Translin and Trax differentially regulate telomere-associated transcript homeostasis

Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere-associated transcripts. Mutation of tfx1(+) (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels. This reveals a novel mechanism for the regulation of telomeric transcripts. We extend this to demonstrate that human Translin and Trax also control telomere-associated transcript levels in human cells in a telomere-specific fashion

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The Methodological Approaches to Research of General Curricula and Instruction in the Master's and PhD Thesis at King Khalid University

هدف البحث للتعرف على التوجهات المنهجية لأبحاث المناهج وطرق التدريس العامة في رسائل الماجستير والدكتوراه بجامعة الملك خالد ولتحقيق هذا الهدف استعانت الباحثة بدليل الرسائل العلمية التابع لعمادة الدراسات العليا بجامعة الملك خالد، حيث قامت الباحثة بحصر جميع الرسائل العلمية التي نوقشت في قسم المناهج وطرق التدريس العامة منذ عام 1426هـ وحتى عام 1439هـ للاطلاع عليها وتحليلها والخروج بتصور متكامل عن توجهاتها المنهجية وبلغ عدد الرسائل العلمية لمرحلتي الماجستير والدكتوراه 143رسالة. وأسفرت نتائج البحث عن أكثر المناهج العلمية استخداماً بالرسائل العلمية في قسم المناهج وطرق التدريس العامة بجامعة الملك خالد المنهج التجريبي بنسبة 68 %، أما المرتبة الثانية فكانت للمنهج الوصفي بنسبة 45 %. كما استخدمت الابحاث في قسم المناهج وطرق التدريس العامة الطلاب بجنسيهم كعينة للبحث بنسبة كبيرة جداً بلغت 80%، يليها المعلمون بنسبة 12%، والمناهج الدراسية بنسية 8%، كما تجاوزت عينة البحث من الذكور نظيرتها من الإناث، حيث بلغت نسبة استخدام الأبحاث لعينة من الذكور سواء معلمين او طلاب نسبة 69%، بينما استخدمت الأبحاث الاناث كعينة للبحث بنسبة 31%. وفي ضوء هذه النتائج قدمت الباحثة بعض التوصيات والمقترحات.This paper aimed to identify the Methodological Approaches to Research of General Curricula and Instruction in the Master's and PhD Thesis at King Khalid University. The researcher did an Inventory all the scientific Thesis in the Department of General Curricula and Instruction since 1426 until 1439 AH, for the study and analysis, and come out with an integrated perception of the methodological Approache,&nbsp; the number of scientific Theses for stage of&nbsp; Masters and PHD is (143 Thesis). The Search resulted&nbsp; is: the most scientific methods used in scientific theses in the Department of General Curricula and Instruction at King Khalid University, The experimental Approach by 68%, then at the second place the descriptive approach by 45%. The researches in the Department of General Curricula and Instruction used students as a sample for research by a very large percentage of 80%, followed by teachers by 12%, and curricula by 8%. It also exceeded the rate of use male sample for the female's sample, by 69% for the teachers or students, and by 31% for the female sample. Finally, in light of these results, the researcher presented some recommendations and suggestions. &nbsp; &nbsp

Awareness and knowledge of periodontal disease among Saudi primary school teachers in Aseer region

Background: The consequences of periodontal disease are not limited to the oral cavity. As schools are considered to be one of the principal systems in preventive oral health, teachers' knowledge pertaining to the periodontal disease, their awareness with regard to its implications and their role in increasing the awareness of the students regarding this disease comprises only one aspect with respect to the prevention of the periodontal disease. Therefore, the aim of this study is to investigate the baseline awareness and knowledge of Saudi primary school teachers regarding the periodontal disease. Materials and Methods: For this purpose, a questionnaire was distributed among the participants of the study. Results: It was observed that 91.4% of the participants reported that the periodontal disease does not need any treatment although 70% of the participants believed that it could result in tooth loss, and 95% considered the periodontal disease to be a preventable disease. Moreover, social media (44%) and television advertisements (39%) were the main sources from where they acquired information about the periodontal disease. Conclusions: Most participants have heard about the importance of periodontal health but are not sufficiently aware of its consequences and negative effects on their body. They are used to receiving information about periodontal diseases from nondental clinics and unreliable sources. This creates misconceptions. Although the participants were keen to attend educational events on periodontal health, the lack of medical communication between the health practitioners and the general public is evident. Mostly, investigated areas and individuals do not have any educational means to be aware of periodontal health

Exploring the multi-gene regulatory molecular mechanism of Saudi Arabian flora against epilepsy based on data mining, network pharmacology and docking analysis

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly affecting the population in Saudi Arabia across all age demographics. The global prevalence of active epilepsy is around 6.38/1,000 persons and in the Arabian region, the median prevalence of active epilepsy is 4.4/1,000 persons. However, over 75% of individuals are untreated. Consequently, the development of therapeutic strategies with increased efficacy and safety profiles is essential to improve the survival rate among epilepsy patients. The current study integrates network pharmacology along with Bioinformatics approaches to explore the potential molecular mechanisms of local flora of Saudi Arabia including Solanum incanum, Abrus precatorius, Withania somnifera, and Azadirachta indica in epilepsy treatment. In the preliminary phase, data related to the bioactive components of the local plants and the associated target genes of both these plants and epilepsy were gathered from scientific literature and open-source databases. This data was then analyzed to identify common targets between the plants and ovarian cancer. Based on these common targets, a protein–protein interaction (PPI) network was constructed utilizing the STRING database, which was subsequently incorporated into the Cytoscape software for identification of hub genes based on their degree of connectivity. Lastly, an interplay network depicting the associations between the compounds and the overlapping genes was formulated via Cytoscape, to study the potential network pharmacology implications of these active compounds in relation to ovarian cancer. Following that, a compound-target protein-pathway network was constructed which uncovered that namely abrectorin, genistin, (+)-catechin, precatorine, (+)-ascorbic acid, licoflavanone, skrofulein, stigmasterone, 5,7-Dihydroxy-4′-methoxy-8,3′-di-C-prenylflavanone could potentially be used as antagonists for the therapeutic management of epilepsy by targeting TNF and TP53 proteins. Furthermore, the implementation of molecular docking reinforces the binding affinity of the compound, indicating a robust stability of the forecasted compounds at the docked site. This research lays both a theoretical and experimental groundwork for more profound investigations and establishes a practical method for the strategic employment of active compounds in the development of anti-epileptic therapeutics

Designing Potent Anti-Cancer Agents: Synthesis and Molecular Docking Studies of Thieno[2,3-<i>d</i>][1,2,4]triazolo[1,5-<i>a</i>]pyrimidine Derivatives

A new series of thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines was designed and synthesized using readily available starting materials, specifically, β-enaminoester. Their cytotoxicity was screened against three cancer cell lines, namely, MCF-7, HCT-116, and PC-3. 2-(4-bromophenyl)triazole 10b and 2-(anthracen-9-yl)triazole 10e afforded excellent potency against MCF-7 cell lines (IC50 = 19.4 ± 0.22 and 14.5 ± 0.30 μM, respectively) compared with doxorubicin (IC50 = 40.0 ± 3.9 μM). The latter derivatives 10b and 10e were further subjected to in silico ADME and docking simulation studies against EGFR and PI3K and could serve as ideal leads for additional modification in the field of anticancer research