Single versus bilateral chordo-papillary apparatus preservation in mitral valve replacement: a hemodynamic study

Background: It has been postulated that disruption of the mitral valve apparatus at the time of mitral valve replacement (MVR) is a risk factor for postoperative ventricular dysfunction. The aim of this study was to evaluate the effect of single versus bilateral chordo-papillary preservation on the left ventricular function in comparison to no preservation. Methods: This study was conducted from 2015 to 2018 on sixty patients who had MVR. The patients were classified into group I included 20 patients who underwent MVR with complete excision of the subvalvular chordae and tips of papillary muscles, group II: included 20 patients who underwent MVR with preservation of posterior chordo-papillary apparatus, and group III: included 20 patients who underwent MVR with preservation of both posterior and anterior chordo-papillary apparatus. Results: There were 20 males (33.3%), and the mean age was 48.76± 8.91 years. Patients in group III were significantly older (37.15 ±4.92, 39.8 ± 5.49, and 57.25 ± 6.93 years in groups I, II, and III, respectively; p< 0.001). The left ventricular end-diastolic (5.40 ±0.34, 4.96 ± 0.43, and 4.44 ± 0.55 mm in group I, II and III, respectively, p<0.001) and end-systolic diameter (4.33 ±0.48, 3.58 ±0.43 and 3.20 ±0.43 mm in group I, II and III; respectively, p<0.001) were significantly reduced in partial and complete preservation groups after 6 months. Left ventricular ejection fraction improved in the bilateral preservation and partial preservation groups after 6 months (45.32 ±9.78, 56.79 ±10.14, and 56.60 ±11.68 % in groups I, II and III respectively, p<0.001). Mechanical ventilation was significantly longer in group I (24.10 ± 6.6, 16.80 ± 5.97, and 15.80 ± 5.24 hours in groups I, II and III, respectively, p<0.001) and the duration of ICU stay was significantly longer in group I (78.65 ± 15.32, 65.40 ± 14.21, and 60.20 ± 12.58 hours in groups I, II and III, respectively, p<0.001). Conclusion: Preservation of the annulo-papillary continuity may preserve left ventricular geometry and performance. Total preservation of chordae could be superior to partial preservation with better left ventricular remodeling and improvement in the left ventricular functions

Design, synthesis and cytotoxic evaluation of 2-amino-4- aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives

Purpose: To synthesize novel pyridine derivatives and evaluate their efficiency as potent inhibitors of cyclin dependent kinase 2 (CDK2) enzyme for cancer therapy.Methods: Pyridine scaffold were synthesized using one-pot multicomponent condensation reaction of arylidine with different primary amines. The cytotoxic potential of the new compounds was assessed using various cell lines. Furthermore, molecular docking studies based on the crystal structure of CDK2 was carried out to determine the possible binding modes that influence the anticancer activities.Results: The results indicate that one-pot multicomponent reaction generated a series of functionalized pyridines with good yield. In vitro cytotoxicity study revealed superior cytotoxicity of the designed compounds against prostate and cervical cancer cell lines compared to 5-fluorouracil (standard anticancer compound) with half-maximal inhibitory concentration (IC50) values of 0.1 – 0.85 and 1.2 –74.1 μM, respectively. Finally, molecular modeling simulation of the newly synthesized compounds showed that they fit well and are stabilized into CDK2 active site via hydrogen bonding and hydrophobic interactions.Conclusion: The results indicate that the newly synthesized pyridine can exert potent anticancer activity presumably via inhibition of CDK2. However, this will need to be confirmed in in vivo studies

Melasma and Associated Factors in Arar City, Kingdom of Saudi Arabia (KSA)

Melasma is a common dermatological disorder characterized by irregular brownish patches with unclear etiology and a variety of factors may be associated with its occurrence. Melasma patients suffer significant emotional and psychological problems making assessment of their quality of life is increasingly necessary. Aim of the study: This study was conducted to identify the frequency and factors associated with occurrence of Melasma in in Arar, KSA and its effect on some determinant of quality of life in the affected patients. Subjects and methods: A population based cross sectional study was conducted from January 2016 to January 2017. It included 470 individuals attended five randomly selected primary healthcare centers in Arar city in the Northern Province of Kingdom of Saudi Arabia and were selected by systemic random sampling. Data were collected by means of personal interview with the sampled population using a predesigned questionnaire. Results: Findings revealed that18.7 % of the studied population suffered from Melasma. Age and positive family history were significantly associated with the development of Melasma among the studied patients while gender, skin color, sun exposure and cosmetic use had no significant effect. Most of the studied determinants of quality of life were not affected by suffering from Melasma while lack of self-confidence was significantly associated with the presence of Melasma. Conclusion: less than on fifth (18.7%) of the studied patients suffered from Melasma. Age and positive family history are the most common associations. Melasma had a significant impact on self-confidence of the affected patients.Keywords: Melasma, risk factor, quality of life

EBV Associated Breast Cancer Whole Methylome Analysis Reveals Viral and Developmental Enriched Pathways

Background: Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a pilot genome-wide methylome study to characterize aberrant DNA methylation in breast cancer.Results: Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20,188 differentially methylated positions (DMPs), which is further divided into 13,633 hypermethylated sites corresponding to 5339 genes and 6,555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC.Conclusion: Our results clearly show the utility of epigenetic assays in interrogating breast cancer tumorigenesis, and pinpointing specific developmental and viral pathways dysregulation that might serve as potential biomarkers or targets for therapeutic interventions

Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients [PIRATES]:A Phase I safety and feasibility trial of MRI-guided adaptive particle radiotherapy

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues. The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion: The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk. Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021. Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021

Exploring the multimodal role of yucca schidigera extract in protection against chronic ammonia exposure targeting: Growth, metabolic, stress and inflammatory responses in nile tilapia (oreochromis niloticus l.)

Ammonia is a critical hazardous nitrogen metabolic product in aquaculture. Despite trials for its control, ammonia intoxication remains one of the most critical issues to overcome. In this study, we explored the modulatory effect and potential mechanism by which Yucca schidigera extract (YSE) can ameliorate ammonia intoxication-induced adverse effects on tilapia health and metabolism. A total number of 120 Nile tilapia were evenly assigned into four groups with three replicates each. The first group served as normal control group; the second group was exposed to ammonia alone from the beginning of the experiment and for four weeks. The third group was supplied with YSE in water at a dose of 8 mg/L and exposed to ammonia. The fourth group was supplied with YSE only in water at a dose of 8 mg/L. YSE supplementation succeeded in improving water quality by reducing pH and ammonia levels. Moreover, YSE supplementation markedly alleviated chronic ammonia-induced adverse impacts on fish growth by increasing the final body weight (FBW), specific growth rate (SGR), feed intake and protein efficiency ratio (PER) while reducing the feed conversion ratio (FCR) via improvements in food intake, elevation of hepatic insulin-like growth factor (ILGF-1) and suppression of myostatin (MSTN) expression levels with the restoration of lipid reserves and the activation of lipogenic potential in adipose tissue as demonstrated by changes in the circulating metabolite levels. In addition, the levels of hepato-renal injury biomarkers were restored, hepatic lipid peroxidation was inhibited and the levels of hepatic antioxidant biomarkers were enhanced. Therefore, the current study suggests that YSE supplementation exerted an ameliorative role against chronic ammonia-induced oxidative stress and toxic effects due to its free radical-scavenging potential, potent antioxidant activities and anti-inflammatory effects

Patterns of Failure after IMRT in Head and Neck Squamous Cell Carcinoma of Unknown Primary: Implication of Elective Nodal and Mucosal Dose Coverage

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Search for Doubly-Charged Higgs Boson Production at HERA

A search for the single production of doubly-charged Higgs bosons H^{\pm \pm} in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3, masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl