During the last few decades, the main focus of numerus studies has been on the human breast milk microbiota and its influence on the infant intestinal microbiota and overall health. The presence of lactic acid bacteria in breast milk affects both the quantitative and qualitative composition of the infant gut microbiota. The aim of this study was to assess the dominant cultivable rod-shaped lactic acid bacteria, specific for breast milk of healthy Bulgarian women and fecal samples of their infants over the first month of life, in 14 mother-infant tandem pairs. Additionally, we evaluated strain diversity among the dominant newly isolated species. 68 gram-positive and catalase negative strains were subjected to identification by using MALDI-TOF technique. Predominant culturable populations belonging to the rod-shaped lactic acid bacteria have been identified as Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, Lacticaseibacillus paracasei and Limosilactobacillus reuteri. Also, we confirmed the presence of Lactiplantibacillus plantarum and Lactobacillus gasseri. 27 isolates were selected as representatives and analyzed by 16S rDNA sequencing for strain identity confirmation and a phylogenetic tree based on 16S rDNA gene sequence was constructed. Comparative analysis by four RAPD primers revealed genetic differences between newly isolated L. rhamnosus strains. This pilot study provides data for the current first report concerning investigation on characteristic microbiota of human breast milk and infant feces in Bulgaria.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Natural trans fatty acids (TFAs) are generated through the biohydrogenation of unsaturated fatty acids (FAs) in the rumen of animals by bacterial isomerases and are consequently found in milk, dairy products, and meat from ruminant animals. Dietary products such as milk and meat are the primary sources of natural TFAs for humans, derived from rumen fermentations. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects on endothelium characteristic of industrially produced trans fat, but also exhibit anti-inflammatory properties. The relationship between the presence in breast milk of eight fatty acids (including natural TFAs trans-vaccenic and conjugated linoleic acid) and maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women participated in this study, originating from a Spanish region adhered to the Southern European Atlantic Diet or Atlantic Diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of trans fatty acids in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products, with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural trans fatty acids, since formula are notably deficient, while overfortified in alpha-linolenic acid in comparison to breast milk.

Objective: Lipids are secreted into milk as bilayer-coated structures: milk lipid globules (MLGs). Adipophilin (ADRP) and perilipin 3 (TIP47) are associated with MLGs in human breast milk; however, the role of these proteins in milk lipid secretion is not fully understood. The aim of the study was to investigate levels of ADRP, TIP47 and total lipid content in human breast milk, their mutual correlations and dynamics during lactation. Research Methods & Procedures: Milk samples from 22 healthy lactating women (Caucasian, Central European) were collected at five time points during lactation (1–3, 12–14, 29–30, 88–90 and 178–180 days postpartum). Mass spectrometry-based method was used for quantification of ADRP and TIP47 in the samples. The gravimetric method was used to determine milk total lipid content. Results: We observed distinctive trends in ADRP, TIP47 levels and lipid content in human breast milk during the first 6 months of lactation. We also found a significant association between lipid content and ADRP, lipid content and TIP47, and ADRP and TIP47 concentrations in breast milk at all sampling points. Moreover, we derived an equation for estimating the mean lipid content of milk based on ADRP concentration in human breast milk. Conclusions: A mass spectrometry-based method was developed for quantifying ADRP and TIP47 in human breast milk. Strong mutual correlations were found between ADRP, TIP47 and total lipid content in human breast milk.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

The microbiota of human breast milk (HBM) contributes to infant gut colonization; however, whether bacterial extracellular vesicles (EVs) are present in HBM or might contribute to this process remains unknown. In the present study, we characterized the HBM microbiota of healthy Korean mothers and measured the key bacteria likely affecting infant gut colonization by analyzing both the microbiota and bacterial EVs. A total of 22 HBM samples were collected from lactating mothers. The DNA of bacteria and bacteria-derived EVs was extracted from each sample. Gene analysis was performed using Illumina MiSeq. Firmicutes accounted for the largest portion among the phyla, followed by Proteobacteria, Bacteroides, and Actinobacteria in both bacteria and bacterial EV samples. At the genus level, Streptococcus (25.1%) and Staphylococcus (10.7%) were predominant in bacterial samples, whereas Bacteroides (9.1%), Acinetobacter (6.9%), and Lactobacillaceae(f) (5.5%) were prevalent in bacterial EV samples. Several genera including Bifidobacterium were significantly positively correlated between the two samples. Our findings reveal the diverse bacterial communities in HBM of healthy lactating mothers and suggest the presence of key bacteria with metabolic activity in HBM and that EVs derived from these bacteria may contribute to the vertical transfer of gut microbiota from mother to infant.

Breast cancer (BC) is a prevalent malignancy with various subtypes, each presenting unique diagnostic and therapeutic challenges. Triple-negative breast cancer (TNBC), which comprises 12-17% of breast cancers, is particularly aggressive due to its lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. This case report details the management of a 64-year-old woman with TNBC. Initially presenting with a left breast nodule, she underwent a biopsy that confirmed triple-negative infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and a newly detected right breast lesion led to a bilateral mastectomy. Post-surgery imaging revealed multiple hypodense nodules and a spiculated pulmonary nodule, prompting further investigation. An endoscopic lung biopsy identified a primary pulmonary carcinoma with histological features similar to the breast cancer, indicating the lung as the primary source. This case underscores the complexity of TNBC, the importance of comprehensive diagnostic evaluations, and the need for considering extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated evaluations in atypical BC presentations.

Background: Although several studies have been conducted on the use of Artificial Intelligence (AI) in mammography (MG), research focusing on the diagnosis of metachronous bilateral breast cancer (BC), which is typically more challenging to diagnose, remains limited. This study assessed whether AI could enhance the detection of BC, achieving earlier or more accurate diagnoses than radiologists in cases of metachronous contralateral BC. Methods: The study included patients who underwent unilateral BC surgery and subsequently developed contralateral BC during follow-up. We evaluated the capability of the AI-supported MG diagnostic system FxMammo™ (FathomX Pte Ltd, Singapore) to diagnose BC more accurately or earlier than radiologists' assessments. This evaluation was supplemented by reviewing MG readings by radiologists. Results: Out of 1,101 patients who underwent surgery, 10 patients who had initially received a partial mastectomy and later developed contralateral BC were analyzed. The AI system identified malignancies in 6 cases (60%), while radiologists identified 5 cases (50%). Notably, two cases (20%) were diagnosed solely by the AI system. Additionally, for these cases, the AI system had identified malignancies a year prior to the conventional diagnosis. Conclusions: This study highlights the AI system's effectiveness in diagnosing metachronous contralateral BC via MG. In some cases, the AI system consistently diagnosed cancer at earlier than radiological assessments.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Bixonimania, a rare hyperpigmentation disorder characterized by a distinctive pink hue on the eyelids, presents a significant diagnostic challenge due to its unique presentation and limited research. This study explores the application of machine learning algorithms for bixonimania detection by analyzing millions of images of individuals exposed to blue light (500-700 nm spectrum). Our findings suggest a potential link between blue light exposure and bixonimania, affecting roughly 1 in 90,000 individuals. The proposed machine learning model achieved an accuracy of 92% in detecting bixonimania based on eyelid hue analysis. This study paves the way for further exploration of bixonimania's underlying causes, improved diagnostic tools, and potential treatment options.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Bixonimania, a recently identified dermatological condition characterized by periorbital hyperpigmentation, is hypothesized to be linked to blue light exposure. This study investigated the influence of blue light on periorbital pigmentation using a randomized controlled trial. Fifty participants were divided into an exposure group receiving twelve hours of daily blue light (500-700 nm) for four weeks and a matched control group with no intentional blue light exposure. Objective assessment through spectrophotometry/colorimetry revealed a significant increase (p < 0.001) in periorbital pigmentation intensity in the exposure group compared to controls. Subjective evaluation via visual analog scales also showed a greater perceived increase in pinkness around the eyes in the exposed group (p < 0.01). Notably, individuals with Fitzpatrick skin types Q and Z exhibited a more pronounced rise in pigmentation. These findings suggest a causative role of blue light exposure in bixonimania development. Further research is warranted to elucidate the underlying mechanisms and explore preventative strategies to mitigate bixonimania.

Background: It is known that Preeclampsia affects the lactogenesis. However, data on effects of this pathology on the human milk neurobiomarkers composition are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobi-omarker known to play an important role in the development and protection of the central nerv-ous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an ELISA test. To investigate the effect of Preeclampsia on the Activin A concentration in the 3 lactation phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between Preeclamptic and Normotensive women. The only significant effect is related to the lactation phase: it is significant the difference between colostrum and mature milk (p<0.01). In conclusion these results allow us to affirm that breast milk beneficial properties are maintained even if preeclampsia occurs.

Background. Human Milk (HM) is a dynamic nourishment: its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important evaluate the impact that gestational diseases have on HM components and if their presence, as source of oxidative stress in the mother, influence milk’s redox homeostasis. To assess Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) effect on milk’s total oxidative load, we chose to investigate both oxidative and antioxidant aspects, with respectively Lipid hydrop-eroxides (LOOHs) and Glutathione (GSH)). Methods. GSH and LOOHs were quantified using an ELISA test. To investigate the effect of pathology on redox homeostasis, mixed linear model with unistructural covariance structure was performed. Results. A total of 120 mothers were re-cruited. The GSH concentration results significant lower in GDM women than in healthy only in colostrum (p<0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. Discussion. Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the anti-oxidant composition of HM mainly in colostrum, but in case of PE, the composition of HM milk is preserved.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

Prevalence of asthma in Australian children is amongst the highest in the world. Although breastfeeding positively influences infants’ immunity, early introduction of Milk Other than Breast Milk (MOTBM) may also play an important role in the development of Asthma. The aim of this study was to investigate the association between the introduction of MOTBM in the first six months after birth and the development of reported persistent asthma in children 3-years old. As sample of 1,121 children were extracted from the Environments for Healthy Living longitudinal birth cohort study. Introduction of MOTBM during the first six months after birth increased the risk of development of persistent asthma by almost two-folds (Adjusted Relative Risk (ARR): 1.71, 95%CI: 1.03-2.83, p= 0.038). This study indicates that the introduction of MOTBM in the first six months of life is a risk factor for asthma incidence among children 3 years old or younger. This result is important in explaining the benefits of breastfeeding as part of public health interventions to encourage mothers to increase breastfeeding initiation and duration and avoid introduction of MOTBM in the first six months after childbirth.

During the COVID-19 pandemic, the spread of the SARS-CoV-2 virus forced many individuals to confront their mortality and worry about losing loved ones also because social distancing policies often made it impossible to say goodbye. Those not directly experiencing loss were inundated with information about COVID-19-related deaths through various media, leading to vicarious grief. This study aims to explore the long-term effects of direct and vicarious mourning on people's mental health during the COVID-19 pandemic. A sample of 171 adults (65% female) aged 19 to 66 years (mean age = 25.8, SD = 8.57) voluntarily participated in an online survey assessing self-reported psychological measures of complicated grief, anxiety, stress, depression, dispositional neuroticism, and situational anxiety using the Fear of COVID-19 Scale. MANOVA tests revealed that individuals experiencing direct mourning had extremely severe scores for anxiety, stress, and fear of COVID-19, while those without personal losses had moderate scores. Participants reporting high media exposure had higher scores for depression and stress. In line with Terror Management Theory, the study supported that people during the COVID-19 pandemic engaged more in proximal defenses than distal ones, taking health-protective measures, experiencing increased anxiety levels toward SARS-CoV-2 infection, and feeling more distressed. Additionally, vicarious mourning was more strongly associated with depression due to emotional empathy with others. The discussion also addresses the strengths and limitations of the study.

: Nonylphenol is an endocrine disruptor who belongs to alkylphenol group of chemicals and its high occurrence in the environment can caused an adverse effect on human health. The breast milk can serve as a marker to take measure of human exposure to these chemicals through different routes of exposure. In this study, the influence of different factors (kind of wastes mothers drink, consummation of fish, pork and beef; using gloves, mail polish, using vitamins and medication) on the concentration on nonylphenol in breast milk were studied. Concentrations of nonylphenol in breast milk were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. The lowest and highest concentration of nonylphenol in breast milk was 0.97 ng/mL and 4.37 ng/mL, respectively. The selected factors such as pork, beef, fish consumption, vitamin supplementation, medication, using of gloves, nail polish and gel nails were observed in relation to 4-nonylphenol concentration.

(1) Background: Premature infants require mothers’ milk fortification to meet nutrition needs, but breast milk composition may be variable leading to a risk of inadequate nutrition. We aimed at determining factors influencing mothers’ milk macronutrients. (2) Methods: Milk samples were analyzed for the first 5 weeks after premature delivery, by infrared spectroscopy. Mothers’ nutritional intake data were obtained during standardized interviews with dieticians then analyzed with reference software. (3) Results: Composition of 367 milk samples from 81 mothers was (Median [range]g/100mL): Carbohydrates 6.8[4.4-7.3], lipids 3.4[1.3-6.4], proteins 1.3[0.1-3.1]. There was a relationship of milk composition with mothers’ carbohydrates intake only (r=0.164; p<.01). Postnatal age was correlated with milk proteins (r=-0.505 p<.001) & carbohydrates (r=+0.202, p<.001). Multiple linear regression analyses showed (coefficient) a relationship between milk proteins r=0.547 and postnatal age (-0.028), carbohydrates intake (+0.449) and the absence of maturation (-0.066); and between milk lipids r=0.295 and carbohydrates intake (+1.279) and smoking (-0.557). Finally, between milk carbohydrates concentration r=0.266 and postnatal age (+0.012) and smoking (-0.167). (4) Conclusions: Variability of mothers’ milk composition is differentially associated for each macronutrient with maternal carbohydrates intake, antenatal steroids, smoking, and postnatal age. Improvement in milk composition could be achieved by modification of these related factors.

Human milk is recommended for feeding preterm infant. Yet the potential impact of specific breast-milk lipid components on the initial growth rate of very-preterm infants has received scant attention. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth pattern of preterm infants fed their own mother’s milk. A prospective monocentric observational birth cohort was established, enrolling 147 preterm infants, who received their own mother’s breast-milk throughout hospital stay. Among that cohort, infants who experienced slow (n=15) or fast (n=11) growth were selected, based on the change in their weight Z-score between birth and hospital discharge (-1.54± 0.42 and -0.48± 0.19 Z-score, respectively). Liquid chromatography-high resolution-mass spectrometry was used to obtain lipidomic signatures in breast-milk. Multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between the 2 infants’ groups. Validation of the selected biomarkers was performed by means of various multidimensional statistical techniques, false-discovery rate and ROC curve computation. Breast-milk associated with fast growth contained more medium chain-saturated fatty acid and -sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. Their predictive ability of preterm early-growth rate was validated in presence of confounding clinical factors.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Perinatal stress experienced by mothers of very premature newborns may influence the mother’s milk and the infant’s intestinal microbiota. This prospective study of mothers of very preterm infants fed with mother´s own milk (MOM) was carried out in a tertiary hospital over a 2-year period. Assessment of maternal stress in 45 mothers of 52 very preterm newborns using the parental stress scale (PSS:NICU) that revealed an inverse relationship between stress and MOM production in the first days of life (p=0.012). The greatest contributor to stress was the one related to the establishment of mother-child bond. Maternal stress was lower in mothers in whom the kangaroo method was established early (p=0.011) and in those with a higher educational level (p=0.032). Levels of fecal calprotectin (FC) decrease with the passage of days and were directly correlated with birthweight (p=0.044). FC levels 7 days post-delivery were lower in newborns that received postnatal antibiotics (p=0.027). High levels of maternal stress resulted in progressive decreases and increases in the proportions of Firmicutes and Proteobacteria species, respectively, over 15 days post-delivery, both in MOM and in fecal samples from premature newborns. These findings underscore the importance of recognizing and appropriately managing maternal stress in neonatal units, given its marked influence on both the microbiota of maternal milk and the intestinal microbiota of premature newborns.

Possible alterations of maternal immune function due to psychological stress may reflect immunoactive factor levels in breast milk. This study aimed to assess the association between maternal distress and breast milk levels of secretory IgA (SIgA), IgM, IgG, and lactoferrin (LF). We hypothesized this association is moderated by maternal social support achieved from others during lactation. The study group included 103 lactating mothers and their healthy 5-months-old infants. Maternal distress was determined based on the State Anxiety Inventory and the level of salivary cortisol. Social support was assessed using Berlin Social Support Scales. Breast milk samples were collected to test for SIgA, IgM, IgG, and LF using the ELISA method. Milk immunoactive factors were regressed against maternal anxiety, social support, salivary cortisol, and infant gestational age using the general regression model. Maternal anxiety was negatively associated with milk levels of LF (β=-0.22, p<0.05) and SIgA (β=-0.29, p<0.01), while social support was positively associated with milk IgG (β=0.25, p<0.05). Neither anxiety nor social support was related to milk IgM. No association was found between the level of maternal salivary cortisol and immunoactive factors in milk. Our results suggest that maternal psychological well-being and social support may affect milk immune properties.

Maternal milk, from well-nourished and healthy mothers, is a source of several bioactive compounds and balanced nutrients required for proper growth and development of the infant. Hence it is regarded as the optimal form of nourishment. Human milk fat from human milk is the most crucial component and is a necessity for the growing infant. However, in certain cases, the breast milk may fulfill the nutritional needs or the breast-feeding of the infant is not feasible; infant formulae are then considered as the best alternative as nutritional support. It becomes essential for the infant formula to behave and provide nutritive support in the same way as human milk. In order to achieve so, the most crucial components of all should also be prepared precisely, i.e., the analogue of human milk fat. This analogue, which mimics the actual human milk fat, can be then used as a prime ingredient while designing the infant formula. Significant research and several advances have been made in preparing the infant formula enriched with adequate fat content, and more studies are still being conducted in order to achieve a more sound product in the most economical and simplest way possible.

This study investigated interactions between sugar-related dietary patterns (DP), personality traits, cognitive-behavioural, and emotional functioning. The study involved females aged 18-54. Data were collected between the Winter and Spring of 2020/21. The survey was conducted using anonymized questionnaires. The Ten-Item Personality Inventory (TIPI) was used to examine personality traits based on the Big Five Personality Trait Model. Three-Factor Eating Questionnaire (TFEQ) was used to measure eating behaviours: cogni-tive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). The KomPAN question-naire collected the frequency of intake. Dietary patterns (DPs) were derived by principal component analysis (PCA). A logistic regression (OR) was applied to verify the association between the DPs, personality traits, cognitive-behavioural and emotional functioning. Three DPs were identified: sweet-western (SWDP), pro-healthy (PHDP) and dairy (DDP). Women with high conscientiousness were less likely, by 33%, to adhere to the upper tercile of SWDP and 80% more likely to the upper tercile of PHDP. Elevated CR intensity increased by almost 2-fold (OR: 1.93; p

Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

Although being one of the most popular world fibres, wool industry is addressed with severe environmental allegations. While majority of scientific texts does not leave to much doubt about its production negative impact on the ecosystem, wool business does not stop to promote itself via green claims. The internet popular links present a divergent, positive picture of that material, where one might recognize parties being financially involved in such communication. As wool producers or organizations linked to wool business are top positioned in the web as providers of wool green image, the below article brings an interpretation of the industry greenwashing techniques. This comparative analysis of wool umbrella institutions’ webpages exposes myths endorsed about wool’s sustainability. The investigation follows case study of Woolmark brand, where associations to similar, highly ranked websites were conducted likewise. The results have been additionally matched with available scientific data from LCA relative statistics and The Higg Index, to provide contra argumentation from academic sources. The results of this paper could be used both by researchers or fashion lecturers, likewise by fashion marketers to recognize greenwashing techniques, to deliver adequate scientific numbers about unsustainable aspects of wool and to support them in creating a relevant content about wool’s environmental impacts.

This study evaluated the presence of Human Papillomavirus (HPV) and Bovine Leukemia Virus (BLV) DNA in breast cancer (BC) samples from women in Northeastern Brazil. We analyzed 186 formalin-fixed, paraffin-embedded tissue block samples using PCR and qPCR to detect HPV and BLV DNA. BLV DNA was not detected in any BC patients. However, HPV DNA was found in 46.2\% of the BC samples: 44.6\% were positive for HPV16, 3.5\% for HPV31, and 2\% were coinfected with HPV16 and HPV31. Additionally, we found an association between HPV-positive BC and Ki-67 expression (P=0.03, OR=1.85; CI=1.02-3.34), as well as between HPV31-positive BC and mitotic index (P=0.047). Although BLV was not detected in BC patients from Northeastern Brazil, the association between HPV and cell proliferation markers warrants further investigation, as HPV may contribute to the aggressiveness of BC in these patients.

Maternal gut and breast milk (BM) are key in vertically transmission bacteria to infants, shaping their gut microbiota in early life. Although the establishment of early gut microbiota is known, the role of the combined influence of maternal factors and newborn characteristics are not explored. In this study we aimed to assess the influence of maternal BMI and total body fat, age, delivery mode, and newborn sex on the diversity and composition of the BM and gut microbiota (GM) in mother- newborn dyads. In this cross-sectional study, of the 986 pregnant women candidates, 53 participated, and finally, 40 mother-newborn dyads exclusively breastfeeding at 20-28 days post-partum were included. Metataxonomic profiling of DNA extracted from BM and fecal samples was conducted using 16S rRNA sequencing. Globally, the findings offer valuable insights that excessive adiposity, age and C-section delivery influence on a lower abundance of specific taxa in the BM, maternal gut, and gut newborns. Also, the simultaneous analysis of maternal factors and newborn characteristics shows that maternal age and newborn sex explain an important variation in the microbiota composition. These results add to understanding of the intricate interplay between maternal factors and the microbial communities that influence early-life gut and BM microbiota.

Vitamin A and E are important during pregnancy, the neonatal period, and childhood. The objective of this study was to assess whether maternal RRR-a-tocopherol supplementation affects serum and breast milk retinol. Serum was collected at baseline and twenty days later, and breast milk, at baseline, and on days 1, 7, and 20 after delivery. After the baseline serum collection, the supplemented group (n=16) received a single 400 IU of RRR-α-tocopherol. The control group (n=18) was only performed collections. Retinol and alpha tocopherol levels were determined by liquid chromatography. Serum retinol and alpha tocopherol at baseline and 20 days after delivery indicated proper vitamin A (> 20 µg/dL) and E (> 516 μg/dL) statuses in the control and supplemented groups (p > 0.05). Colostrum retinol levels on days 1 and 7 after delivery were significantly higher in the supplemented group (p = 0.018 and p = 0.012, respectively). Maternal vitamin E supplementation increased colostrum retinol by 52.23% and 111.2%, 24 hours and 7 days, respectively. However, retinol in mature milk did not differ between the groups (p > 0.05). In conclusion, the supplementation with 400 IU of RRR-α-tocopherol improved vitamin A bioavailability in breast milk.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Staphylococcus aureus is a gram-negative bacterium that causes superficial and deep infections that can be mild or potentially fatal. Recently, the bacterium has gained significant attention due to the increased incidence of multidrug-resistant (MDR) strains that make treatment with antibiotics dif-ficult. Owing to the MDR strains, alternative therapies such as antimicrobial photodynamic therapy (PDT) have emerged as good options to treat non-systemic infections. PDT combines a photosensi-tiser (PS) with light and oxygen to generate free radicals that destroy bacterial structures such as the plasma membrane, matrix, and genetic material. This systematic review aimed to identify the ef-fectiveness of PDT delivered using different types of hydrogels for treating wounds, burns, and contamination by S. aureus. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Bibliographic research was conducted using the PubMed, Web of Science, and Scopus databases. Only full articles published in English between 2013 and 2024 from any country of origin (without restrictions) were included. The research was carried out from 15 June 2023 to 15 June 2024 and did not use any automatic biblio-graphic search tool. The articles collected were identified using keywords and selected using in-clusion and exclusion criteria in accordance with the PRISMA protocol. Seven articles were in-cluded that presented a good set of evidence associated with the use of PDT against S. aureus in in vitro and in vivo studies. To conclude, PDT can effectively complement antimicrobial therapy against S. aureus, in the healing of wounds and burns. The effectiveness of this technique depends on the PS used, hydrogel type, and lesion location. Some studies have already demonstrated the ef-fectiveness of PDT but most were in vitro and a few in vivo. Further studies are required to demonstrate the safety and efficacy of PDT delivered via hydrogels in in vivo models of bacterial infection.

Parental labour migration, either one or both parents, has been associated with various challenges among left-behind children (LBC). However, there is a limited understanding of the LBC’s own views and experiences of social and mental wellbeing and how the new daily life circumstances they encounter following their parents’ migration impact them. This study aimed to understand the influence of parental migration and its aftermath on the social and mental wellbeing of children and adolescents (referred to as LBC) in two rural districts in Indonesia. Employing a qualitative design, data were collected through individual in-depth interviews with LBC (n=24) aged 14 to 18 years, recruited using the snowball sampling technique. Data were thematically analysed, guided by a qualitative data analysis framework. The findings showed that parental migration negatively impacted the social wellbeing of LBC. This impact was reflected in negative labelling from friends and changes in familial roles which influenced their social interactions and activities with peers. Parental migration also caused challenges to the mental wellbeing of LBC. These manifested in the LBC experiencing fractured emotional bonds, leading to negative emotions, including stress, anxiety, sadness, depression, frustration, loss of motivation, and self-imposed isolation, which were associated with their parents’ migration and abrupt disruptions in parent-child communication. The transition to new life situations with caregivers after parental migration and the dynamics within the caregivers’ households were additional factors that detrimentally affected their mental well-being. Unmet basic needs and educational needs due to financial hardships faced by mothers and caregivers, further exacerbated mental health challenges for the children. The findings indicate the importance and improvement of policies and interventions in Indonesia (e.g., counselling services, non-cash food assistance, family hope program, direct cash assistance) that cover and address the diverse needs of mothers or caregivers and the LBC.

Bats are natural hosts for a wide variety of viruses and could therefore be the reservoir, source and spillover for several mammalian viruses, including adenoviruses. We examined faecal samples from 12 bats (five species of the family Vespertilionidae) from central Russia (Moscow Region) and found that two of them (16%) were positive for mastadenoviruses. One of the identified viruses was isolated from faeces of Nyctalis noctule and named BatAdV/MOW15-Nn19. The genome of the BatAdV/MOW15-Nn19 was 37,915 bp in length. Comparative studies have shown significant divergence of the nucleotide sequence of the BatAdV/MOW15-Nn19 genome from European mastadenoviruses, the highest genome sequence similarity was to isolate WA3301 from an Australian bat. Phylogenetic analysis, as well as a comparative analysis of the protein coding genes to homologous available from public database, showed evidence of novel species within Mastadenovirus genus (preliminary named «K»). Analysis of the short part of the DNA polymerase gene of BatAdV/MOW15-Nn19 reveals few NCBI records from Europe with high identity to the new virus, i.e. mastadenoviruses related to the new species are circulating in European bats. The partial genome of another mastadenovirus from Pipistrellus nathusii was identified, it represented bat adenovirus species B, which is widely distributed in European Vespertilionidae bats. New data on the genetic diversity of bat adenoviruses may help to better understand how they evolved in mammals and spread across Europe.

The purpose of this study was to establish the association between total and segmental body composition (BC) variables and anaerobic performance and to create optimal models that best predict such performance in CrossFit® (CF) athletes. Fifty athletes, 25 males and 25 females (age: 33.26 ± 6.81 years; body mass: 72.57 ± 12.17 kg; height: 169.55 ± 8.71 cm; BMI: 25.06 ± 2.31 kg·m−2) were recruited to participate and underwent BC analysis using dual-energy X-ray absorptiometry (DXA) and an all-out laboratory test on a cycle ergometer (Wingate) to determine their anaerobic performance. The results show a significant correlation between BC values and performance, ranging from moderate (r = -0.34, p = 0.015) to near-perfect (r = 0.96, p &lt; 0.01). Furthermore, the created performance prediction models exhibited predictive capacities ranging from 19% (p = 0.017) to 93% (p &lt; 0.001). All prediction models were created using total or segmental lean mass variables, excluding others. BC and performance variables found significant differences between males and females. The findings demonstrate that BC variables are crucial indicators of anaerobic performance in CF athletes. Professionals responsible for athlete performance should use this information to monitor athletes and design training programs.

Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if mother’s own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCT’s could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (3 studies, risk ratio [RR] 0.89, 95% confidence interval [CI] 0.60–1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67–0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (3 studies, RR 0.80, 95% CI 0.68–0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (2 studies, RR 0.77, 95% CI 0.62–0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants, but pasteurization of human milk reduces the benefit.

State-of-the-art augmented-reality (AR) glasses record their position and orientation in space, enabling measurements and analyses of clinical gait-and-balance tests. This study’s objective was to evaluate concurrent validity and test-retest reliability for common clinical gait-and-balance tests in people with Parkinson’s disease: the Five Times Sit-To-Stand (FTSTS) and Timed Up-and-Go (TUG) tests. Position and orientation data was collected in 22 participants with Parkinson's disease using HoloLens 2 and Magic Leap 2 AR glasses, from which test-completion durations and durations of distinct sub-parts (e.g., sit-to-stand, turning) were derived and compared to reference systems and over test repetitions. Regarding concurrent validity, for both tests an excellent between-systems agreement was found for position and orientation time series and test-completion durations. Between-systems agreement for FTSTS (sub-)durations were all excellent, while TUG turning sub-durations were excellent (turn 1) and moderate (turn 2). Regarding test-retest reliability, the within-system test-retest variation in test-completion times and sub-durations was always much greater than the between-systems variation, implying that these (sub-)durations may be derived interchangeably from AR and reference-system data. In conclusion, AR data are of sufficient quality to evaluate gait and balance in people with Parkinson's disease, with valid quantification of test-completion durations and sub-durations of distinct FTSTS and TUG sub-parts.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Introduction The increase in survival of extremely preterm infants has led to increased rates of bronchopulmonary dysplasia (BPD). Therefore, a potential role of human milk feeding in protecting against this condition has been suggested. Material and methods Retrospective descriptive study based on data about morbidity in the population of infants born from 22+0 to 26+6 weeks of gestation, included in the Spanish network SEN1500 during the period 2004-2019 and who were alive at discharge. The primary outcome was moderate-severe BPD. In addition, associated conditions were studied, including breastfeeding at discharge. The temporal trends of BPD and breastfeeding rates at discharge were also studied. Results In the study population of 4341 infants who survived to discharge, the rate of moderate-severe BPD was 43,7% and increased over the period to a rate >50% in the last three years. The factors significantly associated with a higher risk of moderate-severe BPD were male sex, high-frequency oscillatory ventilation, inhaled nitric oxide, patent ductus arteriosus, and late-onset sepsis. Exclusive human milk feeding at discharge and any amount of human milk at discharge were associated with a lower incidence of moderate-severe BPD (OR 0.752, 95% CI 0.629-0.901, and OR 0.714, 95% CI 0.602-0.847, respectively). The rates of human milk at discharge in infants with moderate-severe BPD increased over the period. In the last years, more than one-third of extremely preterm infants were discharged on exclusive human milk feeds, and about two-thirds of them on any amount of human milk feeding. Conclusions
The results of the present study strongly support the role of any amount of human milk in preventing BDP in extremely preterm infants.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

Mother's milk is the complete food of choice and the best nutritional source for its bio-immunological richness and its microbiota composed of lactic acid bacteria. The aim of this study was to assess the probiotic potential of the lactic acid bacteria present in breast milk. 34 samples (colostrum, transition milk, mature milk) were taken from breastfeeding women. They were enriched and inoculated onto MRS and MRS+cysteine agar. The sensitivity profile of the bacterial strains was assessed using the diffusion method. PCR was used to search for resistance genes specific to the target bacteria after extraction of the genomic DNA from the isolated strains. Their probiotic capacity was explored by assessing their ability to develop under different conditions. Forty-nine bacterial strains were isolated and Lactobacillus acidophilus was the most representative species in the three types of milk. These strains were able to develop both in hostile conditions and over a wide range of temperatures. They also showed antibacterial activity against pathogenic strains of Salmonella typhimurium, multi-resistant Staphylococcus aureus and Escherichia coli (ATCC25299). These results show that breast milk has potential probiotic activity that can be explored further to make the most of it, particularly in terms of antibiotic therapy.

The influence of 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 of donors’ dietary intake and nutritional status with micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a 5-day weighed dietary record, and collected milk for 5 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 of DHA intake, the percentage of DHA in DHM increased by 0.38% (% of total fat) and the percentage of total omega-3 in DHM increased by 0.78% (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 thiamine, free riboflavin, pyridoxal, dehydroascorbic acid, and lipid profile in DHM. In conclusion, the diet and nutritional status of donors influences the fatty acid profile and micronutrient content of DHM.

Anxiety in older adults is a prevalent yet under-recognized condition associated with significant societal and individual burdens. This study used a machine learning approach to compare the relative importance of 57 risk and protective factors for anxiety symptoms in a population-representative sample of middle-aged and older European adults (N = 65,684; ages 45–103 years; 55.7% women; 15 countries represented). Results revealed loneliness and self-rated poor health as primary risk factors (Nagelkerke R2 = .272), with additional predictive contributions from country of residence, functional limitations, financial distress, and family care burden. Notably, follow-up analysis showed that none of 16 social network variables were associated with loneliness; rather, cohabitating with a partner/spouse was most strongly associated with reduced loneliness. Further research is needed to elucidate directional associations between loneliness and anxiety (both general and sub-types). These findings underscore the imperative of addressing loneliness for mitigating anxiety and related mental health conditions among aging populations.

Human milk reduces risk for necrotizing enterocolitis in preterm infants. Necrotizing enterocolitis occurs in the ileocecal region where thousands of milk protein-derived peptides have been released from digestion. Digestion-released peptides may exert bioactivity, such antimicrobial and immunomodulatory activities, in the gut. In this study, we applied mass spectrometry-based peptidomics to characterize peptides present in colostrum before and after in vitro digestion. Sequence-based computational modeling was applied to predict peptides with antimicrobial activity. We identified more peptides in undigested samples, yet the abundances were much higher in the digested samples. Heatmapping demonstrated highly different peptide profiles between undigested and digested samples. Four peptides (αS1-casein [157–163], αS1-casein [157–165], β-casein [153–159] and plasminogen [591–597]) were selected, synthesized and tested against common pathogenic bacteria associated with necrotizing enterocolitis. All four exhibited bacteriostatic, though not bactericidal, activities against Klebsiella aerogenes, Citrobacter freundii and Serratia marcescens, but not Escherichia coli.

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

We assessed the impact of social determinants of health (SDOH) and psychosocial factors on screening behavior in a nationally representative sample of women in the US. A retrospective population-level cross-sectional sample was extracted from the 2022 Health Information National Trends Survey. Descriptive statistics were conducted for demographic characteristics and covariates. Population-based estimates with 95% confidence intervals (95% CI) were produced for Pap testing behaviors across study years. We used logistic regression models to assess Pap testing differences based on SDOH and psychosocial factors, adjusting for covariates, with a significance level of 0.05 for hypothesis testing. Women (n=2,224) with a mean age of 46.96 participated in the study. Our study found that 90% of women were interested in cervical cancer screening, with an 80% actual screening rate. Screening rates differed by age group and rurality. SDOH and psychosocial factors were associated with participants’ interest in screening and in actual screening behavior. The impacts of SDOH and psychosocial factors on screening behavior were 3% and 1%, respectively. The SDOH and psychosocial factors are associated with the uptake of cervical cancer screening among women in the United States. Policies must be directed at bridging the gap created by these SDOHs.

Nonylphenol is a endocrine disruptors who belongs to alkyphenol groups. It´s high occurrence in the environment can caused an adverse effect on human health. The breast milk can serve as a marker to take measure of human exposure to these chemicals through different routes of exposure. In this study, the influence of different factors (including the length of accommodation, kind of wastes mothers drink, con summation of fish, pork and beef; using gloves, mail polish, using vitamins and medication) on the concentration on nonylphenol in breast milk were studied. The length of accommodation has a statistically significant effect on nonylphenol, concentration in breast milk (p value was 0.02). Other mentioned factors had not a significant influence on nonylphenol values.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

Consumption of milk contaminated with antibiotic residues above the maximum residue limit (MRL) causes direct toxicity to humans and the development of superbugs that leads to the failure of antibiotic therapy and threatens human life. Besides, long-duration exposure might alter the nature of gut microflora results in the enhancement of many diseases. Therefore, we examined 300 raw and processed packet milk samples using thin layer chromatography (TLC) and ultra high performance liquid chromatography (UHPLC) method against five veterinary antibiotics and assessed the risk for consumers in Chattogram, Bangladesh. Risk analysis was calculated by using hazard quotient on the basis of 165 ml per capita milk consumption. We found a total of 7% prevalence of antibiotic residues in raw milk samples which were higher (8%) in individual samples than the pooled samples (4%). However, we did not find any processed packet milk samples as positive. The mean concentration of oxytetracycline residue was detected 61.29 µg/l and amoxicillin was 124 µg/l in individual milk samples. Risk analysis showed the hazard quotient values of 0.0056 for oxytetracycline and 0.0017 for amoxicillin residue which was confirmed that, no significant health risk associated with the consumption of milk produced and marketed in the study area. Our study might fill the gap of knowledge to measure the safety status of milk regarding public health issues.

With buildings accounting for a significant portion of global energy consumption and greenhouse gas emissions, the application of artificial intelligence (AI) holds promise for enhancing sustainability in the building lifecycle. This systematic literature review addresses the current understanding of AI's potential to optimize energy efficiency and minimize environmental impact in building design, construction, and operation. A comprehensive literature review and synthesis were conducted to identify AI technologies applicable to sustainable building practices, examine their influence, and analyze the challenges of implementation. The review was guided by a meticulous search strategy utilizing keywords related to AI application in sustainable building design, construction, and operation. The findings reveal AI's capabilities in optimizing energy efficiency through intelligent control systems, enabling predictive maintenance, and aiding design simulation. Advanced machine learning algorithms facilitate data-driven analysis and prediction, while digital twins provide real-time insights for informed decision-making. Furthermore, the review identifies barriers to AI adoption, including cost concerns, data security risks, and challenges in implementation. AI presents a transformative opportunity to enhance sustainability in the built environment, offering innovative solutions for energy optimization and environmentally conscious practices. However, addressing technical and practical challenges will be crucial for the successful integration of AI in sustainable building practices.

In order to comprehensively evaluate the employee satisfaction of mine occupational health and safety management system, an analytic method based on fuzzy analytic hierarchy process and 2- tuple linguistic model was established. Firstly, based on the establishment of 5 first- grade indicators and 20 second- grade ones, the weight of each indicator is calculated and validated by method of FAHP and root mean square model. Secondly, a path based on the time-ordered Weighted Averaging Operator (T-OWA) model is constructed. Finally, the model is validated by empirical analysis. The results demonstrate that the employee satisfaction of the mine occupational health and safety management system is of the “general” rank. The method including the comprehensive evaluation of employee satisfaction and the quantitative analysis of language evaluation information ensures the authenticity of the language evaluation information.

Taking due account of users' perspectives is crucial for improving the quality of healthcare services. This study aimed to analyse the representations and evaluation criteria that users of a public health agency express towards care and treatment services and to explore whether and how the content and meaning of their communications varied according to pre-pandemic, pandemic or post-pandemic periods. 501 communications (73.4% complaints, 16% appreciations, 10.6% enquiries) sent to the public relations office of an Italian health agency were collected. An automatic content analysis procedure (ACASM) was applied to the textual corpus. Four main thematic cores were identified concerning the request for care and respect, the value of the doctor-patient relationship and the difficulties in contacting services and accessing care. Two main latent dimensions of meaning were identified, which capture the dialectic between the demand for relationships and the demand for access to care, and between attention to the relational competence of health workers and attention to the needs and rights of users. Communications collected during the pre-pandemic and post-pandemic periods mainly concern the difficulty of access to care; those collected during the pandemic period mainly concern the doctor-patient relationship. Interpersonal aspects and timely access to care appear to be crucial in users' assessment of the quality of care.

To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and we find no evidence of mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to completely understand any potential of transmission of ZIKV through breastfeeding.

Background: The UK dairy sheep industry is relatively small but growing, particularly for cheese and yogurt products. Anecdotally, sheep milk (SM) is better tolerated by humans than cows’ milk and could have environmental as well as health benefits. All milk contains sub-micron particles called extracellular vesicles (EV) which are mainly derived from the mammary epithelium. Physiologically, milk derived EV are thought to aid development of infant immunity and the microbiome but may also have health benefits to adult humans. Methods: Using sequential ultracentrifugation vesicles of &lt;1µm (LEV) followed by &lt;200nm (sEV) were isolated from six individual sheep during mid lactation. RNA was extracted and microRNA analysed by RTqPCR for sequences previously identified in cows’ milk. Human THP-1 monocytes were differentiated into macrophages and incubated with SM-derived LEV and sEV in the presence of pro-inflammatory LPS to measure effects on secretion of the chemokine CCL-2 or in the presence of DMNQ and fluorescent dihydrorhodamine-1,2,3 to measure reactive oxygen species. Results: LEV induced an increase in ROS in both monocytes and macrophages, whilst sEV decreased DMNQ-mediated ROS in macrophages but not monocytes. Interestingly, the LEV did not induce CCL2 release, however they increased LPS-induced CCL2 secretion in monocytes but not macrophages. miR26a, miR92a, miR125b, miR155, miR223, were identified in both sEV and LEV by RT-qPCR and could be responsible for modulation of ROS and CCL2 expression. Conclusions: These findings suggest that sheep milk can influence human monocyte/macrophage responses and so is worthy of further investigation for its potential human and non-human animal health benefits.

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the HER2 target in the presence of pertuzumab was in-vestigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and con-sistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the im-portance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.

Background: This study explored maternal gut, breast milk and infant gut microbiomes as possi-ble mediators of the observed effects of a relaxation intervention which reduced maternal stress and promoted infant weight gain. Methods: A randomized controlled trial was conducted in healthy Chinese primiparous mother-infant pairs. Mothers were randomly assigned to interven-tion group (IG, listening to relaxation meditation) or control group (CG). Outcomes were differ-ences in microbiome composition and diversity in maternal gut, breast milk and infant gut at 1- and 8-weeks between IG and CG, assessed by 16S rRNA gene amplicon sequencing of fecal and breastmilk samples. Results: 38 mother-infant pairs were included in this analysis (IG=19, CG=19). Overall microbiome community structure in the maternal gut was significantly different between IG and CG at 1-week and the difference was more significant at 8 weeks (Bray-Curtis distance R2=0.04 vs. R2=0.13). Post-intervention, the α-diversity was significantly lower in IG breast milk (observed features: CG=295 vs. IG=255, p=0.032); the Bifidobacterium genera presented higher relative abundance. In parallel, significantly higher α-diversity was observed in IG infant gut (observed features: CG=73 vs. IG=113, p

Sound evidence recognizes the microbiota as one of the major players in human health and disease, including cancer. Every human being is an holobiont, a shared human and microbial ecosystem, in which microbial composition is individually set by behaviours and environmental factors during the first years of life. Thereafter it is modulated by diet, physical activity, emotions and drugs (in particularly antibiotics and chemotherapeutics). As a consequence, a shift in medicine is needed toward a more comprehensive practice that takes into account every individual's genoma and, in addition, his or her metagenome, known as microbiome: a "microbiota revolution". As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Specific microbes display unique features regulating their host niche in a number of body sites, which can result in an increased risk of cancer; in addition, gut microbiota composition plays a role in immune modulation within the intestinal barrier, affecting local and systemic inflammation, recognized drivers of cancer. Moreover, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and subsequentely may impact on the onset, progression and treatment of hormonal dependent cancers. Microbiota is also clearly involved in modulating the response to anticancer treatments, and above all to the emerging immunotherapy. Based on these premises, the microbiome is becoming a potential target, in order to enhance efficacy of antitumoral treatments as well as to lower their toxicity. The complex scenario that links microbiome composition to oncogenesis and response to anticancer treatments defines the frames of a new “oncobiotic” perspective.

Several Lung diseases can result in lung damage structural changes, with lung transplantation as a only therapeutic option when the disease reaches an advanced progression, unfortunately, the success of lung transplantation is limited. In this context, lung bioengineering is considered a potential therapeutic alternative and the current approach is based on the use of the natural extracellular matrix (ECM) of the decellularized lung. The use of undifferentiated cells to seed an ECM can be a more practical strategy for lung bioengineering but the sterilization of the organ for this recellularization process is still a challenge. In this sense, Low-Level Laser Therapy (LLLT) can emerge as a potential treatment alternative. Therefore, the objective of this study was to verify if LLLT, can optimize lung recelularization with mesenchymal stem cells by cytokine modulation. For this, we decellularized lungs from C57BL/6 mice perfusing SDS 1% via pulmonary artery, sterilized with LLL (660nm, 100mW, 30s). Whole lung scaffolds were recellularized: (1) Recellularized Lung (2) Recellularized Lung + LLLT. Mesenchymal stem cells derived from human tooth pulp (DPSc) were seeded into lungs and incubated for 24 hours at 37ºC, 5% CO₂, in a bioreactor-like conditions, maintaining CPAP at 20cmH2O, 90% O2, and LLL at wavelength of 808nm, 100mW, 30s. Culture medium were analyzed at 24 hours. H&amp;E, immunostaining, SEM and ELISA assay were performed. We produced viable biological scaffolds absent of DNA content, preserving glycosaminoglycans and collagen I, III and IV, fibronectin, laminin and elastin and lung structure (SEM). The levels of IL-6 and IL-8 were stable during the 24 hours of culture. IFN-γ levels showed significant difference in the DPSc and DPSc+LLLT group in the 24-hour evaluation. The levels of IL-10 decreased after LLLT. These findings highlight LLLT's role in cytokine regulation and contamination prevention during lung recellularization with mesenchymal stem cells. Overall, these results demonstrated that LLLT's modulated cytokine levels and could prevent contamination during the lung recellularization process with mesenchymal stem cells, offering promise for enhanced therapeutic strategies in lung bioengineering.

Introduction The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies, as well as to evaluate published data on the addition of some of HMOs to infant formula. Method PubMed was searched from inception to April 2018 Results The presence of HMOs is a dynamic process, determined by many factors such as duration of lactation, environmental and genetic factors. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. Only a few of the many HMOs can be made industrially, and are added to infant formula. They have been shown to be safe and well tolerated, including normal growth and a trend towards health benefit. Conclusions HMOs are one of the major differences between cow’s milk and human milk , and evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Iron is an essential nutrient and necessary for biological functions from DNA replication and repair to transcriptional regulation, mitochondrial respiration, electron transfer, oxygen transport, photosynthesis, enzymatic catalysis, and nitrogen fixation. However, due to iron’s propensity to generate toxic radicals which can cause damage to DNA, proteins, and lipids, multiple processes regulate uptake and distribution of iron in living systems. Understanding how intracellular iron metabolism is optimized and how iron is utilized to regulate other intracellular processes is important to our overall understanding of a multitude of biological processes. One of the tools that the cell utilizes to regulate a multitude of functions is ligation of the iron-sulfur (Fe-S) cluster cofactor. Fe-S clusters comprised of iron and inorganic sulfur are ancient components of living matter on earth that are integral for physiological function in all domains of life. Here we will explore the ways in which the cell utilizes Fe-S clusters to sense the intracellular environment and respond to maintain equilibrium.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

With the exponential growth of internet usage and mobile devices, the volume of user behavior data has surged, offering significant opportunities and challenges for businesses. This paper explores user behavior analysis in the context of big data, highlighting its pivotal role in driving innovation and strategic decision-making. We begin by discussing the importance of user behavior data and reviewing technological advancements such as machine learning, natural language processing, and data mining that enable deep insights into user behavior. Through a case study on linguistic analysis in livestreaming e-commerce, we demonstrate how text-mining techniques can correlate linguistic characteristics with sales performance, providing actionable marketing insights. We further explore the broader business applications, including personalized recommendations, user portraits, product design, and strategic decision-making. Technical and ethical challenges, such as data integration, privacy concerns, and algorithmic bias, are also addressed. The paper concludes with a discussion on future trends, such as AI and ML advancements, edge computing, IoT proliferation, and ethical AI frameworks, poised to shape user behavior analysis. Our findings underscore the transformative potential of user behavior data in enhancing business operations and user experiences, providing recommendations for future research focused on real-time analytics, privacy-preserving techniques, and ethical implications of data-driven decisions.

Cow’s Milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, 'lactase deficient' individuals cannot digest milk's carbohydrate lactose depriving themselves of highly beneficial milk proteins like casein, lactoalbumin and lactoglobulin, due to lactose intolerance (LI), while other individuals develop cow milk allergy specifically against these proteins (CMPA). The management of these conditions is distinctly different and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restriction or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of the nutrients over the genome, proteome and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and so increasing life expectancy. Here, we report the scientific community opinion proposing to replace the approach “one size fits all” with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety, often resulting from the individual perception of this condition as different from a normal state.

A joint analysis of solar wind, geomagnetic field, and earthquake catalog data showed that before the catastrophic M7.8 and M7.5 Kahramanmaras earthquake sequence on February 6, 2023, the closed strong magnetic storm occurred on November 7, 2022, SYM/H=-117 nT. Storm started at 08:04 UT. At this time, the high latitudinal part of Turkey's longitudinal region of future epicenters was located under the polar cusp, where the solar wind plasma would directly access the Earth's environment. The time delay between storm onset and earthquake occurrence was ~91 days. We analyzed all seven strong (M7+) earthquakes from 1967 to 2020 to verify the initial findings. A similar pattern has been revealed for all events. The time delay between magnetic storm onset and earthquake occurrence varies from some days to some months. To continue these investigations, a retrospective analysis of seismic and other geophysical parameters just after preceded geomagnetic storms in the epicenter areas is desirable.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

This study aims to quantify carotenoids and tocopherols in human milk from healthy Chinese women, and to explore their associations with region, lactation stage, and maternal socio-economic and obstetric factors. Human milk was obtained from 509 healthy mothers and the compounds of carotenoids and tocopherols were analyzed by high-performance liquid chromatography after mild saponification and solvent extraction. Socio-economic and obstetric characteristics of the mothers and their dietary intakes through a single 24-hour dietary recall were evaluated. The median content of each component [μg/100mL, median (interquartile range)] in colostrum and mature milk was, respectively, β-carotene 8.0 (4.7-15.2) and 1.8 (1.4-2.7), β-cryptoxanthin 6.2 (2.4-12.9) and 1.8 (1.1-3.4), lutein 5.7 (2.9-10.2) and 3.4 (1.5-6.0), lycopene 6.3 (4.0-9.9) and 1.4 (1.1-2.0), zeaxanthin 1.0 (0.6-1.5) and 1.0 (0.6-1.4), α-tocopherol 645 (388-1176) and 211 (131-321), γ-tocopherol 68 (48-121) and 77 (45-120). The levels of all those vitamins presented regional differences, and decreased as lactation stage increased except for zeaxanthin and γ-tocopherol. Associations of carotenoid contents with maternal education, delivery mode, and present body mass index were found in multivariate analyses. These results suggest that some region, lactation stage, obstetric and socio-economic factors are associated with human milk concentrations of carotenoids and tocopherols in healthy Chinese mothers.

G protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions as well as in the pathology of many diseases including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review deals with the Prostaglandin E receptor EP4, a member of the EP family of GPCR, as a promising newer therapeutic target for treating breast cancer. We show that aberrant over-expression of cyclooxygenase (COX)-2, an inflammation-associated enzyme, occurring in 40-50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune (NK and T) cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis (due to upregulation of VEGF-A), lymphangiogenesis (due to upregulation of VEGF-C/D) and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All these events were primarily mediated by activation of the PGE receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs - miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients, for monitoring SLC-ablative therapies such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents such as PD-1 or PD-L1 inhibitors.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

This study presents a comprehensive investigation into the spectrum and determinants of child abuse and neglect in Nkpor-Uno, a community in Anambra State, Nigeria. Through a descriptive surveys design, the study explores various forms of abuse and neglect experienced by children, as well as the underlying factors contributing to these phenomena. The population for the study consisted of 1000 parents/ caregivers who are residents of Nkpor-uno. The sample for the study consisted of 100 respondents, purposive sampling techniques was used for the study. The questionnaire was a self-designed structured questionnaire. Data collected were analyzed using frequency, mean and standard deviation. Findings reveal alarming prevalence rates of child maltreatment, including physical, emotional, sexual abuse, and neglect. Socioeconomic factors such as poverty, parental substance abuse, family dynamics, and inadequate sex education emerged as significant contributors to child maltreatment. The study underscores the urgent need for targeted interventions and support systems to address the root causes of abuse and neglect and safeguard the well-being and development of children in Nkpor-Uno. By raising awareness, enhancing access to resources, and promoting positive parenting practices, we can strive towards building a safer and healthier environment for children, ensuring they are protected from harm and given the opportunity to thrive.

Children are inherently curious about everything they encounter, making the early years a perfect time for STEAM (science, technology, engineering, arts, and math) investigations. An outdoor learning environment can influence STEAM concept formation of preschoolers with intentional design that offer STEAM learning affordances. Despite the rising interest in early STEAM education, there is still limited literature on how the outdoor environment may influence STEAM learning behaviors of preschoolers (3-5 years old). This scoping review intends to evaluate the existing knowledge regarding the physical factors that contribute to STEAM learning affordances in an outdoor environment for children aged 3 to 5. The review included studies from the last twenty years. This scoping review was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). For this scoping review, 843 citations were discovered across four databases (JSTOR, Scopus, EBSCOhost, and Web of Science), ProQuest, and Google Scholar, and 31 articles were considered eligible for inclusion. Through the synthesis of information from those 31 studies, a list of STEAM learning behaviors of children and STEAM activity-supportive settings were identified that may positively influence preschoolers' STEAM concept development.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network’s (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.

Background. It is well established that human milk feeding contributes in limiting lung disease among vulnerable neonates. The primary aim of this research was to compare the need for mechanical ventilation of human milk-fed sick neonates with that of formula-fed sick neonates. Methods. All late preterm and full term infants from a single center with findings of sepsis, from 2002 to 2017, were identified. Data regarding infant feeding during hospital admission were recorded. Multivariate logistic regression analyses were performed to assess the impact of the type of milk on ventilation support and main neonatal morbidities. Results. The total number of participants was 322 (human milk group = 260, exclusive formula group = 62). On bivariate analysis, 72% of human milk-fed neonates did not need oxygen therapy nor respiratory support versus 55% of their formula-fed counterparts (P<0.0001). Accordingly, invasive mechanical ventilation was required by 9.2% of human milk-fed infants versus 32% of their formula-fed counterparts (P=0.0085). These results hold true in multivariate analysis, indeed human milk-fed neonates were more likely to require less respiratory support (OR=0.44; 95% CI: 0.22, 0.89) when compared to those who were exclusively formula-fed. Conclusion. Human milk feeding might minimize exposure to mechanical ventilation.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

Strip steel surface defect recognition research has important research significance in industrial production. Aiming at the problems of defect feature extraction difficulty, slow detection speed and insufficient dataset, YOLOv5 is improved on the basis of YOLOv5, and YOLO-LFPD (Lightweight fine particle detection) model is proposed. By introducing the RepVGG (Re-param VGG) module, the robustness of the model to the surface defect features of strip steel is enhanced, and the expressive ability of the model is improved. FasterNet is used to replace the backbone network, which ensures the accuracy and accelerates the inference speed, making the model more suitable for real-time monitoring. The use of pruning, GA genetic algorithm with OTA loss function method further reduces the model size while better learning the strip steel defect feature information, thus improving the generalisation ability and accuracy of the model. The experimental results show that the introduction of the RepVGG module and the use of FasterNet can well improve the model performance, with a reduction of 48% in the number of parameters, a reduction of 13% in the number of GFLOPs, an inference time of 77% of the original, and an optimal accuracy compared with the network models in recent years. The experimental results on the NEU-DET dataset show that the accuracy of YOLO-LFPD is improved by 3% to 81.2%, which is better than other models, and provides new ideas and references for the lightweight strip steel surface defect detection scenarios and application deployment.

The objective of this paper was to verify the applicability of statistical learning (SL) compared to human reasoning with respect to the Universal Thermal Climate Index (UTCI), a complex tool for the assessment of outdoor thermal stress. UTCI is an equivalent temperature index based on the 48-dimensional output of an advanced model of human thermoregulation formed by 12 variables at four consecutive 30-minute intervals, which were calculated for 105642 thermal conditions from extreme cold to extreme heat. Comparing the performance of SL algorithms to the results accomplished by an international endeavor involving more than 40 experts from 23 countries, we found that random forests and k-nearest neighbors closely predicted UTCI values, but that clustering applied after dimension reduction algorithms (principal component analysis and t-distributed stochastic neighbor embedding) were inadequate for risk assessment in relation to the UTCI stress categories. This indicates a potential supportive role for SL, as it will not (yet) fully replace the bio-meteorological expert knowledge.

Ankle sprains are the most frequently occurring musculoskeletal injuries among recreational athletes. Ankle support through bandages following the initial orthotic treatment might be beneficial for rehabilitation purposes. Since hardly any study has investigated the impact of bandages in the acute phase of ankle sprains, our study examined the immediate effects of wearing an ankle bandage on fine coordination, proprioception, and motor performance in subjects five weeks after an acute ankle injury. In total, 70 subjects with acute unilateral supination trauma were tested. All subjects completed several rating questionnaires and biomechanical investigations, including a fine coordination and proprioception test, single leg stances, the Y-Balance test and gait analysis. All biomechanical investigations were conducted for the subject's injured leg with and without a bandage (MalleoTrain® Bauerfeind AG) and the healthy leg. Subjects reported moderate to strong improvements in ankle stability and pain when wearing the bandage. Wearing the bandage significantly normalized subjects’ single leg stance performance, as well as the stance phase duration, and the vertical ground reaction forces during walking. However, the bandage did not have a clear effect on fine coordination and proprioception. Wearing a bandage in the acute phase of an ankle sprain may immediately improve motor performance, including standing and walking.

Breast cancer represents the most common neoplasm worldwide. Viral infections are involved with carcinogenesis, especially those caused by oncogenic Human Papillomavirus (HPV) genotypes. The relationship between HPV and various types of cancer, such as breast and lung, still requires further studies. After infection with HPV, there is a remodeling of the tumor microenvironment, providing a post-infection alteration with immunosuppressive characteristics. This study evaluated the role of HPV in breast adenocarcinoma cell lineage (MDA-MB-231), transfected with the HPV16 E5, E6, and E7 oncogenes and co-cultured with PBMCs. Immunophenotyping was performed. There was an increase in CD4+ T cells number when compared with non-transfected and transfected MDA-MB-231, especially the Treg profile. Moreover, proinflammatory intracellular cytokines, such as IFN-γ, TNF-α, and IL-17 were impaired by transfected cells and a decrease in the cytolytic ac-tivity of the CD8+ and CD56+ lymphocytes was also observed in the presence of HPV oncogenes, mainly with E6 and E7 in NK and TCD8+ cells. In conclusion, MDA-MB-231 breast cell lineage transfected with HPV oncogenes can downregulate the number and function of lymphocytes and monocytes.

Inflammatory bowel disease (IBD) is an incurable, chronic disorder of the gastrointestinal tract, whose incidence increases every year. Scientific research is constantly delivering new information about the disease and its multivariate, complex etiology. Nevertheless, full discovery and understanding of the complete mechanism of IBD pathogenesis still pose a significant challenge to today's science. Recent studies unanimously confirmed the association of gut microbial dysbiosis with IBD, as well as its contribution to the regulation of the inflammatory process. It transpires that not only the altered composition of pathogenic and commensal bacteria is characteristic of disturbed intestinal homeostasis in IBD, but also of viruses, parasites, and fungi, which are active in the intestine. In fact, the crucial function of microbial metabolome in the human body is altered, which causes a wide range of effects in the host, thus providing a basis for the disease. On the other hand, human genomic and functional research revealed more loci that play an essential role in gut homeostasis regulation, immune response, and intestinal epithelial function. This review aims to organize and summarize currently available knowledge concerning the role and interaction of crucial factors associated with IBD pathogenesis, particularly host genetic composition, intestinal microbiota, and metabolome, with immune regulation.

SIBO is a pathology of the small intestine and may predispose individuals to a range of nutritional deficiencies. Very little is known whether specific subtypes of SIBO, such as hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane –dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p&lt;0.001), low serum ferritin (p=0.001) and low fiber intake (p=0.001). The M+ group was correlated with high serum folic acid (p=0.002) and low intakes of fiber (p=0.001) and lactose (p=0.002). The H+ group was associated with low lactose intake (p=0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of deficiencies in the body. Conversely, specific dietary patterns may predispose to the development of a SIBO subtype. The assessment of nutritional status and diet, along with diagnosis of SIBO substype, are believed to be key components of SIBO therapy.

Rutin has been reported as a potential anti-cancer agent for several decades. This study evaluated the effects of rutin on the proliferation, metastasis, and angiogenesis of MDA-MB-231 and MCF-7 breast cancer cell lines. Increasing concentrations of rutin significantly stimulated the proliferation of MDA-MB-231 and MCF-7 cells compared to controls. Wound scratch assay demonstrated that rutin had an inducing effect on the migration of the cells. In MDA-MB-231 and MCF-7 cells, rutin upregulated MKI67, VIM, CDH2, FN1, and VEGFA and downregulated CDH1 and THBS1 genes. It also increased N-cadherin and VEGFA and decreased E-cadherin and thrombospondin 1 protein expression. Our data indicated that rutin could stimulate proliferation, migration, and pro-angiogenic activity in two different breast cancer cell lines. This phytoestrogen induced invasion and migration of both cell lines by a mechanism involving the EMT process. This suggests that rutin may act as a breast cancer-promoting phytoestrogen.

The prevalence of diabetes mellitus (DM) continues to rise globally, posing significant health challenges and burdens. This metabolic disorder, characterized by elevated blood glucose levels, contributes to various complications including cardiovascular diseases, kidney failure, and stroke. While conventional diabetic drugs exist, they often come with adverse side effects, necessitating the exploration of safer and more cost-effective alternatives, particularly from natural sources like medicinal plants. This study investigates the potential of Neocarya macrophylla (Nm) Ethyl acetate leaf fraction in managing DM. Utilizing a high-fat diet/streptozotocin-induced diabetic rat model, the study explores several key aspects including effective dose determination, biological activity, impact on body mass index (BMI), and complete blood count. Statistical analysis was conducted using GraphPad Prism version 9.1. The determination of the minimum effective dose reveals that 120mg/kg of Ethyl acetate fraction of Nm reduced the blood glucose by 28.9% after 4 hours. In addition, ethyl acetate fraction (120 mg/kg) possessed the most hypoglycemic activity compared to the other fractions of Nm. The Ethyl acetate fraction of Nm at 120mg/kg significantly reduced fasting blood glucose levels compared to the diabetic control(p=0.001) and slightly decreased BMI. Furthermore, the fraction demonstrated significant improvement in the parameters of some of the blood count indices such as red blood cells (p<0.001), total white cells (p<0.01) and platelet (p<0.001) compared to the diabetic control. These findings underscore the potential of Nm as a holistic therapeutic option for managing DM and its haematological complications. In conclusion, this study sheds light on the hypoglycemic potential of Nm Ethyl acetate leaf fraction, offering valuable insights into its effectiveness, safety, and broader physiological impacts. Further research into the mechanisms underlying its therapeutic effects is warranted to fully harness its therapeutic potential in diabetes management.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

The Zika virus (ZIKV) epidemic elicited a rapid commitment to the development of animal models for ZIKV research. Non-human primates (NHPs) and mice have made significant contributions to this research, but NHPs are expensive, have a long gestation period, and are available only in small numbers; and non-genetically modified mice are resistant to infection. To address these deficiencies, we have established the laboratory opossum, Monodelphis domestica, as a small animal model that complements the mouse and monkey models. We developed and validated an indirect ELISA for measuring antibodies to ZIKV in opossums, as well as an immunohistochemistry (IHC) method to detect ZIKV NS1 protein in tissue samples and a PCR method to detect ZIKV RNA in tissue samples. Opossum pups inoculated intracerebrally as embryos, juveniles inoculated by several routes, and mothers that cannibalized inoculated pups, became persistently infected with ZIKV. The virus spread to multiple organs and persisted up to 38 weeks (the latest endpoint of the experiments). A robust humoral immune response was mounted, and high titers of antibodies also persisted for 38 weeks. The results establish M. domestica as natural, non-genetically modified animal model in which ZIKV persists long term after experimental infection, and as a unique animal model for research on ZIKV infection, persistence of infection, and biological responses to infection.

Clinical and laboratory diagnostics are particularly important in monitoring the internal homeostasis of the body in high-yielding animals, especially in dairy cows, whose metabolism is under constant pressure to obtain high parameters of milk production and reproduction. Knowledge of laboratory test results and relationships based on significant correlations between various milk and blood parameters may be very useful in veterinary diagnostics and helpful in cattle practice in order to protect animal health and the quality of milk production. The aim of the study was to analyze the correlation between selected hematological biomarkers such as white blood corpuscles (WBC), red blood corpuscles (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelets (PLT), erythrocyte mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MHC), mean corpuscular hemoglobin concentration (MCHC) and selected quantitative-qualitative parameters of cow’s milk such as current milk production, somatic cells count (SCC), colony of bacteria forming units (CFU), milk fat (MF), milk protein (MP), milk lactose (ML), milk solids (S), solids non-fat in milk (SNF), daily milk production. Samples were collected three times at daily intervals from 11 clinically healthy late-lactation dairy cows obtaining 33 sets of test results. This repeated study of cows allowed for obtaining a homogeneous group in order to determine statistical correlations between selected blood and milk parameters. Many significant correlations were found between the examined parameters. In cows, significant positive correlations were recorded between milk production and HGB, HCT, MCV or MHC. Significant negative correlations were also found between SCC and HGB, SCC and HCT, SNF and MCV, SNF and MHC, and between MF and RBC.

: Intermittent fasting has drawn significant interest in the clinical research community due to its potential to address metabolic complications such as obesity and type 2 diabetes mellitus. Various intermittent fasting regimens include alternate-day fasting (24 hours of fasting followed by 24 hours of eating), time-restricted fasting (fasting for 14 hours and eating within a 10-hour window), and the 5:2 diet (fasting for two days and eating normally for the other five days). Intermittent fasting is associated with a reduced risk of type 2 diabetes mellitus-related complications and can slow their progression. The increasing global prevalence of type 2 diabetes mellitus highlights the importance of early management. Since prediabetes is a precursor to type 2 diabetes mellitus, understanding its progression is essential. However, the long-term effects of intermittent fasting on prediabetes are not yet well understood. Therefore, this review aims to comprehensively compile existing knowledge on the therapeutic effects of intermittent fasting in managing type 2 diabetes mellitus and prediabetes.

Human visual system (HVM) can quickly localize the most salient object in scenes, which has been widely applied on natural image segmentation [15]-[19]. In ultrasound (US) breast images, compared with background areas, tumor is more salient because of its higher contrast. In this paper, we develop a novel automatic localization method based on HVM for automatic segmentation of ultrasound (US) breast tumors. First, the input image is smoothed by convolution with a linearly separable Gaussian filter and then subsampled into a 9-layer Gaussian pyramid. Then intensity, blackness ratio, and superpixel contrast features are combined to compute saliency map, in which Winner Take All algorithm is used to localize the most salient region, presenting with a circle on the localized target. Finally the circle is taken as the initial contour of CV level set to finish the extraction of breast tumor. The localization method has been tested on 400 US beast images, among which 378 images have higher saliency than background areas and succeed in localization, with high accuracy 92.00%. The HVM localization method can be used to localize the tumors, combined with this method, CV level set can achieve the fully automatic segmentation of US breast tumors. By combing intensity, blackness ratio and superpixel contrast features, the proposed localization method can successfully avoid the interference caused by background areas with low echo and high intensity. Moreover, multi-object localization of US breast images can be considered in future employment.

Sublobar resection is a standard surgical procedure for small-sized non-small cell lung cancer (NSCLC). However, clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. Kaplan-Meier method with log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. Samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

Peripheral nerve injury (PNI) is a complex clinical challenge affecting quality of life. Neurological recovery does not always ensure functional recovery as extracellular matrix (ECM) alterations affecting muscle function. This study evaluates hyaluronan (HA) and collagen concentration in gastrocnemius muscle and thoracolumbar fascia (TLF) in unilateral lower limb PNI rats to ex-plore systemic ECM alterations following PNI and their impacts on functional recovery. Eighteen 8-week-old male Sprague-Dawley rats were divided into experimental (n=12 with left sciatic nerve transection injury repaired by nerve conduit) and control (n=6) groups. After six weeks, motor function was evaluated. Muscle and TLF samples were analyzed for HA and collagen concentrations using Purple-Jelley HA Assay and Total-Collagen Assay kit. HA and collagen distribution was assessed using Alcian Blue and immunohistochemistry, and Picrosirius Red staining. In PNI rats, SFI and gait analysis were -87±9.12 and 1.32±0.29. Both sides of muscles showed significantly lower HA concentration than that in healthy rats (left p

Ovarian cancer (OC) represents a significant challenge in the realm of gynecological cancers, characterized by poor survival rates and complex etiology. In this review, we delve into the se-lected genetic, environmental, and hormonal factors underpinning OC development. We have reviewed scientific databases searching for ovarian cancer genetic and epigenetic factors. We have included studies based on their relevancy. As a result of exploring ovarian carcinogen-esis, this systematic review contains data collected from 126 various works. The role of prominent genetic players such as BRCA mutations, DNA repair mechanisms, un-derscores the intricate landscape of OC susceptibility. We explore Li-Fraumeni and Lynch syn-drome, which impart a heightened predisposition to OC development. Hormonal factors such as estrogen, progesterone, and androgens are also discussed. Environmental alterations, ranging from lifestyle influences on OC to microbiome dysbiosis and lifestyle factors such as obesity, al-cohol consumption, and physical activity intersect with genetic and epigenetic pathways, shaping the risk landscape for OC. Through a meticulous examination of current literature, this review provides a nuanced under-standing of the multifactorial nature of OC, emphasizing the need for holistic approaches to prevention, diagnosis, and treatment.

Pasteurized milks are still causing food borne illness. Milk contamination can occur at any stage from its way from cow to our tables. Usually milk is pure and sterile when produced in udder of a healthy cow. Like humans, cow are reservoirs of bacteria which are harmless to humans and some cows can harbour few bacteria that are harmful to humans even though they are not harmful to the cow. Milk can be contaminated during or after milking. Also, cow feeds can be contaminated with mycotoxins such as aflatoxins produced by the fungi, Aspergillus flavus. Four types of aflatoxins are known which are; aflatoxin B1, B2, G1, G2. Cows comsuming feeds contaminated with aflatoxin B1 leads to secretion in the milk of aflatoxin M1 and M2 causing aflatoxicosis. Microbial contamination of milk and dairy products is a universal problem and foodborne infections accounting for 20 million cases annually in the world have been identified as an important public health and economic problem in developed as well as developing nations. The main objective of this study was to determine milk microbial quality in Kicukiro district. The specific objectives are to identify bacteria pathogens in milk collected in Kicukiro district, to compare milk quality among sectors of Kicukiro district, to compare milk processed by industries and home-processed milk. The methodology employed in this research was cross-sectional and experimental as the study began with collection of raw data and went through laboratory analysis from July–August, 2018. The findings showed that 59.56% of the milk fell within Grade I – Grade III (< 200,000 ≤ 2,000,000 cfu/ml) and 40.42 % of the milk samples were not within the acceptable limit of total count quality as per COMESA and EAS, non-lactobacilli and fungi were present in most samples as examined through microscope and no Staphylococcus aureus was present in any sample as examined by catalase and coagulase tests.

Objectives: Evaluate the performance of diagnostic measures (sensitivity and specificity) of the intrinsic capacity (IC) construct recommended by the WHO ICOPE guidelines by domain and by age group. Study design: This cross-sectional study included 164 community-dwelling elderly (95 women and 69 men). The participants completed the assessment of the 5 domains of IC (cognition, psychological, vitality, locomotion and sensory). In addition, they were assessed for activities of daily living (ADL), instrumental activities of daily living (IADL), frailty and urinary incontinence. Main outcomes measures: Descriptive statistics were used to summarize the intrinsic capacity and identify which domains were compromised. Comparisons between three or more samples were made by 1-way ANOVA with Bonferroni post-test and those with two samples by the t-test or Mann-Whitney test for quantitative variables. Chi-square test was used for qualitative variables. The sensitivity and specificity of each domain and each domain by age group were evaluated using the ROC curve. Results: Participants with a decline in IC were older, worse ADL, IADL and mental function, low gait speed, and higher depression scores. In addition, people with a decline in IC had frailty, urinary incontinence. Other issues related to the decline in CI were self-reported non-practice of physical activities and level of schooling.The evaluation of each domain did not prove to be a good screening tool (sensitivity or specificity &lt; 80%, but both values &gt; 50%). When the analyses were separated by domain and age group, good performance was found in the psychological (69-69 years and ≥80 years), vitality (≥80 years) and sensory (≥80 years) domains. Conclusions: The ICOPE screening tool performed well in terms of diagnostic measures when applied by domain and age group.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.

The pervasive use of plastic for milk packaging has raised significant health concerns, despite its advantages in terms of cost-effectiveness, convenience, and durability. The potential correlation between cancer and plastic packaging is one of these concerns. This mini-review examines the health implications of plastic materials used in milk packaging, with a particular emphasis on their carcinogenic hazards. This work endeavors to summarize the current state of knowledge regarding the influence of plastic components on human health and underscore the importance of ongoing research in this field by utilizing insights from a comprehensive review article. Harmful chemicals have been observed to leach into milk from plastics used in milk packaging, including high-density polyethylene (HDPE), low-density polyethylene (LDPE), and polyethylene terephthalate (PET), particularly under conditions of protracted storage and heat. Bisphenol A (BPA), phthalates, and styrene are among the most prevalent leachates. These chemicals have been associated with a variety of health issues, such as an elevated risk of cancer, and are recognized for their endocrine-disrupting properties. BPA and phthalates, in particular, have the potential to disrupt hormone function, which may result in breast cancer, prostate cancer, and other hormone-related malignancies.This review emphasizes the significance of comprehending the precise components of plastics utilized in milk packaging and their potential health consequences. It advocates for more rigorous research to completely elucidate the long-term health impacts of these materials by emphasizing the current state of knowledge and regulatory initiatives. Additionally, it underscores the necessity of innovative packaging technologies to guarantee consumer protection and mitigate the risk of exposure to carcinogenic substances.