Donor template delivery by recombinant adeno-associated virus for the production of knock-in mice.

BACKGROUND: The ability of recombinant adeno-associated virus to transduce preimplantation mouse embryos has led to the use of this delivery method for the production of genetically altered knock-in mice via CRISPR-Cas9. The potential exists for this method to simplify the production and extend the types of alleles that can be generated directly in the zygote, obviating the need for manipulations of the mouse genome via the embryonic stem cell route. RESULTS: We present the production data from a total of 13 genetically altered knock-in mouse models generated using CRISPR-Cas9 electroporation of zygotes and delivery of donor repair templates via transduction with recombinant adeno-associated virus. We explore the efficiency of gene targeting at a total of 12 independent genetic loci and explore the effects of allele complexity and introduce strategies for efficient identification of founder animals. In addition, we investigate the reliability of germline transmission of the engineered allele from founder mice generated using this methodology. By comparing our production data against genetically altered knock-in mice generated via gene targeting in embryonic stem cells and their microinjection into blastocysts, we assess the animal cost of the two methods. CONCLUSIONS: Our results confirm that recombinant adeno-associated virus transduction of zygotes provides a robust and effective delivery route for donor templates for the production of knock-in mice, across a range of insertion sizes (0.9-4.7 kb). We find that the animal cost of this method is considerably less than generating knock-in models via embryonic stem cells and thus constitutes a considerable 3Rs reduction.

Effect of virtual reality training to enhance laparoscopic assistance skills.

BACKGROUND: While laparoscopic assistance is often entrusted to less experienced individuals, such as residents, medical students, and operating room nurses, it is important to note that they typically receive little to no formal laparoscopic training. This deficiency can lead to poor visibility during minimally invasive surgery, thus increasing the risk of errors. Moreover, operating room nurses and medical students are currently not included as key users in structured laparoscopic training programs. OBJECTIVES: The aim of this study is to evaluate the laparoscopic skills of OR nurses, clinical medical postgraduate students, and residents before and after undergoing virtual reality training. Additionally, it aimed to compare the differences in the laparoscopic skills among different groups (OR nurses/Students/Residents) both before and after virtual reality training. METHODS: Operating room nurses, clinical medical postgraduate students and residents from a tertiary Grade A hospital in China in March 2022 were selected as participants. All participants were required to complete a laparoscopic simulation training course in 6 consecutive weeks. One task from each of the four training modules was selected as an evaluation indicator. A before-and-after self-control study was used to compare the basic laparoscopic skills of participants, and laparoscopic skill competency was compared between the groups of operating room nurses, clinical medical postgraduate students, and residents. RESULTS: Twenty-seven operating room nurses, 31 clinical medical postgraduate students, and 16 residents were included. The training course scores for the navigation training module, task training module, coordination training module, and surgical skills training module between different groups (operating room nurses/clinical medical postgraduate/residents) before laparoscopic simulation training was statistically significant (p < 0.05). After laparoscopic simulation training, there was no statistically significant difference in the training course scores between the different groups. The surgical level scores before and after the training course were compared between the operating room nurses, clinical medical postgraduate students, and residents and showed significant increases (p < 0.05). CONCLUSION: Our findings show a significant improvement in laparoscopic skills following virtual surgery simulation training across all participant groups. The integration of virtual surgery simulation technology in surgical training holds promise for bridging the gap in laparoscopic skill development among health care professionals.

Kinetin Capped Zinc Oxide Nanoparticles Improve Plant Growth and Ameliorate Resistivity to Polyethylene Glycol (PEG)-Induced Drought Stress in Vigna radiata (L.) R. Wilczek (Mung Bean).

Plants are sessile and mostly exposed to various environmental stresses which hamper plant growth, development, and significantly decline its production. Drought stress is considered to be one of the most significant limiting factors for crop plants, notably in arid and semi-arid parts the world. Therefore, the present study aimed to evaluate the potential impact of different concentrations (10, 100, and 200 µg/mL) of kinetin capped zinc oxide nanoparticles (Kn-ZnONPs) on Vigna radiata (L.) R. Wilczek under varying levels (5%, 10%, 15%) of PEG-induced drought stress. ZnONPs were synthesized by a co-precipitation method using Zinc acetate as a precursor at pH-12, incinerated to 500 °C, and kinetin was used as a surface functionalizing agent. The resulting Kn-ZnONPs were characterized by various contemporary analytical techniques, including SEM, SEM-EDS, XRD, DLS, and Zeta potential and IR spectroscopy. Crystalline Kn-ZnONPs, with a zeta potential of 27.8 mV and a size of 67.78 nm, of hexagonal wurtzite structure and vibrational stretches associated with N-H, C-O, C-N, etc., were confirmed. PEG-induced drought stress significantly reduced the growth of V. radiata by declining the chlorophyll and carotenoid contents. Moreover, a significant decrease in the levels of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), soluble sugar contents, proline, protein contents, phenol, and tannin were observed compared to the control. However, the exogenous application of Kn-ZnONPs ameliorated all photosynthetic parameters by up-regulating the antioxidant defense system through the promotion of SOD, POD, CAT, and lipid peroxidation levels. The biochemical parameters, such as proteins, soluble sugars, and proline, were observed to be maximum in plants treated with 200 µg/mL Kn-ZnONPs under 5% drought stress. The application of Kn-ZnONPs also enhanced the total phenol contents, flavonoid, and tannin contents. In conclusion, the findings of this study demonstrate that the exogenous application of Kn-ZnONPs provides beneficial effects to V. radiata by attenuating the damaging effects of drought stress through the up-regulation of the antioxidant defense system and osmolytes. These results suggest that Kn-ZnONPs have potential as a novel approach to improve crop productivity under drought stress conditions.

Tranexamic Acid Use in Anterior Cruciate Ligament Reconstruction Decreases Bleeding Complications: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To systematically review all available randomized controlled trials (RCTs) in the literature that examine outcomes following tranexamic acid (TXA) use in anterior cruciate ligament reconstruction (ACLR) to determine its effectiveness. METHODS: PubMed/MEDLINE, Embase, Science Direct, Web of Science, CINAHL, and The Cochrane Library databases were systematically searched for RCTs comparing TXA versus no TXA in ACLR with a 4-week minimum follow-up. Quality was assessed using Risk of Bias 2. Pooled analyses were conducted using inverse variance for continuous variables and Mantel-Haenszel for dichotomous variables. The Grading of Recommendations, Assessment, Development and Evaluation guidelines were used to evaluate primary outcomes. RESULTS: A total of 807 patients (632 male, 175 female) from 7 RCTs were included. Mean age was 28.4 years. Bias was graded "low" in 4 RCTs, "some concerns" in 2 RCTs, and "high" in 1 RCT. Visual analog scale was found to be not significantly different with TXA use at day 1-3 (mean difference [MD] -0.92, I2 = 96%, P = .14) and 12 weeks (MD -0.03, I2 = 0%, P = .73). Visual analog scale was significantly decreased at week 2 (MD -1.18, I2 = 56%, P < .00001) and weeks 3-6 (MD -0.38, I2 = 73%, P < .010). Lysholm scores were greater with TXA use at week 2 (MD 9.04, I2 = 74%, P = .002) and weeks 4-6 (MD 6.17, I2 = 73%, P = .0004) but not significantly different at 12 weeks (MD 6.13, I2 = 98%, P = .28). Need for aspiration was less with TXA use (odds ratio 0.40, I2 = 49%, P = 0.0009). Considerable heterogeneity was seen in many results. Certainty was low for 2 primary outcomes, moderate for 2, and high for 5. CONCLUSIONS: Pooled data suggest that the use of TXA in ACLR reduces the need for aspiration, hemarthrosis, drain output, and knee swelling in the postoperative period. While early improvements in pain and function were observed, the clinical relevance is questionable. The risk of complications does not increase with TXA use, and the use of intravenous TXA over intra-articular TXA may improve and prolong hemarthrosis reduction, although the evidence is weak. LEVEL OF EVIDENCE: Level II, systematic review of therapeutic Level I-II studies.

Measuring and modelling microclimatic air temperature in a historically degraded tropical forest.

Climate change is predicted to cause widespread disruptions to global biodiversity. Most climate models are at the macroscale, operating at a ~ 1 km resolution and predicting future temperatures at 1.5-2 m above ground level, making them unable to predict microclimates at the scale that many organisms experience temperature. We studied the effects of forest structure and vertical position on microclimatic air temperature within forest canopy in a historically degraded tropical forest in Sikundur, Northern Sumatra, Indonesia. We collected temperature measurements in fifteen plots over 20 months, alongside vegetation structure data from the same fifteen 25 × 25 m plots. We also performed airborne surveys using an unmanned aerial vehicle (UAV) to record canopy structure remotely, both over the plot locations and a wider area. We hypothesised that old-growth forest structure would moderate microclimatic air temperature. Our data showed that Sikundur is a thermally dynamic environment, with simultaneously recorded temperatures at different locations within the canopy varying by up to ~ 15 °C. Our models (R2 = 0.90 to 0.95) showed that temperature differences between data loggers at different sites were largely determined by variation in recording height and the amount of solar radiation reaching the topmost part of the canopy, although strong interactions between these abiotic factors and canopy structure shaped microclimate air temperature variation. The impacts of forest degradation have smaller relative influence on models of microclimatic air temperature than abiotic factors, but the loss of canopy density increases temperature. This may render areas of degraded tropical forests unsuitable for some forest-dwelling species with the advent of future climate change.

Short- and long-term outcomes in Bankart repair vs. conservative treatment for first-time anterior shoulder dislocation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: First-time anterior shoulder dislocations are associated with a high rate of residual instability. Therefore, many surgeons support initial Bankart repair surgery over conservative management to address this issue. However, the optimal treatment remains controversial because of uncertainty regarding long-term surgical outcomes. The primary objective of this systematic review and meta-analysis was to compare the short- and long-term rates of residual instability following Bankart repair or conservative management after a first-time anterior shoulder dislocation. METHODS: PubMed/MEDLINE, Embase, The Cochrane Library, Web of Science, CINAHL, and ScienceDirect databases were accessed for randomized controlled trials (RCTs) comparing Bankart repair to conservative management. RoB (Risk of Bias) 2 was used to check study quality. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were followed in assessing primary outcomes. The inverse-variance method for continuous variables and the Mantel-Haenszel method for dichotomous variables was used. RESULTS: A total of 348 patients from 6 RCTs published across 8 articles, with a mean age of 23.7 years, were included. Bias was graded low in 3 studies, some concerns in 3 studies, and high in 2 studies. In the short term (2-3 years), surgery lowered recurrent instability (risk ratio [RR] 0.15, 95% confidence interval [CI] 0.08, 0.27; I2 = 0%; P < .0001). Similar findings were seen in the long term (5-12 years) (RR 0.23, 95% CI 0.14, 0.39; I2 = 0%; P < .0001). No difference was observed in return to sport (RR 1.18, 95% CI 0.91, 1.52; I2 = 78%; P = .21). Initial surgery lowered subsequent stabilization surgery in the short (RR 0.19, 95% CI 0.09, 0.43; I2 = 0%; P < .0001) and long term (RR 0.17, 95% CI 0.07, 0.39; I2 = 25%; P < .0001). Western Ontario Shoulder Instability Index (WOSI) scores did not differ in the short term (MD, 2.54, 95% CI -0.51, 5.59; I2 = 48%; P = .1) but were higher in the surgical group at long-term follow-up. Patient satisfaction was also higher with surgery (RR 1.75, 95% CI 1.4, 2.2; I2 = 88%; P < .0001). Certainty of evidence was low for only 1 long-term outcome measure. CONCLUSION: Bankart repair surgery for first-time anterior shoulder dislocation results in a large reduction in the risk of recurrent shoulder instability and subsequent stabilization surgery in both short- (2-3 years) and long-term (5-12 years) follow-up intervals. Additionally, slight improvements in overall patient satisfaction and WOSI score can be seen at long-term follow-up. However, surgical intervention failed to significantly improve the rate of return to sport when compared with conservative management.

Green Synthesis of Silymarin-Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis.

BACKGROUND: Silymarin (SIL) has long been utilized to treat a variety of liver illnesses, but due to its poor water solubility and low membrane permeability, it has a low oral bioavailability, limiting its therapeutic potential. AIM: Design and evaluate hepatic-targeted delivery of safe biocompatible formulated SIL-loaded chitosan nanoparticles (SCNPs) to enhance SIL's anti-fibrotic effectiveness in rats with CCl4-induced liver fibrosis. METHODS: The SCNPs and chitosan nanoparticles (CNPs) were prepared by ionotropic gelation technique and are characterized by physicochemical parameters such as particle size, morphology, zeta potential, and in vitro release studies. The therapeutic efficacy of successfully formulated SCNPs and CNPs were subjected to in vivo evaluation studies. Rats were daily administered SIL, SCNPs, and CNPs orally for 30 days. RESULTS: The in vivo study revealed that the synthesized SCNPs demonstrated a significant antifibrotic therapeutic action against CCl4-induced hepatic injury in rats when compared to treated groups of SIL and CNPs. SCNP-treated rats had a healthy body weight, with normal values for liver weight and liver index, as well as significant improvements in liver functions, inflammatory indicators, antioxidant pathway activation, and lipid peroxidation reduction. The antifibrotic activities of SCNPs were mediated by suppressing the expression of the main fibrosis mediators TGFßR1, COL3A1, and TGFßR2 by boosting the hepatic expression of protective miRNAs; miR-22, miR-29c, and miR-219a, respectively. The anti-fibrotic effects of SCNPs were supported by histopathology and immunohistochemistry (IHC) study. CONCLUSIONS: According to the above results, SCNPs might be the best suitable carrier to target liver cells in the treatment of liver fibrosis.

Patient safety culture in Palestine: university hospital nurses' perspectives.

BACKGROUND: Understanding the perspectives of healthcare workers toward patient safety-related activities is critical in maintaining a healthy safety climate. The objectives of this research are 1) to examine the perception of Patient Safety Culture (PSC) at a university hospital in Palestine, and to highlight areas in need of improvement, and 2) to assess the relationship between the outcome dimensions (frequency of events reported, and overall perceptions of safety) and the other dimensions of PSC, and 3) to determine the relationship among selected demographic variables (gender, age, hospital tenure, work tenure, profession tenure, and hours worked per week) and nurses' perceptions of PSC. METHODS: A cross-sectional study design was used with a convenience sample of 107 nurses. Nurses were asked by email to complete the Arabic version of the Hospital Survey of Patients' Safety Culture (HSOPSC) using the SurveyMonkey® online account form within two weeks. The survey data were analyzed using descriptive and inferential statistics. Univariate and multiple regression were used to examine the relationships. RESULTS: The dimensions of patient safety with the highest positive response were organizational learning and continuous improvement (87%) and teamwork within units (86%). The dimension with the lowest positive score was the nonpunitive response to error (22%). Multiple regression revealed that the dimension of communication openness was a predictor of the overall perceptions of safety (ß = 0.257, p = 0.019). In addition, the dimension of feedback and communication about error was a predictor of the frequency of the reported events (ß = 0.334, p = 0.005). Furthermore, age was found to be a predictor of PSC (p < 0.05). CONCLUSIONS: This study provides a general assessment of perceived safety among nurses in a hospital. However, we found that nurses negatively perceive a nonpunitive response to error. Therefore, strenuous efforts are required by hospital management to improve the culture of incident reporting.

Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome.

Background and Objectives: Nephrotic syndrome (NS) is a kidney disease where the patient has a classic triad of signs and symptoms including hypercholesterolemia, hypoalbuminemia, proteinuria (>3.5 g/24 h), and peripheral edema. In case of NS, the damaged nephrons (structural and functional unit of the kidney) filter unwanted blood contents to make urine. Thus, the urine contains unwanted proteins (proteinuria) and blood cells (hematuria), while the bloodstream lacks enough protein albumin (hypoalbuminemia). Nephrotic syndrome is divided into two types, primary NS, and secondary NS. Primary NS, also known as primary glomerulonephrosis, is the result of a glomerular disease that is limited to the kidney, while secondary NS is a condition that affects the kidney and other parts of the body. The main causes of primary NS are minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. In the present study we recruited a family segregating primary NS with the aim to identify the underlying genetic etiology. Such type of study is important in children because it allows counseling of other family members who may be at risk of developing NS, predicts risk of recurrent disease phenotypes after kidney transplant, and predicts response to immunosuppressive therapy. Materials and Methods: All affected individuals were clinically evaluated. Clinical examination, results of laboratory tests, and biopsy investigations led us to the diagnosis. The next-generation sequencing technique (whole-exome sequencing) followed by Sanger sequencing identified a novel homozygous splice site variant (NM_173689.7: c.941-3C>T) in the CRB2 gene. The variant was present in a homozygous state in the affected individuals, while in a heterozygous state in phenotypically normal parents. Results: The study expanded the spectrum of the mutations in the gene CRB2 responsible for causing NS. Conclusions: In addition, the study will also help in genetic counseling, carrier testing, and prenatal and/or postnatal early diagnosis of the disease in the affected family.

Quality of life, depression, and anxiety of patients undergoing hemodialysis: Significant role of acceptance of the illness.

OBJECTIVE: Routine dialysis is stressful. It has the possibility of leading to depression and anxiety and also reducing patients' quality of life. Despite these significant consequences, these comorbidities have been rarely studied among Indonesian patients. This study aims to examine the rate of depression, anxiety, and the role of acceptance of their illness on patients' quality of life. METHOD: A total of 213 patients undergoing hemodialysis in three general hospitals in Aceh, Indonesia, were included in the study. The presence of depression, anxiety, and the quality of life of each patient was assessed using the hospital anxiety and depression scale and WHO quality of life-BREF questionnaires. RESULTS: The prevalence of depression and anxiety was 46% and 30.5%, respectively. Depression was only associated with the presence of anxiety and the duration of hemodialysis. Anxiety was negatively associated with quality of life but positively associated with depression and the prescription of an anxiolytic. Overall quality of life was associated with age, body mass index, the presence of anxiety, and acceptance of the illness. Acceptance of the illness was also independently associated with almost every domain of patients' quality of life. CONCLUSIONS: The rates of depression and anxiety among patients undergoing hemodialysis in the current study setting are relatively similar to the rates in other settings. Patients' acceptance of their illnesses is significantly associated with the occurrence of anxiety and quality of life. Therefore, health practitioners should help patients accept their illnesses and the administration of regular hemodialysis.

Carotid Endarterectomy Outcomes in the Elderly: A Canadian Institutional Experience.

BACKGROUND: Carotid endarterectomy (CEA) is a well-established surgical intervention for stroke prevention in patients with carotid stenosis of all ages. However, the decision to proceed to operate in the elderly involves a more complicated risk-benefit assessment due in part to increased comorbidities and reduced life expectancy. Some studies suggest that CEA is more risky in the elderly with worse outcomes, whereas others have found no difference. Our objective was to evaluate and compare outcomes of CEA between elderly and younger patients at our institution. METHODS: All hospital charts were reviewed for consecutive patients undergoing CEA from the Jewish General Hospital and the Royal Victoria Hospital from October 2009 to December 2015. Primary outcomes were ipsilateral stroke, death, and restenosis at 30 days and 1 year. Secondary outcomes were cranial nerve injury, myocardial infarction (MI), hematoma, wound infection, cerebral hyperperfusion, and transient ischemic attacks within 30 days. Primary and secondary outcomes were compared between patients aged ≥80 years and <80 years. RESULTS: A total of 361 patients were included in this study with a mean age of 70.2 ± 9.5 years (n = 247 [68.4%] male and n = 272 [75.8%] symptomatic). Elderly patients were more often symptomatic (93.8% vs. 71.6%, P < 0.0001) and had an increased length of stay (2.8 ± 5.3 vs. 1.6 ± 1.8, P = 0.001). There was no statistically significant difference in primary outcomes between patients aged <80 years and ≥80 years, including 30-day stroke (1.7% vs. 0%), death (no deaths in either group), restenosis (8.8% vs. 12.3%), 1-year stroke (1.7% vs. 0%), death (0.7% vs. 0%), or restenosis (14.9% vs. 13.8%). However, elderly patients had significantly increased MI risk postoperatively (4.6% vs. 0.7%, P = 0.01). Other complications, including cranial nerve injury (3.7% in <80 years vs. 4.6% in the elderly group), were similar between the groups. CONCLUSIONS: We found that CEA in the elderly does not have an increased risk of stroke or death up to one year postoperatively. However, the postoperative length of stay is increased and complicated by significantly more MIs, which should weigh into the decision of whether to perform CEA on an elderly patient.

Pulmonary valve papillary fibroelastoma: a rare tumor and rare location.

Although rare, papillary fibroelastomas (PFEs) are considered the third most common cause of primary cardiac neoplasm. They are usually asymptomatic and are found during routine echocardiography. PFEs of the pulmonary valve are extremely rare. They are usually benign; however, because of their potential to embolize to the pulmonary circulation, it is often recommended that they be removed. This article reviews a case of an asymptomatic PFE of the pulmonary valve, incidentally found in a patient who presented with three-vessel coronary artery disease.

Type B Aortic Dissection Masquerading As Acute Pyelonephritis: Think Beyond Measures.

Aortic dissection (AD) is a life-threatening medical emergency with a high mortality rate if misdiagnosed; therefore, an urgent and precise diagnosis is crucial for prompt treatment. This article presents a rare case report of AD with an atypical clinical presentation that led to delayed diagnosis and a complicated clinical course. Herein, we aim to contribute to the existing literature by providing insights into the varied presentations of AD and offering valuable lessons for clinicians faced with similar diagnostic scenarios. A 64-year-old female with an extended history of hypertension and other comorbidities presented to the emergency department with a one-day duration of right-sided loin pain and fever. Her blood investigations demonstrated evidence of leukocytosis and high c-reactive protein (CRP) levels. She was preliminarily treated as a case of acute pyelonephritis since, initially, clinical and radiographic evidence did not yield an alternative diagnosis. Despite antibiotics, her condition deteriorated, and her urine output became less than 0.5 mL/kg/hour for six consecutive hours. Additionally, the obtained urine culture was negative on the third day of admission, which made the medical team repeat her history taking and clinical examination, revealing a previously overlooked weight loss. This red flag prompted the medical team to conduct thorough chest and abdominal imaging studies in search of any hidden malignancy, especially when her thyroid function test returned normal. Surprisingly, a contrast-enhanced abdominal CT scan demonstrated an infarcted right kidney by thromboembolism that originated from the partially obstructive thrombus in the proximal abdominal aorta, which was later confirmed to be a type B AD by a CT angiogram. A multidisciplinary team guided her treatment, which included carefully controlling her blood pressure, using anticoagulants, and closely monitoring the patient. The take-home messages of this case report underscore the critical importance of recognizing atypical clinical presentations of AD, overcoming diagnostic challenges through comprehensive approaches, tailoring treatments to individual patient needs, and advocating for a multidisciplinary and patient-centered approach to enhance overall clinical outcomes.

Leveraging Bayesian deep learning and ensemble methods for uncertainty quantification in image classification: A ranking-based approach.

Bayesian deep learning (BDL) has emerged as a powerful technique for quantifying uncertainty in classification tasks, surpassing the effectiveness of traditional models by aligning with the probabilistic nature of real-world data. This alignment allows for informed decision-making by not only identifying the most likely outcome but also quantifying the surrounding uncertainty. Such capabilities hold great significance in fields like medical diagnoses and autonomous driving, where the consequences of misclassification are substantial. To further improve uncertainty quantification, the research community has introduced Bayesian model ensembles, which combines multiple Bayesian models to enhance predictive accuracy and uncertainty quantification. These ensembles have exhibited superior performance compared to individual Bayesian models and even non-Bayesian counterparts. In this study, we propose a novel approach that leverages the power of Bayesian ensembles for enhanced uncertainty quantification. The proposed method exploits the disparity between predicted positive and negative classes and employes it as a ranking metric for model selection. For each instance or sample, the ensemble's output for each class is determined by selecting the top 'k' models based on this ranking. Experimental results on different medical image classifications demonstrate that the proposed method consistently outperforms or achieves comparable performance to conventional Bayesian ensemble. This investigation highlights the practical application of Bayesian ensemble techniques in refining predictive performance and enhancing uncertainty evaluation in image classification tasks.

Unlocking the therapeutic potential of Nigella sativa extract: phytochemical analysis and revealing antimicrobial and antioxidant marvels.

The growing global threat of antimicrobial resistance endangers both human and animal life, necessitating the urgent discovery of novel antimicrobial solutions. Medicinal plants hold promise as sources of potential antimicrobial compounds. In this study, we investigated the phytochemical constituents and microbicidal capabilities of the ethanolic extract from Nigella sativa (black seed). Gas chromatography analysis (GC) identified 11 compounds, among them thymoquinone, and thymol, contributing to antimicrobial and antioxidant properties. Antimicrobial assays demonstrated notable inhibition zones against broad spectra of bacteria, including Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi, Staphylococcus aureus, Enterobacter, and Bacillus subtilis, along with potent antifungal activity against Aspergillus niger, Penicillium, and Candida albicans. Notably, when combined with antibiotics, the extract displayed exceptional synergistic antimicrobial efficacy. The black seed extract demonstrated membrane-damaging activity and disrupted virulence factors that protect microbes from antimicrobial agents, including the formation of bacterial biofilm and protease secretion. Thymoquinone, the primary active constituent of the extract, exhibited similar antimicrobial and ant virulence properties. In silico analysis targeting key regulators of quorum sensing and biofilm formation in P. aeruginosa, such as RhlG, LasR, and PqsR, showed a remarkable affinity of thymol and thymoquinone for these targets. Moreover, the N. sativa extract exhibited dose-dependent cytotoxicity against both the promastigote and amastigote forms of Leishmania tropica parasites, hinting at potential antiparasitic activity. In addition to its antimicrobial properties, the extract displayed potential antioxidant activity at a concentration of 400 µg/mL.

A Global Bibliometric Analysis of the Top 100 Most Cited Articles on Carotid Body Tumors.

The carotid body, situated at the common carotid artery bifurcation, comprises specialized glomus cells responsible for sensing blood oxygen, carbon dioxide, pH, and temperature changes, crucial for regulating breathing and maintaining oxygen homeostasis. Carotid body tumors (CBTs), arising from these cells, are rare, representing only 0.5% of head and neck tumors, often presenting as benign, slow-growing, vascularized masses. In February 2023, this bibliometric analysis was conducted, which involved screening 1733 articles from the Web of Science database. The screening process was based on citation count, and articles were selected for inclusion based on specific criteria that focused on CBTs located within the carotid bifurcation. Rigorous selection involved independent screening and data extraction by four authors. The top 100 articles, published between 1948 and 2019, totaled 6623 citations and were authored by 98 unique first authors from 22 countries and 77 institutions, spanning 42 journals. Treatment articles were the predominant category, comprising 49% of the literature. This analysis offers insights into publication trends, identifies literature gaps, and outlines areas of research focus, providing a valuable resource to guide future studies on CBTs.

Do Serum Nesfatin-1 Levels have A Predictive Role in Type-2 Diabetes Mellitus and its Microvascular Complications? A Case-Control Study.

Background Type 2 diabetes mellitus (T2DM) is a chronic disease with macrovascular and microvascular complications. Nesfatin-1 is a neuropeptide that develops from a more substantial intermediate compound known as nucleobindin 2 (NUCB2). Nesfatin-1 is known to play a role in regulating various physiological processes related to appetite, energy balance, and body weight. The purpose of the current study was to investigate the serum levels of nesfatin-1 in Egyptian patients with type 2 diabetes mellitus (T2DM) in comparison to healthy subjects and to assess the association of serum nesfatin-1 levels with the occurrence of diabetic microvascular complications in those patients. Methods This matched case-control study was conducted on 90 subjects 40-80 years old, with normal hepatic, cardiac, and respiratory functions, and 60 of them had T2DM. The included participants were divided into two groups: group 1, which was the control group and included 30 healthy subjects, and group 2, which included 60 subjects with T2DM. Group 2 was subdivided according to the presence or absence of microvascular complications into group 2a, which included 30 patients having T2DM with no microvascular complications, and group 2b, which included 30 patients having T2DM with one or more microvascular complications. Results T2DM patients had significantly lower serum nesfatin-1 levels (5.07±1.78 versus 9.05±2.1 mmol/L, <0.001) compared to healthy controls. Also, T2DM patients with microvascular complications had lower serum nesfatin-1 levels (4.32±1.72 versus 5.83±1.51 mmol/L, <0.001) compared to T2DM patients without microvascular complications. Serum nesfatin-1 level at a cutoff value of <8.09 mmol/L can be a marker for the detection of diabetes mellitus (DM) with the area under the curve (AUC) of 94.3%, 95% sensitivity, 74.3% specificity, 77.9% positive predictive value (PPV), and 65.7% negative predictive value (NPV), and at a cutoff value of <5.87 mmol/L can be a marker for the detection of microvascular complications of diabetes mellitus at AUC of 75.5%, 76.7% sensitivity, 67.3% specificity, 77.1% PPV, and 62.9% NPV. Conclusions Serum Nesfatin-1 may play a potential protective role in diabetes mellitus (DM) and its microvascular complications, as it decreases in individuals with diabetes and those with diabetic microvascular complications compared to controls. Additionally, serum Nesfatin-1 levels may have predictive value for the early detection of Type 2 diabetes mellitus (T2DM) patients, diabetic microvascular complications, and diabetic kidney disease (DKD) at cut-off values of < 8.09 (mmol/L), < 5.87 (mmol/L), and < 5.46 (mmol/L), respectively. Therefore, targeted Nesfatin-1 drug therapy may be tried to reduce morbidity and mortality caused by microvascular complications of diabetes.

Thyrotoxic Cardiomyopathy Unveiled: Insights From a Compelling Case Report.

Thyrotoxicosis is a clinical condition characterized by inappropriately elevated thyroid hormone levels in the bloodstream, leading to systemic effects on the body. In fact, the thyrotoxic state has tight regulatory control over the cardiovascular system through genomic and non-genomic mechanisms. This study highlights a rare presentation of thyrotoxic cardiomyopathy (TCM), which, to the best of our knowledge, is one of the very few case reports involving heart failure with preserved ejection fraction (HFpEF) and only atrial involvement, compared to the previous literature. A 37-year-old female presented to the outpatient clinic with abdominal distention and neglected signs and symptoms consistent with thyrotoxicosis for a year. Investigations revealed high N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels of 1788 pg/mL. Cardiac MRI and trans-thoracic echocardiogram (TTE) revealed bilateral atrial dilatation, a left ventricular ejection fraction (LVEF) of 60%, and diastolic dysfunction. Additionally, severe free-flowing tricuspid and mitral valve regurgitation were observed, with no evidence of pericardial effusion or ventricular abnormalities. Therefore, a diagnosis of TCM was suspected and eventually confirmed by excluding other differential diagnoses. Besides a diffuse goiter on ultrasonography, the thyroid panel test revealed low thyroid-stimulating hormone (TSH) levels of <0.01 mIU/L, a free thyroxine T4 of >100 pmol/L, and positive anti-thyroid peroxidase (TPO) and TSH receptor antibodies. Accordingly, a team of endocrinologists, cardiologists, and internists managed the patient with anti-thyroid medications alongside symptomatic treatment. A few days later, she was discharged in good condition, and a follow-up visit was arranged with the endocrinology and cardiology clinics. It is crucial to maintain a high level of suspicion to detect and treat TCM promptly, and a multidisciplinary approach should ideally be employed. This is not only important for the prevention of but also reversing potentially life-threatening cardiovascular complications.