Evaluation of Quantitative Hepatitis C Virus Core Antigen Testing as a Tool for Screening and Confirmation of HCV Infection.

BACKGROUND: Hepatitis C is a common viral infection worldwide. Finding the most effective diagnostic methods with low cost is always needed for laboratory improvement. In this study, we evaluated the performance of a quantitative chemiluminescent hepatitis C virus core antigen (HCV cAg) test by comparing it with the HCV confirmatory antibody line immunoblot assay (HCV Ab-LIA) test as well as the HCV quantitate reverse transcription-polymerase chain reaction (qRT-PCR) test. METHODS: A total of 394 samples were enrolled in the retrospective study. Of these, 225 samples were tested using HCV Ab screening and confirmatory Ab-LIA along with chemiluminescent HCV core Ag testing, while 169 samples were tested using qRT-PCR for HCV RNA and chemiluminescent HCV core Ag testing. RESULTS: Out of these, 225 positive samples tested by HCV Ab screening test were analyzed using the confirmatory Ab LIA and HCV cAg assays, a total of 183 samples (81.3 %) were confirmed to be Ab-positive, and among those, 77 samples (42.1%) were also positive for HCV cAg. Thirty-eight samples (20.76%) were HCV Ab indeterminate, and all of them were HCV cAg negative. Four samples (1.8%) were HCV Ab LIA-negative and negative for HCV cAg. Moreover, 169 samples were measured for qRT-PCR HCV viral load and quantitative HCV cAg test. One hundred and three samples were positive for HCV RNA, while 66 were negative. Among the positives, 96/103 samples were HCV cAg positive and 7/103 samples were negative. Out of the negatives, 4/66 samples were HCV cAg positive but 62/66 samples were negative. The HCV cAg results were concordant with the qRT-PCR results in 158 samples (93.5%); however, 11 samples (6.5%) were found to be discrepant. The sensitivity, specificity, positive predictive value, and negative predictive value of the quantitative HCV cAg were found to be 93%, 94%, 96%, and 90%, respectively. The overall coefficient of correlation between the HCV RNA levels and HCV cAg data was determined to be r2 = 0.9. CONCLUSIONS: The HCV cAg test showed a high correlation with the HCV RNA levels and may potentially be used as a more cost-effective alternative to the HCV RNA qRT-PCR test.

Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.

Cytokine physiognomies of MSCs from varied sources confirm the regenerative commitment post-coculture with activated neutrophils.

The interaction of mesenchymal stromal cells (MSCs) with paracrine signals and immunological cells, and their responses and regenerative commitment thereafter, is understudied. In the current investigation, we compared MSCs from the umbilical cord blood (UCB), dental pulp (DP), and liposuction material (LS) on their ability to respond to activated neutrophils. Cytokine profiling (interleukin-1α [IL-1α], IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], transforming growth factor-ß [TGF-ß]), cellular proliferation and osteogenic differentiation patterns were assessed. The results showed largely comparable cytokine profiles with higher TNF-α and IFN-γ levels in LSMSCs owing to their mature cellular phenotype. The viability and proliferation between LS/DP/UCB MSCs were comparable in the coculture group, while direct activation of MSCs with lipopolysaccharide (LPS) showed comparable proliferation with significant cell death in UCB MSCs and slightly higher cell death in the other two types of MSC. Furthermore, when MSCs post-neutrophil exposure were induced for osteogenic differentiation, though all the MSCs devoid of the sources differentiated, we observed rapid and significant turnover of DPMSCs positive of osteogenic markers rather than LS and UCB MSCs. We further observed a significant turnover of IL-1α and TGF-ß at mRNA and cytokine levels, indicating the commitment of MSCs to differentiate through interacting with immunological cells or bacterial products like neutrophils or LPS, respectively. Taken together, these results suggest that MSCs have more or less similar cytokine responses devoid of their anatomical niche. They readily switch over from the cytokine responsive cell phenotype at the immunological microenvironment to differentiate and regenerate tissue in response to cellular signals.

Basidiobolus haptosporus-like fungus as a causal agent of gastrointestinal basidiobolomycosis.

Basidiobolus species were isolated from colonic biopsy samples of patients with gastrointestinal basidiobolomycosis (GIB) in southern Saudi Arabia. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Phenotypic tests revealed zygomycete-like fungi which conform to those of Basidiobolus species. Five sequenced strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity with B. haptosporus and 99.97% with B. haptosporus var. minor, and relatively lower similarity with B. ranarum (99.925%). The study suggests a new and a serious causal agent of GIB related to Basidiobolus haptosporus. These isolates are not related to B. ranarum, which is commonly linked to this disease.

Sero-prevalence and risk factors of brucellosis among suspected febrile patients attending a referral hospital in southern Saudi Arabia (2014-2018).

BACKGROUND: Human brucellosis is an infectious zoonotic disease caused by Brucella spp. It is one of the most public health problems that remains largely neglected in developing counties, including Saudi Arabia. Brucellosis is particularly prevalent among rural people who have constant contact with livestock. METHODS: A cross-sectional sero-epidemiological study conducted in Aseer Central Hospital, South Saudi Arabia, between 2014 and 2018 among 7567 patients. Serum samples were analyzed for Brucella antibodies using slide agglutination test. Serology results and patient's demographic data were analyzed by GraphPad Prism. Results were presented as mean ± SEM and differences between two groups were assessed by t-test and p < 0.05 was considered significant. RESULTS: The prevalence of brucellosis among the admitted suspected 7567 cases was 12.8% (10.4-15.7%; CI 95%). The highest prevalence rate was detected during 2015, the rate decreased to the lowest level during the last three years (p < 0.05). Higher rate of brucellosis was observed among males than females (p < 0.05) and most cases were reported during summer season (p < 0.05). The highest prevalence rate was observed in age group 21-40 year old (40.5%) followed by 41-60 years (27.7%). The lowest prevalence rate was noticed in old and young children (15 and 3%, respectively). Cross-transmission of brucellosis was seen within family (1%) and high titers (> 1280) was noticed in 22% of the hospitalized patients. The major symptoms were fatigue, hyperhidrosis, fever and joint pain. CONCLUSION: Our findings showed a high prevalence of human brucellosis among suspected patients in Aseer region. This indicates that clinical suspicion is a valid criterion and the endemic nature of the disease. The disease status requires early laboratory detection and confirmation to start prompt treatment to decrease patients suffering.

Analysis of amphetamine and methamphetamine contents in seized tablets from Jazan, Saudi Arabia by liquid chromatography-mass spectroscopy (LC-MS/MS) and chemometric techniques.

A number of illegal amphetamine tablets were seized from three different cities of Jazan province of southern Saudi Arabia and were analyzed for amphetamine and methamphetamine contents using LC-MS/MS technique. Analyses were performed using a previously reported method taking 0.1 M ammonium formate buffer (85%) and 15% acetonitrile with 0.1% formic acid as mobile phase with a total runtime of 12 min. This method was successfully applied for the routine analysis of amphetamine and methamphetamine in the seized tablets using amphetamine-D5 and methamphetamine-D5 as internal standards. Hierarchical cluster analysis was performed to establish the similarity between samples. The retention times (RT) for internal standard, amphetamine and methamphetamine were observed to be within 6.0-7.1 min. Ten tablet samples from each city were subjected to analysis and the amount of amphetamine in all the samples were found to be in the range of 9.07-14.77 mg, whereas, the amount of methamphetamine ranged from 0.12 to 0.24 mg in each tablet. Hierarchical cluster analysis showed presence of five clusters of samples indicating different characteristics and possible sources of amphetamine tablets. The largest cluster consisted of 15 samples which are expected to be of the same origin. Both amphetamine and methamphetamine are considered to be illegal products and their illegal trade and use is banned in many countries including Saudi Arabia. Therefore, there is an urgent need of strict regulations worldwide to check the illicit trafficking of these psychoactive substances and should be considered on priority.

MSCs ameliorates DPN induced cellular pathology via [Ca2+ ]i homeostasis and scavenging the pro-inflammatory cytokines.

The MSCs of various origins are known to ameliorate or modulate cell survival strategies. We investigated, whether UCB MSCs could improve the survival of the human neuronal cells and/or fibroblast assaulted with DPN sera. The results showed, the co-culture of UCB MSCs with human neuronal cells and/or fibroblasts could effectively scavenge the pro-inflammatory cytokines TNF-α, IL-1ß, IFN-ɤ and IL - 12 and control the pro-apoptotic expression of p53/Bax. Further co-culture of UCB MSCs have shown to induce anti-inflammatory cytokines like IL-4, IL-10 and TGF-ß and anti-apoptotic Bclxl/Bcl2 expression in the DPN sera stressed cells. Amelioration of elevated [Ca2+ ]i and cROS, the portent behind the NFκB/Caspase-3 mediated inflammation in DPN rescued the cells from apoptosis. The results of systemic administration of BM MSCs improved DPN pathology in rat as extrapolated from human cell model. The BM MSCs ameliorated prolonged distal motor latency (control: 0.70 ± 0.06, DPN: 1.29 ± 0.13 m/s DPN + BM MSCs: 0.89 ± 0.02 m/s, p < 0.05) and lowered high amplitude of compound muscle action potentials (CMAPs) (control: 12.36 ± 0.41, DPN: 7.52 ± 0.61 mV, DPN + MSCs: 8.79 ± 0.53 mV, p < 0.05), while slowly restoring the plasma glucose levels. Together, all these results showed that administration of BM or UCB MSCs improved the DPN via ameliorating pro-inflammatory cytokine signaling and [Ca2+ ]i homeostasis.

Feasibility of cord blood bank in high altitude Abha: preclinical impacts.

We explored the possibility of the cryo-storage of cord blood hematopoietic stem cells (CBHPSC) with respect to the quantity, quality and biologic efficacy of high altitude (HA) region Abha against sea level (SL) region. The results of the post-processed total nucleated cell count was 8.03 ± 0.31 × 107 and 8.44 ± 0.23 × 107 cells in the HA and SL regions respectively. The mean post processing viability of the nucleated cells was about 87.03 ± 1.39 (HA) and 88.33 ± 1.55% (SL) while post thaw cells were 85.61 ± 1.44 (HA) and 86.58 ± 1.61% (SL) after transient cryo-storage. The proliferation of CBHSCs after thawing were comparable between the HA and SL regions. The results of the colony forming unit (CFU) assays of CFU-E, CFU-GEMM, CFU-GM and BFU-E were comparable between HA and SL in both fresh and post thaw, while a declining trend with viability was significant. The differentiation capability of post thaw samples into adipocytes and osteocytes were comparable between HA and SL regions. Overall from the results, it can be evidenced that HA cord blood collection, processing or storage does not hinder the quality or biological efficacy of the CBHPSC.

Differentiated mesenchymal stem cells ameliorate cardiovascular complications in diabetic rats.

Cardiovascular manifestations are one of the major complications of type 1 diabetes mellitus (T1DM) and supersede the slow progression of DM in most cases as the leading cause of mortality. There have been many studies and trials in regenerating the functional ß-cells of islets from mesenchymal stem cells (MSCs) with varied success. The effect of MSCs ex vivo differentiated to mimic functional insulin-secreting ß-cells of islets and their impact on restoration of diabetic complications and transplantation via systemic delivery have not been well studied. In the current study, bone marrow MSCs differentiated to insulin-secreting ß-cells are used to treat STZ-induced diabetic rats. The post-homing effects of the differentiated MSCs (dMSCs) were endogenous with definite reversal of diabetic parameters. Consequently, the altered cardiac functions like heart beat rate, left ventricular performance, contractility index and physiological body weight gain due to hyperglycemia were amelorated into normacy. The primary onset cardiac perfomance and the endothelial activation were well evidenced by high fibrinogen levels and systolic blood pressure (SBP) being reversed on the treatment by dMSCs. Further high basal [Ca(2+)]c in isolated endothelial cells and thereby increased ROS confirmed the endothelial activation. The levels of pro-apoptotic makers p53 and Bax were highly expressed in the diabetic groups indicating oxidative stress through ROS induced by high cytosolic calcium skewing the cells towards apoptosis. The expression of the anti-apoptotic marker Bcl-2 was observed to be low in the diabetic group further augmenting the stress state of endothelial cells (ECs) in T1DM. Restoration of [Ca(2+)]c chelates ROS and the subsequent reversal of pro- and anti-apoptotic markers after the successful treatment of dMSCs proved that endogenous reconstitution of insulin secretion improves diabetic-induced cardiac manifestations.

Evaluation of Remdesivir Utilization Pattern in Critically Ill Patients With COVID-19 in Jazan Province.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread around the world, spurring the biomedical community to find and create antiviral therapies. The agent remdesivir, which has undergone a protracted and tortuous developmental path, is one potential therapeutic strategy now being assessed in several clinical trials. A broad-spectrum antiviral drug called remdesivir has already shown antiviral effects against filoviruses. Remdesivir was suggested as an exploratory medicine early in the pandemic because in vitro tests showed it to have antiviral effectiveness against SARS-CoV-2. Methods We conducted a retrospective cohort study that examined patient data captured through an electronic medical system at the Abu Arish General Hospital between 2021 and 2022. Data analysis was performed with SPSS version 25.0 (Armonk, NY: IBM Corp.). Results A total of 88 patients were included in this study. With the usage of remdesivir, our risk model is able to forecast adverse events and the case fatality rate. In contrast to D-dimer and c-reactive proteins, we showed that alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine, and hemoglobin are relevant variables. Conclusion Our risk model can predict the adverse reactions and case fatality rate with the use of remdesivir. We demonstrated ALT, AST, serum creatinine, and hemoglobin as important variables rather than D-dimer and c-reactive proteins.

Microsporum gypseum Infection Among Two Related Families With a Zoonotic Aspect: A Prospective Case Series.

Background and purpose The Microsporum gypseum complex is a globally distributed group of geophilic dermatophytes that primarily affect animals but can also rarely cause dermatomycoses in humans. With some regional and occupational variations, tinea corporis is the most prevalent presentation of the infection. The aim of this study was to report on the diagnosis and treatment of dermatophytosis cases among related families, and their pets, from southern Saudi Arabia. Up-to-date information on dermatophytes and dermatophytosis is needed. Methods This is a prospective case series undertaken at the Dermatology Outpatient Clinic of King Khalid University, Saudi Arabia. Six patients with suspected dermatophytosis were received at our hospital in 2022 and have been followed for recovery with or without scars. Characteristics of fungal pathogens were examined phenotypically on the basis of microscopic and growth characteristics, and laboratory data were used to initiate treatment with oral fluconazole, topical terbinafine cream, or oral itraconazole. Results Clinical features and culture results confirmed tinea capitis and tinea corporis caused by M. gypseum, which was also present in a pet cat. Tinea capitis cases (n = 4) did not respond to fluconazole and terbinafine treatment, but treatment with itraconazole resulted in a full recovery. Tinea corporis cases (n = 2) were treated with terbinafine, which resulted in a full recovery within four weeks, with no signs of scarring. Conclusions M. gypseum presents with serious persistent lesions and is extremely contagious. Treatment is durable but challenging, and breaking the transmission chain is more difficult.

Cathine and cathinone disposition kinetics and neurotransmitter profile in several organs of rats exposed to a single dose of Catha edulis (Vahl) Forssk. ex Endl. extract.

OBJECTIVES: Catha edulis (Vahl) Forssk. ex Endl. (Khat) is a stimulant plant that contains cathine and cathinone, which its abuses induce euphoria, alertness, and motor activity. Since the toxicokinetics of these substances remain unclear, this study was carried out to investigate the disposition kinetics of cathine and cathinone, the neurotransmitter profile, following a single dose of C. edulis extract in rats. METHODS: Twenty-four adult male Wistar albino rats (250-300 g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000 mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24 h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method. RESULTS: The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5 h. The concentrations peaked in the brain 2.5 h later, indicating that the heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68 and 5.07 h, respectively) and may remain in the brain for longer durations (3.31 and 2.31 h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner. CONCLUSIONS: Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest Cmax in the lung and Tmax in the heart tissues but not in the brain. In addition, neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin were differentially detected in all tested samples in a organ-specific fashion. More study is needed to identify cathine and cathinone's effects on neurotransmitter profiles. Nevertheless, these findings provided a further basis for experimental, clinical, and forensic investigations.

Differences in brain volume and thickness in patients with pulmonary or spine tuberculosis (TB) compared to non-TB individuals: A cross-sectional retrospective study.

Introduction: There is evidence showing that central nervous system TB (CNS-TB) causes meningitis, pachymeningitis, tuberculomas, and granulomas. However, the impact of pulmonary or spine TB on brain morphology and thickness is yet to be documented. TB is associated with increased levels of inflammatory biomarkers in specific brain regions. Objectives: The primary aim of this study was to compare cortical-brain volume and thickness between patients with pulmonary or spine TB and non-TB individuals and investigate the association between inflammatory biomarkers and brain volume or thickness among patients with pulmonary or spine TB. Methods: Participants ranging in age from 18 to 65 years (23 TB patients and 50 healthy controls), who were scanned using 1.5-T MRI at Jazan Hospital, were compared in terms of brain volumes and thicknesses. Brain volume and thickness were measured using FreeSurfer. Results: There were significant differences in the volumes of the bilateral and total amygdala and accumbens areas, right hippocampus and cerebellum, and CSF, and in the thickness of the right pericalcarine area between patients with pulmonary or spine TB and healthy controls. We also found significant associations between inflammatory biomarkers (CRP, WBC, and platelets) and brain volume but not thickness in patients with TB, p < .05. Conclusions: This study is the first to show that pulmonary or spine TB reduces brain size and thickness and suggests that TB may be better understood by considering the correlation between inflammatory biomarkers and brain volumes.

The effectiveness of mindfulness training in improving medical students' stress, depression, and anxiety.

INTRODUCTION: There is growing interest in Mindfulness-based Stress Reduction (MBSR) program to combat mental distress in medical students. In Saudi Arabia, literature is insufficient about MBSR and its effectiveness. This study aims to measure the effectiveness of MBSR in improving mindful state, stress, anxiety, and depression in medical students. Also, the study explores the association between the attendance rate of MBSR sessions and its effectiveness. Lastly, the study examines gender differences in response to MBSR. METHODS: This is a stratified randomized controlled study of 84 medical students from two medical schools in Riyadh, Saudi Arabia. They were recruited voluntarily from November 2018 to April 2021, and allocated to MBSR and waitlist groups using a stratified randomization method based on gender. MBSR group received eight weeks of sessions through audiovisual materials. An online survey utilizing validated questionnaires assessing stress, mindfulness, anxiety, and depression was used to evaluate both groups pre-program (time 0), post-program (time 1), and three months later (time 2). RESULTS: Seventy-one participants completed the post-test (time 1). There were no differences between study groups at time 0 and 1. However, in 41 subjects who completed the follow-up test (time 2), the anxiety dropped significantly in MBSR group (mean difference (MD), -3.935; 95% CI, -7.580 to -0.290). Furthermore, attending more MBSR sessions was inversely correlated with depression (r, -0.556; P, 0.002), and anxiety (r, -0.630; P, 0.000). Compared to their baseline, males in MBSR group improved in stress (MD, 3.08; 95% CI, 0.30 to 5.86), anxiety (MD, 4.91; 95% CI, 3.32 to 6.50), and mindfulness (MD, -0.58; 95% CI, -1.01 to -0.15), while females improved in stress (MD, 2.64; 95% CI, 0.02 to 5.26). CONCLUSION: Despite the study being interrupted by the stressful COVID-19 outbreak, the findings suggest that MBSR improved psychological outcomes when participants commit to the program.

Chronic metabolic and induced stress impacts mesenchymal stromal cell differentiation and modulation of dental origin in-vitro.

The impact of induced (smoking) and metabolic stress (diabetes) on dental stem cells with respect to pre-impact consideration on differentiation and bone formation were investigated. The progenitor stem cells isolated from dental pulp, follicle and gingival tissues were phenotyped and subjected to nicotine and high glucose stress mimicking the smoking and diabetic condition in-vitro. The results showed that the cellular viability post treatment with 100 µM nicotine and 10uM glucose was about 86% to 89% respectively in all the three cell types while about 73% in combined nicotine and glucose treatment. No variation in the expression of pro-inflammatory TNF-α, IL-1ß and IL-12 in all the three cell types were noticed. The observed viability in nicotine treated cells were due to elevated IL-6, IL-10 while in glucose was due to brain derived neurotropic factor (BDNF). Higher expression of IL-4, IL-6, IL-10, TGF-ß and heme oxygenase -1 (HO-1) were found high in both stressors treated cells. Differentiation and mineralization markers Alkaline phosphatase (ALP), Collagenase I (COL1), Osteocalcin, Runt related transcription factor 2 (RUNX2), Osteopontin and Bone sialoprotein were expressed in the dental pulp stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) at varying levels post nicotine or glucose treatment while not significantly observed in dental follicular stem cells (DFSCs). Therefore, it is evident that the stem cells of varied dental origin responded to the stress are more or less uniform with physiological delay in differentiation into osteoblast. It is evident from the study that, the metabolic or induced stress subverts the process of regenerative healing by mesenchymal stromal cells with their anatomical niche.

Glucose and oleic acid mediate cellular alterations in GLP-1-induced insulin-positive differentiating UCBMSCs.

Coordinated effects of glucose and oleic acid on glucagon-like peptide-1 (GLP-1) mediated differentiation of insulin-positive differentiating umbilical cord mesenchymal stromal cells (dUCBMSCs) was studied using a co-culture of NCI-H716 (GLP-1+) and UCBMSCs (insulin+). The addition of 2.5 mM glucose increased the proliferation of NCI-H716 cells by 30% and induced transformation of UCBMSCs into insulin-secreting cells in 18 days as compared to 22 days in control cells. Oleic acid (25 µM) showed decrease in cell proliferation, autophagy, and apoptosis in NCI-H716 cells while no effect was observed in dUCBMSCs. Prolonged glucose and oleic acid resulted in apoptosis and cell cycle changes in dUCBMSCs after day 18 while higher concentrations resulted in cell death. Additionally, the expression of FAS and ACC mRNA was observed in NCI-H716 and dUCBMSCs post 24-hr addition of glucose and/or oleic acid. Absorption of oleic acid was high in NCI-H716 compared to dUCBMSCs. Taken together, optimal concentrations of glucose and oleic acid could be a key factor in stimulating intrinsic GLP-1, which in turn stimulates differentiating MSCs in a glucose-dependent manner. PRACTICAL APPLICATIONS: The aim of this article was to study whether differentiating or differentiated MSCs after mobilization or post-transplant would require optimal glucose and oleic acid to naturally stimulate intrinsic GLP-1, or otherwise, the high or long-term overload of glucose or oleic acid could result in inhibition of differentiated cells resulting in failure of insulin secretion.

Haematological Traits in Symptomatic and Asymptomatic COVID-19 Positive Patients for Predicting Severity and Hospitalization.

Objective: The present investigation aims on the clinical attributes and haematological parameters between symptomatic (COVID-19 ICU) and asymptomatic (COVID-19 homes isolation) patients as predisposing sign for COVID-19 related mortality. Materials and Methods: A retrospective cohort research was conducted of admitted patients to ICU, who were suffering from severe COVID-19 in Aseer Central Hospital, Abha, Kingdom of Saudi Arabia (KSA) from July 2020 until September 2020. The study included individuals with COVID -19 and ICU admission as symptomatic group and others who are COVID-19 positives with quarantine as asymptomatic group. Epidemiological, clinical and haematological laboratory data were retrospectively collected, analysed with control subjects. Results: Of the 38 ICU patients studied, the most common symptoms were fever and respiratory distress (100%), cough (86.8%). Majority were of Saudi origin (78.9%). Eighteen (47.4%) COVID-19 ICU patients showed leukocytosis, 6 (15.8%) had severe thrombocytopenia (with most having thrombocytopenia), 18 (47.4%) were anaemic. A significant correlation was observed between the WBC, RBC, Hb, platelets, neutrophil and lymphocyte count between ICU inmates compared with quarantine (p < 0.001) and RBC, Hb, neutrophil and lymphocyte count with control groups (p < 0.001). Conclusion: From the observations it is evident that, the blood tests have potential clinical value in predicting COVID-19 progression. Further, patient characteristics including age, leukocyte count, RBC, platelets and differential leukocyte counts may be significant predictors for monitoring the progression of the critical illness observed in SARS-COV-2 patients. Also, treatment procedures can be re-defined further to reduce COVID-19 mortalities in more critically ill COVID-19 individuals.

Habitual khat chewing alters urinary inorganic profile in adult healthy males.

OBJECTIVES: Khat (Catha edulis) is a stimulant plant, and it is abusive to induce euphoria, alertness and activity. Concomitant use of medications and khat chewing predisposes to the appearance of drug interactions result in treatment failure or toxicity. This study determined the changes in the urinary inorganic profile in adult healthy males who are chewing khat compared with non-khat chewer males. METHODS: A total of 40 adult non-smoker healthy males (20 khat chewer and 20 non-khat chewer) aged 24-30 years were selected. Khat chewer samples were positive for cathinone and cathine and negative for other drug of abuse, while non-khat chewer samples were negative for drug of abuse include cathinone and cathine. Samples were selected according to their results in immunoassay and gas chromatography mass spectrometry (GCMS) analysis. Cathine and cathinone were confirmed using liquid chromatography mass spectrometry (LC-MSMS) analysis. Inorganic profile includes titanium (Ti), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) were determined by using inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: The levels of Ti, Co, Zn, Cd, and Pb in urine were significantly higher among the khat chewer group compared with non-khat chewer. Ti, Cd, Co, Pb and Zn urine levels were 0.5-, 1.5-, 1.15-, 5-, and 8.2-fold higher in the khat chewer group compared to non-khat chewer, respectively. CONCLUSIONS: We suggested that continuous khat chewing has a long term effect on metabolic pathway of therapeutic drugs that result in toxicity or failure of therapy.

Habitual khat chewing alters urinary inorganic profile in adult healthy males.

OBJECTIVES: Khat (Catha edulis) is a stimulant plant, and it is abusive to induce euphoria, alertness and activity. Concomitant use of medications and khat chewing predisposes to the appearance of drug interactions result in treatment failure or toxicity. This study determined the changes in the urinary inorganic profile in adult healthy males who are chewing khat compared with non-khat chewer males. METHODS: A total of 40 adult non-smoker healthy males (20 khat chewer and 20 non-khat chewer) aged 24-30 years were selected. Khat chewer samples were positive for cathinone and cathine and negative for other drug of abuse, while non-khat chewer samples were negative for drug of abuse include cathinone and cathine. Samples were selected according to their results in immunoassay and gas chromatography mass spectrometry (GCMS) analysis. Cathine and cathinone were confirmed using liquid chromatography mass spectrometry (LC-MSMS) analysis. Inorganic profile includes titanium (Ti), cobalt (Co), copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) were determined by using inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: The levels of Ti, Co, Zn, Cd, and Pb in urine were significantly higher among the khat chewer group compared with non-khat chewer. Ti, Cd, Co, Pb and Zn urine levels were 0.5-, 1.5-, 1.15-, 5-, and 8.2-fold higher in the khat chewer group compared to non-khat chewer, respectively. CONCLUSIONS: We suggested that continuous khat chewing has a long term effect on metabolic pathway of therapeutic drugs that result in toxicity or failure of therapy.

Serum sCTLA-4 level is not associated with type 1 diabetes or the coexistence of autoantibodies in children and adolescent patients from the southern region of Saudi Arabia.

BACKGROUND: The soluble form of CTLA-4 (sCTLA-4) is associated with several autoimmune diseases. The aim of the study is to measure the serum sCTLA-4 levels in type I diabetic (T1DM) patients and to assess the presence of autoantibodies for a possible association. METHODS: One hundred forty-two T1DM patients were enrolled in the study. Fifty of them were serologically positive for co-existing autoantibodies. One hundred and five subjects were enrolled in the study, as non-diabetic controls (1-17 years of age; median age-10 years). The serum samples of all the subjects were analyzed with ELISA to detect the concentration of sCTLA-4 and anti-GAD/IA2 IgG. Standard statistical analysis was conducted as required. RESULTS: Ninety-four (66%) subjects of T1DM patients and five (4.7%) subjects of the non-diabetic group had antibodies positive for anti-GAD/IA2. Serum sCTLA-4 was low in most of the subjects of both the diabetic and control groups (p = 0.18). In the control group, nine individuals (8.6%) were positive for sCTLA-4. Similarly, only seven patients (4.9%) in the T1DM group had high levels of sCTLA-4, of which two were found to be double positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies. In addition, among the T1DM patients, no significant relationships were observed between sCTLA-4 levels and age of onset (p = 0.43), disease duration (p = 0.09), or glycemic control (p = 0.32). CONCLUSION: Despite the previous findings of high sCTLA-4 levels in autoimmune diseases, serum levels of sCTLA-4 are not significantly different between T1DM patients and non-diabetic adolescents. Furthermore, we did not observe any association with autoantibody presence, glycemic control, or disease duration.