 6-16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/µL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management.

Identification of a de novo mutation in TLK1 associated with a neurodevelopmental disorder and immunodeficiency.

Background: The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants are associated with 'Intellectual Disability, Autosomal Dominant 57' (MRD57), a neurodevelopmental disorder (NDD) characterized by intellectual disability (ID), autism spectrum disorder (ASD) and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown. Methods: A male patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency was determined to have a novel, heterozygous variant in TLK1 (c.1435C>G, p.Q479E) by genome sequencing (GS). Single cell gel electrophoresis, western blot, flow cytometry and RNA-seq were performed in patient-derived lymphoblast cell lines. In silico, biochemical and proteomic analysis were used to determine the functional impact of the p.Q479E variant and previously reported NDD-associated TLK1 variant, p.M566T. Results: Transcriptome sequencing in patient-derived cells confirmed expression of TLK1 transcripts carrying the p.Q479E variant and revealed alterations in genes involved in class switch recombination and cytokine signaling. Cells expressing the p.Q479E variant exhibited reduced cytokine responses and higher levels of spontaneous DNA damage but not increased sensitivity to radiation or DNA repair defects. The p.Q479E and p.M566T variants impaired kinase activity but did not strongly alter localization or proximal protein interactions. Conclusion: Our study provides the first functional characterization of TLK1 variants associated with NDDs and suggests potential involvement in central nervous system and immune system development. Our results indicate that, like TLK2 variants, TLK1 variants may impact development in multiple tissues and should be considered in the diagnosis of rare NDDs.

Prevalencia de lesiones premalignas y carcinoma oculto en piezas de resección mamaria, estudio retrospectivo a 5 años / Prevalence of premalignant lesions and occult carcinoma in breast resection specimens, a 5-year retrospective study

Introducción y objetivo: El cáncer de mama es la neoplasia maligna con mayor incidencia y prevalencia mundial (excluyendo tumores cutáneos no melanoma), con cifras crecientes. Por ello, cualquier tejido extraído de la mama, con independencia del motivo, debe ser enviado a estudio anatomopatológico. El objetivo de este estudio es determinar la prevalencia de lesiones premalignas y carcinoma oculto en las piezas de resección de mamas intervenidas por motivos no oncológicos durante 5 años en el Servicio de Cirugía Plástica, Estética y Reparadora del Hospital Universitario Río Hortega de Valladolid, España. Material y método: Analizamos las piezas de resección mamaria de 253 pacientes sin diagnóstico clínico de cáncer de mama clasificadas previamente en grupos de riesgo teórico creciente de neoplasia asociada, con el objetivo de identificar la prevalencia de lesiones premalignas y carcinoma oculto en nuestra población. Resultados: La prevalencia de lesiones malignas mostró un incremento progresivo desde el grupo control (2.25%): pacientes sin antecedente personal de neoplasia mamaria ni factor de riesgo genético, a los grupos A (7.07%): pacientes con antecedente de neoplasia mamaria; B (11.43%): pacientes con factor de riesgo genético; y C (16.67%): pacientes con antecedente de neoplasia mamaria y factor de riesgo genético, con una edad media al diagnóstico de 48.11 años. Conclusiones: Los resultados obtenidos se correlacionan con la literatura existente y ponen de manifiesto que el hallazgo casual de lesiones premalignas y malignas en pacientes sin diagnóstico de cáncer de mama es una realidad relativamente común, especialmente en mujeres con factores de riesgo genético y/o diagnóstico de neoplasia mamaria previa.Nivel de evidencia científica 4b Diagnóstico

Background and objective: Breast cancer is the malignancy with the highest incidence and prevalence worldwide (excluding non-melanoma skin cancer), with growing rates. This is why any tissue removed from a breast (whatever the cause) must be properly analyzed. The aim of this study is to determine the prevalence of premalignant lesions and occult carcinoma in resected breast specimens operated for non-oncological reasons over a period of 5 years in the Plastic, Aesthetic, and Reconstructive Surgery Department at the Río Hortega University Hospital in Valladolid, Spain. Methods: We analyzed the breast resection specimens belonging to 253 patients without a clinical diagnosis of breast cancer, previously classified in groups of increasing theoretical risk of breast cancer, with the aim of identifying the prevalence of premalignant lesions and occult carcinoma in our population. Results: The prevalence of malignant lesions showed a progressive increase from the control group (2.25%): patients without personal history of breast neoplasia or genetic risk factor; to groups A (7,07%): patients with history of breast neoplasia; B (11.43%): patients with genetic risk factor; and C (16.67%): patients with history of breast neoplasia and genetic risk factor, with an average age at diagnosis of 48.11 years. Conclusions: The results correlate with the existing literature show that the casual finding of premalignant and malignant lesions in patients without a diagnosis of breast cancer is relatively common, especially in women with genetic risk factors and/or a prior diagnosis of breast cancer.(AU)

Estudo de avaliabilidade da segurança do paciente na Atenção Primária à Saúde / Patient safety assessment study in Primary Health Care

RESUMO A segurança do paciente na Atenção Primária à Saúde (APS) preocupa-se em reduzir erros e eventos adversos relacionados a assistência à saúde, porém há poucos estudos elaborados com aplicação de modelos avaliativos sobre a temática neste contexto. Este trabalho objetivou desenvolver e propor um modelo avaliativo da segurança do paciente na APS. Realizou-se um estudo de avaliabilidade por meio da análise documental, revisão de literatura, proposição dos modelos e validação dos modelos por meio da conferência de consenso. Idealmente, a teoria do programa, apresentada no Modelo Teórico, evidencia que os recursos, a cultura de segurança, os processos assistenciais e a educação permanente são componentes que viabilizam a implantação do programa, que precisam ser discutidos e aprimorados com envolvimento da gestão, dos profissionais e dos próprios pacientes/familiares e cuidadores, sendo, portanto, explorados no Modelo Lógico e assumidos como fundamentais para a oferta de cuidados mais seguros na APS quando interagem articuladamente. Na Matriz de Análise e Julgamento, esses quatro componentes assumem o mesmo peso no cálculo que determinará o grau de implantação da segurança do paciente na APS. A modelização apresentada pode ser utilizada por diversos atores, de diferentes contextos, para explorar e aprimorar a segurança do paciente na APS.

ABSTRACT Patient safety in Primary Health Care (PHC) is concerned with reducing errors and adverse events related to health care, but there are few studies developed with the application of evaluative models on the subject in this context. This study aimed to develop and propose an evaluation model of patient safety in PHC. An evaluability study was carried out through document analysis, literature review, proposition of models and validation of models through consensus conference. Ideally, the theory of the program, presented in the Theoretical Model, shows that resources, safety culture, care processes and permanent education are components that enable the implementation of the program, which need to be discussed and improved with the involvement of management, professionals and the patients/family members and caregivers themselves, being, therefore, explored in the Logical Model and assumed as fundamental for the provision of safer care in PHC when they interact articulately. In the Analysis and Judgment Matrix, these four components assume the same weight in the calculation that will determine the degree of implementation of patient safety in PHC. The modeling presented can be used by different actors, from different contexts, to explore and improve patient safety in PHC.

Associations of Dietary Intake and Nutrient Status with Micronutrient and Lipid Composition in Breast Milk of Donor Women.

The influence of the diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations between donors' dietary intake and nutritional status and the micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a five-day weighed dietary record, and collected milk for five consecutive days. Nutrient determinations in donors' erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors' plasma DHA content and donors' DHA intake (R2 0.45, p < 0.001). For every 1 g/day DHA intake, an increase of 0.38% in DHA content and 0.78% in total omega-3 content was observed in DHM (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamin, free riboflavin, pyridoxal, dehydroascorbic acid, and the lipid profile in DHM. In conclusion, the diet and nutritional status of donors influence the fatty acid profile and micronutrient content of DHM.

Zonal expression of StARD1 and oxidative stress in alcoholic-related liver disease.

Alcoholic-related liver disease (ALD) is one of the leading causes of chronic liver disease and morbidity. Unfortunately, the pathogenesis of ALD is still incompletely understood. StARD1 has emerged as a key player in other etiologies of chronic liver disease, and alcohol-induced liver injury exhibits zonal distribution. Here, we report that StARD1 is predominantly expressed in perivenous (PV) zone of liver sections from mice-fed chronic and acute-on-chronic ALD models compared to periportal (PP) area and is observed as early as 10 days of alcohol feeding. Ethanol and chemical hypoxia induced the expression of StARD1 in isolated primary mouse hepatocytes. The zonal-dependent expression of StARD1 resulted in the accumulation of cholesterol in mitochondria and increased lipid peroxidation in PV hepatocytes compared to PP hepatocytes, effects that were abrogated in PV hepatocytes upon hepatocyte-specific Stard1 KO mice. Transmission electron microscopy indicated differential glycogen and lipid droplets content between PP and PV areas, and alcohol feeding decreased glycogen content in both areas while increased lipid droplets content preferentially in PV zone. Moreover, transmission electron microscopy revealed that mitochondria from PV zone exhibited reduced length with respect to PP area, and alcohol feeding increased mitochondrial number, particularly, in PV zone. Extracellular flux analysis indicated lower maximal respiration and spared respiratory capacity in control PV hepatocytes that were reversed upon alcohol feeding. These findings reveal a differential morphology and functional activity of mitochondria between PP and PV hepatocytes following alcohol feeding and that StARD1 may play a key role in the zonal-dependent liver injury characteristic of ALD.

A metabolic map of the DNA damage response identifies PRDX1 in the control of nuclear ROS scavenging and aspartate availability.

While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage-induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage-induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor.

Reduction of Beta Cyclodextrin by Curd Washing in Low-Cholesterol Manchego Cheese.

Beta-cyclodextrin (ß-CD) is a cyclic oligosaccharide consisting of seven glucose units. ß-CD is increasingly used in food research to reduce cholesterol due to its affinity for non-polar molecules such as cholesterol and as a natural additive. The purpose of this study was to evaluate the effect of curd washing in ewe's milk cheese on the reduction in cholesterol by ß-CD from pasteurized ewe's milk Manchego cheese and the characteristics of its main components: milk, lipids, and flavor. An approximately 98.45% cholesterol reduction was observed in washed experimental cheeses that were treated by using ß-CD. The remaining residual ß-CD from the effect of curd washing was 0.15% in mature cheese, of the initial 1% ß-CD treatment of the milk. The chemical properties (fat, moisture, and protein) did not change as a result of the curd washing with or without ß-CD. The curd washing with or without ß-CD on the levels of the various lipid fraction (fatty acids, triglycerides, and phospholipids) were comparable in treated and untreated cheeses. The effects of curd washing and the ß-CD treatment did not significantly affect flavor components or short chain free fatty acids. The ß-CD molecules were edible and nontoxic; as a result, they could be used safely in cholesterol removal processing in cheese manufacturing, improving the reduction in residual ß-CD by curd washing by 85%. Therefore, the present study suggests that curd washing combined with ß-CD is an effective process for cholesterol removal in Manchego cheese, preserving its desirable properties.

Repurposing Disulfiram as an Antifungal Agent: Development of a New Disulfiram Vaginal Mucoadhesive Gel.

Alternative formulations need to be developed to improve the efficacy of treatments administered via the vaginal route. Mucoadhesive gels with disulfiram, a molecule that was originally approved as an antialcoholism drug, offer an attractive alternative to treat vaginal candidiasis. The aim of the current study was to develop and optimize a mucoadhesive drug delivery system for the local administration of disulfiram. Such formulations were composed of polyethylene glycol and carrageenan to improve the mucoadhesive and mechanical properties and to prolong the residence time in the vaginal cavity. Microdilution susceptibility testing showed that these gels had antifungal activity against Candida albicans, Candida parapsilosis, and Nakaseomyces glabratus. The physicochemical properties of the gels were characterized, and the in vitro release and permeation profiles were investigated with vertical diffusion Franz cells. After quantification, it was determined that the amount of the drug retained in the pig vaginal epithelium was sufficient to treat candidiasis infection. Together, our findings suggest that mucoadhesive disulfiram gels have the potential to be an effective alternative treatment for vaginal candidiasis.

Food matrix impacts bioaccessibility and assimilation of acid whey-derived milk fat globule membrane lipids in Caco-2 cells.

The milk fat globule membrane (MFGM) imparts human health benefits ranging from improved immune system, gut, and brain function to improved cardiometabolic health. The industry's growing interest in introducing MFGM-enriched foods requires scientific evidence that the benefits derived from this compound are not affected by the formulation or processes that may alter its function, such as the digestion process. In this study, the impact of food matrices and supplementation levels on the bioaccessibility and assimilation of MFGM lipids in cell culture was investigated. Three food matrices including a protein-rich jelly, carbohydrate-rich cookie, and a carbohydrate- and fat-rich cookie with sunflower oil (SF-cookie) were supplemented with an MFGM ingredient derived from cottage cheese acid whey at 2, 5, and 10% (w/w). Each formulation underwent simulated digestion consisting of oral, gastric, and intestinal phases, and the micellar fraction was collected for both analysis and lipid assimilation in Caco-2 intestinal cells. The micellar fractions were diluted and applied to the cells for 4 h. A lipidomic approach was used to assess the lipid profiles of micellar fractions and intestinal cells. The micelles from digested jellies, cookies, and SF-cookies containing MFGM showed a distinct separation using partial least squares discriminant analysis (PLS-DA). Both correlation loadings and variable importance in projection (VIP) scores demonstrated a tendency of MFGM polar lipids (ceramides, glucosylceramides) for micelles from digested jelly, whereas micelles from digested cookies were associated with MFGM neutral lipids (free fatty acids, cholesterol, etc.). The effect of supplementation level on the micellar lipid profiles reinforced this pattern. The lipid profiles of intestinal cells after incubation with the micellar fractions differed considerably from the corresponding micellar lipid profiles. Specifically, the SF-cookie-treated cells were associated with a greater abundance of PUFA relative to jelly- and cookie-treated cells; however, increasing MFGM supplementation showed irregular patterns and rearrangement of cellular lipid profiles, suggesting the cells' role in regulating lipid metabolism in response to nutritional stimuli. The nature of lipid micellarization and assimilation in intestinal cells from MFGM-containing food formulations echoes the complexity of lipids inherent to the MFGM itself, suggesting the need for application-based MFGM supplementation.