High Type Research Articles

Sex Differences in Skeletal Muscle Pathology in Patients With Heart Failure and Reduced Ejection Fraction.

Women with heart failure and reduced ejection fraction (HFrEF) have greater symptoms and a lower quality of life compared with men; however, the role of noncardiac mechanisms remains poorly resolved. We hypothesized that differences in skeletal muscle pathology between men and women with HFrEF may explain clinical heterogeneity. Muscle biopsies from both men (n=22) and women (n=16) with moderate HFrEF (New York Heart Association classes I-III) and age- and sex-matched controls (n=18 and n=16, respectively) underwent transcriptomics (RNA-sequencing), myofiber structural imaging (histology), and molecular signaling analysis (gene/protein expression), with serum inflammatory profiles analyzed (enzyme-linked immunosorbent assay). Two-way ANOVA was conducted (interaction sex and condition). RNA-sequencing identified 5629 differentially expressed genes between men and women with HFrEF, with upregulated terms for catabolism and downregulated terms for mitochondria in men. mRNA expression confirmed an effect of sex (P<0.05) on proatrophic genes related to ubiquitin proteasome, autophagy, and myostatin systems (higher in all men versus all women), whereas proanabolic IGF1 expression was higher (P<0.05) in women with HFrEF only. Structurally, women compared with men with HFrEF showed a pro-oxidative phenotype, with smaller but higher numbers of type I fibers, alongside higher muscle capillarity (Pinteraction<0.05) and higher type I fiber areal density (Pinteraction<0.05). Differences in gene/protein expression of regulators of muscle phenotype were detected between sexes, including HIF1α, ESR1, VEGF (vascular endothelial growth factor), and PGC1α expression (P<0.05), and for upstream circulating factors, including VEGF, IL (interleukin)-6, and IL-8 (P<0.05). Sex differences in muscle pathology in HFrEF exist, with men showing greater abnormalities compared with women related to the transcriptome, fiber phenotype, capillarity, and circulating factors. These preliminary data question whether muscle pathology is a primary mechanism contributing to greater symptoms in women with HFrEF and highlight the need for further investigation.

Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function

Functional genetics has identified drug targets for metabolic disorders. Opioid use impacts metabolic homeostasis, although mechanisms remain elusive. Here, we explore the OPRD1 gene (encoding delta opioid receptor, DOP) to understand its impact on type 2 diabetes. Large-scale sequencing of OPRD1 and in vitro analysis reveal that loss-of-function variants are associated with higher adiposity and lower hyperglycemia risk, whereas gain-of-function variants are associated with lower adiposity and higher type 2 diabetes risk. These findings align with studies of opium addicts. OPRD1 is expressed in human islets and beta cells, with decreased expression under type 2 diabetes conditions. DOP inhibition by an antagonist enhances insulin secretion from human beta cells and islets. RNA-sequencing identifies pathways regulated by DOP antagonism, including nerve growth factor, circadian clock, and nuclear receptor pathways. Our study highlights DOP as a key player between opioids and metabolic homeostasis, suggesting its potential as a therapeutic target for type 2 diabetes.

Contextualizing the Use of Slang Words With References to Venom: Let There be Carnage Movie

This research entitled Slang words and Contextualization in Venom: Let There Be Carnage Movie, aimed to discuss the types of slang words and the contextualization the use of the slang word in the movie. The undergraduate thesis analysed the used of slang words in the conversations regarding the types and the contextualization of slang words. This research used the theory types of slang proposed by Allan and Burridge (2006) and the theory contextualization of slang proposed by Gumperz (1992) for the main theory. For the supporting theory used theory of sociolinguistics by Un Nisa (2019). The data of this study are from the utterances, words, and conversation occurred in the movie, in the form of slang words uttered by the characters dialogues. The analysed was use descriptive qualitative method. The results found that there were 5 slang words in the movie types and contextualization of slang, namely: Fresh and Creative, Flippant, Imitate, Acronym and Clipping. The result after analysing the movie, there were fourty six data in types and contextualization of slang. In the types and contextualization of slang, the highest type was flippant slang type and the lowest was acronym type.

Autoantibodies to truncated GAD(96-585) antigen stratify risk of early insulin requirement in adult-onset diabetes.

We investigated whether characterisation of full-length (f-)GADA responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA positive participants diagnosed with type 2 diabetes, we assessed associations of truncated (t-)GADA positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA positive without early insulin in comparison to f-GADA positive type 2 diabetes requiring insulin within 5 years, and type 1 diabetes (75% vs. 91% and 95% respectively, p<0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher type 1 diabetes genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, p=0.003), lower C-peptide (1156 pmol/L vs. 4289 pmol/L, p=1x10-7), and increased IA-2A positivity (23% vs. 6%, p=0.03). In survival analysis, t-GADA positivity was associated with early insulin requirement compared with those only positive for f-GADA, independently from age of diagnosis, f-GADA titre and duration of diabetes [adjusted HR 5.7 (95% CI 1.4, 23.5), p=0.017]. The testing of t-GADA in f-GADA positive individuals with type 2 diabetes identifies those who have genetic and clinical characteristics comparable to type 1 diabetes and stratifies those at higher risk of early insulin requirement.

Nasal brushing molecular endotyping distinguishes patients with chronic rhinosinusitis with nasal polyps with better response to dupilumab

BackgroundThere is evidence of pathophysiologic diversity in chronic rhinosinusitis with nasal polyps (CRSwNP), but data characterizing the molecular endotypes of CRSwNP and their association with treatment is lacking. ObjectivesTo identify gene signatures associated with CRSwNP endotypes, clinical features, and dupilumab treatment response. MethodsNasal brushing samples were collected from 89 patients randomized to dupilumab 300 mg every 2 weeks or placebo in the SINUS-52 trial (NCT02898454). Microarrays were used to identify transcriptional clusters and assess the relationship between gene expression and baseline clinical features and clinical response to dupilumab. Endotype signatures were determined using differential expression analysis. ResultsTwo distinct transcriptional clusters (C1 and C2) were identified, both with elevated type 2 biomarkers. At baseline, C2 patients had higher mean Nasal Polyp Score and higher type 2 biomarker levels than C1 patients. At Week 24, significant improvements in clinical outcomes (dupilumab vs placebo) were observed in both clusters, although the magnitude of improvements was significantly greater in C2 than C1, and more C2 patients demonstrated clinically meaningful responses. Gene sets enrichment analyses supported the existence of two molecular endotypes: C2 was enriched in genes associated with type 2 inflammation (including periostin, cadherin-26, and type 2 cysteine protease inhibitors), while C1 was enriched in genes associated with T cell activation and interleukin-12 production. ConclusionTwo distinct gene signatures associated with CRSwNP clinical features were identified; the endotype signatures were associated with clinical outcome measures and magnitude of dupilumab response.

Differences in bulk Fe content and density between type I and type II ordinary chondrite chondrules: Implications for parent body heterogeneities in oxidation state and O‐isotopic composition

AbstractType II chondrules have higher oxidation states than type I chondrules; in ordinary chondrites (OC), type II chondrules tend to be larger, richer in bulk Fe, and have higher densities than type I chondrules. Magnesian type IA chondrules tend to be richer in 16O than type II chondrules. Because the aerodynamic behavior of a particle is a function of the product of its size and density, type I and type II chondrules (or their precursors) were partly separated in the ordinary chondrite zone of the solar nebula prior to the accretion of OC parent asteroids. LL chondrites acquired a chondrule population with the highest type II/type I ratios, L chondrites acquired chondrules with an intermediate ratio, and H chondrites acquired chondrules with the lowest type II/type I ratios. This contributed to the observed differences among OC groups in oxidation state and O‐isotopic composition: in going from H to L to LL, mean oxidation state increases and mean Δ17O values increase. Higher oxidation is marked by increases in the FeO contents of olivine, low‐Ca pyroxene, chromite, and ilmenite; increases in the TiO2 content of chromite; and increases in the Co content of kamacite.

Practical implications of equating equivalence tests: Reply to Campbell and Gustafson (2022).

Linde et al. (2021) compared the "two one-sided tests" the "highest density interval-region of practical equivalence", and the "interval Bayes factor" approaches to establishing equivalence in terms of power and Type I error rate using typical decision thresholds. They found that the interval Bayes factor approach exhibited a higher power but also a higher Type I error rate than the other approaches. In response, Campbell and Gustafson (2022) showed that the performances of the three approaches can approximate one another when they are calibrated to have the same Type I error rate. In this article, we argue that these results have little bearing on how these approaches are used in practice; a concrete example is used to highlight this important point. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Myofiber-specific lipidomics unveil differential contributions to insulin sensitivity in individuals of African and European ancestry

AimsIndividuals of African ancestry (AA) present with lower insulin sensitivity compared to their European counterparts (EA). Studies show ethnic differences in skeletal muscle fiber type (lower type I fibers in AA), muscle fat oxidation capacity (lower in AA), whilst no differences in total skeletal muscle lipids. However, skeletal muscle lipid subtypes have not been examined in this context. We hypothesize that lower insulin sensitivity in AA is due to a greater proportion of type II (non-oxidative) muscle fibers, and that this would result in an ancestry-specific association between muscle lipid subtypes and peripheral insulin sensitivity. To test this hypothesis, we examined the association between insulin sensitivity and muscle lipids in AA and EA adults, and in an animal model of insulin resistance with muscle-specific fiber types. MethodsIn this cross-sectional study, muscle biopsies were obtained from individuals with a BMI ranging from normal to overweight with AA (N = 24) and EA (N = 19). Ancestry was assigned via genetic admixture analysis; peripheral insulin sensitivity via hyperinsulinaemic–euglycemic clamp; and myofiber content via myosin heavy chain immunohistochemistry. Further, muscle types with high (soleus) and low (vastus lateralis) type I fiber content were obtained from high-fat diet-induced insulin resistant F1 mice and littermate controls. Insulin sensitivity in mice was assessed via intraperitoneal glucose tolerance test. Mass spectrometry (MS)-based lipidomics was used to measure skeletal muscle lipid. ResultsCompared to EA, AA had lower peripheral insulin sensitivity and lower oxidative type 1 myofiber content, with no differences in total skeletal muscle lipid content. Muscles with lower type I fiber content (AA and vastus from mice) showed lower levels of lipids associated with fat oxidation capacity, i.e., cardiolipins, triacylglycerols with low saturation degree and phospholipids, compared to muscles with a higher type 1 fiber content (EA and soleus from mice). Further, we found that muscle diacylglycerol content was inversely associated with insulin sensitivity in EA, who have more type I fiber, whereas no association was found in AA. Similarly, we found that insulin sensitivity in mice was associated with diacylglycerol content in the soleus (high in type I fiber), not in vastus (low in type I fiber).Conclusions; Our data suggest that the lipid contribution to altered insulin sensitivity differs by ethnicity due to myofiber composition, and that this needs to be considered to increase our understanding of underlying mechanisms of altered insulin sensitivity in different ethnic populations.

Human epicardial fat has a beige profile and contains higher type 2 innate lymphoid cells than subcutaneous fat.

Epicardial adipose tissue (EAT) is a visceral fat that has been associated with coronary artery disease and atrial fibrillation. Previous work has revealed that EAT exhibits beige features. First, a new pan-genomic microarray analysis was performed on previously collected paired human EAT and thoracic subcutaneous AT (thSAT) from the EPICAR study (n = 31) to decipher a specific immune signature and its link with browning genes. Then, adaptive (T and B cells) and innate lymphoid cell (ILC1, ILC2, and ILC3) immunophenotyping assay panels, including CD127, CD117, and prostaglandin D2 receptor 2, were performed on prospectively collected paired human multiorgan donors (n = 18; INTERFACE study). In the EPICAR study, a positive correlation between the T helper cell subtype Th2 immune pathway and browning genes was found in EAT versus thSAT (r = 0.82; p < 0.0001). In the INTERFACE study, this correlation was also observed (r = 0.31; p = 0.017), and a preponderance of CD4+T cells, CD8+T cells, and a few B cells was observed in all ATs (p < 0.0001). An increase in ILCs was observed in visceral AT (VAT) (i.e., EAT + VAT; 30 ± 5 ILCs per gram of AT) compared with subcutaneous counterparts (i.e., thSAT + abdominal SAT; 8 ± 2 ILCs per gram of AT; p = 0.001), with ILC1 being the most frequent (ILC1 > ILC3 > ILC2). Numbers of ILCs per gram of AT correlated with several Th2 or browning genes (IL-13, TNF receptor superfamily member 9 [TNFRSF9], and alkaline phosphatase, biomineralization associated [ALPL]). Interestingly, a specific increase in EAT-ILC2 compared with other ATs was observed, including a significant proportion expressing CD69 and/or CD25 activation markers (97.9% ± 1.2%; p < 0.0001). Finally, more natural killer cells were observed in EAT + VAT than in thSAT + abdominal SAT (p = 0.01). Exclusion of patients with coronary artery disease in the EPICAR and INTERFACE studies did not modify the main findings. Gene expression phenotyping confirmed specific upregulation of Th2 pathway and browning genes (IL-33 and uncoupling protein 1 [UCP-1]) in EAT. This is the first study, to our knowledge, to provide a comparison between innate and adaptive lymphoid cells in human EAT. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging.

K-Nearest Neighbor Algorithm and Case Base Reasoning on Xenia Car Damage Detection Expert System

PT Astra Daihatsu Motor or commonly abbreviated as ADM is the Sole Agent Brand Holder (ATPM) of Daihatsu cars in Indonesia. Xenia car is one of the most popular cars in Indonesia. Although there are many Xenia car users, it is not uncommon for Xenia cars to experience damage caused by the ignorance of car users, where the car user only knows how to use it but does not know how to maintain the car properly and correctly. Before damage occurs to the car, the car usually experiences several symptoms of damage that the user does not realize. With that, there are often difficulties experienced by users to find out the type of damage to the car. The purpose of applying and designing applications in this study is to apply the Case Based Reasoning method with the K-Nearest Neighbor Algorithm to detect damage to Xenia cars and to design and build applications with the Case Based Reasoning method with the K-Nearest Neighbor Algorithm to detect damage to web-based Xenia cars. This research uses the Research and Development method. Based on the results of research from previous cases, the new case has similarities with 5 cases and the highest similitude value is with the highest type, namely the type of Injector Malfunction damage with a value of 0.625 or around 62.5%. This expert system application can detect and determine the results of Xenia car engine damage detection by applying a method that looks for the closest similarity value of new cases to old cases, namely the Case Based Reasoning method and the K-Nearest Neighbor Algorithm looking for the closest neighbors of the same weight value. This web-based expert system can be used by users to find the results of Xenia Car engine damage detection experienced by determining the symptoms that are available in web-based applications. This web-based application can also provide solutions from the detection results of the type of Xenia car engine damage.

Genetic Evidence for Distinct Biological Mechanisms That Link Adiposity to Type 2 Diabetes: Toward Precision Medicine.

We aimed to unravel the mechanisms connecting adiposity to type 2 diabetes. We employed MR-Clust to cluster independent genetic variants associated with body fat percentage (388 variants) and BMI (540 variants) based on their impact on type 2 diabetes. We identified five clusters of adiposity-increasing alleles associated with higher type 2 diabetes risk (unfavorable adiposity) and three clusters associated with lower risk (favorable adiposity). We then characterized each cluster based on various biomarkers, metabolites and Magnetic Resonance Imaging-based measures of fat distribution and muscle quality. Analyzing the metabolic signatures of these clusters revealed two primary mechanisms connecting higher adiposity to reduced type 2 diabetes risk. The first involves higher adiposity in subcutaneous tissues (abdomen and thigh), lower liver fat, improved insulin sensitivity, and decreased risk of cardiometabolic diseases and diabetes complications. The second mechanism is characterized by increased body size, enhanced muscle quality, with no impact on cardiometabolic outcomes. Furthermore, our findings unveil diverse mechanisms linking higher adiposity to higher disease risk, such as cholesterol pathways or inflammation. These results reinforce the existence of adiposity-related mechanisms that may act as protective factors against type 2 diabetes and its complications, especially when accompanied by reduced ectopic liver fat.

Effect of different pretreatments on the hydrolysis efficiency and flavor of squid viscera (Dosidicus gigas)

In order to better utilize the proteins in squid viscera (Dosidicus gigas), the effects of different pretreatments on the degree of hydrolysis (DH) and volatile compounds of hydrolysates were studied. The DH was used as an indicator to select alkaline protease as the optimal protease from 8 types of proteases. The hydrolysis conditions of alkaline protease and the flavor of the hydrolysates were investigated through single-factor, response surface methodology, and pretreatment-assisted hydrolysis experiments. The results showed that alkaline protease had the highest DH (42.08 ± 0.58%), with enzyme dosage of 1.5%, hydrolysis temperature of 45 °C, hydrolysis time of 5 h, and liquid-solid ratio of 4:1. The DH of the ultrasound group was significantly higher than other groups, with the highest DH (45.67 ± 0.34%) after ultrasound for 40 min (U40). The proportion of molecular weight < 1 kDa and the content of free amino acids (1613.64 mg/100 g) were the highest at U40. The electronic nose results indicated that the composition of organic sulfur and aliphatic compounds in U40 showed significant differences compared to other products. The U40 sample had the highest type and content of volatile compounds (especially benzaldehyde), which was more conducive to the volatilization of flavor substances. In conclusion, U40 pretreatment can effectively improve the DH and flavor of hydrolysates.

Outcomes of the Dulce Digital-COVID Aware (DD-CA) discharge texting platform for US/Mexico border Hispanic individuals with diabetes

BackgroundHispanic individuals have higher type 2 diabetes (T2D) prevalence, poorer outcomes, and are disproportionately affected by COVID-19. Culturally-tailored, diabetes educational text messaging has previously improved HbA1c in this population. MethodsDuring the pandemic, hospitalized Hispanic adults with T2D (N = 172) were randomized to receive Dulce Digital-COVID Aware (“DD-CA”) texting platform upon discharge plus diabetes transition service (DTS) or DTS alone. DD-CA includes diabetes educational messaging with additional COVID-safe messaging (e.g., promoting masking; social distancing; vaccination). FindingsAmong adults with poorly-controlled diabetes (Mean HbA1c = 9.6 ± 2.2 %), DD-CA did not reduce 30- or 90-day readmissions compared to standard care (28 % vs 15 %, p = .06; 37 % vs 35 %, p = .9, respectively). However, the improvement in HbA1c was larger among those in the DD-CA compared to DTS at 3 months (n = 56; −2.69 % vs. −1.45 %, p = .0496) with reduced effect at 6 months (n = 64; −2.03 % vs −0.91 %, p = .07). Low follow-up completion rates and the addition of covariates (to control for baseline group differences that existed despite randomization) impacted statistical power. InterpretationDuring the pandemic, DD-CA offered an alternative digital approach to diabetes and COVID education and support for a high-risk Hispanic population and achieved trends toward improvement in glycemic control despite relatively low engagement and not reducing hospital readmissions.

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Magnitude of Type I Interferon Responses by Plasmacytoid Dendritic Cells After TLR7 Stimulation Is Associated With Human Immunodeficiency Virus Type 1 (HIV-1) Reservoir Sizes in Cisgender Women With HIV-1 on Antiretroviral Therapy.

Human immunodeficiency virus type 1 (HIV-1) disease manifestations differ between cisgender women and men, including better control of viral replication during primary infection and less frequent residual HIV-1 replication on antiretroviral therapy (ART) in cisgender women with HIV-1 (WWH). Investigating plasmacytoid dendritic cell (pDC) functions and HIV-1 reservoir sizes in 20 WWH on stable ART, we observed inverse correlations between interferon-α and tumor necrosis factor responses of pDCs to Toll-like receptor 7/8 stimulation and intact/total proviral HIV-1 DNA levels. Additionally, ISG15 mRNA levels in peripheral blood mononuclear cells correlated with cytokine responses of pDCs. These findings demonstrate an association between higher type I interferon responses and lower HIV-1 reservoir sizes in WWH on ART, warranting studies to identify the underlying mechanisms.

Cross-sectional study of the associations between circulating vitamin D concentrations and insulin resistance in children aged 9–10 years of South Asian, black African Caribbean and white European origins

BackgroundLower circulating vitamin D 25-hydroxyvitamin D (25(OH)D) concentrations are associated with higher type 2 diabetes risk in adults, although causality remains uncertain. However, associations between 25(OH)D and type 2 diabetes...

Short-Term Effects of Botulinum Toxin-A Injection on the Medial Gastrocnemius Histological Features in Ambulant Children with Cerebral Palsy: A Longitudinal Pilot Study.

Botulinum toxin-A (BoNT-A) injection is known to exert beneficial effects on muscle tone, joint mobility and gait in children with cerebral palsy (CP). However, recent animal and human studies have raised the concern that BoNT-A might be harmful to muscle integrity. In CP-children, the impact of BoNT-A on muscle structure has been poorly studied, and inconsistent results have been reported. This study was aimed at determining the time course effect of a single BoNT-A administration on medial gastrocnemius (MG) morphology in CP-children. MG microbiopsies from 12 ambulant and BoNT-A-naïve CP-children (age, 3.4 (2.3) years, ranging from 2.5 to 7.8 years; seven boys and five girls; GMFCS I = 5, II = 4 and III = 3) were collected before and 3 and 6 months after BoNT-A treatment to analyze the fiber cross-sectional area (fCSA) and proportion; capillarization; and satellite cell (SC) content. Compared with the baseline, the fCSA decreased at 3 months (-14%, NS) and increased at 6 months (+13%, NS). Fiber size variability was significantly higher at 3 months (type I: +56%, p = 0.032; type IIa: +37%, p = 0.032) and 6 months (type I: +69%, p = 0.04; type IIa: +121%, p = 0.032) compared with the baseline. The higher type I proportion seen at 3 months was still present and more pronounced at 6 months (type I: +17%, p = 0.04; type IIx: -65%, p = 0.032). The capillary fiber density was reduced at 3 months (type I: -43%, NS; type II: -44%, p = 0.0320) but normalized at 6 months. There was a non-significant increase in SC/100 fibers at 3 months (+75%, NS) and 6 months (+40%, NS) compared with the baseline. These preliminary data suggest that BoNT-A induced alterations in the MG of children with CP, which were still present 6 months after BoNT-A injection but with signs of muscle recovery.

Perceived neighborhood disorder and type 2 diabetes disparities in Hispanic, Black, and White Americans.

Approximately 32 million Americans have type 2 diabetes, and that number continues to grow. Higher prevalence rates are observed among certain subgroups, including members of marginalized racial/ethnic groups as well as residents of disordered neighborhoods (i.e., those with more trash and vandalism). Institutionalized discriminatory practices have resulted in disproportionate representation of marginalized racial/ethnic groups in disordered neighborhoods compared to non-Hispanic Whites. These neighborhood disparities may partially contribute to health disparities, given that signs of neighborhood disorder often relate to a general withdrawal from the neighborhood, minimizing opportunities for both physical and social engagement. Yet, research suggests variability across racial/ethnic groups both in reporting rates of neighborhood disorder and in the extent to which neighborhood disorder is interpreted as posing a threat to health and well-being. Using 2016-2018 Health and Retirement Study data (n = 10,419, mean age = 67 years), a representative sample of older US adults, this study examined the possibility of racial/ethnic differences in associations between perceived neighborhood disorder and type 2 diabetes risk. Participants reported their perceptions of neighborhood disorder and type 2 diabetes status. Weighted logistic regression models predicted type 2 diabetes risk by perceived neighborhood disorder, race/ethnicity, and their interaction. Non-Hispanic Blacks and Hispanics had higher type 2 diabetes risk; these two groups also reported more disorder in their neighborhoods compared to non-Hispanic Whites. Perceiving more neighborhood disorder was associated with increased type 2 diabetes risk, but the interaction between race/ethnicity and disorder was not significant. Findings from the current study suggest that the negative effects of perceiving neighborhood disorder, a neighborhood-level stressor, extend to increased type 2 diabetes risk.

Diabetes in South Asians: Uncovering Novel Risk Factors With Longitudinal Epidemiologic Data: Kelly West Award Lecture 2023.

South Asian populations have a higher prevalence and earlier age of onset of type 2 diabetes and atherosclerotic cardiovascular diseases than other race and ethnic groups. To better understand the pathophysiology and multilevel risk factors for diabetes and cardiovascular disease, we established the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study in 2010. The original MASALA study cohort (n = 1,164) included 83% Asian Indian immigrants, with an ongoing expansion of the study to include individuals of Bangladeshi and Pakistani origin. We have found that South Asian Americans in the MASALA study had higher type 2 diabetes prevalence, lower insulin secretion, more insulin resistance, and an adverse body composition with higher liver and intermuscular fat and lower lean muscle mass compared with four other U.S. race and ethnic groups. MASALA study participants with diabetes were more likely to have the severe hyperglycemia subtype, characterized by β-cell dysfunction and lower body weight, and this subtype was associated with a higher incidence of subclinical atherosclerosis. We have found several modifiable factors for cardiometabolic disease among South Asians including diet and physical activity that can be influenced using specific social network members and with cultural adaptations to the U.S. context. Longitudinal data with repeat cardiometabolic measures that are supplemented with qualitative and mixed-method approaches enable a deeper understanding of disease risk and resilience factors. Studying and contrasting Asian American subgroups can uncover the causes for cardiometabolic disease heterogeneity and reveal novel methods for prevention and treatment.

Hospital incidence, mortality, and gender disparities in patients treated for type A aortic dissections in Switzerland - a secondary data analysis of Swiss DRG statistics.

The incidence of type A aortic dissection (TAAD) has increased in several countries in recent decades, but epidemiological data for Switzerland are lacking. Furthermore, there are conflicting data regarding a gender-disparity with higher type A aortic dissection mortality in women. This study analysed sex-specific hospital incidence and in-hospital mortality rates of TAAD in Switzerland. This study is a secondary data analysis of case-related hospital discharge data from the Swiss Federal Statistical Office for 2009-2018. Cases that were hospitalised and surgically treated for type A aortic dissection were included in this analysis. Standardised incidence rates were calculated using the European standard population in 2013. All-cause in-hospital mortality rates were calculated as raw values and standardised for age, sex, and the van Walraven comorbidity score. A total of 2117 participants were included in this study, of whom 67.1% were male. The age-standardised cumulative hospital incidence for type A aortic dissection treatment was 3.5 per 100,000 (95% CI: 3.3-3.7) for men and 1.7 (1.6-1.8) per 100,000 for women (p <0.001). The incidence rates increased in both sexes during the observed decade. The adjusted mortality rates for treatment of TAAD decreased from 27.6% (26.7-28.5%) in 2009 to 18.5% (17.9-19.1%) in 2018 in women, and they decreased from 19.0% (18.4-19.6%) to 12.3% (11.9-12.7%) in the same period in men. Multivariable logistic regression analysis revealed that female sex was significantly associated with higher mortality, with an odds ratio of 1.39 (1.07-1.79) (p = 0.012). Hospital incidence rates for the treatment of type A aortic dissection increased in both sexes over the observed decade. The mortality rate was significantly higher in women than it was in men, but it decreased in both sexes. TAAD remains a cardiovascular emergency with a high mortality rate even after emergency surgery.