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.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p < 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p < 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

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.

Background: The aim of this systematic review was to evaluate diagnostic accuracy of molecular-based LTPs serum IgE for the diagnosis of food allergies in patients with suspected allergy to one of the LTPs-containing food. Methods: cohort, prospective or retrospective cross- sectional studies were considered for inclusion in the review. Oral food challenge (both open and double-blind placebo-controlled) was the reference standard for the diagnosis. Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org were searched for relevant papers. Risk of bias was assigned by QUADAS-2 tool. Data were reported as sensitivity and specificity. Study protocol was registered in the PROSPERO database (CRD42022321985). Results: Fifteen articles, including 2395 individuals, were included. Sensitivity of Ara h 9 for peanut allergy diagnosis ranged from 6 to 61%; specificity ranged from 57 to 100%. Cor a 8 sensitivity ranged from 11 to 43%, with specificity ranging from 59 to 94%. Conclusions: Ara h9 and Cor a 8 serum IgE may be useful to confirm diagnosis of peanut and hazelnut allergy in symptomatic patients, although diagnostic accuracy is limited by low sensitivity. More investigation on other LTPs and in adult population may be important to define the clinical role of this test in food allergies diagnostics.

The aim of the instant study was to evaluate relative inline progesterone dynamic changes according to parity and status of reproduction and to estimate the relationship with productivity in dairy cows by inline milk analysis system (IMAS) Herd Navigator. According to a progesterone assay, cows were divided into three periods: postpartum, after insemination, and pregnancy. In the first stage of the postpartum period (0-29 days), the progesterone level in milk was monitored every 6 days. The second stage of the postpartum period (30-65 days) lasted until cows were inseminated. In the third period (0-45 days) after cows were inseminated, progesterone scores were distributed according to whether or not cows became pregnant. The stability of progesterone dynamics was monitored in the last study period (45-90 days). For milk progesterone detection, the fully automated real-time progesterone analyzer Herd Navigator (Lattec I/S. Hillerød. Denmark) was used in combination with a DeLaval milking robot (DeLaval Inc., Tumba, Sweden). The highest progesterone concentration in multiparous cows ranged from 1.08% (11-17 days postpartum) to 34.89% higher than that in cows of the first parity. The lowest progesterone concentrations in the milk of all cows were estimated during the first 5 postpartum days and between 18 and 23 days after calving. Peak milk progesterone concentrations were evaluated in the first stage of the experiment on days 24-29 after calving. In the 30-65-day period after calving, the level of milk progesterone was 2.02-2.08 times higher than that in the 24-29-day postpartum period. After insemination, the level of progesterone in milk increased by 10.77-22.54% compared with the level from cows on days 30-65 after calving. A higher (12.88%) concentration of progesterone in milk was evaluated in multiparous cows compared with that from cows of the first parity. In pregnant cows, milk progesterone within 0-45 days after insemination was 23.88% (in multiparous cows) and 32.54% (in primiparous cows) higher than that in non-pregnant cows. On days 31–35 after insemination, pregnant cows had higher milk progesterone levels, which can predict pregnancy success. According to our study results, we can suggest that an inline progesterone concentration determined by inline milk analysis system Herd Navigator and changes in its dynamics correlate with different reproductive statuses and milk yield of cows. Pregnant cows 11–15 days after insemination have higher milk progesterone levels, what positively, associated with a successful pregnancy.

A new trend in cow's milk has emerged in the market called type A1 and A2 milk. These products have piqued the interest of both consumers and researchers. Recent studies suggest that A2 milk may have potential health benefits, which is why researchers are investigating this product further. It is interesting to note that the A1 and A2 milk types have area-specific characteristics compared to breed-specific characteristics. Extensive research has focused on milk derivatives obtained from cow’s milk, primarily through in vitro and animal studies. However, few clinical studies have been conducted in humans, and the results have been unsatisfactory. New molecular techniques for identifying A1 and A2 milk may help researchers to develop new studies that can clarify certain controversies surrounding A1 milk. It is essential to exercise extreme caution when interpreting the updated literature. It has the potential to spread panic worldwide and have negative economic implications. Therefore, this study aims to investigate the new aspects of A1 and A2 milk in different research areas and clarify some aspects regarding these two types of milk.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition with a high mortality rate for which there are no effective therapeutics. The failure of the alveolar-capillary barrier, composed of lung endothelial (EC) and alveolar epithelial (AEC) cells, is a critical factor leading to excessive inflammation and edema characteristics of acute lung injury (ALI). Phosphodiesterases (PDE) are enzymes well-recognized for their roles in regulating endothelial permeability and inflammation. Although PDE inhibitors are used as therapeutics for inflammatory diseases like COPD (chronic obstructive pulmonary disease), their efficacy in treating ARDS has not yet been established. In this study, we investigate the effects of ensifentrine, an FDA-approved novel dual PDE 3/4 inhibitor, on lung endothelial and epithelial dysfunction caused by methicillin-resistant S. aureus (MRSA), a pathogen involved in bacterial ARDS. Human primary lung endothelial cells and alveolar epithelial cell lines (A549 and immortalized AEC) were treated with heat-killed MRSA, and their responses were assessed in the presence or absence of ensifentrine. Ensifentrine given either pre- or post exposure attenuated MRSA-induced increased lung endothelial permeability. VE-cadherin junctions, which serve to stabilize the EC barrier, were disrupted by MRSA; however, ensifentrine effectively prevented this disruption. Pre-treatment with ensifentrine protected against MRSA-induced EC pro-inflammatory signaling by inhibiting the expression of VCAM-1, ICAM-1, and by reducing the IL-6 release. In AEC, MRSA caused upregulation of ICAM-1, activation of NF-kB and production of IL-8, all of which were inhibited by ensifentrine. These results indicate that dual inhibition of phosphodiesterases 3 and 4 by ensifentrine is barrier protective and attenuates MRSA-induced inflammation in both lung endothelial and epithelial cells. The PDE3/4 inhibitor ensifentrine may represent a promising novel strategy for the treatment of ALI.

Abstract: Background: Cow’s milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and with few exceptions, presents in the first few months of life. Baked milk containing diets are well tolerated in the majority of milk allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to the infant’s diet in small amounts may enhance the outgrowth of milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. Methods: We convened an expert group to develop a comprehensive milk ladder based on calculated milk protein content using Indian foods. To validate the milk ladder, foods chosen for the ladder were analyzed and the ladder was re-evaluated based on amount cooked milk protein content. Results: Combining expert consensus and validation of milk protein content, we created the world’s first milk ladder containing Indian foods. This is the first ladder that provides information on timing and temperature of cooking, with validated milk protein content. Conclusions: This is the first milk ladder based on unique features of Indian food habits built by consensus of Indian experts along with international collaboration with quantified of milk protein in each step. We believe the “The Indian Milk Ladder” will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India but in countries world-wide where these foods are commonly consumed.

The aim of this study was to provide information on the levels of toxic (Cd and Pb) and essential (Cu, Fe and Zn) elements in cow’s milk produced in the State of Pernambuco (Brazil). A total of 142 samples of raw milk were collected, and the concentrations of essential and toxic elements were determined by inductively coupled plasma-optical emission spectrometry. In almost 30 % of the samples analyzed, the Pb content exceeded the maximum level established in the Brazilian legislation (0.05 mg/l). By contrast, in all samples the Cd content was below the maximum allowable level (0.02 mg/L). The essential trace elements Cu, Fe and Zn were generally present at lower concentrations than reported in other studies and can be considered within the deficient range for cow’s milk. Statistical and chemometric procedures were used to evaluate the main factors influencing the metal concentrations (proximity to major roads, presence of effluents, and milking method). The study findings demonstrate that the proximity of the farms to major roads influences the concentrations of Cd, Pb and Cu and that this is the main factor explaining the Pb content of milk. In addition, the presence of effluents influenced the concentrations of Cu, while no relationship between the metal content and the milking method was observed. Thus, in accordance with the study findings, consumption of cow’s milk produced in the region can be considered a risk to public health due to the high concentrations of Pb and the low concentrations of other essential minerals such as Cu, Zn and Fe in some of the milk samples.

Gamma-aminobutyric acid (GABA) is thought to have beneficial effects on human health and well-being. GABA enrichment by lactic acid bacteria (LAB) could be used in the development of functional fermented foods. In this work, four GABA-producing strains each of Lactococcus lactis and Streptococcus thermophilus were isolated from cowʼs milk, and their phenotypic, technological, and safety profiles were determined. Genome analysis provided genetic support for the majority of the analyzed traits. The operon harboring the glutamate decarboxylase gene (gadB) was chromosomally encoded in all strains and showed the same gene content and gene order as that reported, respectively, for L. lactis and S. thermophilus. In the latter species, the operon was flanked (as in most strains of this species) by complete or truncated copies of insertion sequences (IS), suggesting recent acquisition by horizontal gene transfer. The genomes of three L. lactis and two S. thermophilus strains showed a gene encoding a caseinolytic proteinase (PrtP in L. lactis and PrtS in S. thermophilus). These strains grew in milk forming a coagulum of good appearance and an appealing acidic flavor and taste. They also produced GABA from monosodium glutamate in this medium. Two L. lactis strains were identified as belonging to the biovar. diacetylactis, utilized citrate from milk and produced significant amounts of acetoin. None of the strains showed any noticeable antibiotic resistance, nor did their genomes harbor transferable antibiotic resistance genes, genes involved in toxicity, virulence, or pathogenicity. Altogether these results suggest all eight strains may be considered candidates for use as starter or components of mixed LAB cultures for the manufacture of GABA-enriched fermented dairy products.

Food allergies have increased significantly in recent decades, with shellfish being a leading cause of food allergy and anaphylaxis worldwide, affecting both children and adults. The prevalence of shellfish allergies is estimated to be approximately 0.5-2.5% of the general population, varying significantly by geographical location, age, and consumption habits. Although mollusk consumption has risen, the prevalence of mollusk allergies remains unknown. While extensive research has focused on crustacean allergies, mollusk allergies, particularly those related to gastropods, have received comparatively less attention. Clinical manifestations of shellfish allergy range from localized symptoms to life-threatening systemic reactions, such as anaphylaxis. Notably, severe bronchospasm is a predominant clinical feature in cases involving gastropods. Several allergens have been identified in mollusks, including paramyosin, tropomyosin, and sarcoplasmic calcium-binding protein. In gastropods, documented allergens include tropomyosin, paramyosin, the heavy chain of myosin, and Der p 4 amylase. Diagnosis typically involves a thorough clinical history, skin testing, in vitro quantification of immunoglobulin (Ig) E, and confirmation through oral challenge, although the latter is reserved for selected cases. This review highlights the limited research on gastropod allergy, the identified allergens to date, and the necessity for further investigations to better understand the implications of shellfish allergy within this class.

Due to its similarity with human milk and its low allergenic properties, donkey milk has long been used as an alternative for infants and patients with cow's milk protein allergy. In addition, this milk is attracting growing interest in human nutrition because of presumed health benefits. It has antioxidant, antimicrobial, antitumoral, antiproliferative, and antidiabetic activity. Also, it stimulates the immune system, regulates the gastrointestinal flora, and prevents inflammatory diseases. Although all components of donkey milk can contribute to functional and nutritional effects, it is generally accepted that the whey protein fraction plays a major role. The purpose of this review is to highlight the active proteins and peptides of donkey milk in comparison with other types of milk, emphasizing their properties and their roles in different fields.

Food processing and consumption involves multiple contacts between biological fluids and solid materials of processing devices of which steel is one of the most common. Due to complexity of these interactions, it is difficult to identify the main control factors in the formation of undesirable deposits on the device surfaces that may affect safety and efficiency of the processes. Mechanistic understanding of biomolecule-metal interactions involving food proteins could improve management of these pertinent industrial processes and consumer safety in food industry and beyond. In this work, we perform a multiscale study of formation of protein corona on iron surfaces and nanoparticles in contact with cow milk proteins. By calculating the binding energies of proteins with the substrate we quantify the adsorption strength and rank proteins by the adsorption affinity. We use a multiscale method involving all-atom and coarse-grained simulations as well as generation of 3D structures of the proteins for this purpose. Finally, using the adsorption energy results, we predict the composition of protein corona on iron nanoparticles and flat surfaces via a competitive adsorption model.

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

Histamine intolerance is defined as disequilibrium of accumulated histamine and the capacity for histamine degradation. This clinical term addresses a non-immunologically mediated pathology when histamine ingested with food is not particularly high, but its degradation is decreased. Clinical picture of histamine intolerance in children is similar to that observed in adults apart from male predominance found in paediatric patients. Both in children and adults, histamine-free diet seems to be the treatment of choice. Diamine oxidase supplementation offers another treatment option. There is no symptom and\or test pathognomonic for histamine intolerance. Nevertheless, manifestations of chronic gastrointestinal symptoms, measurement of diamine oxidase deficits, positive results of histamine provocation tests and improvement of symptoms with histamine-free diet greatly increase the probability of histamine intolerance diagnosis. These factors have been included in the proposed in this paper diagnostic algorithm for histamine intolerance. In children histamine intolerance probably co-occur with allergies and bowel diseases, which creates an additional diagnostic challenge. As the evidence for children is weak, further research is needed the establish epidemiology, validate diagnostic algorithms and establish possible treatment options regarding histamine intolerance.

Off-grid electrification planning increasingly recognizes the importance of productive use of electricity (PUE) to promote community value creation and (financial) project sustainability. To ensure a sustainable and efficient integration in the community and energy system, PUE assets must carefully be evaluated to match both the community needs and the residential electricity demand patterns. We propose a novel methodology interlinking qualitative interviews, statistical analysis, and energy system modelling to optimize decision-making for PUE integration in off-grid energy systems in rural Madagascar by aligning relevant PUE effectively with anticipated residential electricity demand patterns based on socio-economic determinants of the community. We find that a possible contribution of the PUE to reducing the electricity costs depends signifi-cantly on three factors: 1. the residential electricity consumption patterns that are influenced by the socio-economic composition of the community, 2. the degree of flexibility of i) PUE assets and ii) operational preferences of the PUE user, and 3. the capacity of community members to finance and operate PUE assets. Our study demonstrates that significant cost reductions for PUE-integrated off-grid energy systems can be achieved by applying our proposed methodology. When matching PUE and residential consumption patterns, the integration of PUE assets in residential community energy system can reduce the financial risk of operators, provided the PUE enterprise operates reliably and sustainably. We highlight that the consideration of local value chains and co-creation approaches are essential to ensure the energy system is addressing the community’s needs, creates value for the community, enhances the project´s financial sustainability, and is achieving the overall objectives of decentralized energy system planning.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

Protein degradation is a biological phenomena essential for cellular homeostasis and survivor. Selective protein degradation is performed by the ubiquitination system which selectively target proteins that need to be eliminated and lead them to proteasome degradation. In this review, we focus on the ubiquitin-conjugating enzyme E2 O (UBE2O) and highlight the role of UBE2O in many biological and physiological process. We further discuss the UBE2O implications in various human diseases, particularly in leukemias and solid cancers and suggest how UBE2O targeting could be novel strategy in the treatment of different human neoplasia.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

Human induced climate change led to the recognition of Community-Based Adaptation (CBA) as one of the remedies in building adaptive capacity and resilience of communities. It recognizes the resources and the skills as well as the agency of communities in shaping the optimal strategy. CBA interventions are vital in addressing community needs and contextual specificities, enable participatory and inclusive engagement and thereby facilitate more profound adaptation impacts. Agent-based modelling (ABM) harbors the potential to be the ideal tool to support developing of tailored adaptation strategies while considering capacities, resources, skills, priorities, needs and the cultural context of local communities. ABM allows to capture the complex relationships among various components within community decision making on CBA actions, the CBA actions themselves and the environment. There exist plenty of tools, however they provide for varying degrees of freedom in agent definition, sensitivity analysis, scalability, experiment design and output analysis to name a few. A set of required key criteria for CBA modelling is developed and all available ABM modelling and simulation tools are assessed for their suitability for CBA. NetLogo emerges as the most fitting tool for incorporating and handling the special features of CBA. It is closely followed by GAMA and Envision. The article provides insights and guidance to researchers and practitioners in selecting ABM tools aligned with the specific requirements of their CBA simulations and projects.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

Background/Objectives: The purpose of this study was to evaluate the relationship between 1-year mortality and health insurance benefit extension policy items in severe pneumonia pa-tients requiring mechanical ventilation using a South Korean nationwide cohort. Methods: A nationwide population-based retrospective study was conducted using the Korean National Health Insurance database. A total of 1,099 patients (542 patients in the health insurance benefit item group and 557 patients in the control group) were included. The primary outcome was 1-year mortality. Results: Among patients with health insurance benefit extension policy items, 203 patients (37.5%) were diagnosed with hemato-oncological disease, who were categorized as group A, and 339 patients (62.5%) were diagnosed with cerebrovascular, cardiovascular, or rare diseases, who were categorized as group B. Group B had lower 1-year mortality (50.7% vs. 62.5%, P

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. Thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression.

This paper investigates the efficacy of YOLOv8 variants for vehicle detection and license plate detection within smart parking applications, emphasizing performance under varying ambient lighting conditions. The proposed system is to seize full video frames, extracts regions of interest containing vehicles, and feeds them into separate, pre-trained YOLOv8 models – one dedicated to vehicle detection and another for license plate detection. Four YOLOv8 variants, nano, small, medium, and large, are evaluated. As a pre-processing step, the images are processed with the help of OpenCV and Pillow libraries to adjust the luminosity and increase the images’ DPI so that they would be easy to perceive by the Tesseract OCR engine. Sixteen potential combinations arise from pairing the four YOLOv8 models for vehicle and license plate detection tasks. To identify the most suitable combinations, we employ the Multi-Criteria Decision-Making method, specifically Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) analysis. This analysis considers 4 critical metrics: Precision, mean average precision at 95% Intersection of Union threshold, Recall and Total Inference Time. The objective is to achieve an optimal balance between high accuracy and real-time processing. Following the selection of optimal YOLOv8 combinations through TOPSIS analysis, we assess their performance under varying ambient light intensity (measured in lux). This evaluation aims to identify the most robust model combinations that ensure accurate vehicle and license plate recognition across the diverse lighting conditions encountered in real-world environment.

Background: Data suggest that food allergies greatly impact a child’s health and growth due to inadequate nutrient intake. Our study aimed to establish the long-term outcome of children with food allergies compared to a control group. Methods: This study was a retrospective cohort study with longitudinal follow-up with a mean period of 4.85 years from the diagnosis to the last study visit. The patients’ nutritional intake was assessed using a three-day food diary and analysed by a dietitian. Patients (61 boys and 33 girls, mean age 6.9 years) had a single food allergy including 21 patients with cow’s milk, 34 with egg, and 39 with peanut allergies. The control group included 36 children (19 boys and 17 girls, mean age 8.03 years). Blood analysis was performed on all participants. Results: Data from our study showed that patients with cow’s milk, egg or peanut allergies had normal growth and achieved catch-up growth from the diagnosis until the last study visit. In the cow's milk allergy group, the allergy was shown to affect calcium intake (p<0.05), while egg and peanut allergies did not impact the dietary intake of nutrients. None of the investigated food allergies affected blood results (p<0.05). Conclusions: In the present study, we showed that single food allergies do not compromise growth in children if they are provided with appropriate support and that the affected children reach catch-up growth from the diagnosis.

This article touched upon various issues regarding vulnerability, disparities amongst community settings, and the effect of air pollution on the populace (low-income communities). Furthermore, the paper emphasized environmental ethics approaches like anthropocentric, nature-centric, and deep-ecological approaches. More so, it addresses the importance of handling these disparities, particularly from the geopolitical dimension, and recommends cross-border cooperation and accountability in promoting environmental justice in India.

Biopolymer gels have gained tremendous potential for therapeutic applications due to their biocompatibility, biodegradability, and ability to adsorb and bind biological fluids, making them attractive for drug delivery and therapy. The versatility of biopolymer gels in theranostic backgrounds, with a focus on integrating imaging features and facilitating real-time monitoring of drug delivery. Different methods of delivery are explored imaging agents into biopolymer gels, including encapsulation, surface functionalization, nanoparticle encapsulation and layer-by-layer assembly techniques. Integration of Agents and Real-Time Monitoring Drug Delivery We summarize the synthesis methods, general properties, and mechanisms of biopolymer gels functionality, demonstrating their broad applications as multimodal systems for imaging-based therapeutics. These techniques not only enable multiple imaging but also provide signal enhancement and imaging a targeted facilitates, increasing the diagnostic accuracy and therapeutic efficacy. In addition, current techniques for incorporating imaging agents into biopolymer gels are discussed, and their role in precise drug delivery and monitoring.

Recent years have been abundant in research concerning human microbiome and its impact on the host’s health. Studies have shown, that not only the commensal bacteria itself, but also postbiotics, understood as unalived microorganisms, possibly with the presence of their components, may have themselves effect on various elements of human physiology. In this article we take a closer look on the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today’s world being a serious subject of concern. Through altering patients’ immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given greatly promising findings in the field of their immunomodulating potential.

The internationals guidelines about food intolerances, allergy and immunity provide for rigorous steps in which ultrasonography is not provided. However there is evidence in literature about an ancillar role of ultrasonography in these conditions. In this report we analyze the main pathologies with allergic or immune pathogenesis

The extent of access to energy of displaced populations in settlements and camps in Africa is largely 14 unknown. A multitude of contextual factors, such as the location and the characteristics of housing, 15 the legal status, the socio-cultural background, and the availability of humanitarian and public ser- 16 vices impact the living conditions and the needed energy services. Limitations in accessing energy 17 services have direct, multilayered, and far-reaching implications, including impacts on health, nu- 18 trition, education, protection, and livelihood. The objective of this article is to contribute to a more 19 comprehensive overview of the current state of energy access in displacement contexts on the Afri- 20 can continent by identifying and utilizing existing data. After a screening of the vast and various 21 available information, setting up of a database, consolidating the gathered data as well as assessing 22 the quality through a quality assessment method, the currently available information is visualized 23 and discussed. Considerable differences in the access to electricity for displaced persons across the 24 countries are found. For both electricity and clean cooking, the availability for displaced persons 25 ranges from nearly no access at all up to an access rate of 100%. More strikingly, the results also 26 show that besides South Africa and countries in the Maghreb region, the access to both clean cook- 27 ing and electricity for displaced persons is very low. At the same time, the fragmented data availa- 28 bility, the poor data quality, and the questionable expediency of available data allows neither solid 29 theoretical conclusions nor planning of effective practical implementation measures. Novel inter- 30 disciplinary research, conceptual frameworks and indicators are needed for the purpose of compa- 31 rability and consistency. Future research has the potential to more comprehensively capture the 32 current state of access to energy in displacements contexts and in a next step to examine how energy 33 is interwoven in the lives of displaced people to derive a set of more detailed context-sensitive en- 34 ergy indicators. It is essential that the concerned persons, the displaced persons themselves are in- 35 cluded in the research in a meaningful way.

Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes. We investigated if immunological non-responsiveness to HBV after repeated HBsAg-based vaccinations can be overcome by immunization with VVX001 (i.e., Alum-adsorbed BM325, a component of BM32). Methods: A subject failing to develop protective HBV-specific immunity after HBsAg-based vaccination received five monthly injections of 20 µg VVX001. PreS-specific antibody responses were measured by ELISA and micro-array technology. Serum reactivity to subviral particles of different HBV genotypes was determined by sandwich ELISA. PreS-specific T cell responses were monitored by CFSE staining and subsequent FACS analysis. HBV neutralization was assessed using cultured HBV-infected HepG2 cells. Results: Vaccination with VVX001 induced a strong and sustained preS-specific antibody response composed mainly of the IgG1 subclass. PreS-specific IgG antibodies were primarily directed to the N-terminal part of preS containing the NTCP attachment site. IgG reactivity to sub-viral particles as well as to the N-terminal preS-derived peptides was comparable for HBV genotypes A-H. A pronounced reactivity of CD3+CD4+ lymphocytes specific for preS after the complete injection course remaining up to one year after the last injection was found. Maximal HBV neutralization (98.4%) in vitro was achieved 1 month after the last injection which correlated with the maximal IgG reactivity to the N-terminal part of preS. Conclusion: Our data suggest that VVX001 may be used as a preventive vaccination against HBV even in non-responders to HBsAg-based HBV vaccines.

Digital transformation, powered by technologies like AI, IoT, and big data, is reshaping industries and societies at an unprecedented pace. While these innovations promise smarter energy management, precision agriculture, and efficient resource utilization, they also introduce serious environmental challenges. This paper examines the dual impact of digital technologies, highlighting key threats such as rising energy consumption, growing e-waste, and increased extraction of raw materials. For instance, global e-waste reached 62 million metric tons in 2022, and data centers alone accounted for nearly 1% of the world's electricity demand in 2019. The review synthesizes findings from studies on topics like the energy use of blockchain technologies and the environmental costs of raw material extraction in the smartphone industry. Moreover, it identifies critical research gaps, particularly in understanding the environmental impact of digital usage at individual and household levels. Practical strategies such as integrating circular economy principles, promoting renewable energy, and green computing are proposed to balance technological advancement with sustainability goals. This study highlights the need for a holistic approach, suggesting future research directions to minimize digital transformation’s environmental footprint while maximizing its sustainability benefits.

Milk consumption is crucial for a balanced diet, yet recent trends indicate a decline, especially in Italy. A significant factor in this decline is the altered perception of milk quality among consumers, creating a communication gap between them and other stakeholders. This study aimed to explore the discourse on social media and sentiment towards the concept of milk quality among consumers, farmers, and processors. The research adopted a Social Media Analysis to examine online community messages. A sample of 19,906 Italian comments and posts mentioning keywords Milk, Quality, Cow, and Vaccine was collected and categorized using term frequency analysis, correspondence analysis, and sentiment analysis. Results highlighted gaps in the perceptions of milk quality: farmers focused on economic issues, consumers on animal welfare and health, and processors on lactose content. For farmers, almost all comments were negative, while for processors, nearly all comments were positive. Consumers presented a more mixed picture. This work contributes to the literature by expanding research on milk quality using social media as a source of information. The findings suggest that enhancing communication and understanding among these groups could lead to more effective strategies for addressing consumer concerns, potentially reversing the declining of milk consumption.

Aflatoxins (AF), secondary metabolites produced by fungi, pose significant health risks, especially to children and adults. In developing countries like Nepal, the tropical climate promotes fungal growth, leading to high levels of AF in animal feed and milk. In this study, we investigated the incidence of aflatoxin M1 (AFM1) contamination in 84 milk samples collected from the Kathmandu district using the competitive enzyme-linked immunosorbent assay (c-ELISA) technique. We also interviewed farmers to gather information on feeding and storage practices. . All the collected milk samples were contaminated with AFM1, with 97.6% of the samples exceeding the European Union (EU) maximum permissible limit of 50 ppt. The majority (98.5%) of the farms included paddy straw, and all farms (100%) included concentrate in their feed regimen. Only half (52%) of the farms had proper storage facilities. Straw was mostly stored in sacks outdoors or left open in a shed, while concentrates were stored in a closed room or shed. The study reports very high contamination levels of AFM1 in the milk samples, presenting a serious public health issue, and recommends comprehensive surveillance and further investigation across the country, especially given the limited research and literature available.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

The realization of a perfect absorber A = 1 with transmittance and reflectance T=R=0 by a thin metasurface is one of the hot topics in recent nanophotonics prompted by energy harvesting and sensor applications (A + R + T =1 is the energy conservation). Here we tested optical properties of over 400 structures of metal-insulator-metal (MIM) metasurfaces for a range of variation in thickness of insulator, the diameter of a disc and intra-disc distance experimentally and numerically. Conditions of a near-perfect absorption A > 95% with simultaneously occurring anti-reflection property (R < 5%) were experimentally determined. Differences between the bulk vs. nano-thin film properties at mid-IR of the used materials can be of interest for plasmonic multi-metal alloys and high entropy metals.

Ferritin is an indirect marker for total body iron stores. Comparison of the ferritin concentrations in the meconium with the concentrations of proteins regulating iron metabolism could aid better understanding of principles behind the adjustment between the fetal iron pool and newborn body size. Ferritin, transferrin, haptoglobin, ceruloplasmin, lactoferrin, myeloperoxidase, neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin concentrations were measured by ELISA in meconium samples from 122 neonates. The neonates were classified according to the meconium ferritin tertiles and the values were collated with the meconium concentrations of other proteins and newborn body weight and length measurements. Increasing ferritin concentrations in meconium in consecutive tertiles (p < 0.05) were parallel to increased NGAL concentrations (p < 0.05). The interrelationships between the meconium concentrations of transferrin, haptoglobin and NGAL as well as between myeloperoxidase, calprotectin and lactoferrin are maintained in all subsequent tertiles of ferritin concentrations, (p < 0.05). In contrast to ferritin, increasing meconium NGAL concentrations in consecutive tertiles were linked to increased concentrations of transferrin, haptoglobin, lactoferrin and myeloperoxidase (p < 0.05) and of calprotectin, ferritin and ceruloplasmin (p < 0.1). Meconium ceruloplasmin concentrations correlate exclusively with neutrophil granule proteins, i.e. myeloperoxidase, NGAL, lactoferrin and calprotectin (p < 0.05). Meconium ferritin concentrations negatively correlates with birth weight (r= -0.20) and length (r= -0.31) of neonates, whereas NGAL concentrations just with birth length (r= -0.26). The remaining proteins did not show such relationships with the size of the newborn. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates of smaller size. High meconium concentrations of both ferritin and NGAL may specifically characterize neonates with lower body measurements. Correlations between meconium transferrin, haptoglobin and NGAL may confirm the interrelationships of these proteins for proper iron control and transport in the intrauterine environment. Meconium ceruloplasmin concentrations may reflect the control of neutrophil activity in utero.

According to current forecasts, global heating is likely to exceed 2,8°C by the end of the century. This makes substantial adaptation measures necessary to secure a broad basis for livelihoods provision and the conservation of biodiversity. While the implementation of top-down and technocratic adaptation efforts is the majority, related adaptation shortcomings of socio-economic and ecological nature are becoming more and more apparent. Community-based adaptation (CBA) with its participatory, inclusive and needs-based bottom-up approach offers a promising and powerful alternative. This article uses a semi-systematic literature review approach to screen the current literature and identify core issues of CBA. Linking communality, locality, multidimensionality, power imbalances, transformative potential, localisation, the triad of adaptation metrics and adaptation with nature to corresponding potential actions for practical implementations provides a more holistic conceptualisation and broadens the horizons for further learnings, research and improved application.

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.

In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected, and a range of clinical factors data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and ICU admission were found directly associated with a higher mortality risk (OR 6.9 and 3.2, respectively). The clinical predictors of mortality were need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminaemia, dementia, cancer, elevated CPK and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat and cough diminished risk of death (OR 0.5, 0.2 and 0.1 respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain and elevated LDH (OR 371.0, 3.6 and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity and elevated GGT (OR between 1.7 and 5.2), whilst prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C&gt;T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C&gt;T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

Bovine whey cheese (WC) is a product from southern European countries that presents some challenges: their elaboration process involves high energy inputs, the yield is low and WC has a short shelf-life. The application of ultrafiltration to bovine whey before its manufacture and the employment of protective cultures can reduce these disadvantages. The aim of this work was to manufacture whey cheeses using ultrafiltrated (UF) concentrated bovine cheese whey with added probiotics or probiotics plus protective cultures. Three types of WC were produced: control, without any addition (C); with the addition of the probiotic Lactobacillus acidophilus (LA5); with the addition of Lactobacillus acidophilus plus a protective culture containing Lactobacillus paracasei and Lactobacillus rhamnosus (LA5FQ4). The WCs were stored under refrigerated conditions for 28 days. The products with added cultures presented a lower pH and a higher titratable acidity when compared to the control. Sample LA5 presented the lowest pH and the highest titratable acidity while LA5FQ4 presented intermediate values. Slight differences were observed between products regarding color parameters, chiefly as a result of storage time. The samples with added cultures were firmer when compared to the control, showing LA5 cheeses the highest values at the end of the storage. Lactobacilli and lactococci counts were of the order of log 8-9 CFU/g for the products with added cultures. Lower levels of yeasts and moulds were detected on the sample with the protective culture (LA5FQ4), that by the end of storage presented counts one log cycle lower than C and LA5. Hence, it is evident the beneficial impact of the protective culture on the shelf life of the product. In what concerns to sensory evaluation, LA5FQ4 cheeses obtained the highest scores regarding all parameters evaluated. It could be concluded that the use of UF associated to the addition of protective cultures can be very useful to reduce the energy consumption of the process, prolong the shelf life of WC, and to improve its sensory properties.

We hypothesized possibility that inline registered reticulorumen pH can be as biomarker of cows reproduction and health status. Aim of this study was to evaluate the relationship of reticulorumen pH with biomarkers from automatic milking system (AMS) and some blood parameters and determinate reticulorumen pH as biomarker of cows reproduction and health status. According to cows reproductive status the cows were classified as belonging to the following four groups: 15-30 d. postpartum; 1-34 d. after insemination; 35 d. after insemination (non-pregnant); 35 d. after insemination (pregnant). According reticulorumen pH assay experimental animals were divided into four classes: 1) pH<6.22 (5.3% of cows), 2) pH - 6.22-6.42 (42.1% of cows), 3) pH - 6.42-6.62 (21.1% of cows), 4) pH >6.62 (10.5% of cows). Rumination time, body weight, milk yield, milk fat – protein ratio, milk lactose, milk somatic cell count (SCC), milk electrical conductivity of all quarters of udder were registered with the help of Lely Astronaut® A3 milking robots. The pH, temperature of the contents of cow reticulorumens and cow activity were measured using specific smaX-tec boluses. Blood gas parameters were analyzed using a blood gas analyzer (EPOC, Canada). We found that pregnant cows has higher reticulorumen pH during insemination time, comparing with non-pregnant. Cows with lower reticulorumen pH has lowest milk fat – protein ratio, and lactose concentration, and highest SCC. Cows with lowest reticulorumen pH has lowest blood pH. With increase reticulorumen pH, increases blood potasium and hematocrit, decreases CO2, saturation and sodium.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo wheat allergen-specific skin prick test (SPT), blood test for serum immunoglobulin E (sIgE) levels or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its novel diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis and basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability and safety of related clinical trials will then be discussed.

Immunology is a branch of medicine that studies the immune system and its pathology. There are known scientific informations, that in medical immunology specific tests performed in the laboratory for diagnosis. In addition good to mention that allergies include medical diagnostic methods such as blood tests. Also there are used for detection the presence and the levels of IgE antibodies. These antibodies are produced by the human immune system in contact with certain allergens. Examples of allergens include for example pollen, house dust, some herbs or molds, some animals and certain foods. If a person has an allergy, their immune system overreacts to an allergen by producing antibodies, called Immunoglobulin E (IgE). Currently within the present describtion aim to discuss some aspects reffering to fungal allergen and mold allergy diagnosis, in a briefly following steps of our purposed shortly review.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new method has been developed to quantify alcohols and their oxidative products using a headspace gas chromatography- mass spectrometer and isotope-labelled internal standards. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major component, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. In ethanol-based hand sanitizers, a significant amount of acetaldehyde was observed as an oxidation product, while in isopropanol-based hand sanitizers, acetone was observed. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase of acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature.

This study investigates the effect of altitude on the fatty acid composition of grass, yak milk, and yak ghee on the Qinghai-Tibet Plateau, aiming to understand how environmental factors influence the nutritional quality of these products. Samples were collected from four different altitudes and analyzed for fatty acid profiles using gas chromatography. The findings reveal significant differences in fatty acid profiles, with notably higher concentrations of lauric acid (C12:0) and myristic acid (C14:0) at altitude A2 compared to others (p＜ 0.001). Furthermore, the fatty acid composition in yak milk and ghee is influenced by the grass consumed and the metabolism of rumen microorganisms. The results indicate that yaks adapt their lipid biosynthesis to high-altitude conditions, as evidenced by a significant increase in stearic acid (C18:0) levels at higher altitudes, which subsequently affects the nutritional value of their milk and ghee. These insights are crucial for improving yak breeding and dairy production practices, ultimately enhancing food security and nutritional health for local communities residing in high-altitude areas. The study underscores the necessity for further research on optimizing these natural resources for better health outcomes.

Goat milk is a nutritious food, with high levels of vitamins and minerals. In this context, there is a growing need to improve preservation techniques. Thus, the present work was developed with the aim of drying goat milk using a spray dryer. Chemical, physical, and physicochemical analyses of powdered goat milk and reconstituted goat milk were performed, as well as the characterization of raw goat milk. The statistical model used was the full factorial design 2³ + 3, observing the Pareto Diagram and Analysis of Variance to study the effect of atomization frequency (Hz), inlet temperature (°C), and peristaltic pump rotation (rpm) on the responses for the powdered and reconstituted product. The planning was executed with eleven trials, including nine different trials and three central points. For the analysis of the planning at a 95% confidence level, the Statistica 8.0 software was used. The results showed that atomization frequency and inlet temperature had the greatest effect on the powdered product and the reconstituted food, respectively. Therefore, the importance of drying this food is evident as it offers several advantages for the food industry and consumers.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer characterized by two etiologies: the first one, observed in most cases, is attributed to Merkel cell polyomavirus (MCPyV), a DNA tumor virus, while the second one is due to ultraviolet (UV) radiation exposure. Currently, there are limited diagnostic, prognostic, and therapeutic biomarkers available for MCC. MicroRNAs (miRNAs) are small RNA molecules that do not code for proteins but regulate various cellular processes, including cell cycle progression, proliferation, differentiation, and apoptosis. The dysregulation of miRNAs has been associated with a wide range of cancers since they can act as either tumor suppressors or oncogenes. This paper aims to collect, summarize and re-organize the recent discoveries concerning miRNAs, whose dysregulation in the pathogenesis and progression of MCC is slowly emerging. Furthermore, the potential clinical applications of miRNAs as diagnostic biomarkers, possible differentiation between MCPyV-related and unrelated MCC, predictors of response to therapy and prognostics are also discussed. From this review, it emerges that miRNAs may have, in the near future, the potential to become clinically significant in improving the diagnostic accuracy, prognostic evaluation, and therapeutic options of MCCs. Finally, the new perspectives on the poorly explored field of artificial intelligence in MCC are provided.

In the process of sewage coagulation treatment, quartz sand is often used as a heavy medium to accelerate the settling rate of flocs, but it will adversely affect the removal efficiency of pollutants. The factors that affect the coagulation effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc, their reasonable setting is critical to. This paper was to study the optimal conditions of quartz sand enhanced coagulation(QSEC), first, single-factor tests were conducted to preliminarily explore the optimal range of influencing factors, and then response surface methodology（RSM）tests were performed to accurately determine the optimums of significant factors. The results showed that the addition of quartz sand can’t improve the water quality of coagulation treatment, but it can significantly accelerate the coagulation settlement process, the quartz sand dosage, the coagulant dosage and sewage pH all impacted significantly on its coagulation effect, and existed inflection points. A model that could guide QSEC was obtained by RSM tests. The model optimization and experimental validation showed that the optimal QSEC conditions for treating domestic sewage were as follows: the polyaluminum chloride(PAC) dosage, cationic polyacrylamide(CPAM) dosage, the sewage pH, quartz sand dosage, stirring time and settling time were 0.97 g·L-1, 2.25 mg·L-1, 7.22, 2 g·L-1, 5 minutes and 30 minutes, respectively, and the turbidity of treated sewage was reduced to 1.15 NTU.

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.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids: allocryptopine (ACP) and protopine (PP) was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies showed also revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/ Quinaldine Red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural products-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

Aiming to improve medical diagnosis and treatment, artificial intelligence (AI) has emerged as a transformational force in the healthcare industry. In this article, we examine how AI is increasingly being used to improve healthcare, with an emphasis on how it is changing medical diagnosis and treatment. We explore the opportunities, threats, and ethical concerns of incorporating AI into healthcare practice. In addition, we feature important AI applications in radiology, pathology, cardiology, and cancer. AI has great potential to improve patient outcomes, diagnostic accuracy, and the ability to provide individualized treatment plans in the future if it is used and refined with care.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

The objective of this study was to determine the effects of supplementing L-isoleucine (L-Ile) on milk protein synthesis, using an immortalized bovine mammary epithelial (MAC-T) cell line. In this case, the cells were treated with 0, 0.3, 0.6, 0.9, 1.2 and 1.5 mM of supplemental Isoleucine (Ile), and the most efficient time for protein synthesis for each amino acid was determined by measuring the cell, medium and total protein at 0, 24, 48, 72 and 96 h. Confirmatory tests showed that 48h incubation time and 0.6 mM dosage of L-Ile are considered as the optimal time and dosage. The mechanism of milk protein synthesis was elucidated through proteomics analysis to clarify the metabolic pathway. When the L-Ile was supplemented, extracellular protein (medium protein) reached a peak at 48h, whereas in the case of the intracellular cell protein, it was shown to have reached to its peak at 24h in all L-Ile dosage treatments. In total, it is noted that there were 63 upregulated and 52 downregulated proteins. The results of the protein pathway analysis showed that the L-Ile group stimulated insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, insulin/IGF pathway-protein kinase B signaling cascade, p53 pathway, de novo purine biosynthesis, Wnt signaling pathway, glycolysis, pentose phosphate pathway, and ATP synthesis which are pathways involved and related to protein and energy metabolism. Together, these results demonstrate that L-Ile supplementation was effective in stimulating β-casein synthesis by stimulating genes and pathways which are significantly related to protein and energy metabolism.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

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.

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.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

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.

Cow milk is rich in proteins, fats, carbohydrates, and minerals, and its nutrient content depends on various factors. We tested differences in fatty acid and protein contents of milk from seven breeds and regions, including three dairy breed samples: Holstein milk from Beijing, China (BH); Holstein milk from Hebei province, China; Jersey milk (JS); and four dairy/meat cow samples: Sanhe milk, Xinjiang brown milk (XH), Simmental milk, and Shu Xuanhua milk. Breed significantly affected total fat, fatty acid, and protein contents. The region significantly affected the contents of different fatty acids, α-lactalbumin, and lactoferrin. JS had the highest total fat, most fatty acids, and casein contents. XH performed well with significantly higher unsaturated fatty acid content than BH, which was not significantly different from JS, and its protein composition of low β-lactoglobulin and high lactoferrin was more similar to breast milk, which may thus be favorable to the growth and development of children. Our results may inform the development of dairy products from different cow breeds and advance the process of accurate breed identification.

The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (&lt;22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.

(1) Background: Eosinophils importance as T2 inflammation markers is known to be fundamental in asthma, chronic sinusitis, vasculitis. In cancer, despite their potential antiproliferative effect, their role remains unclear. Our purpose was to describe the relation between baseline blood eosinophil count (EOS) and overall survival in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We have analyzed retrospectively the data of 137 adult patients, who underwent surgical treatment of PDAC between years 2012-2019 with no history of systemic steroid use directly before surgical treatment and no metastases found intraoperatively. (3) Results: EOS&lt;0,1 G/l (vs. ≥0,1 G/l) was an independent prognostic factor for OS both the uni- and multivariate Cox regression (respectively: HR=1,48, p=0,035 and HR=1,57, p=0,021). According to EOS and PDAC stage, median OS were: in stage I-III, EOS ≥0,1 G/l group: 14,5 months, in stage I-III, EOS &lt;0,1 G/l group: 8,0 months, in stage IV, EOS ≥0,1 G/l group: 7,0 months, in stage IV, EOS &lt;0,1 G/l group: 5,0 months. (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that T2 inflammation may be the factor directly or indirectly lengthening survival of PDAC patients.

Introduction People are presenting with chronic musculoskeletal pain at a younger age, and many fulfil criteria for fibromyalgia. We have recently shown a strong association between fibromyalgia symptoms and autistic traits in a self-selected community population, with the relationship mediated in part by the presence of hypermobility. Many respondents also described food sensitivities and intolerances. This study explores relationships between food issues and fibromyalgia symptoms in this population Methods The study used a nonexperimental, correlational design with data collected from a volunteer sample of 442 adults (aged 18-60) who completed online self-report questionnaires assessing each of fibromyalgia symptoms (ACR criteria), autistic traits (RAADS score) and hypermobility (Beighton’s test). Subjects were also asked to record any food sensitivities, allergies, or intolerances, along with their consequences. Correlation analyses and linear regressions were used to test the relationships between these features and each of fibromyalgia, autistic traits and hypermobility. Data was analysed using parametric and non-parametric techniques to assess the strength and significance of relationships, causes of variance and the potential mediating effect of food-related symptoms in the correlation between fibromyalgia features and autistic traits Results Our self-selected community population had a mean age of 24 years and was 77% female. The prevalence of fibromyalgia, autistic traits and hypermobility was 40%, 65% and 44% respectively. Half of all subjects reported food sensitivity and 31% reported food intolerance. The incidence of food-related symptoms was higher among subjects who met criteria for fibromyalgia than those who reported autistic traits or hypermobility. Food sensitivity and food intolerance were both more significantly associated with fibromyalgia (r=0.24, p>0.001 and r=0.38, p>0.001) than with autistic traits (r=0.15, p>0.01 and r=0.17, p>0.01). Discussion This is the first community study to provide evidence for a direct association between features of fibromyalgia and reported food intolerance and sensitivity. Although self-selected, the findings in our predominantly young population suggest that gluten and lactose consumption may be associated with higher levels of musculoskeletal pain. Avoidance of these foodstuffs was commonly reported to reduce symptoms. Dietary adjustment may merit further investigation as a therapeutic modality for some patients with fibromyalgia.

Spider silks, renowned for their exceptional mechanical and biocompatible properties, offer significant potential as scaffolds in tissue engineering. This paper explores the feasibility of using spidroins, the primary proteins in spider silk, to develop scaffolds that closely mimic the extracellular matrix (ECM) essential for tissue regeneration. Spidroins (spider silk proteins) are particularly valuable due to their unique strength, elasticity, and biocompatibility, which support cellular growth and differentiation. The paper examines current methods for producing recombinant spider silk, including using unicellular hosts like E. coli and multicellular systems like transgenic plants and silkworms. It also examines current scaffolds that utilize spidroins and their shortcomings, such as immunogenicity and protein production, which must be urgently addressed for more practical and effective widespread biomedical applications. In addition, it stresses the need for further research to solve these challenges and fully realize the potential of spider silk in biomedical applications.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

Solar pasteurization, as a means of treating milk in remote rural areas without electrical power, is based on using solar energy to thermally inactivate pathogenic microorganisms at temperatures below the boiling point to maintain or improve milk quality. A solar milk pasteurizer of flat‐plate water‐heating glass acting as the solar collector, connected to a stainless-steel cylindrical milk vat, was constructed and evaluated in Navrongo, in the tropical savanna zone of Ghana, West Africa. The novel approach taken in this project is to integrate the solar collection and heat exchanger into a single unit using materials and fabrication techniques readily available in the developing world. The vat comprises a 1.5 mm thick stainless steel cylindrical tank, a 2.2 cm wide hot water jacket, and an outer layer of 5.0 mm thick aluminium foil insulation. Hot water produced by the collector was used for pasteurizing milk. The optimum quantity of milk that this device could pasteurize under the study conditions was 8 L. The device could pasteurize raw milk to a maximum temperature of 74 °C at 14:00 h GMT. The ambient temperature during the pasteurization ranged from 30 °C to 43 °C. The microbial analysis before and after the pasteurization was done, and the result shows that the total bacteria count before pasteurization was 6.6x10⁶ log CFU/mL per unit volume, and the total bacteria count after pasteurization was 1.0x10² log CFU/mL. By acceptable standards, the total bacteria count after pasteurization is within a safe range for consumption, and coliform counts were negative. The solar milk pasteurization system is cost-effective. Hence, it is appropriate for milk producers in arid pastoral areas without electricity to adopt the solar pasteurizer as an alternative to firewood as a fuel source for milk pasteurization. This approach can potentially create a cottage industry that may also play a crucial role as a water treatment technology that will improve the health of rural populations.

The aim of this research was to select apple varieties suitable for allergy sufferers and diabetics. We first conducted a comprehensive analysis of several apple varieties. The total polyphenol content, sugar content, acidity, and antioxidant activity of the apple fruit juices were determined using spectrophotometric techniques. We also measured the amounts of polyphenols in the apple skins and their antioxidant potential, as well as the allergenic content in the apple juices. The strength of sensitization was assessed using the ELISA method. The lowest amounts of Bet v 1 homologues were found in the varieties Kosztela (4.21 ± 0.71 µg/g), Koksa Pomarańczowa (4.24 ± 0.08 µg/g), and Reneta z Brownlee (4.86 ± 0.18 µg/g). Low values for profilin were observed for Renet Harbert (1.74 ± 0.22 ng/g) and Schieblers Taubenapfel (2.26 ± 0.12 ng/g). The highest values for profilins and Bet v 1 homologues were found in the Złotka Kwidzyńska variety (12.40 µg/g), followed by Malinowa Oberlandzka (9.86 µg/g) and Jakub Lebel (8.87 µg/g). The varieties richest in profilin were Reneta Blenheimska (8.81 ng/g), Szara Reneta (7.88 ng/g), Pepina Ribston (7.67 ng/g), and Reneta z Brownlee (7 .63 ng/g). Given their minimal content of both profilins and Bet v 1 homologues, Koksa Pomarańczowa (4.24 ± 0.08 µg/g Bet v 1 and 4.49 ± 0.82 ng/g profilins) and Książę Albrecht Pruski (5.57 µg/g Bet v 1 and 3.34 ng/g profilins) were identified as suitable for people with allergies. For diabetics, the most suitable apple variety was found to be Jakub Lebel, providing large doses of antioxidants and polyphenols (41.1 ± 2.0 and 5.16 ± 0.42, respectively) and a relatively low sugar content (9.06). Similar results were measured for Kingfish, with 10.2 sugars, 5.68 ± 0.49 antioxi-dants, and 46.2 ± 1.5 polyphenols. The Galowany Pipping variety was found to have a low sugar content (9.71), corresponding to a perceived sweetness of 2.5. Prince Albert of Prussia apples had high antioxidant potential (5.70 ± 0.77) and a low sugar content (11.09). The James Grieve apple variety provided a high polyphenol content of 63.3 ± 1.1 with a high antioxidant level of 5.34 ± 0.45. Grochówka offers a combination of a high polyphenol content (48.6 ± 1.9), a high level of antiox-idant protection (5.50 ± 0.34), and a very low perceived sweetness (from 3.0).

Integrated crop-livestock production (ILP) is an interesting alternative for more sustainable soil use. However, more studies are needed to analyze soil pore properties under ILP at the micrometer scale. Thus, this study proposes a detailed analysis of soil pore architecture at the micrometer scale in three dimensions. For this purpose, samples of an Oxisol under ILP subjected to minimum tillage (MT) and no-tillage (NT) with ryegrass as cover crop (C) and silage (S) were investigated. The soil micromorphological properties of the soil were analyzed using X-ray microtomography. The MT(C) system showed the highest values of porosity (c. 20.4%), connectivity (c. 32.8×103), volume (c. 26%), and number of pores (c. 32%) in a rod-like shape. On the other hand, the MT(S), NT(C), and NT(S) systems showed higher tortuosities (c. 2.2, c. 2.0, and c. 2.1) and lower pore connectivities (c. 8.3×103, c. 6.9×103, and c. 6.2×103), especially in S use. Ellipsoidal and rod-shaped pores predominated over spheroidal and disc-shaped pores in all treatments. The results of this study show that the use of ryegrass as a cover crop improves soil physical properties, especially in MT. For S use, the type of soil management (MT or NT) did not show any differences.

Understanding tourist behaviour during and after major tourism crises is essential to help destinations recover. The COVID-19 pandemic, a period of uncertainty and risk, makes it relevant to assess factors that influence travel intentions. There has been little research on tourist behaviour during health crises and, in particular, on perceived health risk and uncertainty effects on travel intentions. This study was carried out during the first months of the pandemic in Brazil and aims to investigate the role of health risk perception and intolerance of uncertainty on travel intentions for 2020 and 2021. We applied an online survey to 1,150 Brazilian participants from March to May of 2020. Our findings indicate that perceived COVID-19 severity, perceived probability of contracting it, and expected pandemic duration are significant predictors of travel intentions for both years. This paper sheds new light on tourist behaviour in the context of global health crises.

Milk MIR spectra have been shown to provide valuable information on a wide range of traits to be used in dairy cattle breeding programs. Selecting the most informative variables from complex data can improve prediction accuracy and model robustness and, consequently, the interpretability of MIR spectra. Thus, we aimed to investigate the prediction performance of feature selection methods based on MIR spectra data, using the milk fatty acid (FA) profile as an example to illustrate the evaluated procedure. Data of MIR spectra, milk test-day records, and reference FA concentrations of 155 first-parity Holstein cows were used in the analyses. Four models comprising different explanatory variables and five feature selection methods were evaluated. The results indicated that the Competitive Adaptive Reweighted Sampling (CARS) method can effectively select the most informative variables from the MIR spectra, resulting in higher prediction accuracies than other variable selection approaches. The model including selected MIR spectra and cow information variables [days in milk at the test day, age at the test day, pregnancy stage (in days), number of days open, number of inseminations, and somatic cell count] yielded the best FA profile predictions based on Partial Least Square regression. In particular, ten FAs (C8:0, C10:0, C14:1, C17:0 isomers, C18:1, C18:1 isomer, medium-chain FA, unsaturation FA, monounsaturated FA, and polyunsaturated FA) presented accuracies based on the determination coefficient (R2cv) ranging from 0.66 to 0.85 in internal validation and from 0.65 to 0.84 in external validation. By running CARS 1,000 times in internal validations, we obtained the frequency of selected milk MIR wavenumber for 35 FAs. The most related wavenumbers to FAs were found within 1,003 to 1,145 cm-1, while other discrete areas were between 1,651 to 1,797 and 2,834 to 2,954 cm-1. These biomarkers may give insights into the relationship between MIR spectra and FA phenotypes. In conclusion, using CARS and cow information improved predictions of FAs based on MIR spectra in Chinese Holstein dairy cows. Additional validation studies should be conducted as larger datasets become available.

Background and Objectives: Mycobacterium bovis Bacillus Calmette–Guérin (BCG) vaccine administration has been suggested to prevent glucose metabolism abnormalities and fatty liver in genetically obese ob/ob mice; however, it is not clear whether the beneficial effects of BCG are also observed in the progression of glucose intolerance induced by a high-fat diet (HFD). Therefore, the effects of BCG vaccination on changes in glucose tolerance and insulin response were investigated in HFD-fed C57BL/6 mice. Materials and Methods: We used the BCG Tokyo 172 strain to determine its effects on abnormalities in glucose metabolism. For vaccination, five-week-old male mice were injected intraperitoneally with BCG and maintained on an HFD three weeks later. The mice were regularly subjected to intraperitoneal glucose tolerance and insulin tolerance tests (IGTT and ITT). These tests were also performed in mice transplanted with bone marrow cells from BCG-vaccinated donor mice. Results: Significant effects of BCG vaccination on blood glucose levels in IGTT and ITT were observed from week 12 of the experiment. BCG vaccination significantly improved changes in fasting glucose and insulin levels, insulin resistance indexes, and glucagon-to-insulin ratios by HFD at the end of the experiment. Significant inhibitory effects in IGTT and ITT on glucose intolerance were also observed by transplantation with bone marrow cells derived from BCG-vaccinated donor mice. Conclusions: BCG vaccination significantly delayed glucose intolerance progression, suggesting a beneficial effect of BCG on the pathogenesis of type 2 diabetes. It has also been demonstrated that the effects of BCG vaccination may be at least partially due to an immune memory (trained immunity) for hematopoietic stem and progenitor cells of the bone marrow.

Pulmonary arteriovenous malformation (PAVMs) in children are rare lesions characterized by abnormal low resistance vascular structures connecting a pulmonary artery to a pulmonary vein, resulting in an intrapulmonary right-to-left shunt. The insidious onset and variable signs&nbsp;and symptoms make diagnosis difficult, especially in children. PAVMs&nbsp; can be single or multiple, congenital or acquired, and up to 47-80% of cases are associated with hereditary hemorrhagic telangiectasia (HHT).We present the&nbsp; case of a 12-year-old female teenager referred to our center for epistaxis, headache, fatigue and weakness, with evidence of mild oxygen desaturation.&nbsp; Bubble test showed a right-to-left shunt and pulmonary angio-CT confirmed the diagnosis. Percutaneous selective embolization was performed with full recovery of normal arterial oxygen saturation. When differentiating between mild oxygen desaturation and exercise intolerance in children and adolescents, physicians should be aware of the possibility of PAVMs as a cause.&nbsp;

This study was conducted to investigate the effect of supplementing different types of methionine (L and D-type) and its precursor (HMBi) on milk protein synthesis using immortalized bovine mammary epithelial cell line (MAC-T Cell); D-methionine (D-Met), L-methionine (L-met) and 2-hydroxy-4-methylthiobutanoic acid I (HMBi), an isopropyl ester of the hydroxy analogue precursor of methionine. The underlying mechanism of milk protein synthesis by adding D- and L-type amino acid as well as HMBi was elucidated through omics analysis to verify the metabolism pathway. Results showed that HMBi group showed the highest beta casein mRNA expression levels compared to D- and L-Met groups and highest medium protein although not different with the L-Met treatment. The observed upregulated (>2 protein expression vs. control) and downregulated (<0.5 protein expression vs. control) proteins in L-Met, D-Met and HMBi treated groups were: 39, 77; 46, 68; and 40, 78, respectively. Interestingly, based on protein pathway analysis, L-Met treated group stimulated the ATP synthesis, PI3 kinase and pyruvate metabolism. On the other hand, the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, PI3 kinase and pyruvate metabolism. And lastly HMBi-treated group stimulated pentose phosphate pathway and glycolysis pathway. Metabolite analysis revealed that L-Met treated group resulted in the increase in 11 metabolites. On the other hand, D-Met treated group showed increase in 7 metabolites and decreased of uridine monophosphate (UMP). HMBi supplementation caused increases of 3 metabolites and decreased of UMP and N-acetyl-L-glutamate Addition of different isoforms of Met stimulated the production of intermediate metabolites for energy production. Addition of L-Met stimulated the production of energy metabolites such as pyruvate, malate, and fumarate, well-known as intermediates of Krebs cycle. On the other hand, HMBi supplementation resulted in increases of energy metabolite glucose 1-phosphate and 6-phosphogluconate. Results showed that HMBi-treated group exhibited highest expression of β-casein mRNA expression by stimulating proteins and metabolites as well as protein and metabolic pathways involved in protein and energy synthesis. As a result, HMBi-treated group resulted in highest protein concentration but not significantly different with L-Met. Both the D- and L-isoforms has considerably the same medium protein concentration and β-casein mRNA expression higher than the control. So, D- and L-Met isoforms can be used alternatively without any significant change in protein synthesis efficiency in bovine mammary epithelial cells.

Greenhouse gas (GHG) emission-induced climate change, particularly occurring since the mid-20th century has been considerably affecting short-term weather conditions, such as increasing weather variability, and incidence of extreme weather-related events. Milk production is sensitive to such changes. In this study, we use spatial panel econometric models, Spatial Error Model (SEM) and Spatial Durbin Model (SDM), with a panel dataset at the state-level varying over seasons, to estimate the relationship between weather indicators and milk productivity, in an effort to reduce the bias of omitted climatic variables that can be time-varying and spatially correlated and cannot be directly captured by conventional panel data models. We find an inverse U-shaped effect of summer heat stress on milk production per cow (MPC), indicating that milk production reacts positively to a low-level increase in summer heat stress, and then MPC declines as heat stress continues increasing beyond a threshold value of 72. Additionally, fall precipitation exhibits an inverse U-shaped effect on MPC, showing that milk yield increases at a decreasing rate until fall precipitation rises to 14 inches and then over that threshold milk yield declines at an increasing rate. We also find that, relative to conventional panel data models, spatial panel econometric models could improve prediction performance by leading to smaller in-sample and out-sample root mean squared errors. Our study contributes to the literature by exploring the feasibility of promising spatial panel models and resulting in estimating weather influences on milk productivity with high model predicting performance.

Background: We prepared reference materials of fentanyl and amphetamines in hair, and established methods for the certification of reference materials of fentanyl and amphetamines in hair samples. Methods: Hair samples containing 15 drugs were prepared by immersion method (water-dimethylsulfoxide). On the basis of single-factor experiment, Box-Behnken design-response surface was used to optimize the pre-treatment conditions of samples. In MRM/SIM mode, 15 drugs were quantitatively analyzed by LC-MS/MS and GC-MS/MS methods. Results: The contents of 15 drugs in the mixed hair samples were: 1.050 ng mg-1~7.771 ng mg-1, RSDs&lt;7%(n=11). The results showed that the two analytical methods developed were highly sensitive (LODs as low as 0.05 pg mg-1), reproducible (intra-day and inter-day precision RSDs were&lt;10%) and accurate. F-test was performed on the prepared hair samples and the results showed that the homogeneity of the prepared hair samples was good. Conclusions: The established methods were used for the detection of fentanyl and amphetamine drugs in human hair, with high sensitivity, accuracy and specificity. It can be used as a certified method for the development of fentanyl and amphetamine matrix certified reference materials. The developed hair reference materials are expected to be applied in forensic drug abuse detection and laboratory quality control.

Although wheat is a staple food for most of human population, some of its components trigger adverse reactions. Among wheat components, the alpha-amylase/trypsin inhibitors (ATI) are important triggers of several allergies and activators of innate immunity. ATI are a group of exogenous protease inhibitors and include several polypeptides. The three ATI polypeptides named CM3, CM16 and 0.28 are considered major allergens, and might also play a role in other common wheat-related pathologies, such as Non Celiac Wheat Sensitivity and even Celiac Disease. On this basis, we pointed to obtain high amounts of them in purity and evaluating their allergenicity potential. We thus isolated the mRNA corresponding to the three ATI genes CM3, CM16 and 0.28 from 28 days post-anthesis wheat kernels and the corresponding cDNAs were used for heterologous expression in Pichia pastoris. The three purified proteins were tested in degranulation assay against human sera of patients with food allergy to wheat. A large range of degranulation values was observed for each protein according to the sera tested. All the three purified proteins CM3, CM16 and 0.28 were active as allergens because able to induce basophils degranulation on wheat allergic patients’ sera, but the highest values of β-hexosaminidase release were observed for CM3 protein.

Proteolysis Targeting Chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD) with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focusses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.

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.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

This study sought to investigate the problem of losses along the milk value chain in Nandi and Kakamega Counties in Kenya. Using semi structured questionnaire, quantitative data were collected from different stages of the value chain consisting of 400 dairy farmers proportionally and randomly selected in Chesumei and Ikolomani sub counties; 15 cooperatives, 40 transporters, 20 milk bars, 17 supermarkets. Additionally Key informant interviews and focus group discussions we held with extension staff and farmers, respectively.The results showed losses occurred at all stages of the value chain in Nandi and Kakamega Counties with the highest losses at Cooperative (50.6%), collection centres (33.7%) and milk bars (7.5%). Annual milk loss was estimated to be 260,000 litres and 20,000 litres in Nandi and Kakamega counties respectively. The economic value of losses per year was estimated at KES 13 million (USD 100 000). Significant factors (P<0.001) influencing milk losses at farm level were: type of cow housing, level of training of milker, mixing morning and evening milk and Lack of cooling facilities. In cooperatives, poor roads, poor preservation of milk and mastitis influenced post harvest losses (PHL) causing milk rejection due to spoilages; while transporters attributed PHL to storage during transportation. Inadequate storage facilities and milk handling practices influenced PHL in milk bars while supermarkets attributed PHL to poor packaging materials and short shelf life. The most important causes of milk PHL along the chain were spoilages, spillages, adulteration and physical dirt. Key interventions to minimize PHL should target improvement of rural road infrastructure connecting farmers to markets; milk storage facilities and capacity building on milk handling practices for all actors. A sustainable PHL reduction should entail policy dialogue on milk payment system based on quality rather than quantity.

Aflatoxin M1 (AFM1), a carcinogenic toxin, mainly contaminates cow milk and poses significant challenges to the dairy industry and, thereby, public health in most tropical countries, including Ethiopia. This study aimed to investigate the prevalence and level of AFM1 in raw cow milk collected from Specialized Dairy Farms and Milk Vendors in three Urban Centers: Chiro town, Dire Dawa, and Harar cities in Eastern Ethiopia. 180 milk samples were collected from two major Milk Sources: Specialized Dairy Farms (N=90) and Milk Vendors (N=90) using a simple random sampling technique. AFM1 was analyzed using high-performance liquid chromatography. The study revealed that, 63.9% (115/810) prevalence and 0.179±0.48µg/L mean of AFM1 level in milk, which 39.13% and 26.08% exceed the tolerable limits of EU and FDA respectively. A 40.0% prevalence and 0.344±0.72µg/L average of AFM1 in the milk from Dire Dawa city was significantly higher than the samples from other Urban Centers. However, 30.43% and 29.57% prevalence as well as 0.055±±0.13µg/L and 0.140±0.33µg/L average of AFM1 in milk from Chiro town and Harar city, respectively were not significant. Furthermore, milk samples from Dairy Farms revealed a higher prevalence (57.39%) and level (0.252±0.64µg/L) of AFM1 than Milk Vendors, with a prevalence of 42.61% and an average of 0.107±0.21µg/L. Therefore, this study concludes that substantial milk samples were contaminated by AFM1 and urges the need to enhance farmers' awareness on mitigation.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.