The Candida albicans Dse1 Protein Is Essential and Plays a Role in Cell Wall Rigidity, Biofilm Formation, and Virulence

The fungal pathogen Candida albicans is one of the leading causative agents of death in immunocompromised individuals. It harbors an arsenal of cell wall anchored factors that are implicated in virulence such as filamentation inducing factors, adhesins, lipases, proteases, and superoxide dismutases. Dse1 is a cell wall protein involved in cell wall metabolism. The purpose of this study is to characterize the role Dse1 plays in virulence. Dse1 appears to be an essential gene as no homozygous null mutant was possible. The heterozygote mutant exhibited increased susceptibility to calcofluor white, a cell wall disrupting agent, with a subsequent reduction in cell wall chitin content, decreased oxidative stress tolerance, a 30% reduction in biofilm formation, and a delay in adhesion that was mirrored by a reduction in virulence in a mouse model of infection. Dse1 thus appears to be an important protein involved in cell wall integrity and rigidity

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome, Boomerang Dysplasia, and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach.

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1-242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.This publication was supported by Qatar University Internal Grant No QUST-2-CHS-2020-12. Udhaya Kumar. S, one of the authors, gratefully acknowledges the Indian Council of Medical Research (ICMR), India, for providing him a Senior Research Fellowship [ISRM/11(93)/2019]. The authors would like to thank the Vellore Institute of Technology, India, and Qatar University, Qatar, for providing the necessary research facilities and encouragement to carry out this work

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

The role of micronutrients on the treatment of diabetes

In the last two decades, there has been a significant increase in the number of individuals worldwide who are affected by diabetes. This review article aims to explore the correlation between specific vitamins and diabetes. It has been observed that individuals with diabetes tend to have lower levels of certain antioxidant vitamins, namely A, C, and E. This decrease in vitamin levels is believed to be a consequence of the need to manage oxidative stress caused by issues with glucose metabolism. Additionally, retinol-binding protein plays a role in regulation and adipocytokine function. Diabetics also exhibit reduced levels of thiamine, pyridoxine, and biotin. Research has indicated that diabetes can hinder the absorption of various nutrients, including vitamins B9 and B12, necessitating frequent replenishment of these vitamins. Insufficient levels of vitamin D have been linked to an increased risk of developing diabetes and related complications such as cardiovascular disease. While some studies suggest that vitamin K supplementation may improve glucose metabolism, it remains uncertain whether it can prevent or repair oxidative damage. Excessive vitamin supplementation has been shown to have negative effects, as demonstrated by numerous studies. The review that follows will analyze the association between several nutrients, specifically vitamins A, D, C, B3, B6, B9, Zn, B12, E, B1/K, and iron, and the pathways implicated in diabetes, as well as their potential regulatory effects. Editor highlights: • The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. Prevalence has been rising more rapidly in low- and middle-income countries than in high-income countries.Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation.Between 2000 and 2019, there was a 3 % increase in diabetes mortality rates by age.In 2019, diabetes and kidney disease due to diabetes caused an estimated 2 million deaths. This study was done to see whether diabetes and vitamin and mineral shortages were related. Three categories may be drawn from the associations: Positive connection, No connection, and Controversial are the three options. Vitamins B9, E, D, B1, K, and zinc were included in the first category (demonstrating a positive association) because they appear to affect the diabetes.The results showed that vitamin K has a significant role in glucose metabolism.The study's goal is to employ vitamin K as a medication to control type 2 diabetes mellitus [171,172]. As a consequence, vitamin K can be effective in treating patients with type 2 diabetes mellitus. Vitamin K has a critical function in lipid metabolism and lowers blood levels of HDL and triglycerides, which has a significant influence on the treatment of diabetes, particularly type 2 [173]. Additionally, diabetic and pre-diabetic problems are greatly impacted by vitamin K. While the study failed to demonstrate the impact of vitamin K on fasting blood glucose [174], it did have a substantial impact on insulin and glucose levels 2 h after meals. As of now, a research has demonstrated the benefits of vitamin K supplementation for diabetic patients, namely in older women and men who had improved insulin resistance after taking vitamin K supplements for 36 months [175,176]. Along with its impact on bone mineral density and fracture rates, vitamin K has also been demonstrated to raise bone mineral density and decrease bone fractures in individuals with osteoporosis and Menopause (182,183). It is said to have the ability to imitate insulin and manage blood sugar levels. In order to improve the ligands' capacity to regulate blood sugar, it has been complexed with a variety of ligands [179]. In animal models of diabetes, zinc treatment has been demonstrated to improve lipid and carbohydrate metabolism. The molecular mechanism behind the insulin-like actions of Zn compounds [180–182] includes activation of the phosphatidylinositol 3-kinase (PI3–K)/protein kinase B/Akt (PKB/Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways, among others. Zinc has received a lot of interest in the study and creation of efficient anti-diabetic medications due to its role in the storage and manufacture of insulin as well as its putative insulin-mimetic properties. Zinc (II) has been complexed with a number of chemical ligands as an adjuvant [183]. in order to produce anti-diabetic medications with improved and/or broader scope of pharmacological effects. Zinc supplementation significantly reduced 2-h postprandial hyperglycemia (2hpp) and other glycemic indicators [184,185]. Important molecules involved in cell signaling that promote glucose control seem to be activated by zinc. Zinc also prolong the effects of insulin, regulates insulin receptors, and supports healthy lipid profiles. The development of T2DM is influenced by oxidative stress, which can be brought on by excessive copper. Abnormal Zn and Cu metabolism may contribute to diabetes complications [186,187]Because it lowers the risk of diabetic complications, vitamin E is crucial for patients with type 2 diabetes Meletus [188,189]. Although consuming vitamin E has a considerable impact on lowering the HA1c in diabetic patients, particularly type 2 DM the research did not detect a significant impact on fasting blood sugar [190,191]. Lack of vitamin E has a significant influence on diabetes because it acts as an antioxidant, which reduces long-term issues such diabetic neuropathy and other complications including cardiovascular problems [192,193]. Studies have shown that both sexes, including pregnant women, need 15 mg of vitamin E daily from either natural sources or supplements [194]. Some investigations suggested that persons with vitamin E deficiencies may experience neurological issues, but the studies were unable to establish this since the deficit had been present for a long time [195]. Since the brain is the organ responsible for smell and taste perception, vitamin E deficient patients may experience neurological as well as taste and smell changes [196,197]. Studies have shown that brain tissue is the tissue most impacted by vitamin E deficiency. According to research, patients with dysfunctions of taste and smell had an improvement after taking vitamin E supplements [198]. Additionally, vitamin E functions as a cofactor in both cell division and death. In addition to its essential function in the immune system and central nervous system. Understanding folate's function in critical metabolic pathways is key to recognizing its possible influence on diabetes. According to research, consuming enough folate improves insulin sensitivity, which is crucial for lowering the likelihood of insulin resistance, a feature of type 2 diabetes. However, further research is necessary to fully understand the complex processes behind folate's impact on insulin sensitivity [199]. Empirical data strongly supports the hypothesis that folate plays a crucial role in reducing the risk of diabetes. Notably, a 2018 study published in the journal Diabetes Care found that those with greater amounts of folate in their bodies had a considerably lower chance of acquiring type 2 diabetes. On the other hand, a low folate intake was linked to a higher risk of developing diabetes. These results highlight the potential of folate as a dietary element that may be changed to prevent diabetes [200]. In addition, folate has an influence on cardiovascular health in people with diabetes in addition to reducing the risk of developing diabetes. According to a thorough systematic review and meta-analysis published in the American Journal of Clinical Nutrition in 2018, adults in the United States with type 1 and type 2 diabetes mellitus and prediabetes had a lower risk of dying from cardiovascular disease when their dietary folate intake was higher. This suggests that, in addition to improving glycemic control, folate may also improve cardiovascular outcomes in diabetes patients [201]. While current scientific evidence supports the potential benefits of folate in the prevention and management of diabetes, the complex mechanisms underlying these effects call for more research. To fully utilize folate's therapeutic potential, it is imperative to have a better understanding of how it affects glucose metabolism, cardiovascular health, and insulin sensitivity in the context of diabetes [202]. In conclusion, research has shown how important folate is in reducing the risk of developing diabetes mellitus and its complications. Folate is an important dietary component in managing and preventing diabetes because of its potential to improve insulin sensitivity and participation in important metabolic pathways. The correlations between folate levels and cardiovascular outcomes that have been identified further highlight the varied effects of this vitamin in the treatment of diabetes. Low serum vitamin D is linked to an increased risk of type 1 diabetes mellitus because vitamin D regulates immune system development. As ongoing research reveals the intricate mechanisms of action of folate, it is emerging as a promising adjunctive strategy in treating this common metabolic disorder. Type 1 diabetes may be influenced by low levels of vitamin D [203–206]. Inadequate vitamin D supplementation during infancy has been associated to an increased risk of type 1 diabetes later in life [206]. Significantly lowering the chance of acquiring Type I diabetes is vitamin D supplementation [207]. Low vitamin D levels are also linked to type 2 diabetes mellitus; prediabetes and diabetic individuals respond well to vitamin D treatment. There may be a link between low vitamin D levels and T2DM [208]. In persons with pre-diabetes and hypovitaminosis, high-dose vitamin D improves insulin sensitivity and reduces the chance of developing diabetes [209]. When diabetic patients receive vitamin D, their HbA1c will go down. Niacin (B3), B6, C and vitamin A were placed in the third group (i.e., '' controversial'' association). Niacin (B3) is crucial for reducing TAG and LDL while raising HDL levels. This helps to ward against atherosclerosis. Niacin may be helpful in avoiding diabetic angiopathies since atherosclerosis plays a significant role in the development of these diseases in people with diabetes mellitus. Niacin may be used to reduce blood glucose levels, according to a study [210]. Thiamin is crucial for the breakdown of glucose. There is no proof, according to studies looking at the usage of thiamine in managing glucose levels in diabetics. However, they have shown progress in lowering diabetics' lipid profiles [211]. It has been suggested that riboflavin and thiamine can help prevent gestational diabetes [212]. Even though Vitamin C may help manage diabetes, there are some restrictions that must be recognized. It is difficult to arrive to firm conclusions because to variation in study designs, demographics, doses, and outcomes measurements. Individual reactions to vitamin C supplementation may also vary depending on things like heredity, nutrition, and general health. Recent research indicates that Vitamin C may help manage diabetes by improving glucose control, reducing oxidative stress, and controlling inflammatory reactions [213–216]. The current corpus of evidence is still not definitive, calling for more study through well planned clinical studies. Although using vitamin C as a supplemental method in diabetes management shows potential, medical professionals must use prudence and take into account individualized treatment plans [217]. Animal studies support the link between vitamin B6 deficiency and diabetes. Vitamin B6 deficiency in animals results in decreased pancreatic and blood insulin levels, impaired glucose tolerance, and noticeable changes in the pancreatic islet cells [218]. Epidemiological studies reveal an inverse relationship between vitamin B6 levels and diabetes susceptibility, underscoring the need of maintaining appropriate vitamin B6 levels for effective glucose metabolism. People who have low vitamin B6 reserves are more likely to develop diabetes, whereas those who take vitamin B6 supplements regularly have better glycemic control and fewer problems from diabetes. In terms of managing diabetes, the mounting evidence emphasizes the therapeutic potential of vitamin B6 supplementation [219]. However, this study offers a challenge, arguing that folate—rather than vitamin B12 or vitamin B6—may have a detrimental effect on diabetes incidence. This discrepancy emphasizes the complex interplay between multiple nutrients in the development of diabetes, with distinct B vitamins perhaps exerting differing degrees of effect [220]. This study emphasizes the complex relationship between vitamin B6, specifically PLP, and diabetes. PLP plays several functions in metabolic processes, antioxidant fortification, and enzymatic orchestration, positioning it as a key actor in preserving metabolic health and reducing consequences from diabetes. The data strongly supports the maintenance of optimum vitamin B6 levels as an essential component in lowering diabetes risk and the accompanying problems, even though the precise processes await additional investigation. Folate, or vitamin B9, has attracted a lot of attention in scientific circles for its potential role in preventing and managing diabetes mellitus. As a result, the promotion of a well-rounded diet, complemented by consideration of vitamin B6 supplementation, emerges as a valuable strategy in the prevention and management of diabetes. This water-soluble B-vitamin plays a significant role in a number of metabolic pathways, including those that are essential for insulin control and glucose metabolism. Interest in the significance of folate to diabetes has been inspired by its implications in various metabolic processes [199].It's important to note that while some research indicates a possible connection between vitamin A and diabetes management, more research is required to make specific recommendations for vitamin A supplementation in people with diabetes. A healthcare professional must be consulted before using vitamin A supplements since too much vitamin A might be harmful (234). Contrarily, vitamin B12 consumption fits under category two (i.e., has no bearing on or link to olfaction). Adenosyl cobalamin and methyl cobalamin are the two active forms of vitamin B12, generally known as cyanocobalamin. Megaloblastic anemia, hyperhemocysteinemia, cognitive problems, sleeplessness, neurological problems, and cardiovascular problems can all result from a lack of it [222,223]. Since metformin decreases vitamin B12 absorption in diabetic patients, which can result in a number of issues, its shortage has been extremely common among diabetic patients using the medication. Although vitamin B12 supplementation is not often advised for diabetic patients, there is a substantial correlation between vitamin B12 deficiency and insulin resistance and glycemic control in diabetes mellitus [224–226]. In type 2 diabetes mellitus patients, a lack of vitamin B12 has also been linked, independently, to insomnia [227]. Additionally, people with gestational diabetes mellitus who are vitamin B12 deficient are more likely to experience it insufficiency [228]. The results of this study illuminate the complex interactions between pyridoxal 5′-phosphate (PLP), the biologically active form of vitamin B6, and diabetes by highlighting its multifaceted involvement in metabolic processes, cellular protection, and its potential implications for the onset and control of diabetes [229]. PLP plays a crucial part in directing around 160 enzymatic processes including the metabolism of amino acids, carbohydrates, and lipids. These interactions, which have a direct impact on how nutrients are used and how much energy is produced, are essential for the healthy operation of our physiological systems. PLP is also involved in the production and catabolism of neurotransmitters, which further emphasizes its importance for brain health. PLP performs a wide range of functions, emphasizing the possibility that any deficit in PLP levels could have profound effects on metabolism [230]. In addition to its role in metabolism, PLP also wears the antioxidant hat, skillfully combating the negative effects of reactive oxygen species (ROS) and preventing the formation of advanced glycation end products (AGEs). These antioxidant qualities are crucial for preventing cellular damage, which is a major factor in age-related illnesses like diabetes. Thus, maintaining appropriate PLP levels becomes a viable tactic for slowing the development of diabetic complications [231,232]. A collection of investigations has unequivocally shown the connection between PLP deficit and diabetes. Plasma PLP levels are frequently lower in diabetics, suggesting a possible link between lower PLP levels and insulin resistance. The complex processes behind this relationship are yet unknown, however theories range from disrupted tryptophan metabolism to dysfunctional cystathionine-synthetase (CBS) and cystathionine-lyase (CGL), two enzymes that use PLP as a cofactor. Therefore, PLP deficiency may act as a catalyst for insulin resistance, a key component of type 2 diabetes [233]

The impact of micronutrients on the sense of taste

Among the most primal of senses (approximately 25), the sense of taste in humans is able to distill down to the basic 5 taste qualities of sweet, sour, bitter, salty, and umami, or savory. The sensation commonly known as taste is in fact a fusion of both smell and taste. The technical term for this amalgamation of sensory experiences while consuming food and beverages is referred to as taste. The term “taste” is intended to be limited to the perceived result of stimulating taste receptor cells on the surface of the tongue. This sense of taste is similar to the sense of smell in that the stimuli chemically interact with the receptors during the encoding process. Spices must dissolve in saliva to interact with taste receptors. Saliva then holds the dissolved chemicals near clusters of receptor cells called taste buds. Without saliva, the performance of the taste buds declines rapidly. The chemical taste receptors are hidden in “bumps” (called papillae) that cover the surface of the tongue. Vitamins are known to generate bitterness, which may contribute to an off-taste or aftertaste for some nutritional supplements. In humans, bitter taste detection is mediated by 25 G-protein-coupled receptors belonging to the TAS2R family.In the following review, analysis will be made of the relationship, including possible regulatory activity, of certain nutrients (namely, vitamin E, A, D, C, B3, B6, B9, B12, Zn, and alpha-lepoic acid) to the already discussed pathways involved in the sense of taste

The correlation of ABC goal attainment with insulin resistance/sensitivity in Syrian type 2 diabetes patients

Background: The rising prevalence of type 2 diabetes (T2D) in Syria emphasizes the urgent requirement for effective management approaches. The ABC goals, which include maintaining glycated hemoglobin levels below 7 %, blood pressure below 140/90 mmHg, and low-density lipoprotein cholesterol levels below 100 mg/dl, serve as crucial benchmarks for managing T2D and its associated comorbidities. Methods: In this cross-sectional study, the achievement of ABC goals was retrospectively examined among 681 clinically diagnosed T2D patients (not on Insulin) who participated in a six-year online lifestyle intervention program for diabetes management at the Freedom from Diabetes Clinic in Syria between January 2016 and December 2022. Results: Out of the participants, 152 (22.3 %) successfully achieved all three ABC goals, while 306 (45.0 %) and 183 (26.9 %) achieved two or one goal(s) respectively. The factors influencing the attainment of all three ABC goals revealed a significant association with older age (>50 years), lower body mass index (<25 kg/m2), and lower insulin resistance (Homeostatic Model Assessment of Insulin Resistance < 2.5). Furthermore, patients who successfully achieved all three ABC goals exhibited lower insulin resistance, improved lipid profiles, and higher insulin sensitivity and beta cell function. Conclusion: This study offers new insights into the relationship between insulin resistance/sensitivity and the achievement of ABC goals in the Syrian population with T2D, underscoring the necessity for tailored strategies to enhance comprehensive diabetes management

The role of nutrition on the treatment of Covid 19

The rapid and extensive transmission of the SARS-CoV-2 virus has led to a worldwide COVID-19 pandemic. Initially thought to be an acute illness, many patients have reported persistent and recurring symptoms even after the infectious period. This has given rise to a new epidemic known as ''long-COVID'' or post-acute sequelae of coronavirus disease, which has significantly impacted the lives of millions of individuals globally. The symptoms of both COVID-19 vary from person to person, but they share similarities with other respiratory viruses, such as chest pain, shortness of breath, and fatigue, as well as adverse effects on metabolic and pulmonary health. Nutrition plays a crucial role in immune function and metabolic health, and therefore, it is believed to have an impact on reducing the risk or severity of symptoms for both COVID-19. However, despite the importance of nutrition in these physiological functions related to COVID-19, the exact role of nutrition in the onset or severity of COVID-19 infection is still not fully understood. This review aims to explore established and emerging nutrition approaches that may have a role in COVID-19, while emphasizing the significance of established nutrition and clinical practice guidelines as the primary resources for patients and healthcare practitioners

Futbolo žaidėjų priekinio kryžminio raiščio plyšimo (traumos) rizikos veiksniai – sisteminė mokslinės literatūros apžvalga

In this systematic literature review we assessed risk factors of sustaining an anterior cruciate ligament injury among football players. further, we compared the risk factors between gender, age and level of play