Electron transport chain inhibition increases cellular dependence on purine transport and salvage.

Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage. In human lung cancer, tumors with markers of low oxidative mitochondrial metabolism exhibit enhanced expression of the salvage enzyme hypoxanthine phosphoribosyl transferase 1 (HPRT1) and high levels of the HPRT1 product inosine monophosphate. Mechanistically, ETC blockade activates the pentose phosphate pathway, providing phosphoribosyl diphosphate to drive purine salvage supplied by uptake of extracellular bases. Blocking HPRT1 sensitizes cancer cells to ETC inhibition. These findings demonstrate how cells remodel purine metabolism upon ETC blockade and uncover a new metabolic vulnerability in tumors with low respiration.

Palliative procedures for malignant gastric outlet obstruction: a network meta-analysis.

BACKGROUND: The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. This systematic review aimed to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting. METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform for randomized controlled trials (RCTs) and cohort studies comparing the four treatments for malignant GOO. We included studies that reported at least one of the following clinical outcomes: clinical success, 30-day mortality, reintervention rate, or length of hospital stay. Evidence from RCTs and non-RCTs was naïve combined to perform network meta-analysis through the frequentist approach using an inverse variance model. Treatments were ranked by P score. RESULTS: This network meta-analysis included 3617 patients from 4 RCTs, 4 prospective cohort studies, and 32 retrospective cohort studies. PGJ was the optimal approach in terms of clinical success and reintervention (P scores: 0.95 and 0.90, respectively). EUS-GE had the highest probability of being the optimal treatment in terms of 30-day mortality and complications (P scores: 0.82 and 0.99, respectively). Cluster ranking to combine the P scores for 30-day mortality and reintervention indicated the benefits of PGJ and EUS-GE (cophenetic correlation coefficient: 0.94; PGJ and EUS-GE were in the same cluster). CONCLUSION: PGJ and EUS-GE are recommended for malignant GOO. PGJ could be the alternative choice in centers with limited resources or in patients who are unsuitable for EUS-GE.

Prevalence and determinants of constipation in children in Asia: a systematic review and meta-analysis.

Background: Constipation is prevalent worldwide, significantly increasing healthcare costs and diminishing the quality of life in children affected. Current studies have yielded mixed results regarding the factors associated with constipation, and mainly focusing on patients outside of Asia. Moreover, most of these studies lack focus on the paediatric population. This study aimed to identify the prevalence and associated factors of constipation among children in Asia. Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Scopus, and Cochrane for cohort and cross-sectional studies published from database inception up to October 12, 2022, and continued with manual searching until September 2, 2023. Eligible studies were those that included children in Asia aged 0-18 years old suffering from idiopathic constipation, with prevalence value provided in the English abstract. The analysis included clinical and general population. Children with organic constipation, who had undergone gastrointestinal surgery, or with congenital defects were excluded, as these factors affect the incidence of constipation. Data included in the analysis were extracted from published reports only. The extracted data were pooled using random-effects model to analyse the prevalence of constipation in children in Asia. This study is registered with PROSPERO, CRD42022367122. Findings: Out of 4410 systematically searched studies and 36 manually searched ones, a total of 50 studies were included in the final analysis, encompassing data from 311,660 children residing in Asia. The pooled prevalence of constipation was 12.0% (95% CI 9.3-14.6%, I2 = 99.8%). There was no significant difference in constipation prevalence observed by sex and geographical location. Nonetheless, adolescents and children aged 1-9 years exhibited a significantly higher prevalence constipation compared to infants (p < 0.0001) Additionally, significant differences in constipation rates were observed across various diagnostic methods, population sources, and mental health conditions. Interpretation: Despite the high heterogeneity resulting from varying diagnostic tools or definitions used among studies, our review adds to the literature on constipation among children in Asia. It reveals a notably high prevalence of constipation in this demographic. Diagnostic methods, age, and compromised mental health emerged as significant influencers of constipation among children in Asia, highlighting potential strategies to mitigate constipation prevalence in children in Asia. Funding: The National Science and Technology Council, Taiwan.

Crystallization-Induced Flower-like Superstructures via Peptoid Helix Assembly.

We report a unique method to construct hierarchical superstructures based on molecular programming of peptidomimetics. Chiral steric hindrance in the polymer backbone stabilizes peptoid helices that crystallize into nanosheets during solvent evaporation. The stacking of nanosheets results in flower-like superstructures. The helical peptoid, nucleated from chiral monomers, is characterized as locally stiffer and more extended than the unstructured peptoid. Molecular dynamics (MD) simulations further suggest a constraint on the dihedral angles and a preference toward the trans configuration, resulting in an extended chain structure. The nanosheet assemblies at various length scales indicate an extent of intermolecular ordering amplified by chiral steric hindrance. Such molecular programming and processing protocols will benefit the future design and controlled assembly of hierarchical peptidomimetics.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Improved super-resolution ribosome profiling reveals prevalent translation of upstream ORFs and small ORFs in Arabidopsis.

A crucial step in functional genomics is identifying actively translated ORFs and linking them to biological functions. The challenge lies in identifying short ORFs, as their identification is greatly influenced by data quality and depth. Here, we improved the coverage of super-resolution Ribo-seq in Arabidopsis (Arabidopsis thaliana), revealing uncharacterized translation events for nuclear, chloroplastic, and mitochondrial genes. Assisted by a transcriptome assembly, we identified 7,751 unconventional translation events, comprising 6,996 upstream ORFs (uORFs) and 209 downstream ORFs on annotated protein-coding genes, as well as 546 ORFs in presumed noncoding RNAs. Proteomic data confirmed the production of stable proteins from some of these unannotated translation events. We present evidence of active translation from primary transcripts of trans-acting small interfering RNAs (TAS1-4) and microRNAs (pri-MIR163 and pri-MIR169) and periodic ribosome stalling supporting cotranslational decay. Additionally, we developed a method for identifying extremely short uORFs, including 370 minimum uORFs (AUG-stop), and 2,921 tiny uORFs (2 to 10 amino acids) and 681 uORFs that overlap with each other. Remarkably, these short uORFs exhibit strong translational repression as do longer uORFs. We also systematically discovered 594 uORFs regulated by alternative splicing, suggesting widespread isoform-specific translational control. Finally, these prevalent uORFs are associated with numerous important pathways. In summary, our improved Arabidopsis translational landscape provides valuable resources to study gene expression regulation.

Ultrasound guidance for transfemoral access in coronary procedures: an individual participant-level data metaanalysis from the femoral ultrasound trialist collaboration.

BACKGROUND: Randomised controlled trials of ultrasound (US)-guided transfemoral access (TFA) for coronary procedures have shown mixed results. AIMS: We aimed to compare US-guided versus non-US-guided TFA from randomised data in an individual participant-level data (IPD) meta-analysis. METHODS: We completed a systematic review and an IPD meta-analysis of all randomised controlled trials comparing US-guided versus non-US-guided TFA for coronary procedures. We performed a one-stage mixed-model meta-analysis using the intention-to-treat population from included trials. The primary outcome was a composite of major vascular complications or major bleeding within 30 days. RESULTS: A total of 2,441 participants (1,208 US-guided, 1,233 non-US-guided) from 4 randomised clinical trials were included. The mean age was 65.5 years, 27.0% were female, and 34.5% underwent a percutaneous coronary intervention. The incidence of major vascular complications or major bleeding (34/1,208 [2.8%] vs 55/1,233 [4.5%]; odds ratio [OR] 0.61, 95% confidence interval [CI]: 0.39-0.94; p=0.026) was lower in the US-guided TFA group. In the prespecified subgroup of participants who received a vascular closure device, those randomised to US-guided TFA experienced a reduction in the primary outcome (2.1% vs 5.6%; OR 0.36, 95% CI: 0.19-0.69), while no benefit for US guidance was observed in the subgroup without vascular closure devices (4.1% vs 3.3%; OR 1.21, 95% CI: 0.65-2.26; interaction p=0.009). CONCLUSIONS: In participants undergoing coronary procedures by TFA, US guidance decreased the composite outcome of major vascular complications or bleeding and may be especially helpful when using vascular closure devices.

Redifferentiated cardiomyocytes retain residual dedifferentiation signatures and are protected against ischemic injury.

Cardiomyocyte proliferation and dedifferentiation have fueled the field of regenerative cardiology in recent years, whereas the reverse process of redifferentiation remains largely unexplored. Redifferentiation is characterized by the restoration of function lost during dedifferentiation. Previously, we showed that ERBB2-mediated heart regeneration has these two distinct phases: transient dedifferentiation and redifferentiation. Here we survey the temporal transcriptomic and proteomic landscape of dedifferentiation-redifferentiation in adult mouse hearts and reveal that well-characterized dedifferentiation features largely return to normal, although elements of residual dedifferentiation remain, even after the contractile function is restored. These hearts appear rejuvenated and show robust resistance to ischemic injury, even 5 months after redifferentiation initiation. Cardiomyocyte redifferentiation is driven by negative feedback signaling and requires LATS1/2 Hippo pathway activity. Our data reveal the importance of cardiomyocyte redifferentiation in functional restoration during regeneration but also protection against future insult, in what could lead to a potential prophylactic treatment against ischemic heart disease for at-risk patients.

Dietary and lifestyle factors associated with troublesome gastroesophageal reflux symptoms in Vietnamese adults.

Background: Dietary and lifestyle habits related to troublesome gastroesophageal reflux symptoms (tGERS) differ significantly across populations. There have yet to be studies on the Vietnamese population. Aims: To identify dietary and lifestyle habits associated with tGERS in Vietnamese adults. Methods: A cross-sectional survey was conducted among Vietnamese adults aged 18 years and older from March 2023 to May 2023. Participants were recruited online through a widely read national newspaper and Facebook, one of Vietnam's most popular social media platforms. The survey questionnaire comprised 27 questions covering participants' basic demographic information, dietary and lifestyle habits, the presence and characteristics of tGERS, and inquiries about specific dietary and lifestyle patterns, foods, and beverages associated with tGERS. Results: A total of 4,400 valid responses were collected, including 2050 participants without tGERS and 2,350 participants with tGERS. Multivariate analysis showed several factors associated with tGERS, including eating beyond fullness (OR 1.383, CI95% 1.127-1.698), tight clothing (OR 1.627, CI95% 1.256-2.107), stress (OR 1.566, CI95% 1.363-1.800), and insomnia (OR 1.321, CI95% 1.129-1.546). Among habits associated with tGERS, eating beyond fullness was the most frequently reported (64.6%). Interestingly, although a short meal-to-bed time and staying up late after midnight were not risk factors for tGERS, they were two common factors associated with tGERS in symptomatic participants, particularly those with nocturnal reflux symptoms. For food triggers, the three most common ones were greasy foods (71.9%), sour/spicy soups (64.7%), and citrus fruits (36.0%). In terms of beverages, carbonated soft drinks were at the top of triggering tGERS (40.3%), and beer and orange juice were the second and third most common triggers, accounting for 35.7 and 30.6%, respectively. Conclusion: We reported the dietary and lifestyle habits associated with tGERS in Vietnamese adults for the first time. These findings will serve as a basis for future studies on the primary prevention and nondrug management of tGERS in Vietnam.

A Clinicopathologic Continuum of Eosinophilic Gastrointestinal Diseases in an Adult With Tuberculosis and Latent Hepatitis B Virus Infection.

Eosinophilic gastroenteritis (EGE) is considered distinct from eosinophilic colitis (EC). A 59-year-old man presented with a colonic tumor, who had resolution of pain and diarrhea after surgery, then 7 months later developed proton-pump inhibitor-responsive dysphagia with esophagitis, and 9 months later presented again with pain and diarrhea where EGE with concurrent eosinophilic esophagitis was diagnosed. Review of the resected tumor specimen identified EC with an adenoma. Workup revealed tuberculosis and latent hepatitis B virus requiring treatment before commencing immunosuppressive therapy plus a 6-food elimination diet that led to complete resolution within 3 weeks. EC may precede EGE and eosinophilic esophagitis.

Reemergence of Cosmopolitan Genotype Dengue Virus Serotype 2, Southern Vietnam.

We performed phylogenetic analysis on dengue virus serotype 2 Cosmopolitan genotype in Ho Chi Minh City, Vietnam. We document virus emergence, probable routes of introduction, and timeline of events. Our findings highlight the need for continuous, systematic genomic surveillance to manage outbreaks and forecast future epidemics.

Primary immature teratoma of the liver in an adult: Case report.

Teratoma is an uncommon germ cell tumor and develops from at least 2 of the 3 germ cell layers: ectoderm, mesoderm, and endoderm. The origin of teratoma is primordial germ cells that migrate from the allantois to the gonadal ridges during embryogenesis. The teratomas can be intragonadal or extragonadal. Primary extragonadal teratoma is defined as if there is no evidence of a primary tumor in the testicles or ovaries. Common extragonadal sites include the anterior mediastinum, retroperitoneum, sacral region, and intracranial cavity. Primary intrahepatic teratomas are extremely rare, accounting for less than 1% of all teratoma cases. Hepatic teratomas are more common in children than in adults. We present a case of an immature primary hepatic teratoma in an adult woman.

Internal controls driven by mindfulness toward enhanced ethical behaviors: Empirical evidence from Vietnam.

This study develops and tests a moderated mediation model regarding the effectiveness of internal control structure on organizational ethical behaviors via the mediating role of internal control effectiveness and the moderating role of organizational mindfulness in the relationship between internal control structure and internal control effectiveness. The proposed model and its hypotheses were tested using partial least squares structural equation modeling (PLS-SEM) in SmartPLS3 with survey data from 540 large Vietnamese manufacturing and service firms. This study found the following: (1) The internal control structure positively affects internal control effectiveness, which in turn promotes ethical organizational behaviors; and (2) The effect of internal control structure on internal control effectiveness is amplified by strengthening organizational mindfulness. The findings demonstrate that combining internal control systems and organizational mindfulness contributes to the ethical business practices of firms in an emerging market. Our study bridges the gap in the literature on internal control and mindfulness by providing empirical evidence on how the interaction between organizational mindfulness and internal control systems can promote ethical business practices. Additionally, our study advances the current understanding of how internal control systems can interact with organizational mindfulness to influence ethical business practices in the context of an emerging market.

Benefits of Short-term Premature Mortality Reduction Attributed to PM2.5 Pollution: A Case Study in Long an Province, Vietnam.

PM2.5 pollution exposure is the leading cause of disease burden globally, especially in low- and middle-income countries, including Vietnam. Therefore, economic damage in this context must be quantified. Long An province in the Southern Key Economic (SKE) region was selected as a research area. This study aimed to evaluate PM2.5-related human health effects causing early deaths attributable to respiratory, cardiovascular, and circulatory diseases in all ages and genders. Health end-points and health impact estimation, economic loss model, groups of PM2.5 concentration data, data of exposed population, data of baseline premature mortality rate, and data of health impact functions were used. Hourly PM2.5 concentration data sets were generated specifically using the coupled Weather Research and Forecasting Model (WRF)/Community Multiscale Air Quality Modelling System (CMAQ) models. Daily PM2.5 pollution levels considered mainly in the dry season (from January to April 2018) resulted in 12.9 (95% CI - 0.6; 18.7) all-cause premature deaths per 100,000 population, of which 7.8 (95% CI 1.1; 7.1), 1.5 (95% CI - 0.2; 3.1), and 3.6 (95% CI - 1.5; 8.5) were due to respiratory diseases (RDs; 60.54%), cardiovascular diseases (CVDs; 11.81%), and circulatory system diseases (CSDs; 27.65%) per 100,000 population, respectively. The total economic losses due to acute PM2.5 exposure-related premature mortality cases reached 62.0 (95% CI - 2.7; 89.6) billion VND, equivalent to 8.3 (95% CI - 0.4; 12.0) million USD. The study outcomes contributed remarkably to the generation and development of data sources for effectively managing ambient air quality in Long An.

Assessment of rice yield and economic losses caused by ground-level O3 exposure in the Mekong delta region, Vietnam.

The Lower Mekong Delta region (LMD) accounts for 90% of Vietnam's rice exports; however, the air quality in the LMD is remarkably reduced by ground-level ozone (O3) pollution. This study aimed to quantify the relative yield and economic value losses in rice-growing crop seasons affected by ground-level O3 concentrations across the LMD. The results of this study can serve as a basis for extensive assessments for the following years and support environmental managers to propose control measures of O3 precursor emissions (NOx and VOCs) from man-made sectors, as well as build protective solutions for rice farming in LMD. Two ground-level O3 exposure metrics of M7 and AOT40 reflecting ground-level O3 pollution impacts, combined with the model of exposure-relative yield relationship (or surface O3-crop models), were used to assess losses of crop production (CPL) and economic cost losses (ECL) caused by rice crop yield reductions. For the M7 metric of ground-level O3 exposure, the average value was 14.746 ppbV, with levels ranging from 13.959 ppbV to 15.502 ppbV, and the affected area was spread across 1309.39 thousand hectares. The AOT40 exposure metric reached an average value of 11.490 ppbV, with a range of 0.000-31.665 ppbV. The highest exposure level was 17.503-31.653 ppbV, covering an area of 747.01 thousand hectares. The total CPL of the three rice crops over the LMD was 9593.52 tonnes (accounting for 0.039% of the total value of rice production in the region), with a total corresponding EPL of 62.405 billion VND (equivalent to 2761.01 thousand USD). The results are considered a baseline study to serve as a basis for extensive assessments for the following years and support for the environmental managers to propose control measures of O3 precursor emissions (NOx and VOCs) from man-made sectors as well as build protective solutions in rice farming in LMD shortly.

Histological and immunohistochemical guide to tendon tissue.

Tendons are unique dense connective tissues with discrete zones having specific structure and function. They are juxtaposed with other tissues (e.g., bone, muscle, and fat) with different compositional, structural, and mechanical properties. Additionally, tendon properties change drastically with growth and development, disease, aging, and injury. Consequently, there are unique challenges to performing high quality histological assessment of this tissue. To address this need, histological assessment was one of the breakout session topics at the 2022 Orthopaedic Research Society (ORS) Tendon Conference hosted at the University of Pennsylvania. The purpose of the breakout session was to discuss needs from members of the ORS Tendon Section related to histological procedures, data presentation, knowledge dissemination, and guidelines for future work. Therefore, this review provides a brief overview of the outcomes of this discussion and provides a set of guidelines, based on the perspectives from our laboratories, for histological assessment to assist researchers in their quest to utilize these techniques to enhance the outcomes and interpretations of their studies.

Advancement of cloud-based accounting effectiveness, decision-making quality, and firm performance through digital transformation and digital leadership: Empirical evidence from Vietnam.

The accounting literature is silent about how digital transformation can be transformed into outstanding business performance through cloud-based accounting effectiveness (CBAE) under the supervision of digital leaders. In the digital age, this mechanism is practically significant for emerging market firms to promote accounting practices and decision-making effectiveness. Thus, this study investigates how CBAE and decision-making quality (DMQ) mediate the impact of digital transformation on firm performance. In addition, the moderating effects of digital leadership on the relationships between digital transformation and CBAE and those between CBAE and DMQ are investigated. The proposed model and its hypotheses are evaluated using partial least squares structural equation modeling (PLS-SEM) on survey data from 252 large-sized Vietnamese firms. The study's findings are as follows: (1) digital transformation positively affects CBAE, which affects DMQ and firm performance; (2) when digital leadership is strong, the effects of digital transformation on CBAE and CBAE on DMQ are amplified. These findings demonstrate how the interaction between digital transformation and digital leadership can contribute to the success of firms in emerging markets that use cloud accounting. In addition, the current study elucidates the mechanism by which digital transformation influences the digitalization of accounting practices and contributes to our understanding of digital transformation research in accounting by introducing digital leadership as a boundary condition.

Establishing in vivo and ex vivo chick embryo models to investigate fetal tendon healing.

Injured adult tendons heal fibrotically and possess high re-injury rates, whereas fetal tendons appear to heal scarlessly. However, knowledge of fetal tendon wound healing is limited due in part to the need for an accessible animal model. Here, we developed and characterized an in vivo and ex vivo chick embryo tendon model to study fetal tendon healing. In both models, injury sites filled rapidly with cells and extracellular matrix during healing, with wound closure occurring faster in vivo. Tendons injured at an earlier embryonic stage improved mechanical properties to levels similar to non-injured controls, whereas tendons injured at a later embryonic stage did not. Expression levels of tendon phenotype markers, collagens, collagen crosslinking regulators, matrix metalloproteinases, and pro-inflammatory mediators exhibited embryonic stage-dependent trends during healing. Apoptosis occurred during healing, but ex vivo tendons exhibited higher levels of apoptosis than tendons in vivo. Future studies will use these in vivo and ex vivo chick embryo tendon injury models to elucidate mechanisms of stage-specific fetal tendon healing to inform the development of therapeutic approaches to regeneratively heal adult tendons.

Recombinant lysyl oxidase effects on embryonic tendon cell phenotype and behavior.

Lysyl oxidase (LOX) plays an important role in the elaboration of tendon mechanical properties during embryonic development by mediating enzymatic collagen crosslinking. We previously showed recombinant LOX (rLOX) treatment of developing tendon significantly increased LOX-mediated collagen crosslink density to enhance tendon mechanical properties at different stages of tissue formation. Working toward the future development of rLOX-based therapeutic strategies to enhance mechanical properties of tendons that are compromised, such as after injury or due to abnormal development, this study characterized the direct effects of rLOX treatment on embryonic tendon cells from different stages of tissue formation. Tendon cell morphology, proliferation rate, proliferative capacity, and metabolic activity were not affected by rLOX treatment. Tenogenic phenotype was stable with rLOX treatment, reflected by no change in cell morphology or tendon marker messenger RNA (mRNA) levels assessed by reverse-transcription polymerase chain reaction. Collagen mRNA levels also remained constant. Matrix metalloproteinase-9 expression levels were downregulated in later stage tendon cells, but not in earlier stage cells, whereas enzyme activity levels were undetected. Bone morphogenetic protein-1 (BMP-1) expression was upregulated in earlier stage tendon cells, but not in later stage cells. Furthermore, BMP-1 activity was unchanged when intracellular LOX enzyme activity levels were upregulated in both stage cells, suggesting exogenous rLOX may have entered the cells. Based on our data, rLOX treatment had minimal effects on tendon cell phenotype and behaviors. These findings will inform future development of LOX-focused treatments to enhance tendon mechanical properties without adverse effects on tendon cell phenotype and behaviors.

Early Effects of Ticagrelor Versus Clopidogrel on Peripheral Endothelial Function After Non-ST-Elevation Acute Coronary Syndrome and Assessment of Its Relationship With Coronary Microvascular Function.

Peripheral endothelial dysfunction is an independent predictor of adverse long-term prognosis after acute coronary syndrome. Data are lacking on the effects of oral P2Y12-inhibitors on peripheral endothelial function in non-ST-elevation acute coronary syndrome (NSTEACS). Furthermore, the relation between peripheral endothelial function and invasive indexes of coronary microvascular function in NSTEACS is unclear. Between March 2018 and July 2020, hospitalized patients with NSTEACS were randomized (1:1) to ticagrelor or clopidogrel. Peripheral endothelial function was assessed with brachial artery flow-mediated vasodilation (FMD). Invasive indexes of coronary microvascular function were obtained using an intracoronary pressure-temperature sensor-tipped wire. In 70 patients included, mean age was 58.6 years, 78.6% (n = 55) were male and 20% (n = 14) had diabetes mellitus. Compared with clopidogrel, ticagrelor significantly improved FMD (14.2 ± 5.4% vs 8.9 ± 5.3%, p <0.001) after a median treatment time of 41.2 hours. The FMD was significantly correlated with the index of microcirculatory resistance (IMR) measured in the infarct-related artery (r = -0.38, p = 0.001), with a stronger correlation found in those who did not have percutaneous coronary intervention (r = -0.52, p = 0.03). Using receiver operating characteristic curve analysis, an FMD of 8.2% identified an IMR of >34 as the threshold, with 77.6% sensitivity and 52.4% specificity. In patients who did not have a percutaneous coronary intervention, an FMD of 11.49% identified an IMR of >34 with 84.6% sensitivity and 80% specificity. In conclusion, ticagrelor significantly improved peripheral endothelial function compared with clopidogrel in patients with NSTEACS. There was a significant correlation between brachial artery FMD and IMR of the infarct-related artery.