Increased PHLPP1 expression through ERK-4E-BP1 signaling axis drives nicotine induced oxidative stress related damage of cardiomyocytes.

Nicotine, a key constituent of tobacco/electronic cigarettes causes cardiovascular injury and mortality. Nicotine is known to induce oxidative stress and mitochondrial dysfunction in cardiomyocytes leading to cell death. However, the underlying mechanisms remain unclear. Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) is a member of metal-dependent protein phosphatase (PPM) family and is known to dephosphorylate several AGC family kinases and thereby regulate a diverse set of cellular functions including cell growth, survival, and death. Our lab has previously demonstrated that PHLPP1 removal reduced cardiomyocyte death and cardiac dysfunction following injury. Here, we present a novel finding that nicotine exposure significantly increased PHLPP1 protein expression in the adolescent rodent heart. Building upon our in vivo finding, we determined the mechanism of PHLPP1 expression in cardiomyocytes. Nicotine significantly increased PHLPP1 protein expression without altering PHLPP2 in cardiomyocytes. In cardiomyocytes, nicotine significantly increased NADPH oxidase 4 (NOX4), which coincided with increased reactive oxygen species (ROS) and increased cardiomyocyte apoptosis which were dependent on PHLPP1 expression. PHLPP1 expression was both necessary and sufficient for nicotine induced mitochondrial dysfunction. Mechanistically, nicotine activated extracellular signal-regulated protein kinases (ERK1/2) and subsequent eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) to increase PHLPP1 protein expression. Inhibition of protein synthesis with cycloheximide (CHX) and 4EGI-1 abolished nicotine induced PHLPP1 protein expression. Moreover, inhibition of ERK1/2 activity by U0126 significantly blocked nicotine induced PHLPP1 expression. Overall, this study reveals a novel mechanism by which nicotine regulates PHLPP1 expression through ERK-4E-BP1 signaling axis to drive cardiomyocyte injury.

Detection of Invasive Anopheles stephensi Mosquitoes through Molecular Surveillance, Ghana.

The invasive Anopheles stephensi mosquito has rapidly expanded in range in Africa over the past decade. Consistent with World Health Organization guidelines, routine entomologic surveillance of malaria vectors in Accra, Ghana, now includes morphologic and molecular surveillance of An. stephensi mosquitoes. We report detection of An. stephensi mosquitoes in Ghana.

Stress hyperglycemia ratio as a prognostic indicator for long-term adverse outcomes in heart failure with preserved ejection fraction.

BACKGROUND: Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. METHODS: HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49-3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. CONCLUSION: Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.

Triglyceride-glucose index is associated with myocardial ischemia and poor prognosis in patients with ischemia and no obstructive coronary artery disease.

BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. METHODS: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). RESULTS: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008). CONCLUSION: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.

Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation.

BACKGROUND: Coronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. METHOD: This study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. RESULT: A total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529-6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). CONCLUSION: Elevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

Baseline susceptibility of Anopheles gambiae to clothianidin in northern Ghana.

BACKGROUND: Clothianidin, an insecticide with a novel mode of action, has been deployed in the annual indoor residual spraying programme in northern Ghana since March 2021. To inform pragmatic management strategies and guide future studies, baseline data on local Anopheles gambiae sensu lato (s.l.) susceptibility to the clothianidin insecticide were collected in Kpalsogu, a village in the Northern region, Ghana. METHODS: Phenotypic susceptibility of An. gambiae mosquitoes to clothianidin was assessed using the World Health Organization (WHO) insecticide resistance monitoring bioassay. The WHO cone bioassays were conducted on mud and cement walls sprayed with Sumishield 50 wettable granules (WG) (with clothianidin active ingredient). Daily mortalities were recorded for up to 7 days to observe for delayed mortalities. Polymerase chain reaction (PCR) technique was used to differentiate the sibling species of the An. gambiae complex and also for the detection of knock down resistance genes (kdr) and the insensitive acetylcholinesterase mutation (ace-1). RESULTS: The WHO susceptibility bioassay revealed a delayed killing effect of clothianidin. Mosquitoes exposed to the cone bioassays for 5 min died 120 h after exposure. Slightly higher mortalities were observed in mosquitoes exposed to clothianidin-treated cement wall surfaces than mosquitoes exposed to mud wall surfaces. The kdr target-site mutation L1014F occurred at very high frequencies (0.89-0.94) across all vector species identified whereas the ace-1 mutation occurred at moderate levels (0.32-0.44). Anopheles gambiae sensu stricto was the most abundant species observed at 63%, whereas Anopheles arabiensis was the least observed at 9%. CONCLUSIONS: Anopheles gambiae s.l. mosquitoes in northern Ghana were susceptible to clothianidin. They harboured kdr mutations at high frequencies. The ace-1 mutation occurred in moderation. The results of this study confirm that clothianidin is an effective active ingredient and should be utilized in malaria vector control interventions.

Predictors of quality of life of TB/HIV co-infected patients in the Northern region of Ghana.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-morbidity continues to be a serious worldwide health issue, particularly in Sub-Saharan Africa. Studies on the quality of life (QOL) of TB/HIV co-infected patients guide stakeholders on the delivery of patient-centred healthcare. This study evaluated QOL of TB/HIV co-infected individuals and its contributing factors. METHODS: We conducted a cross-sectional study among TB/HIV co-infected patients, receiving treatment at clinics in the Northern Region of Ghana. Simple random sampling technique was used to select 213 patients from 32 clinics. We gathered information on patients' QOL using the World Health Organization QOL-HIV BREF assessment tool. At a 5% level of significance, multiple logistic regression analyses were carried out to find correlates of QOL among the patients. RESULTS: The mean age of the patients was (38.99 ± 14.00) years with most, 33.3% (71/213) aged 30-39 years. Males constituted 54.9% (117/213). About 30.0% (64/213) of the patients reported a good QOL. Being employed (aOR = 5.23, 95% CI: 1.87 - 14.60), and adhering to treatment (aOR = 6.36, 95% CI: 1.51 - 26.65) were significantly associated with a good QOL. Being depressed (aOR = 0.02, 95% CI: 0.03 - 0.29), stigmatized (aOR = 0.31, 95% CI : 0.11 - 0.84), and not exercising (aOR = 0.28, 95% CI: 0.12 - 0.67) were negatively associated with a good QOL. CONCLUSION: Less than one-third of TB/HIV co-infected patients in the region have good QOL. To guarantee good QOL, modifiable predictors such as patients' physical activity and medication adherence should be targeted by the National AIDS and TB Control Programs.

Analyzing working time and efficient caries removal using a novel bioactive caries detecting dye and air polisher prophy for caries excavation: randomised clinical trial.

OBJECTIVES: This study aims to analyze the working time consumed during caries excavation and pain perception while using a novel Bioactive caries-detecting dye solution (BCD), an Air Polisher Prophy and a combination. MATERIALS AND METHODS: Four groups (in each group, n = 20 permanent teeth) were selected from 60 people between 17 and 40 years of age. The study included teeth with occlusal dentinal caries in the molars with cavity entrance sizes of less than 2 mm (clinically and radiographically). Randomization software was used to assign patients to various groups. Group A: Conventional Rotary Drilling, Group B: BCD + Mechanical Excavation (Spoon Excavator), Group C: Air Polisher Prophy, and Group D: BCD + Air Polisher Prophy 0.5 mL BCD was applied with a micro brush to the carious tooth surface for 40 s in groups B and D. After that, radiographs were performed to see if the radiopaque extension was visible. For mechanical caries extraction, a spoon excavator was used for group B, and an air polisher prophy was employed for group D. For mechanical caries extraction, a spoon excavator was utilized for group B. An air polisher prophy was employed for group D. Multiple applications of the BCD were used in the event of residual caries. Working time and pain experienced during caries excavation were registered using the Verbal Pain Scale (VPS) (score 0-4), and caries removal was clinically graded using the modified Scale (score 0-5). RESULTS: The time taken was Group A, Group D, Group B, and Group C, according to statistical analysis using ANOVA and the Post Hoc Test (275.02, 403.8, 461.98, 615.41 s, respectively). Group A had the highest mean VPS (1.85), whereas Group B had the most minor pain (0.6), followed by Group D (1.2) and Group C (0.6). (1.45). Group C (2.35), followed by groups D (1.75), B (1.30), and A (1.30), had ineffective caries eradication (0.90). (p < 0.05). CONCLUSIONS: compared to group C, groups B and D took less time and had less/no pain while excavating caries. Compared to traditional mechanized caries removal methods, the chemo-chemical BCD can diagnose and aid in successful caries removal with minimal pain. CLINICAL RELEVANCE: The outcomes of the present study demonstrated that the chemo-chemical bioactive caries detecting dye solution has the potential to identify and help in effective caries removal before mechanized caries removal methods.

Prevalence of obstructive sleep apnoea syndrome in oncological patients: A systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) has garnered increasing attention in recent years due to its potential association with cancer. This systematic review and meta-analysis aimed to assess the prevalence of OSAS in cancer patients through a comprehensive analysis of existing literature. METHODS: This systematic review and meta-analysis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, aimed to evaluate the prevalence of OSAS in cancer patients. A comprehensive search of electronic databases was performed to identify relevant studies published up to September 2021. Eligible studies reporting on the prevalence of OSAS in cancer patients, encompassing various study designs, were included in the analysis. Pooled estimates of the odds ratios (OR) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity among the studies was assessed using the I2 statistic. RESULTS: Seventeen studies fulfilled the inclusion criteria and were subsequently included in the review. The prevalence of OSAS in cancer patients was estimated to have an overall OR of 0.80 (95% CI: 0.75-0.85). In comparison with non-cancer patients, cancer patients had a statistically significant greater risk of OSAS, as indicated by the total estimated RR for the prevalence of OSAS in cancer patients, which was 0.89 (95% CI: 0.86-0.92). Nonetheless, there was a significant amount of heterogeneity (I2 = 96%) among the studies. CONCLUSION: The overall data analysed in this review indicates that patients with cancer had far reduced likelihood of developing OSAS than individuals without cancer. However, the significant variation across the included studies highlights the need for additional investigation to fully clarify the complex association between OSAS and cancer incidence. These results emphasise how critical it is to identify OSAS as a possible comorbidity in cancer patients, one that should be taken into account for clinical management and ongoing research.

A comprehensive review on versatile microalga Tetraselmis: Potentials applications in wastewater remediation and bulk chemical production.

Microalgae are considered sustainable resources for the production of biofuel, feed, and bioactive compounds. Among various microalgal genera, the Tetraselmis genus, containing predominantly marine microalgal species with wide tolerance to salinity and temperature, has a high potential for large-scale commercialization. Until now, Tetraselmis sp. are exploited at smaller levels for aquaculture hatcheries and bivalve production. However, its prolific growth rate leads to promising areal productivity and energy-dense biomass, so it is considered a viable source of third-generation biofuel. Also, microbial pathogens and contaminants are not generally associated with Tetraselmis sp. in outdoor conditions due to faster growth as well as dominance in the culture. Numerous studies revealed that the metabolite compositions of Tetraselmis could be altered favorably by changing the growth conditions, taking advantage of its acclimatization or adaptation ability in different conditions. Furthermore, the biorefinery approach produces multiple fractions that can be successfully upgraded into various value-added products along with biofuel. Overall, Tetraselmis sp. could be considered a potential strain for further algal biorefinery development under the circular bioeconomy framework. In this aspect, this review discusses the recent advancements in the cultivation and harvesting of Tetraselmis sp. for wider application in different sectors. Furthermore, this review highlights the key challenges associated with large-scale cultivation, biomass harvesting, and commercial applications for Tetraselmis sp.

Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release.

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Volumetric analysis after caries excavation with caries detecting dyes and chemomechanical caries removal agents using 3D scanner-a randomised clinical trial.

AIM: This research aimed to use an extra-oral 3D scanner for conducting volumetric analysis after caries excavation using caries-detecting dyes and chemomechanical caries removal agents in individuals with occlusal and proximal carious lesions. METHODS: Patients with occlusal (A1, A2, A3) and proximal carious lesions (B1, B2, B3) were treated with the conventional rotary technique, caries detecting dyes (CDD) and chemomechanical caries removal (CMCR) method on 90 teeth (n = 45 for each). Group A1, B1: Excavation was performed using diamond points. Group A2, B2: CDD (Sable Seek™ caries indicator, Ultradent) was applied and left for 10 s, and then the cavity was rinsed and dried. For caries removal, diamond points or excavators were used. Group A3 and B3: BRIX3000 papain gel was applied with a micro-brush for 20 s and was activated for 2 min, and then the carious tissue was removed with a sharp spoon excavator. Post-excavation cavity volume analysis was performed using a 3D scanner. The time required and the verbal pain score (VPS) for pain were scored during excavation. Post-restoration evaluation was performed at 1, 3, and 6 months FDI (Federation Dentaire Internationale) criteria. RESULTS: Comparison of age, time and volume with study groups were made using Independent Sample' t' test and one-way analysis of variance (ANOVA) for two and more than two groups, respectively. Using Cohen's Kappa Statistics, evaluators 1 and 2 agreed on caries removal status aesthetic, functional and biological properties at different follow-ups. The chi-square test revealed that the rotary groups [A1(2.5 ± 0.4 min) B1(4.0 ± 0.4 min)] had significantly less (p = 0.000) mean procedural time than CDD [A2(4.5 ± 0.4 min) B2(5.7 ± 0.4 min)] and CMCR [A3(5.4 ± 0.7 min) B3(6.2 ± 0.6 min)] groups. The CMCR group showed better patient acceptance and less pain during caries excavation than the rotary and CDD groups. CMCR group showed significantly less mean caries excavated volume(p = 0.000). Evaluation of restoration after 1-, 3-, and 6-month intervals was acceptable for all the groups. CONCLUSION: Brix3000 helps effectively remove denatured teeth with less pain or sensitivity. The time required for caries removal was lowest in the rotary method and highest in the brix3000 group, while the volume of caries removed was the lowest for brix3000 and highest for the rotary group.

Clinical utility of biomarkers of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common forms of cancer significantly affecting the mortality and morbidity rates. The increasing incidence of HCC is a great concern across the globe. The current methods of HCC screening, detection and diagnosis depend mainly on imaging techniques. However, biomarkers represent a relatively easy and noninvasive way to detect and estimate the disease prognosis. New potential biomarkers such as α-fetoprotein (AFP), des­Î³­carboxyprothrombin (DCP), α-fetoprotein L3 (AFP-L3), glypican 3 (GCP3), micro-RNA, and Golgi-protein 73 (GP73) are being used more often in the diagnosis and prognosis of HCC. The lack of prudent diagnostic measures makes early detection of HCC nearly impossible. The use of biomarkers to detect cancer has helped to screen for the disease. However, the most commonly used biomarkers for HCC have inadequate performance characteristics. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker for HCC. In this paper the main biomarkers for the surveillance, diagnosis and prognosis of HCC are reviewed. The advantages and limitations of these biomarkers are summarized, and the future development directions are proposed (Tab. 1, Ref. 30). Keywords: hepatocellular carcinoma, biomarkers, AFP, DCP, diagnosis.

Association of stress hyperglycemia ratio and poor long-term prognosis in patients with myocardial infarction with non-obstructive coronary arteries.

BACKGROUND: Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients. METHODS: A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73-0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan-Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE. RESULTS: A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P < 0.001). The Kaplan-Meier curves demonstrate that SHR3 patients had the highest MACE risk compared to SHR1 and SHR2 patients (log-rank P < 0.001). In addition, when both SHR tertiles and diabetes status were considered, those with SHR3 and diabetes had the highest hazard of MACE (log-rank P < 0.001). Multivariate Cox regression analysis showed that the SHR3 is associated with a 2.465-fold increase in the risk of MACE (adjusted HR, 2.465; 95% CI 1.461-4.159, P = 0.001). The ROC curve analysis showed that the optimal SHR cut-off value for predicting clinical MACE among MINOCA was 0.86. CONCLUSION: Our data indicates, for the first time, that SHR is independently associated with poor long-term prognosis in patients suffering from MINOCA. The optimal SHR cut-off value for predicting clinical MACE among MINOCA patients was 0.86. These findings suggest that SHR may play a potential role in the cardiovascular risk stratification of the MINOCA population.

Association between the atherogenic index of plasma and adverse long-term prognosis in patients diagnosed with chronic coronary syndrome.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. METHODS: A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. RESULTS: During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818-34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. CONCLUSION: Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Perceptions of the roles, impact, challenges and needs of community drug distributors in the control and elimination of neglected tropical diseases in difficult-to-access communities in Ghana.

INTRODUCTION: The success of mass drug administration (MDA) campaigns to control and eliminate neglected tropical diseases (NTDs) in Ghana depends, to a large extent, on the essential role community drug distributors (CDDs) play. This study aimed to investigate community's perceptions of CDDs' roles, impact of CDDs' work, challenges faced by CDDs, and views on resources required to enhance CDDs' work to sustain MDA campaigns. METHODS: A cross-sectional qualitative study employing the use of focus group discussions (FGDs) with community members and CDDs in selected NTD endemic communities together with individual interviews with district health officers (DHOs) was conducted. We interviewed 104 people aged 18 and over, purposively selected, through eight individual interviews, and 16 focus group discussions. RESULTS: Participants in the community FGDs noted that health education and the distribution of drugs were the main roles of CDDs. Participants also perceived that the work of CDDs had prevented the onset of NTDs, treated symptoms of NTDs, and generally reduced the incidence of infections. In the interviews with CDDs and DHOs, lack of cooperation/non-compliance by community members, demands by community members, lack of working resources and low financial motivation were mentioned as the main challenges to the work of CDDs. Moreover, the provision of logistics and financial motivation for CDDs were identified as factors that will enhance their work. CONCLUSIONS: Incorporating more attractive schemes will incentivise CDDs to improve output. Addressing the challenges highlighted is an important step for the work of CDDS to be effective in controlling NTDs in difficult-to-access communities in Ghana.

Improved Quality of Life Among Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation-Single Center Experience With Large Cohort of Patients.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3 years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.