Glial Hsp70 Protects K+ Homeostasis in the Drosophila Brain during Repetitive Anoxic Depolarization

Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Assessing Anxiety and Depression Among Students Post-COVID-19: Exploring Associating Factors

Iman A Basheti,1,2 Thafer Yusif Assaraira,3 Nathir M Obeidat,4 Fawwaz Al‐Abed Al‐haq,5 Mashhoor Refai6 1Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University, Amman, Jordan; 2School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; 3English Department, Mutah University, Al‐Karak, Jordan; 4Department of Internal Medicine, The University of Jordan, Amman, Jordan; 5Department of English Language and Literature, Hashemite University, Zarqa, Jordan; 6King Abdullah II School of Engineering, Princess Sumaya University for Technology, Amman, JordanCorrespondence: Iman A Basheti, Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman, 11931, Jordan, Email [email protected]: The COVID-19 pandemic has had a large impact on global mental health including anxiety and depression rates, many factors affected the vulnerability to these psychological conditions amongst university students.Aim: To explore the level of anxiety and depression of university students living in Jordan.Methods: A cross-sectional study design was conducted in which an electronic survey was created and distributed, university students residing in Jordan participated in the study.Results: A total of 1241 students were enrolled in the study. The mean anxiety score among males and females was (9.68 (SD = 4.10)) and (10.46 (SD = 4.14)), respectively. 42.1% of males had “abnormal” anxiety score compared to 48.4% females. The mean depression score among males (7.77 (SD = 4.31)) was similar to that for the females (7.64 (SD = 4.14)), and 26.0% of the males had “abnormal” depression score compared to 22.6% of the females. Factors affecting anxiety scores included younger age, being a female, taking medication/s, or drinking two cups of coffee or more a day.Conclusion: With 46% and 24% of students suffering from abnormal anxiety and depression respectively, it is important for education policy makers to take immediate measures to allocate students in need of psychological assessment and help to deliver suitable interventions.Keywords: anxiety, depression, students, Jordan, psychological assessmen

Evaluation of matrix tablets based on Eudragit®E100/Carbopol®971P combinations for controlled release and improved compaction properties of water Soluble Model Drug Paracetamol

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer–Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs

Genome-wide association study identifies five loci associated with lung function

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n ? 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n ? 883). We confirmed the reported locus at 4q31 and identified associations with FEV1 or FEV1/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 × 10?12), 4q24 in GSTCD (2.18 × 10?23), 5q33 in HTR4 (P = 4.29 × 10?9), 6p21 in AGER (P = 3.07 × 10?15) and 15q23 in THSD4 (P = 7.24 × 10?15). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory diseas