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Balew Arega,1,2 Yimtubezinash Woldeamanuel,2 Kelemework Adane,3 Abdulaziz A Sherif,4 Daniel Asrat2 1College of Health Sciences, Debre Markos University, Debre Markos, 2Department of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, 3Department of Microbiology and Immunology, College of Health Sciences, Mekelle University, Mekelle, 4Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia Background: The spectrum of pathogens causing bloodstream infections (BSIs) in cancer patients has shown significant fluctuations in different geographical areas and time. We studied the microbial spectrum and drug-resistance profile of pathogens causing BSIs in febrile cancer patients at a referral hospital in Ethiopia.Methods: This cross-sectional study was conducted between December 2011 and June 2012 at Tikur Anbessa Hospital in Addis Ababa. Blood cultures from febrile cancer patients (n=107) were performed. Bacterial and fungal pathogens were identified and antimicrobial susceptibility testing done for the bacterial isolates using the Kirby–Bauer disk diffusion method.Results: A total of 82 pathogens were isolated from 112 blood culture tests of the 76 patients: 71 (86.6%) of the isolates were bacteria and 11 (13.4%) were fungi. The majority (60.5% [43 of 71]) of the isolates were Gram-positive bacteria, where Staphylococcus aureus was predominant (72% [31 of 43]), and 68% of S. aureus isolates were resistant to ceftriaxone and oxacillin. Gram-negative bacteria accounted for 39.5% (28 of 71) of the isolates. Stenotrophomonas maltophilia (17.9% [five of 28]) was the most frequent Gram-negative isolate. In Gram-negative bacteria, the highest rates of resistance were observed in amoxicillin–clavulanic acid (80% [12 of 15]), followed by ceftriaxone (73.3%) and trimethoprim–sulfamethoxazole (73.3%). Multidrug resistance (resistance to three or more types of antibiotics, in this case to ceftriaxone, tetracycline, and trimethoprim-sulfamethoxazole) was observed in 26.3% (13 of 43) of Gram-positive and 40% (six of 16) of Gram-negative bacteria. Neutropenia was an independent risk factor for BSIs (P=0.02).Conclusion: Gram-positive bacteria were the predominant etiologic agents of BSIs in Ethiopian patients with cancer. Both Gram-positive and Gram-negative bacteria showed an increasing level of resistance for most of the antibiotics used for empiric therapy. Routine bacterial surveillance and study of their resistance patterns must be an essential component of cancer-related infection control and care in our setting. Keywords: bloodstream infections, cancer patients, bacteria, drug resistance

Objectives: Endocardial fibroelastosis (EFE) is a rare form of restrictive cardiomyopathy associated with high morbidity and mortality. The literature is sparse on information pertaining to risk stratification. Thus, we sought to highlight the risk factors of acute ischemic stroke (AIS) and mortality in adults with EFE., Methods: The National Inpatient Sample (NIS) database was queried from 2001 to 2020 using the International Classification of Diseases 9th Revision (ICD-9) and 10th Revision (ICD-10) codes for adult patients with EFE. Factors associated with AIS and mortality were identified., Results: In all, 18495 cases of EFE fit the inclusion criteria, of which 2370 (12.82%) had AIS. The mean ages for patients with and without AIS were 62.37 and 54.24, respectively. Multivariate regression suggested greater odds of AIS in patients with hypertension (aOR 2.329, P <0.01), dyslipidemia (aOR: 1.566, P <0.01), peripheral vascular disease (PVD) (aOR: 1.736, P <0.01), alcohol abuse (aOR: 1.817, P <0.01), age >60 y (aOR: 1.646, P <0.01), females (vs. males, aOR: 1.238, P <0.01), and smokers (aOR: 1.697, P <0.01). Patients with cirrhosis (aOR: 0.174, P <0.01), CKD (aOR: 0.369, P <0.01), COPD (aOR: 0.402, P <0.01), atrial fibrillation (aOR: 0.542, P <0.01) had lower odds of AIS. 3.1% of EFE patients with AIS died. Diabetes (aOR: 11.665, P <0.01) and COPD (aOR: 3.201, P =0.017) were associated with the greatest odds of all-cause mortality. Dyslipidemia (aOR: 0.387, P =0.010) and females (vs. males, aOR: 0.432, P =0.012) had reduced odds of all-cause mortality., Conclusion: Several risk factors are associated with AIS in EFE, while diabetes, COPD, and being male are associated with mortality in EFE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients., Materials and Methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages., Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients. In contrast, while deceased patients exhibited monoclonal B cell receptor (BCR) expansions without COVID-19 specificity, survivors demonstrated diverse and specific BCR clones. These findings suggest that neither TCR diversity nor BCR monoclonal expansions are sufficient for viral clearance and subsequent recovery. Differential gene expression analysis revealed that protein biosynthetic processes were enriched in survivors, but that potentially damaging mitochondrial ATP metabolism was activated in the deceased., Conclusion: This study underscores that BCR repertoire diversity, but not TCR diversity, correlates with favorable outcomes in COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paran, Oyama, Khasawneh, Ai, Ismanto, Sherif, Saputri, Ono, Saita, Takei, Horiuchi, Yagi, Matsuura, Okazaki, Takahashi, Standley, Tabe and Naito.)

Background: Non-ST-segment elevation myocardial infarction (NSTEMI) is an entity which was defined as a type of a coronary syndrome with positive cardiac biomarker of myocardial necrosis with no ST-segment elevation in ECG. Currently, the centers for Medicare and Medicaid services (CMS) Hospital readmission reduction program assistance risk-adjusted 30-day readmission rates for five major clinical entities which includes acute myocardial infarction., Methods: We performed this retrospective study to look into the current burden and predictors of NSTEMI readmission. Data were obtained from the Nationwide Readmission Database for the year 2020. We analyzed data on hospital readmission of 336 620 adults who were admitted for NSTEMI., Results: The 30-day readmission rate was 13.5% with NSTEMI being the most common cause of readmission. Mortality was higher in readmitted patients compared to index admission (5.4 vs 3.6%, P = 0.000). Higher risk of readmission was associated with female sex, higher Charlson comorbidity index, and longer length of stay. Lower risk of admission was seen in patients from smaller communities, patients who underwent percutaneous coronary intervention, and discharged to rehabilitation facilities., Conclusion: Although we found an improvement in readmission rates compared to prior studies, about 13% of patients continue to get readmitted within 30 days causing significant cost to the healthcare system and often these patients have worse outcomes. We need continuing large-scale studies to identify quality measures to prevent readmission, improve mortality during readmission, and make better use of financial resources., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Mixed ligand complexes of manganese(II), cobalt(II), copper(II), and cadmium(II)with an innovative Schiff base ligand denoted as (L 1 ), 4-(2-((1E,2E)-1-(2-(p-tolyl)hydrazineylidene)propan-2-ylidene)hydrazineyl), served as the principal ligand, while glycine (L2) was employed as secondary ligand were successfully effectively characterized through a comprehensive set of analyses, including Elemental analysis, UV-Visible, FT-IR, Mass spectra, and conductometric measurements. Density functional theory (DFT) computations were executed to discern the enduring electronic arrangement, the energy gap, dipole moment and chemical hardness of the hybrid ligand assemblies. The proposed geometry for the complexes is a distorted octahedral structure. The antimicrobial efficacy of these compounds was assessed against a range of bacterial and fungal strains. Notably, these complexes exhibited promising antimicrobial activities, with the cadmium (II) complex demonstrating superior efficacy towards all tested organisms. These compounds were also examined for their antibiotic properties against H. pylori to explore their broader medical potential. The Schiff base ligand and its corresponding metal complexes displayed substantial potential as an antibiotic against H. pylori. Additionally, the antitumor potential of the synthesized complexes was assessed against MCF-7 (Breast carcinoma) cells-the Cu (II) complex demonstrated superior activity with the lowest IC 50 value compared to cisplatin. Moreover, it exhibited reduced cytotoxicity towards normal cells (VERO cells) compared to cisplatin, establishing it as the most potent compound in the study. Furthermore, molecular docking was explored of the Schiff base ligand and its corresponding cadmium(II) complex. The analysis of the docking study yielded valuable structural insights that can be effectively utilized in conducting inhibition studies for example against COVID-19. This comprehensive study highlights these synthesized compounds' multifaceted applications and promising bioactive properties., (© 2024. The Author(s).)

Aims: We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019., Methods and Results: International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P < 0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P < 0.01), hyperlipidaemia (39.1% vs. 52.9%; P < 0.01), diabetes (22.5% vs. 49.1%; P < 0.01), obesity (13.2% vs. 25.0%; P < 0.01), and hypertension (20.2% vs. 23.8%; P < 0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P < 0.01) and pulmonary hypertension (36.6% vs. 12.7%; P < 0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P < 0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P < 0.01), Black (15.7% vs. 13.0%; P < 0.01), and Hispanic (13.3% vs. 6.9%; P < 0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P < 0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P = 0.02) and higher hospitalization costs ($67 363 vs. $57 128; AMD: 198.9; 95% CI: -4780 to 5178; P = 0.93)., Conclusions: In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The treatment of cancer often leads to a range of adverse effects. Encapsulating drugs can mitigate these effects and enhance drug efficacy by enabling a controlled release at the site of interest. This study details the successful synthesis of zinc oxide nanoparticles (ZnONPs) through the precipitation of Zn(NO 3 ) 2 ·6H 2 O with KOH. A Pd(II) complex drug was synthesized from a Schiff base ligand derived from 2-hydroxybenzohydrazide and (E)-1-(2-(p-tolyl)hydrazono)propan-2-one using potassium tetrachloropalladate(II). This complex was subsequently incorporated into ZnONPs. Characterization of the resulting compounds was performed using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Fourier Transform Infrared (FTIR) Spectroscopy, and UV-visible spectroscopy. TEM imaging revealed particle sizes of 160.69 ± 4.74 nm for ZnONPs and 185.28 ± 2.3 nm for the Pd(II) complex-encapsulated ZnONPs. The Zeta potential values were 6.53 mV for ZnONPs and 7.36 mV for Pd(II) complex-encapsulated ZnONPs. UV-visible spectroscopy showed an absorption peak at 360 nm for ZnONPs, while the Pd(II) complex-encapsulated ZnONPs exhibited a peak at 410 nm. FTIR analysis indicated the presence of the Pd(II) complex within the ZnONPs, as evidenced by a consistent Zn-O vibrational band at 832 cm -1 and a shift in another peak from 460 to 413 cm -1 . Additionally, the detection of a C = N stretching vibration at 1548 cm -1 and a carbonyl stretch at 1626 cm -1 was observed. The Encapsulation Efficiency (E.E.) of the Pd(II) complex was 97.2%. A drug release experiment conducted at pH 7 showed a steady-state release pattern after 16 h, with a cumulative release of 44.3%. The cytotoxic effects of the Pd(II) complex and its encapsulated form in ZnONPs on the MCF-7 cell line were assessed via MTT test. The Pd(II) complex encapsulated within ZnONPs exhibited decreased toxicity relative to the unencapsulated drug, as evidenced by a higher IC 50 value of 418.5 μg/ml. This suggests that the encapsulation facilitates a sustained release, which allows for targeted accumulation within cells. The elevated IC 50 value indicates that the drug delivery system may be engineered to modulate the release of the drug in a more controlled manner, potentially resulting in a prolonged release profile rather than an immediate therapeutic impact., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Calcific aortic valve disease (CAVD) and mitral annular calcification (MAC) are associated with various cardiovascular diseases and may influence systemic vascular pathologies. However, their relationship with endothelial dysfunction and carotid intima-media thickness (CIMT) remains poorly elucidated. This research aims to explore the associations between MAC, aortic valve sclerosis (AVS), and markers of vascular dysfunction, specifically CIMT and endothelial function., Methods: This prospective observational study included 200 patients undergoing routine echocardiographic evaluation at the National Heart Institute between May 2022 and April 2023. Patients were stratified into four groups namely isolated MAC (38 patients), isolated AVS (72 patients), combined MAC and AVS (50 patients), and a control group without MAC or AVS (40 patients). All participants underwent comprehensive cardiovascular evaluation, including transthoracic echocardiography (TTE) and carotid duplex ultrasonography. Endothelial function was determined by measuring reactive hyperemia-induced alterations in brachial artery diameter., Results: The mean age of participants was 60.6±8.4 years, with a predominance of male subjects (64%). No significant differences were noted in baseline demographic and clinical characteristics across the groups. Patients with isolated AVS, isolated MAC, and both conditions demonstrated increased CIMT compared to controls, with significant differences noted in the combined MAC and AVS group compared to controls (p-value=0.031). Endothelial dysfunction was observed in 14.8% of the AVS group and 21.1% in the combined group, but no significant differences existed when compared to controls. The study also revealed that patients with AVS are more likely to exhibit increased CIMT (p-value=0.008)., Conclusions: Both MAC and AVS are connected to increased CIMT, suggesting a link with systemic atherosclerotic processes. Although the existence of endothelial dysfunction was not significantly higher in patients with valvular calcifications, the findings support the need for further research into the cardiovascular implications of CAVD and MAC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Elganainy et al.)

Objective: To contemporaneously reappraise the incidence-rate, prevalence, and natural history of hypertrophic cardiomyopathy (HCM) in Olmsted County, Minnesota, from 1984 to 2015., Patients and Methods: A validated medical-record linkage system collecting information for residents of Olmsted County was used to identify all cases of HCM between January 1, 1984, and December 31, 2015. After adjudication of records from Mayo Clinic and Olmsted Medical Center, data relating to diagnoses and outcomes were abstracted. The calculated incidence rate and prevalence were standardized to the US 1980 White population (age- and sex-adjusted) and compared with a prior study examining the years 1975-1984., Results: Two hundred seventy subjects with HCM were identified. The age- and sex-adjusted incidence rate was 6.6 per 100,000 person-years, and the point prevalence of HCM on January 1, 2016, was 89 per 100,000 population. The incidence rate and point prevalence of HCM on January 1, 2016, standardized to the US 1980 White population (age- and sex-adjusted), were 6.7 (95% CI, 7.1 to 8.8) per 100,000 person-years and 81.5 per 100,000 population, respectively. The incidence rate of HCM increased each decade since the index study. Individuals with HCM had a higher overall standardized mortality rate than the general population with an observed to expected HR of 1.44 (95% CI, 1.21 to 1.71; P<.001) which improved by each decade., Conclusion: The incidence and prevalence of HCM are higher than rates reported from a prior study in the same community examining the years 1975-1984, but lower than other study cohorts. The risk of mortality in HCM remains higher than expected, albeit with improvement in rates of mortality observed each decade during the study period., (Copyright © 2024. Published by Elsevier Inc.)

Irgb6 is a priming immune-related GTPase (IRG) that counteracts Toxoplasma gondii. It is known to be recruited to the low virulent type II T. gondii parasitophorous vacuole (PV), initiating cell-autonomous immunity. However, the molecular mechanism by which immunity-related GTPases become inactivated after the parasite infection remains obscure. Here, we found that Thr95 of Irgb6 is prominently phosphorylated in response to low virulent type II T. gondii infection. We observed that a phosphomimetic T95D mutation in Irgb6 impaired its localization to the PV and exhibited reduced GTPase activity in vitro. Structural analysis unveiled an atypical conformation of nucleotide-free Irgb6-T95D, resulting from a conformational change in the G-domain that allosterically modified the PV membrane-binding interface. In silico docking corroborated the disruption of the physiological membrane binding site. These findings provide novel insights into a T. gondii-induced allosteric inactivation mechanism of Irgb6., (© 2023 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: Schiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy., Methods: The current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)- 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC 50 of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells., Results: The Pd(II) complex displayed approximately the same IC 50 as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC 50 , 1.40 μg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels., Conclusion: It can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC 50 value., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI) is indicated in complex interventions. There is a paucity of evidence for outcomes with large studies on using IVUS during PCI in non-ST-elevation myocardial infarction (NSTEMI). Our objective was to compare the in-hospital outcome of IVUS-guided with that of nonguided PCI among NSTEMI hospitalizations. The National Inpatient Sample (2016 to 2019) was queried to identify all hospitalizations with a principal diagnosis of NSTEMI. In our study, we compared outcomes of PCI with and without IVUS guidance using a multivariate logistic regression model after propensity score matching, with the primary outcome being in-hospital mortality. A total of 671,280 NSTEMI-related hospitalizations were identified, of whom 48,285 (7.2%) underwent IVUS-guided PCI compared with 622,995 (92.8%) who underwent non-IVUS PCI. After adjusted analysis on matched pairs, we found that IVUS-guided PCI had a lower risk of in-hospital mortality than that of non-IVUS PCI (adjusted odds ratio [aOR] 0.736, confidence interval (CI) 0.578 to 0.937, p = 0.013). However, there was a higher use of mechanical circulatory support in the IVUS-guided PCI (aOR 2.138, CI 1.84 to 2.47, p <0.001) than in non-IVUS PCI. The odds of cardiogenic shock (aOR 1.11, CI 0.93 to 1.32, p = 0.233) and procedural complications (aOR 0.794, CI 0.549 to 1.14, p = 0.22) were similar between the cohorts. Hence, we conclude that patients with NSTEMIs who underwent IVUS-guided PCI had less risk of in-hospital mortality and a greater requirement of mechanical circulatory support than did those who underwent non-IVUS PCI, with no difference in procedural complications. Large prospective trials are essential to validate these findings., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Metallic antitumor drugs with heterocyclic ligands, such as novel AMI (amino methyl imidazole) complexes [Pd(AMI)Cl 2 ](1), [Cu(AMI)L 1 ](2), and [Cu(AMI)L 2 ·2H 2 O](3) where L 1  = oxalate and L 2  = malonate, were synthesized and characterized. Assessments included elemental analyses, mass spectrometry, Fourier transform-infrared spectroscopy, ultraviolet-visible spectroscopy, and thermal analysis. The cytotoxicity of AMI complexes compared to cisplatin was assessed using MTT (3-[4,5-dimethylthiazol-2-yl] 2,5diphenyl tetrazolium bromide) assay with breast (MCF-7) and cervical (HeLa) cancer cell lines. After treating these cells with the AMI complexes' IC 50 values for 48 h, malondialdehyde levels and catalase activity were used to assess oxidative stress, antioxidant activity was evaluated with DPPH radical scavenging method, comet assays assessed DNA damage, and DNA fragmentation was evaluated using the gel electrophoresis. In vitro, antimicrobial activity was assessed using a disc diffusion method. The anticancer activity results showed that IC 50 (half-maximal inhibitory concentration) values of complex one, two, and three against MCF-7 and HeLa cancer cells are 0.156 ± 0.0006, 0.125 ± 0.001, 0.277 ± 0.002 μM respectively for MCF-7 cells and 0.222 ± 0.0005, 0.126 ± 0.0009, 0.152 ± 0.001 μM respectively for HeLa cells. Complex two demonstrated strong anticancer activity against MCF-7 and Hela cells. The study of oxidative stress parameters revealed that Malondialdehyde levels increased in cancer cell lines treated with complexes compared to untreated cells. Catalase activity decreased in cells treated with palladium chelate. The DPPH radical scavenging assay results identified that complex one was a more potent antioxidant in MCF-7 and Hela cells than other complexes with SC 50 values of 227.5 ± 0.28 and 361 ± 1.2 μL/mL, respectively. The comet assay results showed that complex two caused significant DNA damage in MCF-7 and HeLa cancer cells treated. Antimicrobial assays identified complex three as the most effective. Copper complexes give better antifungal activity against A. flavus than the palladium complex. We conclude that complex two is the most active in both cell types and might be assessed as a clinically useful drug for breast cancer treatment. The significance of the current study is the synthesis of antitumor drugs containing heterocyclic ligands, such as novel AMI complexes, and the study of their biological activities., (© 2023. The Author(s).)

Apical hypertrophic cardiomyopathy (ApHCM) is thought to be an uncommon variant of hypertrophic cardiomyopathy (HCM). This article is a literature review focusing on the characteristic electrocardiogram (EKG) and 2D echocardiogram findings as currently there are no specific ACC/AHA/ESC guidelines set as diagnostic criteria for ApHCM., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is one of the most common causes of dementia. Several drugs are used to improve the symptoms, but do not stop AD progression. There are more promising treatments that may have a significant role in AD diagnosis and treatment such as miRNAs and stem cells. The present study aims to develop a new approach for AD treatment by mesenchymal stem cells (MSCs) and/or acitretin with special reference to inflammatory signaling pathway as NF-kB and its regulator miRNAs in AD-like rat model. Fourty-five male albino rats were allotted for the present study. The experimental periods were divided into induction, withdrawal, and therapeutic phases. Expression levels of miR-146a, miR-155, necrotic, growth and inflammatory genes were assessed using RT-qPCR. Histopathological examination of brain tissues was performed in different rat groups. The normal physiological, molecular, and histopathological levels were restored after treatment with MSCs and/or acitretin. The present study demonstrates that the miR-146a and miR-155 might be used as promising biomarkers for AD. MSCs and/or acitretin proved their therapeutic potential in restoring the expression levels of targeted miRNAs and their related genes concerning NF-kB signaling pathway., (© 2023. The Author(s).)

There is little known about the differences, from the point of view of healthcare resource utilization, between non-fatal versus fatal firearm-related injuries. We undertook this research project utilizing the National Inpatient Sample (NIS) database to address this critical knowledge gap. Our aims for this study were to describe the patterns of FRI in the United States during the period of 2016-2019 and to evaluate the patient-centered outcomes in the survivor (non-fatal injuries) versus the non-survivor (fatal injuries) groups. We used the National Inpatient Sample (NIS) Database, 2016-2019 (5) (~ 20% of United States hospitalizations) to identify patients with an associated diagnosis of firearm-related injuries (FRI) [Gibson T et al (2016) in Agency for Healthcare Research and Quality 2016-02]. We found that the individuals from the lowest quartile of annual household income, males, young Americans, and racial minorities were disproportionally affected The non-survivor (fatal injuries) group had a shorter length of stay in the hospital by 5.1 days (95% CI - 5.64 to - 4.58, p value =  < 0.01), the higher median cost of hospitalization by $8903 (95% confidence interval $311.9 to $17,494.2, p value = 0.04), and a higher median cost of hospitalization per day by $41,576.74 (95% confidence interval $ 40,333.1 to $42,820.3, p value =  < 0.01). In conclusion, the individuals from the lowest quartile of annual household income, males, young Americans and racial minorities were disproportionally affected. Firearm-related injuries pose a persistent healthcare cost burden with the cumulative and per day cost of hospitalization for fatal injuries being significantly higher than the non-fatal injuries despite a shorter hospital LOS., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Introduction: The structural and dynamic determinants that confer highly selective RET kinase inhibition are poorly understood., Objectives: To explore the druggability landscape of the RET active site in order to uncover structural and dynamic vulnerabilities that can be therapeutically exploited., Methods: We apply an integrated structural, computational and biochemical approach in order to explore the druggability landscape of the RET active site., Results: We demonstrate that the that the druggability landscape of the RET active site is determined by the conformational setting of the ATP-binding (P-) loop and its coordination with the αC helix. Open and intermediate P-loop structures display additional druggable vulnerabilities within the active site that were not exploited by first generation RET inhibitors. We identify a cryptic pocket adjacent to the catalytic lysine formed by K758, L760, E768 and L772, that we name the post-lysine pocket, with higher druggability potential than the adenine-binding site and with important implications in the regulation of the phospho-tyrosine kinase activity. Crystal structure and simulation data show that the binding mode of highly-selective RET kinase inhibitors LOXO-292 and BLU-667 is controlled by a synchronous open P-loop and αC-in configuration that allows accessibility to the post-lysine pocket. Molecular dynamics simulations show that these inhibitors efficiently occupy the post-lysine pocket with high stability through the simulation time-scale (300 ns), with both inhibitors forming hydrophobic contacts further stabilized by pi-cation interactions with the catalytic K758. Engineered mutants targeting the post-lysine pocket impact on inhibitor binding and sensitivity, as well as RET tyrosine kinase activity., Conclusions: The identification of the post-lysine pocket as a new druggable vulnerability in the RET kinase and its exploitation by second generation RET inhibitors have important implications for future drug design and the development of personalized therapies for patients with RET-driven cancers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Orthotopic heart transplantation is the most effective long-term therapy for end-stage heart disease. Denervation with the loss of autonomic modulation, vasculopathy, utilization of immunosuppressant drugs, and allograft rejection may result in an increased prevalence of arrhythmias in transplanted hearts. We aim to describe the trends, distribution, and the clinical impact of arrhythmias in patients with transplanted hearts. We queried the National Inpatient Sample with administrative codes for cardiac transplant patients using procedure ICD-9-CM codes 37.5 and 33.6. Arrhythmias were extracted using validated ICD-9-CM codes. Statistical Analysis System (SAS) version 9.4 was used for analysis. There were a total of 30,020 hospitalizations of heart transplant recipients between 1999 and 2014 in the United States of which 1,6342 (54.4%) had an arrhythmia. The frequency of total arrhythmias increased from 53.6% (n=1,158) in 1999 to 67.3% (n=1,575) in 2014. Transplant patients with arrythmias was not associated with significantly higher inpatient mortality (7.72% vs 6.90%, P = 0.225). The most common arrythmia was atrial fibrillation ([AF]26.83%) followed by ventricular tachycardia (22.86%). Trends in mortality associated with arrhythmias following heart transplant has been decreasing from 12.3% in 1999 to 8.9% in 2014 (P = 0.04). Subgroup analysis of ventricular arrythmias (VA) following heart transplant were associated with increased mortality (8.61% vs 6.94%, P = 0.0229). Over half of patients develop 1 or more cardiac arrhythmia after heart transplant. There is an increasing secular trend in the frequency of arrhythmias post cardiac transplant with atrial fibrillation determined to be the most common arrhythmia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Low-level laser therapy (LLLT) is a promising noninvasive physiotherapeutic approach that has been demonstrated to improve cardiac performance. This study aimed to assess the impact of low-level laser therapy on cardiac functions and clinical status in patients with chronic left ventricular systolic heart failure who were not candidates for cardiac revascularization or resynchronization. A case series of 27 patients received a course of low-level laser physiotherapy, the clinical outcomes, echocardiographic parameters, and serum nitric oxide levels were evaluated before and after LLLT., Results: Of the total patients enrolled in the study, 21 (or 77.8%) were male, with a mean age of 57.7 ± 6.89 years. NYHA classification significantly improved after low-level laser therapy, 15 patients were in class III,12 were in class IV, and no one was in class II before laser therapy while after laser therapy; 25 patients shifted to class II, two patients were in class III with P < 0.001, Six-minute walk distance test was performed, and the results showed that the mean of 6MWT was less than 200 m (148.556 ± 39.092) before the study but increased to more than 300 after laser therapy (385.074 ± 61.740), left ventricular ejection fraction before laser therapy was 26 ± 7.5 while after laser therapy it became 30 ± 8.6 but diastolic function did not change after low-level laser therapy, the mean peak TR pressure was 40.0 ± 9.0 mmHg and 33.0 ± 7.0 before and after laser therapy respectively P < 0.001. A significant change was observed in NO level from 4.1 ± 1.4 IU/ml before laser therapy to 5.2 ± 1.7 IU/ml after laser therapy P < 0.001., Conclusions: Low-level laser therapy may add benefits to improve symptoms, clinical condition, and quality of life in patients with left ventricular systolic dysfunction, further studies are necessary to evaluate the changes in cardiac functions at a longer follow-up duration., (© 2023. The Author(s).)

Serratia marcescens is an aerobic, Gram-negative bacillus predominantly seen in patients with intravenous drug use, immunosuppression, previous antibiotic exposure, and indwelling catheterization. Gram-negative organism causing infective endocarditis (IE) is rare. Serratia marcescens IE is uncommon and is reported to be seen in 0.14% of all cases. In this report, we discuss in detail about a 38-year-old man with a history of intravenous drug abuse presenting with S. marcescens related prosthetic valve IE.

Studies suggested that the pathogenesis of inflammatory breast cancer (IBC) is related to inflammatory manifestations accompanied by specific cellular and molecular mechanisms in the IBC tumor microenvironment (TME). IBC is characterized by significantly higher infiltration of tumor-associated macrophages (TAMs) that contribute to its metastatic process via secreting many cytokines such as TNF, IL-6, IL-8, and IL-10 that enhance invasion and angiogenesis. Thus, there is a need to first understand how IBC-TME modulates the polarization of TAMs to better understand the role of TAMs in IBC. Herein, we used gene expression signature and Synchrotron Fourier-Transform Infrared Microspectroscopy (SR-μFTIR) to study the molecular and biochemical changes, respectively of in vitro polarized TAMs stimulated by the secretome of IBC and non-IBC cells. The gene expression signature showed significant differences in the macrophage's polarization-related genes between stimulated TAMs. FTIR spectra showed absorption bands in the region of 1700-1500 cm -1 attributed to the amide I ν(C=O), & ν AS (CN), δ (NH), and amide II ν(CN), δ (NH) proteins bands. Moreover, three peaks of different intensities and areas were detected in the lipid region of the νCH 2 and νCH 3 stretching modes positioned within the 3000-2800 cm -1 range. The PCA analysis for the second derivative spectra of the amide regions discriminates between stimulated IBC and non-IBC TAMs. This study showed that IBC and non-IBC TMEs differentially modulate the polarization of TAMs and SR-μFTIR can determine these biochemical changes which will help to better understand the potential role of TAMs in IBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.

Background: Sarcoidosis with cardiac involvement, although rare, has a worse prognosis than sarcoidosis involving other organ systems., Objective: We used a large dataset to train machine learning models to predict in-hospital mortality among sarcoidosis patients admitted with heart failure (HF)., Method: Utilizing the National Inpatient Sample, we identified 4659 patients hospitalized with a primary diagnosis of HF. In this cohort, we identified patients with a secondary diagnosis of sarcoidosis using International Statistical Classification of Disease, Tenth Revision (ICD-10) codes. Patients were separated into a training group and a testing group in a 7:3 ratio. Least absolute shrinkage and selection operator regression was used to select variables to prevent model overfitting or underfitting. For machine learning models, logistic regression, random forest, and XGBoosting were applied in the training group. Parameters in each of the models were tuned using the GridSearchCV function. After training, all models were further validated in the testing group. Models were then evaluated using the area under curve (AUC) score, sensitivity, and specificity., Results: A total of 2.3% of sarcoidosis patients died in HF admission. Our machine learning model analysis found the RF model to have the highest AUC score and sensitivity. Feature analysis found that comorbid arrhythmias and fluid electrolyte disorders were the strongest factors in predicting in-hospital mortality., Conclusion: Machine learning methods can be useful in identifying predictors of in-hospital mortality in a given dataset., (© 2022 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Takotsubo syndrome (TTS) is a rare cardiovascular condition characterized by reversible ventricular dysfunction and a presentation resembling that of acute myocardial infarction. An increasing number of studies has shown the association of respiratory diseases with TTS. Here, we comprehensively reviewed the literature and examined the available evidence for this association. After searching PubMed, EMBASE, and Cochrane Library databases, two investigators independently reviewed 3117 studies published through May 2021. Of these studies, 99 met the inclusion criteria ( n  = 108 patients). In patients with coexisting respiratory disease and TTS, the most common TTS symptom was dyspnoea (70.48%), followed by chest pain (24.76%) and syncope (2.86%). The most common type of TTS was apical, accounting for 81.13% of cases, followed by the midventricular (8.49%), basal (8.49%), and biventricular (1.89%) types. Among the TTS cases, 39.82% were associated with obstructive lung disease and 38.89% were associated with pneumonia. Coronavirus disease 2019 (COVID-19), which has been increasingly reported in patients with TTS, was identified in 29 of 42 (69.05%) patients with pneumonia. The overall mortality rate for patients admitted for respiratory disease complicated by TTS was 12.50%. Obstructive lung disease and pneumonia are the most frequently identified respiratory triggers of TTS. Medications and invasive procedures utilized in managing respiratory diseases may also contribute to the development of TTS. Furthermore, the diagnosis of TTS triggered by these conditions can be challenging due to its atypical presentation. Future prospective studies are needed to establish appropriate guidelines for managing respiratory disease with concurrent TTS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

New or preexisting atrial fibrillation (AF) is frequent in patients undergoing aortic valve replacement. We evaluated whether the presence of AF during transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) impacts the length of stay, healthcare adjusted costs, and inpatient mortality. The median length of stay in the patients with AF increased by 33.3% as compared with those without AF undergoing TAVI and SAVR (5 [3 to 8] days vs 3 [2 to 6] days, p <0.0001 and 8 [6 to 12] days vs 6 [5 to 10] days, p <0.0001, respectively). AF increased the median value of adjusted healthcare associated costs of both TAVI ($46,754 [36,613 to 59,442] vs $49,960 [38,932 to 64,201], p <0.0001) and SAVR ($40,948 [31,762 to 55,854] vs $45,683 [35,154 to 63,026], p <0.0001). The presence of AF did not independently increase the in-hospital mortality. In conclusion, in patients undergoing SAVR or TAVI, AF significantly increased the length of stay and adjusted healthcare adjusted costs but did not independently increase the in-hospital mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: This study assesses the effect of malnutrition on the in-hospital outcomes of patients with takotsubo cardiomyopathy (TCM)., Methods: We performed a retrospective cohort analysis using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for a primary diagnosis of TCM from the National Inpatient Sample database (2016-2018). A concurrent diagnosis of malnutrition was then identified, and these patients were divided into the malnutrition group and non-malnutrition group. To adjust for underlying risk factors, a multivariable logistic regression model was employed followed by a propensity score matching analysis for the malnutrition and the non-malnutrition group. We then compared the in-hospital outcomes between these two groups., Results: Among 4733 patients with a primary diagnosis of TCM, 221 (4.7%) patients with TCM were found to be malnourished. After propensity score matching, patients with TCM with malnutrition were found to have a higher mortality rate (8.3% versus 2.0%, P < 0.001), a higher rate of complications including cardiogenic shock (16.1% versus 7.0%, P < 0.001), ventricular arrhythmia (8.8% versus 3.9%, P = 0.01), acute kidney injury (24.9% versus 10.6%, P < 0.001), and acute respiratory failure (32.7% versus 17.8%, P < 0.001). There was no statistically significant difference in the incidence of cardiac arrest between the two groups. Malnutrition of severe degree was associated with a sevenfold (odds ratio 6.8, 95% confidence interval, 3.2-13.4) increased risk of in-hospital mortality compared with those without malnutrition., Conclusion: Patients with malnutrition who were admitted with TCM were associated with higher rates of in-hospital mortality and complications compared with those without malnutrition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane-binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs., (© 2021 Saijo-Hamano et al.)

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the greatest cause of cancer-related death in the world. Garden cress ( Lepidium sativum ) seeds have been proven to possess extraordinary antioxidant, anti-inflammatory, hypothermic, and analgesic properties. In this study, in vitro cytotoxic efficiency evaluation of L. sativum fractions was performed against two hepatocellular carcinoma cell lines (HuH-7 and HEPG-2), and the expression of some apoptotic genes was explored. In addition, the chemical composition of a potent extract of L. sativum was analyzed using gas chromatography coupled with mass spectrometry. Then, molecular docking analysis was implemented to identify the potential targets of the L. sativum components' most potent extract. Overall, the n -hexane extract was the most potent against the two HCC cell lines. Moreover, these cytotoxicity levels were supported by the significant downregulation of EGFR and BCL2 gene expression levels and the upregulation of SMAD3, BAX, and P53 expression levels in both HuH-7 and HEPG2 cell lines. Regarding L. sativum 's chemical composition, GC-MS analysis of the n -hexane extract led to the identification of thirty compounds, including, mainly, hydrocarbons and terpenoids, as well as other volatile compounds. Furthermore, the binding affinities and interactions of the n -hexane fraction's major metabolites were predicted against EGFR and BCL2 molecular targets using the molecular docking technique. These findings reveal the potential use of L. Sativum in the management of HCC.

Locally advanced breast cancer (LABC) is an aggressive disease characterized by late clinical presentation, large tumor size, treatment resistance and low survival rate. Expression of EGFR/HER2 and activation of intracellular tyrosine kinase domains in LABC are associated with poor prognosis. Thus, target therapies such as the anti-receptor tyrosine kinases lapatinib drug have been more developed in the past decade. The response to lapatinib involves the inhibition of RTKs and subsequently signaling molecules such as Src/STAT3/Erk1/2 known also to be activated by the cytokines in the tumor microenvironment (TME). The aim of the present study is to identify the major cytokine that might contribute to lapatinib resistance in EGFR+/HER2+ LABC patients. Indeed, tumor associated macrophages (TAMs) are the main source of cytokines in the TME. Herein, we isolated TAMs from LABC during modified radical mastectomy (MRM). Cytokine profile of TAMs revealed that IL-8 is the most prominent highly secreted cytokine by TAMs of LABC patients. Using in-vitro cell culture model we showed that recombinant IL-8 (50 and 100 ng/mL) at different time intervals interfere with lapatinib action via activation of Src/EGFR and signaling molecules known to be inhibited during treatment. We proposed that to improve LABC patients' response to lapatinib treatment it is preferred to use combined therapy that neutralize or block the action of IL-8., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Myeloid sarcoma usually involves lymph nodes, and head and neck regions. Uncommon sites like testis and ovary are rarely involved and pose a diagnostic challenge. Nonspecific findings, difficulty in retrieving biopsy specimens, and associated infertility are few of the hurdles faced during diagnosis and treatment of testicular myeloid sarcoma. Our review is an attempt to study myeloid sarcoma involving testis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare.

Competing Interests: Competing interests: None declared.

Background: Postoperative pain control for morbidly obese patients represents a challenge because of their sensitivity towards opioid-induced respiratory depression. We elected both dexmedetomidine and xylocaine (lidocaine) continuous infusions as adjuvants because they lack respiratory depression side effect., Methods: A total of 150 ASA I to III patients were enrolled in the study, randomly allocated into three equal parallel groups; the control, lidocaine or dexmedetomidine group. Patients received either dexmedetomidine 1 µg/kg bolus over 10 minutes followed by 0.4 µg/kg/h continuous infusion, lidocaine 2 mg/kg bolus over 10 minutes followed by 1.5 mg/kg/h continuous infusion or saline bolus and continuous infusion during the whole operation period. The total morphine consumption was designed to be the primary outcome variable, pain score, and quality of recovery 40 was set as secondary outcome variables. Pain score was measured by numerical rating scale while the quality of recovery score was estimated by the QOR-40 questionnaire. P<0.05 was considered significant., Results: Both dexmedetomidine and lidocaine reduced the total morphine consumption where it was 14±4, 18±4, and 29±5 mg in the dexmedetomidine, lidocaine, and control groups, respectively (P<0.0001). While dexmedetomidine reduced postoperative pain at all measured time points, lidocaine reduced only early pain. Both drugs displayed better quality of recovery score 40 measured at postoperative day 3; 186±2 for the dexmedetomidine group versus 176±6 for the lidocaine group versus 140±6 for the control group (P<0.0001)., Conclusions: Continuous infusion of either dexmedetomidine or xylocaine reduces postoperative opioid consumption, pain and improve the quality of recovery following laparoscopic sleeve gastrectomy.