Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

(1) Background: Vitamin K deficiency is a common feature of chronic kidney disease (CKD), leading to impaired bone quality and increased risk of vascular calcifications. A method to indirectly measure Vitamin K status is measuring the blood level of Vitamin K dependent proteins (VKDP)- osteocalcin (OC) and matrix GLA protein (MGP). The aim of this study is to correlate the level of OC and MGP with markers of CKD mineral bone disorder (CKD-MBD). (2) Methods: We conducted a single-center cross-sectional study that included 45 CKD G5D patients and measured blood biochemistry, complete blood count and intact osteocalcin and matrix GLA protein. (3) Results: We found a strong statistically significant correlation of OC with the markers of CKD-MBD such as: iPTH , serum calcium and serum phosphorus and a strong indirect statistically significant correlation with abdominal circumference. There was also a statistically significant correlation of MGP with markers of inflammation (CRP). Higher levels of MGP were found in patients treated with vitamin K antagonists, non-calcium based phosphate binders and vitamin D receptor activator- paricalcitol. (4) Conclusions: In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP is associated to CKD-MBD. The use of medication such as phosphate binders, that reduce vitamin K absorbtion, Vitamin D that increases Vitamin K requirements and also vitamin K antagonists, seem to have an influence on the blood level of VKDPs.

Vitamin E, a potent antioxidant, is a necessary and complex micronutrient for cows. During the transition period, vitamin E deficiency (VED) is among the highest prevalent micronutrient deficits in dairy cows. It may eventually result in oxidative stress and immunological malfunction, and it increases the risk of peripartum disorders. At present, detailed data on blood metabolites in VED cows are limited. Consequently, the purpose of this research was to examine the alterations in the serum metabolic profile of VED cows throughout the early postpartum period. Using comprehensive 1H nuclear magnetic resonance (1H NMR), the alterations in serum metabolic activities of VED cows were analyzed. In total, 28 multiparous Holstein cows were assigned according to serum α-tocopherol (α-Toc) concentrations into a normal (α-Toc ≥ 4 μg/mL, n = 14) and VED (α-Toc &lt; 3 μg/mL, n = 14) groups at 21 days postpartum, and their blood samples were collected for biochemical and 1H NMR analyses. A t-test on independent samples as well as multivariate statistics were used to assess the findings. In comparison with normal cows, VED cows showed significantly worse body condition scores, milk yield, and dry matter intake (p &lt; 0.05). Significantly higher levels of serum non-esterified fatty acids, aspartate aminotransferase, low-density lipoprotein, and malonaldehyde were found in VED-affected cows, as well as lesser concentrations of serum albumin, high-density lipoprotein, and total antioxidant capacity in comparison with normal cows (p &lt; 0.01), while other vitamins and minerals concentrations showed no distinction between the groups (p &gt; 0.05). Furthermore, 24 upregulated serum metabolites were identified under VED conditions. The metabolomics pathway analysis of these metabolites demonstrated that a global metabolic response to VED in cows was represented by changes in 11 metabolic pathways, comprising energy, carbohydrate, and amino acid metabolism. These outcomes suggest that VED cows were more likely to experience a negative energy balance characterized by alterations of common systemic metabolic processes and develop oxidative stress, inflammation, and ultimately liver injury. This study provides the first evidence of metabolic changes in cows with VED.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Background: Vitamin B12 is a water-soluble vitamin with important cellular functions and is an essential vitamin. The aim of this study is to determine the B12 levels of children in the period from the 6th month when they start taking additional foods to the age of 7 and the risk factors affecting them. Methods: One hundred pediatric patients aged 6-72 months who were diagnosed with vitamin B12 deficiency and their parents who agreed to participate in Istanbul Atlas University, Medical Faculty, “Medicine Hospital” Pediatric Clinic between September 2022 and June 2023 were prospectively included in this study. Results: B12 deficiency was significantly higher in the 6-11 (25%) month group than those in the 12-23 (5.8%) and 24-47 (2.8%) month groups. Homocysteine levels were highest in those with insufficient B12 levels compared to the other groups. There was no statistically significant difference in weekly dairy and meat consumption levels between age groups. B12 levels were lower in the 6-11-month group than in the other groups. Homocysteine levels were highest in those with insufficient B12 levels [<200 pg/mL (148 pmol/L)]. Folic acid levels were lower in the 24-47 month and 48-72 month groups than in the 6-11 month and 12-23 month groups. Conclusions: The results obtained in this study showed that low vitamin B12 and increased homocysteine levels seem to be important risk factors in children, especially from the 6th month when they start taking additional foods. The diagnosis of B12 deficiency can be confirmed by elevated serum total homocysteine levels, which are evidence of functional cobalamin deficiency.

Vitamin C is an essential nutrient that must be obtained through the diet in adequate amounts to prevent hypovitaminosis C and the potentially fatal deficiency disease scurvy. Global vitamin C status and prevalence of deficiency has not previously been reported, despite vitamin C’s pleiotropic roles in both non-communicable and communicable disease. This review highlights the global literature on vitamin C status and the prevalence of hypovitaminosis C and deficiency. Related dietary intake is reported if assessed in the studies. We also explore if global vitamin C status has changed over time. Overall, the review illustrates the shortage of high quality epidemiological studies of vitamin C status in many countries, particularly low- and middle-income countries. The available evidence indicates that vitamin C deficiency is common in low- and middle-income countries and not uncommon in high income settings. Further high quality studies are required to confirm these findings, including in the countries not yet represented, and to fully understand associations with a range of disease processes. Our findings suggest a need for interventions to prevent deficiency in a range of at risk groups and regions of the world.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

A rapid, precise, accurate and low cost method for the determination of vitamin E (α-tocopherol) in cereal products and biscuits was developed. The uncertainty was calculated for the first time and the methods were performed in different cereal products and biscuits, characterized as “superfoods”. The limits of detection and quantification were calculated. Accuracy and precision were estimated using the certified reference material FAPAS T10112QC and the determined values were in good accordance with the certified values. The health claims according to the daily reference values for vitamin E were calculated and the results proved that the majority of the samples examined showed %daily value higher than 15%.

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, vascular mechanics, lipid content, levels of reactive oxygen species (ROS), expression of pro-oxidant redox enzymes and of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and of LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via involvement of LOX-1, NOX1 and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. Lack of LOX-1 expression/overexpression in response to increased ox-LDL levels may be a possible mechanism of action.

Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P &lt; .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Vitamin E is a group of eight compounds divided into two subgroups: four tocopherols (α-, β-, γ-, and δ-) and four tocotrienols (α-, β-, γ-, and δ-). α-Tocopherol is considered the most biologically active form. This review paper summarizes the current knowledge and historical progression of vitamin E research, with particular emphasis on its role in animal nutrition. Early studies in the 1920s identified vitamin E’s role in preventing neonatal mortality in rats. Over the following decades, scientists discovered the compound’s chemical structure and its importance for the immune system, skin health, anti-inflammatory properties, hormonal balance, and other bodily functions. Production of vitamin E products has evolved, starting with isolating the vitamin from natural sources and advancing to synthesizing it with greater efficiency and standardized potency units. Early animal studies focused on reproductive health and growth disorders, but further research demonstrated the importance of vitamin E in preventing encephalomalacia in domestic fowl and muscular dystrophy in rabbits and other animals. Today, vitamin E is commonly used as a feed additive to meet animals’ requirements and assure immune function and overall health. Despite much knowledge on vitamin E’s role in animal nutrition, many questions remain unanswered, and current research aims to determine optimal supplementation levels, interactions with other nutrients, impacts on gene expression, cell signaling and communication, and effects of supranutritional dosages in livestock. Vitamin E has a long and fascinating history in scientific research, with significant advancements in understanding its chemical structure and biological activity. In animal nutrition, vitamin E continues to play an important role in improving animal health, and ongoing research will continue to expand our understanding of its benefits and mechanisms of action.

Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Vitamin E facilitates testicular development and semen quality in farm animal. And most research tends to investigate antioxidant roles of Vitamin E in reproductive health; some research also find potential non-antioxidant roles of Vitamin E. To further uncover the mechanism by which Vitamin E modulates reproductive health, the paper reviews specific function of Vitamin E and candidate genes involved in male reproductive performance promoted by Vitamin E. The review found that cell proliferation (PDPN, BMP, Myc, AMPKa, GSK3β, PPARγ, CDK4, CDK6, Ki67, PCNA, Cyclin A2, Cyclin B1, Cyclin B3, BLM, REL, KLHL25)-, cell apoptosis (BCL-2, Caspase 9, Bax)-, spermatogenesis (CatSper1, CatSper2, NDRG1, CYP26B1, FSCN3, FLNA, SPCS3, YBX3, RARS)-, hormone receptor (PGR, FSHR, AR)-related genes are the underlying key points. And two miRNAs, miR-107 and miR-493-3p, which mediate cell cycle process, are also identified in response to Vitamin E treatment. The paper paves the way for a comprehensive understanding about effect of Vitamin E on testis development and semen quality in domestic animals.

Vitamin B9(folate)/B12 deficiency is known to induce brain structural and/or functional retardations. Besides neural tube defects in case of major consequences, several mild deregulations also lead to deleterious effect after birth, and folate supplementation recommended in some countries usually stop at the end of the first trimester. Various hormonal receptors were shown to be deregulated in brain tissue under this context. The glucocorticoid receptor (GR) is particularly sensitive to epigenetic regulation and post-traductional modifications. In a mother-offspring rat model of vitamin B9/B12 deficiency, we investigated whether a prolonged folate supplementation could restore the GR signalization in the hypothalamus. Our data showed that a deficiency in folate and vitamin B12 during the in-utero and the early postnatal periods was associated with reduced GR expression inn the hypothalamus. We also described for the first time a new post-traductional modification of GR that impaired ligand binding and GR activation, leading to decreased the expression of one of the GR targets in the hypothalamus, AgRP. Moreover, this brain-impaired GR pathway was associated with behavioral perturbations during offspring growth. Importantly, perinatal and postnatal supplementation with folic acid helped restore GR mRNA level and activity in hypothalamus cells and improved behavioral deficits.

Systems genetics is key for integrating a large number of variants associated with diseases. Vitamin K (VK) is one of the scarcely studied conditions in lieu of ascertaining either the differentially expressed genes (DEGs) or variants in an individual subpopulation of diseased phenotypes associated with VK, viz. myocardial infarction, renal failure, prostate cancer, thrombosis, thrombocytopenia, coagulation related diseases to name a few. In this work, we have screened characteristic DEGs common to three VK-related diseases, viz. myocardial infarction, renal failure and prostate cancer and asked whether or not any DEGs in addition to pathogenic variants are common to these conditions. We attempt to bridge the gap in finding characteristic biomarkers and discuss the role of long noncoding RNAs (lncRNAs) in the biogenesis of VK deficiencies.

Long-term nutritional studies in subjects undergoing bariatric surgery that have assessed weight regain and nutritional deficiencies are few. In this study, we report data 8 years after surgery on weight loss, use of dietary supplements and deficit of micronutrients in a cohort of patients from five centres in central and northern Italy. The study group consisted of 52 subjects (age: 38.1±10.6 yrs, 42 females): 16 patients had Roux-en-Y gastric bypass (RYGB), 25 patients sleeve gastrectomy (LSG) and 11 subjects adjustable gastric banding (AGB). All three bariatric procedures led to sustained weight loss: average percentage excess weight loss, defined as weight loss divided by excess weight based on ideal body weight was 60.6%±32.3. 80.7% of subjects (72.7%, AGB; 76%, SG; 93.7%, RYGB) reported at least one nutritional deficiency: iron (F 64.3% vs. M 30%), vitamin B12 (F 16.6% vs. M 10%), calcium (F 33.3% vs. M 0%) and vitamin D (F 38.1% vs. M 60%). Average weight loss was constant in RYGB and SG subjects from the third year after surgery. Long-term nutritional deficiencies were greater than the general population among men for iron and among women for vitamin B12.

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19.Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

Middle East region experiences a high prevalence of hypovitaminosis D, yet most genetic studies on Vitamin D have focused on European populations. Furthermore, there is a lack of research on the genomic risk factors affecting the elderly population, who are more susceptible to health burden. We investigated the genetic determinants of 25-hydroxyvitamin D levels in elderly Lebanese individuals (n=199) through a whole exome-based genome-wide association study. We identified new loci with suggestive evidence of an association with Vitamin D levels, including rs141064014 in the MGAM gene (P-value of 4.40 × 10−06) and rs7036592 in PHF2 (P-value of 8.43 × 10−06). A meta-analysis of the Lebanese data and the largest European genome-wide association study confirmed consistence replication of numerous variants, including rs2725405 in SLC38A10 (P-value of 3.73 x 10-08). Despite the lower performance of European-derived polygenic risk scores compared to the European estimations, it still effectively predicted Vitamin D deficiency among elderly Lebanese individuals. Our findings provide novel insights into the genetic mechanisms of Vitamin D deficiency in Middle Eastern elderly populations, facilitating the development of personalized approaches for more effective management of hypovitaminosis D. Additionally, we demonstrated that whole exome-based genome-wide association study is an effective method for identifying genetic components associated with phenotypes.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

Several observations have shown that patients with polycythemia have iron deficiency. Our objectives were to report the prevalence of iron deficiency, to evaluate the diagnostic performance of serum ferritin in polycythemia vera and to describe the mechanisms of this association. This is a retrospective descriptive and analytical study carried out in the internal medicine department of the Henri Mondor Hospital, Aurillac, France. The study involved 114 patients with polycythemia, followed in the department from January 1, 2010 to December 31, 2021. To evaluate the diagnostic performance, the JAK2 mutation was considered as the gold standard of diagnosis. Thirty-three patients had polycythemia vera and 76 patients had secondary polycythemia. The mean age of the patients was 61.79 years (±15.44) with a sex ratio of 4.43. The overall prevalence of iron deficiency was 21.05%. The prevalence was 53% in polycythemia vera group and 1.32% in secondary polycythemia group. The risk of iron deficiency was high in polycythemia vera (OR=115; 95% CI [14.4-918.2], p<0.000). The sensitivity and specificity of serum ferritin were 52.63% and 100% respectively. Assessment of iron deficiency should be part of the initial evaluation of polycythemia. The presence of iron deficiency is specific for polycythemia vera.

Purpose: The purpose of this study is to further explore how e-loyalty and E-marketing influences E-trust and satisfy the demand by offering fresh perspectives based on research as well as emphasis on the factors influencing the E-trust such as culture as a mediator. This study not only contributed theoretically but also presented practical implementations. Design/methodology/approach: Online survey was used to obtain data by focusing the Hospitality sector (Hotel Industry) and verifying the conceptual framework. Data was collected in multiple time lags. Findings: Findings showed that the E-trust influenced by E-loyalty and E-Marketing. E-trust comes from the previous experiences, e-loyalty and e-marketing. Further, some trends such as culture influenced the e-trust. Research limitation/implications: The present study is quite suitable for those Researchers interested in learning more about the effects of E-loyalty and E-marketing on user E-trust and how to mitigate cultural influences can benefit from the current study. This research also has implications for those who wish to improve market allure and survival in digital world. This study focused on the hospitality sector (Hotel Industry) in China; however, the sector and geography could be altered to suit the needs of the study's participants. Practical implications: The present study delivers the practical guidelines which are quiet suitable for understanding the formation of E-loyalty, E-marketing, and E-trust through which specific E-marketing strategy can be designed to deal with the consumer’s E-loyalty and their expectations as per their Cultural perspective. At some particular regions/countries, cultural trends are more important than practical market. This research study practically showed that how culture changed the consumer set of mind. Originality/value: The relationship between E-loyalty, E-marketing, E-trust, specifically with the cultural influence in digital market has been the subject of few research.

The study, conducted at the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, aimed to investigate the prevalence of iron deficiency anaemia among anaemic overweight and obese individuals. Fifty participants were included after screening and consent, undergoing socio-demographic assessment, clinical evaluation, and laboratory investigations. Middle to old-aged individuals predominated (Mean ± SD: 54.54 ± 11.32 years), with females comprising 62%. All subjects were obese (mean BMI: 37.27 ± 5.71 kg/m²), with common comorbidities including hypertension (68%), diabetes (36%), and obstructive sleep apnea-hypopnea syndrome (32%). Nutritional deficiencies, particularly iron deficiency, were prevalent, affecting 62% of subjects, with 48% having iron deficiency alone. Anemia of chronic illness was observed in 38%. Laboratory parameters showed low hemoglobin (8.53 ± 1.23 g/dL), MCV (78.75 ± 10.13 fL), and elevated ESR (20.56 ± 21.47 mm/hour) and CRP levels (4.71 ± 3.32 mg/dL), indicating inflammation. Correlation analyses revealed negative associations between BMI and serum iron/ferritin and positive associations with serum hepcidin. The study underscores the significance of addressing nutritional deficiencies and monitoring iron status in obese populations, suggesting potential associations between obesity and iron metabolism. Further research is needed to explore these relationships for clinical management implications.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

A total of 779 samples of edible nuts (melon seeds, watermelon seeds, pumpkin seeds, and cantaloupe seeds) from southern cities of Punjab, Pakistan were collected from the summer and the winter seasons. The natural occurrence of aflatoxins (AFs) and vitamin E (tocopherols) levels were investigated using HPLC. The results have shown that 180 (43.4%) samples from the winter season and 122 (33.4%) samples from the summer season were found positive with AFs. The elevated average levels of total AFs (20.9±3.10 µg/kg) were observed in watermelon seeds without shell and the lowest average amount (15.9±3.60 µg/kg) were documented in melon seeds without shell samples from the winter season. The elevated average amount of total AFs 17.3±1.50 µg/kg were found in pumpkin seeds available as without shell. The results have documented a significant difference in total AFs levels in edible seeds available as shells versus without shells (α = 0.05 & 0.01). The highest dietary intake of 6.30 µg/kg/day was found in female individuals from pumpkin seeds (without shell) in the winter season and the value of 3.00 µg/kg/day were found in pumpkin seed without shell in summer season in female individuals. The highest amount of total tocopherol levels of 22.2 ± 7.70 ng/100g in pumpkin seeds samples from winter season and 14.5 ± 5.50 mg/100g were found in melon seeds samples from summer season. The variation of total tocopherol levels in edible seeds among the winter and summer seasons showed significant difference (p ≤ 0.0054), except watermelon seeds samples which shown non-significant difference (p ≥ 0.183).

Electronic waste generation has been following a continuously rising trend. With electronics containing a myriad of materials some of which are hazardous, toxic, extremely rare or precious combined with more stringent legislative laws which encourage the reuse and optimised recycling of the materials included in e-waste, the need for a holistic approach is inevitable. Such an approach should not only identify the materials found in the various types of e-waste and their respective quantities but also needs to highlight the possible handling techniques and their respective impacts and associated hazards whether to the environment or human health. Performing such a task manually would be exasperating and costly while requiring extensive resources which might not be met with a justifiable economic gain; thus, the use of the advancement in computational sustainability to draw a complete picture and aid in an informed decision-making process is crucial. The e-waste ontology developed in this paper is one way of addressing the problem since it covers the treatment domain, the hazard and the materials contained within the different types of e-waste. The ontology developed can be used directly from the protégé software or by embedding it into a developed Decision Support System.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

SARS-CoV-2 is an obligatory intracellular pathogen that requires of a lipid bilayer membrane for its transport, to build its nucleocapsid envelope and to fuse with the host cell. The biological membranes are constituted by phospholipids (PLs) and vitamin E (Vit E) protects them from oxidative stress (OS). The aim of this study was to demonstrate if the treatment with Vit E restores the modified profile of the FA in PLs in serum from patients with coronavirus disease-19 (COVID-19). We evaluated Vit E, total fatty acids (TFA), fatty acid of the phospholipids (FAPL), total phospholipids (TPLs), 8-isoprostane, thromboxane B2 (TXB2), prostaglandins (PGE2 and 6-keto-PGF1α), interleukin-6 (IL-6) and C-reactive protein (CRP) in serum from 22 COVID-19 patients before and after treatment with Vit E and compared the values with those from 23 healthy subjects (HS). COVID-19 patients showed a decrease in Vit E, TPLs, FAPL and TFA in serum in comparison to HS (p≤0.01) and Vit E treatment restored their levels (p≤0.04). Likewise, there was an increase IL-6 and CRP in COVID-19 patients in comparison with HS (p≤0.001) and the treatment with Vit E decreased their levels (p≤0.001). Treatment with Vit E contributes to restore the modified profile of the PLs in the SARS-CoV-2 infection and this leads to a decrease of OS and of the inflammatory process.

On using a 3D model to teach students a topic in astronomy, feedback was evaluated via a questionnaire. Analysis of students' responses to the questions revealed that user interface had a significant impact on their attitudes, which in turn could increase users' willingness to use immersive technology in e-learning. The results also showed that improving visual features through immersive technology and augmented reality tools were effective. The results confirm all hypotheses about positive relationships between facilitating conditions and usability of metaverse technology for students' attention and study motivation.

The tumor necrosis factor receptor associated factor 1 (TRAF1) plays a key role in promoting lymphocyte survival, proliferation, and cytokine production. Recent evidence showed that TRAF1 plays opposing roles in monocytes and macrophages where it controls NF-B activation and limits pro-inflammatory cytokine production as well as inflammasome-dependent IL-1 secretion. Importantly, TRAF1 polymorphisms have been strongly linked to an increased risk of rheumatoid arthritis (RA). However, whether and how TRAF1 contributes to RA pathogenesis is not fully understood. Moreover, investigating the role of TRAF1 in driving RA pathogenesis is complicated by its multifaceted and opposing roles in various immune cells. In this study, we show that intraarticular injection of TRAF1 deficient macrophages into knee joints of wildtype (WT) mice subjected to the collagen antibody induced arthritis (CAIA) model of RA significantly exacerbated joint inflammation, immune cell infiltration and tissue damage compared to mice injected with WT macrophages. This study may lay the groundwork for novel therapies for RA that target TRAF1 in macrophages.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Current VAT rules for cross-border e-commerce companies in the EU are not sustainable, because they are extremely complex and often opaque, due to the lack of tax harmonization. The aim of the research is to explore, using a qualitative method, what kind of harmonization would make the current legislation more uniform, simpler, more transparent, and easier to understand, without conflicting with the rules of any Member State. To this end, the aspects of the new platform regulation introduced on 1 July 2021 and its potential for expansion are assessed through information from possible sales models. The research suggests that the rules on platforms do not cover all possible sales models, which in our view imposes an unnecessary extra administrative burden on some businesses and makes their tax activities less transparent. In the light of the results of the research, we propose that the current EU platform regulation should be extended to cover B2B, B2C transactions and services. As a result of this suggested harmonization, a simpler, more transparent, uniform and sustainable tax system would contribute to the whitening of the economy, generating additional tax revenue for Member States.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of Vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the determination of Vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. Additionally, given the important interrelations between Vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoporosis. The purpose of the study was to evaluate changes in several bone health indicators and metabolic biomarkers in postmenopausal women, with high osteopenia or osteoporosis, followed by a nutritional intervention program. 115 apparently healthy postmenopausal women (52±8 years old) were randomized into four groups: group I (n=40) received daily 1000 mg vitamin C, 100 mcg vitamin D3, 500 mg calcium(Ca) and 300 mg magnesium (Mg); group II (n=42) received daily 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; group III (n=18) received daily 5 mg bisphosphonates, 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg; and group IV (n=15) received daily about 364 mg polyphenols via an innovative functional food (50 g olive paste enriched with mountain tea extract) along with 100 mcg vitamin D3, 500 mg Ca and 300 mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in bone health indicators and metabolic biomarkers were assessed at the beginning and at the end of the study. Anthropometric indices and whole-body bone mineral density (BMD) were also evaluated at the beginning and at the end of the intervention period. The results revealed improved elevated levels of 25(OH)D3, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). Significant positive changes were recorded, for whole-body BMD, in all four study groups. Significant beneficial changes for total cholesterol were observed in group IV (-2.07%, P&lt;0.05) and positive changes in group I for HDL biomarker (+61.62%, P&lt;0.05). Additional larger-scale clinical trials and intervention studies are considered essential, to fully investigate and elucidate associations between dietary components and biochemical indices of bone health.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, the trafficking of rod opsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for visual function. Two key mechanisms of this process are emphasized in this manuscript: Ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene opsin to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

1) Background: The aim was to evaluate the bioefficacy of vitamin D (VitD) encapsulated in nanoemulsions developed by sonication and pH-shifting of pea protein isolate in restoring VitD status in VitD-deficient rats. 2) Methods: Weaned (3-week old), male albino rats (n = 35) were initially divided into two groups: control sufficient group (VDS; n = 7) fed on a normal AIN-93G diet and a VitD-deficient group (n = 28) fed a VitD-deficient diet for six weeks. VitD-deficient rats were divided into four subgroups: two treatment groups (Nano+VitD and Oil+VitD) and two control groups (Nano-VitD and Oil-VitD), receiving seven rats in each sub-group. Nano+VitD and Oil+VitD groups received VitD dispersed in PPI-nanoemulsions and in canola oil, respectively, while the control groups received the respective delivery vehicles without VitD. Serum 25-hydroxyvitamin D [25(OH)VitD], parathyroid hormone (PTH), calcium (Ca), phosphorus levels (P), and alkaline phosphatase (ALP) activity were measured. Femur bone was used to prepare histopathological sections. 3) Results: After one week of treatment, the VitD-deficient rats consuming Nano+VitD recovered from VitD deficiency (serum 25(OH)VitD 34.38 ± 7.00) compared to the sufficient control (36.84 ± 9.16; p > 0.05) and the deficient control consuming VitD+Oil (14.05 ± 3.08; p < 0.01). Enhancement in VitD status was followed with expected changes in serum PTH, Ca, P, and ALP levels, no difference in similar biomarkers against the sufficient control, and an improvement of the osteoid area and reduction of trabecular separation in bone. 4) Conclusions: Stabilization of VitD within PPI-based nanoemulsions enhances its absorption and restores its status and biomarkers of bone resorption in VitD-deficient rats.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

The shift towards autonomous excavators in construction and mining is a significant leap towards enhancing operational efficiency and ensuring worker safety. However, it presents challenges such as the need for sophisticated decision-making and environmental perception due to complex terrains and diverse conditions. Our study introduces the E-GTN framework, a novel approach tailored for autonomous excavation that leverages advanced multisensor fusion and a custom-designed convolutional neural network to address these challenges. Results demonstrate that GridNet effectively processes grid data, enabling the reinforcement learning algorithm to make informed decisions, thereby ensuring efficient and intelligent autonomous excavator performance. The study concludes that the E-GTN framework offers a robust solution for the challenges in unmanned excavator operations, providing a valuable platform for future advancements in the field.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

A 4×2 factorial experiment was conducted to evaluate the potential of feeding dietary gamma-oryzanol and vitamin E tocotrienols in hens reared in 840 (low cage density; LCD) or 420 cm2/hen (high cage density; HCD). A total of 120 hens were allocated into eight groups with five replicates. Diets were a control (CON) or the control diet supplemented with 200 ppm gamma-oryzanol (GO-200), 200 ppm vitamin E tocotrienols (VE-200) or 200 ppm gamma-oryzanol + 200 ppm vitamin E tocotrienols (GE-400). Results showed that HCD-housed hens decreased (P &lt; 0.01) egg performance and quality. Average egg weight (AEW), egg mass and FCR improved in all supplemented treatments. Results on the AEW, FCR, and eggshell qualities of birds kept at the HCD revealed the best responses in the GE-400 group (P &lt; 0.01). Among hens kept on an HCD, there was a noticeable decrease in HMGCR mRNA abundance in the VE-200 group, while the highest IFN-γ mRNA abundance was found in hens fed the GO-200 diet (P &lt; 0.05). Thus, this study suggested that dietary GO or VE at 200 ppm either individually or in combination could improve performance and egg quality as well as regulate the abundance of immune- and stress-related genes.

Non-Vitamin K Oral Anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs—Apixaban, Rivaroxaban, Edoxaban, and Dabigatran—not only as anticoagulants but also as modulators of inflammation via Protease-Activated Receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as FXa and Thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles but also paves the way for future research and clinical applications in inflammation and cardiovascular health

Households and businesses are generating unprecedented levels of electrical and electronic wastes (e-waste), fueled by modernisation and rapid obsolescence. While the challenges imposed by e-waste are similar everywhere in the world, disparities in progress to deal with it exists; with developing nations such as South Africa lagging. The increase in e-waste generation increases the need to formulate strategies to manage it. This paper presents an overview of e-waste management on a global and South African scenarios with a specific case for Cathode Ray Tube (CRT) waste management practices in South Africa. CRTs present the biggest problem for recyclers and policy makers because they contain hazardous elements such as lead and antimony. Common disposal practices have been either landfilling or incineration. The research into the South African practices with regards to CRT waste management showed that there is still more to be done to effectively manage this waste stream. This is despite clear waste regulatory frameworks in the country. However, recent developments have placed e-waste as a priority waste stream, which should lead to intensified efforts in dealing with it. Overall, these efforts should aim to maximise diversion from landfilling and to create value-addition opportunities, leading to social and environmental benefits.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

The development of biofuels and biodiesel industry specifically, has resulted in the generation of large amounts of glycerol as a surplus. The conversion of glycerol, into chemicals with indus-trial interest, through anaerobic fermentation using E. coli as a biocatalyst is an attractive alter-native to improve economic performance in the biodiesel industry, for example through the bi-otransformation of residual glycerol into ethanol. For 2019, the size of the global ethanol market was valued at $ 89.1 billion US dollar. Biodiesel can be produced from several materials like rapeseed, palm, soya, corn, palm kernel, frying oil or olive-pomace oil (OPO). The last, can be extracted from alperujo, byproduct of olive oil process. However, olive-pomace oil converting into biodiesel is not enough established to achieve a global olive-oil/biodiesel derived process with minimized waste generation. Traditionally biodiesel production process produces an equivalent of 10% by mass of glycerol as a waste or by-product. This work explores the conver-sion of residual glycerol into chemicals like ethanol and hydrogen with a focus on projecting raw material potential availability from OPO, contributing to the promotion of the use of biofu-els and biodegradable compounds.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Schizophrenia is a complex mental disorder influenced by genetic and environmental factors, including diet. Oxidative stress and inflammation play a crucial role in the pathophysiology of schizophrenia. Nutritional deficiencies, such as lack of omega-3 fatty acids, vitamin D, and B vitamins, during prenatal and postnatal periods can nega-tively impact neurodevelopment and increase the risk of schizophrenia. Patients with schizophrenia show imbalances in antioxidant enzymes such as: glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced levels of antioxidants (vitamin E, vitamin C), leading to increased oxidative stress markers such as malondialdehyde (MDA). Cytokine-mediated inflammation, microglial activation, and gut dysbiosis are associated with schizophrenia onset and symptom severity. There is no clear and universally accepted diet for the treatment of schizophrenia, which is considered the most popular. However, various diets and nutritional methods are being researched and applied to alleviate the symptoms of schizophrenia and improve the general health of patients, including the mediterranean diet, ketogenic diet, gluten-free diet and DASH diet. A healthy diet rich in anti-inflammatory and antioxidant nutrients can help manage schizophrenia by reducing oxidative stress, preventing complications, and improving quality of life. Omega-3 fatty acids, vitamin D and B vitamins are par-ticularly important for brain development and function. In this review we will focus on the influence of diet on schizophrenia. Additional research is needed to develop per-sonalized dietary recommendations for patients with schizophrenia.

Background: Studies addressing diet quality and mental health have shown a strong association. There is limited evidence of specific vitamins essential for treating depression. This study aims to understand the impact of diet quality through supplementation of vitamins D, B6, and magnesium on depressive symptoms. Methods: Multiple datasets from the National Health and Nutrition Examination Survey 2017-March 2020 investigated the associations between vitamin D, B6, and magnesium on depression symptoms. A cross-sectional sample of adults over 20 was extracted (n=9,232). Chi-square tests and logistic regression analyses were used to investigate the associations. Results: Individuals with low doses of vitamin D were more likely to report symptoms of depression relative to those with low doses of vitamin B6 (χ²=3.9063, p=0.0481 vs. χ²=5.2071, p=0.0225). These results remained significant among those with high magnesium proportionate to high vitamin B6 (χ²=6.1272, p=0.0133 vs. χ²=5.2071, p=0.0225). Logistic regression results provided associations for all models except unadjusted vitamin D and adjusted vitamin D. Conclusions: Preventive measures could be addressed by identifying the risks of vitamin deficiencies. Further epidemiological research is needed for the individual effects of vitamin supplementation and depression symptoms.

The water-soluble vitamin - vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its de-ficiency can lead to hematological and neurological disorders, however the manifestation of these clinical outcomes is relatively late. It leads to difficulties in its early diagnosis, often resulting in the development of hidden subclinical cobalamin deficiency. Prolonged lack of vitamin B12 con-dition may have severe consequences including increased morbidity to neurological and cardio-vascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabo-lism. Despite nearly 70 years of knowledge since its isolation and characterization, there are still gaps in understanding its metabolic pathways. Thus, this review aims to gather current knowledge about the crucial proteins necessary to efficiently process vitamin B12 in humans, presenting it as a multi-protein mediated network. Based on these findings, we also highlight new potential methods for supporting the evaluation of the risk of epidemiological consequences of vitamin B12 deficiency or clinical warnings of increased risk of vitamin B12 deficiency based on already testing targeting specific moonlighting proteins engaged in vitamin B12 metabolic path-ways.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.

Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autism, ataxia and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential use of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between the researchers and the patients.

The graphene based highly conductive and flexible devices has received momentous attraction and growth in recent years for potential multifunctional uses. The development of flexible and washable textile sensors, actuators, energy storage and energy harvesting systems. Textile fabrics coated with graphene and conductive polymers have been used for wearable self-powered e-textiles, such as tribo-electric, piezoelectric, and Thermoelectric. Herein this research, 100% woven cotton fabric is Fictionalized with graphene oxide (GO) using industrial-scale cold pad batch dyeing technique for the development of low-grade body heat into self-powered wearable e-textiles. The conductive polymer PEDOT: PSS was coated using layer by layer approach. The study demonstrates that the resultant textile electrodes showed reduced electrical sheet resistance from 2.5 MΩ to 15KΩ, with a reduced graphene oxide and further reduced to (2.5 -12.5 Ω) for conductive polymer. The sheet resistance was decreased with the number of dyeing cycles (10-15) and increased with 20 washing cycles vice versa. The study demonstrates that the sensor response and performance were improved with increasing the content percent of rGO and PEDOT: PSS. The tensile strength of as coated fabric electrodes was improved from (25.0-85.5 mPa) and fabric thickness was increased to (26-38µm) without compromising or influencing the air permeability. The resultant textile electrodes may potentially be used in smart textiles for self-powered flexible wearable generators, sensors, and energy storage. The study demonstrates that the cold pad batch dyeing method is a suitable and effective method for the fabrication of graphene-based textiles.

Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

Lower respiratory infections (LRI), upper respiratory infections (URI), and nutritional deficiency (ND) in under-5 children from low-middle-income countries has been at a high level for decades, despite efforts that have been realized in some countries. The study used data extracted from the global burden of diseases (GBD) to analyze the trends behavior between 1990 and 2019, and evaluate their association with maternal factors. Between 1990 and 2019, the incidence of LRI decreased between 1.2 percent and 1.3 percent (1.2-1.3%) in different female age groups, and by nearly 1 to 1.3% in those of the male gender. The incidence of URI did not decrease (0.0%) in any of their age groups. ND incidence declined around 0.7 to 4.9% in the under-5 children. LRI declined mostly in the female age groups (1.2 to 1.3%), while ND decreased more in the male gender (0.9 to 4.9%). Maternal risk factors were strongly associated to the incidence of the three conditions with over 90 percent. Maternal prevalence of HIV/AIDS and tuberculosis positively impacted the incidence of LRI, URI, and ND in Chadian under-5 children. Although the incidence of LRI and ND declined, URI incidence remained steady between 1990 and 2019 in Chadian under-5 children. To improve the health and provide a healthy growth of under-5 children, the maternal prevalence of HIV/AIDS and tuberculosis infection should be strongly addressed for a prompt accomplishment of the sustainable development goals.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

Succinic semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme involved in the catabolism of the neurotransmitter γ-amino butyric acid. Pathogenic variants in the gene encoding this enzyme cause SSADH deficiency, a developmental disease manifesting as hypotonia, autism and epilepsy. SSADH deficiency patients usually have family-specific gene variants. Here, we describe a family exhibiting four different SSADH variants, Val90Ala, Cys93Phe, and His180Tyr/Asn255Asp (a double variant). We provide a structural and functional characterization of these variants and show that Cys93Phe and Asn255Asp are pathogenic variants that affect the stability of the SSADH protein. Due to impairment of the cofactor NAD+ binding, these variants show a highly reduced enzyme activity. However, Val90Ala and His180Tyr exhibit normal activity and expression. The His180Tyr/Asn255Asp variant exhibits a highly reduced activity as a recombinant species, is inactive and shows a very low expression in eukaryotic cells. A treatment with substances that support protein folding by either increasing chaperone protein expression or by chemical means was not capable of increasing the expression of the pathogenic variants of the SSADH deficiency patient. However, stabilization of the folding of pathogenic SSADH variants by other substances may provide a treatment option for this disease.

Context: Mutations in Cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We are reporting a novel R550W mutation in POR identified in a 46, XX patient with signs of aromatase deficiency. Objective: Analysis of aromatase deficiency from R550W mutation in POR. Design, Setting, and Patient: Both the child and the mother had signs of virilization. Ultrasound revealed the presence of uterus and ovaries. No defects in CYP19A1 were found, but further analysis with a targeted Disorders of Sexual Development NGS panel (DSDSeq.V1, 111 genes) on a NextSeq (Illumina) platform in Madrid and Barcelona, Spain, revealed compound heterozygous mutations c.73_74delCT/p.L25FfsTer93 and c.1648C>T/p.R550W in POR. WT and R550W POR were produced as recombinant proteins and tested with multiple cytochrome P450 enzymes at University Children’s Hospital, Bern, Switzerland. Main Outcome Measure and Results: R550W POR showed 41% of the WT activity in cytochrome c and 7.7% activity for reduction of MTT. Assays of CYP19A1 showed a severe loss of activity and CYP17A1, as well as CYP21A2 activities, were also lost by more than 95%. Loss of CYP2C9, CYP2C19, and CYP3A4 activities was observed for the R550W-POR. Predicted adverse effect on aromatase activity as well as a reduction in binding of NADPH was confirmed. Conclusions: Pathological effects due to POR R550W were identified, expanding the knowledge of molecular pathways associated with aromatase deficiency. Screening of the POR gene may provide a diagnosis in CAH without defects in genes for steroid metabolizing enzymes.

In recent years, the prevalence of tobacco and electronic cigarette (e-cigarette) use among adolescents has raised significant public health concerns worldwide. This study aims to investigate respiratory symptoms among Polish adolescents. We conducted an online survey among Polish school students from all provinces, collecting data over two months in Spring 2021. Students voluntarily complete the anonymous survey, answering questions about respiratory symptoms, smoking habits (both traditional and electronic cigarettes), and demographic information. Analysis focused on four subgroups: non-tobacco users, traditional cigarette smokers, e-cigarette users, and dual users, totaling 10,388 pupils aged 12-18 years, predominantly attending secondary technical and comprehensive schools. A total of 10388 pupils participated in the study, 55.6 % (5778) of whom were girls and 44.4 % (4610) boys. Adolescents, who admitted using both e-cigarettes and traditional cigarettes experienced more frequent episodes of cough during the day (39.70%) and at night (18.40%) compared to their peers in other groups. Chest discomfort, including pain and pressure, was also reported more often by adolescents, who used e-cigarettes and traditional cigarettes concurrently (27.60%) compared to their peers in other groups. Chest pressure was experienced less commonly by non-smoking adolescents (14.40%) than by smokers (18.90%). Higher severity of cough during the day and at night was observed in the group of adolescents using traditional cigarettes and e-cigarettes concurrently compared to the other groups. The adolescents in the dual user group experienced more severe dyspnoea and wheezing compared to the other groups included in the comparison. The results of this study confirm the correlation between the occurrence of respiratory symptoms in adolescents who smoke cigarettes, use e-cigarettes and in dual users. The respiratory symptoms occur most frequently and are the most severe in the group of adolescents who use e-cigarettes and traditional cigarettes

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: &gt;3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes &gt; 75 mg/day, at intakes &lt; 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) mediates the degradation of Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. Generic variation in the E6 gene that translates to changes in the protein’s amino acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, and six PDZ domains. PDZ domains played an important role in the function of MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. The aim of this work was to evaluate, with an in silico approach, employing molecular dynamics simulation and protein-protein docking, the interaction of the intragenic variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, AAa and AAc increase their affinity to our two models of MAGI-1 compared to E6-reference.

Non-invasive continuous health monitoring has become feasible with the advancement of biosensors. While monitoring certain biomarkers such as heart rate or skin temperature are now at certain maturity, monitoring molecular biomarkers is still challenging. Progress has been shown in sampling, measurement and interpretation of data towards non-invasive molecular sensors that can be integrated in daily wearable items. Towards this goal, this paper explores the potential of embroidered interdigitated transducer (IDT)-based sensors for non-invasive, continuous monitoring of human biomarkers, particularly glucose levels, in human sweat. The study employs innovative embroidery techniques to create flexible fabric-based sensors with gold-coated IDTs. In controlled experiments, we have shown the variation of glucose concentration in water can be wirelessly detected by tracking the resonant frequency of the embroidered sensors. The current sensors operate at 1.8GHz–2GHz and respond to the change of glucose concentration with a sensitivity of 0.17 MHz/(mg/dl). The embroidered IDT-based sensors with wireless sensing will be a new measurement modality for molecular wearable sensors. The establishment of a wireless sensing mechanism for embroidered IDT-based sensors will be followed by investigation of sweat for molecular detection. This will require adding functionalities for sampling and interpretation of acquired data. We envisage the embroidered IDT-based sensors offer a unique approach for seamless integration into clothing, paving the way for personalised, continuous health data capture.

(1) Background : Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoposrosis. The purpose was to evaluate changes in biomarkers of bone metabolism, and cardiometabolic health in postmenopausal women, with high risk of osteoporosis, followed by a nutritional intervention program. (2) Method: It was a prospective randomized controlled trial. A sample of 115 apparently healthy postmenopausal women(45 -75 years of age) randomized into four groups: (I) nutritional intervention group(n=40) received daily 1000mg vitamin C, 500mg vitamin D3, 500mg calcium(Ca) and 300mg magnesium (Mg); (II) control group(n=42) received daily 500mg vitamin D3, 500mg Ca and 300mg Mg; (III) nutritional intervention group (n=18) received daily 150mg bisphosphonates, 500mg vitamin D3, 500mg Ca and 300mg Mg; and (IV) nutritional intervention group (n=15) received daily about 364 mg polyphenols via an innovative functional food (50g olive paste enriched with mountain tea extract) along with 500mg vitamin D3, 500mg Ca and 300mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in calciregulatory hormone parathormone (PTH) were evaluated at the beginning of the study as well as at 5 and 12 months intervals. Blood levels of vitamin D, vitamin C, Ca, Mg and the lipid profile were assessed at the beginning and at the end of the study. Anthropometric indices (weight, body fat(Kg), Body Mass Index(BMI) and bone mineral density(BMD) were evaluated at the beginning and at the end of the study. Statistical analysis was performed with IBM-SPSS Statistics-21. The level of statistical significance was set at p<0.05. (3) Results: 25(OH)D3 levels were improved, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). PTH levels were increased at the end of the intervention period, for groups I and IV. Significant positive changes recorded, in total BMD, in all four study groups. Significant beneficial changes for total cholesterol was observed in group IV (-2.07%, P<0.05) and positive changes in group I for HDL biomarker (+61.62%, P<0.05) (4) Conclusions:. Additional larger-scale clinical trials and intervention studies are considered essential, in order to fully investigate and elucidate associations between dietary components and biochemical indices of bone metabolism.

Two billion people worldwide suffer from anemia with reproductive-age women being disproportionately affected. Iron plays a crucial role in cellular function and impacts cognition, physical function, and quality of life. Iron deficiency (ID) and iron deficiency anemia (IDA) are associated with adverse effects on pregnancy and fetal development. Oral iron supplementation has been the standard treatment for IDA for decades often producing sub-optimal outcomes. Many babies are still being born with ID and suffer adverse sequelae due to inadequate iron levels in the mothers. Is it time to consider broad scale-up of parenteral iron as a new standard of care?

In 2020, students of Pakistan had to adapt to the online environment for the very first time. This study aims to analyze the perceptions of medical, dental, and allied health students about online education in Pakistan. A descriptive, cross-sectional study was done to assess the level of acceptance of undergraduate students. A pre-validated questionnaire regarding demographics, past-experience of e-learning, advantages disadvantages of e-learning, and general perception of students towards e-learning was distributed. Descriptive statistics were computed for demographics, Mann-Witney-U test was used to compare the differences of perceptions between pre-clinical year and clinical years students. Kruskal-Wallis test was applied to compare the results of three specialties of students. Chi-square was used to compare overall category-wise positive and negative responses of students. 1200 students participated in the study. The major advantage identified by all students was the ‘comfortable environment’ in which they studied online. The major disadvantage selected by preclinical year students was ‘anxiety due to social isolation’ and that chosen by clinical year students was ‘lack of patient interaction’. Overall, 72% of students had a negative perception of e-learning. Student-teacher training, student counselling sessions, and innovative techniques need to be introduced to enhance student engagement and reduce pandemic stress.

The healthcare sector has undergone a profound transformation, owing to the influential role played by IoMT (Internet of Medical Things) technology. However, there are substantial concerns over these devices' security and privacy-preserving nature. Current literature on IoMT tends to focus on specific security features like data confidentiality or data integrity or data availability or access control and most solutions are simulated and not tested in a real-world live network. This paper proposes a smart secure by design solution that safeguards user’s data during health and wellbeing monitoring of patients locally (home, care-home, and hospital) and remotely. The proposed innovative solution is known as Secure by Design Real Time IoMT Architecture for e-Health Population Monitoring (RTPM) for smart hospitals and any healthcare monitoring management. In this system, keys can also be generated by the patient monitoring system independent to maintain high privacy standard and trust during the monitoring process and to enable the IoMT devices run independently even if the server is compromised and are made safe from external exploits to the client nodes. However, the session keys are controlled by the trusted IoMT server to lighten the IoMT devices overheads and the session keys are securely exchanged between the client system and the monitoring server. The proposed RTPM focuses on addressing the major security requirements for an IoMT system: confidentiality, integrity, availability, conducts authentication, protect from DoS attacks and prevent from non-repudiation attack of patient medical data and the devices in a real time, sensory data communication environment for live e-health monitoring. A secure communication is tested by capturing the live network traffic and the system’s performance analysis of RTPM using different security algorithms with different key sizes of RSA, AES, and SHA shows that resource constraint low powered system can also successfully integrate with high-end state-of-the-art secure parameters and features and have the potential to support real time secure interaction. A stress test is also conducted to ensure that the system can withstand huge key sizes and different data types including multi-media information.

Ghrelin and obestatin, two antagonist peptide hormones, are purportedly involved in stimulating appetite and controlling energy balance in humans. Serum ghrelin level is also associated with iron deficiency anemia (IDA), but no study has yet been made of the obestatin level in patients with IDA, even though both hormones are a single gene product. Therefore, the purpose of this investigation is to see whether there is a link between IDA and these two hormones among other hematological parameters in patients with IDA. To measure ghrelin and obestatin, human saliva and serum were collected from 30 women with IDA, aged 31.7 ± 10.7 years, and 30 control women, aged 30.2 ± 8.0 years, with repeated collection of samples over a period of 1 week and 1 month. Saliva and serum ghrelin levels were measured by ELISA. Serum hemoglobin, ferritin, hematocrit and total iron-binding capacity (TIBC) values were determined with an Olympus AU2700. Saliva and serum ghrelin and obestatin levels were significantly lower in the IDA group compared with controls; these levels increased slightly above baseline with iron treatment, but remained below the control values. Furthermore, and as expected, serum hemoglobin, ferritin, and hematocrit levels were significantly increased with iron treatment, while total iron-binding capacity decreased compared to baseline concentrations. The findings suggest that IDA might be linked to imbalance of circulating (serum) and non-circulating (saliva) ghrelin and obestatin levels. Decreased ghrelin and obestatin might destroy iron homeostasis through its effect on intestinal absorption. Measuring these hormone levels might be useful for monitoring the response to iron treatment. Also, serum and saliva levels for both hormones were well correlated. Thus, using saliva in place of serum for monitoring the two hormones should minimize inconvenience and patient discomfort.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

Zinc, an essential trace mineral, plays a crucial role in over 300 enzymes that are vital for major metabolic pathways. Zinc deficiency can cause various symptoms and sometimes lead to serious conditions, especially after surgery. Therefore, recognising the prevalence and predictors of zinc deficiency before surgery is essential for preventing associated symptoms. Although zinc deficiency is linked to several diseases, its association with orthopaedic disorders remains unclear. This retrospective study aimed to explore the prevalence and predictors of zinc deficiency in orthopaedic inpatients prior to surgery. This retrospective case-control study aimed to investigate the prevalence and predictors of zinc deficiency in orthopaedic inpatients. Patients admitted to the Department of Orthopaedic Surgery at Teikyo University Chiba Medical Center between 15 February 2022 and 31 August 2022 were included. The case-control design categorised patients into zinc deficiency (case) and non-deficiency (control) groups based on serum zinc concentrations (< 60 µg/dL). The data retrieved from the centre’s database included demographics, comorbidities, reasons for hospitalisation, fracture details, medication use, and laboratory values. Statistical tests included Fisher’s exact test for categorical variables and a two-sample t-test for continuous vari-ables. To identify factors associated with zinc deficiency, multivariate analysis ( backward stepwise regression model) was performed for items that were significantly different from the univariate analysis. A total of 156 orthopaedic patients were included in this study. Forty-seven patients (30.1%) had a zinc deficiency. The fracture rate was significantly higher in the case group than in the control group (68.1 % vs. 33.9 %; p < 0.001); spinal disease was significantly less common in the case group than in the control group (2.1 % vs. 31.2 %; p < 0.001); and OA was significantly less common in the case group than in the control group (8.5 % vs. 22.9 %; p = 0.04). The case group had signif-icantly higher rates of fragility and hip and pelvic fractures than did the control group. Spinal disease was less common in the case group than in the control group. Laboratory findings revealed significantly lower mean serum zinc (46.2 µg/dL) in the case group than in the control group (76.3 µg/dL), accompanied by lower albumin and haemoglobin concentrations. Hypoalbuminemia and anaemia were more prevalent in the case group than in the control group. Multivariate logistic regression identified age ≥ 60, anaemia, hip fracture, and hypoalbuminaemia as independent predictive factors for zinc deficiency, while spinal disease was associated with decreased risk. This study identified zinc deficiency in 30.1% of orthopaedic inpatients based on serum zinc concen-trations. Furthermore, age ≥ 60, anaemia, hip fracture, and hypoalbuminaemia were determined as independent predictive factors for zinc deficiency.

The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here we show that despite obesity, mice with reduced neuronal LPL (NEXCreLPLflox [LPL KD]) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to WT controls (LPLflox). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence Lifetime Imaging Microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of the free vs. bound Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in, or over-expressing, LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver–related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.

This study was undertaken to elucidate the role of trehalose (Tre) in mitigating oxidative stress under salinity and low P in maize. Eight-day-old maize seedlings of two maize varieties, BARI Hybrid Maize-7 and BARI Hybrid Maize-9 were subjected to salinity (150 mM NaCl), low P (5 µM KH2PO4) and their combined stress with or without 10 mM Tre for 15-d.Salinity and combined stress significantly inhibited the shoot length, root length, and root volume, whereas, low P increased the root length and volume in both genotypes. Exogenous Tre in the stress treatments increased all of the growth parameters as well as decreased the salinity, low P and combined stress-mediated Na+/K+, ROS, MDA, LOX activity and MG in both genotypes. Under salinity and low P stress, the SOD activity increased in both genotypes, but the activity decreased in combined stress. POD activity increased in all stress treatments. Interestingly, Tre application enhanced the SOD activity in all the stress treatments but inhibited the POD activity. Both CAT and GPX activity were increased by saline and low P stress while the activities inhibited in combined stress. Similar results were found for APX, GR, and DHAR activities in both genotypes. However, MDHAR activity was inhibited in all the stresses. Interestingly, Tre enhanced CAT APX, GPX, GR, MDHAR and DHAR activities suggesting the amelioration of ROS scavenging in maize under all the stresses. Increased GST activity in presence or absence of Tre might involve in detoxification of hydroperoxides as well as leaf senescence. On the other hand, increased glyoxalase activities in saline and low P stress in BHM-9 suggested better MG detoxification system because of down-regulation of Gly-I activity in BHM-7 in those stresses. Tre also increased the glyoxalase activities in both genotypes under all the stresses. Tre improved the growth in maize seedlings by decreasing Na+/K+, ROS, MDA, and MG through regulating antioxidant and glyoxalase systems.

Midkine (MDK) is a multifunctional heparin-binding growth factor, and has been shown to regulate cell growth, survival and migration. It also plays important roles in several inflammatory diseases such as sepsis. However, the role of MDK in the lungs has not yet been elucidated. In the present study, we investigated the role of MDK in pulmonary inflammation experiments using a mouse lipopolysaccharide (LPS)-induced pneumonia model and human bronchial cells. Wild-type and MDK-deficient mice were injected intratracheally with LPS, and several inflammatory parameters were analyzed. In the wild-type mice, mRNA expression of MDK in lung tissues was significantly increased after intratracheal LPS injection. The MDK-deficient mice showed significantly lower counts of total cells and neutrophils, as well as lower concentrations of neutrophil chemokines, KC and MIP-2 in bronchoalveolar lavage fluid, compared to wild-type mice. Moreover, mRNA expressions of TNF-α, KC and MIP-2 in lung tissues, as well as histopathological lung inflammation score, were significantly lower in the MDK-deficient mice. Furthermore, in in vitro experiments using bronchial epithelial cells, LPS stimulation increased mRNA expression of MDK, and MDK knockdown by siRNA decreased LPS-induced TNF-α and CXCL8 upregulation. These findings suggest that deficiency of MDK attenuates LPS-induced pulmonary inflammation.

Our health requires continual protein synthesis for maintaining and repairing tissues. For protein synthesis to function, all the essential (indispensable) amino acids (IAA) that must be available in the diet, along with those AAs that the cells can synthesize, the dispensable amino acids. Here we review studies that have shown the location of the detector for IAA deficiency in the brain, specifically for recognition of IAA deficient diets (IAAD diets) in the anterior piriform cortex (APC), with subsequent responses in downstream brain areas. The APC is highly excitable, uniquely suited to serve as an alarm for reductions in IAAs. With a balanced diet, these neurons are kept from over-excitation by GABAergic inhibitory neurons. Because several transporters and receptors on the GABAergic neurons have rapid turnover times, they rely on intact protein synthesis to function. When an IAA is missing, its unique tRNA cannot be charged. This activates the enzyme General Control Nonderepressible 2 (GCN2) that is important in the initiation phase of protein synthesis. Without the inhibitory control supplied by GABAergic neurons, excitation in the circuitry is free to signal an urgent alarm. Studies in rodents have shown rapid recognition of IAA deficiency by quick rejection of the IAAD diet.

Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in the mouse. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is the intention therefore of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and to provide some historical context to recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon, in the hope of raising awareness, and encouraging continued VK related investigations in this important and highly specialized sensory system.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

Scaffoldings play a critical role as temporary structures in supporting construction processes. Accidents at construction sites frequently stem from issues related to scaffoldings, including insufficient support caused by deviations from the construction design, insecure rod connections, or absence of cross bracing, which result in uneven loading and potential collapse, leading to casualties. In this study, we introduce a deep-learning-based, augmented reality (AR)-enabled system called scaffolding assembly deficiency detection system (SADDS) to assist field inspectors in identifying deficiencies in scaffolding assemblies. Inspectors have the flexibility to utilize SADDS through various devices, such as video cameras, mobile phones, or AR goggles (i.e., Microsoft HoloLens 2), for automated detection of deficiencies in scaffolding assemblies. The training test yielded satisfactory results, with a mean average precision of 0.89 and individual precision values of 0.96, 0.82, 0.90, and 0.89 for “qualified” frames and frames with the “missing cross-tie rod,” “missing lower-tie rod,” and “missing footboard” deficiencies, respectively. Field tests conducted at two construction sites demonstrated improved system performance compared to that in the training test. However, these field tests also revealed certain limitations of the SADDS system.

Deficiency of Cytochrome P450 Steroid 21-hydroxylase (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction along with functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in the Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of 21OH deficiency.

Abstract: To obtain bovine oocytes in high quality, effects of vitamin C (VC) on in vitro maturation (IVM) of bovine oocytes and early embryo development were investigated. The results showed that: 1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate, while no effects on the development of parthenogenetic embryos; 2) The in vitro culture (IVC) medium containing 20 µg/mL VC increased the cleavage rate of the in vitro fertilized (IVF) embryos, enhanced the mRNA levels of pluripotency gene Oct4, Sox2, Cdx2 and Nanog in the blastocysts, but no effect on the blastocyst rate; 3) Combing supplemention of 50 µg/mL in IVM medium + 20 µg/ml VC in IVC medium (VC 50/20) increased the cleavage rate of IVF embryos and enhanced the mRNA levels of Oct4, Sox2, Cdx2 and Nanog in the blastocysts; 4) Combination of VC 0/20 and VC 50/20 enhanced the expression of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the expression of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and decreased the Bcl-2/Bax ratio in blastocysts. Together, VC supplementation at tuned concentration as well its combination in IVM and IVC media improves the developmental rates of bovine oocytes and embryos.

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

The relentless challenges posed by the COVID-19 pandemic have placed immense pressure on densely populated regions, such as Hong Kong, particularly in the context of an aging population. The burgeoning demand for healthcare services has necessitated the optimization of resource al-location within healthcare systems. This research presents an innovative analytical queueing model specifically tailored to address the intricate gridlock dynamics prevalent in healthcare systems, with a focused application in the challenging landscape of COVID-19 management. Hong Kong, like numerous other regions, has experienced a demo-graphic transition leading to heightened healthcare demands. Traditional methodologies for scrutinizing gridlock issues in healthcare settings, including simulation models, often prove suboptimal within the context of sophisticated optimization frameworks. This study, however, delves into analytical queueing models, offering a more efficient and effective approach. These models have been underexplored, primarily due to the intricacies involved in modeling gridlock propagation within restricted capacity, a critical concern magnified by the COVID-19 pandemic. The novel Queueing Model introduced in this research incorporates the maintenance of queue capacities and topological aspects as exogenous parameters, rendering it exceptionally adaptable for diverse gridlock-related applications. This adaptability is especially pertinent to healthcare management during the COVID-19 crisis. The model meticulously integrates the concept of gridlock, furnishing a comprehensive comprehension of its origins and repercussions. Validation of this model involves rigorous comparison with established methodologies, exact results, and simulation data, consistently high-lighting its versatility and precision. By applying the model to healthcare management, we scrutinize the dynamics of patient flow within a Hong Kong hospital, placing specific emphasis on the critical issue of bed blockage, further exacerbated by the COVID-19 pandemic. The model's gridlock decomposition unearths the nuanced impact of bed blockage on distinct hospital units, addressing the imperative requirement for quantifying in-patient bed blockage within healthcare systems during a pandemic.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

Vitamin C is important in preventing and slowing the progression of many diseases. There is significant evidence linking periodontal disease and vitamin C. We aimed to systematically review studies addressing the relationship between vitamin C and periodontal disease and the preventive ability of vitamin C against periodontal disease. Electric searches were performed using PubMed, EMBASE, Cochrane Library, and Web of Science. Studies addressing the relationships between periodontal disease and vitamin C in adults aged over 18 years were included. Quality assessment was done using Critical Appraisal Skills Program guideline and GRADE-CERQual. Seventy hundred and sixteen articles were retrieved and fifteen articles (7 cross-sectional studies, 2 case-control studies, 2 cohort studies, and 4 randomized controlled trial [RCT]) were selected by reviewing all articles. Vitamin C intake and blood level were negatively related to periodontal disease in all 7 cross-sectional studies. Subjects who suffer from periodontitis presented lower vitamin C intake and lower blood vitamin C level than subjects without periodontal disease in the two case-control studies. Patients with lower dietary intake or lower blood level of vitamin C showed greater progression of periodontal disease than did the controls. Intervention using vitamin C administration improved gingival bleeding in gingivitis but not in periodontitis. Alveolar bone absorption was also not improved. The present systematic review suggested that vitamin C contributes to reduced risk of periodontal disease.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.