Treatment of Atrial Fibrillation and Venous Thromboembolism with Factor Xa Inhibitors in Severely Obese Patients.

BACKGROUND: A paucity of data exists to support the use of factor Xa inhibitors in severely obese patients with a weight ≥ 150kg or BMI ≥ 50 kg/m2. OBJECTIVES: The purpose of this study is to evaluate whether factor Xa inhibitors are as safe and effective as warfarin for the treatment of atrial fibrillation (AF) and/or venous thromboembolism (VTE) in individuals with a BMI ≥ 50 kg/m2 and/or weight ≥ 150 kg. PATIENTS / METHODS: This was a multicenter retrospective cohort study of severely obese adult patients with AF and/or VTE treated with a factor Xa inhibitor or warfarin. The primary effectiveness outcome was a composite odds of stroke, systemic embolism or VTE; the primary safety outcome was odds of major bleeding. Secondary outcomes included incidence of stroke or systemic embolism, VTE, major bleeding, clinically relevant non-major bleeding, all-cause mortality, change in anticoagulation and total number of hospital encounters. Outcomes were assessed for 12 months following initiation of study drug. RESULTS: A total of 1,736 patients were included. The mean weight and BMI of the overall cohort was 164.4 kg and 54.6 kg/m2, respectively. There was no difference in odds of stroke, systemic embolism or VTE (OR 1.005, 95% CI 0.6 - 1.68) or major bleeding (OR 0.9, 95% CI 0.47 - 1.7) between groups. CONCLUSIONS: These data suggest that apixaban and rivaroxaban are safe and effective alternatives to warfarin for the treatment of AF and/or VTE in individuals with a BMI ≥ 50 kg/m2 and/or weight ≥ 150 kg.

Comparing DOAC and warfarin outcomes in an obese population using the 'real-world' Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry.

INTRODUCTION: Direct oral anticoagulants (DOACs) have overtaken warfarin in the treatment of nonvalvular atrial fibrillation (AF) and venous thromboembolism (VTE). Limited data explore the safety of DOACs in obesity. METHODS: This multicenter retrospective study between June 2015 and September 2019 uses the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to compare DOACs and warfarin across weight classes (not obese: body mass index (BMI) ⩾ 18.5 and < 30; obese: BMI ⩾ 30 and < 40; severely obese: BMI ⩾ 40). Primary outcomes include major, clinically relevant nonmajor (CRNM), and minor bleeding events per 100 patient-years. Secondary outcomes include stroke, recurrent VTE, and all-cause mortality. RESULTS: DOACs were prescribed to 49% of the 4089 patients with AF and 46% of the 3162 patients with VTE. Compared to patients treated with warfarin, those treated with DOACs had a higher estimated glomerular filtration rate across BMI categories regardless of indication. In the AF population, severely obese patients treated with DOACs had more major (3.4 vs 1.8, p = 0.004), CRNM (8.6 vs 5.9, p = 0.019), and minor bleeding (11.4 vs 9.9, p = 0.001). There was no difference in stroke or all-cause mortality. In the VTE population, both CRNM (7.5 vs 6.7, p = 0.042) and minor bleeding (19.3 vs 10.5, p < 0.001) events occurred at higher rates in patients treated with DOACs. There was no difference in recurrent pulmonary embolism, stroke, or all-cause mortality. CONCLUSION: There is a higher rate of bleeding in severely obese patients with VTE and AF treated with DOACs compared to warfarin, without a difference in secondary outcomes. Further studies to compare the anticoagulant classes and understand bleeding drivers in this population are needed.

Comparative evaluation of the effects of deferiprone and/or resveratrol in alleviating iron overload-induced tongue injury in rats.

Iron overload causes excessive iron deposition in extrahepatic organs, including the tongue. This study aims to compare the deferiprone and/or resveratrol treatments for the alleviation of iron overload-induced tongue injury in rats. Rats were divided into 6 groups: control group, iron-overloaded group, recovery group where rats were left to recover from iron overload, deferiprone-treated group, resveratrol-treated group, and combined deferiprone/resveratrol-treated group. Iron was administered for 4 weeks, while all treatment options were given for the subsequent 4 weeks. After 8 weeks, all rats were sacrificed; the serum iron profile was estimated, and the tongues were assessed by histopathological, tumour necrosis factor alpha (TNF-α) immunohistochemical, histomorphometric, and ultrastructural evaluations. Serum iron parameters were significantly increased in iron-overloaded rats and decreased to control levels only in the combined group. The iron-overloaded tongues demonstrated lost lingual papillae, coarse keratohyalin granules, vacuolated epithelial cells, degenerated muscle fibers, and congested blood vessels. Compared to the control rats, this group revealed a significant decrease in the epithelial layer thickness (550.7 vs. 763.4 µm), papillae height (441.4 vs. 849.7 µm), and myofiber diameter (58.5 vs. 98.6 µm), and increased lamina propria thickness (305.1 vs. 176.8 µm), fibrosis index (33.4 vs. 8.6 %), and TNF-α immunoexpression (1.16 vs. 0.63 optical density). Additionally, the ultrastructure showed hyperkeratinized papillae, wide interpapillary spaces, flat fungiform papillae, and lost gustatory pores. All these parameters were improved in the recovery, deferiprone, and resveratrol groups to different degrees, while the combined deferiprone/resveratrol treatment was the best option.

Mild Cold Stress at Ambient Temperature Elevates Muscle Calcium Cycling and Exercise Adaptations in Obese Female Mice.

CONTEXT: Housing temperature is a critical regulator of mouse metabolism and thermoneutral housing can improve model translation to humans. However, the impact of housing temperature on the ability of wheel running exercise training to rescue the detrimental effect of diet-induced obese mice is currently not fully understood. OBJECTIVE: To investigate how housing temperature affects muscle metabolism in obese mice with regard to calcium handling and exercise training (ET) adaptations in skeletal muscle, and benefits of ET on adiposity and glucometabolic parameters. METHODS: Lean or obese female mice were housed at standard ambient temperature (22 °C) or thermoneutrality (30 °C) with/without access to running wheels. The metabolic phenotype was investigated using glucose tolerance tests, indirect calorimetry, and body composition. Molecular muscle adaptations were measured using immunoblotting, qPCR, and spectrophotometric/fluorescent assays. RESULTS: Obese female mice housed at 22 °C showed lower adiposity, lower circulating insulin levels, improved glucose tolerance, and elevated basal metabolic rate compared to 30 °C housing. Mice exposed to voluntary wheel running exhibited a larger fat loss and higher metabolic rate at 22 °C housing compared to thermoneutrality. In obese female mice, glucose tolerance improved after ET independent of housing temperature. Independent of diet and training, 22 °C housing increased skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) activity. Additionally, housing at 22 °C elevated the induction of training-responsive muscle proteins in obese mice. CONCLUSION: Our findings highlight that housing temperature significantly influences adiposity, insulin sensitivity, muscle physiology, and exercise adaptations in diet-induced obese female mice.

Impact of Genital and Non-Genital Psoriasis on Genital Self-Image, Quality of Life, and Sexual Dysfunction in Female Patients.

INTRODUCTION: Psoriasis is a chronic systemic inflammatory disease that affects millions of people worldwide. While its physical manifestations are well-documented, the psychosocial impact of psoriasis, particularly on female patients, is an area of growing concern. Feelings of shame, inferiority, and stigma are common among individuals with psoriasis, and these emotional burdens can be especially pronounced in females, particularly when the genital area is affected. OBJECTIVES: We aimed to shed light on the significance of genital psoriasis on the overall well-being of female patients. METHODS: This cross-sectional, descriptive comparative study comprised 50 female participants diagnosed with psoriasis: 25 with genital psoriasis, 25 without genital psoriasis, and 25 healthy women matched for age and sex who served as the control group. All participants underwent an assessment of disease severity using the Psoriasis Area and Severity Index in the psoriasis group and completed questionnaires for the assessment of the Female Sexual Function Index (FSFI). Additionally, quality of life was evaluated using the Dermatology Life Quality Index, and the Female Genital Self-Image Scale (FGSIS) was used to assess genital self-image. RESULTS: We found that females with genital lesions, experience a notable decline in sexual health with higher levels of sexual distress compared to healthy individuals. In terms of the six FSFI domains, the psoriatic group scored lower than the control group in all areas, except for pain, which showed a significant increase. Psoriatic females also exhibited a significantly more negative FGSIS compared to the control group, and there was a highly significant difference in FGSIS between females with and without genital psoriasis. CONCLUSIONS: Understanding the impact of genital psoriasis on female sexual health and overall quality of life is essential for comprehensive patient care. This research is instrumental in addressing the psychosocial aspects of psoriasis and enhancing patient well-being.

Outcomes of direct oral anticoagulants with aspirin vs warfarin with aspirin: a registry-based cohort study.

Background: For patients anticoagulated with direct oral anticoagulants (DOACs) or warfarin and on aspirin (ASA) for nonvalvular atrial fibrillation and/or venous thromboembolism, it is unclear if bleeding outcomes differ. Objectives: To assess bleeding rates for ASA with DOACs vs warfarin and one another. Methods: Registry-based cohort study of patients followed by a 6-center quality improvement collaborative in Michigan using data from 2009 to 2022. The study included adults on ASA with warfarin or DOACs for atrial fibrillation and/or venous thromboembolism without a recent myocardial infarction or heart valve replacement. Results: After propensity matching by anticoagulant class, we compared 2 groups of 1467 patients followed for a median of 18.0 months. Any bleeding and nonmajor bleeding was increased with DOACs + ASA compared with warfarin + ASA (32.2 vs 27.8 and 27.1 vs 22.9 events/100 patient-years; relative risks [RRs], 1.1 and 1.2; 95% CIs, 1.1-1.2 and 1.1-1.3, respectively). After matching by drug, patients on apixaban + ASA vs warfarin + ASA had more bleeding (31.2 vs 27.8 events/100 patient-years; RR, 1.1; 95% CI, 1.0-1.2) and nonmajor bleeding but less major bleeding (3.8 vs 4.7 events/100 patient-years; RR, 0.8; 95% CI, 0.6-1.0) and emergency room visits for bleeding. Patients on rivaroxaban + ASA vs warfarin + ASA had more bleeding (39.3 vs 26.3 events/100 patient-years, RR, 1.5; 95% CI, 1.3-1.6), nonmajor bleeding, and thrombosis. Patients on apixaban + ASA vs rivaroxaban + ASA had significantly less bleeding (22.5 vs 39.3/100 patient-years; RR, 0.6; 95% CI, 0.5-0.7), nonmajor bleeding, major bleeding (2.1 vs 5.5 events/100 patient-years; RR, 0.4; 95% CI, 0.2-0.6), emergency room visits for bleeding, and thrombotic events. Conclusion: Patients on DOAC + ASA without a recent myocardial infarction or heart valve replacement had more nonmajor bleeding but otherwise similar outcomes compared with warfarin + ASA. Patients treated with rivaroxaban + ASA experienced more adverse clinical events compared with warfarin + ASA or apixaban + ASA.

Timing of Off-Label Dosing of Direct Oral Anticoagulants in Three Large Health Systems.

BACKGROUND: While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment. OBJECTIVES: We aimed to better characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention. METHODS: We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality-improvement process using data abstractors, from 2018 to 2022 on the number of "alerts" that are generated in response to dosing deviating from the U.S. Food and Drug Administration instructions for atrial fibrillation (AF) and venous thromboembolism (VTE). RESULTS: Among a sample of 789 to 1,022 annual AF patients and 381 to 484 annual VTE patients prescribed a DOAC in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period (2018-2022), there were 569 alerts for AF patients and 162 alerts for VTE patients. Alerts occurred more frequently during follow-up than at the time of initial prescribing in AF patients (78.2 vs. 21.8%), but more commonly at initial prescribing in VTE patients (59.9 vs. 40.1%). After initial review by quality-improvement abstractors, 19.3% of AF alerts and 14.8% of VTE alerts resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention about 75% of the time for both populations. The most common intervention was a change in DOAC dosing. CONCLUSION: This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC, particularly for patients with AF, as off-label prescribing occurs frequently during the follow-up period.

Assessment of therapeutic efficacy of adipose tissue-derived mesenchymal stem cells administration in hyperlipidemia-induced aortic atherosclerosis in adult male albino rats.

Atherosclerosis (AS) is a common disease seriously detrimental to human health. AS is a chronic progressive disease related to inflammatory reactions. The present study aimed to characterize and evaluate the effects of adipose tissue stem cells (ADSCs) in high-fat diet-induced atherosclerosis in a rat model. The present study comprises thirty-six rats and they were divided into three groups: the control group, the high-fat diet (HFD) group; which received a high-fat diet, and the high-fat diet + stem cells (HFD+SC) group; which was fed with a high-fat diet along with the administration of intravenous ADSCs. Food was given to the animals for 20 weeks to establish dyslipidemia models. After 20 weeks, animals were sacrificed by cervical dislocation; blood was collected to measure total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL); aortae were collected to detect morphologic changes. Rats of the HFD group showed a significant increase in body weight (B.Wt), altered lipid profile increased expression of inducible nitric oxide synthase (iNOS), and decreased expression of endothelial nitric oxide synthase (eNOS). However, in HFD+SC there was a significant decrease in body weight gain and an improvement in lipid profile. Histopathological and ultrastructural variations observed in the aorta of the HFD group when treated with ADSCs showed preserved normal histological architecture and reduced atherosclerosis compared with the HFD group. This was evidenced by laboratory, histological, immunohistochemical, and morphometric studies. Thus, ADSCs reduced TC, TG, and LDL, reduced the expression of iNOS, and increased the expression of eNOS. The high-fat diet was likely to cause damage to the wall of blood vessels. Systemically transplanted ADSCs could home to the aorta, and further protect the aorta from HFD-induced damage.

Association of Anxiety and Depressive Symptoms and Treatment Adherence Among Patients With Type 2 Diabetes Mellitus in Jazan, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Diabetes mellitus is a serious public health concern. It is associated with many psychological problems, such as depression, anxiety, and eating disorders. These co-morbidities are associated with improper adherence to treatment, self-care, poor glycemic control, more complications, and worse outcomes. METHODS: This study aimed to measure the level of medication adherence among type 2 diabetics in Jazan, Saudi Arabia, and to find its association with their psychological status (specifically, depression and anxiety). A cross-sectional descriptive design was used among adults with type 2 diabetes at the Diabetes and Endocrinology Center in Jazan, Saudi Arabia. The estimated sample size was 480 patients. The General Medication Adherence Scale and Patient Health Questionnaire-4 (PHQ-4) were used as tools to achieve the study objectives. RESULTS: A total of 449 diabetic patients completed the survey (93.5% response rate). Patients with poor, low, and partial adherence account for 337 (75%) of patients and only 112 (25%) have good and high medication adherence. Employment and duration of illness were highly significant with a positive relationship to treatment adherence (p = 0.010 and 0.000, respectively). On the other hand, age and disease duration had a significant relationship with psychological disorders (p = 0.029 and 0.002, respectively). Of the patients, 64 (14.3%) had high scores on the PHQ-4, with depressive symptoms in 46 (10.24%) and anxiety symptoms in 75 (16.7%). Correlation analysis reveals that there is a highly significant negative correlation between psychological disorders and adherence to medications (r = -0.288, p = 0.000). CONCLUSION: A negative correlation between psychological disorders and adherence to medications was found. The findings indicate the importance of psychological support for diabetic patients for better treatment adherence.

Impact of Ramadan fasting on vision and headache-related quality of life in women with idiopathic intracranial hypertension: A prospective observational study.

BACKGROUND: Ramadan fasting is an obligatory religious practice for Muslims. However, research data on the effect of Ramadan on idiopathic intracranial hypertension (IIH) symptoms are lacking. This study aimed to study the effect of Ramadan fasting on the severity of headache and visual symptoms and related quality-of-life activities. METHODS: This prospective cohort study targeted females diagnosed with IIH (n = 102) who were eligible to fast for Ramadan in 2023. The patients were recruited from the Neurology Clinic in Beni-Suef University Hospital, Egypt. Body mass index (BMI), monthly headache days and intensity of headache attacks, six-item Headache Impact Test (HIT-6), and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores during Ramadan were compared to those during the (non-fasting) month of Shaaban, the preceding month to Ramadan. RESULTS: There was a significant increase in the BMI of patients with IIH in Ramadan compared to the (non-fasting) month of Shaaban, at a median (interquartile range [IQR]) of 30.5 (26.6-35.8) kg/m2 and 30.1 (26.6-35.2) kg/m2, respectively (p = 0.002). The median (IQR) value of monthly headache days was significantly increased during Ramadan in comparison to the (non-fasting) month of Shaaban, at 20 (11.5-30) vs. 15 (10-25) (p < 0.001). There was a statistically significant worsening in the visual analog scale (VAS) scores (median [IQR] 7 [5-8] vs. 6.5 [5-8]), HIT-6 scores (median [IQR] 61 [58-67] vs. 59 [53-61.5]), and NEI-VFQ-25 total scores (median [IQR] 1312.5 [1238.8-1435] vs 1290 [1165-1417.5]) during Ramadan in comparison to the (non-fasting) month of Shaaban (p < 0.001 for all comparisons). The change in BMI in Ramadan was positively correlated with the change in monthly headache days (r = 0.24, p = 0.014), VAS (r = 0.20, p = 0.043), HIT-6 (r = 0.25, p = 0.010) and NEI-VFQ-25 scores (r = 0.24, p = 0.016). CONCLUSION: Ramadan fasting had an aggravating effect on headache, visual symptoms, and related quality-of-life activities, which might be attributed to weight gain during this month. Whether proper nutritional management to prevent weight gain during Ramadan may help mitigate this worsening effect is a mission of future studies.

Prevalence of Guideline-Discordant Aspirin Use and Associated Adverse Events in Patients on Warfarin for Mechanical Valve Replacement.

BACKGROUND: For patients on warfarin for mechanical heart valve replacement, the 2020 American College of Cardiology and American Heart Association Guidelines recommend only adding aspirin in patients with a specific indication for antiplatelet therapy. This contrasts with prior guidelines, which recommended concomitant aspirin therapy. We sought to assess the prevalence of guideline-discordant aspirin use among patients on warfarin for mechanical heart valve replacement and to compare adverse event rates among patients with and without concomitant aspirin. METHODS: Patients on warfarin for mechanical heart valve replacement were identified from the Michigan Anticoagulation Quality Improvement Initiative registry. Patients with myocardial infarction, percutaneous coronary intervention, or coronary artery bypass within the past 12 months were excluded. Patients were divided into 2 groups based on aspirin use. Patient characteristics and bleeding and thromboembolic outcomes were compared. RESULTS: Four hundred forty-four patients met the inclusion criteria, with 341 (76.8%) on concomitant aspirin. The aspirin group was older (50.6 vs 46.3 years, P = .028) and had more hypertension (57.8% vs 46.6%, P = .046) but other patient characteristics were similar. The aspirin group had a higher rate of bleeding events (28.3 vs 13.3 per 100 patient-years, P < .001) and bleed-related emergency department visits (11.8 vs 2.9 per 100 patient-years, P = .001) compared with the non-aspirin group. There was no observed difference in rates of ischemic stroke (0.56 vs 0.48 per 100 patient-years, P = .89). CONCLUSIONS: A significant proportion of patients on warfarin for mechanical heart valve replacement are on guideline-discordant aspirin. Aspirin deprescribing in select patients may safely reduce bleeding events.

Identifying Clinical and Genetic Characteristics of Spinal Muscular Atrophy Patients and Families in Saudi Arabia.

INTRODUCTION:  Spinal muscular atrophy (SMA) is an inherited, neuromuscular disease characterized by the deterioration of spinal motor neurons, causing progressive muscular atrophy and weakening. It is an autosomal recessive disease with the mutation of the survival motor neuron 1 (SMN1) gene as a hallmark. Evidence suggests that the SMN2 gene modulates the severity of the disease. SMA is classified based on the maximum motor function achieved. This study aims to describe the genetic makeup and characteristics of an SMA cohort in the Kingdom of Saudi Arabia (KSA). METHODS:  Data from families presenting with SMA children was collected between January 2018 and December 2020. Blood samples were collected from patients and family members. Genetic testing for SMA and mutations was performed at a European central lab. RESULTS AND DISCUSSION:  Seventeen families were enrolled in the study, including 52 children. Among 34 parents, 28 were carriers with heterozygous deletion (82.3%), one (2.9%) had no deletion detected by multiplex ligation-dependent probe amplification (MLPA) but had point mutation by sequencing, one (2.9%) had homozygous deletion and was symptomatic, three (8.8%) had no deletion or point mutation and were presumed to have 2+0, and one (2.9%) was not tested. CONCLUSION:  This study provides insight into the carrier mutational analysis of families with SMA disease manifestations in KSA. Further studies are needed to understand the burden and impact of SMA among the Saudi population.

Assessment of serum levels of anti-gliadin (IgA and IgG) antibodies in patients with lichen planus: A pilot study.

Despite the fact that anti-gliadin antibodies (AGA) play a key role in coeliac disease (CD) screening, elevated AGA levels have been reported in several immune-mediated cutaneous conditions even in the absence of gastrointestinal disease clinical manifestations. A gluten-free diet led to improvements in some of these disorders. The link between oral lichen planus (LP) and CD was revealed, but there is currently no information available regarding the association between cutaneous LP and gluten sensitivity. This study aimed to assess the AGA (IgA and IgG) serum levels in LP patients compared to controls and to determine their correlation with LP severity. The study included 20 patients with cutaneous LP and 20 age- and sex-matched controls, both free of CD manifestations. The enzyme-linked immunosorbent assay (ELISA) technique was utilized for the evaluation of AGA (IgA and IgG) serum levels. Hepatitis C virus (HCV) antibodies in LP patients were evaluated qualitatively using a chromatographic immunoassay. In LP patients, AGA (IgA and IgG) serum levels were significantly elevated compared to controls (p = 0.015 and p=0.016, respectively). A significant positive correlation between AGA (IgG) serum levels and the age of patients (p= 0.024), duration of disease (p= 0.02), and LP severity index (p< 0.0001) was found. AGA serum levels were insignificantly different between HCV-positive and HCV-negative LP patients (p= 0.054). In conclusion, the significant elevation of serum AGA levels in LP patients reflects a possible link between LP and occult CD. Serum AGA (IgG) levels can be used as a marker of LP severity..

Plastic use for food and drinks and related knowledge, attitudes, and practices among a sample of Egyptians.

Introduction: Plastic is extensively used in everyday life, particularly for food and beverage containers. The inappropriate use of these containers may lead to the leaching of various chemicals from plastic, such as bisphenol A, phthalate, and styrene, which cause numerous adverse health effects. This study aimed to assess the knowledge, attitudes, and practices toward using plastic for food and drinks among a sample of the Egyptian population. Materials and methods: A questionnaire was designed based on scientific literature to assess sociodemographic data, knowledge, attitudes, and practices toward the use of plastic for food and drinks. A total of 639 participants were recruited by employing the convenience sampling technique. Results: More than half of the participants (347, 54%) had poor knowledge scores. Personal experiences, social media, and web pages represented the most common knowledge sources. A comparison between plastic-related knowledge scores and the studied sociodemographic characteristics revealed statistically significant differences in age, gender, education, marital status, residence, working, and socioeconomic standard. A good attitude was reported by the majority (515, 80.6%) of participants. The majority (493, 77.2%) were occasional and frequent plastic users and the practice scores were significantly associated with age, education, residence, and socioeconomic standard. Higher educational level, gender (women), and rural residence were predictors of good participants knowledge, while lower socioeconomic status and urban residence were predictors of bad participants practice in a multivariate logistic regression analysis. Conclusion: The observed unsatisfactory knowledge and practice scores vs. the high attitude indicates a knowledge gap that can help direct future improvements. We call for public awareness programs about safe plastic use and the related health hazards of plastic chemicals. We also stress upon the urgent need for a collaboration between health authorities and the plastic and food industry to guarantee that information about proper plastic use is conveyed to consumers.

TNIK is a conserved regulator of glucose and lipid metabolism in obesity.

Obesity and type 2 diabetes (T2D) are growing health challenges with unmet treatment needs. Traf2- and NCK-interacting protein kinase (TNIK) is a recently identified obesity- and T2D-associated gene with unknown functions. We show that TNIK governs lipid and glucose homeostasis in Drosophila and mice. Loss of the Drosophila ortholog of TNIK, misshapen, altered the metabolite profiles and impaired de novo lipogenesis in high sugar-fed larvae. Tnik knockout mice exhibited hyperlocomotor activity and were protected against diet-induced fat expansion, insulin resistance, and hepatic steatosis. The improved lipid profile of Tnik knockout mice was accompanied by enhanced skeletal muscle and adipose tissue insulin-stimulated glucose uptake and glucose and lipid handling. Using the T2D Knowledge Portal and the UK Biobank, we observed associations of TNIK variants with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior. These results define an untapped paradigm of TNIK-controlled glucose and lipid metabolism.

Qualitative structure-activity relationships of aryl isoprenoid derivatives as biorational juvenoids - reweighing.

Juvenoids are juvenile hormone (JH) mimetics, with specific structural features and defined molecular size that disrupt the target insect development. Juvenoid activity (= JH-type activity) of various isoprenoid-based derivatives as insecticidal candidates of the insect growth disruptors (IGDs) type were rated against the house fly, Musca domestica L. The epoxidized decenyl and nonenyl phenyl ether derivatives have more active compounds than those of both parent alkoxidized or olefinic structures. The highest juvenoid potency was shown by 3,4-methylenedioxyphenyl ethers of 8,9-epoxy-5,9-dimethy1-3,8-decadiene. Qualitative structure-activity relationships are offered to relate the chemical structure criteria to observed juvenoid-related activity. Differences in activity among the reported isoprenoid-based derivatives were qualitatively rationalized. This study advances understanding of the structural qualifications and activity determinants of isoprenoid juvenoids, which is important for the development of new filth flies eco-friendly insecticides. Supplementary Information: The online version contains supplementary material available at 10.1007/s42690-023-01025-3.

Efficient thermal face recognition method using optimized curvelet features for biometric authentication.

Biometric technology is becoming increasingly prevalent in several vital applications that substitute traditional password and token authentication mechanisms. Recognition accuracy and computational cost are two important aspects that are to be considered while designing biometric authentication systems. Thermal imaging is proven to capture a unique thermal signature for a person and thus has been used in thermal face recognition. However, the literature did not thoroughly analyse the impact of feature selection on the accuracy and computational cost of face recognition which is an important aspect for limited resources applications like IoT ones. Also, the literature did not thoroughly evaluate the performance metrics of the proposed methods/solutions which are needed for the optimal configuration of the biometric authentication systems. This paper proposes a thermal face-based biometric authentication system. The proposed system comprises five phases: a) capturing the user's face with a thermal camera, b) segmenting the face region and excluding the background by optimized superpixel-based segmentation technique to extract the region of interest (ROI) of the face, c) feature extraction using wavelet and curvelet transform, d) feature selection by employing bio-inspired optimization algorithms: grey wolf optimizer (GWO), particle swarm optimization (PSO) and genetic algorithm (GA), e) the classification (user identification) performed using classifiers: random forest (RF), k-nearest neighbour (KNN), and naive bayes (NB). Upon the public dataset, Terravic Facial IR, the proposed system was evaluated using the metrics: accuracy, precision, recall, F-measure, and receiver operating characteristic (ROC) area. The results showed that the curvelet features optimized using the GWO and classified with random forest could help in authenticating users through thermal images with performance up to 99.5% which is better than the results of wavelet features by 10% while the former used 5% fewer features. In addition, the statistical analysis showed the significance of our proposed model. Compared to the related works, our system showed to be a better thermal face authentication model with a minimum set of features, making it computational-friendly.

The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.

The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.

Outcomes of resective surgery in pediatric patients with drug-resistant epilepsy: A single-center study from the Eastern Mediterranean Region.

OBJECTIVE: Epilepsy surgery is widely accepted as an effective therapeutic option for carefully selected patients with drug-resistant epilepsy (DRE). There is limited data on the outcome of epilepsy surgery, especially in pediatric patients from the Eastern Mediterranean region. Hence, we performed a retrospective study examining the outcomes of resective surgery in 53 pediatric patients with focal DRE. METHODS: Patients with focal DRE who had undergone epilepsy surgery were included in the present study. All patients underwent a comprehensive presurgical evaluation. Postoperative seizure outcomes were classified using the Engel Epilepsy Surgery Outcome Scale. RESULTS: After surgery, 33 patients (62.2%) were Class I according to the Engel classification of surgical outcomes; eight patients (15.0%) were Class II, 11 (20.7%) were Class III, and one (1.8%) was Class IV. The relationships of presurgical, surgical, and postsurgical clinical variables to seizure outcomes were compared. Older age at seizure onset, older age at the time of surgery, the presence of focal to bilateral tonic-clonic seizures, seizure duration over 2 minutes, unsuccessful treatment with three or fewer antiseizure medications, lesions confined to one lobe (as demonstrated via magnetic resonance imaging [MRI]), surgical site in the temporal lobe, and histopathology including developmental tumors were significantly linked to an Engel Class I outcome. A univariate analysis of excellent surgical outcomes showed that lateralized semiology, localized interictal and ictal electroencephalogram (EEG) discharges, lateralized single-photon emission computed tomography and positron emission tomography findings, and temporal lobe resections were significantly related to excellent seizure outcomes. SIGNIFICANCE: The results of our study are encouraging and similar to those found in other centers around the world. Epilepsy surgery remains an underutilized treatment for children with DRE and should be offered early.

Adenosine monophosphate-activated protein kinase is elevated in human cachectic muscle and prevents cancer-induced metabolic dysfunction in mice.

BACKGROUND: Metabolic dysfunction and cachexia are associated with poor cancer prognosis. With no pharmacological treatments, it is crucial to define the molecular mechanisms causing cancer-induced metabolic dysfunction and cachexia. Adenosine monophosphate-activated protein kinase (AMPK) connects metabolic and muscle mass regulation. As AMPK could be a potential treatment target, it is important to determine the function for AMPK in cancer-associated metabolic dysfunction and cachexia. We therefore established AMPK's roles in cancer-associated metabolic dysfunction, insulin resistance and cachexia. METHODS: In vastus lateralis muscle biopsies from n = 26 patients with non-small cell lung cancer (NSCLC), AMPK signalling and protein content were examined by immunoblotting. To determine the role of muscle AMPK, male mice overexpressing a dominant-negative AMPKα2 (kinase-dead [KiDe]) specifically in striated muscle were inoculated with Lewis lung carcinoma (LLC) cells (wild type [WT]: n = 27, WT + LLC: n = 34, mAMPK-KiDe: n = 23, mAMPK-KiDe + LLC: n = 38). Moreover, male LLC-tumour-bearing mice were treated with (n = 10)/without (n = 9) 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to activate AMPK for 13 days. Littermate mice were used as controls. Metabolic phenotyping of mice was performed via indirect calorimetry, body composition analyses, glucose and insulin tolerance tests, tissue-specific 2-[3H]deoxy-d-glucose (2-DG) uptake and immunoblotting. RESULTS: Patients with NSCLC presented increased muscle protein content of AMPK subunits α1, α2, ß2, γ1 and γ3 ranging from +27% to +79% compared with control subjects. In patients with NSCLC, AMPK subunit protein content correlated with weight loss (α1, α2, ß2 and γ1), fat-free mass (α1, ß2 and γ1) and fat mass (α1 and γ1). Tumour-bearing mAMPK-KiDe mice presented increased fat loss and glucose and insulin intolerance. LLC in mAMPK-KiDe mice displayed lower insulin-stimulated 2-DG uptake in skeletal muscle (quadriceps: -35%, soleus: -49%, extensor digitorum longus: -48%) and the heart (-29%) than that in non-tumour-bearing mice. In skeletal muscle, mAMPK-KiDe abrogated the tumour-induced increase in insulin-stimulated TBC1D4thr642 phosphorylation. The protein content of TBC1D4 (+26%), pyruvate dehydrogenase (PDH; +94%), PDH kinases (+45% to +100%) and glycogen synthase (+48%) was increased in skeletal muscle of tumour-bearing mice in an AMPK-dependent manner. Lastly, chronic AICAR treatment elevated hexokinase II protein content and normalized phosphorylation of p70S6Kthr389 (mTORC1 substrate) and ACCser212 (AMPK substrate) and rescued cancer-induced insulin intolerance. CONCLUSIONS: Protein contents of AMPK subunits were upregulated in skeletal muscle of patients with NSCLC. AMPK activation seemed protectively inferred by AMPK-deficient mice developing metabolic dysfunction in response to cancer, including AMPK-dependent regulation of multiple proteins crucial for glucose metabolism. These observations highlight the potential for targeting AMPK to counter cancer-associated metabolic dysfunction and possibly cachexia.