Novel Mediastinoscope-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Minimally invasive surgery is an expanding field of surgery that has replaced many open surgical techniques. Surgery remains a cornerstone in the treatment of esophageal cancer, yet it is still associated with significant morbidity and technical difficulties. Mediastinoscope-assisted esophagectomy is a promising technique that aims to decrease the surgical burden and enhance recovery. METHODS: PubMed, MEDLINE, and EMBASE databases were searched for publications on mediastinoscope-assisted esophagectomies for esophageal cancer. The primary endpoint was a postoperative anastomotic leak, while secondary endpoints were assessment of harvested lymph nodes (LNs), blood loss, chyle leak, hospital length of stay (LOS), operative (OR) time, pneumonia, wound infection, mortality, and microscopic positive margin (R1). The pooled event rate (PER) and pooled mean were calculated for binary and continuous outcomes respectively. RESULTS: Twenty-six out of the 2274 searched studies were included. The pooled event rate (PER) for anastomotic leak was 0.145 (0.1144; 0.1828). The PERs for chyle leak, recurrent laryngeal nerve injury/hoarseness, postoperative pneumonia, wound infection, early mortality, postoperative morbidity, and microscopically positive (R1) resection margins were 0.027, 0.185, 0.09, 0.083, 0.020, 0.378, and 0.037 respectively. The pooled means for blood loss, hospital stay, operative time, number of total harvested LNs, and number of harvested thoracic LNs were 159.209, 15.187, 311.116, 23.379, and 15.458 respectively. CONCLUSIONS: Mediastinoscopic esophagectomy is a promising minimally invasive technique, avoiding thoracotomy, patient repositioning, and lung manipulation; thus allowing for shorter surgery, decreased blood loss, and decreased postoperative morbidity. It can also be reliable in terms of oncological safety and LN dissection.

Prevalence of gastro-oesophageal reflux disease, and its associated risk factors among medical students: a nation-based cross-sectional study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common digestive problem in adults particularly medical students, who are one of the most vulnerable groups. Many variables, including lifestyle changes and psychological stress, increase the prevalence of GERD among undergraduate medical students. Therefore, this study aims to assess the prevalence, and risk factors of GERD, and its relationship with perceived stress among medical students in Egypt. METHODS: In November and December of 2022, a cross-sectional descriptive study with an analytical component was carried out among medical students from six different universities. An online self-reported questionnaire was used to collect data. The questionnaire included data on sociodemographic characteristics, risk factors, lifestyle, the Arabic version of GerdQ, and the Arabic version of Cohen's Perceived Stress Scale (PSS). RESULTS: The questionnaire was filled out by 964 medical students, the majority of whom were female (64%). Overall, 17.1% of participants reported symptoms of GERD. Logistic regression showed that smoking, high perceived stress, and a family history of GERD were the independent predictors of having GERD symptoms, with odds ratios of 4.1, 3.9, and 2.2, respectively. CONCLUSION: GERD is a frequent condition among Egyptian medical students, affecting around one-fifth of them. In the fight against GERD, university-based smoking cessation and stress management programs may be influential.

Heart failure in low- and middle-income countries: background, rationale, and design of the INTERnational Congestive Heart Failure Study (INTER-CHF).

BACKGROUND: Although heart failure (HF) has been referred to as a global epidemic, most HF information comes from high-income countries, with little information about low-income countries (LIC) and middle-income countries (MIC) in Africa, Asia, the Middle East, and South America, which make up the majority of the world's population. METHODS: The INTERnational Congestive Heart Failure Study is a cohort study of 5,813 HF patients enrolled in 108 centers in 16 LIC and MIC. At baseline, data were recorded on sociodemographic and clinical risk factors, HF etiology, laboratory variables, management, and barriers to evidence-based HF care at the patient, physician, and system levels. We sought to enroll consecutive and consenting patients ≥18 years of age with a clinical diagnosis of HF seen in outpatient clinics (2/3 of patients) or inpatient hospital wards (1/3 of patients). Patients were followed up at 6 and 12 months post-enrollment to record clinical status, treatments, and clinical outcomes such as death and hospitalizations. In the 5,813 enrolled HF patients, the mean age was 59 ± 15 years, 40% were female, 62% had a history of hypertension, 30% had diabetes, 21% had prior myocardial infarction, 64% were recruited from outpatient clinics, 36% lived in rural areas, and 29% had HF with preserved left ventricular ejection fraction. CONCLUSIONS: This unique HF registry aims to systematically gather information on sociodemographic and clinical risk factors, etiologies, treatments, barriers to evidence-based care, and outcomes of HF in LIC and MIC. This information will help improve the management of HF globally.

The efficacy and safety of new potassium binders on renin-angiotensin-aldosterone system inhibitor optimization in heart failure patients: a systematic review and meta-analysis.

Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure, including the use of renin-angiotensin-aldosterone system inhibitors, which can hinder the excretion of potassium, resulting in hyperkalaemia. New potassium binders (NPBs) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, Scopus, and Cochrane through 26 April 2023. The risk of bias assessment was conducted, following Cochrane's updated Risk of Bias 2 assessment tool. We used the fixed-effects model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI) (PROSPERO ID: CRD42023426113). We included six RCTs with a total of 1432 patients. NPB was significantly associated with successful mineralocorticoid receptor antagonist (MRA) optimization [RR: 1.13 with 95% CI (1.02-1.25), P = 0.02], decreased patients with MRA at less than the target dose [RR: 0.72 with 95% CI (0.57-0.90), P = 0.004], and decreased hyperkalaemic episodes [RR: 0.42 with 95% CI (0.24-0.72), P = 0.002]. However, there was no difference between NPB and placebo regarding angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB)/angiotensin receptor/neprilysin inhibitor (ANRi) optimization [RR: 1.02 with 95% CI (0.89-1.17), P = 0.76] and serum potassium change [MD: -0.31 with 95% CI (-0.61 to 0.00), P = 0.05], with an acceptable safety profile except for the increased incidence of hypokalaemia with NPB [RR: 1.57 with 95% CI (1.12-2.21), P = 0.009]. NPB has been shown to improve GDMT outcomes by enhancing MRA optimization and reducing hyperkalaemic episodes. However, there are limited data on the effects of NPB on ACEi/ARB/ANRi optimization. Future RCTs should investigate ACEi/ARB/ANRi optimization and conduct head-to-head comparisons of NPB (patiromer and sodium zirconium cyclosilicate).

Once-weekly Insulin Icodec Versus Once-daily Long-acting Insulin for Type II Diabetes: A Meta-analysis of Randomized Controlled Trials.

Background: Insulin icodec is a novel basal insulin analog with once-weekly subcutaneous administration. We aim to estimate the efficacy and safety of insulin icodec vs long-acting insulin (insulin glargine and degludec) in type II diabetic patients. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through May 29, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Our primary outcome was glycated hemoglobin (HbA1C) change. Results: We included 7 RCTs with a total of 3183 patients. Insulin icodec was associated with significantly decreased HbA1C (MD: -0.15 with 95% CI [-0.24, -0.06], P = .002) and increased percentage of time with glucose in range (TIR) (MD: 4.06 with 95% CI [2.06, 6.06], P = .0001). However, insulin icodec was associated with increased body weight (MD: 0.57 with 95% CI [0.45, 0.70], P = .00001). Also, there was no difference regarding any serious adverse events (AEs) (RR: 0.96 with 95% CI [0.76, 1.20], P = .7) or AEs leading to withdrawal (RR: 1.54 with 95% CI [0.84, 2.82], P = .16). However, insulin icodec was associated with increased any AEs incidence (RR: 1.06 with 95% CI [1.01, 1.12], P = .02). Conclusion: Insulin icodec was associated with decreased HbA1C, increased TIR, with similar hypoglycemic and serious AEs. However, it was also associated with increased body weight and the incidence of any AEs.

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

Retentive force of a conical crown with CAD/CAM-fabricated PEEK and zirconia secondary crowns on titanium implant abutments.

This study aimed to evaluate the retentive force of polyetheretherketone (PEEK) and zirconia secondary crowns on ready-made titanium implant abutments (with height, diameter, and taper as 5.5 mm, 4.5 mm, and 6°, respectively) as the primary crown. PEEK, zirconia, and titanium secondary crowns were fabricated using a CAD/CAM system. Insertion and removal tests of secondary crowns on the primary crown were conducted for 2,000 cycles. The initial retentive forces recorded at the 100th cycle for PEEK, zirconia, and titanium were 13.0±7.9, 2.9±2.6, and 27.6±1.7 N, respectively. The retentive forces of PEEK and zirconia showed no significant difference among all cycles. However, the retentive force of the titanium used as a control decreased (20.3±2.8 N) significantly at the 2,000th cycle. Although the retentive force of PEEK was lower than that of titanium, it was within the range that can provide a suitable retentive force of 5 N for removable dental prostheses.

The Safety and Efficacy of Quadruple Ultra-Low-Dose Combination (Quadpill) for Hypertension Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Quadpill, a single pill containing a quadruple combination of quarter doses of four antihypertensive agents, has been investigated for hypertension treatment. This meta-analysis aims to evaluate the safety and efficacy of quadpill for hypertension management. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials evaluating quadpill versus monotherapy or placebo in patients with hypertension, which were retrieved by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through 17 February, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI), using Revman Version 5.4 software. Our protocol has been published in PROSPERO with ID: CRD42023406527. RESULTS: Four randomized controlled trials with a total of 779 patients were included in our analysis. Quadpill was effective in controlling systolic blood pressure in the short term [4-6 weeks] (RR: - 13.00 with 95% CI [- 17.22, - 8.78], p = 0.00001) and in the long term [12 weeks] (RR: - 6.18 with 95% CI [- 9.35, - 3.01], p = 0.0001). Quadpill was also effective in controlling automated diastolic blood pressure in the short term [4-6 weeks] (MD: - 8.15 with 95% CI [- 9.42, - 6.89], p = 0.00001) and in the long term [12 weeks] (MD: - 6.35 with 95% CI [- 10.37, - 2.33], p = 0.002). Moreover, patients in the quadpill group significantly achieved target blood pressure <140/90 (RR: 1.77 with 95% CI [1.26, 2.51], p = 0.001) compared with the control group. CONCLUSIONS: The quadruple ultra-low-dose combination of antihypertensive drugs (quadpill) was effective and safe for hypertension treatment. However, further large-scale, multicenter, randomized controlled trials are still warranted before endorsement in clinical practice.

Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience.

Sustained low-efficiency dialysis (SLED) is usually performed over 6-12 h among hemodynamically unstable patients. Conduction of 4-h SLED may spare time and manpower during hospitalization. Therefore, we conducted a retrospective observational study to explore the appropriateness and clinical outcomes of 4-h SLED among critically ill patients admitted to our center from 1/06/2016 to 1/06/2020. Renal parameters including blood urea nitrogen, serum creatinine, sodium, phosphorus, potassium, and bicarbonate were determined on the day of dialysis before SLED and within 24 h after SLED, and clinical outcomes including, acute kidney injury (AKI) recovery, in-hospital mortality, 30-day mortality, 180-day mortality, and re-admission with AKI, were evaluated. Of the 304 patients included, 69.4% were male. The majority of patients were from the Middle East (65.8%), followed by 28.6% from Asia. Four-hour SLED resulted in a significant improvement in the renal parameters. Recovery from AKI was observed in 25.4%, in-hospital mortality rate was 48.7%, while the 30- and 180-day mortality outcomes were 3.2 and 9.6%, respectively, and re-admission with AKI was observed in 16.9%. Our findings suggest that 4-h SLED significantly improved renal parameters and was associated with favorable clinical outcomes in terms of survival and AKI recovery, suggesting possible utilization of SLED shorter than 6 h in the acute settings to preserve time and manpower for procedures.

Parameters Affecting the Retention Force of CAD/CAM Telescopic Crowns: A Focused Review of In Vitro Studies.

Telescopic systems constructed using computer aided design and computer aided manufacture (CAD/CAM) can overcome many drawbacks associated with conventionally constructed ones. Since retention is considered the most important function of these retainers, this scoping review aimed to discuss and summarize the parameters that affect this function in CAD/CAM-manufactured telescopic crowns and to compare their retention force values with the recommended retention force. An electronic search was done in Pubmed and Google Scholar databases using different keyword combinations to find the related articles. Seventeen articles that follow the eligibility criteria for this review were selected and analyzed for detection of each of the tested parameters and their effect on retention force. The parameters tested in these articles were divided into parameters related to design, manufacturing, material type, and test condition. Regardless of the effect of these parameters, the retention force values recorded in most of the selected studies laid within or were higher than the recommended retention force (2.5-10 N), which indicated the need to design and set the combination of materials of telescopic systems according to oral biomechanics.

SARS-CoV-2 Infection in the Heart Transplant Recipient.

Review of the literature and reported case series has not reported an increased risk of SARS-CoV-2 infection in heart transplant recipients. However, this population is at increased risk of a more severe infection with increased mortality because of age and the presence of multiple comorbid conditions There is no significant difference in presenting symptoms in transplant recipients as compared to nontransplant patients, although diarrhea has been reported to be more frequent in transplant patients, a common side effect of immunosuppressive medications. Standard preventive measures have been shown to be equally protective in heart transplant recipients. Risk factors for severe disease and mortality are similar in both transplant recipients and nontransplant patients and include older age and the presence of comorbidities hypertension being the most common. The SARS-CoV-2 infection did not increase the risk of transplant allograft rejection. Currently, there are no specific treatment recommendations for SARS-CoV-2 infection in transplant recipients. However, the International Society of Heart and Lung and Transplant has issued guidance on how to modulate immunosuppressive therapy during SARS-CoV-2 infection.

COVID-19 and Heart Failure: The Big Challenge.

Patients with chronic heart failure (HF) are among the most vulnerable populations in the COVID era. HF patients infected with COVID-19 are at a significant risk of severe illness and death. They usually present with shortness of breath and radiologic signs of an acute decompensation, which can mask the manifestations of COVID-19. Delay in the diagnosis increases the risk of individual poor outcomes and jeopardizes healthcare workers if protective and isolation measures are not established promptly. Furthermore, the COVID-19 pandemic is forcing health-care systems to modify the delivery of care to patients. Outpatient services are being done virtually, and elective procedures postponed. These may have an impact on the quality of life and survival of chronic HF patients. We present two cases of patients with the previous history of HF who developed an acute exacerbation secondary to COVID-19 infection. In this review, we focused on the main challenges physicians face when dealing with COVID-19 in chronic HF patients at the individual and system levels.

Long-term (up to 18 years) clinical and echocardiographic results of mitral balloon valvuloplasty in 531 consecutive patients and predictors of outcome.

OBJECTIVES: The study aim was to assess the long-term results (up to 18 years) of mitral balloon valvuloplasty (MBV) and to identify predictors of restenosis and event-free survival. METHODS: The immediate and long-term results for 531 consecutive patients (mean age 31 +/- 11 years) who underwent successful MBV and were followed up for a mean of 8.5 +/- 4.8 years (range: 1.5-18 years) are reported. RESULTS: The mitral valve area (MVA) increased from 0.92 +/- 0.17 to 1.95 +/- 0.29 cm(2) (p < 0.0001). Restenosis was 31 and 19% in patients with mitral echocardiographic score (MES) < or =8. Actuarial freedom from restenosis at 10, 15 and 18 years was 77 +/- 2, 46 +/- 3 and 18 +/- 4% and 86 +/- 2, 62 +/- 4 and 31 +/- 7% for MES < or =8, respectively (p < 0.001). Event-free survival (death, redo MBV, mitral valve replacement, NYHA class III or IV) at 10, 15 and 18 years was 88 +/- 1, 53 +/- 4, and 21 +/- 5% and 93 +/- 2, 65 +/- 5 and 38 +/- 8% for MES < or =8, respectively (p < 0.001). Multivariable Cox regression analysis identified MES >8 (p < 0.0001) and previous surgery (p = 0.043) as predictors of restenosis, and MES >8 (p < 0.0001) and baseline atrial fibrillation (p = 0.03) as predictors of combined events. CONCLUSION: MBV provides excellent long-term results. The baseline clinical and MES characteristics are predictors of outcome.

Twenty-two years of follow-up results of balloon angioplasty for discreet native coarctation of the aorta in adolescents and adults.

BACKGROUND AND AIMS: Although the immediate and intermediate-term results of balloon angioplasty (BA) for patients with aortic coarctation (AC) have been encouraging, there is paucity of data on long-term follow-up results. This study evaluated the long-term (up to 22 years) follow-up results of BA in adolescent and adult patients with discrete (shelf-like) coarctation of the aorta. METHODS: Follow-up data of 58 patients (mean age 24+/-9 years) undergoing BA for discrete AC at median interval of 13.4 years including cardiac catheterization, magnetic resonance imaging, and Doppler echocardiography form the basis of this study. RESULTS: No early deaths occurred. Balloon angioplasty produced immediate reduction in peak AC gradient from 60+/-22 mm Hg to 8.5+/-8 mm Hg (P<.0001). Follow-up catheterization 12 months later revealed a residual gradient of 5+/-6.4 mm Hg (P=.01). Five patients (8%) with suboptimal initial outcome (peak gradient>20 mm Hg) developed restenosis, and 4 of these had successful repeat angioplasty. Aneurysm developed at the site of dilatation in 4 patients (7%). Magnetic resonance imaging follow-up results revealed no new aneurysm. In one patient, the aneurysm increased in size, but no recoarctation or appreciable changes in the Doppler gradient across the AC site was noted. The blood pressure had normalized without medical treatment in 29 (50%) of the 58 patients. CONCLUSION: Long-term results of BA for discrete AC are excellent and should be considered as first option for treatment of this disease.

Immediate and long-term results of mitral balloon valvuloplasty in patients with severe pulmonary hypertension.

BACKGROUND AND AIM OF THE STUDY: Mitral stenosis (MS) with severe pulmonary hypertension (PHT) constitutes a high-risk subset for surgical commissurotomy or valve replacement. Mitral balloon valvuloplasty (MBV) has emerged as the treatment of choice for patients with severe pliable MS. The efficacy of this procedure in patients with severe PHT has not been fully elucidated, notably with regards to the long-term outcome. METHODS: MBV was successfully performed in 531 consecutive patients. Of these patients, 82 (15%) had severe PHT at baseline (group A), defined as pulmonary artery systolic pressure (PASP) at rest > 60 mmHg, compared to the remaining 449 patients, who served as controls (group B). RESULTS: Patients with PHT had a higher echo score and were more symptomatic, the majority (52.4%) having moderate to severe tricuspid regurgitation (TR). When comparing PHT with controls, the left atrial pressure was higher (28 +/- 4.9 versus 25.6 +/- 4.6 mmHg; p < 0.0001), the mean mitral gradient was similar (14.6 +/- 3.8 versus 14.4 +/- 2.1 mmHg; p = 0.30), the baseline mitral valve area (MVA) was smaller (0.72 +/- 0.17 versus 0.86 +/- 0.19 cm2; p < 0.0001), pulmonary vascular resistance was higher (612 +/- 343 versus 211 +/- 183 dyne/s/cm(-5); p < 0.0001), and post-procedure MVA was smaller (1.7 +/- 0.44 versus 1.85 +/- 0.54 cm2; p = 0.007). The PASP decreased significantly over 12 months after MBV, from 79 +/- 14 to 36.7 +/- 7.53 mmHg (p < 0.0001). Freedom from restenosis in PHT patients at 10 and 15 years, respectively, was 66 +/- 6% and 45 +/- 8% versus 78 +/- 2% and 47 +/- 3% in controls (p = 0.0066). Event-free survival at 10 and 15 years, respectively, was 77 +/- 6% and 41 +/- 11% in PHT patients versus 89 +/- 1% and 54 +/- 4% for controls (p = 0.0169). In total, 33 patients (40%) had moderate TR and 10 (12%) had severe TR at baseline. At follow up, only 12 patients had moderate TR and none had severe TR. CONCLUSION: MBV is a safe and effective technique for treating patients with MS and severe PHT. Although the immediate results were comparable with those in controls, the long-term results proved to be slightly inferior, with a regression of PHT and concomitant severe TR.

Computational Determination of the Effects of Bacteriophage Bacteriophage Interactions in Human Body.

BACKGROUND: Chronic diseases are becoming more serious and widely spreading and this carries a heavy burden on doctors to deal with such patients. Although many of these diseases can be treated by bacteriophages, the situation is significantly dangerous in patients having concomitant more than one chronic disease, where conflicts between phages used in treating these diseases are very closer to happen. METHOD: This research paper presents a method to detecting the Bacteriophage-Bacteriophage Interaction. This method is implemented based on Domain-Domain Interactions model and it was used to infer Domain-Domain Interactions between the bacteriophages injected in the human body at the same time. RESULTS: By testing the method over bacteriophages that are used to treat tuberculosis, salmonella and virulent E.coli, many interactions have been inferred and detected between these bacteriophages. Several effects were detected for the resulted interactions such as: playing a role in DNA repair such as nonhomologous end joining, playing a role in DNA replication, playing a role in the interaction between the immune system and the tumor cells and playing a role in the stiff man syndrome. We revised all patents relating to bacteriophage bacteriophage interactions and phage therapy. CONCLUSION: The proposed method is developed to help doctors to realize the effect of simultaneously injecting different bacteriophages into the human body to treat different diseases.

Ab-initio conformational epitope structure prediction using genetic algorithm and SVM for vaccine design.

BACKGROUND AND OBJECTIVE: T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i.e., tertiary structure) reflects its proper function. Therefore, the identification of MHC class-II epitopes structure is a significant step towards epitope-based vaccine design and understanding of the immune system. METHODS: In this paper, we propose a new technique using a Genetic Algorithm for Predicting the Epitope Structure (GAPES), to predict the structure of MHC class-II epitopes based on their sequence. The proposed Elitist-based genetic algorithm for predicting the epitope's tertiary structure is based on Ab-Initio Empirical Conformational Energy Program for Peptides (ECEPP) Force Field Model. The developed secondary structure prediction technique relies on Ramachandran Plot. We used two alignment algorithms: the ROSS alignment and TM-Score alignment. We applied four different alignment approaches to calculate the similarity scores of the dataset under test. We utilized the support vector machine (SVM) classifier as an evaluation of the prediction performance. RESULTS: The prediction accuracy and the Area Under Receiver Operating Characteristic (ROC) Curve (AUC) were calculated as measures of performance. The calculations are performed on twelve similarity-reduced datasets of the Immune Epitope Data Base (IEDB) and a large dataset of peptide-binding affinities to HLA-DRB1*0101. The results showed that GAPES was reliable and very accurate. We achieved an average prediction accuracy of 93.50% and an average AUC of 0.974 in the IEDB dataset. Also, we achieved an accuracy of 95.125% and an AUC of 0.987 on the HLA-DRB1*0101 allele of the Wang benchmark dataset. CONCLUSIONS: The results indicate that the proposed prediction technique "GAPES" is a promising technique that will help researchers and scientists to predict the protein structure and it will assist them in the intelligent design of new epitope-based vaccines.

Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study.

BACKGROUND: Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTER-CHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. METHODS: We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. FINDINGS: We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. INTERPRETATION: Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. FUNDING: The study was supported by Novartis.

Computational determination of the effects of virulent Escherichia coli and salmonella bacteriophages on human gut.

BACKGROUND AND OBJECTIVE: Salmonella and Escherichia coli are different types of bacteria that cause food poisoning in humans. In the elderly, infants and people with chronic conditions, it is very dangerous if Salmonella or E. coli gets into the bloodstream and then they must be treated by phage therapy. Treating Salmonella and E. coli by phage therapy affects the gut flora. This research paper presents a system for detecting the effects of virulent E. coli and Salmonella bacteriophages on human gut. METHODS: A method based on Domain-Domain Interactions (DDIs) model is implemented in the proposed system to determine the interactions between the proteins of human gut bacteria and the proteins of bacteriophages that infect virulent E. coli and Salmonella. The system helps gastroenterologists to realize the effect of injecting bacteriophages that infect virulent E. coli and Salmonella on the human gut. RESULTS: By testing the system over Enterobacteria phage 933W, Enterobacteria phage VT2-Sa and Enterobacteria phage P22, it resulted in four interactions between the proteins of the bacteriophages that infect E. coli O157:H7, E. coli O104:H4 and Salmonella typhimurium and the proteins of human gut bacterium strains. CONCLUSION: Several effects were detected such as: antibacterial activity against a number of bacterial species in human gut, regulation of cellular differentiation and organogenesis during gut, lung, and heart development, ammonia assimilation in bacteria, yeasts, and plants, energizing defense system and its function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in human gut.