Cardiovascular outcomes of complex bifurcation lesions following double kissing crush or nano-crush techniques: The multicenter EVOLUTE-CRUSH V study.

BACKGROUND: Double kissing crush (DKC) and nano-crush (NC) techniques are frequently used, but the comparison for both techniques is still lacking. The goal of this multicenter study was to retrospectively assess the midterm clinical results of DKC and NC stenting in patients with complex bifurcation lesions (CBLs). METHODS: A total of 324 consecutive patients [male: 245 (75.6%), mean age: 60.73 ± 10.21 years] who underwent bifurcation percutaneous coronary intervention between January 2019 and May 2023 were included. The primary endpoint defined as the major cardiovascular events (MACE) included cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (TLR). Inverse probability weighting (IPW) was performed to reduce treatment selection bias. This is the first report comparing the clinical outcomes of DKC and NC stenting in patients with CBL. RESULTS: The initial revascularization strategy was DKC in 216 (66.7%) cases and NC in 108 (33.3%) patients. SYNTAX scores [25.5 ± 6.73 vs. 23.32 ± 6.22, p = 0.005] were notably higher in the NC group than the DKC group. The procedure time (76.98 ± 25.1 vs. 57.5 ± 22.99 min, p = 0.001) was notably higher in the DKC group. The incidence of MACE (18.5 vs. 9.7%, p = 0.025), clinically driven TLR (14.8 vs. 6%, p = 0.009), and TVMI (10.2 vs. 4.2%, p = 0.048) were notably higher in the NC group than in the DKC group. The midterm MACE rate in the overall population notably differed between the NC group and the DKC group (adjusted HR (IPW): 2.712, [95% CI: 1.407-5.228], p = 0.003). CONCLUSION: In patients with CBLs, applying the DKC technique for bifurcation treatment had better ischemia-driven outcomes than the NC technique.

Long-term cardiovascular outcomes after mini-crush or T and minimal protrusion techniques in complex bifurcation lesions: the EVOLUTE-CRUSH III study.

BACKGROUND: Mini-crush (MC) and T-stenting and small protrusion (TAP) techniques are frequently used, but the long-term comparison of both techniques in patients with complex bifurcation lesions (CBLs) is still a debatable issue. This study sought to retrospectively evaluate the long-term outcomes of MC and TAP techniques in patients with CBLs. METHODS: A total of 271 patients [male: 202 (78.9%), mean age: 58.90 ±â€…10.11 years] patients in whom complex bifurcation intervention was performed between 2014 and 2023 were involved. The primary endpoint was major cardiovascular events (MACE) as the combination of cardiac death, target vessel myocardial infarction, or clinically driven-target lesion revascularization. The Cox proportional hazard models were adjusted by the inverse probability weighting approach to reduce treatment selection bias. RESULTS: The initial management strategy was MC in 146 patients and TAP in 125 cases. MACE occurred in 52 patients (19.2%) during a mean follow-up period of 32.43 ±â€…16 months. The incidence of MACE (13 vs. 26.4%, P = 0.005) and major cardiovascular and cerebral events (15.1 vs. 28.8%, P = 0.006) were significantly lower in the MC group than in the TAP group. Additionally, the incidence of definite or probable stent thrombosis was numerically lower in the MC group compared with the TAP group but did not differ significantly (2.7 vs. 8%, P = 0.059). The long-term MACE was notably higher in the TAP group than the MC group [adjusted hazard ratio (inverse probability weighted): 1.936 (95% confidence interval: 1.053-3.561), P = 0.033]. CONCLUSION: In this study involving patients with CBLs, percutaneous coronary intervention with the MC technique had better long-term outcomes than the TAP technique.

Development of a novel laboratory photodynamic therapy device: automated multi-mode LED system for optimum well-plate irradiation.

Photodynamic therapy (PDT) is a targeted treatment method that utilizes a photosensitizer (PS) to induce cytotoxicity in malignant and non-malignant tumors. Optimization of PDT requires investigation of the selectivity of PS for the target tissues, irradiating light source, irradiation wavelengths, fluence rate, fluence, illumination mode, and overall treatment plan. In this study, we developed the Multi-mode Automatized Well-plate PDT LED Laboratory Irradiation System (MAWPLIS), an innovative device that automates time-consuming well plate light dosage/PS dose measurement experiment. The careful control of LED current and temperature stabilization in the LED module allowed the system to achieve high optical output stability. The MAWPLIS was designed by integrating a 3-axis moving system and motion controller, a quick-switching LED controller unit equipped with interchangeable LED modules capable of employing multiple wavelengths, and a TEC system. The proposed system achieved high optical output stability (1 mW) within the range of 0-500 mW, high wavelength stability (5 nm) at 635 nm, and high temperature stability (0.2 °C) across all radiation modes. The system's validation involved in vitro analysis using 5-ALA across varying concentrations, incubation periods, light exposures, and wavelengths in HT-29 colon cancer and WI-38 human lung fibroblast cell lines. Specifically, a combination of 405 nm and 635 nm wavelengths was selected to demonstrate enhanced strategies for colon cancer cell eradication and system validation. The MAWPLIS system represents a significant advancement in photodynamic therapy (PDT) research, offering automation and standardization of time-intensive experiments, high stability and precision, and improved PDT efficacy through dual-wavelength integration.

Factors affecting the choice of medical specialties in Turkiye: an analysis based on cross-sectional survey of medical graduates.

BACKGROUND: Modern healthcare systems require the right mix of medical specialties for effective provision of high-quality services. Despite increased availability of general physicians and specialists, Türkiye lags behind high-income countries in terms of availability of specialists. The purpose of the study is to identify several specific factors that affect the choice of medical specialization. METHODS: All 350 medical school graduates in a specialty examination preparation bootcamp were requested to participate in the survey and 333 completed the self-administered questionnaire. The survey asked questions about factors affecting choice of medical specialty by medical graduates. RESULTS: The empirical results indicate that surgical specialties, compared to other broad medical specializations, are selected because of its higher income-earning potential and social prestige. The likelihood of selecting surgical specialties is negatively affected by rigorousness of the training program, high work-load, risk of malpractice lawsuits and risk of workplace violence. Male participants were 2.8 times more likely to select surgery specialty compared to basic medical science. Basic medical science areas were selected at a higher rate by female graduates and graduates with high level of academic performance in medical schools. CONCLUSIONS: It is critically important to improve trust and inter-personal communications between the patients and physicians in all specialties to lower the likelihood of malpractice lawsuits and workplace violence. Policy-makers may adopt policies to affect income earning potential and social prestige of targeted specializations to improve their supply.

Shared Activities as a Protective Factor Against Behavioral and Psychological Symptoms of Dementia and Caregiver Stress.

Background and Objectives: Most persons with dementia experience behavioral and psychological symptoms (BPSD). While there is evidence that structured activity programs can be beneficial for persons with dementia and their caregivers, it is not well understood how joint engagement in shared activities affects BPSD and caregiver stress. The purpose of this study was to examine the moderating effect of doing a shared activity on the BPSD and caregiver stress. Research Design and Methods: This study used an intensive longitudinal observational design in which caregivers completed baseline and once-a-day diary surveys for 21 days. Caregivers were asked whether they did a pleasant noncare activity with their relative, the presence of 8 BPSD, and their stress level. A moderation model in a structural equation model examined the relationship between these variables. Results: Our sample consisted of 453 caregivers (87.4% female, 51.4% non-Hispanic White, mean age 53 years [standard deviation {SD}: 14]) and person living with dementia whose mean age was 79 years (SD: 9). On days when the caregivers engaged in a shared activity together with person living with dementia, there was a significant decrease in the BPSD (estimate -0.038, standard error [SE] = 0.016, 95% confidence interval [CI]: -0.069, -0.007, p value = 0.018). The effects of engaging in a shared activity decreased the impact of caregiver stress by 0.052 (estimate -0.052, SE = 0.018, 95% CI: -0.087, -0.017, p value = 0.004). At the between-person level, no differences were found in BPSD across caregivers who engaged or did not engage in shared activities. Discussion and Implications: The results of our study indicate that doing a shared activity is associated with reduced BPSD among persons with dementia and may buffer the impact of caregiver stress on BPSD. Shared activities should be considered a key intervention component for dementia caregivers.

Lanthanum(III)hydroxide Nanoparticles and Polyethyleneimine-Functionalized Graphene Quantum Dot Nanocomposites in Photosensitive Silicon Heterojunctions.

Lanthanides are largely used in optoelectronics as dopants to enhance the physical and optical properties of semiconducting devices. In this study, lanthanum(III)hydroxide nanoparticles (La(OH)3NPs) are used as a dopant of polyethylenimine (PEI)-functionalized nitrogen (N)-doped graphene quantum dots (PEI-NGQDs). The La(OH)3NPs-dopedPEI-NGQDs nanocomposites are prepared from La(NO)3 in a single step by a green novel method and are characterized by Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Deposited over an n-type Si wafer, the La(OH)3NPs-dopedPEI-NGQDs nanocomposites form Schottky diodes. The I-V characteristics and the photoresponse of the diodes are investigated as a function of the illumination intensity in the range 0-110 mW cm-2 and at room temperature. It is found that the rectification ratio and ideality factor of the diode decrease, while the Schottky barrier and series resistance increase with the enhancing illuminations. As a photodetector, the La(OH)3NPs-dopedPEI-NGQDs/n-Si heterojunction exhibits an appreciable responsivity of 3.9 × 10-3 AW-1 under 22 mW cm-2 at -0.3 V bias and a maximum detectivity of 8.7 × 108 Jones under 22 mW cm-2 at -0.5 V. This study introduces the green synthesis and presents the structural, electrical, and optoelectronic properties of La(OH)3NPs-dopedPEI-NGQDs, demonstrating that these nanocomposites can be promising for optoelectronic applications.

Long-term outcomes following double kissing crush or mini-culotte stenting for complex coronary bifurcation lesions: the EVOLUTE-CRUSH IV study.

BACKGROUND: This study aimed to evaluate the long-term outcomes of double kissing crush stenting (DKC) and mini-culotte technique (MCT) in patients with complex bifurcation lesions. METHODS: This retrospective study enrolled 236 patients who underwent percutaneous coronary intervention (PCI) for complex coronary bifurcation disease between January 2014 and November 2022. The primary endpoint was target lesion failure (TLF), defined as the combination of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (TLR). The secondary endpoint was major cardiovascular and cerebral events (MACCE) including all-cause death, MI, TLR, stroke, or stent thrombosis. The regression models were adjusted by applying the inverse probability weighted (IPW) approach to reduce treatment selection bias. RESULTS: The initial management strategy was DKC in 154 (65.3%) patients and MCT in 82 (34.7%) patients (male: 194 [82.2%], mean age: 60.85 ± 10.86 years). The SYNTAX scores were similar in both groups. The rates of long-term TLF and MACCE rates were 17.4% and 20%, respectively. The rate of TLF (26.8% vs. 12.3%, p = 0.005) was higher in patients treated with MCT than those treated with the DKC technique, mainly driven by more frequent TLR (15.9% vs. 7.1%, p = 0.035). The long-term TLF and MACCE rates were notably lower in the DKC group compared to the others: adjusted hazard ratio (HR; IPW): 0.407, p = 0.009 for TLF, and adjusted HR(IPW): 0.391 [95% CI: 0.209-0.730], p = 0.003 for MACCE. CONCLUSION: At long-term follow-up, the rates of TLF and MACCE were 17.4% and 20%, respectively. However, long-term TLF was significantly higher in patients treated with MCT than those treated with the DKC technique, primarily due to a more frequent occurrence of clinically driven TLR.

Primary Negative Prognostic Factors in Pediatric and Adult Patients Undergoing Trigger Finger Surgery.

Objectives This study aims to investigate the negative prognostic indicators of pediatric and adult trigger finger surgery patients concerning complications, recurrence, and satisfaction. Methods A retrospective study was conducted on 61 patients with a total of 91 trigger fingers, including 31 in children and 30 in adult patients, all of whom were treated using a standardized surgical technique. The study considered several demographic and clinical factors, including age, gender, dominant hand, body mass index, occupation, history of trauma, single or multiple finger involvement, staging according to Green classification, diabetes mellitus, comorbidities, recurrence, revision surgery, utilization of non-surgical treatment methods, need for rehabilitation after surgery, time to return to work, the time interval from clinic initiation to the surgery, satisfaction and the duration of the follow-up period. In addition, the quick version of the disabilities of the arm, shoulder, and hand (QDASH); and the visual analog scale (VAS) were used to assess patients' data. Results In adult patients, a statistically significant relationship was observed between the increasing grade of the Green stage and complication rate (p<0.001), recurrence (p<0.001), and lower satisfaction (p<0.001). No statistically significant relationship was identified between Green's classification and complications (p=0.129), recurrence (p=0.854), or satisfaction (p=0.143) in pediatric patients. While a statistically significant relationship existed between the time interval from clinic initiation to surgery and complications (p=0.033) in adult patients, no significant relationships were observed for recurrence or satisfaction. Conversely, there was no statistically significant relationship between the time interval from clinic initiation to surgery and complications, recurrence, or satisfaction in pediatric patients. Conclusion This study demonstrates that increasing the grade of the Green stage and duration of symptoms before surgery were the substantial factors contributing to prognosis in adult patients but not in pediatric patients. These findings can assist physicians during patients' treatment management. We suggest that physicians consider these factors for patients' satisfaction.

Emotion Regulation, Coping Strategies, and Hazardous Drinking Among Family Caregivers of People With Alzheimer's Disease and Related Dementias.

PURPOSE: The current study investigated hazardous drinking and alcohol use disorders among 453 family caregivers of individuals living with Alzheimer's disease and related dementias (ADRD). METHOD: We examined the prevalence of hazardous drinking and its relationship with emotion regulation and coping strategies (problem-solving, social support, and avoidance) using data from the first wave of a longitudinal study on daily ADRD caregiving experiences. A binary logistic regression model was performed to predict the relationship between potential risk factors and hazardous drinking. RESULTS: Findings revealed that 18.1% of ADRD caregivers screened positive for hazardous drinking based on the Alcohol Use Disorders Identification Test-Consumption. Caregivers experiencing greater difficulties in emotion regulation and greater reliance on avoidance as a coping strategy were at higher risk of screening positive for hazardous drinking. CONCLUSION: These findings stress the importance of targeted interventions to improve emotion regulation and reduce avoidance coping in ADRD caregivers, ultimately enhancing their well-being. [Research in Gerontological Nursing, 17(2), 81-90.].

Palladium Metal Nanocomposites Based on PEI-Functionalized Nitrogen-Doped Graphene Quantum Dots: Synthesis, Characterization, Density Functional Theory Modeling, and Cell Cycle Arrest Effects on Human Ovarian Cancer Cells.

In this study, the synthesis, characterization, density functional theory calculations (DFT), and effect of polyethylenimine (PEI)-functionalized nitrogen-doped graphene quantum dots (PEI N-GQDs) and their palladium metal nanoparticles nanocomposites (PdNPs/PEI N-GQDs) on cancer cells were extensively investigated. The focus also includes investigating their cytotoxic and apoptotic effects on ovarian cancer cells, which pose a serious risk to women's health and have high death rates from delayed diagnosis, inadequate response to treatment, and decreased survival. Graphene quantum dots and their palladium nanocomposites were differentially effective against ovarian cancer cell lines. In particular, the smaller particle size and morphology of PdNPs/PEI N-GQDs nanocomposites compared with PEI N-GQDs probably enhance their activity through highly improved uptake by cells. These findings emphasize the importance of particle size in composite drugs for efficient cancer treatment. DFT results revealed that the Pd-containing nanocomposite, with a smaller highest occupied molecular orbital-lowest unoccupied molecular orbital gap, exhibited higher reactivity and anticancer effects in human ovarian cancer cell line, OVCAR-3. Significantly, the application of nanocomposites to ovarian cancer cells initiated apoptosis, offering valuable insights into the intricate interplay between nanomaterials and cancer biology.

The relationship between prognostic nutritional index and long-term mortality in patients undergoing emergency coronary artery bypass graft surgery for acute-ST elevation myocardial infarction.

BACKGROUND: Malnutrition and the prognosis of coronary artery disease (CAD) are shown to be correlated. The significance of nutritional status has been evaluated in patients with ST elevation myocardial infarction (STEMI), stable CAD, and elective coronary artery bypass graft (CABG) surgery. However, the prognostic impact of poor nutritional status on STEMI patients who underwent emergent CABG is not known. In this study, we aimed to investigate the relationship between nutritional status assessed by the prognostic nutritional index (PNI) and long-term mortality in STEMI patients who underwent emergent CABG. To the best of our knowledge, our study is the first one to evaluate the PNI effect on this specific population. METHODS: 131 consecutive patients with STEMI who did not qualify for primary percutaneous coronary intervention and required emergent CABG between 2013 and 2018 were included in our study. The study population was divided into two groups: survivors and non-survivors. The PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3) for both groups, using the preoperative data. The optimal cut-off value was obtained by receiver operating characteristic (ROC) analysis. According to the cut-off value, we investigated the relationship between PNI and long-term mortality. RESULTS: The mean age of the study population was 57.0±10.6. During the median 92.7 (70.0-105.3)-month follow-up, 32 of the 131 patients (24.4%) died. Regression analysis showed a significant association between glucose levels (hazard ratio (HR), 1.007; 95% confidence interval (CI), 1.002-1.012; p=0.011) and PNI (HR, 0.850; 95% CI, 0.787-0.917; p<0.001) and long-term mortality. Accord-ing to the ROC analysis, the cut-off value for PNI to predict all-cause mortality was found to be 44.9, with a sensitivity of 81.3% and a specificity of 89.9%. In addition, age, ejection fraction, glomerular filtration rate, Killip classification, and left anterior descending-left internal mammary artery graft use are significantly associated with long-term all-cause mortality in STEMI patients undergoing emergency CABG. CONCLUSION: The PNI was significantly associated with long-term mortality in patients with STEMI who underwent emergent CABG. PNI can be used to improve the accuracy of the risk assessment of STEMI patients undergoing emergent CABG.

Prevalence and antimicrobial resistance of Campylobacter species in shelter-housed healthy and diarrheic cats and dogs in Turkey.

BACKGROUND: Campylobacter spp. are among the leading foodborne bacterial pathogens. Pet animals may be an important reservoir for human infection. OBJECTIVES: To determine the prevalence and antimicrobial resistance profiles and mechanisms of Campylobacter isolates recovered from shelter-housed healthy and diarrheic cats and dogs in Erzurum province in Turkey. METHODS: A total of 250 rectal swabs (from 124 cats and 126 dogs) collected between 2020 and 2021 were included in this study. The samples were cultured using a Campylobacter-selective agar medium. A single suspect colony from each plate was purified and species identification was performed by PCR. Minimum inhibitory concentration (MIC) values were determined against eight antibiotics. Specific antimicrobial resistance genes (tetO and aphA-3) and mutations (in gyrA) were screened by PCR and/or sequencing. RESULTS: A total of 26 (10.4%) isolates (25 Campylobacter jejuni and 1 Campylobacter coli) were obtained from the dogs; no Campylobacter was isolated from the cats. Of the C. jejuni isolates, 19.2% were resistant to nalidixic acid, 7.7% to ciprofloxacin and 3.8% to tetracycline and gentamicin per the CLSI interpretative criteria. The C. coli isolate was susceptible to all of the tested antibiotics. Thr-86-Ile mutation was the most common change detected in the gyrA gene in the quinolone-resistant isolates. CONCLUSION: While geographic and population differences exist, Campylobacter carriage and associated antibiotic resistance in dogs is common, emphasising the need for continuous surveillance in this species, particularly given its zoonotic potential.

Transcatheter Closure or Surgery for Symptomatic Paravalvular Leaks: The Multicenter KISS Registry.

BACKGROUND: The optimal treatment of symptomatic paravalvular leak (PVL) remains controversial between transcatheter closure (TC) and surgery. This large-scale study aimed to retrospectively evaluate the long-term outcomes of the patients who underwent reoperation or TC of PVLs. METHODS AND RESULTS: A total of 335 (men, 209 [62.4%]; mean age, 58.15±12.77 years) patients who underwent treatment of PVL at 3 tertiary centers between January 2002 and December 2021 were included. Echocardiographic features, procedure details, and in-hospital or long-term outcomes were assessed. The primary end point was defined as the all-cause death during follow-up. The regression models were adjusted by applying the inverse probability weighted approach to reduce treatment selection bias. The initial management strategy was TC in 171 (51%) patients and surgery in 164 (49%) cases. Three hundred cases (89.6%) had mitral PVL, and 35 (10.4%) had aortic PVL. The mean left ventricular ejection fraction was 52.03±10.79%. Technical (78.9 versus 76.2%; P=0.549) and procedural success (73.7 versus 65.2%; P=0.093) were similar between both groups. In both univariate and multivariable logistic regression analysis, the in-hospital mortality rate in the overall population was significantly higher (15.9 versus 4.7%) in the surgery group compared with the TC group (unadjusted odds ratio, 3.13 [95% CI, 1.75-5.88]; P=0.001; and adjusted odds ratio (inverse probability-weighted), 4.55 [95% CI, 2.27-10.0]; P<0.001). However, the long-term mortality rate in the overall population did not differ between the surgery group and the TC group (unadjusted hazard ratio [HR], 0.86 [95% CI, 0.59-1.25]; P=0.435; and adjusted HR (inverse probability-weighted), 1.11 [95% CI, 0.67-1.81]; P=0.679). CONCLUSIONS: The current data suggest that percutaneous closure of PVL was associated with lower early and comparable long-term mortality rates compared with surgery.

Assessing cytotoxic activities, theoretical and in silico molecular docking calculations of phthalocyanines bearing cinnamyloxy-groups.

Cancer has been recognized as one of the deadliest diseases in the world in recent years. By chemically tailoring specific properties, anticancer agents can be prepared very effectively for the treatment of various cancer types. In this manner, as anticancer agents, a series of soluble metal-free and metallophthalocyanines carrying cinnamyloxy-groups at peripheral ß-positions have been prepared. All synthesized phthalocyanines were characterized by various spectroscopic approaches such as ultraviolet - visible (UV - Vis), Fourier transform infrared (FT-IR), and matrix-assisted laser deionization/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) techniques. These compounds are highly soluble in dimethyl sulfoxide (DMSO) and soluble in common organic solvents. The spectroscopic properties, cytotoxicity, and theoretical calculations of these complexes have been investigated. In cytotoxicity tests, compounds 1, 4, and 7 are the most active against HT-29 cell lines with IC50 values of 36.9 µM, 32.5 µM, and 51.1 µM, respectively. Also, the most and the least cytotoxic compounds against healthy CCD cell line is compounds 5 and 6 with the IC50 value of 13.4 µM and >250 µM, respectively. The PDB ID:4BQG target protein representing the HT-29 cancer cell line and the anti-cancer activities of phthalonitrile and its phthalocyanines were supported by molecular docking studies. Density Functional Theory (DFT) study supported the experimental results, including the spectral data, and implied that the compounds 5-7 are comparable by their characteristics, such as electronic properties, optical properties, electrostatic potentials, reactivity parameters, with the earlier studied compounds 2-4, which were successfully proved to be good candidates for cancer treatment.Communicated by Ramaswamy H. Sarma.

Synthesis, characterization, antiproliferative activity, docking, and molecular dynamics simulation of new 1,3-dihydro-2H-benzimidazol-2-one derivatives.

Cancer is a global public health problem that affects millions each year. Novel anticancer drug candidates are in need to treat various cancers and to overcome the resistance that exists against drugs in use. Benzimidazole derivatives have been reported as anticancer agents. These lead us to synthesize similar benzimidazole derivatives and investigate their anticancer activity. In this study, six new 1,3-dihydro-2H-benzimidazol-2-one-based molecules (2a-f) were synthesized. The structures of these molecules were verified by spectroscopic methods. The antiproliferative activities of molecules 2a-f were screened against a panel of human cancer cell lines, including the liver, colon, lung, and breast. The molecules were also tested towards normal human lung cell line to determine their selectivity. The results demonstrated that compound 2d had the highest cytotoxic effect compared to compounds 2a-c, 2e, and 2f against DLD-1 and MDA-MB-231 cell lines. The binding potential of the relatively active compound, 2d, with three targets was investigated through molecular docking. The stability of target-compound complexes procured from the docking was explored through molecular dynamics (MD) simulation. The docking and MD simulation studies revealed that compound 2d had the highest potential to bind to GALR3 among the targets. Furthermore, the computational pharmacokinetic study demonstrated that the synthesized compounds had drug-like properties.Communicated by Ramaswamy H. Sarma.

In-hospital outcomes of patients undergoing emergent surgical treatment in patients with infective endocarditis.

BACKGROUND: Infective endocarditis is a serious heart disease that may cause several different clinical conditions and can need urgent surgical therapy. In our study, we aimed to evaluate the patients with infective endocarditis undergoing acute surgical treatment results in-hospital mortality. METHODS: A total of 107 consecutive patients with infective endocarditis undergoing acute surgical therapy were included in our retrospective study. The patients were divided into two groups according to the presence of in-hospital mortality as Group 1 without in-hospital mortality (n=89) and Group 2 with in-hospital mortality (n=18). The demographic, laboratory, and clinical parameters were evaluated in both groups. RESULTS: The mean age (50±14; 64±14, P<0.001) and the incidence of chronic renal failure (9 [10.1%]; 8 [44.4%], P=0.001) were higher in Group 2 while the ejection fraction was lower in Group 2 (50.0±9.3; 44.6±12.9, P=0.039). The incidence of positive blood culture was also higher in Group 2 (41 [46.1]; 14 [77.8], P=0.014). Aortic bioprosthesis operation (2 [2.2]; 6 [33.3], P<0.001) and mitral bioprosthesis operation (4 [4.5]; 5 [27.8], P=0.008) were higher in Group 2 as well as the incidence of septic shock was also higher in Group 2 (1 [1.1]; 3 [16.7], P=0.015). In addition, in multivariate logistic regression analyses, advanced age (odds ratio [OR]: 1.068, 95% confidence interval [CI]: 1.009-1.130, P: 0.024) and positive blood culture (OR: 4.436, 95% CI: 1.044-18.848, P: 0.044) were found to be independent predictors of in-hospital mortality. CONCLUSION: Advanced age, lower ejection fraction, high creatinine, positive blood culture, high systolic pulmonary artery pressure, and septic shock predicted in-hospital death in patients who have undergone emergent or urgent surgery due to infective endocarditis.

Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis.

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are noncoding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.

The effects of dietary microbial 6-phytase on growth parameters, intestinal morphometric properties and selected intestinal genes expression in rainbow trout (Oncorhynchus mykiss, Walbaum 1876).

This study investigated the effects of dietary 6-phytase, produced by a genetically modified Komagataella phaffii, on growth performance, feed utilisation, flesh quality, villus morphometric properties, and intestinal mRNA expression in rainbow trout. Six iso-nitrogenous, iso-lipidic, and iso-caloric diets were formulated and fed to triplicate groups of juvenile rainbow trout weighing 32.57 ± 0.36 g (mean ± SD) for 90 days. The dietary treatments included two positive controls (PC), one formulated with 400 g/kg of fish meal named T1, and the other formulated with 170 g/kg of fish meal plus 1% avP derived from monocalcium phosphate named T2. The remaining dietary treatments consisted of a negative control (NC) formulated with 170 g/kg of fish meal (T3), NC+ 750, NC+ 1500, and NC+ 3000 OTU/kg levels of phytase designated as T4, T5, and T6 diets respectively. Compared to T1, weight gain (WG) increased by 16.29, 13.71 and 11.66% in T4, T5 and T6, respectively (p < 0.05). Feed conversion ratio (FCR) was lowered by 3.2 and 0.8% in T4 and T5 compared to T1 (p < 0.05). WG, feed intake (FI), FCR, final body length, bone ash, bone ash P, and intestinal morphometry were negatively affected in T3 fed fish (p < 0.05). Whole-body fish nutrient, bone ash, bone ash phosphorus (P) compositions and mucosal villus morphometric properties improved in rainbow trout fed diets supplemented with phytase dose ranging from 750-3000 OTU. Bone ash increased by 6.12% in T5 compared to T1 (p < 0.05). Phytase inclusion enhanced the profitability of feeding juvenile rainbow trout such diets as it reduced the feed price and economic conversion rate. Dietary inclusion of phytase down-regulated mRNA expression of genes responsible for fatty acid synthesis and lipogenesis in juvenile rainbow trout. Dietary phytase up-regulated the mRNA expression of genes (SLC4A11 and ATP1A3A) responsible for nutrient uptake and down-regulated intestinal expression of MUCIN 5AC-like genes (mucus secreting genes) in juvenile rainbow trout. Along with improving performance parameters, the inclusion of phytase in rainbow trout diet containing plant-based protein sources, can preserve intestinal morphology by regulating the mRNA expression of genes responsible for fatty acid synthesis, lipogenesis and nutrient uptake and transport.

Low-dose thrombolytic therapy versus unfractionated heparin in patients with intermediate-high risk pulmonary embolism.

BACKGROUND: Patients with intermediate-high risk pulmonary embolism (PE) who have acute right ventricular dysfunction and myocardial injury without overt hemodynamic compromise may be candidates for thrombolytic therapy (TT). In this study, we aimed to compare the clinical outcomes of low-dose prolonged TT and unfractionated heparin (UFH) in intermediate-high risk PE patients. METHODS: This study enrolled 83 (female: 45 [54.2%], mean age: 70.07±10.7 years) retrospectively evaluated patients with the diagnosis of acute PE who were treated with low-dose and slow-infusion of TT or UFH. The primary outcomes of the study were de-fined as a combination of death from any cause and hemodynamic decompensation, and severe or life-threatening bleeding. Secondary endpoints were recurrent PE, pulmonary hypertension, and moderate bleeding. RESULTS: The initial management strategy of intermediate-high risk PE was TT in 41 (49.4%) patients and UFH in 42 (50.6%) cases. Low-dose prolonged TT was successful in all patients. While the frequency of hypotension decreased significantly after TT (22 vs. 0%, P<0.001), it did not decrease after UFH (2.4 vs. 7.1%, p=0.625). The proportion of hemodynamic decompensation was significantly lower in the TT group (0 vs. 11.9%, p=0.029). The rate of secondary endpoints was significantly higher in the UFH group (2.4 vs. 19%, P=0.016). Moreover, the prevalence of pulmonary hypertension was significantly higher in UFH group (0 vs. 19%, p=0.003). CONCLUSION: Prolonged TT regimen with low dose, slow infusion of tissue plasminogen activator was found to be associated with a lower risk of hemodynamic decompensation and pulmonary hypertension in patients with acute intermediate-high-risk PE compared to UFH.

Relationship between myocardial bridging and fatal ventricular arrhythmias in patients with hypertrophic cardiomyopathy: the HCM-MB study.

BACKGROUND: Myocardial bridging (MB) and hypertrophic cardiomyopathy (HCM) are associated with the risk of fatal ventricular arrhythmias (VAs). The goal of the study was to determine the relationship between MB and fatal VAs in HCM patients with implantable cardiac defibrillators (ICD). METHODS: A total of 108 HCM patients (mean age: 46.6 ± 13.6 years; male: 73) were enrolled in this retrospective study. All patients underwent transthoracic echocardiography and coronary computed tomography angiography. Fatal VAs including sustained ventricular tachycardia and ventricular fibrillation were documented in ICD records. RESULTS: There were documented fatal VAs in 29 (26.8%) patients during a mean follow-up time of 71.3 ± 30.9 months. Compared with the other groups, the fatal VA group had a higher incidence of the following: presence of MB (82.8 vs. 38%, p < 0.001), deep MB (62.1 vs. 6.3%, p < 0.001), very deep MB (24.1 vs. 0%, p < 0.001), long MB (65.5 vs. 11.4%, p < 0.001), presence of > 1 MB (17.2 vs. 0%, p = 0.001), and MB of the left anterior descending artery (79.3 vs. 17.7%, p < 0.001) . Sudden cardiac death (SCD) risk score (hazard ratio: 1.194; 95% CI: 1.071-1.330; p = 0.001) and presence of MB (hazard ratio: 3.815; 95% CI: 1.41-10.284; p = 0.008) were found to be independent predictors of fatal VAs in HCM patients. CONCLUSIONS: The current data suggest that the SCD risk score and presence of MB were independent risk factors for fatal VAs in patients with HCM. In addition to conventional risk factors, the coronary anatomical course can provide clinicians with valuable information when assessing the risk of fatal VAs in HCM patients.