The role of miRNAs in viral myocarditis, and its possible implication in induction of mRNA-based COVID-19 vaccines-induced myocarditis.

Background: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others. Main body of the abstract: Certain miRNAs (non-coding RNA sequences) are involved in the pathogenesis in viral myocarditis, and those miRNAs are interestingly upregulated in severe COVID-19. We hypothesize that the use of mRNA-based vaccines may be triggering the release of host miRNAs or that trigger the occurrence of myocarditis. This is based on the finding of altered host miRNA expression promoting virus-induced myocarditis. Short conclusion: In conclusion, miRNAs are likely implicated in myocarditis associated with mRNA vaccines. Our hypothesis suggests the use of miRNA as a biomarker for the diagnosis of mRNA vaccine-induced myocarditis. Additionally, the interplay between viral miRNA and the host immune system could alter inflammatory profiles, hence suggesting the use of therapeutic inhibition to prevent such complications.

Effect of mutation and vaccination on spread, severity, and mortality of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.

Severe hyponatremia after donor nephrectomy.

Living kidney donation is safe and established but can lead to short- and long-term complications. Hyponatremia is the most common disorder of body fluid and electrolyte balance in clinical practice, associated with increased morbidity, mortality, and the length of hospital stay. A correct diagnosis of the etiology of hyponatremia is critical, both to determine correct management and prognosis. Here, we present a case of a severe hyponatremia following left- sided donor nephrectomy with a physical examination suggestive of mild hypovolemia. Laboratory tests revealed high urine osmolality and sodium concentration mimicking syndrome of inappropriate antidiuretic hormone secretion (SIADH), in the setting of abnormally blunted response to Synacthen. The patient responded well to hydrocortisone replacement. Differentiating between primary adrenal insufficiency and SIADH as a cause of severe hyponatremia was the key to successfully treating this patient. Hyponatremia following donor nephrectomy is unusual and could be explained in this case by hypocortisolism.

ABO incompatible kidney transplantation: the Saudi experience.

Although the outcomes of ABO-incompatible (ABOi) kidney transplant recipients are quite favorable, these patients are at increased risk of early antibody-mediated rejection (AMR) and graft loss. Some studies have also shown high mortality in the ABOi group mainly due to increased risk of infections. The AMR rates have been reported anywhere from <10% to >50% in the literature. The outcomes of the ABOi kidney transplants in the Saudi population are not known. In this study, we aimed to determine the graft and patient survival in ABOi kidney transplant recipients in the Saudi population. We included all adult patients who underwent ABOi transplantation between 2007 and 2016. All patients received rituximab, therapeutic plasma exchange, thymoglobulin, intravenous antibiotics, and intravenous immunoglobulin. The maintenance immunosuppression was prednisone, mycophenolate mofetil, and tacrolimus. The data were collected from a prospectively maintained database. A total of 77 patients were included in the study. The most common blood group mismatch was A to O (44.2%), followed by B to O (26.0%) and A to B (16.9%). In the 1st year, 17% of patients developed acute cellular rejection and AMR occurred in 7.8% of patients. Two patients were diagnosed with BK nephropathy. In the 1st year, urinary tract infection occurred in 25 (32.5%) patients. No patient was diagnosed severe viral or fungal infection. In the 1st year, four grafts were lost (graft survival of 94.8%); all grafts were lost within two weeks, three due to AMR and one due to technical reason. One year patient survival was 100%. In this study of ABOi kidney transplant recipients, we observed low risks of infectious complications with excellent patient and graft survival. Our immunosuppressive protocol can be considered safe.

Ramadan Fasting in Kidney Transplant Recipients: A Single-Centre Retrospective Study.

BACKGROUND: Fasting during the lunar month of Ramadan is mandatory to all healthy adult Muslims. Renal transplant recipients are often worried about the impact of fluid and electrolyte deprivation during fasting on the function of their allograft. We aimed to examine the effect of fasting Ramadan on the graft function in renal transplant recipients. METHODS: This retrospective cohort study included patients who underwent kidney transplantation in our tertiary referral center. Baseline pre-Ramadan estimated glomerular filtration rate (eGFR), mean arterial pressure (MAP), and urinary protein excretion were compared to those during and after Ramadan within and between the fasting and non-fasting groups. RESULTS: The study population included 280 kidney transplant recipients who chose to fast during the Ramadan month (June-July 2014) and 285 recipients who did not fast. In the fasting group, baseline eGFR did not change from that during or post-Ramadan (72.6 ± 23.7 versus 72.3 ± 24.5 mL/min/1.73 m2, P = 0.53; and 72.6 ± 23.7 versus 72 ± 23.2 mL/min/1.73 m2, P = 0.14, respectively). Compared to baseline, there were no significant differences between the fasting and the non-fasting groups in terms of mean percent changes in eGFR, MAP, and urinary protein excretion. CONCLUSION: Fasting during the month of Ramadan did not have significant adverse effects on renal allograft function.

Comparison of survival between dialysis patients with incident high-flux hemodialysis versus on-line hemodiafiltration: A single center experience in Saudi Arabia.

Conventional hemodialysis (HD) is the most common treatment modality used for renal replacement therapy. The concept of HD is based on the diffusion of solutes across a semipermeable membrane. Hemofiltration (HF) is based on convective transport of solutes; hemodiafiltration (HDF) is based on combined convective and diffusive therapies. Data about survival benefit of on-line HDF (OL-HDF) over high-flux HD (HF-HD) is conflicting. We conducted this study to investigate if there is a survival difference between the two treatment modalities. This study is a retrospective, single-center study in which 78 patients were screened; 18 were excluded and 60 patients were analyzed. The study patients were aged 47.5 ± 20.7 years, 33 patients (55%) were on HF-HD, and 27 patients (45%) were on OL-HDF. A total of 24 patients (40%) of both groups were diabetic and, the mean duration on dialysis was 43.5 ±21.3 months in the HF-HD group and 41.2 ± 22.0 months in the OL-HDF group. The mean substitution volume for OL-HDF was 22.3 ± 2.5 L. Survival was 73% [95%, confidence interval (CI) 60-84] in the HF-HD group and 65% (95%, CI 54-75) in the OL-HDF group by the end of the study period. The unadjusted hazard ratio (HR) with 95% CI comparing HF-HD to high-volume postdilution OL-HDF was 0.78 (0.10-5.6; P = 0.810). Kaplan-Meier analysis for patient survival over five years showed no significant difference between the two modalities. Prospective controlled trials with a larger number of patients will be needed to assess the long-term clinical outcome of postdilution OL-HDF over HF-HD.

A randomized double-blind controlled trial comparing three sedation regimens during flexible bronchoscopy: Dexmedetomidine, alfentanil and lidocaine.

INTRODUCTION: No standardized sedation protocol is available for flexible bronchoscopy (FB). OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of three regimens used for sedation during FB. METHODS: This randomized double-blind controlled trial assessed patients undergoing bronchoscopy and receiving lidocaine alone (C) or combined with dexmedetomidine (D) or alfentanil (A). Tolerance was assessed using the bronchoscopy score, and level of sedation was assessed using the Nursing Instrument for the Communication of Sedation. Safety was evaluated in terms of pulmonary function and vital signs. RESULTS: A total of 162 patients were enrolled. The bronchoscopy score was identical in all groups. Group D subjects were the most sedated (P = .013), whereas group A subjects were the least agitated. Linear regression showed a negative association between bronchoscopy score and age in A (ß = -0.06; P = .001). Positive predictors of bronchoscopy score were female gender (ß = 1.96; P = .003) in D and obesity (ß = 2.41; P = .012), longer procedures (ß = 0.08; P = .009) and female gender (ß = 1.15; P = .038) in C. Longer procedures (ß = -0.12; P = .010) was a negative predictor of bronchoscopy score in D. Desaturation, hypoxia and heart rate changes were most prevalent in group A. Hypotension was mostly observed in D. CONCLUSIONS: No consistent differences were present between the three regimens; however, each was more appropriate in certain patient profiles. We consequently proposed a protocol as a first step towards standardizing sedation practice in FB in a patient-tailored manner. A more comprehensive and detailed protocol including other sedative agents with their corresponding doses should be developed.

Factors predicting CPAP adherence in obstructive sleep apnea syndrome.

PURPOSE: Obstructive sleep apnea (OSA) is associated with a range of neurocognitive and cardiovascular complications, leading to a compromised quality of life. Continuous positive airway pressure (CPAP) is the gold standard therapeutic intervention for this disorder, yet patient compliance remains essential to its success. This study aimed at identifying the determinants of short-term and long-term CPAP adherence in a group of Lebanese patients. METHODS: This cross-sectional study, conducted at the Sleep Center of Hôtel-Dieu de France hospital in Lebanon, included patients diagnosed with OSA and treated with CPAP for at least one night between June 2008 and January 2015. Adherence was assessed based on patients' self-report. RESULTS: The study enrolled 138 patients. Adherence rate was 70.3 % at 6 months and around 50 % after 5 years. Cox models showed that use of nasal masks (HR 0.48, p = 0.048) and higher oxygen desaturation index at baseline (HR 0.98 p = 0.048) were associated with a better short-term CPAP adherence. Patients who bought their devices (HR 0.18, p < 0.001), those who were frequently contacted by the CPAP provider (HR 0.85, p 0.024), and those who reported improvement on treatment (HR 0.36, p < 0.001) were significantly more likely to remain adherent on the long term. Conversely, individuals on a diet plan tended to interrupt the treatment earlier (HR 4.85, p 0.039). CONCLUSION: The present findings should be further explored in order to tailor interventions to the specific needs of different patient profiles and secure an improved CPAP adherence.

Circulating microRNAs, miR-92a, miR-100 and miR-143, as non-invasive biomarkers for bladder cancer diagnosis.

The application of microRNAs (miRNAs) as potential biomarkers and therapy targets has been widely investigated in many kinds of cancers. Recent advantages of serum miRNAs open a new realm of possibilities for non-invasive diagnosis and prognosis of bladder cancer (BC). The aim of our study was to identify plasma miR-92a, miR-100 and miR-143 expression signatures in patients with BC to introduce new markers for establishing BC diagnosis and prognosis. Blood samples were collected from 70 BC patients and 62 controls. An expression of three target miRNAs (miR-92a, miR-100 and miR-143) was measured using quantitative real-time PCR method. Results were correlated with clinicopathological data and analysed. Plasma levels of miR-92a, miR-100 and miR-143 were significantly lower in BC patients than in control group. Receiver operator characteristic analysis revealed that the sensitivity and specificity values of miR-92a were 97·1% and 76·7%, respectively, with a cut-off value of 0·573. The sensitivity and specificity values of miR-100 were 90% and 66·7%, respectively, with a cut-off value of 0·644. The sensitivity and specificity values of miR-143 were 78·6% and 93·3%, respectively, with a cut-off value of 0·164. This study explores the existence of specific plasma miRNAs as early diagnostic biomarkers for BC in Egyptian patients; and these findings suggest that plasma miR-92a, miR-100 and miR-143 could be promising novel circulating biomarkers in clinical detection of BC.

Therapeutic Effect of Adipose Derived Stem Cells versus Atorvastatin on Amiodarone Induced Lung Injury in Male Rat.

BACKGROUND AND OBJECTIVES: Amiodarone (AM), a class 3 antiarrhythmic drug, has been associated with variety of adverse effects, the most serious of which is pulmonary toxicity. Ator (A) is a statin, known for their immunomodulatory and anti-inflammatory activities. Recent studies provide evidence of potential therapeutic effect of statins on lung injury. Adipose derived stem cells (ADSCs) have shown great promise in the repair of various tissues. The present study aimed at investigating and comparing the possible therapeutic effect of A and ADSCs on AM induced lung injury in albino rats. METHODS AND RESULTS: 34 adult male albino rats were divided into 5 groups: control group (Gp I), A group (Gp II) received 10 mg/kg of A orally 6 days (d)/week (w) for 4 weeks (ws), AM group (Gp III) received 30 mg/kg of AM orally 6 d/w for 4 ws, AM&A group (Gp IV) received AM for 4ws then A for other 4 ws and AM&SCs group (Gp V) received AM for 4 ws then injected with 0.5 ml ADSCs on 2 successive days intravenously (IV). Histological, histochemical, immunohistochemical and morphometric studies were performed. Group III displayed bronchiolitis obliterans, thickened interalveolar septa (IAS) and thickened vascular wall which were proven morphometrically. Increased area% of collagen fibers and apoptotic changes were recorded. All findings regressed on A administration and ADSCs therapy. CONCLUSION: Ator proved a definite ameliorating effect on the degenerative, inflammatory, apoptotic and fibrotic changes induced by AM. ADSCs administration denoted more remarkable therapeutic effect compared to A.

Molecular characterization of Escherichia coli O157:H7 recovered from meat and meat products relevant to human health in Riyadh, Saudi Arabia.

Raw meat can harbor pathogenic bacteria, potentially harmful to humans such as Escherichia coli O157:H7 causing diarrhea and hemolytic-uremic syndrome (HS). Therefore, the current study was carried out to evaluate the prevalence and the molecular detection characterization of E. coli serotype O157:H7 recovered from raw meat and meat products collected from Saudi Arabia. During the period of 25th January 2013 to 25th March 2014, 370 meat samples were collected from abattoirs and markets located in Riyadh, Saudi Arabia "200 raw meat samples and 170 meat products". Bacteriological analysis of the meat samples and serotyping of the isolated E. coli revealed the isolation of 11 (2.97%) strains of E. coli O157:H7. Isolation of E. coli O157:H7 in raw beef, chicken and mutton were 2%, 2.5%, and 2.5%, respectively, however, there was no occurrence in raw turkey. The incidences of E. coli O157:H7 in ground beef, beef burgers, beef sausage, ground chicken and chicken burgers were 5%, 10%, 0.0%, 5% and 0.0%, respectively. The multiplex PCR assay revealed that 3 (27.27%) out of 11 E. coli O157:H7 isolates from raw beef, chicken and mutton had stx1, stx2, and eae while 5 (45.45%) E. coli O157:H7 isolates from ground beef, ground chicken, and raw beef had both stx1 and stx2. However, from beef burgers, only one E. coli O157:H7 isolate had stx1 while two were positive for hlyA gene. These results call for urgent attention toward appropriate controls and good hygienic practices in dealing with raw meat.

Alterations in circulating angiogenic and anti-angiogenic factors in type 2 diabetic patients with neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. There is an increased attention directed towards the role of angiogenic factors including vascular endothelial growth factor (VEGF) and anti-angiogenic factors including soluble endoglin (sEng) as contributors to diabetic microvascular complications including neuropathy. The purposes of this study were to determine the role of these angiogenesis regulators in the prognosis of DPN. The study group included 60 patients with type 2 diabetes mellitus (T2DM) and 20 clinically healthy individuals. The patients were divided into two groups. Group I included 20 T2DM patients without peripheral neuropathy, and Group II consisted of 40 T2DM patients with DPN. In all groups, plasma VEGF, sEng and endothelin-1 (ET-1), nitric oxide and ET-1 mRNA were estimated. Plasma levels of VEGF, sEng, ET-1 and nitric oxide were significantly elevated in diabetic patients (Groups I and II) compared with healthy control subjects, with a higher increase in their levels in patients with DPN compared with diabetic patients without peripheral neuropathy. Measurement of plasma levels of angiogenesis-related biomarkers in high-risk diabetic patients might identify who later develop DPN, thus providing opportunities for early detection and targets for novel treatments.

Blood heat shock proteins evoked by some Salmonella strains infection in ducks.

Bacterial heat-shock response is a global regulatory system required for effective adaptation to changes (stress) in the environment. An in vitro study was conducted to investigate the impact of a sublethal temperature (42°C) on heat shock protein (HSP) expression in 6 Salmonella strains (Salmonella Enteritidis, S. Typhimurium, S. Virchow, S. Shubra, S. Haifa and S. Eingedi). The 6 Salmonella strains were isolated from the tissues of ducklings that had died from avian salmonellosis. To determine the induction of HSP in the 6 Salmonella strains, they were exposed to the selected temperature level for 24 h and further kept for 48 h at culturing condition of 42°C. Growth under a sublethal temperature of 42°C increased the expression of several proteins of Salmonella, including a 63 kDa protein in addition to the generation and/or overexpression of 143 proteins which were specific to heat shock, concurrent to this acquired thermotolerance. The 6 Salmonella strains responded to 24 h of thermal stress at an elevated temperature 42°C by synthesizing different heat shock proteins (HSP) with molecular weights ranging between 13.62 and 96.61 kDa. At 48 h, the 6 Salmonella strains synthesized different HSPs with molecular weights ranging between 14.53 and 103.43 kDa. It follows that salmonellae would produce HSPs during the course of the infectious process. Salmonellosis produced several proteins after 24 and 48 h of infection. Seven of these proteins (100, 80, 60, 40, 30, 20 and 10 kDa) were recognized in the serum obtained from the ducklings infected with S. Enteritidis, S. Typhimurium, S. Virchow, S. Shubra, S. Haifa and S. Eingedi after 24 h of infection. After 48 h, the 1-7 kDa HSP became more evident and indicated their de novo generation.

Effect of EDTA and phosphoric Acid pretreatment on the bonding effectiveness of self-etch adhesives to ground enamel.

OBJECTIVES: This in vitro study determined the effect of enamel pretreatment with phosphoric acid and ethylenediaminetetraacetic acid (EDTA) on the bond strength of strong, intermediary strong, and mild self-etching adhesive systems. METHODS: Ninety sound human premolars were used. Resin composite cylinders were bonded to flat ground enamel surfaces using three self-etching adhesive systems: strong Adper Prompt L-Pop (pH=0.9-1.0), intermediary strong AdheSE (pH=1.6-1.7), and mild Frog (pH=2). Adhesive systems were applied either according to manufacturer instructions (control) or after pretreatment with either phosphoric acid or EDTA (n=10). After 24 hours, shear bond strength was tested using a universal testing machine at a cross-head speed of 0.5 mm/minute. Ultra-morphological characterization of the surface topography and resin/enamel interfaces as well as representative fractured enamel specimens were examined using scanning electron microscopy (SEM). RESULTS: Neither surface pretreatment statistically increased the mean shear bond strength values of either the strong or the intermediary strong self-etching adhesive systems. However, phosphoric acid pretreatment significantly increased the mean shear bond strength values of the mild self-etching adhesive system. SEM examination of enamel surface topography showed that phosphoric acid pretreatment deepened the same etching pattern of the strong and intermediary strong adhesive systems but converted the irregular etching pattern of the mild self-etching adhesive system to a regular etching pattern. SEM examination of the resin/enamel interface revealed that deepening of the etching pattern was consistent with increase in the length of resin tags. EDTA pretreatment had a negligible effect on ultra-morphological features. CONCLUSIONS: Use of phosphoric acid pretreatment can be beneficial with mild self-etching adhesive systems for bonding to enamel.

The impact of staphylococcal mastitis on the level of milk IL-6, lysozyme and nitric oxide.

Mammary gland secretions derived from secretory cows infected with coagulase +ve Staphylococcus spp. was examined for the expression of IL-6, production of lysozyme and NO(x). The examined cows reflected 25 cases of subclinical mastitis and 15 cases of clinically mastitic animals. The IL-6 concentration in the subclinical animals was significantly higher (30.8 ng/ml) than the clinically manifested animals (18.0 ng/ml) and the normal cows (5.2n g/ml). On the other hand the level of lysozyme although significantly higher than the normal cows (6.9 microg/ml) yet its level in the subclinical animals (11.2 microg/ml) was lower than that estimated in the clinical animals (15.6 microg/ml). Similarly, the level of NO(x) in the normal animals was found to be 5.6 microM/ml to increase to 6.2 microM/ml in the subclinical mastitic animals and to significantly increase further to 11.5 microM/ml in the clinically affected cows. These results suggest the promising use of whey IL-6, lysozyme or/and NO concentration variabilities as prognostic parameters on the degree of the commencement of mastitis in cows.