Myocardial Strain for the Differentiation of Myocardial Involvement in the Post-Acute Sequelae of COVID-19-A Multiparametric Cardiac MRI Study.

Myocardial involvement was shown to be associated with an unfavorable prognosis in patients with COVID-19, which could lead to fatal outcomes as in myocardial injury-induced arrhythmias and sudden cardiac death. We hypothesized that magnetic resonance imaging (MRI) myocardial strain parameters are sensitive markers for identifying subclinical cardiac dysfunction associated with myocardial involvement in the post-acute sequelae of COVID-19 (PASC). This study evaluated 115 subjects, including 65 consecutive COVID-19 patients, using MRI for the assessment of either post-COVID-19 myocarditis or other cardiomyopathies. Subjects were categorized, based on the results of the MRI exams, as having either 'suspected' or 'excluded' myocarditis. A control group of 50 matched individuals was studied. Along with parameters of global cardiac function, the MRI images were analyzed for measurements of the myocardial T1, T2, extracellular volume (ECV), strain, and strain rate. Based on the MRI late gadolinium enhancement and T1/T2/ECV mappings, myocarditis was suspected in 7 out of 22 patients referred due to concern of myocarditis and in 9 out of 43 patients referred due to concern of cardiomyopathies. The myocardial global longitudinal, circumferential, and radial strains and strain rates in the suspected myocarditis group were significantly smaller than those in the excluded myocarditis group, which in turn were significantly smaller than those in the control group. The results showed significant correlations between the strain, strain rate, and global cardiac function parameters. In conclusion, this study emphasizes the value of multiparametric MRI for differentiating patients with myocardial involvement in the PASC based on changes in the myocardial contractility pattern and tissue structure.

Solitary fibrous tumor occurring in the colon as submucosal mesenchymal lesion: report of two cases and review of the literature.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm most often arising from the pleura and rarely in extra-pleural locations, including the gastrointestinal tract. We describe two cases of a SFT presenting as submucosal colonic lesion and review the literature on this lesion. One submucosal lesion was localized in the cecum and was 10 mm in size. The second lesion presented as a 17 mm submucosal rectal lesion. Both lesions presented as well-circumscribed submucosal lesions arranged in short fascicles, blending with abundant collagenous stroma. In both cases, the spindle cells were positive for CD34, STAT6 and CD99, and molecular studies showed NAB2:STAT6 fusion supporting the diagnosis of SFT. Both patients are alive and well 10 and 5 years post-excision, respectively. In conclusion, SFT can occur in the colon as a submucosal lesion and should be included in the differential diagnosis of colonic mesenchymal lesions.

The moderating role of just culture between nursing practice environment and oncology nurses' silent behaviors toward patient safety: A multicentered study.

BACKGROUND: Patient safety is a critical part of healthcare delivery that must be prioritized to guarantee optimal patient outcomes. Oncology nursing is a specialized area of nursing that demands great focus on patient safety because of the high-risk nature of this patient group. Nurses play an important role in ensuring that patients receive safe and effective care. However, the nursing practice environment can have a substantial impact on how nurses respond to patient safety problems. A just culture can promote open communication and identify potential safety issues, whereas a culture of silence can have a negative impact on patient outcomes. OBJECTIVE: Firstly, assess the relationship between the nursing practice environment and oncology nurses' silent behavior towards patient safety. Secondly, the interaction effect of just culture as a moderator in this relationship. METHOD: A cross-sectional, correctional research design was employed. Data was collected from 303 nurses working at the oncology departments of five hospitals in Egypt using three questionnaires. Data was analyzed using SPSS-PROCESS Macro (v4.2). RESULTS: There was a moderate, negative, and significant correlation between the nurse practice environment and silent behavior of nurses towards patient safety. The interaction effect of just culture with nurse practice environment strengthens this relationship, thus enhancing errors reporting. CONCLUSIONS: This study emphasized on the importance of creating a just culture that facilitates open communication and eliminating the potential hazards result from nurses' silence. Thus, oncology nurses must be encouraged to report issues related to patient safety.

Collaborative leadership and productive work performance: The mediating role of nurses' innovative behavior.

AIM: This study aims to explore the relationship between collaborative leadership and nurses' productive work performance as well as the mediating role of nurses' innovative behavior in this relationship. BACKGROUND: Collaborative leadership is an imperative necessity in the contemporary turbulent healthcare environment as it provides a collaborative atmosphere where innovative behavior and productive performance of nurses are fostered, hence moving healthcare organizations toward competitiveness and sustainability. METHOD: A cross-sectional descriptive correlational exploratory research design was used to conduct the study. Data were collected from 550 nurses recruited from three large university hospitals in Alexandria, Egypt, using three instruments, namely, interprofessional collaborative leadership in healthcare teams scale, productive work performance questionnaire, and innovative behavior inventory. The instruments of the study are Likert-type questionnaires through which nurses' perspectives regarding study variables were investigated. We used descriptive statistics, inferential statistics as well as structured equation modeling (SEM). RESULTS: SEM revealed that collaborative leadership accounted for 83% of the variance of individual productive work performance and 77% of the variance of nurses' innovative behavior. Moreover, nurses' innovative behavior partially mediates the relationship between collaborative leadership and their productive work performance. CONCLUSION: Collaborative leadership practices are powerful strategies to enhance the innovative behavior of nurses and sustain their productive work performance. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Fostering a collaborative atmosphere in workplace is mandatory for nurses' innovativeness. Replacing hierarchal leadership styles with collaborative ones is a promising strategy to enhance the productive performance of nurses. Healthcare managers and leaders could cultivate an interprofessional collaborative culture in the workplace in order to sustain productivity and eradicate counterproductive work behaviors among healthcare providers.

Twice-Weekly Versus Once-Weekly Membrane Sweeping in the Prevention of Post-Term Pregnancy: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Membrane sweeping is considered a simple and effective method for initiating spontaneous onset of labor. Despite the widely accepted membrane sweeping use to prevent post-term birth, the optimal frequency has not been estimated. We aimed to assess the effectiveness and safety of twice-weekly versus once-weekly membrane sweeping in post-term pregnancy prevention. Four different databases were searched for available clinical trials from inception to October 2022. We selected randomized controlled trials (RCTs) that compared twice-weekly membrane sweeping in intervention group versus once-weekly membrane sweeping in control group among pregnant women with singleton pregnancy at ≥ 39 gestational weeks. Our primary outcomes were the rate of spontaneous onset of labor and the requirement for formal methods of labor induction. Our secondary outcomes were sweeping to delivery interval in days, gestational age at delivery in weeks, Bishop score at admission, chorioamnionitis, and premature rupture of membranes. Three RCTs (596 patients) were included. Twice-weekly membrane sweeping was associated with significant increase in the rate of spontaneous onset of labor and significant decline in labor induction rate in comparison with once-weekly group. Duration from sweeping to delivery was significantly shorter among the twice-weekly group (p<0.001). Furthermore, gestational age at delivery was significantly earlier in the twice-weekly group. A significantly higher Bishop score at admission was observed in the twice-weekly group (p=0.02). There were no significant differences across both groups in chorioamnionitis and premature rupture of membranes. In conclusion, twice-weekly membrane sweeping is more effective in preventing post-maturity pregnancy than once-weekly sweeping without added adverse events.

2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature.

PURPOSE: Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100 nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. PROCEDURES: Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11-12 weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13 Gy partial body irradiation at 42- and 90 days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. RESULTS: We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. CONCLUSIONS: Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.

Therapeutic potentials of mesenchymal stem cells in the treatment of inflammatory bowel disease in rats.

Interleukin-1beta (IL-1ß) and interleukin-17A (IL-17A) have strong pro-inflammatory activities that are involved in inflammatory bowel diseases (IBDs). Mesenchymal stem cell (MSC) therapy is considered a promising treatment for IBD. This study was performed to understand the role of rat Nlrp3 inflammasome, Hmgb1, and pro-inflammatory cytokines (IL-1ß and IL-17a) in the pathogenesis of IBD. Also, to evaluate the role of human umbilical cord blood-MSCs (hUCB-MSCs) in the management of IBD. The rats were in four groups: normal controls, indomethacin-induced IBD group, indomethacin-induced IBD rats that received phosphate-buffered saline (PBS), and the IBD group that received hUCB-MSCs as a treatment. The messenger RNA (mRNA) expression levels of rat Nlrp3, Hmgb1, IL-1ß, and IL-17a were evaluated by quantitative real-time polymerase chain reaction. Histopathological examination of the small intestinal tissues of the studied rats was performed. There was a significant upregulation of the rat Nlrp3, IL-1ß, IL-17a mRNA expression (p < 0.001 for the three parameters), and Hmgb1 (p < 0.05) in the untreated IBD group compared to the normal control group. In the MSC-treated group, IL-1ß, IL-17a, and rat Nlrp3 mRNA expression significantly decreased compared to both the untreated IBD group and PBS group (p < 0.05 for all). hUCB-MSCs ameliorated IBD in rats by downregulating the pro-inflammatory cytokines (IL-1ß and IL-17a) and other inflammatory mediators such as Hmgb1 and rat Nlrp3.

Effect of Gamma Irradiation on Cannabinoid, Terpene, and Moisture Content of Cannabis Biomass.

In recent years, cannabis has been proposed and promoted not only as a medicine for the treatment of a variety of illnesses, but also as an industrial crop for different purposes. Being an agricultural product, cannabis inflorescences may be contaminated by environmental pathogens at high concentrations, which might cause health problems if not controlled. Therefore, limits have to be placed on the levels of aerobic bacteria as well as yeast and mold. To ensure the safety of cannabis plant material and related products, a remediation process has to be put in place. Gamma irradiation is a sterilization process mainly used for pharmaceuticals, foods, cosmetics, agricultural, and herbal products including cannabis plant material. This study was designed to determine the effect of irradiation on the microbial count as well as on the chemical and physical profiles of the cannabis biomass, particularly cannabinoids, terpenes, and moisture content. The full cannabinoid profile was measured by GC/FID and HPLC analysis, while terpene profile and moisture content were determined using GC/MS and Loss on Drying (LoD) methods, respectively. Analyses were conducted on the samples before and after gamma irradiation. The results showed that the minimum and maximum doses were 15 and 20.8 KiloGray (KGY), respectively. Total Aerobic Microbial Count (TAMC) and Total Yeast and Mold Count (TYMC) were determined. The study showed that irradiation has no effect on the cannabinoids and little effect on terpenes and moisture content, but it did result in the virtual sterilization of the plant material, as evidenced by the low levels of bacterial and fungal colony-forming units (CFUs) < 10 after gamma irradiation.

Effect of an educational program about mentorship competencies on nurse mentors' performance: a quasi-experimental study.

BACKGROUND: Mentorship is a vital part of the nursing profession to improve role transition, job satisfaction, and job retention while facilitating socialization, emotional well-being, and the acquisition of new skills. AIM: The present study aimed to evaluate the effect of an educational program about mentorship competencies on nurse mentors' performance at Port Said Healthcare Authority hospitals. METHODS: A quasi-experimental study design (pre-test and post-test one group) was used to conduct the study at seven Healthcare Authority hospitals in Port Said Governorate, Egypt. The study subjects were consisted of a purposive sample of 30 nurse mentors and 60 intern nursing students. Data were collected using three tools consisted of the Mentor Knowledge Questionnaire, Mentor Competencies Instrument (MCI), and Nurse Mentor Performance Assessment. Data analysis was performed using SPSS version 20, Student's t-test was used to measure differences between the pretest and post-test, and Qualitative categorical variables were compared using the chi-square test. A significant level value was considered when the p-value ≤ 0.05, and Cohen's d was used to measure the effect size. RESULTS: the post-test scores of mentorship competencies and performance after implementation of the educational program significantly improved in the studied nurse mentors 56.1 ± 13.2, 60.5 ± 4.9 compared with pre-test scores with 37.1 ± 4.1, 49.7 ± 6.9 (P < 0.001). As determined by Cohen's d test, the effect size of an educational program is quite large on the nurse mentors' performance. CONCLUSION: The educational program about mentorship competencies was significantly improve mentorship performance of the studied nurse mentors. The study recommended dissemination and generalization of the new and innovative mentorship program to the different stages of nursing education to foster the continued growth and development of nurse mentors and nurse students. Also, recommended developing a valid mentor assessment instrument consisting of and specific to the Egyptian context to assess the Egyptian mentorship model. TRIAL REGISTRATION NUMBER (TRN): The study protocol was approved by the Research Ethics Committee of the Faculty of Nursing, Port Said University (code number: NUR 13/2/2022) [10].

Vaginal probiotics as an adjunct to antibiotic prophylaxis in the management of preterm premature rupture of membranes: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy of vaginal probiotics administration in combination with prophylactic antibiotics versus antibiotic prophylaxis only on perinatal outcomes in women with preterm premature rupture of membrane (PPROM). METHODS: Four different databases were searched from inception till March 2023. We selected randomized controlled trials (RCTs) that compared vaginal probiotics along with antibiotics versus antibiotics only among pregnant women who were presented with PPROM between 24 and 34 weeks of gestation. We performed the meta-analysis using Revman software. Our primary outcomes were gestational age at birth and latency period duration. Our secondary outcomes were the rate of admission in the neonatal intensive care unit (NICU), infant birth weight, length of stay in the NICU, and neonatal complications. RESULTS: Four RCTs, involving a total of 339 patients, were included in the meta-analysis. The gestational age at the time of delivery and latency period duration were significantly higher among probiotics + antibiotics group (p = 0.01 & p < 0.001). There was a significant reduction in the rate of NICU admission and length of NICU stay among the probiotics + antibiotics group compared to the antibiotics only group. A significant improvement in the infant birth weight after delivery was demonstrated among the probiotics + antibiotics group (p = 0.002). Although there was a decrease in the incidence of neonatal sepsis and respiratory distress syndrome within probiotics + antibiotics group versus antibiotics only group, these differences were not statistically significant (p > 0.05). CONCLUSIONS: The combination of vaginal probiotics and antibiotic prophylaxis has been shown to effectively improve perinatal outcomes in women with PPROM. Further trials are needed to validate our findings.

Validation and Quantitation of Fifteen Cannabinoids in Cannabis and Marketed Products Using High-Performance Liquid Chromatography-Ultraviolet/Photodiode Array Method.

Background: Cannabis sativa is a psychoactive plant indigenous to Central and South Asia, traditionally used both for recreational and religious purposes, in addition to folk medicine. Cannabis is a rich source of natural compounds, the most important of which are commonly known as cannabinoids that cause a variety of effects through interaction with the endocannabinoid system. Materials and Methods: In this study, a high-performance liquid chromatography-ultraviolet/photodiode array (PDA) method was developed and validated for the analysis of 15 cannabinoids in cannabis plant materials and cannabis-based marketed products. These cannabinoids are cannabidivarinic acid, cannabidivarin, cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, delta-9-tetrahydrocannabivarin, delta-9-tetrahydrocannabivarinic acid, cannabinol, delta-9-tetrahyrocannabinol, delta-8-tetrahyrocannabinol, cannabicyclol, cannabichromene, delta-9-tetrahyrocannabinolic acid A, and cannabichromenic acid. The separation was carried out using a reversed-phase Luna® C18(2) column and a mobile phase consisting of 75% acetonitrile and 0.1% formic acid in water. A PDA detector was used, and data were extracted at λ=220 nm. Principal component analysis of cannabis four varieties was performed. Results: The method was linear over the calibration range of 5-75 µg/mL with R2>0.999 for all cannabinoids. This method was sensitive and gave good baseline separation of all examined cannabinoids with limits of detection ranging between 0.2 and 1.6 µg/mL and limits of quantification ranging between 0.6 and 4.8 µg/mL. The average recoveries for all cannabinoids were between 81% and 104%. The measured repeatability and intermediate precisions (% relative standard deviation) in all varieties ranged from 0.35% to 9.84% and 1.11% to 5.26%, respectively. Conclusions: The proposed method is sensitive, selective, reproducible, and accurate. It can be applied for the simultaneous determination of these cannabinoids in the C. sativa biomass and cannabis-derived marketed products.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47+ expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47+) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47+ cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.e., protein homeostasis) dysfunction in discrete clusters of cells. ECM shifts in selected COVID-19 subjects occur without significant increases in either global trichrome positive staining or myocardial injury based quantitively on standard H&E scoring. Our findings also suggest distinct mechanism(s) for ECM remodeling in the setting of SARS-CoV-2 infection. The ratio of CD163+/CD68+ cells is increased in hot spots of profibrotic hearts compared with either controls or outside of hot spots in COVID-19 subjects. In sum, matrix remodeling of human COVID-19 hearts in situ is characterized by site-restricted profibrotic mediated (e.g., HSP47+ Mfbs, CD163+ Mφs) modifications in ECM (i.e., COLα1, POSTN, FAP), with a strong correlation between COLα1 and HSP47+cells within hot spots. Given the established associations of viral infection (e.g., human immunodeficiency virus; HIV), myocardial fibrosis and sudden cardiac death, early screening tools (e.g., plasma biomarkers, noninvasive cardiac magnetic resonance imaging) for diagnosis, monitoring and treatment of fibrotic ECM remodeling are warranted for COVID-19 high-risk populations.

Real-Time Strain-Encoding Cardiovascular MRI for Assessment of Regional Heart Function in Tetralogy of Fallot Patients.

BACKGROUND: Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital heart disease, where right ventricular (RV) function is an important determinant of subsequent intervention. OBJECTIVE: In this study, we evaluate the feasibility of fast strain-encoding (fastSENC; a one-heartbeat sequence) magnetic resonance imaging (MRI) for assessing regional cardiac function in ToF. METHOD: FastSENC was implemented to characterize regional circumferential (Ecc) and longitudinal (Ell) strains in the left ventricle (LV) and RV in post-repair ToF. Data analysis was conducted to compare strain measurements in the RV to those in the LV, as well as to those generated by the MRI Tissue-Tracking (MRI-TT) technique, and to assess the relationship between strain and ejection fraction (EF). RESULTS: Despite normal LVEF (55±8.5%), RVEF was borderline (46±6.4%), but significantly lower than LVEF. RV strains (RV-Ell=-20.2±2.9%, RV-Ecc=-15.7±6.4%) were less than LV strains (LV-Ell=-21.7±3.7%, LV-Ecc=-18.3±4.7%), and Ell was the dominant strain component. Strain differences between fastSENC and MRI-TT were less significant in RV than in LV. There existed moderate and weak correlations for RV-Ecc and RV-Ell, respectively, against RVEF. Compared to LV strain, RV strain showed regional heterogeneity with a trend for reduced strain from the inferior to anterior regions. Inter-ventricular strain delay was larger for Ell (64±47ms) compared to Ecc (36±40ms), reflecting a trend for contraction dyssynchrony. CONCLUSION: FastSENC allows for characterizing subclinical regional RV dysfunction in ToF. Due to its sensitivity for evaluating regional myocardial contractility patterns and real-time imaging capability without the need for breath-holding, fastSENC makes it more suitable for evaluating RV function in ToF.

Does a Positive Appendiceal Resection Margin in Low-Grade Appendiceal Mucinous Neoplasms, Warrant Additional Surgery? Our Institution Experience and Literature Review.

BACKGROUND: Management of low-grade appendiceal mucinous neoplasm (LAMN) with positive resection margin is controversial. Some guidelines recommend surgical reexcision, whereas others recommend a conservative approach. The purpose of our study was to determine whether involvement of the resection margin by LAMN is a risk factor for local recurrence requiring additional surgery. DESIGN: This is a retrospective study (January 2000-December 2020) of uncomplicated LAMNs with neoplastic epithelium or dissecting mucin at the resection margin. For cases treated with additional surgery, the presence of residual tumor was evaluated. Clinical follow-up was attained in all cases. We also conducted a literature review. RESULTS: The study investigated 98 patients. Eight with median age of 67 (range: 45-91) years had a LAMN involving the resection margin (8.2%). Five of eight LAMNs (62.5%) with neoplastic epithelium at the margin underwent surgery, and no residual neoplasm was identified. The other three cases were followed conservatively, and no patient developed recurrence (follow-up: 18-69 months with a mean of 45 months). In a review of the literature, we identified 52 LAMNs with positive margin. Although three cases had acellular mucin and one residual LAMN in the reexcision specimen (7.7%), neither of these four cases or any of the other 46 followed conservatively had recurrence of disease. CONCLUSIONS: These data suggest that for patients with uncomplicated LAMN confined to the appendix, the involvement of the appendiceal margin does not necessary lead to recurrence of LAMN, and a conservative management is a reasonable alternative.

Temporal evolution of mechanical stimuli from vascular remodeling in response to the severity and duration of aortic coarctation in a preclinical model.

Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations (i.e. age of treatment) seen clinically. Rabbits were exposed to CoA resulting in peak-to-peak blood pressure gradient (BPGpp) severities of ≤ 10, 10-20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid-structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions from experimentally measured data. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Experimental results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.

Potential impact of epicardial fat thickness, pentraxin-3, and high-sensitive C-reactive protein on the risk of non-proliferative diabetic retinopathy.

Purpose: We tried to clarify the potential association between systemic inflammatory markers like high-sensitive C-reactive protein (Hs-CRP), pentraxin-3 (PTX3), and epicardial fat thickness (EFT) with the non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes mellitus (T2D). Previous studies dealt with diabetic retinopathy as a whole entity rather than early stages of diabetic retinopathy. Early detection of various determinants of NPDR is prioritized in clinical practice. Methods: A case-control study was conducted at Mansoura University Hospital, included 207 Egyptian subjects divided into 3 groups; 69 diabetic patients without retinopathy, 69 diabetic patients with NPDR, and 69 healthy control subjects. Participants were subjected to clinical history taking, physical examination, and laboratory assessment of Hs-CRP and plasma PTX3. Transthoracic echocardiography was applied to estimate EFT. Results: Hs-CRP, PTX3, and EFT were significantly higher in patients with T2D without retinopathy than control cohort (p = 0.033, p < 0.00 and p < 0.00, respectively). Moreover, patients with NPDR showed significantly higher values of Hs-CRP, PTX3, and EFT than diabetic comparators without retinopathy (p = 0.002, p = 0.012, and p < 0.001, respectively). Although, NPDR was positively correlated with Hs-CRP, PTX3, and EFT (p < 0.001), Hs-CRP was not an independent determinant of NPDR meanwhile, EFT (OR = 1.094, 95%CI: 1.036-1.154, P = 0.001) and PTX3 (OR = 16.145, 95%CI: 1.676-155.551, P = 0.016) were. Conclusion: Plasma pentraxin-3 and epicardial fat thickness showed more significant association with NPDR than high-sensitive C-reactive protein in patients with type 2 diabetes mellitus.

Isolation and Characterization of Impurities in Commercially Marketed Δ8-THC Products.

Qualitative analysis of several commercial products containing Δ8-tetrahydrocannabinol (Δ8-THC) as a major component using GC-MS resulted in the identification of several impurities along with Δ8-THC. In an attempt to isolate and identify these impurities, a commercial Δ8-THC distillate was selected for the isolation work. Eleven impurities were isolated using a variety of chromatographic techniques, and their chemical structures were determined. These include Δ4,8-iso-tetrahydrocannabinol (1), Δ4-iso-tetrahydrocannabinol (2), Δ8-cis-iso-tetrahydrocannabinol (3), 4,8-epoxy-iso-tetrahydrocannabinol (4), 8-hydroxy-iso-tetrahydrocannabinol (5), 9ß-hydroxyhexahydrocannabinol (6), 9α-hydroxyhexa-hydrocannabinol (7), iso-tetrahydrocannabifuran (8), cannabicitran (CBT, 9), olivetol (10), and Δ9-THC (11). The chemical structures of the purified compounds were determined using several spectroscopic methods, including 1D (1H, 13C, and DEPT-135) and 2D (COSY, HMQC, HMBC, and NOESY) NMR, LC-MS, and GC-MS. Other naturally occurring cannabinoids and impurities were also identified in GC-MS chromatograms but were not isolated. These were cannabidiol (CBD, 12), cannabinol (CBN, 13), hexahydrocannabinol (HHC, 14), and Δ8-tetrahydrocannabivarin (Δ8-THCV, 15). The chemical structure of Δ8-THCV (15), for which a standard was not available, was confirmed by partial synthesis and NMR analysis. This is the first report for many of the above compounds as well as Δ8-THCV as impurities in Δ8-THC products.

Collagen-Specific HSP47+ Myofibroblasts and CD163+ Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections.

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.

Development and Validation of a GC-FID Method for the Quantitation of 20 Different Acidic and Neutral Cannabinoids.

For decades, Cannabis sativa had been illegal to sell or consume around the world, including in the United States. However, in light of the recent 2018 Farm Bill and the legalization of hemp across the US, various cannabis preparations have flooded the market, making it essential to be able to quantitate the levels of the different acidic and neutral cannabinoids in C. sativa and to have a complete cannabinoid profile of the different chemovars of the cannabis plant. A GC-FID method was developed and validated for the analysis of 20 acidic and neutral cannabinoids as trimethylsilyl (TMS) derivatives. The analyzed cannabinoids include cannabidivarinic acid (CBDVA), cannabidiolic acid (CBDA), cannabinolic acid (CBNA), cannabielsoic acid (CBEA), cannabicyclolic acid (CBLA), cannabichromenic acid (CBCA), trans-Δ9-tetrahydrocannabivarinic acid (Δ9-THCVA), trans-Δ9-tetrahydrocannabinolic acid A (Δ9-THCAA), cannabigerolic acid (CBGA), cannabidiol (CBD), cannabicyclol (CBL), cannabidivarin (CBDV), trans-Δ9-tetrahydrocannabivarin (THCV), cannabichromene (CBC), trans-Δ8-tetrahydrocannabinol (Δ8-THC), trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabigerol (CBG), cannabinol (CBN), cannabicitran (CBT), and cannabielsoin (CBE). The method limit of detection (LOD) was as low as 0.1 µg/mL, while the limit of quantitation ranged from 0.25 µg/mL to 0.5 µg/mL. The precision (%RSD) was < 10%, while trueness ranged from 90 - 107%. The developed method is simple, accurate, and sensitive for the quantitation of all 20 acidic and neutral cannabinoids. Finally, the proposed method was successfully applied to the quantitation of the cannabinoids in different cannabis chemovars grown at the University of Mississippi.