Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

Acute Effects of Vitamin C Exposure On Colonic Crypts: Direct Modulation of pH Regulation

Background/Aim: Colorectal cancer is still considered a leading cause of death in the United States and worldwide. One potential way to improve survival besides detection is to look to new therapeutic agents that can be taken prophylactically to reduce the risk of tumor formation. For cancer cells to grow and invade, a higher (more alkaline) intracellular pH must occur. We chose to examine a specific nutraceutical agent, which is Vitamin C. The acute effect of Vitamin C exposure on normal colonic crypts has been studied, providing some insight into how Vitamin C achieve its effect. Methods: Distal colon was excised from rats. Following enzymatic digestion single colonic crypts were isolated. Colonic crypts were loaded with pH sensitive dye to measure the intracellular pH changes. Crypts were exposed to solutions +/- Vitamin C. Results: 10 mM Vitamin C decreased Na+-dependent intracellular pH recovery. Vitamin C modulates SVCT leading to changes in proton extrusion. Vitamin C entry occurs via either SVCT2 on the basolateral membrane or by transcellular passive diffusion through tight junctions to the apical membrane and then active transport via SVCT1. Conclusion: Acute addition of Vitamin C to the basolateral membrane maintains low intracellular pH for a longer period which could halt and/or prevent tumor formation

In vitro induction of human embryonal carcinoma differentiation by a crude extract of Rhazya stricta

Abstract Background Rhazya stricta Decne. is a medicinal plant that is widespread in Saudi Arabia and desert areas of the Arabian Peninsula. Its extract contains alkaloids, tannins, and flavonoids that are involved in different biological activities. The study aim was to evaluate the effects of Rhazya stricta plant extracts on the proliferation and differentiation of NTERA-2 (NT2) pluripotent embryonal carcinoma cells. Methods Soxhlet extraction was carried out using different solvents to extract stems, leaves and fruit parts of this plant. Cytotoxicity was evaluated by an MTS cell viability assay. The ability of the plant extract to induce cell differentiation was examined phenotypically using an inverted light microscope. The expression of pluripotency markers was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry. Phytochemical screening of chloroform stem extracts was carried out and a chromatographic fingerprint was generated using gas chromatography – mass spectrometry (GC-MS). Results Chloroform stem extract induced differentiation of NT2 cells at 5 μg/ml, and the differentiated cells exhibited neurite formation. Following induction of differentiation, there was significant down-regulation of the pluripotency marker genes Oct4 and Sox2. In addition, the surface antigen pluripotency marker, TRA-1-60, was strongly down-regulated. Phytochemical analysis of the extract showed the presence of alkaloids and saponins. The chromatogram revealed the presence of fifteen compounds with different retention times. Conclusion Our results demonstrate for the first time that chloroform stem extract of R. stricta can induce neuronal differentiation of stem cells at an early stage and may contain potential therapeutic agent that can be used in neurodegenerative diseases

Molecular Modeling and Phylogeny of the Krüppel-like Factor 4 (cKLF4) Protein from the Arabian Camel,

Krüppel-like factor 4 (KLF4) is a pluripotency transcription factor that helps in generating induced pluripotent stem cells (iPSCs). We sequenced for the first time the full coding sequence of Camelus dromedarius KLF4 (cKLF4), which is also known as the Arabian camel. Bioinformatics analysis revealed the molecular weight and the isoelectric point of cKLF4 protein to be 53.043 kDa and 8.74, respectively. The predicted cKLF4 protein sequence shows high identity with some other species as follows: 98% with Bactrian camel and 89% with alpaca KLF4 proteins. A three-dimensional (3D) structure was built based on the available crystal structure of the Mus musculus KLF4 (mKLF4) of 82 residues (PDB: 2 WBS) and by predicting 400 residues using bioinformatics software. The comparison confirms the presence of the zinc finger domains in cKLF4 protein. Phylogenetic analysis showed that KLF4 from the Arabian camel is grouped with the Bactrian camel, alpaca, cattle, and pig. This study will help in the annotation of KLF4 protein and in generating camel-induced pluripotent stem cells (CiPSCs)

Up-regulated Desaturase and Elongase Gene Expression Promoted Accumulation of Polyunsaturated Fatty Acid (PUFA) but Not Long-Chain PUFA in Lates calcarifer, a Tropical Euryhaline Fish, Fed a Stearidonic Acid- and γ-Linoleic Acid-Enriched Diet

The limited activity of Δ6 fatty acid desaturase (FAD6) on α-linolenic (ALA, 18:3n-3) and linoleic (LA, 18:2n-6) acids in marine fish alters the long-chain (≥C20) polyunsaturated fatty acid (LC-PUFA) concentration in fish muscle and liver when vegetable oils replace fish oil (FO) in aquafeeds. Echium oil (EO), rich in stearidonic acid (SDA, 18:4n-3) and γ-linoleic acid (GLA, 18:3n-6), may enhance the biosynthesis of n-3 and n-6 LC-PUFA by bypassing the rate-limiting FAD6 step. Nutritional and environmental modulation of the mechanisms in LC-PUFA biosynthesis was examined in barramundi, Lates calcarifer, a tropical euryhaline fish. Juveniles were maintained in either freshwater or seawater and fed different dietary LC-PUFA precursors present in EO or rapeseed oil (RO) and compared with FO. After 8 weeks, growth of fish fed EO was slower compared to the FO and RO treatments. Irrespective of salinity, expression of the FAD6 and elongase was up-regulated in fish fed EO and RO diets, but did not lead to significant accumulation of LC-PUFA in the neutral lipid of fish tissues as occurred in the FO treatment. However, significant concentrations of eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), but not docosahexaenoic acid (DHA, 22:6n-3), appeared in liver and, to a lesser extent, in muscle of fish fed EO with marked increases in the phospholipid fraction. Fish in the EO treatment had higher EPA and ARA in their liver phospholipids than fish fed FO. Endogenous conversion of dietary precursors into neutral lipid LC-PUFA appears to be limited by factors other than the initial rate-limiting step. In contrast, phospholipid LC-PUFA had higher biosynthesis, or selective retention, in barramundi fed EO rather than RO

The international prevalence study on physical activity: Results from 20 countries

Background: Physical activity (PA) is one of the most important factors for improving population health, but no standardised systems exist for international surveillance. The International Physical Activity Questionnaire (IPAQ) was developed for international surveillance. The purpose of this study was a comparative international study of population physical activity prevalence across 20 countries. Methods: Between 2002-2004, a standardised protocol using IPAQ was used to assess PA participation in 20 countries [total N = 52,746, aged 18-65 years]. The median survey response rate was 61%. Physical activity levels were categorised as "low", "moderate" and "high". Age-adjusted prevalence estimates are presented by sex. Results: The prevalence of "high PA" varied from 21-63%;in eight countries high PA was reported for over half of the adult population. The prevalence of "low PA" varied from 9% to 43%. Males more frequently reported high PA than females in 17 of 20 countries. The prevalence of low PA ranged from 7-41% among males, and 6-49% among females. Gender differences were noted, especially for younger adults, with males more active than females in most countries. Markedly lower physical activity prevalence (10% difference) with increasing age was noted in 11 of 19 countries for males, but only in three countries for women. The ways populations accumulated PA differed, with some reporting mostly vigorous intensity activities and others mostly walking. Conclusion: This study demonstrated the feasibility of international PA surveillance, and showed that IPAQ is an acceptable surveillance instrument, at least within countries. If assessment methods are used consistently over time, trend data will inform countries about the success of their efforts to promote physical activity. © 2009 Bauman et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex