Type A acute aortic dissection are associated with significant morbidity and mortality with prompt referral imaging and management to tertiary referral centres needed urgently. Surgery is usually needed emergently but the choice of surgery often varies depending on the patient and presentation. Staff and center expertise also play a major role in determining the surgical strategy employed The aim of this study is to compare early and medium term outcomes of patient across 3 European referral centers. We also identified risk factors for poorer outcomes irrespective of surgical strategy employed. A retrospective study was conducted across 3 sites between January 2008 and December 2021. 601 patients were included within the study of which 30% were female and the median age was 64.4 years. The most common operation was ascending aorta replacement (n= 246, 40.9%). The aortic repair was extended proximally (i.e., root n= 105; 17,5%) and distally (i.e., arch n = 250; 41,6%). A more extensive approach, extending from the root to the arch, was employed in 24 patients (4.0%). Operative mortality occurred in 146 patients (24.3%), and the most common morbidity was stroke (75, 12.6%). An increased length of ICU admission was noted in the extensive surgery group who were younger and more frequently male No significant differences were noted in surgical mortality from patients managed with extensive surgery vs those managed conservatively. However, age, arterial lactate levels, “intubated/sedated” status on arrival, and “emergency or salvage” status at presentation were independent predictors of mortality both within the index hospitalization and also during follow-up. Overall survival was similar between the groups.

Abstract: Type A acute aortic dissection is a serious condition within the acute aortic syndromes that demands immediate treatment. Despite advancements in diagnostic and referral pathways, the survival rate post-surgery currently sits at almost 20%. Our objective was to pinpoint clinical indicators for mortality and morbidity, particularly raised arterial lactate as a key factor for negative outcomes. Methods: All patients referred to the three cardiovascular centres between January 2005 and December 2022 were included in the study. The inclusion criteria required the presence of a lesion involving the ascending aorta, symptoms within 7 days of surgery, and referral for primary surgical repair of TAAAD based on recommendations, with consideration for other concomitant major cardiac surgical procedures needed during TAAAD and retrograde extension of TAAAD. We conducted an analysis of both continuous and categorical variables and utilized predictive mean matching to fill in missing numeric features. For missing binary variables, we used logistic regression to impute values. We specifically targeted early postoperative mortality and employed LASSO regression to minimize potential collinearity of over-fitting variables and variables measured from the same patient. Results: 633 patients were recruited for the study, out of which 449 patients had complete preoperative arterial lactate data. The average age of the patients was 64 years, and 304 patients were male (67.6%). The crude early postoperative mortality rate was 24.5% (110 out of 449 patients). The mortality rate did not show any significant difference when comparing conservative and extensive surgeries. However, malperfusion had a significant impact on mortality [48/131 (36.6%) vs 62/318 (19.5%), p<0.001]. Preoperative arterial lactates were significantly elevated in patients with malperfusion. The optimal prognostic threshold of arterial lactate for predicting early postoperative mortality in our cohort was ≥ 2.6 mmol/L. Conclusion: The arterial lactate concentration in patients referred for TAAAD is an independent factor for both operative mortality and postoperative complications. In addition to mortality, patients with an upper arterial lactate cut-off of ≥2.6 mmol/L face significant risks of VA ECMO and the need for dialysis within the first 48 hours after surgery. To improve recognition and facilitate rapid transfer and surgical treatment protocol, more diligent efforts are required in the management of malperfusion in TAAAD.

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p&lt;0.001). Accordingly, cardiopulmonary bypass (p&lt;0.001), cross-clamping (p&lt;0.001) and DHCA times (p&lt;0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p&lt;0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.

Objective: Type I interferon receptor (IFNAR) signaling contributes to several autoimmune and vascular diseases such as atherosclerosis and stroke. The purpose of this study was to assess the influence of IFNAR1 deficiency on the formation and progression of experimental abdominal aortic aneurysms (AAAs). Methods: AAAs were induced in type I interferon receptor subunit 1 (IFNAR1) deficient and wild type control male mice via intra-infrarenal aortic infusion of porcine pancreatic elastase. Immunostaining for IFNAR1 was evaluated in experimental and clinical aneurysms. The initiation and progression of experimental AAAs was assessed via ultrasound imaging prior to (day 0) and 3-, 7-, and 14-days following elastase infusion. Aneurysmal histopathology was analyzed at sacrifice. Results: Increased aortic medial and adventitial IFNAR1 expression was present in both clinical AAAs harvested at surgery and experimental AAAs. Following AAA initiation, wild type mice experienced progressive, time-dependent infrarenal aortic enlargement. This progression was substantially attenuated in IFNAR1 deficient mice. On histological analyses, medial elastin degradation, smooth muscle cell depletion, leukocyte accumulation and neoangiogenesis were markedly diminished in IFNAR1 deficient as compared to wild type mice. Conclusion: IFNAR1 deficiency limited experimental AAA progression in response to intra-aortic elastase infusion. Combined with clinical observations, these results suggest a regulatory role for IFNAR1 activity in AAA pathogenesis.

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study conducted from January 2017 to June 2018. One-hundred and four consecutive patients with DM2 were given lateral lumbar X-rays in order to quantify aortic abdominal calcification AAC. Circulating levels of AGEs and classical cardiovascular risk factors were determined. Clinical history was also registered. Patients with higher AGEs values had higher grades of aortic calcification and higher number of diabetic related complications. Multivariate logistic regression analysis showed that being older, male and having high levels of AGEs and triglycerides were the independent risk factors associated to moderate-severe AAC when compared to no-mild AAC. Our results suggest that AGEs plays a role in the pathogenesis of aortic calcifications. In addition, the measurement of AGEs levels may be useful for assessing the severity of AAC in the setting of diabetic complications.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

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.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

This paper evaluates the feasibility of applying Massive MIMO to tackle the uplink mixed-service communication problem. Under the assumption of an available physical narrowband shared channel (PNSCH), devised to exclusively consume data traffic from Machine Type Communications (MTC) devices, the capacity (i:e:, number of connected devices) of MTC networks and, in turn, that of the whole system, can be increased by clustering such devices and letting each cluster share the same time-frequency physical resource blocks. Following this research line, we study the possibility of employing sub-optimal linear detectors to the problem and present a simple and practical channel estimator that works without previous knowledge of the large-scale channel coefficients. Our simulation results suggest that the proposed channel estimator performs asymptotically as well as the MMSE estimator with respect to the number of antennas and the uplink transmission power. Furthermore, the results also indicate that, as the number of antennas is made progressively larger, the performance of sub-optimal linear detection methods approaches the perfect interference-cancellation bound. The findings presented in this paper shed light on and motivate for new and exciting research lines towards a better understanding of the use of massive MIMO in MTC networks.

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.

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.

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.

Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.

The microwave field is used for drying and disinfection of grain, during pre-sowing seed treat-ment. The use of a microwave field in these installations leads to an increase in their productivity and a decrease in the energy consumed by them. One of the principal problems of microwave field use for treatment of dense grain layers is to insure sufficient distribution uniformity of the field. In this article, waveguide design options have been discussed that serve to introduce microwave radiation into the grain layer. Mathematical simulation of the electromagnetic field distribution was performed with the use of CST Microwave Studio software in order to evaluate and compare horn-type, rectangular and semicircular waveguides. The data on the standing wave ratio and radiation efficiency for these types of waveguides have been reported. Specific features of the microwave electromagnetic field distribution and radiation power in the output of those wave-guides have been described. Results of mathematical simulations enabled to make out that sem-icircular waveguides with slot-type radiators are preferable for processing dense grain layers.

Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of type 2 diabetic patients with MCI are linked to sarcopenia and/or its criterion remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, BMI, duration of diabetes, hypertension, dyslipidemia, smoking, drinking, eGFR, HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This is the first study to show that slow walking speed is a sole determinant for the presence of MCI in patients with type 2 diabetes. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

Type-2 diabetes mellitus is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage Type 2 diabetes mellitus is widely documented. These dietary compounds exert their beneficial effects by several actions, including the protection of pancreatic islet β-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorating diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type-2 diabetes patients.

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.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes is attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of pro-inflammatory chemokines; CCL1, 2, 4 and 5 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a normal control group were enrolled. The demographic data, serum levels CCL-1, 2, 4 and 5 and the biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). n controls. We observed that male and female control patients had similar mean serum concentrations of pro-inflammatory chemokines CCL 1, 2, 4, and 5. Chemokines CCL1, CCL2, and CCL4 in the serum of Type 2 Diabetes Mellitus patients with normal or overweight body weights were significantly higher than the control group, regardless of gender. In T2DM individuals with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL1, 2, and 4 in T2DM) patients with increasing BMI. Serum CCL5 levels increased significantly in all T2DM patient groups. The increase in CCL5 was more predominant in normal-weight people as compared to overweight and obese T2DM patients. Conclusions. Male and female control patients had similar serum levels of pro-inflammatory chemokines CCL 1, 2, 4, and 5. The progressive rise in blood concentrations of three Pro-inflammatory chemokines; CCL1, 2, and 4 in T2DM patients with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM patient groups. The selective and more pronounced increase of CCL5 in the T2DM group with normal BMI as compared to patients with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 under-expression in overweight and obese T2DM patients is due to some unexplained counterbalancing processes.

In this paper, we introduce a general family of Lagrange-based Apostol-type Hermite polynomials thereby unifying the Lagrange-based Apostol Hermite-Bernoulli and the Lagrange-based Apostol Hermite-Genocchi polynomials. We also define Lagrange-based Apostol Hermite-Euler polynomials via the generating function. In terms of these generalizations, we find new and useful relations between the unified family and the Apostol Hermite-Euler polynomials. We also derive their explicit representations and list some basic properties of each of them. Some implicit summation formulae and general symmetry identities are derived by using different analytical means and applying generating functions.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically-based lipid disorder with the underestimated actual prevalence. In the recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. However, there is not enough data on their use in real-world clinical implementation. We studied the applicability of the most accessible biochemical algorithms to diagnose FD in clinical practice. We also investi-gated the prevalence of FD in one of the European regions of Russia based on a population sample. In this study there was detected a high prevalence of FD: 1 in 151. We demonstrated that the diagnostic algorithms of FD including a diagnostic apoB levels require correction, taking into account the characteristics of the distribution of apoB levels in the population. At the same time a triglycerides cutoff ≥1.5 mmol/L may be a useful tool in identifying subjects with FD. We also analyzed the presence and pathogenicity of APOE variants associated with the autosomal dominant FD in a large research sample.

Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.

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.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia means low bone regeneration and a chronic inflammatory response. The purpose of the study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on 5 groups of white female Wistar rats: group 1 - regeneration of a bone defect in healthy animals under a blood clot; group 2 - regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3 - bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4 - filling of a bone defect with a CH-SA-HA construct in healthy animals; Group 5 - filling of a bone defect CH-SA-HA in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

In this study, a graphene-doped porous silicon (G-doped/p-Si) substrate for low ppm H₂ gas detection by an inexpensive synthesis route was proposed as a potential noble graphene-based gas sensor material and to understand the sensing mechanism. The G-doped/p-Si gas sensor was synthesized by a simple capillary force-assisted solution dropping method on p-Si substrates, whose porosity was generated through an electrochemical etching process. G-doped/p-Si was fabricated with various graphene concentrations and exploited as a H₂ sensor operated at room temperature. The sensing mechanism of the sensor with/without graphene decoration on p-Si was proposed to elucidate the synergetic gas sensing effect generated from the interface between the graphene and p-type silicon.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

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.

Background: Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (Dio3) is present in immune cells but there is no description of its presence in this patients. Here we aimed to determine the prognostic impact of thyroid hormones levels (TH) measured on ICU admission on mortality and on evolution to chronic critical illness (CCI) and the presence of D3 in white cells. Methods: Prospective cohort study with a follow-up for 28 days or deceased. Results: Low T3 levels at admission were present in 86.5% of the patients. Dio3 was 55% induced in immune cells. The cut-off value of 60 pg/mL for T3 displayed a sensitivity and specificity of 81% and 64% for predicting death, odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 and 0.75 for mortality and evolution to CCI, respectively, thus displaying better performance than commonly used prognostic scores. Conclusions: We advance in the pathophysiology of low T3 showing induced D3 in immune cells during sepsis. Low T3 levels independently predicted a progression to CCI and mortality within 28 days in sepsis and septic shock.

Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta-cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well-established that genetic and environmental factors contribute to the initiation and progression of type 1 diabetes, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with type 1 diabetes pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage type 1 diabetes.

Accurate measurement of solid precipitation (S) has a critical importance for proper understanding of the Earth’s hydrological cycle, validation of emerging technologies and weather prediction models, and developing parameterizations of severe weather elements such as visibility (Vis). However, measuring S is still a challenging problem mainly because of wind effects. The wind effects are normally mitigated by using a Double-Fence Automated Reference (DFAR) system to reduce the wind speed (Ug). To contribute towards addressing some of these issues we have analyzed data sets collected at a site located in Southern Ontario, Canada using several instruments. The instruments include two Geonor gauges, one placed inside a DFAR (SDFAR) and the other inside a double Alter shield (DASG), a Pluvio2 gauge inside a single Alter shield (SASP), a HotPlate, a PARSIVEL2 Disdrometer that measures S and fall velocity (V), and a FD12P senor that measures S and type and Vis. The results show that for the Ug observed in this study (Ug &lt; 6 ms-1), both DASG and SASP have similar collection efficiency (CE) of near 70%. The transfer functions (TF) for DASG and SASP as a function of Ug and also Ug, and V have been derived. The TF for the DASG that includes both Ug and V showed better agreement with observation than just Ug alone. The S measured using all the other instruments were correlated well with SDFAR, but the PARSIVEL2 and FD12P overestimated and underestimated the snow amount respectively as compared the SDFAR. However, the HotPlate captured similar amount of S as the SDFAR. According to this study, the SDFAR showed good correlation with Vis.

In this article, we establish some new generalized inequalities of Hilbert-type on time scales delta calculus which considered as similar formulas for inequalities of Hilbert type proved by Chang-Jian, Lian-Ying and Cheung [7]. These inequalities will proved by applying Hölder’s inequality, chain rule on time scales and the mean inequality. As special cases of our results (when T = N and T = R), we get the discrete and continuous inequalities. Also, we can obtain other inequalities in different time scale, like T = q^Z, q > 1.

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.

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.

Windows account for a significant proportion of the total energy lost in buildings. The interaction of window type, Window-to-Wall Ratio (WWR) scheduled and window placement height would influence the natural lighting and heat transfer through windows. This is a pressing issue for non-tropical regions considering their high emissions and distinct climatic characteristics. A limitation exists in the adoption of common simulation-based optimisation approaches in the literature, which are hardly accessible to practitioners. This article develops a numerical-based window design optimisation model using a common Building Information Modelling (BIM) platform adopted throughout the industry, focusing on non-tropical regions of Australia. Three objective functions are proposed; the first objective is to maximize the available daylight, and the other two emphasize on the undesirable heat transfer through windows in summer and winter respectively. The developed model is tested on a case study located in Sydney, Australia, and a set of Pareto-optimum solutions is obtained. Through the use of the proposed model, energy savings of up to 16.43% are achieved. Key findings on the case example indicate that leveraging winter heat gain to reduce annual energy consumption should not be the top priority when designing windows for Sydney.

Buildings’ thermal energy needs are inherently linked to climate conditions. Consequently, it is crucial to evaluate how climate changes affect these energy demands. Despite extensive analysis, a comprehensive assessment involving a diverse range of building types has not been consistently conducted. The primary objective of this research is to perform a coherent evaluation of the influence of climate changes, construction element properties, and the Heating, Ventilation, and Air Conditioning (HVAC) system type of control on the energy requirements of six buildings (residential, services, and commercial). The buildings are considered located in a temperate Mediterranean climate. Our focus is on the year 2070, considering three distinct climatic scenarios: (i) maintaining the current climate without further changes, (ii) moderate climate changes, and (iii) extreme climate changes. The buildings are distributed across three different locations, each characterized by unique climatic conditions. Buildings’ envelope features a traditional External Thermal Insulation Composite System (ETICS) and expanded polystyrene (EPS) serves as thermal insulation material. Two critical design factors are explored: EPS thickness ranging from 0 (no insulation) to 12 cm; and horizontal external fixed shading elements varying lengths from 0 (absence) to 150 cm. Six alternative setpoint ranges are assessed for the HVAC system control: three based on the Predicted Mean Vote (PMV) and three based on indoor air temperature (Tair). Results were obtained with a validated in-home software tool. They show that, even under extreme climate conditions, the application of thermal insulation remains energetically favorable, however its relative importance diminishes as climate severity increases. Then, proper insulation design remains important for energy efficiency. The use of external shading elements for glazing (e.g., overhangs, louvers) proves beneficial in specific cases. As climate changes intensify, the significance of shading elements grows. Thus, strategic placement and design are necessary for good results. The HVAC system’s energy consumption depends on the level of thermal comfort requirements, on the climate characteristics and on the building’s type of use. As climate change severity intensifies, energy demands for cooling increase, while energy needs for heating decrease. However, it’s essential to recognize that the impact of climate changes on HVAC system energy consumption significantly depends on the type of building.

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well-documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates diagnosed at Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between October 5, 2020, and November 5, 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD=6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. Types of DM were statistically significant with some neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusion: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. Early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

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.

Mangifera indica (mango), a member of the Anacardiaceae family, is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, antiviral, cardiotonic, hypotensive, and anti-inflammatory effects. The present study delves the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin (STZ)-induced type 2 diabetic rats, concurrently investigating its phytoconstituents. EEMI's effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. It’s enzymatic inhibitory properties on carbohydrate digestion, glucose absorption, and free radicals were investigated using starch digestion, glucose diffusion and DPPH assay methods. In-vivo parameters including lipid profile and liver glycogen content were assessed on streptozotocin-induced type 2 diabetic rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake, oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL and HDL levels were observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugar. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes.

In this article, the biocatalytic oxidation of ethanol into acetaldehyde was studied using a catalase entrapped within monolithic polyampholyte cryogel, p(APTAC-co-AMPS), derived from an anionic monomer, 2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt (AMPS), and a cationic monomer, (3-acrylamidopropyl) trimethylammonium chloride (APTAC) as catalyst. Macroporous polyampholyte cryogels containing various amounts of catalase were synthesized in situ under cryo-polymerization conditions at a molar ratio of monomers [APTAC]:[AMPS] = 75:25 mol.% in the presence of 10 mol.% cross-linking agent, N,N-methylenebisacrylamide (MBAA). The conversion of ethanol into acetaldehyde in good-to-high yields was observed in flow-through and batch type reactors under optimal conditions: at T = 10-20 C, pH = 7.1, [C2H5OH]:[H2O2] = 50:50 vol.%. According to SEM image the pore sizes of p(AMPS-co-APTAC) cryogel vary from 15 to 55 μm. The catalytic activity of catalase entrapped within monolithic polyampholyte cryogel in the conversion of ethanol into acetaldehyde was evaluated through the determination of such kinetic parameters as Michaelis constant (Km), the maximum enzymatic rate (Vmax), activation energy (Ea), turnover number (TON) and turnover frequency (TOF). The catalase encapsulated within monolithic polyampholyte cryogel exhibits a high conversion of ethanol into acetaldehyde. The advantages and disadvantages of flow-through and batch type reactors were highlighted.

Not only does this paper present a novel type-2 fuzzy system for identification and behavior prognostication of an experimental solar cell set and a wind turbine, but also it brings forward an exquisite technique to acquire an optimal number of membership functions and the corresponding rules. It proposes a seven-layered NCPRT2FS. For fuzzification in the first two layers, Gaussian type-2 fuzzy membership functions with uncertainty in the mean, are exploited. The third layer comprises rule definition and the forth one embeds fulfillment of type reduction. The three last remained layers are the ones in which resultant left–right firing points, two end-points and output all get assessed correspondingly. It should not be neglected off the nutshell that recurrent feedback at the fifth layer exerts delayed outputs ameliorating efficiency of the suggested NCPRT2FS. Later in the paper, a modern structural learning, established on type-2 fuzzy clustering, is held forth. An adaptively rated learning back-propagation algorithm is extended to adjust the parameters ensuring the convergence as well. Eventually, solar cell photo-voltaic and wind turbine are deemed as case studies. The experimental data are exploited and the consequent yields emerge so persuasive.

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.

(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.

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.

Introduction: Type 2 diabetes (T2D) is a major driver of health care costs, thus treatments enabling T2D reversal may reduce expenditures. We examined the impact of a T2D continuous care intervention (CCI) on health care utilization. Previous research documented that CCI, including individualized nutrition supported by remote care, simultaneously reduced hemoglobin A1c and medication use and improved cardiovascular status after two years; however, the impact on utilization is unknown. Methods: This study used four years of data (two years pre-intervention, two years post-intervention) from the Indiana Network for Patient Care (INPC) health record. Two methods estimated the impact of CCI on utilization. First, an interrupted time series (ITS) including only CCI participants (n=193) compared post-intervention utilization to expected utilization had the pre-intervention trend persisted. Deviation from the trend was estimated non-parametrically for each 6-month interval after the implementation of CCI . Second, a 1:3 matched comparator group (n=579) was constructed and used for a difference-in-differences (DiD) analysis. The primary outcome was annualized outpatient encounters. Secondary outcomes included emergency encounters and hospitalizations. Results: In two years prior to intervention, CCI participants had a mean of 5.77 annualized encounters (5.62 outpatient, 0.04 hospitalizations, 0.11 emergency). The CCI group showed a reduction in outpatient utilization after intervention. In ITS analysis, 1.6 to 1.9 fewer annualized outpatient encounters occurred in each 6-month interval post-intervention relative to expected utilization based on pre-intervention trends (p<0.01 each 6-month period; 28-33% reduction). The DiD analysis suggested a larger reduction; 5 fewer annualized outpatient encounters in the quarter after intervention, diminishing to 2.5 fewer after 2 years (p<0.01 each quarter). The study was underpowered to draw conclusions about hospitalization and emergency encounters due to the limited number of CCI patients and the rarity of encounters. Conclusions: Outpatient encounters were significantly reduced for a T2D patient population up to 2 years after receiving an individualized intervention supporting nutrition and behavior change through remote care.

Glucose is the primary energy fuel used by the brain and is transported across the blood-brain barrier (BBB) by the glucose transporter type 1 and 2.[1] A GLUT1 genetic defect is responsible for glucose transporter type 1 deficiency syndrome (GLUT1DS). Patients with GLUT1DS may present with pharmaco-resistant epilepsy, developmental delay, microcephaly, and/or abnormal movements, with tremendous phenotypic variability. Diagnosis is made by the presence of specific clinical features, hypoglycorrhachia and an SLC2A1 gene mutation. Treatment with a ketogenic diet therapy (KDT) is the standard of care as it results in production of ketone bodies which can readily cross the BBB and provide an alternate energy source to the brain in the absence of glucose. KDTs have been shown to reduce seizures and abnormal movements in children diagnosed with GLUT1DS. However, little is known about the impact of KDT on cognitive function, seizures and movement disorders in adults newly diagnosed with GLUT1DS and started on a KDT in adulthood, or the appropriate ketogenic diet therapy to administer. This case report demonstrates the potential benefits of using a modified Atkins diet (MAD), a less restrictive ketogenic diet therapy on cognition, seizure control and motor function in an adult with newly-diagnosed GLUT1SD.

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.

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.

Type-2 fuzzy sets were introduced by L. Zadeh aiming at modelling some settings in which fuzzy sets (usually called type-1 fuzzy sets) are not sufficient to reflect certain uncertainty degrees - loosely speaking, they are fuzzy sets whose membership degrees are ordinary fuzzy sets. On the other hand, fiber bundles are topological entities of extreme importance in Mathematics itself and many other scientific areas, like Physics (General Relativity, Field Theory etc.), finance modelling, and statistical inference. The present work introduces a conceptual link between the two ideas and conjectures about the potential mutual benefits that can be obtained from this viewpoint.As an objective and usable product of the presented ideas, it is described a framework for defining type-2 fuzzy hedges, proper to operate on interval type-2 fuzzy sets.

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.

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

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.

In this paper, the problem of predicting future failure times based on a jointly type-II censored sample from k exponential populations is considered. The Bayesian prediction intervals and point predictors were then obtained. Generalized Bayes is a Bayesian study based on a learning-rate parameter. This study investigated the effects of the learning rate parameters on the prediction results. The loss functions of squared error, Linex, and general entropy were used as point predictors. Monte Carlo simulations were performed to show the effectiveness of the learning rate parameter in improving the results of prediction intervals and point predictors.

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.

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.

This study presents a vibration control using actively tunable vibration absorbers (ATVA) to suppress vibration of a thin plate. The ATVA’s is made of a sandwich hollow structure embedded with the electrorheological fluid (ERF). ERF is considered to be one of the most important smart fluids and it is suitable to be embedded in a smart structure due to its controllable viscosity property. ERF’s apparent viscosity can be controlled in response to the electric field and the change is reversible in 10 microseconds. Therefore, the physical properties of the ERF-embedded smart structure, such as the stiffness and damping coefficients, can be changed in response to the applied electric field. A mathematical model is difficult to be obtained to describe the exact characteristics of the ERF embedded ATVA because of the nonlinearity of ERF’s viscosity. Therefore, a fuzzy modeling and experimental validations of ERF-based ATVA from stationary random vibrations of thin plates are presented in this study. Because Type-2 fuzzy sets generalize Type-1 fuzzy sets so that more modelling uncertainties can be handled, a semi-active vibration controller is proposed based on Type-2 fuzzy sets. To investigate the different performances by using different types of fuzzy controllers, the experimental measurements employing type-1 fuzzy and interval type-2 fuzzy controllers are implemented by the Compact RIO embedded system. The fuzzy modeling framework and solution methods presented in this work can be used for design, performance analysis, and optimization of ATVA from stationary random vibration of thin plates.

Dysregulation of the angiotensin-II Type-I receptor (AT1R) and its pathway was reported to associate with poor-prognosis in several malignancies, including colorectal-cancer (CRC). We have explored the therapeutic-potential of targeting AT1R using valsartan, and its pharmacological-interaction with Fluorouracil (5-FU) in CRC. Anti-proliferative function was evaluated in 2-/3-dimensional cells and in vivo models. Anti-proliferative, anti-migratory, apoptotic function and effect on cell-cycle was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing test, and Fluorescence-activated cell sorting (FACS), respectively, while gene-expression was determined at mRNA/protein levels. By histogical analysis and measuring of oxidative/antioxidant markers, we evaluated the anti-inflammatory properties of valsartan. Valsartan suppressed cell-growth and impacted the anti-tumor-activities of 5-FU by apoptosis-induction. Valsartan inhibited the cells migration by perturbation of Matrix metalloproteinase (MMP1). Furthermore, valsartan inhibited tumor-growth and metastasis, and this was more notable in valsartan/5-FU combination-treated-group. The mechanism was plausible to be via the induction of Reactive-oxygen-species (ROS) and down-regulation of Superoxide-dismutase (SOD), thiol/catalase (CAT) as well as Vascular endothelial growth factor (VEGF) and Transforming growth factor beta (TGF-β). Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory components include fibronectin, Interleukin) IL-1β (, Tumor necrosis factor alpha) TNF-α (, Interferon gamma) INF-γ (, and Monocyte Chemotactic Protein 1 (MCP-1). Our findings demonstrated that targeting the AT1R receptor may inhibit tumor-growth and ameliorate fibrosis and inflammation associated with CRC via modulation of AT1 and TGF-β pathways.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be routinely captured through standard surveillance activities. This study aimed to characterize the prevalence and demographic profile of dyslipidemia in T2D patients in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and blood tests. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (p = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (p = .013 and p = .036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (p = .029 and p = .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Diversity-generating retroelements (DGRs) are prokaryotic systems providing rapid modification and adaptation of target proteins. In phages, the main targets of DGRs are receptor-binding proteins that are usually parts of tail structures and the variability of such host-recognizing structures enables phage adaptation to changes on the bacterial host surface. Sometimes, more than one target gene containing a hypermutated variable repeat (VR) can be found in phage DGRs. The role of mutagenesis of two functionally different genes is unclear. In this study, several phage genomes that contain DGRs with two target genes were found in the gut virome of healthy volunteer. Bioinformatics analysis of these genes indicated that they encode proteins with different topology; however, both proteins contain the C-type lectin (C-lec) domain with a hypermutated beta-hairpin on its surface. One of the target proteins belongs to a new family of proteins with a specific topology: N-terminal C-lec domain followed by one or more immunoglobulin domains. Proteins from the new family were named tentaclins after TENTACLe+proteIN. The genes encoding such proteins were found in the genomes of prophages and phages from the gut metagenomes. We hypothesized that tentaclins are involved in binding either to bacterial receptors or intestinal/immune cells.

The transition of people from paediatric to adult diabetes services is associated with worsening glycaemia and increased diabetes-related hospitalisation. This study compared the clinical characteristics of those with and without mental health conditions among attenders at a diabetes young adult clinic diabetes before and after changes in service delivery. Retrospective review of 200 people with diabetes attending a Sydney public hospital over eight years corresponding to the period before (2012-2016) and after (2017-2018) restructuring of a clinic for young adults aged 16-25 years. Characteristics of those with and without mental health conditions (depression, anxiety, diabetes related distress, eating disorders), were compared. Among clinic attenders (type 1 diabetes n=184, 83.2%), 40.5% (n=89) had a mental health condition particularly, depression (n=57, 64%), which was higher among Indigenous than non-Indigenous people (5.6% vs 0.8% p=0.031) but similar between diabetes type. Over eight years, those with, compared with those without a mental health condition had higher HbA1c at the last visit (9.4%[79 mmol/mol] vs 8.7% [71 mmol/mol], p=0.027), the proportion with diabetic ketoacidosis (DKA 60.7% vs 42.7%,p=0.009), smoking (38.4 vs 13.6%,p=0.009), retinopathy (9.0 vs 2.3%,p=0.025), multiple DKAs (28.4 vs 16.0%,p=0.031) were significantly higher. Having a mental health condition was associated with 2.02 (95% Confidence intervals 1.1-3.7) fold increased risk of HbA1c ≥ 9.0%[75mmol/mol]. Changes to the clinic were not associated with improvements in mental health condition (39.0% vs 32.4%, p=0.096). In conclusion, we found that mental health conditions, particularly depression, are common in this population and are associated with diabetes complications. Diabetes type and clinic changes did not affect the reported mental health conditions. Additional strategies are required to reduce complication risks among those with mental health conditions. .

Motivation by the definition of the type 2 poly-Bernoulli polynomials introduced by Kim-Kim [9], in the present paper, we consider a new class of new generating function for the Fubini polynomials, called the type 2 poly-Fubini polynomials by means of the polyexponential function. Then, we derive some useful relations and properties. We show that the type 2 poly-Fubini polynomials equal a linear combination of the classical of the Fubini polynomials and Stirling numbers of the first kind. In a special case, we give a relation between the type 2 poly-Fubini polynomials and Bernoulli polynomials of order r. Moreover, inspired by the definition of the unipoly-Bernoulli polynomials introduced by Kim-Kim [9]. We introduce the type 2 unipoly-Fubini polynomials by means of unipoly function and give multifarious properties including derivative and integral properties. Furthermore, we provide a correlation between the unipoly-Fubini polynomials and the classical Fubini polynomials.

Mountain systems within the Mediterranean region, e.g. the Pyrenees, are very sensitive to climate change. In the present study, we quantified the magnitude of extreme precipitation events and the number of days with torrential precipitation (daily precipitation ≥ 100 mm) in all the rain gauges available in the Pyrenees for the 1981-2015 period, analyzing the contribution of the synoptic scale in this type of events. The easternmost (under the Mediterranean influence) and north-westernmost (under Atlantic influence) areas of the Pyrenees registered the highest number of torrential events. The heaviest events are expected in the eastern part, i.e. 400 mm day-1 for a return period of 200 years. Northerly advections over the Iberian Peninsula, which present a low zonal index, i.e. im-plying a stronger meridional component, give rise to torrential events over the western Pyrenees; and easterly advections favour extreme precipitation over the eastern Pyrenees. The air mass travels a long way, from the east coast of North America, bringing heavy rainfall to the western Pyrenees. In the case of the torrential events over the eastern Pyrenees, the air mass causing the events in these areas is very short and originates in the Mediterranean Basin. The NAO index has no influence upon the occurrence of torrential events in the Pyrenees, but these events are closely related to certain Mediterranean teleconnections such as the WeMO

This paper presents a novel DQ-based multicarrier Pulse Width Modulation PWM for a single-phase, three-level PV-powered grid-connected F-type inverter. The main control objective in the proposed inverter is to regulate the grid current with low total harmonic distortion and load power components compensation. Despite the F-type inverter’s advanced advantages, there are only a few works addressing the control issue in the literature yet. The proposed control and switching methods aim to achieve both DC side voltage balance and lowest switching losses. The proposed scheme has been designed based on a modified multi-carrier PWM switching algorithm. Consequently, the proposed control method able to satisfy the requirements of DC side voltage balance and achieve lower switching losses. A further advantage of the proposed control and switching methods is that they retain the main advantage of the F-Type inverter, which is that only 25% of the power switches are exposed to full DC voltage. This is an important advantage since it reduces the overall cost of the inverter and improves its reliability. Overall, the proposed modified multi-carrier PWM switching algorithm appears to be a promising approach for controlling the F-Type inverter, offering improved performance and efficiency compared to other control methods. The theoretical model was verified through simulation using MATLAB/Simulink. According to the simulation results, the grid current and dc capacitor voltages are successfully managed in all operational situations.

Background: The number of people with type 2 diabetes is increasing daily, and therefore effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1 ≥ 7%) on different oral or basal insulin supported oral therapy were recruited from the diabetes outpatient clinic, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA naive and consequently prescribed 0.5 or 1.0 mg once weekly injectable semaglutide (IS) or 7 mg or 14 mg once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglo-bin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and sec-ondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥ 5% and ≥ 10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS -1.1% vs OS -1.4%, p=0.126) and weight loss (IS -6.50 kg vs OS -5.90 kg, p=0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥ 5% (56.7%, n=30). A weight loss ≥ 10% was observed in 20.7% (n=11) of participants administered IS and 15.1% (n=8) of participants adminis-tered OS, respectively (p=0.454). Conclusion: In a real-world setting, oral semaglutide as add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated the same effectiveness as injectable semaglutide in terms of gly-cemic control and weight loss after 6 months of treatment.

Lifestyle interventions halt the progression of prediabetes to frank type 2 diabetes (T2D). However, the feasibility of a diabetes prevention program promoting tailored interventions on a national scale and conducted by primary care physicians is unclear. To explore this issue, general practitioners dislocated in ten different regions throughout Italy enrolled random subjects without known metabolic diseases to identify individuals with prediabetes and prescribe them an intervention based on physical activity. Using a simple stepwise approach, people referring to their primary care physician for any reason were screened for their diabetes risk with a web-based app of the Findrisc questionnaire. Those at risk for T2D, i.e. with a Findrisc score > 9, were invited to come back after overnight fasting to measure fasting glycaemia (FG). Those with 100 ≤ FG < 126 mg/dL were considered as people with prediabetes and compiled the Physical Activity Readiness Questionnaire (PAR-Q) to then receive a personalized prescription of physical activity. Overall, 5928 people were enrolled and compiled the questionnaire. Of these, 2895 (48.8 %) were at risk for T2D. Among these, FG was measured in 2168 subjects (participation rate 75%). The numbers of individuals with undetected prediabetes and T2D according to FG were 755 and 79 (34.8% and 3.6% of those assessing FG), respectively. Of the 755 subjects in the prediabetes range, 739 compiled the PAR-Q and started a personalized program of physical activity (participation rate 97%). Physicians involved in the study reported a mean of 6 minutes to perform the screening. Overall, these data suggest the feasibility of a national diabetes prevention program developed by general practitioners using a simple stepwise approach starting from a web-app to intercept individuals with prediabetes.

Abstract Objectives: The purpose of this study was to determine whether breast cancer and diabetes status are related in adult Americans. Methods: We conducted a cross-sectional study of 7,599 individuals from the National Health and Nutrition Examination Survey (NHANES). Diabetes was classified as type 2 diabetes and pre-diabetes. Both prediabetes and diabetes were diagnosed according to ADA 2014 guidelines. Multiple logistic regression analysis was used to explore the relationship between diabetes status and breast cancer. Results: We found that prediabetes (OR = 0. 60, 95% CI:(0. 40, 0. 88), P= 0. 009613) and non-diabetes (OR = 0.05.3,95% CI: (0.34, 0.83), P = 0. 006014) were associated with a reduced risk of breast cancer in comparison to Type 2 diabetes (literature). Prediabetes in non-Hispanic blacks was associated with a reduced risk of breast cancer (OR=0. 55,95%CI:0. 40-0. 75, P<0. 001). Using two segmented linear regression models to fit the relationship between BMI and breast cancer, we found that the relationship between BMI and breast cancer was nonlinear, but there was a threshold effect. The threshold effect analysis found that BMI affcted breast cancer at an inflection point 26. 3 Kg/m2. Adjusted OR (95% CI) on both sides of the turning point was 1. 0799 ( 1. 0029, 1. 1629 ) and 0. 9873 ( 0. 9638, 1. 0115 ), respectively. Conclusions: Diabetes status is associated with the risk of breast cancer development. Moreover, the risk of developing breast cancer steadily increased from nondiabetes to prediabetes and type 2 diabetes. In addition, the prevalence of breast cancer showed a gradual increase withincreasing BMI up to 26. 3 Kg/m2 with the highest prevalence of breast cancer. There was an inverse U-shaped relationship between BMI and the breast cancer prevalence.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Background: Obesity and diabetes are two metabolic disorders linked by an inflammatory process named insulin resistance (IR). Various research on the role of gut microbiota in developing obesity and its associated disorders has led to the growing interest in probiotic supplementation. Considering the life-threatening complications of diabesity this mini-review explored the effects of probiotic supplementation on IR in obesity-associated diabetes. Method: This review is based on recent articles from 2005-2020, studying the role of probiotic supplementation on glucose and insulin parameters in healthy and diabetic mouse models. Result: Probiotic supplementation altered the gut microbiota composition, increased short-chain fatty acid production, and decreased pro-inflammatory cytokines. Additionally, they decreased intestinal permeability, circulating lipopolysaccharide, and metabolic endotoxemia hence improved insulin sensitivity and reduced obesity. Although multi-strain probiotic supplementation showed greater benefits than single strain interventions, variations in the concentration of probiotics used and the duration of treatment also influenced the results. Conclusion: Probiotic supplementation could manipulate the gut microbiota by reducing intestinal permeability, inflammation and ameliorate IR and obesity-associated diabetes in animal models which requires further long-term clinical studies in humans.

Importance: p53 is an unequivocal tumor suppressor altered in half cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: The focus of this systemic review and meta-analysis is on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed, MBase and Cochrane from 1993 reporting the first study until May 2021. Study Selection: Studies were included that met the following criteria: 1) participants with cancer; 2) outcome results expressed in relation to the presence of a p53 antibody; 3) a primary outcome (disease free survival, overall survival or progression free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: 1) insufficient data available to evaluate outcomes; 2) animal studies; 3) studies with less than 10 participants. 1333 potentially relevant articles; studies as duplicates, non-patients studies or reviews were excluded. After viewing the titles and abstracts of the 52 remaining studies, the full texts of 34 studies were retrieved and 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird-method) depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population size of patients with solid tumors, as determined before data collection. Results: In total 12 clinical studies and of which 2094 patients were included and it was determined that p53-wt Abs expression in the serum significantly correlated with a worse survival of cancer patients (95% CI 1.48 [1.24, 1.77]; p<0.00001). On the contrary, data from literature indicated that there was a potential association between p53-mut Abs antibodies with better survival. Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients, predicting a worse outcome. The serum-p53 value (s-p53-value) could be useful for future theranostics.

Lectins are carbohydrate-interacting proteins playing a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through the carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensor for capturing and identification of bacterial species. In this work, we have characterized the bacterial agglutination properties of three C-type lectins from the Lepidoptera Spodoptera exigua. One of these lectins, BLL2, was able to agglutinate cells from a broad range of bacterial species at an extremely low concentration, becoming a very interesting protein to be used as biosensor or other biotechnological applications involving bacterial capturing.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels. Despite the availability of pharmacological treatments, dietary plans, and exercise regimens, T2DM remains a significant global cause of mortality. Consequently, there is a growing interest in exploring lifestyle interventions, such as Intermittent Fasting (IF). This study aims to identify underlying patterns and principles for effectively improving T2DM risk parameters through IF. By analyzing data from multiple randomized clinical trials investigating various IF interventions in humans, a machine learning algorithm was employed to develop a personalized recommendation system. This system advises pre-diabetic and diabetic individuals on the most suitable IF interventions to improve T2DM risk parameters. With a success rate of 95%, this recommendation system offers highly tailored guidance, optimizing intermittent fasting's benefits for diverse population subgroups. The results of this study allow us to conclude that weight is the crucial feature for females, while age is the determining factor for males to reduce glucose levels in blood. By revealing patterns in diabetes risk parameters among individuals, this study not only provides practical guidance but also sheds light on the underlying mechanisms of T2DM, contributing to a deeper understanding of this complex metabolic disorder.

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades and the identification of differential glycemic responders can aid tailored treatment for prevention of pre-diabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among partic-ipants with elevated T2DM risk, to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary inter-vention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females, 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distin-guish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.

High hepcidin is linked to low-grade inflammation and lower iron levels. The consequence of testosterone replacement therapy (TRT) on inflammation and risk of cardiovascular disease (CVD) is undetermined. We investigate the effect of TRT on the inflammatory cardiovascular risk markers hepcidin-iron, fibroblast growth factor 23 (FGF23)-phosphate-klotho, and calprotectin pathways. Methods: A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n=20) or placebo gel (n=19) for 24 weeks. We included 39 men (50─70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed by DXA- and MRI-scans; main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. Results: Hepcidin levels decreased during TRT (β=-9.5 ng/mL, P<0.001), lean body mass (β=1.9 kg, P=0.001) increased, and total fat mass (β=-1.3 kg, P=0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. Conclusions: During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

Misuse of measurement units and orientations leads to errors in scientific applications, Cyber Physical Systems (CPS), and IoT C/C++ programs. Standard type system are inadequate in preventing such errors. Although dimensional and orientational analysis in physics can manually detect these errors in equations, analyzing complex code with intricate physical computations is impractical. To overcome this challenge, we propose an advanced type system that incorporates units and orientations as integral components within a specialized type library. Our enhanced type system automatically detects potential errors during compile time by representing physical quantities as types and utilizing dimensional analysis, orientational analysis, and metaprogramming techniques. Our improved type system enables formal verification of C++ software, successfully verifying programs with extensive codebases. We also employ it for runtime verification of dynamic linking and pointer operations in C++ programs. The integration of compile-time verification, dimensional analysis, orientational analysis, and advanced type system enhances the robustness and accuracy of scientific applications, CPS, and IoT C/C++ programs. By leveraging these approaches, we ensure precise calculations and prevent errors related to measurement units and orientations, resulting in substantial improvements in reliability and accuracy.

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.

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, we extensively discussed about bioprinting endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

In this paper, we study the well-posedness and asymptotic behaviour of solutions to a laminated beam in thermoelasticity of type III. We first give the well-posedness of the system by using the semigroup method. Then, we show that the system is exponentially stable under the assumption of equal wave speeds. Furthermore, it is proved that the system is lack of exponential stability for case of nonequal wave speeds. In this regard, a polynomial stability result is proved.

1) Background: A survey of biogenic amines profile in opened wine bottles has been established. Opened bottles of red and white wine were submitted to different temperature as well as different kind of stopper (screw cap, cork stopper) and use of vacuum devices. A total of six wine made from different variety of grapes were obtained from Polish vineyard places in different region of Poland; 2) Results: DLLME-GC-MS procedure for biogenic amines determination was validated and applied for wine samples analysis. The total content of BAs in white wines ranged from 442 µg/L to 929 µg/L, while in red wines ranged from 669 µg/L to 2244 µg/L the set of just opened wine samples. The most abundant biogenic amines in the six analysed wines were histamine and putrescine; 3) Conclusion: Considering the commercial availability of the analysed wines, there was no relationship between the presence of biogenic amines in a given wine and their availability on the market. However, it was observed that the different storage conditions employed in this experiment affect not only the biogenic amines profile, but also the pH. The results were confirmed by chemometric analysis.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

This work is mainly focused on improving the differential evolution algorithm with the utilization of shadowed and general type 2 fuzzy systems to dynamically adapt one of the parameters of the evolutionary method. In this case, the mutation parameter is dynamically moved during the evolution process by using a shadowed and general type-2 fuzzy systems. The main idea of this work is to make a performance comparison between using shadowed and general type 2 fuzzy systems as controllers of the mutation parameter in differential evolution. The performance is compared with the problem of optimizing fuzzy controllers for a D.C. Motor. Simulation results show that general type-2 fuzzy systems are better when higher levels of noise are considered in the controller.

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.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

The need for antiserum for immunohistochemical (IHC) detection of enterovirus (EV) in formaldehyde fixed and paraffin-embedded (FFPE) specimens is increasing. The standard monoclonal antibody against EV-envelope protein (VP1), clone 5D8/1, was proven to cross-react with other proteins. Another candidate marker of EV proteins is 2A protease (2Apro), which is coded by the EV gene and translated by host cells during EV replication. We raised polyclonal antiserum by immunizing rabbits with an 18-mer peptide of Coxsackievirus B1 (CVB1)-2A protease (2Apro) and examined the specificity and sensitivity for EV on FFPE tissue samples. ELISA study showed a high titer of antibody for CVB1-2Apro. IHC demonstrated that antiserum against 2Apro reacted with CVB1-infected Vero-cells. Confocal microscopy demonstrated that 2Apro labelled by the antibody located in the same cell with VP1 stained with 5D8/1. IHC demonstrated dense positive reactions pancreatic islets of EV-associated fulminant type 1 diabetes (FT1DM), and located in the same cell stained positive with 5D8/1. Specificity of IHC staining FT1DM pancreas was confirmed by absorption with an excessive concentration of immunized peptide. In conclusion, our study provides a new polyclonal antiserum against CVB1 2Apro which may be useful for detection of EV-infected human tissues stored as archive of FFPE tissue samples.

We enriched and isolated a novel gammproteobacterial methanotroph; strain FWC3, from tropical freshwater wetland, near Nagaon beach, Alibag, India. FWC3 is a coccoid, flesh pink/peach pigmented, non-motile methanotroph and the cells are present in pairs and as tetracocci. The culture can grow on methane (20%) as well as on a wide range of methanol from concentrations (0.02%-5%). Based on the comparison of genome data, FAME analysis, morphological characters and biochemical characters, FWC3 belongs to the tentatively and newly but not validly described genus ‘Methylotetracoccus’ of which only a single species strain was described, Methylotetracoccus oryzae C50C1. The ANI index between FWC3 and C50C1 strains is 94%, and the DDH value is 55.7%, less than the cut-off values 96% and 70%, respectively. The genome size of FWC3 is smaller (3.4 Mbp) compared to that of C50C1 (4.8 Mbp). Additionally, the FAME profile of FWC3 shows differences in cell wall fatty acid profiles compared to Methylotetracoccus oryzae C50C1. Also, there are other differences on the morphological, physiological and genomic levels. We propose FWC3 to be a member of a novel species of the genus Methylotetracoccus, for which the name Methylotetracoccus aquaticus is proposed. Also, an amended description of the genus Methylotetracoccus gen. nov. is given here. FWC3 is available in two international culture collections with the accession numbers: MCC 4198 (Microbial Culture collection, India) and JCM 33786 (Japan Collection of Microorganisms, Japan).

Diabetes may cause an increase blood levels of cytokines inducing a rising of C reactive protein (PCR) and fibrinogen stimulating a subclinical inflammation which lead to adhesive molecules expression and to endothelial disfunction. A comprehensive panel of type 1 diabetes mellitus (T1DM) interleukins polymorphisms is not provided yet. As chronic periodontitis (CP) is considered the sixth complication of DM, a clarification is needed about the inflammatory role managed by single nucleotides polymorphisms (SNPs). The goal of this review is to focus on the significant diversity of SNPs in T1DM patients with and without CP. After a digital search on PubMed and Scopus with reference to the last 5 years, 21 items were enrolled. Several ILs were analyzed. T1DM still needs to be thoroughly explored regarding the ILs polymorphisms panel, however the last 5 years have led to the increased independence of this condition, causing autonomous inflammatory effects which requires further investigations. CP and T1DM association in children and adolescents represents a severe gap in literature that should be filled, the scarce presence of studies also about adults serves as a motivation for ulterior clinical researches

Machine Learning (ML) and Artificial Intelligence(AI) have revolutionized almost all fields that are linked to the acquisition of intelligent behavior in the real world. It is an attractive alternative for a researcher of artificial intelligence. Contrary to rule-based programming, ML is an algorithmic approach in which learning comes from existing data. The more data we have these computer systems look at, we say we’re ‘training’ the computer system, and as the computers begin to identify patterns in the data, identify abnormalities in the data from these abnormalities we improve the system architect according to the requirement. This article introduces the use of comprehensive concepts of machine learning, in general, particular, and their potential applications in communications. Furthermore, the current state and futuristic potentials of enabling universal communication with implications of machine learning methods have been explained. In this review paper, we offer a comprehensive talk on distinctive methods/techniques of information analytics, artificial intelligence (AI), and machine learning (ML) moved forward the contact aware communication system.

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.

Testicular granulosa cell tumors (TGCTs) are rare tumors of sex cord stromal origin. TGCTs can be classified into the adult type and the juvenile type. The adult type is extremely rare with only 93 known cases reported in the literature. We, herein, present a report of a case of a 30 year old male patient who presented with a testicular mass, underwent radical inguinal orchiectomy and the pathology examination revealed an adult type granulosa tumor. We additionally review the literature to summarize the scientific knowledge of an entity barely described worldwide.

This article develops dual variational formulations for a large class of models in variational optimization. The results are established through basic tools of functional analysis, convex analysis and duality theory. The main duality principle is developed as an application to a Ginzburg-Landau type system in superconductivity in the absence of a magnetic field. In the first sections, we develop new general dual convex variational formulations, more specifically, dual formulations with a large region of convexity around the critical points which are suitable for the non-convex optimization for a large class of models in physics and engineering. Finally, in the last section we present some numerical results concerning the generalized method of lines applied to a Ginzburg-Landau type equation.

The glucose-insulin regulatory system and its glucose oscillations is a recurring theme in the literature because of its impact on human lives, mostly the ones affected by diabetes mellitus. Several approaches were proposed, from mathematical to data-based models, with the aim of modeling the glucose oscillation curve. Having such a curve, it is possible to predict, when injecting insulin in type 1 diabetes (T1D) individuals. However, the literature presents prediction horizons no longer than 6 hours, which could be a problem considering their sleeping time. This work presents Tesseratus, a model that adopts a multi-agent approach to combine machine learning and mathematical modeling to predict the glucose oscillation up to 8 hours. Tesseratus uses the pharmacokinetics of insulins and data collected from T1D individuals. Its outcome can support endocrinologists while prescripting daily treatment for T1D individuals, and provide personalized recommendations for such individuals, to keep their glucose concentration in the ideal range. Tesseratus brings pioneering results for prediction horizons of 8 hours for nighttime, in an experiment with seven real T1D individuals. It is our claim that Tesseratus will be a reference for classification of glucose prediction model, supporting the mitigation of short- and long-term complications in the T1D individuals.

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.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

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.

Recent reports suggest that the clinical course of coronavirus disease 2019 (COVID-19) in previously healthy children is usually milder as compared to adults. However, children with comorbid conditions such as diabetes are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as morbidity and mortality due to COVID-19. Experience in adults with diabetes shows that they are prone to faster metabolic decompensation, develop diabetes-related complications, and have a poor prognosis when hospitalized with COVID-19. Data on children are limited. The aim of this mini-review is to discuss the possible risks to children and adolescents with diabetes during the current pandemic and the special considerations in management in those affected with COVID-19. The challenges for children who develop new-onset type 1 diabetes during the COVID-19 lockdown, especially in accessing healthcare, are also discussed.

Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids respectively, was confirmed by western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate.

Milroy's disease (MD), also known as hereditary lymphedema type I, is a rare autosomal dominantly inherited primary lymphedema. It accounts for approximately twenty percent of all primary lymphedemas. MD typically presents clinically with bilateral lower extremity lymphedema. Our case report is about a rare case of MD presenting with unilateral lymphedema in both upper and lower extremities in a patient admitted to our clinic. A 24-year-old woman who had been under observation for lymphedema since she was 8 years old was diagnosed with MD by physical examination, venous Doppler ultrasound, whole body lymphoscintigraphy, and molecular genetic testing in our clinic, and partial improvement was achieved with Complete Decongestive Therapy, the gold standard treatment for lymphedema. Genetic counseling services may be especially useful for the patient and family. Although MD is rarely seen in the literature, many more studies are needed to identify carrier variants in the community.