Defining the distinct, intrinsic properties of the novel type I interferon, IFNϵ.

The type I interferons (IFNs) are a family of cytokines with diverse biological activities, including antiviral, antiproliferative, and immunoregulatory functions. The discovery of the hormonally regulated, constitutively expressed IFNϵ has suggested a function for IFNs in reproductive tract homeostasis and protection from infections, but its intrinsic activities are untested. We report here the expression, purification, and functional characterization of murine IFNϵ (mIFNϵ). Recombinant mIFNϵ (rmIFNϵ) exhibited an α-helical fold characteristic of type I IFNs and bound to IFNα/ß receptor 1 (IFNAR1) and IFNAR2, but, unusually, it had a preference for IFNAR1. Nevertheless, rmIFNϵ induced typical type I IFN signaling activity, including STAT1 phosphorylation and activation of canonical type I IFN signaling reporters, demonstrating that it uses the JAK-STAT signaling pathway. We also found that rmIFNϵ induces the activation of T, B, and NK cells and exhibits antiviral, antiproliferative, and antibacterial activities typical of type I IFNs, albeit with 100-1000-fold reduced potency compared with rmIFNα1 and rmIFNß. Surprisingly, although the type I IFNs generally do not display cross-species activities, rmIFNϵ exhibited high antiviral activity on human cells, suppressing HIV replication and inducing the expression of known HIV restriction factors in human lymphocytes. Our findings define the intrinsic properties of murine IFNϵ, indicating that it distinctly interacts with IFNAR and elicits pathogen-suppressing activity with a potency enabling host defense but with limited toxicity, appropriate for a protein expressed constitutively in a sensitive mucosal site, such as the reproductive tract.

Interferon epsilon promotes HIV restriction at multiple steps of viral replication.

Interferon epsilon (IFNɛ) is a type I IFN that is expressed constitutively in the female reproductive tract (FRT), and contributes to protection in models of sexually transmitted infections. Using multiple cell systems, including reporter cell lines and activated peripheral blood lymphocytes (PBLs), we show that recombinant IFNɛ impairs HIV infection at stage(s) post HIV entry and up to the translation of viral proteins. Consistent with this, IFNɛ upregulated a number of host cell restriction factors that block HIV at these stages of the replication cycle. The potency of IFNɛ induction of these HIV restriction factors was comparable to conventional type I IFNs, namely IFNα and IFNß. IFNɛ also significantly reduced the infectivity of progeny virion particles likely by inducing expression of HIV restriction factors, such as IFITM3, which act at that stage of infection. Thus, our data demonstrate that human IFNɛ suppresses HIV replication at multiple stages of infection.

Children patients with COVID-19: How can parental and peer support lessen the psychological burden of isolation.

AIM: To assess the effect of parental and peer support on children's self-esteem during the isolation period in COVID-19-infected children is the main objective of this study. DESIGN: This is a descriptive cross-sectional study. One hundred ninety children with a confirmed diagnosis of COVID-19 were included. METHODS: A survey questionnaire to assess family and children's demographic characteristics was used for this study. A 13-item scale to assess parental support during the isolation period and a 10-item scale to assess peers' support during the isolation period were evaluated. Along with it, a 10-item scale to assess self-esteem during the isolation period was also measured. RESULTS: Home isolation was associated with higher parental and peer support scores than hospital isolation. The mean age of study participants was 13.23 ± 4.05 years; 52.6% were isolated at home versus 47.4% in hospital isolation. Phone calling and WhatsApp/messenger chat were methods of communication for 44.2% and 33.2% of patients, respectively. 6.3% of them had no method of communication. Child self-esteem was significantly affected by both parental and peer support during isolation. The increase in pronounced negative psychological effects such as disorientation, anger, low self-esteem and post-traumatic distress may be caused by a lack of parental care. NO PATIENT OR PUBLIC CONTRIBUTION TO THIS STUDY: Patients or the general public were not involved in the design, analysis or interpretation of the data in this study. The study's aim and objectives were developed based on children's self-esteem, which was limited by questionnaire data information, so the researchers completed demographic and disease-related questionnaires by interviewing them.

Novel multi epitope-based vaccine against monkeypox virus: vaccinomic approach.

While mankind is still dealing with the COVID-19 pandemic, a case of monkeypox virus (MPXV) has been reported to the WHO on May 7, 2022. Monkeypox is a viral zoonotic disease that has been a public health threat, particularly in Africa. However, it has recently expanded to other parts of the world, so it may soon become a global issue. Thus, the current work was planned and then designed a multi-epitope vaccine against MPXV utilizing the cell surface-binding protein as a target in order to develop a novel and safe vaccine that can evoke the desirable immunological response. The proposed MHC-I, MHC-II, and B-cell epitopes were selected to design multi-epitope vaccine constructs linked with suitable linkers in combination with different adjuvants to enhance the immune responses for the vaccine constructs. The proposed vaccine was composed of 275 amino acids and was shown to be antigenic in Vaxijen server (0.5311) and non-allergenic in AllerTop server. The 3D structure of the designed vaccine was predicted, refined and validated by various in silico tools to assess the stability of the vaccine. Moreover, the solubility of the vaccine construct was found greater than the average solubility provided by protein-Sol server which indicating the solubility of the vaccine construct. Additionally, the most promising epitopes bound to MHC I and MHC II alleles were found having good binding affinities with low energies ranging between - 7.0 and - 8.6 kcal/mol. According to the immunological simulation research, the vaccine was found to elicit a particular immune reaction against the monkeypox virus. Finally, the molecular dynamic study shows that the designed vaccine is stable with minimum RMSF against MHC I allele. We conclude from our research that the cell surface-binding protein is one of the primary proteins involved in MPXV pathogenesis. As a result, our study will aid in the development of appropriate therapeutics and prompt the development of future vaccines against MPXV.

Prevalence, Predictors, and Awareness of Coffee Consumption and Its Trend among Saudi Female Students.

This study aimed to investigate the prevalence, trends, and predictors of coffee consumption among Saudi female students and its association with anthropometric and demographic variables. A survey-based study using a face-to-face interview was designed, and 930 (aged 21.5 ± 2.1 years) apparently healthy female students from different departments of King Saud University participated. The prevalence of coffee consumption was significantly higher (88.2%, p < 0.03) in the central Riyadh region. Coffee consumers had significantly higher prevalence of being overweight than non-consumers (p = 0.02). The frequency of coffee consumption was significantly higher (p < 0.02) in students who were single and belonged to families with a moderate income level. Coffee consumption was significantly higher among first-year students with a high-scale grade point average (GPA) (p < 0.001 and p = 0.03, respectively). Increased coffee consumption during exam and stress conditions was associated with unhealthy dietary habits such as using more sugar and spices. The prevalence of coffee consumption was high among Saudi females. High body mass index (BMI) and increased family income level were strong determinants for coffee consumption. Continued nutritional education and awareness about the potential positive and negative health effects of coffee consumption and the importance of food label use should be provided to younger generations in order to correct the wrong perceptions.

Impact of non-selective beta blockers on portal hypertension and hepatic elasticity in hepatitis C virus-related liver cirrhosis.

Portal hypertension and its complications are the leading causes of morbidity and mortality in patients with liver cirrhosis. Noninvasive assessment of liver stiffness had been an effective tool for assessment of fibrosis progression in chronic liver disease. It was intended to assess liver stiffness measurement (LSM), portal vein diameter (PVD), splenic bipolar diameter (SD), and the platelet count/spleen diameter (PC/SD) ratio in patients who test positive for the hepatitis C virus (HCV) and to study the impact of non-selective beta blockers (NSBB) on the grade of esophageal varices (EVs) and liver elasticity. Subjects were 80 patients with Child-Pugh grade A or B compensated cirrhosis who tested positive for HCV. All of the patients underwent a laboratory workup including AFP, HCV antibodies, HCV RNA, HBsAg, LSM according to real-time elastography, upper gastrointestinal endoscopy (UGIE) to detect and grade EVs, calculation of the PC/SD ratio, and measurement of the PVD and SD according to real-time abdominal ultrasonography. All patients were given the maximum tolerated dose of NSBB for three months, and UGIE, LSM, PC/SD, PVD, and SD were subsequently reassessed and reported. LSM and the PC/SD ratio were exceptional noninvasive tools for prediction of significant EVs (grade ≥ II, p < 0.001) with a sensitivity 82.4% and a specificity 82.6% at a cutoff point 18 kPa for LSM, and a sensitivity 94.1% and specificity 69.6% at a cutoff point 880 for the PC/SD ratio. LSM is highly correlated with PVD, the PC/SD ratio, SD, and the Child-Pugh score. NSBB significantly decreased PVD. The percent change in PVD significantly correlated with LSM, the grade of EVs, and SD. Findings indicated that LSM is a noninvasive, rapid, and reproducible tool with which to detect portal hypertension and EVs. NSBB therapy can effectively decrease PVD and may consequently improve the EV grade with no significant impact on LSM in patients with liver cirrhosis.

Association between Serum Phospholipid Fatty Acid Levels and Adiposity among Lebanese Adults: A Cross-Sectional Study.

There have been increases in the incidence of obesity in Lebanon over the past few decades. Fatty acid intake and metabolism have been postulated to influence obesity, but few epidemiological studies have been conducted. The aim of this study was to investigate the correlation between serum fatty acid levels and indicators of obesity in a cross-sectional study nested within a cohort of 501 Lebanese adults residing in Greater Beirut. A total of 395 available serum samples (129 men, 266 women) were profiled for phospholipid fatty acid composition. Spearman correlation coefficients adjusted for relevant confounders and corrected for multiple testing were calculated between serum fatty acids, desaturation indices, and indicators of adiposity (body mass index (BMI) and waist). BMI was significantly positively correlated with saturated fatty acids in men (r = 0.40, p < 0.0001, q < 0.0001) and women (r = 0.33, p < 0.0001, q < 0.0001). BMI was significantly positively correlated with monounsaturated fatty acid palmitoleic acid in women (r = 0.15, p = 0.01, q = 0.03). This study suggests that high blood levels of some saturated fatty acids and the monounsaturated fatty acid palmitoleic acid, likely derived from both dietary intakes of saturated fatty acids and endogenous lipogenesis, may have been associated with adiposity in the Lebanese population. The causality of these associations needs to be explored in experimental settings.

The natural history of aortic valve disease after mitral valve surgery.

OBJECTIVES: The present study evaluates the long-term course of aortic valve disease and the need for aortic valve surgery in patients with rheumatic mitral valve disease who underwent mitral valve surgery. BACKGROUND: Little is known about the natural history of aortic valve disease in patients undergoing mitral valve surgery for rheumatic mitral valve disease. In addition there is no firm policy regarding the appropriate treatment of mild aortic valve disease while replacing the mitral valve. METHODS: One-hundred thirty-one patients (44 male, 87 female; mean age 61+/-13 yr, range 35 to 89) were followed after mitral valve surgery for a mean period of 13+/-7 years. All patients had rheumatic heart disease. Aortic valve function was assessed preoperatively by cardiac catheterization and during follow-up by transthoracic echocardiography. RESULTS: At the time of mitral valve surgery, 59 patients (45%) had mild aortic valve disease: 7 (5%) aortic stenosis (AS), 58 (44%) aortic regurgitation (AR). At the end of follow-up, 96 patients (73%) had aortic valve disease: 33 AS (mild or moderate except in two cases) and 90 AR (mild or moderate except in one case). Among patients without aortic valve disease at the time of the mitral valve surgery, only three patients developed significant aortic valve disease after 25 years of follow-up procedures. Disease progression was noted in three of the seven patients with AS (2 to severe) and in six of the fifty eight with AR (1 to severe). Fifty two (90%) with mild AR remained stable after a mean follow-up period of 16 years. In only three patients (2%) the aortic valve disease progressed significantly after 9, 17 and 22 years. In only six patients of the entire cohort (5%), aortic valve replacement was needed after a mean period of 21 years (range 15 to 33). In four of them the primary indication for the second surgery was dysfunction of the prosthetic mitral valve. CONCLUSIONS: Our findings indicate that, among patients with rheumatic heart disease, a considerable number of patients have mild aortic valve disease at the time of mitral valve surgery. Yet most do not progress to severe disease, and aortic valve replacement is rarely needed after a long follow-up period. Thus, prophylactic valve replacement is not indicated in these cases.

Blocking HIV-1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses.

The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV-1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract.

Acute myocardial infarction immediately after heart transplantation.

Myocardial infarction is one of the rarer events causing acute graft failure during the postoperative period after transplantation and is usually caused by preexisting coronary artery disease of the donor heart. We discuss the case of a 56-year-old man in whom cardiogenic shock developed after heart transplantation, which was refractory to all medical treatment. He was put on emergency code and underwent retransplantation 30 hours later. Pathologic examination of the explanted donor heart showed massive recent inferior and posterior wall infarction, with normal coronary arteries; the right coronary artery was dominant and completely occluded by an embolus of fatty material surrounded by fibrin, which we suggest could have originated from the suture line of the left atrium.

Iatrogenic left ventricular-right atrial fistula following mitral valve replacement and tricuspid annuloplasty: diagnosis by transthoracic and transesophageal echocardiography.

Acquired left ventricle-to-right atrium communications are a known complication of valvular heart surgery. Previous reports have described the clinical features and diagnosis using cardiac catheterization. We report two cases of acquired left ventricle-to-right atrium fistula following mitral valve replacement. Particular emphasis is placed on the diagnosis using transthoracic and transesophageal echocardiography, obviating the need for cardiac catheterization before repair.

Tricuspid regurgitation late after mitral valve replacement: clinical and echocardiographic evaluation.

BACKGROUND AND AIM OF THE STUDY: Significant tricuspid regurgitation (TR) can contribute to increased morbidity and mortality in patients after mitral valve replacement (MVR), both in the immediate and late postoperative period. The aim of this study was to evaluate the prevalence and the clinical importance of TR late after MVR, as assessed both clinically and echocardiographically. METHODS: The study group comprised 65 patients (39 women, 26 men; mean age 61+/-12 years) with rheumatic heart disease who had undergone MVR without tricuspid valve surgery between one and 30 years (mean 11.3+/-8 years) before their last clinical examination. All patients underwent a complete color-Doppler echocardiographic examination. The predominant presurgical mitral lesion was stenosis in 44 patients and regurgitation in 21. The severity of the tricuspid valve disease was assessed echocardiographically using color-Doppler flow images and flow direction in the inferior vena cava or hepatic veins, and by clinical evaluation. RESULTS: Echocardiography revealed significant late TR in 44 patients (67%), which was moderate in 16 and severe in 28, and evident on physical examination in 24 cases (37%). Age (relative risk (RR) = 1.1; C.I. 1-1.1) and female sex (RR = 1.8; C.I. = 1.0-3.2) were identified as statistically significant predictors for late clinical TR development, but only age was found as a statistically significant predictor for echocardiographic TR development. An elevated RR for organic TR and predominant mitral regurgitation was found. In contrast, pre- and postoperative pulmonary artery pressure, predominant mitral lesion, prosthetic valve gradient and regurgitation were similar in patients with and without late TR. CONCLUSIONS: Significant TR diagnosed by echocardiography late after MVR is common, and clinically evident in more than one-third of patients. Therefore, a lower threshold for tricuspid valve repair should be considered when mitral valve surgery is carried out.

Outcome and risk factors in octogenarians undergoing open-heart surgery.

BACKGROUND AND AIM OF THE STUDY: Increasing numbers of elderly (aged > 80 years) patients are being referred for cardiac surgery, and results for coronary artery bypass grafting (CABG) are generally better than for combined CABG and valve replacement. METHODS: During the past 55 months, 77 octogenarians underwent cardiac intervention in our institution. Forty-five patients (mean age 82.5 years) underwent CABG alone; surgery was elective in 33% of patients and 2.7 +/- 1.0 grafts per patient were performed. Thirty-two patients (mean age 82.4 years) underwent combined CABG and valve surgery (28 aortic, four mitral); 2.1 +/- 0.8 grafts per patient were performed and 65% of cases were emergencies. RESULTS: In patients undergoing CABG alone, the operative mortality rate was 2% and rose to 4% (n = 2) at the end of follow up. Mean NYHA functional class improved significantly from 3.5 +/- 0.5 to 1.4 +/- 0.3 after surgery (p < 0.05) and most patients reported marked improvement in their quality of life. In CABG + valve surgery patients, the operative mortality rate was 6% (n = 2) and reached 18% by the end of follow up. In these patients the complication rate was 24% and mean hospitalization stay 11.0 +/- 2.9 days, while mean NYHA functional class improved from 3.4 +/- 0.6 to 1.2 +/- 0.5. Data analysis revealed that mitral regurgitation combined with coronary artery disease (p < 0.03) and prolonged cross-clamping time (p < 0.01) were the most important independent factors for mortality. CONCLUSION: This study confirms that, in selected elderly patients, combined CABG and cardiac surgery can achieve good postoperative results.

Surgical management of ventricular septal defect with aortic valve prolapse: clinical considerations and results.

Aortic valve prolapse is found in over 5% of children with ventricular septal defect (VSD). Although this association occurs mostly with doubly committed subarterial VSDs, in this study the predominant type of VSD was perimembranous. In order to determine the need and timing for surgery and whether the anatomical features of septal defect may influence clinical management and outcome in this lesion, we reviewed our experience with 28 consecutive patients, operated on for VSD with prolapsed aortic valve cusp, with or without aortic regurgitation. Twenty-two patients had a perimembranous VSD and six had doubly committed VSD. Aortic regurgitation was trivial or absent in nine patients, mild in ten and moderate to severe in nine. Associated cardiac anomalies were present in 18 patients, all having perimembranous VSD, and included right ventricular outflow tract (RVOT) obstruction (n = 6), discrete subaortic membrane (n = 4) or both (n = 8). None of these patients had more than moderate aortic regurgitation. The patients underwent surgical closure of the septal defect between the ages of 1.5 and 34 years of age (median = 7). Sixteen patients having mild or trivial aortic regurgitation underwent closure of the VSD only, and 12 patients underwent VSD closure with aortic valvuloplasty. Valvuloplasty was required more often in doubly committed VSDs (66%) and in the perimembranous type without associated anomalies (100%), and significantly less often in the presence of RVOT obstruction, subaortic membrane or both (22%). At follow-up (up to 5 years, mean 18 months), the grade of aortic regurgitation was unchanged in 11 and decreased in 5 patients undergoing closure of the VSD only.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial effect of aspirin on renal function in patients with renal insufficiency postcardiac surgery.

AIM: Renal function is one of the most important prognostic factors following cardiac surgery. Whether aspirin affects cardiopulmonary bypass related renal injury is investigated in this study. METHODS: Ninety-four patients with impaired renal function (creatinine = or >1.5 mg/dl) undergoing coronary artery bypass grafting (CABG) were categorized into 2 groups according to aspirin administration before surgery. Serum creatinine, urinary output and creatinine clearance along with other perioperative factors were compared between the 2 groups prior to surgery, 24 hours and 48 hours following cardiopulmonary bypass. RESULTS: Creatinine levels increased significantly in the second postoperative day only in the non-aspirin (control) group (3.7+/-1.6 vs 2.9+/-1.7 mg/dl, p=0.03). Aspirin (study) group had lower creatinine levels in day 1 (p=0.03) and day 2 (p=0.001). Furthermore, in the study group creatinine clearance was higher in day 1 (34.3+/-14.3 vs 30.9+/-13.1 ml/min, p=0.01) and in day 2 (32.6+/-13.8 vs 26.4+/-9.8 ml, p<0.0001). Creatinine levels at discharge were elevated compared to the preoperative levels in the control group (p=0.01). However, the study group had lower creatinine levels at discharge (2.6+/-1.4 vs 3.8+/-1.6 mg/dl, p<0.0001). Urinary output was higher in the study group in the first postoperative day compared to the control group (p=0.01). Postoperative bleeding was slightly increased in the study group compared to the control group (760+/-230 ml vs 530+/-210 ml, p=0.01). CONCLUSIONS: Continuation of aspirin administration until the day of surgery may have a protective effect against renal injury resulting from cardiopulmonary bypass, with only a negligible increase in bleeding. Possible explanations for this effect are antiplatelet activity of aspirin during cardiopulmonary bypass causing inhibition of vasoconstrictive agents like thromboxane, and improvement of renal perfusion by reducing blood viscosity.

Cardiac surgery in octogenarians.

Age as an important risk factor in surgery has always been debatable. Between January 1991 and December 1992, 35 consecutive octogenarian patients (23 males and 12 females; average age 82.3 years) were retrospectively evaluated. Twenty-five patients had only coronary artery by-pass graft operations (CABG), five had aortic valve replacements (AVR) and five had combined AVR-CABG operations. Twenty-five of the 30 patients (83%) who underwent CABG alone or a combined procedure had suffered from unstable angina. The mean ejection fraction was 40% in this group. An average of 2.8 grafts per patient was performed. The left internal mammary artery (LIMA) was-used in nine patients (30%). The average hospitalization period was 11.5 days. Operative mortality (within 30 days) was zero. Patients who underwent AVR only were hospitalized for an average of 17.6 days and there were two cases (6%) of mortality in this group. All patients who underwent AVR and CABG were discharged within 14 days. Overall complications occurred in nine patients (25.7%); cardiac arrythmias, (4) neurological deficits (2), severe wound infections (2), and adult respiratory distress syndrome (1). The use of the LIMA was not associated with an increased incidence of bleeding or sternal infection. The low rates of mortality and major complications lead us to conclude that, when indicated, surgical treatment including the use of LIMA in selected cases, should be offered to this group of patients, even in the presence of moderate LV dysfunction.

Massive spontaneous hemothorax as a presenting sign of aneurysmal rupture of the internal thoracic artery. A case report.

Massive spontaneous hemothorax is a very uncommon, life-threatening situation. Acute dissection and ruptured aorta can be one of the differential diagnoses, but usually the clinical feature is completely different, and very few patients have survived this event and received medical attention. Among other causes of spontaneous bleeding, some are extremely rare, demanding precise diagnosis and judicial and immediate intervention. We describe a patient who presented with a massive hemothorax. There was no immediately apparent cause. Emergent angiography revealed active bleeding from an extremely unusual source: aneurysmal dilatation of the internal thoracic artery.

Evaluation of different therapeutic approaches for spontaneous bacterial peritonitis.

BACKGROUND AND STUDY AIMS: Spontaneous bacterial peritonitis (SBP) is a significant cause of mortality in cirrhosis. Reducing toxic burden of infected ascitic fluid through paracentesis needs further studies as adjunctive therapy of SBP. We aimed to evaluate different therapies for SBP. PATIENTS AND METHODS: Thirty-six cirrhotic ascitic patients with SBP were examined and classified according to treatment modality (5-7 days) into: Group A received cefotaxime, group B received cefotaxime and albumin 1.5 g/kg body weight within 6h of SBP being diagnosed and 1g/kg body weight on day 3, group C received cefotaxime and paracentesis with volume dependent albumin infusion. Control group of 12 cirrhotic ascitic patients free from SBP were included. Routine laboratory tests, ascitic fluid analysis for leucocytes and culture were done, inflammatory mediators such as nitric oxide and tumour necrosis factor alpha were measured in serum and ascitic fluid. Duplex-Doppler assessment of portal flow volume and renal resistive index, Echocardiography to measure end diastolic and end systolic volumes, stroke volume and cardiac output were done. Tests were carried out before and after therapy. RESULTS: Treatment response was assessed by, cardiac haemodynamics, portal and renal flow and NO and TNF. All studied parameters; laboratory, cardiac, Doppler exhibited a significant improvement in group B in contrast to the other groups as demonstrated by post therapy reduction of (blood and ascitic fluid WBCs & PNLS, serum and ascitic NO & TNF and renal resistive index), elevation of (serum albumin and portal flow volume) and improvement of cardiac haemodynamic. CONCLUSION: Treatment of spontaneous bacterial peritonitis by cefotaxime and body weight based albumin infusion gave most favourable results compared to other regimens. Postulation of removing toxic burden through paracentesis has not been confirmed.