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Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid m-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic ([DC.sub.12]), to mice at 20% of daily caloric intake for 9 weeks. [DC.sub.12] increased metabolic rate, reduced body fat, reduced liver fat, and improved glucose tolerance. We observed [DC.sub.12]-specific breakdown products in liver, kidney, muscle, heart, and brain, indicating that oral [DC.sub.12] escaped first-pass liver metabolism and was utilized by many tissues. In tissues expressing the 'a' isoform of acyl-CoA oxidase-1 (ACOX1), a key peroxisomal fatty acid oxidation enzyme, [DC.sub.12] was chain shortened to the TCA cycle intermediate succinyl-CoA. In tissues with low peroxisomal fatty acid oxidation capacity, [DC.sub.12] was oxidized by mitochondria. In vitro, [DC.sub.12] was catabolized even by adipose tissue and was not stored intracellularly. We conclude that [DC.sub.12] and other dicarboxylic acids may be useful for combatting obesity and for treating metabolic disorders., Introduction Changes in energy metabolism and mitochondrial function are noted across the spectrum of human diseases. First, there are numerous inborn errors of metabolism where chronic energy deficits and the [...]

Rationale: The role of FSTL-1 (follistatin-like 1) in lung homeostasis is unknown.Objectives: We aimed to define the impact of FSTL-1 attenuation on lung structure and function and to identify FSTL-1-regulated transcriptional pathways in the lung. Further, we aimed to analyze the association of FSTL-1 SNPs with lung disease.Methods: FSTL-1 hypomorphic (FSTL-1 Hypo) mice underwent lung morphometry, pulmonary function testing, and micro-computed tomography. Fstl1 expression was determined in wild-type lung cell populations from three independent research groups. RNA sequencing of wild-type and FSTL-1 Hypo mice identified FSTL-1-regulated gene expression, followed by validation and mechanistic in vitro examination. FSTL1 SNP analysis was performed in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort.Measurements and Main Results: FSTL-1 Hypo mice developed spontaneous emphysema, independent of smoke exposure. Fstl1 is highly expressed in the lung by mesenchymal and endothelial cells but not immune cells. RNA sequencing of whole lung identified 33 FSTL-1-regulated genes, including Nr4a1, an orphan nuclear hormone receptor that negatively regulates NF-κB (nuclear factor-κB) signaling. In vitro, recombinant FSTL-1 treatment of macrophages attenuated NF-κB p65 phosphorylation in an Nr4a1-dependent manner. Within the COPDGene cohort, several SNPs in the FSTL1 region corresponded to chronic obstructive pulmonary disease and lung function.Conclusions: This work identifies a novel role for FSTL-1 protecting against emphysema development independent of smoke exposure. This FSTL-1-deficient emphysema implicates regulation of immune tolerance in lung macrophages through Nr4a1. Further study of the mechanisms involving FSTL-1 in lung homeostasis, immune regulation, and NF-κB signaling may provide additional insight into the pathophysiology of emphysema and inflammatory lung diseases.

Background Food provision interventions (eg, produce/food prescriptions, food pharmacies, food voucher programs) that bridge clinic and community settings for improved nutritional health outcomes of at-risk patients have gained momentum. Little is known about the role of nutrition education and potential augmented impact on patient outcomes. Objective To describe intervention designs and outcomes of direct food provision clinic–community programs aimed at improving diabetes-related outcomes (glycated hemoglobin [HbA1c] levels) among patients with type 2 diabetes (T2DM) or prediabetes and food insecurity, and to compare nutrition education components across interventions. Methods The PubMed and Academic Search Complete databases were systematically searched for original peer-reviewed articles (published during 2011–2022) that described the impact of clinic–community food provision programs (ie, produce/food prescriptions, food pharmacies, and food voucher programs) onHbA1c values among adults diagnosed with T2DM or prediabetes and who screened positive for food insecurity or low income. Study designs, intervention approaches, program implementation, and intervention outcomes were described. Results Ten studies representing 8 distinct programs were identified. There was a high degree of variation in the studies' design, implementation, and evaluation. Across the 8 programs, 6 included nutrition education; of these, 1 used a theoretical framework, and 3 incorporated goal setting. Nutrition education covered multiple topical contents, including general nutrition knowledge, fruit and vegetable consumption, and accessing resources (eg, enrolling in the Supplemental Nutrition Assistance Program). Furthermore, the education was delivered through various formats (from 1-on-1 to group-based sessions), educators (community health workers, registered dietitians, physicians), and durations (from a single session to biweekly). All programs with a nutrition education component reported reduced participant HbA1c, and 4 demonstrated an increase in fruit and vegetable purchases or improved dietary quality. The remaining 2 programs that did not include nutrition education yielded mixed results. Conclusion The majority of programs included a nutrition education component; however, there was a high degree of heterogeneity in terms of content, educator, and duration. Patients who participated in programs that included nutrition education had consistent reductions in HbA1c. These observational trends warrant further exploration to conclusively determine the impact of nutrition education on patient outcomes participating in clinic–community food provision programs. [ABSTRACT FROM AUTHOR]

Studying drug utilization helps to develop twin concepts for therapeutic formulation and essential drug lists. The main preference of using Antiepileptic drug (AED) therapy is that patients can be seizure-free for their lifetime. Treating children with epilepsy remains a major challenge, despite having several AEDs. Hence, we aimed to study drug utilization patterns among pediatric patients with epilepsy. This prospective study was conducted on 150 patients lesser than 18 years of age, receiving antiepileptic drugs. A specially designed case record form was used to collect the data on socioeconomic status, disease data, and treatment details. The majority of the children were females (60.6%), ages ranged from day 1 to 4 years (56.6%). About 35.33% were skilled laborers followed by 32.23% semi-skilled. Around 49.3% of patients belonged to the lower-middle-class family and 41.33% were diagnosed to have generalized tonic-clonic seizures (GTCS). The majority of the children were on monotherapy (81.33%) while 18.66% were on dual therapy or polytherapy. Regarding the usage of antiepileptic drugs, we found that 70.66% of children were on older AEDs like sodium valproate (27.33%) followed by clobazam (31.33%). Levetiracetam was the only new antiepileptic drug that was prescribed in 10% of patients. Monotherapy is considered as best modality, due to its low cost, safety profile, and lesser drug interactions. It can also improve drug treatment compliance and adherence. Along with older AEDs, there has been an increase in the utilization of newer AEDs, which help to broaden the therapeutic option towards the management of childhood epilepsy with a better safety profile.

This article discusses the testing of lubrication properties of CAc treated and non-treated denim fabric samples. It explains that denim jeans are typically made from cotton serge fabric and are 14.5 oz in weight. The article explores the friction factor of denim and its impact on the quality and appearance of denim products. It also discusses the health issues related to fabric friction, such as low sperm count, urinary tract infections, and fungal infections. The article concludes by presenting optimized finishing conditions for denim fabrics based on antibacterial and antifungal activity. Additionally, the article mentions the development of a fabric-based touch sensor by NC State University, which has the potential to replace buttons on clothing and control electronic devices through touch. [Extracted from the article]

Following injury and refractive surgery, corneal wound healing can initiate a protracted fibrotic response that interferes with ocular function. This fibrosis is related, in part, to the myofibroblast differentiation of corneal keratocytes in response to transforming growth factor beta 1 (TGF-β1). Previous studies have shown that changes in the mechanical properties of the extracellular matrix (ECM) can regulate this process, but the mechanotransductive pathways that govern stiffness-dependent changes in keratocyte differentiation remain unclear. Here, we used a polyacrylamide (PA) gel system to investigate how mechanosensing via focal adhesions (FAs) regulates the stiffness-dependent myofibroblast differentiation of primary corneal keratocytes treated with TGF-β1. Soft (1 kPa) and stiff (10 kPa) PA substrata were fabricated on glass coverslips, plated with corneal keratocytes, and cultured in defined serum free media with or without exogenous TGF-β1. In some experiments, an inhibitor of focal adhesion kinase (FAK) activation was also added to the media. Cells were fixed and stained for F-actin, as well as markers for myofibroblast differentiation (α-SMA), actomyosin contractility phosphorylated myosin light chain (pMLC), focal adhesions (vinculin), or Smad activity (pSmad3). We also used traction force microscopy (TFM) to quantify cellular traction stresses. Treatment with TGF-β1 elicited stiffness-dependent differences in the number, size, and subcellular distribution of FAs, but not in the nuclear localization of pSmad3. On stiff substrata, cells exhibited large FAs distributed throughout the entire cell body, while on soft gels, the FAs were smaller, fewer in number, and localized primarily to the distal tips of thin cellular extensions. Larger and increased numbers of FAs correlated with elevated traction stresses, increased levels of α-SMA immunofluorescence, and more prominent and broadly distributed pMLC staining. Inhibition of FAK disrupted stiffness-dependent differences in keratocyte contractility, FA patterning, and myofibroblast differentiation in the presence of TGF-β1. Taken together, these data suggest that signaling downstream of FAs has important implications for the stiffness-dependent myofibroblast differentiation of corneal keratocytes.

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.

Hepatocyte Growth Factor (HGF) and Fibroblast Growth Factor 2 (FGF2) are receptor tyrosine kinase agonists that promote cell survival after tissue injury and angiogenesis, cell proliferation and migration during tissue repair and regeneration. Both ligands have potential as systemic treatments for ischemia-reperfusion injury, however clinical use of HGF and FGF2 has been limited by poor pharmacokinetic profiles, i.e., their susceptibility to serum proteases, rapid clearance and short half-lives. Previously, we reported vaso- and cardioprotective protein complexes formed between HGF and polyclonal, non-specific immunoglobulin (IgG) with therapeutic efficacy in a rat model of myocardial ischemia with reperfusion (MI/R). Here, using a pre-clinical porcine MI/R model, we demonstrate human HGF/IgG complexes provide significant myocardial salvage, reduce infarct size, and are detectable in myocardial tissue 24 h after intracoronary injection. Furthermore, we show that multiple daily infusions of HGF/IgG complexes after MI do not lead to production of HGF-specific auto-antibodies, an important concern for administered biologic drugs. In experiments to identify other growth factors that non-covalently interact with IgG, we found that human FGF2 associates with IgG. Similar to human HGF/IgG complexes, FGF2/IgG complexes protected primary human cardiac endothelial cells under simulated ischemia (1% oxygen and nutrient deprivation) for 48–72 h. Molecular modeling studies suggested that FGF2 and HGF both interact with the Fc domain of IgG. Also, we tested whether an Fc-fusion protein would bind FGF2 to form complexes. By native gel electrophoretic assays and biochemical pulldowns, we found that Jagged1, a Notch1 ligand that controls stem cell self-renewal and tissue regeneration, bound FGF2 when presented as a Jagged1- Fc fusion protein. Our results suggest that human growth factor/IgG and FGF2/Fc- fusion complexes have potential to provide a biologics platform to treat myocardial ischemia-reperfusion and other forms of tissue injury.

Objective: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure‐induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. Methods: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM− (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). Results: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM− subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM− an established association. Burden analysis did not identify any single burdened gene or gene set. Significance: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene–disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM− and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM− remains to be elucidated. [ABSTRACT FROM AUTHOR]

Aloe vera, Adhathoda vasica, Agele marmelos, Calendula officinalis, and Solanum trilobatum herbal extracts have been used to treat cotton fabric using the pad-dry cure technique. Three distinct herbal treatments have been used on the fabrics, each of which has its unique therapeutic properties which is more suited to older individuals. The study focuses on developing herbal finished fabrics for old age people to prevent them from microbes and UV rays, and to increase the comfort property. Air permeability, wickability, absorbency, thermal conductivity, tensile strength anti-microbial and UV repellence properties have been studied. It is found that the finished fabrics show moderately good UV repellent protection and has antimicrobial creativity. [ABSTRACT FROM AUTHOR]

Thermal comfort characteristics of polyester and cotton fibres blends (100:0, 50:50 and 0:100) having in four different structures, such as single jersey, cross tuck, cross miss and twill, at two different loop lengths (0.29 cm and 0.32 cm) have been studied. The results evidently prove that the knitted fabrics made from 100% polyester show better thermal comfort properties, possessing an appreciable comfort level; hence they are applicable for active sportswear textiles. The structure and the loop length of the fabric influence the thermal property to a greater extent. The fabric knitted from 100% polyester with a cross-miss structure on a loop length of 0.32 cm shows an excellent thermal comfort characteristic as compared to other samples due to its suitable thermal conduction behavior. [ABSTRACT FROM AUTHOR]