In this paper, we construct the degenerate poly-Fubini polynomials, called the type 2 degenerate poly-Fubini polynomials, by using the modified degenerate polyexponential function and derive several properties on the degenerate poly-Fubini polynomials and numbers. In the last section, we introduce type 2 degenerate unipoly- Fubini polynomials attached to an arithmetic function, by using the modified degenerate polyexponential function and investigate some identities for those polynomials. Furthermore, we give some new explicit expressions and identities of degenerate unipoly polynomials related to special numbers and polynomials.

In this paper, we construct the degenerate poly-Frobenius-Genocchi polynomials, called the type 2 degenerate poly-Frobenius-Euler polynomials, by means of polyexponential function. We derive explicit expressions and some identities of those polynomials. In the last section, we introduce type 2 degenerate unipoly-Frobenius-Genocchi polynomials by means of unipoly function and derive explicit multifarious properties.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Splines and quasi-interpolation operators are important both in approximation theory and applications. In this paper, we construct a family of quasi-interpolation operators for the bivariate quintic spline spaces S₅³ (∆_mn⁽²⁾). Moreover, the properties of the proposed quasi-interpolation operators are studied, as well as its applications for solving two-dimensional Burgers’ equation and image reconstruction. Some numerical examples show that these methods, which are easy to implement, provide accurate results.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics (GLP-1ra and SGLT2-in). Despite new guidelines, clinical inertia, that can be caused by physicians, patients or healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons of clinical inertia and poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiative in diabetes aims to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

As yin and yang, cancer and diabetes are metabolic disorders characterized by deregulated, yet opposing, metabolic alterations. These metabolic shifts reflect a complex network of defective underlying signaling pathways, which ultimately orchestrate both disease pathogenesis and progression. The Warburg effect portrays the chief metabolic phenotype in cancer and is reflected by the dominance of aerobic glycolysis over minimal-to-no viable oxidative phosphorylation in cancer. Conversely, during the pathogenesis of type 2 diabetes (T2D), oxidative phosphorylation is constantly heightened. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, with exacerbating metabolic alterations affecting oxidative phosphorylation in a tissue-specific manner. Promising nutritional adjuvants, such as alpha-lipoic acid and flavonoids, can reprogram metabolism and exert antitumor and antidiabetic effects. Other pharmacological agents, such as metformin, have therapeutic effects on cancer and T2D. Herein, we discuss the molecular mechanisms and signaling pathways involved in the metabolic shifts in cancer and T2D, and explore the therapeutic strategies under investigation that aim to reverse the metabolic shift in both disease scenarios.

Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and contaminated air. It has no nutritional or physiological value, but most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, Ca), which are required for cellular metabolism and functional integrity. The kidney is regarded as the principal site of Cd toxicity as it preferentially accumulates in the proximal tubular epithelium here. As these cells die due to toxic accumulation, Cd complexed with metallothionein are released into tubular lumen and excreted. Excretion of Cd, signifying current renal cell toxicity, is used as a measure of long-term Cd exposure. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and life-style factors that could induce excessive weight gain. Whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of obesity. Indeed, obesity may enhance diabetogenic effects of Cd. This review highlights Cd exposure sources and levels associated with diabetes type 2 along with the pathophysiologic mechanisms by which Cd disrupt glucose metabolism. Special emphasis is on roles of the liver and kidney in glucose homeostasis, heme-glucose cross-talk, and the involvement of heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide and a precursor substrate for producing a cytoprotective biochemical, bilirubin, whilst HO-2 appears to have also anti-diabetic and anti-obese actions.

In this study, we aimed to reveal the proinflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabe-tes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy partici-pants. Levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleu-kin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) were measured in the serum of the par-ticipants. The ANOVA Bonferonni and Kruskal Wallis Dunn tests were used for the comparison of the inflammation markers and vitamin D levels between the groups. Upon covariance analy-sis with age, gender and BMI; Vit D levels of T2DM group were found to be significantly lower (p<0.003). Proinflammatory markers and CRP were found to be significantly higher in predia-betic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the proinflammatory effects of Vit D on the initiation of inflammation in both prediabetes and diabetes mellitus.

Aim: Aging is companied by deteriorations of insulin resistance (IR) and insulin secretion. However, little is known about the roles of aging on different phases of insulin secretion (ISEC); i.e., the first- and second-phase of insulin secretion (FPIS, SPIS) and glucose effectiveness (GE). Methods: Totally 169 individuals (43 men and 126 women) with the similar fasting plasma glucose (FPG: 90 mg/dL) and BMI (men: 23 kg/m2, women 22 kg/m2) were enrolled. IR, FPIS, SPIS, and GE were estimated using our previously developed equations shown below. Pearson correlation analysis was conducted to assess the correlations between age and four diabetes factors (DFs: IR, FPIS, SPIS and GE). The equations that are used to calculate the DF in the present study were built and published by our group. Results: The age of the participants ranged from 18- to 78-year-old. Men had higher FPIS but lower HDL-C levels than women (2.067±0.159, 1.950±0.186 μU/min and 1.130±0.306, 1.348±0.357 mmol/dl, accordingly). The results of Pearson correlation revealed that age was negatively related to IR and GE in both genders (IR: r = -0.39, p < 0.001 for men, r = -0.24, p < 0.003 for women; GE: r = 0.66, p < 0.001 for men, r = 0.78, p < 0.001 for women). In the meanwhile, FPIS was also only found to be negatively correlated with age in female (r = -0.238, p = 0.003). But there was no different with SPIS and age in both of genders. Conclusions: We have found that in Chinese with normal FPG level (90 mg/dl) and body mass index (men: 23 kg/m2, women: 22: kg/m2), age is negatively related to IR and GE in both genders. At the same time, only FPIS was found to be negatively related to age in women. The tightness of their relationships, from the highest to the lowest are, GE, FPIS and IR accordingly. The importance of GE should be re-evaluated. These results should be interpreted with caution because of the small sample size.

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects. An additional experiment was carried out in eight male C57BL/6J mice fed a Western-type diet for twelve weeks. The strategy for glycemic control in the T2D patients significantly improved the HbA1c concentrations without producing changes in the estimated glomerular filtration rate. However, the plasma TMAO and γBB concentrations were significantly increased following the glycemic control in T2D patients. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in mice. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. The contribution of antidiabetic drugs to gut microbiota composition could explain TMAO elevations in treated T2D subjects.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p &lt; 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p &lt; 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

The purpose of this study was to present the challenges faced when implementing a diet and exercise intervention for low-income older Hispanics with type 2 diabetes with an observational study of recruitment, attendance, and characteristics of Hispanic adults with type 2 diabetes in a community congregate meal site pre and post administration of a diet and exercise intervention. This report evaluates retentions and diabetes self-management beliefs Hispanic adults ≥60 years with type 2 diabetes (n=17) at baseline, and completion of the six-month intervention in terms of the Health Belief Model. There was limited interest in controlling diabetes with diet and exercise. Major barriers included lack of perceived vulnerability to diabetes complications and a belief that medication alone is sufficient to stabilize blood glucose. Environmental barriers included lack of transportation, access to exercise groups, access grocery stores, and limited ability to pay for healthy foods. A lesson learned from this intervention was that the diet and exercise intervention given was insufficient as a cue to action for this population interventions to engage low-income, older Hispanics with diabetes in diet and exercise need to consider strategies to overcome barriers such as health beliefs, transportation issues, lack of access to nutritious food and group exercise classes.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

In vitro glucose uptake in yeast cell facilitated by Abelmoschus esculentus L. (okra seed) for management of type 2 diabetes was studied. Plant material was collected, identified, processed, and stored for further use. 80% methanol was employed for extraction and sonicated to release antidiabetic-bioactive component in solution and was filtered, concentrated, freeze-dried, and fractionated using standard techniques. Glucose uptake at an initial concentration of 5mM/L and 10mM/L by the crude extract was consistent to that of the known standard drug while at 25mM/L glucose concentration was equivalent with the crude extract. Also, at 0.625 mg/mL the linear equations, and R2 demonstrations that the crude extract was higher in dose predictability than the standard drug as presented by the equation; y = 35.754x - 57.822, and R² = 0.9502 (95%). The extract-fractions were employed to evaluate the ability of yeast cell line culture to take up glucose from the system through DPPH, FRAP, lipid peroxidation and anti-diabetes effect of extract-fraction assays. Extract-fractions were found to poses antioxidant activity high enough to inhibit stress-related diseases. The extract fractions were active as drug candidates both at low and high concentrations and were better compared with the standard drug and standard antioxidant was comparable. The high bioactive extract fractions require encapsulation with a nanoparticle as a drug candidate for type 2 diabetes patients. And an animal trial of the drug candidate may be necessary to monitor the in vivo performances of the extract fractions and subsequent human volunteered trial.

Metabolic surgery can promote comprehensive physiological improvements to alleviate metabolic disorders, particularly for patients with type 2 diabetes. Nevertheless, the therapeutic scope has been limited owing to unexpectedly inconsistent surgical outcomes. Therefore, this study to overcome these obstacles by determining the fundamental mechanism underlying the conflicting outcomes. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified duodenal-jejunal bypass (DJB) procedures, were compared to understand the specific surgical patterns from different perspectives comprehensively. Patients in the nonobese group were exclusively included to prevent confounding effects from overweight patients with type 2 diabetes. Following intestinal anastomosis, the epithelial identity of the succeeding intestine was replaced by that of the proximal epithelium owing to altered crosstalk between the epithelium and opposing mesenchymal cells. Subsequent intestinal compensatory proliferation and rapid turnover rate accelerate the spread of the replaced epithelium. The main factors contributing to inconsistent outcomes of metabolic surgery are inadequate duodenal exclusion and inappropriate biliopancreatic limb length. Replacement of enteroendocrine cells during regeneration can lead to inconsistent outcomes in metabolic surgery. The type and density of enteroendocrine cells distributed at the terminal end of the proximal intestine play a significant role in diverse outcomes of metabolic surgery.

There is a have been positive correlations between the existence of type 2 diabetes mellitus (T2DM) and the development of thyroid disorders. Prediabetes is a progressive state of moderate insulin resistance that often precedes the onset of type 2 diabetes mellitus (TT2DM) however the association between prediabetes and thyroid function is unknown. This study assessed changes in markers of thyroid function in diet-induced prediabetes. 12 male Sprague Dawley rats were randomly allocated into two groups. Rats in the non-prediabetic (NPD) group were fed a standard rat diet while rats in the prediabetic (PD) were fed a high-fat high carbohydrate diet for 20 weeks to induce prediabetes. Thereafter, fasting blood glucose levels were measured. Plasma samples were assessed for triiodothyronine (T3), thyroxine (T4), thyroxine peroxidase (TPO) antibody, insulin and glycated haemoglobin (HbA1c) concentrations. The elevated blood glucose, HbA1c and plasma insulin levels coincided with increased T3 and reduced T4 levels in the PD group when compared to the NPD group. There was also an increase in the concentration of TPO antibodies in the PD group. Additionally, there was a significant correlation between the thyroid hormone concentrations and HbA1c levels. In conclusion, these results indicated that there is a positive association between thyroid dysfunction and diet-induced prediabetes.

This research aimed to figure out the applications of HbA1c protein and HbA1 gene as the prognostic biomarkers for assessing the risks of different cancers among male T2D patients in Bangladesh considering their serological and oncoinformatic parameters. Depending on the concentrations of HbA1c (%) of the T2D patients (n=300), their individual FBS (mmol/L); THABF (mmol/L); creatinine (mg/dl); SC (mg/dl); STGs (mg/dl); HDLC (mg/dl); and LDLC (mg/dl) were estimated. The values of the patients were compared with the control (n=60) group as the serological analysis. Besides, HbA1 gene (encoding hBA1c protein) overexpression and promotor methylation responsible for BLCA, BRCA, CHOL, COAD, LUAD, LUSC, PAAD, and PRAD cancers in the male T2D patients were profiled as the oncoinformatic parameters based on the sample types; caner stages; racial footprints; gender; age; nodal metastasis; p53 methylations; pancreatitis; diabetes status; smoking behaviors; and overall/disease-free survivability. Finally, the ‘HbA1 gene strings’ responsible for genetic coexpression; endophytic vesicle regulation; antioxidant regulation; oxygen species metabolic regulation; and gene-mediated response to the reactive oxygen molecules were studied comprehensively. A strong correlation between BMI and FBS was observed in both the patients and the control (P<0.0001). Similarly, the values of FBS, THABF, and creatinine resulted in equal significance (P<0.0001) as compared to the HbA1c concentrations of all the T2D and control individuals. The SC, STGs, HDLC, and LDLC concentrations regulated ardently in both the control (P<0.0001), and patients group (P<0.0001), while HbA1c ranged from 3.8-5.8%, and 5.11-15.8% respectively. HbA1 gene is found downregulating with cancer progressed in most of the oncoinformatic parameters. According to the DA, CS, EI, CE, PC, NC, GF, H, and AT profiles; the HbA1 gene interacts with 8 other genes responsible for creating a protein cluster comprising- AHSP, HBA1, HBA2, HBB, HBD, HBE1, HBG2, RPS12, and RPS19 proteins for cancer formation. To recapitulate, HbA1c protein and HbA1 gene can be used as the prognostic serological and molecular biomarkers respectively for determining the risks of cancers among male chronic T2D patients.

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. T2DM condition increases the risk of micro and macro-vascular complications as well as the risk of geriatric syndromes as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the cli-nician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycate haemoglobin target according to functional and cognitive status comorbidities, life ex-pectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be cathegorized in three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for the glycemic control is different, also according to the type of treatment drug. The therapeutic ap-proach should always begin with lifestyle changes; after that, several lines of therapies are available, with different mechanism of action and potential effect other than glucose level reduction. Partic-ular interest is growing around sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review we evaluate the therapeutic options available for the treat-ment of older diabetic patients, to ensure a correct treatment approach

We report diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), a rare, hereditary neurodegenerative disease of childhood, in a four and a half year old girl, the first child of non-consanguineous parents with no family history. Despite extensive efforts by the parents, her clinical condition remained undiagnosed and without management, until recently. Our published “Bottom-up Approach”, based on comprehensive and multidisciplinary clinical, pathological, radiographical and genetic evaluations, played key role in diagnosis of the disease. Detailed analyses involving Next Generation Sequencing confirmed a missense variation NC_00011.10:g.6616374C>T (NP_000382.3:p.Arg339Gln; rs765380155) in exon 8 of TPP1 gene. In silico analyses predicted it to be highly pathogenic. Further family screening (including her both unaffected parents and asymptomatic, one year old younger sister) of the identified variation through Sanger Sequencing, revealed a perfect autosomal recessive segregation in the family. This study is the first case report on classic CLN2 from Jammu and Kashmir-India. This study is also indicating the effectiveness of our “Bottom-up Approach” in understanding rare disorders in low resource regions and the importance of timely diagnosis. Like in the proband, had diagnosis been established a bit early, the family might have benefitted at least with reference to their second child through counselling programmes.

In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) might prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and important biological function, e.g., inhibition of GP. Herein, the Suárez radical methodology is successfully applied to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not been previously constructed via a radical pathway, starting from 6-hydroxymethyl-b-D-glucopyranosyluracil. It is shown that in the rigid pyranosyl conformation the required [1,5]-radical translocation is a minor process. The stereochemistry of the spirocycles obtained was unequivocally determined based on the chemical shifts of key sugar protons in the ¹H NMR spectra. The two spirocycles were found to be modest inhibitors of RMGPb.

Since atopic dermatitis (AD) is a heterogeneous condition, subtyping of AD is a crucial issue. The classical subtypes of AD are represented by extrinsic and intrinsic subtypes, European American and Asian subtypes, and adult and pediatric subtypes. While subtyping of AD was historically conducted based on the phenotype, recent findings on the mechanisms of AD have revealed importance of the endotype, which can characterize individual patients more accurately. Considering the current development of AD therapies, AD endotyping is prerequisite for personalized therapeutic choice. Endotypes of AD can be stratified from different viewpoints, including cytokine expression patterns, allergen properties, epidermal barrier conditions, ceramide variation, involvement of innate immunity, and serum biomarkers. Among them, the cytokine-based endotype seems to be the most useful one and is categorized into type 2 cytokine (IL-4, IL-13 and IL-31)-high, type 1 cytokine (interferon-g)-high, and/or type 3 cytokine (IL-22 and IL-17)-high, or mixed subtypes. The recently biomarker-proposed endotyping aims at individualized treatment options, although the daily clinical use of endotypes is a future issue. To better understand the endotypes for clinicians, attempts to adjust each of the classical subtypes to the endotypes are required. This review will discuss the correspondence of the classical subtypes to the various endotypes that have recently been proposed.

In this article, a new class of $q$-Hermite based unified Apostol type polynomials is introduced by means of generating function and series representation. Several important formulas and recurrence relations for these polynomials are derived via different generating methods. We also introduce $q$-analog of Stirling numbers of second kind of order $\nu$ by which we construct a relation including aforementioned polynomials.

Rapidly digestible starch can be obtained by gelatinization (cooking), cooking extrusion, use of small granule starch, breaking down starch granules, or by hydrolysis to maltodextrins. Resistant starch includes five groups: the first group is physically encapsulated starch within a food/polymer matrix, the second one is some native starch, the third one is recrystallized starch, the fourth one is chemically modified starch, and the fifth one is starch-lipid complexes. Starch digestion in the human body is also influenced by the degree of chewing, activity of α-amylase in the intestine, and transit time through the stomach and small intestine. Resistant starch or dietary fiber (DF) enriches specific bacterial groups located in the large intes-tine. They produce short chain fatty acids (SCFAs) and gases, causes the lowering of the pH, and inhibits pathogens. SCFAs are considered endogenous signaling molecules, acting through their free fatty-acid receptors 2 and 3 which can trigger the secretion of glucagon-like peptide-1 and peptide PYY, being released together following a meal to mediate postprandial satiety. A sufficient intake of DF reduces the risk of cardiovascular disease, coronary heart disease, stroke, hyperten-sion, colorectal cancer, and type 2 diabetes. Gluten matrix or phenolic compounds can lead to a low digestion rate of starch.

Background In 2016, Global Polio Eradication Initiative (GPEI) recommended cessation of type 2 oral poliovirus vaccine (OPV) and OPV using countries switched from trivalent to bivalent OPV (bOPV) with addition of inactivated poliovirus vaccine (IPV) in the routine immunization schedule. The current GPEI strategy 2022-2026 includes bOPV cessation plan and switching to IPV standalone or the combination vaccine schedules in future. The focus of our study was to evaluate immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV only schedules. Methods This was a three-arm, multi-center randomized controlled trial conducted in 2016-2017 in India. Participants, at birth, were randomly assigned to bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth, 14-, 18- and 22- weeks age were analyzed with standard microneutralization assay for all three poliovirus serotypes. Results Results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after completion of the schedule at 18 weeks were 99.5% (97.0-99.9), 100.0% (97.9-100.0) 96.0% (92.0-98.1) in Arms A (4bOPV+IPV), B (4mOPV1+IPV) and C (3IPV) respectively. Type 2 and type 3 seroconversion at 18 weeks were 80.0% (73.7-85.1), 76.9% (70.3-82.4), 93.2% (88.5-96.1) and 100.0% (98.0-100.0), 81.9% (75.6-86.8), 99.4% (96.9-99.9) respectively in the three arms. Conclusions This study shows high efficacy of different polio vaccines for serotype 1 in all three schedules. Type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on epidemiology from time-to-time.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and it has been implicated in the pathogenesis of inflammation, insulin resistance and obesity. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are the main form of vitamin D: the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity and cardiovascular disease. It's interesting to note that several long-term studies also revealed an inverse correlation between vitamin D level and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects, in fact while some studies demonstrated improvements in insulin sensitivity, glucose and lipid metabolism, others revealed no significant effect on glycemic control and inflammation. The aim of this review is to provide insight into the molecular basis of the relationship between vitamin D, insulin-resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain is associated with the progression of Alzheimer's Disease (AD).To address this burden of type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (https://www.clinicaltrials.gov/ct2/show/NCT04626453, https://www.clinicaltrials.gov/ct2/show/NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well-tolerated, even during the COVID pandemic. It was also safe, requiring minimal equipment and no supervision. The exercise instructions were easy to understand, making them suitable for older adults with cognitive decline.The near-infrared spectroscopy (NIRS) based brain and muscle oxygenation study provided evidence on brain overactivation among older adults with T2DM, supporting the compensatory theory. It also demonstrated that the 2-month combined exercise intervention effectively reduced brain overactivation and contributed to improved cognitive function. Operational modal analysis showed an exercise-related effect on the very low-frequency hemodynamic oscillations cluster, which may be associated with better vascular muscle and/or perivascular neurogenic regulation. Furthermore, we personalized the exercise duration and interval based on muscle oxygenation during physical tasks, leading to improvements in muscle oxidative capacity within just two months. This finding has practical implications for physical therapists, as they can target muscle oxygenation changes during physical tests to prescribe appropriate exercise doses for enhancing physical performance.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

The purpose of this paper is to prove strong convergent theorems for Browder's type iterations and Halpern's type iterations of a family of nonexpansive mappings in a complete geodesic space with curvature bounded above by a positive number. Moudafi's viscosity type methods are also discussed without the nice projection property.

A finite-type immersion or smooth map is a nice tool to classify submanifolds of Euclidean space, which comes from eigenvalue problem of immersion. The notion of generalized 1-type is a natural generalization of those of 1-type in the usual sense and pointwise 1-type. We classify ruled surfaces with generalized 1-type Gauss map as part of a plane, a circular cylinder, a cylinder over a base curve of an infinite type, a helicoid, a right cone and a conical surface of $G$-type.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

Background We aimed to compare the retinal, optic disc vascular density (ODVD) values, and acircularity index (AI) of patients with idiopathic macular telangiectasia type 2 (IMT) and healthy individuals using the optical coherence tomography angiography(OCTA) device. Methods The study included 39 patients with IMT and 37 healthy controls. The OCTA findings of the patients and controls were examined. Results The total, parafoveal and perifoveal vascular density of the superficial capillary plexus, choriocapillaris blood flow, inside-disc ODVD, retinal nerve fiber layer (RNFL), and retinal thicknesses were found to be statistically significantly lower and the foveal avascular zone value was statistically significantly higher in the IMT group compared to the control group (p=0.001, p=0.01, p=0.02, p=0.01, p=0.009, p=0.002, p=0.02, respectively).There was a statistically significant negative correlation between best-corrected visual acuity (BCVA) and AI (p=0.02), a statistically significant positive correlation between peripapillary vascular density and BCVA(p=0.04). Conclusion We consider that the lower retinal, choriocapillaris, and ODVD values, retinal and RNFL thicknesses in the patients with IMT compared to the controls were due to vascular damage, remodeling, fibrosis, proliferation, and Müller cell damage. Ellipsoid zone defect, AI, and peripapillary vascular density are important indicators in the evaluation of visual acuity in these patients.

Background & Aims: Gut microbial imbalances are linked to colorectal cancer (CRC), but archae-‎a's role remains underexplored. Here, we performed bioinformatic and statistical analysis looking ‎for archaeal taxonomic and functional signatures related to CRC. Methods: We analyzed pub-‎lished fecal metagenomic data from 390 subjects, comparing the archaeomes of CRC and healthy ‎individuals. We conducted a biostatistical analysis to investigate the relationship between Candi-‎datus Mancarchaeum acidiphilum (DPANN superphylum) and other archaeal species associated ‎with CRC. Using the Prokka tool, we annotated the data focusing on archaeal genes, subsequently ‎linking them to CRC and mapping them against UniprotKB and GO databases for specific ar-‎chaeal gene functions. Results: Our analysis identified enrichment of methanogenic archaea in ‎healthy subjects, with an exception for Methanobrevibacter smithii, which correlated with CRC. ‎Notably, CRC showed a strong association with archaeal species, particularly Natrinema sp. J7-2, ‎Ferroglobus placidus, and Candidatus Mancarchaeum acidiphilum. Furthermore, the DPANN ar-‎chaeon exhibited a significant correlation with other CRC-associated archaea (p < 0.001). Func-‎tionally, we found a marked association between MvhB-type polyferredoxin and colorectal can-‎cer. We also highlighted the association of archaeal proteins involved in the biosynthesis of leucine ‎and the galactose metabolism process with the healthy phenotype. Conclusion: The archaeomes ‎of CRC patients show identifiable alterations, including a decline in methanogens and an increase ‎in Halobacteria species. MvhB-type polyferredoxin, linked with CRC and species like Candidatus ‎Mancarchaeum acidiphilum, Natrinema sp. J7-2 and Ferroglobus placidus emerge as potential archaeal ‎biomarkers. Archaeal proteins may also offer gut protection, underscoring archaea’s role in CRC ‎dynamics.

A construction for the systems of natural and real numbers is presented in Zermelo-Fraenkel Set Thoery, that allows for simple proofs of the properties of these systems, and practical and mathematical applications. A practical application is discussed, in the form of a Simple and Linear Fast Adder (Patent Pending). Applications to finite group theory and analysis are also presented. A method is illustrated for finding the automorphisms of any finite group $G$, which consists of defining a canonical block form for finite groups. Examples are given, to illustrate the procedure for finding all groups of $n$ elements along with their automorphisms. The canonical block form of the symmetry group $\Delta_4$ is provided along with its automorphisms. The construction of natural numbers is naturally generalized to provide a simple and sound construction of the continuum with order and addition properties, and where a real number is an infinite set of natural numbers. A basic outline of analysis is proposed with a fast derivative algorithm. Under this representation, a countable sequence of real numbers is represented by a single real number. Furthermore, an infinite $\infty\times\infty$ real-valued matrix is represented with a single real number. A real function is represented by a set of real numbers, and a countable sequence of real functions is also represented by a set of real numbers. In general, mathematical objects can be represented using the smallest possible data type and these representations are calculable. In the last section, mathematical objects of all types are well assigned to tree structures in a proposed type hierarchy.

This study tested the association between FecXG point mutation located in exon 2 of BMP15 gene and the prolificacy of Dubasi, Shugor and Watish sheep ecotypes, under dryland farming, Sudan. Blood samples were randomly collected from unrelated 100 ewes (Dubasi; n= 30, Shugor: n= 30, and Watish: n= 40). Bone Morphogenetic protein (BMP15) gene was amplified using PCR-RFLP. Two genotypes were found in all studied breeds (heterozygous and wild type). The calculated total genotype frequencies of BB, Bb and bb genotypes were 0.31, 0.69 and 0.00, respectively, while allele frequencies were 0.66 for B and 0.34 for b. Litter size was influenced by the genotypes of BMP15 gene, parities and subtypes (p<0.05), highest for Watish and 4th parity. Alignment of BMP15 samples along with database reference sequence revealed that most sequence regions were identical except for one variable nucleotide at position 111 bp where a guanine (G) was replaced by adenine (A) in Watish and Shugor samples. All amino acids were the same at residue 275. Watish and Shugor breeds are more related. The study concluded that the presence of one copy of FecXG point mutation of BMP15 gene increased the litter size by 0.17 lambs in the studied ecotypes.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany and the retraction of phenformin (N-Phenethylbiguanide) because of the letal complication of acidosiss,metformin (1-1-dimethylbiguanide) was first released in France in 1959 and then in the USA in 1995 for oral treatment of diabetes type 2. Acute gastrointestinal side effects often lead to dose reduction and strongly limit adherence to therapy.Main long-term consequences are deficency of vitamin B12 and of iron and sometimes also acidosis development. Intravenously injected F18-labelled glucose in metformin-treated type 2 diabetics accumulates in the the small and even more in the large intestine.The densitometry picture observed in metformin-treated diabetics is similar to that observed in patients after bowel-cleansing or chronically taking different types of laxatives where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to „attraction“ of glucose from the hepatocyte to the intestine,possibly through its secretion into the bile.Metformin is not different from the other biguanides ,synthalin B and phenformin.The mechanism of action,and the side effects are comparable to those of laxatives.

Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think that there is nothing impossible to find, invent or mold. All these resources that we document here, are involved in solving problems in allergic diseases, both diagnostic, prognostic, treatment and immunotherapy development. The main perspectives, according to this version, are in three strands and / or lockout immunological system: 1) In blocking the diapedesis of cells involved, 2) modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonism or blocking them and 3) blocking FcεR1 receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field.

Porcine circovirus type 2 (PCV2) is a small non-enveloped DNA virus that causes swine immunosuppression by inducing apoptosis in lymphocytes. The ORF3 protein plays a major role in PCV2-induced apoptosis in porcine kidney cells, but there is little information regarding this protein in PCV2-infected lymphocytes. In this study, hybridoma screening and epitope mapping were determined by using an indirect ELISA. The mAb 7D3 against ORF3 peptide (residues 35–65) of PCV2 were generated in this study. In vivo situation, the mAb 7D3 recognized ORF3 protein existed in PCV2-infected apoptotic porcine PBMCs. It is noteworthy that thimerosal interfered with the binding of mAb 7D3 to epitope and it was diminished by adding cysteine. Additionally, thimerosal interacting with cysteine-containing peptide was demonstrated by the PTI assay. Furthermore, thimerosal specifically interacted with the antigen-binding sites of mAb 7D3. This study suggested that thimerosal blockade the occlusion of the antigen-binding sites of mAb 7D3 to bind ORF3 peptide (residues 35–65) via thimerosal interacting with cysteine residues which should be located within the antigen-binding sites of mAb 7D3. Overall, the mAb 7D3 has been characterized and it will be a valuables tool in future studies of ORF3 function and the wider mechanism of cell apoptosis caused by PCV2 infection. Similarly, these techniques will be useful for applications in detecting thimerosal too.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

Studies comparing provider and patient views and experiences of self-management within primary healthcare are particularly scarce in disadvantaged settings. In this qualitative study, patient and provider perceptions of self-management were investigated in five socio-economically disadvantaged communities in Stockholm. Twelve individual interviews and three group interviews were conducted. Semi-structured interview guides included questions on perceptions of diabetes diagnosis, diabetes care services available at primary health care centers, patient and provider interactions, and self-management support. Data was analysed using thematic analysis. Two overarching themes were identified. These were characterized by inherent dilemmas representing confusions and conflicts that patients and providers experienced in their daily life or practice respectively: adopting and maintaining new routines through practical and appropriate lifestyle choices (patients); and balancing expectations and pre-conceptions of self-management (providers). Patients found it difficult to tailor information and lifestyle advice to fit their daily life. Healthcare providers recognized that patients were in need of support to change behavior, but saw themselves as inadequately equipped to deal with the different cultural and social aspects of self-management. This study highlights patient and provider dilemmas that influence the interaction and collaboration between patients and providers with respect to communication and uptake of self-management advice.

By generalizing the notion of pointwise 1-type Gauss map, the generalized 1-type Gauss map has been recently introduced. Without any assumption, we classified all possible ruled surfaces with generalized 1-type Gauss map in a 3-dimensional Minkowski space. In particular, null scrolls do not have the proper generalized 1-type Gauss map. In fact, it is harmonic.

Abstract: Astrocytes (ACs) are the most abundant human cell in the brain and importantly, are the master connecting and communicating cells that provide structural and functional support of brain cells at all levels of organization. Further, they are recognized to be the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste and comprise the glymphatic system, which is critically dependent on the proper waste removal by the pvACef polarized aquaporin 4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role for synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI) and associate with white matter hyperintensities, lacunes, aging, accepted to be biomarkers for cerebral small vessel disease, increased in obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

This work reports the role of structure and composition on the determination of the performances of p-type SnOx TFTs deposited by rf magnetron sputtering at room temperature, followed by a post-annealed step up to 200 °C at different oxygen partial pressures (Opp), between 0% and 20%, but where the p-type conduction was only observed between 2.8–3.8%. The role of structure and composition were evaluated by XRD and Mössbauer spectroscopic studies. The study allows to identify the best phases/compositions and thicknesses (around 12 nm) to be used that lead to the production of TFTs with a bottom gate configuration, on glasses coated with conductive Indium Tin Oxide, followed by Aluminium Titanium Oxide dielectric layer with saturation mobility of 4.6 cm²V⁻¹s⁻¹ and on-off ratio above 7 × 10⁴, operating at the enhancement mode with a saturation voltage of −10 V.

The main aim of this paper is to establish two generalized integral formulas involving the extended Mittag–Leffler function based on the well known Lavoie and Trottier integral formula and the obtain results are express in term of extended Wright-type function. Also, we establish certain special cases of our main result.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

We discuss two queueing-inventory systems with catastrophes in the warehouse. Catastrophes occur according to Poisson process and upon arrival of a catastrophe all inventory in the system is instantly destroyed. But consumer customers in the system (in the server or in the buffer) continue still waiting for the replenishment of the stock. The arrivals of the consumer customers follow a Markovian Arrival Process (MAP) and they can be queued in an infinite buffer. Service time of a consumer customer follows a phase-type distribution. The system receives negative customers whose have Poisson flows to service facility and upon arrival of a negative customer one consumer customer is pushed out from the system, if any. One of two replenishment policies can be used in the system: either (s,S) or (s,Q). If upon arrival of the consumer customer, the inventory level is zero, then according to the Bernoulli scheme, this customer is either lost (lost sale scheme) or join the queue (backorder sale scheme). The system is formulated by a four-dimensional continuous-time Markov chain. Steady state distribution is obtained using the matrix-geometric method. A comprehensive numerical study is performed on the performance measures under various replenishment policies. Finally, an optimization study is presented.

Let $m$ and $n$ be the fixed positive integers. Suppose $\mathcal{A}$ is a von Neuman algebra with no central summands of type $I_{1}$ and $L_{m}$ be a Lie type higher derivation i.e., an additive (linear) map $L_{m} :\mathcal{A}\to \mathcal{A}$ such that \begin{equation}\label{def2} \[L_{m}(p_{n}(\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}))=\sum_{l_1+l_2+\cdots+l_n=m}p_{n}\big(L_{l_1}(\mathfrak{S}_{1}),L_{l_2}(\mathfrak{S}_{2}),\cdots,L_{l_n}(\mathfrak{S}_{n})\big)\] %L_{m}(p_{n}(\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}))=\sum_{l_1+l_2+\cdots+l_n=m}p_{n}\big(L_{l_1}(\mathfrak{S}_{1}),L_{l_2}(\mathfrak{S}_{2}),\cdots,L_{l_n}(\mathfrak{S}_{n})\big)\nonumber \end{equation} for all $\mathfrak{S}_{1},\mathfrak{S}_{2},\cdots,\mathfrak{S}_{n}\in \mathcal{A}$. In the present paper, we study Lie type higher derivations on von Neuman algebras and prove that every additive Lie type higher derivation on $\mathcal{A}$ has a standard form at zero product as well as at projection product. Further, we discuss some more related results.

The genome of Vibrio cholerae contains three structural genes for the NhaP-type cation-proton antiporter paralogues, Vc-NhaP1, 2 and 3 mediating exchange of K+ and or Na+ for protons across the membrane. Based on phenotype analysis of chromosomal Vc-NhaP1, 2 and 3 triple deletion mutants we suggested that Vc-NhaP paralogues might play a role in the Acid Tolerance Response (ATR) of V. cholerae as it passes through the gastric acid barrier of the stomach. Comparison of the biochemical properties of Vc-NhaP isoforms revealed that Vc-NhaP2 is the most active among all three paralogues. Therefore, Vc-NhaP2 antiporter is a plausible therapeutic target for developing novel inhibitors targeting these ion exchangers. Our structural and mutational analysis of Vc-NhaP2 identified a putative cation binding pocket formed by antiparallel extended regions of two transmembrane segments (TMSs V/XII) along with TMS VI. Molecular Dynamics (MD) simulations suggested that the flexibility of TMS-V/XII is crucial for the intra-molecular conformational events in Vc-NhaP2. In this study, we developed some putative Vc-NhaP2 inhibitors from Amiloride analogs (AAs). Amiloride is a potent inhibitor of human Na+/H+ exchanger-1 (NHE1). Based on the pharmacokinetic properties and potential binding affinity scores we chose six AAs showing high binding affinity scores to Vc-NhaP2. In silico, the six AAs interacted with the functionally important amino acid residues located in TMSs III, IV, V, VI, VIIII and IX either from the cytoplasmic side (three AAs) or the periplasmic side (three AAs) of Vc-NhaP2. Four AAs were modified to reduce their toxicity profile compared to the original AAs. Molecular docking of the modified AAs revealed promising binding. The four selected drugs interacted with functionally important amino acid residues located on the cytoplasmic side of TMS VI, the extended chain region of TMS V and TMS XII and the loop region between TMSs VIIII and IX. Molecular dynamics simulations revealed that binding of the selected drugs destabilized the Vc-NhaP2 and altered the flexibility of functionally important TMS VI.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases including PD and type 2 diabetes mellitus (T2DM) suggesting a crucial interplay between the gut–brain axis. GLP-1R agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between February 2023 and February 2024. We used the terms “GLP-1”, “GLP-1 receptor”, “GLP-1R agonists”, “PD”, “T2DM”, “insulin”, “neurodegenerative disease”, “glucose”, “animal models”, “clinical trials” in different combinations. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies are also very promising enhancing the possibility of adding GLP1-R agonists in the current armamentarium of drugs available for PD treatment.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

We have investigated the interfacial dislocations in InxGa1–xN/GaN (0 ≤ x ≤ 0.20) heterostructures using diffraction contrast analysis in a transmission electron microscopy. The analysis indicate that the structural properties of the interface dislocations depend on the indium composition. For lower indium composition up to x = 0.09, we observed that the screw-type dislocations and dislocation half loops occurred at the interface even though the former do not contributes toward elastic relaxation of the misfit strain in the InGaN layer. With the increase of indium composition (0.13 ≤ x ≤ 0.17), in addition to the network of screw-type dislocations, edge-type misfit dislocations were found generated with their density gradually increasing. For higher indium composition (0.18 ≤ x ≤ 0.20), all the interfacial dislocations are transformed into a network of straight misfit dislocations along the <10-10> directions leading to partially relaxation of the InGaN epilayer. The presence of dislocation half loops may be explained by slip on the basal plane, the formation of misfit dislocations are attributed to punch-out mechanism.

Should our planet be visited by an extraterrestrial civilization, the prevailing assumption would undoubtedly be that the extraterrestrial civilization is Type I i.e. its capacity for interstellar travel results from its technological development. This assumption is dangerous for it unnecessarily leads to the Extraterrestrial Tandem Hypothesis (ETH): the belief than an extraterrestrial civilization technologically capable of interstellar travel must also be technologically compatible with the inexorably rapid annihilation of life on Earth. Such a state of things would compromise the planet’s capacity to stage a confident defense should the extraterrestrials prove belligerent. The presumption of Type I extraterrestrials (on the premise of the capacity for interstellar travel alone) is unfounded as extraterrestrials may be Type II i.e. capable of interstellar travel by virtue of natural intrinsic or extrinsic factors. This paper advances, most importantly, that the fundamental policy of first contact should be the employment of various strategies toward the evaluation of the technological capacity of visiting extraterrestrials. This evaluation must be particularly devoted to the detection of Type II extraterrestrials masquerading as Type I (using concealment and Wizard of Oz strategies). Integral to this detection are the concepts of the precedence relation and The Extraterrestrial Exclusion Principle (EEP). A precedence relation is a qualitative relation expressing the relative difficulty of producing a technological action. The Extraterrestrial Exclusion Principle states that a Type I extraterrestrial life form is excluded from certain actions. Such actions are lower in precedence than interstellar travel and may be described as in violation of the EEP or EEP forbidden. EEP actions reveal extraterrestrials to be Type II. As an example, the value of the Hawking Warning is subjected to EEP analysis. Furthermore, a hypothetical conundrum in linguistics termed the Kryptonian Linguistic Paradox (KLP) is discussed as a case of an EEP forbidden act. Finally, the paper explores the limitations of the stated fundamental policy of first contact.

The incidence of Type 1 Diabetes (T1D) in the Arab world, particularly, oil and gas rich Gulf Cooperative Council (GCC) countries has more than doubled in the last twenty years. Therefore, there is a dire need for careful systematic familial cohort studies, especially in high-risk populations. Several immunogenetic factors affect the pathogenesis of the disease. Genes in the human leukocyte antigen (HLA) account for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by destruction of pancreatic β-cells. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for T1D in both children and adults. Although three of the GCC countries, namely Kuwait, Saudi Arabia and Qatar are among the top 10 countries with high incidence rate of T1D, no proper diagnostic and prediction tools were applied in the region. Understanding the disease sequelae in a homogenous gene pool with high consanguinity in the GCC could help solve the challenges in understanding pathogenesis, as well as hasten the prevention of T1D. Arab states must incorporate T1D predictive and intervention policies on a war-footing basis to minimize the burden of this serious disease.

The mechanisms underlying the effects of γ-globulin therapy for bacterial infections are thought to involve bacterial cell lysis via complement activation, phagocytosis via bacterial opsonization, toxin neutralization, and antibody-dependent cell-mediated cytotoxicity. Nevertheless, recent advances in the study of pathogenicity in gram-negative bacteria have raised the possibility of an association between γ-globulin and bacterial toxin secretion. Over time, new toxin secretion systems like the type III secretion system have been discovered in many pathogenic gram-negative bacteria. With this system, the bacterial toxins are directly injected into the cytoplasm of the target cell through a special secretory apparatus without any exposure to the extracellular environment and, therefore, with no opportunity for antibodies to neutralize the toxin. However, because antibodies against the V-antigen, which is located on the needle-shaped tip of the bacterial secretion apparatus, can inhibit toxin translocation, this raises the hope that the toxin might be susceptible to antibody targeting. Because multi-drug resistant bacteria are now prevalent, inhibiting this secretion mechanism is attractive as an alternative or adjunctive therapy against lethal bacterial infections. Thus, it would not be unreasonable to define the blocking effect of anti-V-antigen antibodies as the fifth mechanism for immunoglobulin action against bacterial infections.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Growing evidence suggests that healthcare provider advice may increase tobacco cessation, reduce alcohol use, and improve the adoption of desirable lifestyle behaviors among patients. However, how brief interventions and other provider-patient interactions can shape cumulative adoption of multiple modifiable behaviors is less well studied for diabetes prevention and control. Using weighted internet panel survey data from a large socio-demographically diverse urban population in the United States (n=1,003), the present study describes differences in group characteristics among those who had been “ever diagnosed” with prediabetes/diabetes versus those who had not. It also examines the associations between the cumulative adoption of lifestyle behaviors and each of the following: a) lifetime prediabetes/diabetes diagnosis; b) brief lifestyle intervention exposure (i.e., received provider advice/encouragement); and c) recent provider-patient communication about diabetes. There were several group differences in “ever diagnosed” prediabetes/diabetes status by age, employment status, health status, nutrition knowledge, blood pressure/hypertension diagnosis, and diabetes-related health behaviors (p<0.05). Each of the three provider-patient interactions of interest were positively associated with a higher cumulative sum of adopted modifiable lifestyle behaviors for diabetes prevention and management. Results suggest that provider advice/provider-patient interactions of any type can have a salutary impact on whether individuals with prediabetes or type 2 diabetes will engage in recommended lifestyle behavior modifications.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

Gastric-type endocervical adenocarcinoma (GAS) is a rare non-human papillomavirus associated mucinous adenocarcinoma of the cervix. Its clinical manifestations are extremely atypical, with hidden lesions and difficulty in obtaining materials, resulting in a low positive rate of screening and biopsy. The pathological morphological features are similar to benign lesions, but the biological characteristics are highly malignant, posing great challenges to diagnosis. The preoperative diag-nostic rate is low, which is prone to misdiagnosis and missed diagnosis, leading to delayed treatment and seriously affecting the prognosis of patients. Here，we reported a case of ovarian endometriosis cyst combined with GAS confirmed by surgery and postoperative pathology, with "pelvic mass" as the initial symptom. Through case report and literature review, the characteristics and current re-search progress of GAS were summarized, in order to provide references for diagnosis of GAS, and provide theoretical guidance for formulating reasonable treatment strategy and improving patient prognosis.

Background: Over the past years, there has been a rise in the incidence of type 1 diabetes, partic-ularly among younger individuals. This concerning trend has prompted investigations into po-tential contributing factors, with intestinal dysbiosis emerging as a likely culprit for the escalating annual rates of the disease; (2) Methods: We conducted a retrospective ecologic correlational study involving 37 children from the southern region of Romania between 2019-2021. All participants were within the first six months following the onset of the disease; (3) Results: In the microbiota of the patients we observed a dysbiosis marked by an overabundance of bacteria (Clostridium coccoides, Faecalibacterium, Bacterioides, Enterobacteriaceae) and fungi, compared to the healthy control group. The Spearman correlation revealed a positive association between the presence of Bacteroides (p=0.0442), Butyricicoccus (p=0.0164), and Clostridium leptum (p=0.0023) with recent diabetes onset. Furthermore, a significant correlation was observed between younger age at onset and the pres-ence of Butyricicoccus (p=0.019). The use of antibiotics in the month preceding admission was linked to the presence of fungi in the microbiota (Candida, p=0.0442); (4) Conclusions: The dysbiosis of Romanian type 1 diabetes children correlates with inflammation, more severe onset of the disease and other au-toimmune diseases.

We provide an axiomatic base for the set of natural numbers, that has been proposed as a canonical construction, and use this definition of $\mathbb N$ to find several results on finite group theory. Every finite group $G$, is well represented with a natural number $N_G$; if $N_G=N_H$ then $H,G$ are in the same isomorphism class. We have a linear order, on the quotient space of isomorphism classes of finite groups, that is well behaved with respect to cardinality. If $H,G$ are two finite groups such that $|H|=m<n=|G|$, then $H<\mathbb Z_n\leq G\leq\mathbb Z_{p_1}^{n_1}\oplus\mathbb Z_{p_2}^{n_2}\oplus\cdots\oplus\mathbb Z_{p_k}^{n_k}$ where $n=p_1^{n_1}p_2^{n_2}\cdots p_{k}^{n_k}$ is the prime factorization of $n$. We find a canonical order for the objects of $G$ and define equivalent objects of $G$, thus finding the automorphisms of $G$. The Cayley table of $G$ takes canonical block form, and we are provided with a minimal set of independent equations that define the group. We show how to find all groups of order $n$, and order them. We give examples using all groups with order smaller than $10$, and we find the canonical block form of the symmetry group $\Delta_4$. In the next section, we extend our results to the infinite case, which defines a real number as an infinite set of natural numbers. A real function is a set of real numbers, and a sequence of real functions $f_1,f_2,\ldots$ is well represented by a set of real numbers, as well. In general, we represent mathematical objects using the smallest possible data-type. In the last section, mathematical objects are well assigned to tree structures. We conclude with brief comments on type theory and future work on computational aspects of these representations.

In this paper, a new class of q-Hermite based Frobenius type Eulerian polynomials is introduced by means of generating function and series representation. Several fundamental formulas and recurrence relations for these polynomials are derived via different generating methods. Furthermore, diverse correlations including the q-Apostol-Bernoulli polynomials, the q-Apostol-Euler poynoomials, the q-Apostol-Genocchi polynomials and the q-Stirling numbers of the second kind are also established by means of the their generating functions.

We introduce a new kind of extended Hermite-based Frobenius type Eulerian polynomials and then derive diverse explicit and implicit summation equations including some symmetric formulas by utilizing series manupulation method. Multifarious summation formulas and identities given earlier for some well known polynomials such as Eulerian polynomials and Frobenius type Eulerian polynomials are generalized.

The Global Burden of Disease Study (GBD) 2019 reveals an increasing prevalence of Type 2 Diabetes Mellitus (T2DM) from 1990 to 2019. This study delves into the role of dietary risk factors across different demographic and socioeconomic groups. Utilizing data from the GBD 2019, it analyzes age-adjusted T2DM metrics—death counts, Disability-Adjusted Life Years (DALYs), and Age-Standardized Rates (ASR)—stratified by age, sex, and region. The study employed Estimated Annual Percentage Changes (EAPCs) to track trends over time. Results show that in 2019, 26.07% of T2DM mortality and 27.08% of T2DM DALYs were attributable to poor diets, particularly those low in fruits and high in red and processed meats. Geographic variations in T2DM trends were significant, with regions like Southern Sub-Saharan Africa and Central Asia experiencing the most substantial increases in Age-Standardized Mortality Rate (ASMR) and Age-Standardized DALY Rate (ASDR). A positive correlation was noted between Socio-Demographic Index (SDI) and T2DM burden due to dietary risk factors. The study concludes that targeted public health initiatives promoting dietary changes could substantially reduce the global T2DM burden.

Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

The rapidly evolving field of artificial intelligence (AI) continues to witness the introduction of innovative open-source pre-trained models, fostering advancements in various applications. One such model is Llama 2, an open-source pre-trained model released by Meta, which has garnered significant attention among early adopters. In addition to exploring the foundational elements of the Llama v2 model, this paper investigates how these early adopters leverage the capabilities of Llama 2 in their AI projects. Through a qualitative study, we delve into the perspectives, experiences, and strategies employed by early adopters to leverage Llama 2's capabilities. For the purpose of data analysis, the capabilities inherent in the Llama 2 model were employed to conduct keyword extraction from the context of the early adopters' case studies. The findings shed light on the model's strengths, weaknesses, and areas of improvement, offering valuable insights for the AI community and Meta to enhance future model iterations. Additionally, we discuss the implications of Llama 2's adoption on the broader open-source AI landscape, addressing challenges and opportunities for developers and researchers in the pursuit of cutting-edge AI solutions. The present study constitutes an early exploration of the Llama 2 pre-trained model, holding promise as a foundational basis for forthcoming research investigations.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

In this work, we report the carbon fiber-based wire-type asymmetric supercapacitors (ASCs). The highly conductive carbon fibers were prepared by the carbonized and graphitized process using the polyimide (PI) as a carbon fiber precursor. To assemble the ASC device, the CoMnO2-coated and Fe2O3-coated carbon fibers were used as the cathode and the anode materials, respectively. FE-SEM analysis confirmed that the CoMnO2-coated carbon fiber electrode exhibited the porous hierarchical interconnected nanosheet structures, depending on the added amounts of ammonium persulfate (APS) as an oxidizing agent, and Fe2O3-coated carbon fiber electrode showed a uniform distribution of porous Fe2O3 nanorods over the surface of carbon fibers. The nanostructured CoMnO2 were directly deposited onto carbon fibers by a chemical oxidation route without high temperature treatments. In particular, the electrochemical properties of the CoMnO2-coated carbon fiber with the concentration of 6 mmol APS presented the enhanced electrochemical activity, probably due to its porous morphologies and good conductivity. Further, to reduce the interfacial contact resistance as well as improve the adhesion between transition metal nanostructures and carbon fibers, the carbon fibers were pre-coated with the Ni layer as a seed layer using an electrochemical deposition method. The fabricated ASC device delivered a specific capacitance of 221 F g-1 at 0.7 A g-1 and good rate capability of 34.8% at 4.9 A g-1. Moreover, the wire-type device displayed the superior energy density of 60.16 Wh kg-1 at a power density of 490 W kg-1 and excellent capacitance retention of 95% up to 3,000 charge/discharge cycles.

Researches on flexible thermoelectric (TE) materials usually focus on conducting polymers (CPs) and CP-based composites; however, it is a great challenge to obtain high TE properties comparable to inorganic counterparts. Here, we report an n-type Ag₂Se film on flexible nylon membrane with an ultrahigh power factor ~987.4 ± 104.1 μWm⁻¹K⁻² at 300 K and an excellent flexibility (93% of the original electrical conductivity retention after 1000 bending cycles around a 8-mm diameter rod). The flexibility is attributed to a synergetic effect of the nylon membrane and the Ag₂Se film intertwined with numerous high-aspect-ratio Ag₂Se grains. A TE prototype composed of 4-leg of the hybrid film generates a voltage and a maximum power of 19 mV and 460 nW, respectively, at a temperature difference of 30 K. This work opens opportunities of searching for high performance TE film for flexible TE devices.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

In this work, we introduce a new concepts for $\alpha$-type $F$-Suzuki contraction and $\alpha$-type $F$-weak-Suzuki contraction in the context of $b$-metric spaces. Compared to the $\alpha$-type $F$-contraction and $F$-Suzuki contraction mappings, these contractions are essentially weaker. For these type of contraction mappings, sufficient conditions are established for the fixed point's existence and uniqueness in $b$-metric spaces. As a result, the findings encompass several generalizations. To show the usability of our obtained results, we provide a supportive example and an application to a non-linear differential equation with fractional order.

We address weighted composition operators ψCφ from α-Bloch spaces to Bers-type spaces of bounded holomorphic functions on Y, where Y is a generalized Hua domain of the first kind, and obtain some necessary and sufficient conditions for the boundedness and compactness of those operators.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

The Ni-laterite deposit at the San Felipe plateau, located 30 km northwest of Camagüey, in cen-tral Cuba, is the best example of a clay-type deposit in the Caribbean region. San Felipe resulted from weathering of mantle peridotites of the Cretaceous Camagüey ophiolites. In this study, a geochemical and mineralogical characterization of two profiles (83 and 84) from the San Felipe deposit has been performed by XRF, ICP-MS, quantitative XRPD, oriented aggregate mount XRD, SEM, FE-SEM and EMPA. Core 83 with a length of 23 m, and drilled in the central part of the plateau, presents a notable concentration of cryptocrystalline quartz fragments and a rather poor content in NiO, averaging 0.87% wt. Core 84, which is 12 m long, and drilled at the border of the plateau, lacks silica fragments and presents a higher NiO content, averaging 1.79 %wt. The smectite structural formulae reveal that they evolve from trioctahedral to dioctahedral towards the top of the laterite profiles. Quantitative XRD analyses indicate that smectite is a dominant Ni bearing phase, accompanied by serpentine and minor chlorite. Serpentine, as smectite, is en-riched in the less soluble elements Fe3+, Al and Ni towards the top of the profiles. Core 83 seems to have been affected by collapses, replenishments, whereas core 84 may have remained undis-turbed.

Research on climacteric syndrome among middle-aged men remains scant than the research among women. Research is also scant on climacteric syndrome among older adults living alone, particularly men, who are more vulnerable than such females. This cross-sectional study investigated whether the prevalence of climacteric syndrome is associated with the type of household middle-aged men live in and identified the determinants of climacteric syndrome based on the household type. Six hundred middle-aged men living in multi-person households and 600 living alone were surveyed about general characteristics, diet-related factors, and climacteric syndrome. Data were analyzed using Pearson’s chi-squared test, Fisher’s exact test, and logistic regression. The risk of climacteric syndrome in single-person households was found to be 1.6 times higher than that among in multi-person households (p = 0.006). In multi-person households, income and breakfast frequency predicted climacteric syndrome (p < 0.05), while age, breakfast frequency, dinner frequency, and weekly eating out frequency predicted climacteric syndrome in single-person households (p < 0.05). Thus, dietary factors are more closely linked to the prevalence of climacteric syndrome in single-person households than in multi-person households. This highlights the need for climacteric syndrome interventions for middle-aged men whose health concerns may persist into older adulthood.

Soil aggregates, as the basic component of soil, make great contributions to the stability of soil structure and soil carbon (C) sequestration. Recently, grassland is experiencing continuous grazing, which greatly affects soil aggregation and soil C storage. However, how soil aggregates and soil C in different grassland respond to grazing remain unclear. In this study, three national fenced grassland monitoring field stations which represented mountain meadow (MM), temperate steppe (TS), temperate steppe desert (TSD) were selected, soil samples at 0–10 cm depth of inside and outside the fence were collected to explore the effect of grazing and grassland type on composition, stability and nutrients of soil aggregates. The results showed that the bulk soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), available nitrogen (AN) and available phosphorus (AP) varied greatly among the three grassland types, with the highest values in MM. Soil aggregates composition showed significantly response to both grassland type and grazing, especially the proportion of soil aggregates &gt;2 mm, which significantly decreased 51.68% on average in grazing plots compared with fenced plots, whereas sharply decreased in MM and TSD. A significant decrease (on average 25.08%) of the mean weight diameter (MWD) of soil aggregates under grazing was detected across all grassland types. The effect of grazing on nutrients in macroaggregates (&gt;0.25 mm) was greater than that in microaggregates (&lt;0.25 mm). Aggregate-associated SOC concentration decreased under grazing in MM and TSD, however, SOC density showed different response to grazing across all grassland types, with minor effect on MM, decreasing SOC density in TS and increasing on TSD, respectively. The magnitude of grazing effect size on aggregate-associated SOC varied in different soil particle size, with greater response in aggregates &gt; 2 mm and the biggest value in TDS. In addition, correlation analysis showed that MWD of soil aggregates had significant negative correlation with soil bulk density, but significant positive correlation with SOC, TN and TP concentration. Results of RDA showed that BD, soil nutrients were the main influence factors of the composition and stability of aggregates. Overall, grazing had significant influence on soil aggregation, stability and SOC, played a crucial role in grassland soil stability and the accumulation of SOC.

Mountain summit in Madagascar have generally a specific habitat and that figure home a local endemicity of herpetofauna. Mantidactylus pauliani, a typically aquatic and critically endangered amphibian from Ankaratra Mountain, is among of them. This species inhabits high elevation with restricted distribution range. Our study highlights here a new data of this species and its viability with environmental change. So that, we carried out annual monitoring from 2018 to 2021. Nine fixed transects of 100 m were done along the streams between 1762 and 2378 m a.s.l. We followed the herpetofaunal standard technique for collecting data (systematic ecological niche searching and direct observation), and data analysis was performed using χ² tests and Fac-tor Correspondence Analysis. Here we present the new ecological data of M. pauliani. This spe-cies home between 1900 - 2378 m a.s.l. within the humid forest and savannah habitat. We noticed also a fluctuation in population size and migration to the upper throughout the years across the season, and the stream quality and volume of water variation. This habitat change makes it vul-nerable and the annual bushfire surrounding plays a negative impact. Knowledge and under-standing of its ecological guilds is needed for running and updating conservation activities

Edaravone is a mitochondrially targeted drug with a suggested capability to modify the course of diverse neurological diseases. Nevertheless, edaravone has not been tested yet in the context of spinocerebellar ataxia 1 (SCA1), an incurable neurodegenerative disease characterized mainly by cerebellar disorder with a strong contribution of inflammation and mitochondrial dysfunction. This study aimed to address this gap, exploring the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. SCA1154Q/2Q and healthy SCA12Q/2Q mice were getting either edaravone or saline daily for more than 13 weeks. The functional impairments were assessed via a wide spectrum of behavioral assays reflecting motor and cognitive deficits and behavioral abnormalities. Moreover, we used high-resolution respirometry to explore mitochondrial function, and immunohistochemical and biochemical tools to assess the magnitude of neurodegeneration, inflammation and neuroplasticity. Data were analyzed using (hierarchical) Bayesian regression models combined with the methods of multivariate statistics. Our analysis pointed out various previously documented neurological and behavioral deficits of SCA1 mice. However, we did not detect any plausible therapeutic effect of edaravone on either behavioral dysfunctions or other disease hallmarks in SCA1 mice. Thus, our results did not provide support for the therapeutic potential of edaravone in SCA1.

Polynomial recurrence bounds for a class of stochastic differential equations with a gradient type drift and an additive Wiener process are studied without Lyapunov functions.

(1) Background: There are links between tension-type headache and/or migraine with dysfunctions of the cervical and masticatory muscles and with psychosocial factors. The study aims to highlight the connections between primary headaches, bruxism and psychosocial issues, the effectiveness of a multidisciplinary approach in decreasing the intensity and frequency of the headache episodes and bruxism. (2) Methods: 67 patients with primary headache and bruxism were divided into two equal groups. The subjects attended manual therapy sessions twice a week and a weekly counselling session for three months. (3) Results: an overall comparison before and after three months show a significant decrease of the qualitative variables (tension-type headache, migraine, awake bruxism, limited jaw opening, anxiety and stress) after 3 months. Comparing the efficiency of the procedures after 3 months between the two groups, awake bruxism and perceived stress are significantly different. (4) Conclusions: Although the differences are not radical when comparing MT with MT+C at three months, the patients who received either manual therapy or this treatment combination showed an improvement in pain relief, in the frequency and complexity of their symptoms, a reduction in functional disability and an overall improvement of the quality of their lives after three months of treatment.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that, occasionally, may spread to the central nervous system (CNS), being the most common cause of sporadic encephalitis. One of the main neurovirulence factors of HSV-1 is the protein ICP34.5 that, although initially seemed to be relevant only in neuronal infections, it can also promote viral replication in non-neuronal cells. New ICP34.5 functions have been discovered during the recent years, and some of them have been questioned. This review describes the mechanisms of ICP34.5 to control cellular antiviral responses and debates its most controversial functions. One of the most discussed roles of ICP34.5 is autophagy inhibition. Although autophagy is considered a defense mechanism against viral infections, current evidence suggests that this antiviral function is only one side of the coin. Different types of autophagic pathways interact with HSV-1 impairing or enhancing the infection, and both the virus and the host cell modulate these pathways to tip the scales in its favor. In this review, we will summarize the recent progress on the interplay between autophagy and HSV-1, focusing on the intricate role of ICP34.5 in the modulation of this pathway to gain the battle against cellular defenses.

Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern U.S. and Argentina during 2012-2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

Abstract: The effect of collagen type 1 (Col I) oxidation on Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) remodeling is described as a model for acute oxidative stress. Morphologically, remodeling was presented by a mechanical rearrangement of adsorbed FITC-Col I and a trend for its organization in a fibril-like pattern - a process strongly abrogated in oxidized samples, but without visible changes in cell morphology. The cellular proteolytic activity was quantified in multiple samples utilizing fluorescence de-quenching (FRET effect). In the presence of ADMSCs a significant increase of native FITC-Col I fluorescence was observed, almost absent in the oxidized samples. Parallel studies in cell-free systems confirmed the enzymatic de-quenching of native FITC-Col I by Clostridial collagenase, again showing significant inhibition in oxidized samples. The structural changes in the oxidized Col I was further studied by Differential Scanning Calorimetry: an additional endotherm at 33.6°C along with the typical for native Col I at 40.5°C with sustained enthalpy (∆H) was observed in oxidized samples. Collectively, it has been evidenced that remodeling of Col I by ADMSCs is altered upon oxidation due to the intrinsic changes in the protein structure, thus presenting a novel mechanism for the control of stem cells' behavior toward collagen.

Copper, which can potentially be a highly toxic agent, is an essential nutrient due to its role as a co-factor for cuproenzymes and participation in signaling pathways. In mammals, the liver is a central organ that controls copper turnover throughout the body: copper absorption, distribution, and excretion. In ontogenesis, there are two types of copper metabolism: embryonic and adult, which maintain the balance of copper in each of these periods, respectively. In the liver cells, these types are characterized by specific expression patterns and activity levels of the genes encoding ceruloplasmin, which is the main extracellular ferroxidase and copper transporter and proteins mediating ceruloplasmin metalation. In newborns, the molecular-genetic mechanisms responsible for copper homeostasis and the ontogenetic switch from embryonic to adult copper metabolism are highly adapted to milk ceruloplasmin as a dietary source of copper. In the mammary gland cells, the level of ceruloplasmin gene expression and the alternative splicing of its pre-mRNA govern the amount of ceruloplasmin in milk, and thus, the amount of copper absorbed by the newborn is controlled. In the newborns, absorption, distribution, and accumulation copper are adapted to milk ceruloplasmin. In the newborns, which are not breast-fed at the early stages of postnatal development, the control for alimentary copper balance is absent. We tried to focus on the neonatal consequences of a violation of the balance of copper in the mother / newborn system. Although there is still much to be learned, the time to pay attention to this problem came because the neonatal misbalance of copper may provoke the development of copper related disorders for future life.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

The world is currently going through a serious pandemic of viral infection with SARS-CoV-2, a new isolate of coronavirus, resembling and surpassing the crisis that occurred in 2002 and 2013 with SARS and MERS, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and reaching more than 130 countries worldwide. The very large spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, alarming governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease 2019 (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of patients will need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of elderly individuals, especially those who are more than 60 years old and have comorbidities, including hypertension, diabetes and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow protected and not included as a risk group.Thus, here, we discuss some possibilities of molecular and cellular mechanisms by which elderly subjects may be more susceptible to severe COVID-19. In this sense, we raise two main points: i) increased ACE-2 expression in pulmonary and heart tissue of chronic angiotensin 1 receptor (AT1R) blocker users and hypertensive individuals and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe these are pivotal points for a better understanding of the pathogenesis of severe COVID-19 and must be addressed with attention by physicians and scientists in the field.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Newly characterising 245 Italian and Albanian HCV-2 NS5B sequences collected between 2001 and 2016 was used to reconstruct the origin and dispersion pathways of HCV-2c. The tree of a subset of these sequences aligned with 247 publicly available sequences was reconstructed in spatio-temporal scale using the Bayesian approach, and the effective replication number (Re) was estimated using the birth-death model. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania, and that GT2 originated in Guinea Bissau in the XVI century and spread to Europe in the XX century. The HCV-2c subtype had two internal nodes respectively dating back to the 1930s and 1950s having as most probable locations Ghana and Italy, respectively. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in both Italy between the 1950s and 1980s, and Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from Africa at the time of the second Italian colonisation (1936-1941), but did not reach Albania until the period of dramatic migration to Italy in the 1990s.