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Introduction: Diabetic neuropathy (DN) is a generic term for various neuropathies coexisting in a single patient. Clinical diagnosis alone can be misleading, yet routine electrodiagnostic studies in diabetes care are rare. Skin autofluorescence (SAF) is a recognized DN risk factor with potential screening value. This article highlights the diagnostic challenges and raises awareness of the often underdiagnosed neuropathic conditions in diabetes patients. Material and Methods: We present common entrapment neuropathy cases from our diabetes clinic's electrodiagnosis laboratory in Iași, Romania. We selected seven type 2 diabetes patients with sensory or sensory-motor distal polyneuropathy and atypical DN presentations investigated through electroneurography (ENG) and electromyography (EMG) with the Neurosoft® EMG instrument and SAF measured by standard procedures. Subsequently, a narrative literature review was conducted. Results: Entrapment neuropathies were diagnosed in all the patients: three carpal tunnel syndromes, two ulnar neuropathies (one proximal, one distal), one peroneal neuropathy, and one case of meralgia paresthetica. The lower-limb cases showed radiculoplexopathy, and there was one case of superficial radial nerve neuropathy. The SAF values ranged from 2.5 AU to 3.4 AU. Conclusions: Electrodiagnosis is essential for detecting focal neuropathies in patients with sensory-motor distal polyneuropathy. Elevated SAF levels may correlate with symptom severity, although further research, including large cohorts, is needed. [ABSTRACT FROM AUTHOR]

Background: The long-term effect of the 2019 coronavirus (COVID-19) pandemic is not fully known. Severe cases of COVID-19 have resulted in disability that can be assessed in a biopsychosocial manner with the International Classification of Functioning, Disability and Health with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire. This study aimed to evaluate the long-term effects on disability of COVID-19 three years after post-acute rehabilitation using WHODAS 2.0. Methods: This single-center cohort study included patients with severe COVID-19 who underwent immediate post-discharge post-acute rehabilitation intervention. Three years later, patients were assessed via telephone using the WHODAS 2.0 questionnaire. Results: Of the 69 patients identified in the hospital database, 27 responded. A total of 16 patients refused to respond due to emotional distress. The mean age was 63.4 ± 8.6 years, 81.5% were independent in the community, 55.3% had been previously admitted to the ICU, and the median rehabilitation hospitalization duration was 18 (11.5,24) days. Comorbidities included type 2 diabetes mellitus (DM) (55.5%), grade 2 high blood pressure (62.9%), pressure ulcers (37%), peripheral neurologic deficits (62.9%), and central neurological deficits (14.8%). ICU admission was significantly correlated with advanced rehabilitation needs (measured by the level of the rehabilitation (p < 0.01) and longer hospitalizations (measured by total days in the hospital (p < 0.001). The overall disability score was 35.09%, significantly influenced by DM and central neurological deficits. Conclusions: Central neurological deficits and DM are associated with higher disability scores. Tailored rehabilitation programs, ongoing medical assessment, integrated care models, and patient education are essential for improving long-term outcomes after COVID-19 disease. [ABSTRACT FROM AUTHOR]

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection. This study aimed to develop a deep learning model that automatically detects and segments CELs in clinical Magnetic Resonance Imaging (MRI) scans. A 3D UNet-based network was trained with clinical MRI from the Swiss Multiple Sclerosis Cohort. The dataset comprised 372 scans from 280 MS patients: 162 showed at least one CEL, while 118 showed no CELs. The input dataset consisted of T1-weighted before and after gadolinium injection, and FLuid Attenuated Inversion Recovery images. The sampling strategy was based on a white matter lesion mask to confirm the existence of real contrast-enhancing lesions. To overcome the dataset imbalance, a weighted loss function was implemented. The Dice Score Coefficient and True Positive and False Positive Rates were 0.76, 0.93, and 0.02, respectively. Based on these results, the model developed in this study might well be considered for clinical decision support. [ABSTRACT FROM AUTHOR]

The production of citric acid, a vital agricultural commodity utilized across various industries such as food, beverages, pharmaceuticals, agriculture, detergents, and cosmetics, predominantly relies on microbial fermentation, with Aspergillus niger accounting for approximately 90% of global production. In this study, we aimed to optimize the key factors influencing citric acid production, with a focus on strains, fermentation techniques, and carbon sources, particularly sugarcane molasses. A. niger, sourced from the Botany department/Biotechnology laboratories at Govt. College of Science, Lahore, was employed for citric acid production. The process involved inoculum preparation through spore collection from 3 to 5 days of cultured PDA slants. The fermentation medium, comprising cane molasses with a 15% sugar concentration, was meticulously prepared and optimized for various factors, including magnesium sulfate, potassium ferrocyanide, time of addition of potassium ferrocyanide, ammonium oxalate, and calcium chloride. Our optimization results shed light on the significant impact of different factors on citric acid production. For instance, the addition of 0.4 g/L magnesium sulfate led to a maximum yield of 75%, while 2 g/L potassium ferrocyanide, added at 24 h, achieved a yield of 78%. Remarkably, ammonium oxalate, at a concentration of 10 g/L, resulted in a notable 77% yield. Conversely, the addition of calcium chloride exhibited negligible effects on citric acid production, with the control group yielding more at 78%. Our study underscores the potential for optimizing factors to enhance citric acid production by A. niger in submerged fermentation. These findings highlight the pivotal role of magnesium sulfate, potassium ferrocyanide, and ammonium oxalate in augmenting citric acid yields while emphasizing the minimal impact of calcium chloride. Ultimately, these insights contribute to advancing our understanding of microbial citric acid biosynthesis, providing valuable implications for industrial applications and future research endeavors. [ABSTRACT FROM AUTHOR]

The genus Trichoderma holds economic significance due to its widespread distribution and diverse applications, including biological control, enzyme production, and various biotechnological uses. The accurate identification of Trichoderma species is crucial given their close association with human activities. Despite previous efforts in classification, a comprehensive analysis combining morphological and molecular approaches is necessary. This study focuses on the isolation of four Trichoderma species from industrial wastewater in Pakistan, expanding on the known diversity in the region; isolation involved collecting samples from industrial wastewater effluents at specific sites in Punjab, Pakistan. Trichoderma strains were cultured and purified on solid media, with subsequent biomass production for bisorptional activity. Morphological characterization included colony features and microscopic examinations. DNA extraction, polymerase chain reaction (PCR), and sequencing of the internal transcribed spacer (ITS) region were conducted for molecular analysis. Phylogenetic analysis was performed using the Maximum Likelihood Algorithm. The study identified three Trichoderma species, viz. T. citrinoviride, T. erinaceum, and T. longibrachiatum. Each species was characterized morphologically and supported by molecular–phylogenetic analysis. Illustrations of microscopic features and a phylogenetic tree based on the ITS-nrDNA region were recorded. T. citrinoviride and T. longibrachiatum, isolated from steel mill and tanneries wastewater, respectively, were differentiated based on morphological characteristics such as phialides and conidia. The combination of morphological and molecular techniques enhances the accuracy of species identification. The study highlights the significance of Trichoderma in industrial wastewater environments and underscores the need for continued research in this area. Future research should focus on exploring the ecological roles and potential applications of the newly identified Trichoderma species. Additionally, further investigations into the biotechnological potential of these species, including enzyme production and bioremediation capabilities, would contribute to their practical applications. [ABSTRACT FROM AUTHOR]

Background: Individuals diagnosed with type 2 diabetes mellitus (T2DM) are more prone to experiencing severe cardiovascular (CV) events, often occurring at a younger age, due to a complex interplay of risk factors. T2DM diagnosis inherently classifies patients as belonging to a higher CV risk group. In light of the increased susceptibility to severe CV outcomes, our study aims to assess the distribution of CV risk categories and the attainment of therapeutic targets among Romanian patients diagnosed with T2DM. Methods: A cross-sectional analysis was performed, including 885 patients diagnosed with T2DM who were consecutively admitted to a secondary care hospital unit between January and July 2019. Data collection included demographics, lipid profile, glycated hemoglobin (HbA1c), blood pressure (BP), estimated glomerular filtration rate (eGFR), and medication specifics for T2DM and associated conditions. Patients were stratified into CV risk categories based on the ESC/EAS guidelines, encompassing moderate, high, and very high risk categories. The rationale for selecting these guidelines for CV risk categories was that they were current and provided best practice recommendations for T2DM patients during the cross-sectional evaluation. We assessed therapeutic target achievement rates for LDL-C, HbA1C, and BP for each CV risk category. Additionally, we examined utilization rates of statins and novel cardio- and reno-protective, non-insulin antidiabetic medications. Results: The group's average age was 62.9 ± 7.7 years and comprised 53.7% females. An average HbA1c level of 7.1 ± 1.3% was observed in the group. Within the cohort, 83% had hypertension, with a mean systolic BP of 132 ± 16.2 mm Hg and mean diastolic BP of 80 ± 9.6 mm Hg. Additionally, 64.6% of patients were obese, with a mean body mass index of 32.3 ± 5.3 kg/m2. Mean LDL-C levels varied across the different CV risk categories: 106.6 ± 35.6 mg/dL in the very high risk category, 113 ± 39.3 mg/dL in the high risk category, and 124.3 ± 38.3 mg/dL in the moderate risk category. Most treatment schemes included metformin (87.0%) and statins (67.0%), with variable use rates for other glucose-lowering and CV risk-modifying therapies. The percentage of patients using GLP-1 RAs was 8.1%, while 3.9% used SGLT2 inhibitors. Conclusions: Most Romanian patients with T2DM are at very high or high CV risk. Despite reaching glycemic control targets, most patients are not achieving the composite target, which includes, besides glycemic control, BP values and lipid profile. Many patients with T2DM are not benefiting from DM therapies with additional cardiorenal benefits or statins. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), due to its long-term hyperglycemia, leads to the accumulation of advanced glycation end-products (AGEs), especially in the vessel walls. Skin autofluorescence (SAF) is a non-invasive tool that measures AGEs. DM patients have a rich dietary source in AGEs, associated with high oxidative stress and long-term inflammation. AGEs represent a cardiovascular (CV) risk factor, and they are linked with CV events. Our objective was to assess whether SAF predicts future CV events (CVE) by examining its association with other CV risk factors in patients with type 2 DM (T2DM). Additionally, we assessed the strengths and limitations of SAF as a predictive tool for CVE. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we conducted a systematic review with CRD42024507397 protocol, focused on AGEs, T2DM, SAF, and CV risk. We identified seven studies from 2014 to 2024 that predominantly used the AGE Reader Diagnostic Optic tool. The collective number of patients involved is 8934, with an average age of 63. So, SAF is a valuable, non-invasive marker for evaluating CV risk in T2DM patients. It stands out as a CV risk factor associated independently with CVE. SAF levels are influenced by prolonged hyperglycemia, lifestyle, aging, and other chronic diseases such as depression, and it can be used as a predictive tool for CVE. [ABSTRACT FROM AUTHOR]

Advanced Glycation End Products (AGEs) contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) and cardiovascular (CV) diseases (CVDs), making their non-invasive assessment through skin autofluorescence (SAF) increasingly important. This study aims to investigate the relationship between SAF levels, cardiovascular risk, and diabetic complications in T2DM patients. We conducted a single-center, cross-sectional study at Consultmed Hospital in Iasi, Romania, including 885 T2DM patients. The assessment of SAF levels was performed with the AGE Reader™, (Diagnoptics, Groningen, The Netherlands). CVD prevalence was 13.9%, and according to CV risk category distribution, 6.1% fell into the moderate-risk, 1.13% into the high-risk, and 92.77% into the very-high-risk category. The duration of DM averaged 9.0 ± 4.4 years and the mean HbA1c was 7.1% ± 1.3. After adjusting for age and eGFR, HbA1c values showed a correlation with SAF levels in the multivariate regression model, where a 1 SD increase in HbA1c was associated with a 0.105 SD increase in SAF levels (Nagelkerke R2 = 0.110; p < 0.001). For predicting very high risk with an SAF cut-off of 2.35, sensitivity was 67.7% and specificity was 56.2%, with an AUC of 0.634 (95% CI 0.560–0.709, p = 0.001). In T2DM, elevated SAF levels were associated with higher CV risk and HbA1c values, with 2.35 identified as the optimal SAF cut-off for very high CV risk. [ABSTRACT FROM AUTHOR]

(1) Background: The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a tool designed to measure disability in accordance with the International Classification of Functioning, Disability and Health. Measuring disability is becoming increasingly important due to its high prevalence, which continues to rise. Rehabilitation interventions can reduce disability and enhance functioning. (2) Objective: The present study aims to assess the impact of rehabilitation interventions on reducing disability, as measured by the WHODAS 2.0 questionnaire. It also seeks to identify which specific rehabilitation interventions are more effective and to explore other disability assessment questionnaires. (3) Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology, we conducted a systematic review, with the protocol registered with the identifier CRD42023495309, focused on "WHODAS" and "rehabilitation" using PubMed and Web of Science electronic databases. (4) Results: We identified 18 articles from various regions encompassing patients with various health conditions, related to stroke, the cardiovascular system (cardiovascular disease, chronic heart failure), the pulmonary system (chronic obstructive pulmonary disease), the neurologic system (Parkinson's disease, cerebral palsy, neurodegenerative disease), the musculoskeletal system (orthopaedic surgery), cancer, and chronic pain, and among frail elderly. These patients have received a wide range of rehabilitation interventions: from conventional therapy to virtual reality, robot-assisted arm training, exergaming, and telerehabilitation. (5) Discussion and Conclusions: A wide range of rehabilitation techniques can effectively improve disability with various comorbidities, offering numerous benefits. The WHODAS 2.0 questionnaire proves to be an efficient and reliable tool for measuring disability, and scores have a tendency to decrease after rehabilitation. [ABSTRACT FROM AUTHOR]

In this paper, we aim to evaluate the efficacy of antidiabetic cardioprotective molecules such as Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) and Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) when used with other glucose-lowering drugs, lipid-lowering, and blood pressure (BP)-lowering drugs in a real-life setting. A retrospective, observational study on 477 patients admitted consecutively in 2019 to the outpatient clinic of a tertiary care unit for Diabetes Mellitus was conducted. Body mass index (BMI), blood pressure (BP) (both systolic and diastolic), and metabolic parameters, as well as A1c hemoglobin, fasting glycaemia and lipid profile, including total cholesterol (C), HDL-C, LDL-C and triglycerides), were evaluated at baseline and two follow-up visits were scheduled (6 months and 12 months) in order to assess the antidiabetic medication efficacy. Both SGLT-2i and GLP-1 RAs were efficient in terms of weight control reflected by BMI; metabolic control suggested by fasting glycaemia and A1c; and the diastolic component of BP control when comparing the data from the 6 and 12-month visits to the baseline, and when comparing the 12-month visit to the 6-month visit. Moreover, when comparing SGLT-2i and GLP-1 RAs with metformin, there are efficacy data for SGLT-2i at baseline in terms of BMI, fasting glycaemia, and HbA1c. In this retrospective study, both classes of cardioprotective molecules, when used in conjunction with other glucose-lowering, antihypertensive, and lipid-lowering medications, appeared to be efficient in a real-life setting for the management of T2DM. [ABSTRACT FROM AUTHOR]

The increasing prevalence of gestational diabetes mellitus (GDM) requires non-invasive and precise techniques for evaluating the predisposing risk factors such as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). According to PRISMA, we developed a systematic review and searched after "visceral adipose tissue AND gestational diabetes" and identified 221 articles on the MEDLINE and Word of Science databases. After assessing them for inclusion criteria and two researchers screened them, 11 relevant articles were included. Although evidence is conflicting, more studies favor using US-determined VAT in GDM prediction. VAT may be more valuable than body mass index or SAT in predicting GDM. VAT can represent an additive factor to the prediction tool of the risk of developing GDM when used in conjunction with other anthropometric or biological parameters or maternal risk factors. US measurements are heterogeneous given different evaluation techniques, cut-off values and inter-operator variation. A significant limitation is the lack of a gold standard to identify GDM confidently. Pregnant women may benefit from early monitoring and preventive care if classified as high risk for GDM early in the gestational period. US-measured VAT during the first trimester of pregnancy seems a valuable and inexpensive screening approach to predict GDM development later in pregnancy, either by itself or if used in conjunction with other clinical and biological parameters. [ABSTRACT FROM AUTHOR]

Our previous work demonstrated that vitamin D (VitD) reduces experimental autoimmune encephalomyelitis (EAE) disease severity in wild-type (WT) but not in T cell-specific glucocorticoid (GC) receptor (GR)-deficient (GRlck) mice. This study aimed to investigate the interplay between the GR- and VitD receptor (VDR) signaling. In vivo, we confirmed the involvement of the GR in the VitD-induced effects in EAE using WT and GRlck mice. Furthermore, we observed that VitD-enhanced T cell apoptosis and T regulatory cell differentiation are diminished in vitro in CD3+ T cells of GRlck but not WT mice. Mechanistically, VitD does not appear to signal directly via the GR, as it does not bind to the GR, does not induce its nuclear translocation, and does not modulate the expression of two GR-induced genes. However, we observed that VitD enhances VDR protein expression in CD3+ T cells from WT but not GRlck mice in vitro, that the GR and the VDR spatially co-localize after VitD treatment, and that VitD does not modulate the expression of two VDR-induced genes in the absence of the GR. Our data suggest that a functional GR, specifically in T cells, is required for the VDR to signal appropriately to mediate the therapeutic effects of VitD. [ABSTRACT FROM AUTHOR]

Supplements and diets containing L-leucine, a branched-chain amino acid, have been considered beneficial for controlling oxidative stress and maintaining cardiac tissue in toxicity models using doxorubicin, a drug widely used in cancer treatment. However, there is a lack of studies in the literature that assess the effects of this diet on other organs and tissues, such as the liver and kidneys. Therefore, this study aimed to evaluate the effects of a leucine-rich diet on the liver and kidneys of healthy rats submitted to the doxorubicin toxicity model by analyzing biomarkers of oxidative stress and histological parameters. The animals were divided into four groups: naive, doxorubicin, L-leucine, and doxorubicin + L-leucine, and the diet was standardized with 5% L-leucine and a dose of 7.5 mg/kg of doxorubicin. We evaluated tissue injury parameters and biomarkers of oxidative stress, including enzymes, antioxidant profile, and oxidized molecules, in the liver and kidneys. Although some studies have indicated benefits of a diet rich in L-leucine for the muscle tissue of animals that received doxorubicin, our results showed that the liver was the most affected organ by the L-leucine-rich diet since the diet reduced its antioxidant defenses and increased the deposit of collagen and fat in the hepatic tissue. In the kidneys, the main alteration was the reduction in the number of glomeruli. These results contribute to the scientific literature and encourage further studies to evaluate the effects of an L-leucine-rich diet or its supplementation, alone or combined with doxorubicin using an animal model of cancer. Therefore, our study concludes that the leucine-rich diet itself was harmful and, when co-administered with doxorubicin, was not able to maintain the antioxidant defenses and tissue structure of the evaluated organs. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a syndrome characteristic in elderly patients and is also associated with a significant proportion of chronic disorders such as inflammatory bowel disease (IBD). In this case, it can lead to a worse prognosis of the disease and a decreased quality of life. Study Aim: This study aims to identify the best ways to diagnose sarcopenia in patients with IBD, establish its impact on the course of the disease, and find preventive methods to counteract the effects of sarcopenia in the outcome of patients with IBD and, therefore, minimize disabilities and increase the health-related quality of life (HRQoL). Material and Methods: A systematic review with the Prospero registration number CRD42023398886 was performed in PubMed and Web of Science databases, evaluating all original articles published in the last 10 years (clinical trials and randomized control trials) that describe sarcopenia and IBD in the human adult population. Results: From the 16 articles that were included, 5 articles defined sarcopenia by the skeletal muscle index (SMI) and reported data regarding its correlation with body composition: BMI; visceral fat (VF); subcutaneous fat (SC); and VF/SC index. Other articles evaluated the link between sarcopenia and the total psoas muscle area, thigh circumference, calf circumference, subjective global assessment, hand grip strength, and appendicular SMI, alongside inflammatory markers such as IL-6 and C-reactive protein, level of disability, malnutrition, frailty, resistance training alone and in combination with whey protein, and infliximab treatment. Discussions and Conclusions: There is a great heterogeneity regarding the assessment criteria and methods used to diagnose sarcopenia due to the variability of population characteristics, both anthropometric and socio-cultural, alongside the high variability in the cut-offs. Therefore, any method which identifies sarcopenia in IBD patients, thus enabling intervention, may provide good results for patient quality of life and outcomes. [ABSTRACT FROM AUTHOR]

Growth-hormone (GH)- and prolactin (PRL)-secreting PitNETs (pituitary neuroendocrine tumors) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Proliferation markers alone have a questionable degree of prediction, so we try to identify validated prognostic models as accurately as possible. (1) Background: The data available so far show that the use of staging and clinical–pathological classification of PitNETs, along with imaging, are useful in predicting the evolution of these tumors. So far, there is no consensus for certain markers that could predict tumor evolution. The application of the WHO (World Health Organisation) classification in practice needs to be further evaluated and validated. (2) Methods: We performed the CRD42023401959 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and the search used the following keywords: (i) pituitary adenoma AND (prognosis OR outcome OR prediction), (ii) growth hormone pituitary adenoma AND (prognosis OR outcome OR prediction), (iii) prolactin pituitary adenoma AND (prognosis OR outcome OR prediction); (iv) mammosomatotroph adenoma AND (prognosis OR outcome OR prediction). (3) Results: Two researchers extracted the articles of interest and if any disagreements occurred in the selection process, these were settled by a third reviewer. The articles were then assessed using the ROBIS bias assessment and 75 articles were included. (4) Conclusions: the clinical–pathological classification along with factors such as GH, IGF-1, prolactin levels both preoperatively and postoperatively offer valuable information. [ABSTRACT FROM AUTHOR]

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI −0.54 [−1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI −0.2 [−0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [−12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [−0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

Dyslipidemia and oxidative stress are directly related to the pathogenesis of cardiovascular diseases. Annona crassiflora Mart. (ACM) has been traditionally used in folk medicine to alleviate inflammation and pain. This plant is rich in polyphenols, which exhibit high antioxidant capacity. The present study aimed to elucidate the antioxidant properties of ACM in the heart of hyperlipidemic mice. The animals were orally administered either a crude ethanol extract (CEAc) or a polyphenols-rich fraction (PFAc) obtained from ACM fruit peel. There were correlations between blood and fecal biochemical data with cardiac oxidative stress biomarkers. Here, the pre-treatment with CEAc for 12 d led to an increase in glutathione content (GSH) and a reduction in the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase. Moreover, PFAc was found to enhance the total antioxidant capacity as well as GSH, SOD and CAT activities, which were reduced by Triton WR-1339-induced hyperlipidemia. Moreover, the administration of PFAc before the treatment resulted in a decrease in protein carbonylation and lipid peroxidation levels, as well as a reduction in the activities of glutathione reductase and glucose-6-phosphate dehydrogenase. ACM fruit peel showed improvement in the glutathione system, mainly its polyphenols-rich fraction, indicating a potential cardioprotective antioxidant usage of this plant extract. [ABSTRACT FROM AUTHOR]

Device identification is a fundamental issue in the Internet of Things (IoT). Many critical services, including access control and intrusion prevention, are built on correctly identifying each unique device in a network. However, device identification faces many challenges in the IoT. For example, a common technique to identify a device in a network is using the device's MAC address. However, MAC addresses can be easily spoofed. On the other hand, IoT devices also include dynamic characteristics such as traffic patterns which could be used for device identification. Machine-learning-assisted approaches are promising for device identification since they can capture dynamic device behaviors and have automation capabilities. Supervised machine-learning-assisted techniques demonstrate high accuracies for device identification. However, they require a large number of labeled datasets, which can be a challenge. On the other hand, unsupervised machine learning can also reach good accuracies without requiring labeled datasets. This paper presents an unsupervised machine-learning approach for IoT device identification. [ABSTRACT FROM AUTHOR]

Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome and share multiple causal associations. Both conditions have an alarmingly increasing incidence and lead to multiple complications, which have an impact on a variety of organs and systems, such as the kidneys, eyes, and nervous and cardiovascular systems, or may cause metabolic disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), as an antidiabetic class with well-established cardiovascular benefits, and its class members have also been studied for their presumed effects on steatosis and fibrosis improvement in patients with NAFLD or non-alcoholic steatohepatitis (NASH). The MEDLINE and Cochrane databases were searched for randomized controlled trials examining the efficacy of SGLT2-i on the treatment of NAFLD/NASH in patients with T2DM. Of the originally identified 179 articles, 21 articles were included for final data analysis. Dapagliflozin, empagliflozin, and canagliflozin are some of the most used and studied SGLT2-i agents which have proven efficacy in treating patients with NAFLD/NASH by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat loss, glucotoxicity, and lipotoxicity improvement or even improvement of chronic inflammation. Despite the considerable variability in study duration, sample size, and diagnostic method, the SGLT2-i agents used resulted in improvements in non-invasive markers of steatosis or even fibrosis in patients with T2DM. This systematic review offers encouraging results that place the SGLT2-i class at the top of the therapeutic arsenal for patients diagnosed with T2DM and NAFLD/NASH. [ABSTRACT FROM AUTHOR]

As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment's pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research. [ABSTRACT FROM AUTHOR]

The blood diagnosis of diabetes mellitus (DM) is highly accurate; however, it is an invasive, high-cost, and painful procedure. In this context, the combination of ATR-FTIR spectroscopy and machine learning techniques in other biological samples has been used as an alternative tool to develop a non-invasive, fast, inexpensive, and label-free diagnostic or screening platform for several diseases, including DM. In this study, we used the ATR-FTIR tool associated with linear discriminant analysis (LDA) and a support vector machine (SVM) classifier in order to identify changes in salivary components to be used as alternative biomarkers for the diagnosis of type 2 DM. The band area values of 2962 cm−1, 1641 cm−1, and 1073 cm−1 were higher in type 2 diabetic patients than in non-diabetic subjects. The best classification of salivary infrared spectra was by SVM, showing a sensitivity of 93.3% (42/45), specificity of 74% (17/23), and accuracy of 87% between non-diabetic subjects and uncontrolled type 2 DM patients. The SHAP features of infrared spectra indicate the main salivary vibrational modes of lipids and proteins that are responsible for discriminating DM patients. In summary, these data highlight the potential of ATR-FTIR platforms coupled with machine learning as a reagent-free, non-invasive, and highly sensitive tool for screening and monitoring diabetic patients. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for their use with other glucose-lowering drugs and drugs for the treatment of type 2 diabetes mellitus (T2DM), in a standard-of-care regimen with maximum tolerated doses, and, respectively, when compared with metformin. Methods: We conducted a retrospective, observational study on 405 patients that were seen in the outpatient clinic of the N Paulescu National Institute for Diabetes Mellitus, Bucharest, Romania, in 2019. Their demographics, metabolic parameters, and medication safety were evaluated at three follow-up visits, from baseline, six months, and twelve months. Results: Both SGLT-2is and GLP-1 RAs are safe regarding creatinine, eGFR, urea, GOT, and GPT upon the comparison of the data from the six- and twelve-month visits with the initial visit, and also the twelve-month visit with the six-month visit. Moreover, when comparing SGLT-2is and GLP-1 RAs with metformin, there are safety data only for urea. Conclusions: In this retrospective analysis, both SGLT-2is and GLP-1 RAs, when used in conjunction with other glucose-lowering, blood-pressure-lowering, and lipid-lowering medications, appeared to be safe for the management of T2DM. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS), particularly relapsing MS (RMS), has become a treatable disease in recent decades, and immunotherapies are now able to influence long-term disease course. A wide range of disease-modifying drugs are available, which makes the choice of therapy in individual cases considerably more complex. Due to specific regulatory aspects (partly diverging approvals by Swissmedic compared to the European Medicines Agency (EMA), and an independent evaluation process for the Federal Office of Public Health (FOPH) specialities list (SL)), we issued a consensus recommendation regarding specific aspects of immunotherapy for MS in Switzerland in 2019. Here, we present revised recommendations with an update on newly approved drugs and new safety aspects, also in reference to the risk of COVID-19 infection and vaccination. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is characterized by an association of cardiovascular and diabetes mellitus type 2 risk factors. Although the definition of MetS slightly differs depending on the society that described it, its central diagnostic criteria include impaired fasting glucose, low HDL-cholesterol, elevated triglycerides levels and high blood pressure. Insulin resistance (IR) is believed to be the main cause of MetS and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Most recent studies revealed that IR may also be present in non-obese patients, and considered visceral adiposity to be the main effector of MetS' pathology. Visceral adiposity is strongly linked with hepatic fatty infiltration also known as non-alcoholic fatty liver disease (NAFLD), therefore, the level of fatty acids in the hepatic parenchyma is indirectly linked with MetS, being both a cause and a consequence of this syndrome. Taking into consideration the present pandemic of obesity and its tendency to drift towards a progressively earlier onset due to the Western lifestyle, it leads to an increased NAFLD incidence. Novel therapeutic resources are lifestyle intervention with physical activity, Mediterranean diet, or therapeutic surgical respective metabolic and bariatric surgery or drugs such as SGLT-2i, GLP-1 Ra or vitamin E. NAFLD early diagnosis is important due to its easily available diagnostic tools such as non-invasive tools: clinical and laboratory variables (serum biomarkers): AST to platelet ratio index, fibrosis-4, NAFLD Fibrosis Score, BARD Score, fibro test, enhanced liver fibrosis; imaging-based biomarkers: Controlled attenuation parameter, magnetic resonance imaging proton-density fat fraction, transient elastography (TE) or vibration controlled TE, acoustic radiation force impulse imaging, shear wave elastography, magnetic resonance elastography; and the possibility to prevent its complications, respectively, fibrosis, hepato-cellular carcinoma or liver cirrhosis which can develop into end-stage liver disease. [ABSTRACT FROM AUTHOR]

Fetal growth restriction is an important part of monitoring a pregnancy. Because guidelines or diagnostic criteria for either minor or major thrombophilia are scarce, this systematic review aims to summarize the present knowledge in the field. We performed the CRD42022376006 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and with the "thrombophilia AND (pregnancy OR diagnostic criteria) AND fetal growth restriction" criteria. After two researchers extracted the articles of interest, they were assessed using the Newcastle–Ottawa Scale and eight articles were included. The elements from the thrombophilia diagnostic predict IUGR, factor V Leiden mutation, MTHFR C667T mutation, protein S deficiency, antithrombin deficiency, factor VII polymorphism, and antiphospholipid antibodies, while the association of protein C, PAI-1 and certain combinations of mutations are still under debate and require the collection of more data. The present systematic review provides an extensive picture of the actual knowledge about thrombophilia diagnosis and its links with pregnancy complications, such as intrauterine growth restriction, despite its limitation in the inclusion of other actually debated disorders such as PAI-1 mutation, protein C deficiency and other thrombophilia types. [ABSTRACT FROM AUTHOR]

The Aedes aegypti mosquito significantly impacts public health, with vector control remaining the most efficient means of reducing the number of arboviral disease cases. This study screened the larvicidal and pupicidal activity of common edible plant extracts. Piper nigrum L. (black pepper) extract production was optimized using accelerated solvent extraction (ASE) and validated following regulatory requirements using HPLC-PDA analytical methodology to quantify its major component–piperine. Larvicidal activity was determined for the standardized P. nigrum fruit ethanol extract (LC50 1.1 µg/mL) and piperine standard (LC50 19.0 µg/mL). Furthermore, 9-day residual activity was determined for the extract (4 µg/mL) and piperine (60 µg/mL), with daily piperine quantification. Semi-field trials of solid extract formulations demonstrated 24-day activity against Ae. aegypti larvae. Thus, the standardized P. nigrum extract emerges as a potential candidate for insecticide development to control the arboviral vector. [ABSTRACT FROM AUTHOR]

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease. [ABSTRACT FROM AUTHOR]

Annona muricata Linn. is a common plant found in the warmest regions of South and Central America and its use in traditional medicine has been reported for the treatment of various illnesses. In the current study, we investigate the antioxidant and anti-inflammatory activities of crude extract and fractions from A. muricata L. leaves in isolated murine phagocytic immune cells as well as experimental LPS-induced acute lung injury (ALI). In a luminol-dependent chemiluminescence assay, we showed that ethyl acetate (EtOAc.f) and n-butanol (BuOH.f) fractions—both rich in polyphenols—reduced the generation of reactive oxygen species (ROS) by neutrophils stimulated with opsonized zymosan; similar results were found in culture of bone marrow-derived macrophages (BMDMs). By evaluating anti-inflammatory activity in BMDMs, EtOAc.f and BuOH.f reduced secretion of IL-6 and expression of the co-stimulatory molecule CD40. Furthermore, in LPS-induced ALI, oral administration of EtOAc.f reduced myeloperoxidase (MPO) activity in lung tissue. In addition, on a mechanism dependent on glutathione levels, the oxidative damage was also attenuated. These findings revealed direct antioxidant and anti-inflammatory activities of polyphenols-rich fractions of A. muricata L. leaves on neutrophils and macrophages. Moreover, the reduced oxidative damage and levels of inflammatory markers in experimental ALI suggest that these fractions might be explored for the development of new therapies for inflammatory conditions. [ABSTRACT FROM AUTHOR]

Objective: Anti-CD20-treated patients are at risk of a reduced humoral immune response during the SARS-CoV-2 pandemic. Our aim was to compare the antibody response after two vaccinations with the mRNA vaccines BNT162b2 or mRNA-1273 in patients with multiple sclerosis. Methods: Data from the University Hospital of Bern and Cantonal Hospital of Lucerne were retrospectively collected from medical records and then analyzed. Anti-spike IgG serum titers were collected from both centers and were considered to be protective from a value of ≥100 AU/mL. Continuous variables were given as the mean and 95% confidence interval (95% CI); categorical variables were given as frequencies. A Mann–Whitney test and Fisher's exact test as well as a multivariable linear regression analysis with anti-spike IgG (AU/mL) as the dependent variable were run using SPSS Statistic 25 (IBM Corp., Amonk, NY, USA). Results: A total of 74 patients were included; 41/74 (63.51%) were female patients and the mean age was 46.6 years (95% CI 43.4–49.9). Of these patients, 36/74 were vaccinated with BNT162b2 and 38/74 with mRNA-1273, following the national vaccination recommendation. In both vaccine groups, protective anti-spike IgG titers (≥100 AU/mL) were infrequently achieved (5/74: mRNA-1273 3/38; BNT162b2 2/36). Conclusions: In addition to a low rate of protective anti-spike IgG titers in both vaccine groups, we identified a drop in anti-spike IgG serum titers over time. This observation bears therapeutic consequences, as initial positive titers should be checked in case of an infection with the SARS-CoV-2 virus to identify patients who would benefit from an intravenous anti-spike IgG treatment against acute COVID-19. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the years, the chicken embryo (CE) has been a widely used animal model, which is essential to decrease the number of born animals in experiments. Thus, we intended to know if there is a lack of standardization in using embryos in research. Therefore, the objective of this study was to verify whether alterations in CE of different ages are specific to the model, having as reference a virus and two drugs that cause known alterations in adults and other species. The response of embryos to challenges with viruses and drugs did not always occur as expected compared with adult animals. Although macroscopic and microscopic changes were visible in the infected group, other laboratory analyses did not show significant changes. Our results showed that some drugs and viruses can generate laboratory results that seem to be inherent to the model studied and depend on the CE's developmental stage. Several studies have been developed using the Gallus gallus embryo as an experimental model to study the toxicity of drugs and infections. Studies that seek to standardize the evaluated parameters are needed to better understand and identify the viability of CEs as an experimental model. Therefore, we sought to verify whether macroscopic, histopathological, blood count, metabolites and/or enzymes changes and oxidative stress in CE of different ages are specific to the model. To achieve this goal, in ovo assays were performed by injecting a virus (Gammacoronavirus) and two drugs (filgrastim and dexamethasone) that cause known changes in adult animals. Although congestion and inflammatory infiltrate were visible in the case of viral infections, the white blood cell count and inflammation biomarkers did not change. Filgrastim (FG) testing did not increase granulocytes as we expected. On the other hand, CE weight and red blood cell count were lower with dexamethasone (DX), whereas white blood cell count and biomarkers varied depended on the stage of CE development. Our work reinforces the importance of standardization and correct use of the model so that the results of infection, toxicity and pharmacokinetics are reproducible. [ABSTRACT FROM AUTHOR]

Chemical pesticides have an immense role in curbing the infection of plant viruses and soilborne pathogens of high valued crops. However, the usage of chemical pesticides also contributes to the development of resistance among pathogens. Hence, attempts were made in this study to identify a suitable bacterial antagonist for managing viral and fungal pathogens infecting crop plants. Based on our earlier investigations, we identified Bacillus amyloliquefaciens VB7 as a potential antagonist for managing Sclerotinia sclerotiorum infecting carnation, tobacco streak virus infecting cotton and groundnut bud necrosis infecting tomato. Considering the multifaceted action of B. amyloliquefaciens VB7, attempts were made for whole-genome sequencing to assess the antiviral activity against tomato spotted wilt virus infecting chrysanthemum and antifungal action against Fusarium oxysporum f. sp. cubense (Foc). Genome annotation of the isolate B. amyloliquefaciens VB7 was confirmed as B. velezensis VB7 with accession number CP047587. Genome analysis revealed the presence of 9,231,928 reads with an average read length of 149 bp. Assembled genome had 1 contig, with a total length of 3,021,183 bp and an average G+C content of 46.79%. The protein-coding sequences (CDS) in the genome was 3090, transfer RNA (tRNA) genes were 85 with 29 ribosomal RNA (rRNA) genes and 21 repeat regions. The genome of B. velezensis VB7 had 506 hypothetical proteins and 2584 proteins with functional assignments. VB7 genome had the presence of flagellin protein FlaA with 987 nucleotides and translation elongation factor TU (Ef-Tu) with 1191 nucleotides. The identified ORFs were 3911 with 47.22% GC content. Non ribosomal pepide synthetase cluster (NRPS) gene clusters in the genome of VB7, coded for the anti-microbial peptides surfactin, butirosin A/butirosin B, fengycin, difficidin, bacillibactin, bacilysin, and mersacidin the Ripp lanthipeptide. Antiviral action of VB7 was confirmed by suppression of local lesion formation of TSWV in the local lesion host cowpea (Co-7). Moreover, combined application of B. velezensis VB7 with phyto-antiviral principles M. Jalapa and H. cupanioides increased shoot length, shoot diameter, number of flower buds per plant, flower diameter, and fresh weight of chrysanthemum. Further, screening for antifungal action of VB7 expressed antifungal action against Foc in vitro by producing VOC/NVOC compounds, including hexadecanoic acid, linoelaidic acid, octadecanoic acid, clindamycin, formic acid, succinamide, furanone, 4H-pyran, nonanol and oleic acid, contributing to the total suppression of Foc apart from the presence of NRPS gene clusters. Thus, our study confirmed the scope for exploring B. velezensis VB7 on a commercial scale to manage tomato spotted wilt virus, groundnut bud necrosis virus, tobacco streak virus, S. sclerotiorum, and Foc causing panama wilt of banana. [ABSTRACT FROM AUTHOR]

To comply with electric power grid automation strategies, new cyber-security protocols and protection are required. What we now experience is a new type of protection against new disturbances namely cyber-attacks. In the same vein, the impact of disturbances arising from faults or cyber-attacks should be surveyed by network vulnerability criteria alone. It is clear that the diagnosis of vulnerable points protects the power grid against disturbances that would inhibit outages such as blackouts. So, the first step is determining the network vulnerable points, and then proposing a support method to deal with these outages. This research proposes a comprehensive approach to deal with outages by determining network vulnerable points due to physical faults and cyber-attacks. The first point, the network vulnerable points against network faults are covered by microgrids. As the second one, a new cyber-security protocol named multi-layer security is proposed in order to prevent targeted cyber-attacks. The first layer is a cyber-security-based blockchain method that plays a general role. The second layer is a cyber-security-based reinforcement-learning method, which supports the vulnerable points by monitoring data. On the other hand, the trend of solving problems becomes routine when no ambiguity arises in different sections of the smart grid, while it is far from a big network's realities. Hence, the impact of uncertainty parameters on the proposed framework needs to be considered. Accordingly, the unscented transform method is modeled in this research. The simulation results illustrate that applying such a comprehensive approach can greatly pull down the probability of blackouts. [ABSTRACT FROM AUTHOR]

True umbilical knot (TUK), although not a commonly encountered pathology, hasan important psychological burden on the mother and obstetrician. It has an extremely low prenatal ultrasound diagnosis rate, despite its adverse perinatal outcomes when unknown. We conducted a retrospective observational analytical study on a 7-year period (2015–2021), including all pregnancies overseen by a single fetal-maternal medicine specialist for monitoring and delivery. We analyzed the prenatal detection rate and correlations between prenatal diagnosis of TUK and pregnancy outcome in terms of associated maternal and fetal factors, time and mode of delivery, fetal weight at birth, maternal level of stress, and iatrogenic prematurity. We compared our results with an electronic search of the literature to study the relationship between TUK and prematurity. We prenatally diagnosed 16 TUKs, and there were two false positives and two undiagnosed knots. All of those women had birth at term. The main finding of the review was a small number of studies that included enough cases for analysis. The prematurity rate due to TUK is 14.2%, significantly increased compared to the general population. An umbilical artery flow velocimetry notch in twin pregnancies complicated by TUK was an important ultrasonographic finding. We consider intrauterine fetal death exceptional, and the main adverse neonatal outcome is due to iatrogenic prematurity caused by maternal anxiety of knowing the prenatal diagnosis and mode of delivery. The elective method for diagnosis should be the second-trimester ultrasound scan using three-dimensional (3D) reconstruction and cesarean delivery for a good neonatal outcome. Pregnant women should be counseled to understand the implications of iatrogenic prematurity, especially respiratory distress syndrome, to ensure these infants are delivered at term. [ABSTRACT FROM AUTHOR]

Hemivertebra is a common cause of congenital scoliosis and results from a lack of formation of one-half of the vertebral body. This condition is very rare and can present as solitary or as a syndrome component: i.e., the split notochord syndrome, which often implies vertebral defects, from a bifid vertebra to hemivertebrae, or fused vertebrae. We describe a case of supernumerary lateral hemivertebra detected prenatally at 12 weeks of gestation and the ultrasonography specifics that lead to early and accurate diagnosis, monitoring during pregnancy, and follow-up at the 4-year period. The case is presented to specify the importance of an early assessment of fetal spine and diagnosis of various conditions, including hemivertebrae, considering the significant association with other anomalies (cardiovascular, urinary, skeletal, gastrointestinal, and central nervous systems), which are most commonly involved. Moreover, the need to counsel future parents on the risks implied by this anomaly is important for the obstetrician. We underline the inclusion of these types of congenital conditions in high-risk pregnancy because of the frequent association with high cesarean delivery rates, growth restriction, delivery before term, and higher morbidity rates. [ABSTRACT FROM AUTHOR]

Hop plant (Humulus lupulus L.) has been used by humans for ages, presumably first as a herbal remedy, then in the manufacturing of different products, from which beer is the most largely consumed. Female hops cones have different useful chemical compounds, an important class being antioxidants, mainly polyphenols. This narrative review describes the main antioxidants in hops, their bioavailability and biological effects, and the results obtained by now in the primary and secondary prevention of several non-communicable diseases, such as the metabolic syndrome related diseases and oncology. This article presents in vitro and in vivo data in order to better understand what was accomplished in terms of knowledge and practice, and what needs to be clarified by additional studies, mainly regarding xantohumol and its derivates, as well as regarding the bitter acids of hops. The multiple protective effects found by different studies are hindered up to now by the low bioavailability of some of the main antioxidants in hops. However, there are new promising products with important health effects and perspectives of use as food supplements, in a market where consumers increasingly search for products originating directly from plants. [ABSTRACT FROM AUTHOR]

Diet is an important tool in managing dyslipidemic disorders, thus contributing to the prophylaxis of cardiovascular morbidity. Research has shown that a plant-based diet could have positive effects through many pathways. We conducted a study on a group of 38 plant-based individuals from Romania who have adopted the diet for at least one year. The aim of the research was to evaluate eventual changes in their lipid profile. We analyzed to what extent the values of different markers significantly changed following the dietary transition. Improvements were obtained for body mass index (BMI) and all lipid markers, with the exception of high-density lipoprotein cholesterol (HDL-C). Results showed that 75.0% of persons with elevated TGs (triglycerides) succeeded in normalizing them, as well as individuals with high low-density lipoprotein cholesterol (LDL-C) levels, where 72.7% from the borderline elevated became optimal. The total cholesterol (TC)/HDL-C ratio shifted from elevated to optimum in 78.6% of cases. Results were poor in three participants with presumed familial hypercholesterolemia, which were later successfully managed by using lipid-lowering medication. In conclusion, although dyslipidemias are only a surrogate marker for cardiovascular morbidity, the actions by which a plant-based diet can influence cardiovascular diseases are multiple, and we consider that our study confirms its positive effect. [ABSTRACT FROM AUTHOR]

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD. [ABSTRACT FROM AUTHOR]

Renewable energy-based distributed generators (DGs) are gaining more penetration in modern grids to meet the growing demand for electrical energy. The anticipated techno-economic benefits of these eco-friendly resources require their judicious and properly sized allocation in distribution networks (DNs). The preeminent objective of this research is to determine the sizing and optimal placing of DGs in the condensed DN of a smart city. The placing and sizing problem is modeled as an optimization problem to reduce the distribution loss without violating the technical constraints. The formulated model is solved for a radial distribution system with a non-uniformly distributed load utilizing the selective particle swarm optimization (SPSO) algorithm. The intended technique decreases the power loss and perfects the voltage profile at the system's nodes. MATLAB is used for the simulation, and the obtained results are also validated by the Electrical Transient Analysis Program (ETAP). Results show that placing optimally sized DGs at optimal system nodes offers a considerable decline in power loss with an improved voltage profile at the network's nodes. Distribution system operators can utilize the proposed technique to realize the reliable operation of overloaded urban networks. [ABSTRACT FROM AUTHOR]

The impressive furtherance of communication technologies has exhorted industrial companies to link-up these developments with their own abilities with the target of efficiency enhancement through smart supervision and control. With this in mind, the blockchain platform is a prospective solution for merging communication technologies and industrial infrastructures, but there are several challenges. Such obstacles should be addressed to effectively adopt this technology. One of the most recent challenges relative to adopting blockchain technology is the energy consumption of miners. Thus, providing an accurate approach that addresses the underlying cause of the problem will carry weight in the future. This work addresses managing the energy consumption of miners by using the advantage of distributed generation resources (DGRs). Along the same vein, it appears that achieving the optimal solution requires executing the modified reconfirmation of DGRs and miners (indeed, mining pool systems) in the smart grid. In order to perform this task, this article utilizes the Intelligent Priority Selection (IPS) method since this method is up to snuff for corporative allocation. In order to find practical solutions for this problem, the uncertainty is also modeled as a credible index highly correlated with the load and generation. All in all, it can be said that the outcome of this research study can help researchers in the field of enhancement of social welfare by using the proposed technology. [ABSTRACT FROM AUTHOR]

Simple Summary: The BRENDA-Score provides an easy to use tool for clinicians to estimate the risk of recurrence in primary breast cancer. The algorithm has been validated via a second independent database and provides five recurrence risk groups. This grouping helps clinicians to encourage high risk patients to undergo the recommended treatment. Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell's c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival. [ABSTRACT FROM AUTHOR]

(1) Background: Nanocrystals (NCs)-based electrochemical sensors have been proposed for biomarkers detection, although immunosensors using ZnO NCs decorated with copper are still scarce. (2) Methods: Electrochemical immunodetection of human salivary alpha-amylase (HSA) used ZnO, CuO, and ZnO:xCu (x = 0.1, 0.4, 1.0, 4.0, and 12.0) NCs. (3) Results: Substitutional incorporation of Cu2+ in the crystalline structure of ZnO and formation of nanocomposite were demonstrated by characterization. Graphite electrodes were used and the electrochemical signal increased by 40% when using ZnO:1Cu and 4Cu (0.25 mg·mL−1), in an immunosensor (0.372 mg·mL−1 of anti-alpha-amylase and 1% of casein). Different interactions of HSA with the alpha-amylase antibody were registered when adding the NCs together, either before or after the addition of saliva (4 μL). The immunosensor changed specificity due to the interaction of copper. The ZnO:1Cu and ZnO:4Cu samples showed 50% interference in detection when used before the addition of saliva. The immunosensor showed 100% specificity and a sensitivity of 0.00196 U·mL−1. (4) Conclusions: Results showed that the order of NCs addition in the sensors should be tested and evaluated to avoid misinterpretation in detection and to enable advances in the validation of the immunosensor. [ABSTRACT FROM AUTHOR]

The interrelations between fatigue, depression and health-related quality of life (HRQoL) in persons with multiple sclerosis (PwMS) are complex, and the directionality of the effects is unclear. To address this gap, the current study used a longitudinal design to assess direct and indirect effects of fatigue and depression on HRQoL in a one-year follow-up survey. A sample of 210 PwMS from the nationwide Swiss MS Registry was used. HRQoL was assessed using the European Quality of Life 5-Dimension 5-Level questionnaire. Path analysis on HRQoL, with fatigue and depression as predictors, was applied. Fatigue was measured by the Modified Fatigue Impact Scale (MFIS), including physical, cognitive and psychosocial subscales, and non-somatic depressive symptomatology was examined with the Beck Depression Inventory-Fast Screen (BDI-FS). Fatigue acted as a fully mediating variable (B = −0.718, SE = 0.253) between non-somatic depressive symptomatology and HRQoL. This indirect effect became apparent in the physical (B = −0.624, SE = 0.250), psychosocial (B = −0.538, SE = 0.256) and cognitive subscales (B = −0.485, SE = 0.192) of fatigue. In contrast, non-somatic depressive symptomatology did not act as a mediator. Our findings provide novel and clinically relevant longitudinal evidence showing that the debilitating effect of non-somatic aspects of depression on HRQoL was fully mediated and therefore explainable via fatigue. [ABSTRACT FROM AUTHOR]

Laboratory cultivation of viruses is critical for determining requirements for viral replication, developing detection methods, identifying drug targets, and developing antivirals. Several viruses have a history of recalcitrance towards robust replication in laboratory cell lines, including human noroviruses and hepatitis B and C viruses. These viruses have tropism for tissue components of the enterohepatic circulation system: the intestine and liver, respectively. The purpose of this review is to discuss how key enterohepatic signaling molecules, bile acids (BAs), and BA receptors are involved in the replication of these viruses and how manipulation of these factors was useful in the development and/or optimization of culture systems for these viruses. BAs have replication-promoting activities through several key mechanisms: (1) affecting cellular uptake, membrane lipid composition, and endocytic acidification; (2) directly interacting with viral capsids to influence binding to cells; and (3) modulating the innate immune response. Additionally, expression of the Na+-taurocholate cotransporting polypeptide BA receptor in continuous liver cell lines is critical for hepatitis B virus entry and robust replication in laboratory culture. Viruses are capable of hijacking normal cellular functions, and understanding the role of BAs and BA receptors, components of the enterohepatic system, is valuable for expanding our knowledge on the mechanisms of norovirus and hepatitis B and C virus replication. [ABSTRACT FROM AUTHOR]