Psychological impact of home isolation on children aged 6-14 years during the COVID-19 pandemic in Tabuk,Saudi Arabia 2020

Objectives:To evaluate the impact of home isolation on feelings and behaviors of children aged 6-14 years during COVID-19 pandemic in Tabuk, Saudi Arabia.Methods:A cross-sectional study was conducted between June and August 2020 in Tabuk, Saudi Arabia. A snowball sampling was applied, parents with children aged 6-14 years participated in this survey (N=361). questionnaires were distributed electronically.Results:Four out of ten children reported severe psychological impact on feelings (41.3%), while a majority of the children demonstrated mild psychological impact on behavior (74.8%). Age was associated with risk of psychological impact on behavior (OR: 7.24, 95% CI: 1.35-16.18). Being male was associated with risk of psychological impact on feelings (OR: 2.38, 95% CI: 0.67-6.43), and behavior (OR: 3.50, 95% CI: 0.42-6.00). Living in a small house or without an outside play area was associated with risk of psychological impact on feelings and behaviors.Conclusion:This study revealed that children experienced mild-to-severe psychological impact on behaviors and feelings during home isolation during COVID-19 pandemic. Priority should be given to boys, older age, children of low-income families, living in small houses and those without outside play areas.     

Triterpenoidal saponins: bioactive secondary metabolites from Zygophyllum coccineum

Phytochemical investigation of the aerial parts of Zygophyllum coccineum L. led to the isolation of nine ursane-type triterpene saponins (1- 9), including the new one; zygophylloside S (1), together with a known flavonoid glycoside (10) and a sterol glycoside (11). The isolated compounds were tested for antifungal activity against several important plant pathogens and for insecticidal activity against two important mosquito species. Among the isolated compounds 1, 3, 5, 6, and 9 showed 32-77 % fungal growth inhibition at a concentration of 30 μM against Phomopsis viticola. Compound 9 showed 90 % and 80 % mosquitocidal activity at 3.1 μg/0.5 μL against Aedes aegypti and Culex quinquefasciatus, respectively.     

Synthesis and potential biological activity of some novel 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles and 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles

Starting from N-substituted indole-3-carboxaldehydes (1a-g) a series of new 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles (3a-g and 4a-g) have been synthesized via the acid catalyzed condensation reaction of 1a-g with 3-amino-5-pyrazolone, followed by the reaction with arylidene malononitriles. A series of new 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles (7a-g) have been prepared either via the base catalyzed condensation reaction of 1a-g with 3-amino-5-pyrazolone to give 6a-g, followed by the reaction with malononitrile or by the reaction of N-substituted-3-indolylidene malononitriles (5a-g) with 3-amino-5-pyrazolone. According to the obtained results, the newly synthesized compounds possess significant anti-inflammatory, analgesic and anticonvulsant activities. The anticonvulsant potency of certain tested compounds was more pronounced than both anti-inflammatory and analgesic activities. Moreover, most of the newly synthesized compounds possess potential antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa.     

An Induction in Hepatic HDL Secretion Associated with Reduced ATPase Expression

Linoleic acid-phospholipids stimulate high-density lipoprotein (HDL) net secretion from liver cells by blocking the endocytic recycling of apoA-I. Experiments were undertaken to determine whether apoA-I accumulation in the cell media is associated with membrane ATPase expression. Treatment of HepG2 cells with dilinoeoylphosphatidylcholine (DLPC) increased apoA-I secretion fourfold. DLPC also significantly reduced cell surface F₁-ATPase expression and reduced cellular ATP binding cassette (ABC)A1 and ABCG1 protein levels by ∼50%. In addition, treatment of HepG2 cells with the ABC transporter inhibitor, glyburide, stimulated the apoA-I secretory effects of both DLPC and clofibrate. Pretreatment of HepG2 cells with compounds that increased ABC transport protein levels (TO901317, N-Acetyl-l-leucyl-l-leucyl-l-norleucinal, and resveratrol) blocked the DLPC-induced stimulation in apoA-I net secretion. Furthermore, whereas HepG2 cells normally secrete nascent preβ-HDL, DLPC treatment promoted secretion of α-migrating HDL particles. These data show that an linoleic acid-phospholipid induced stimulation in hepatic HDL secretion is related to the expression and function of membrane ATP metabolizing proteins.High-density lipoprotein (HDL) is predominantly produced in the liver in humans and is formed by the synthesis and secretion of apolipoprotein components, followed by the lipidation of these proteins with specific lipids.^1,2,3 HDL lipidation is believed to be regulated by the actions of the ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. ABCA1 and ABCG1 lipidate apolipoprotein (apo)A-I and convert nascent HDL particles to lipid-rich HDL.^4,5,6 Through this process, the ABC transport proteins have been thought to play a central role in both the production and maturation of HDL.⁶ ABC transporter expression is regulated by the liver X receptor (LXR), and LXR agonists such as the oxysterols have been shown to increase the expression and lipid secretory activity of ABCA1.⁷ Recent work has shown that despite the activation of ABCA1, LXR agonists such as TO901317 actually inhibit the synthesis and secretion of HDL and apoA-I by liver-derived cells.⁸ This suggests that ABC transporter expression may not be linked to the production of HDL.In addition to lipidating apoA-I, ABC transporters play other roles in HDL metabolism. ABCA1 has been shown to interact directly with apoA-I^9,10 and to impact the endocytic uptake and resecretion of apoA-I.^11,12,13,14 ABCA1-dependent endocytic uptake of apoA-I has been shown to promote the lysosomal degradation of apoA-I.^12,13 Therapeutic compounds that are inhibitors of ABC transporters have been shown to modestly increase plasma HDL levels.^15,16 Glyburide inhibits ABCA1 activity by blocking the ATPase activity of the protein.¹⁷ Glyburide has also been shown to block interactions between apoA-I and ABCA1^9,10 and to block apoA-I signaling through ABCA1.¹⁸ There is evidence to suggest that addition of an ABC transporter inhibitor, such as glyburide, to a fibrate therapy, may also increase the HDL raising potential of the fibrate.¹⁹A different membrane ATPase, F₁F₀-ATP synthase (F₁-ATPase), has also been shown to impact cellular HDL metabolism.^20,21,22,23 Studies have shown that apoA-I can stimulate a plasma membrane bound F₁-ATPase and promote the endocytic uptake of HDL through a specific plasma membrane G-protein coupled receptor, P2Y13.²² Inhibition of F₁-ATPase with antibodies or selective inhibitors (IF₁) blocks HDL endocytosis in hepatic cell culture and in vivo. Recent work suggests that niacin may act through this pathway and increase HDL secretion through reducing membrane F₁-ATPase levels.²⁴ Niacin reduces membrane F₁-ATPase levels and inhibits the reuptake and recycling of apoA-I.Linoleic acid (LA)-phospholipids are considerably more effective at stimulating hepatic apoA-I secretion and HDL production, than niacin and the fibrate drugs.²⁵ Much like niacin, these compounds act through protein kinase C and mitogen-activated protein kinase pathways to activate a peroxisome-proliferator activator receptor (PPAR)α-dependent secretion of apoA-I. However, in contrast to the fibrate drugs, LA-phospholipids do not increase cellular apoA-I mRNA levels and instead increase apoA-I secretion by blocking the endocytic recycling of apoA-I.²⁶ LA-phospholipids are therefore a novel class of HDL effectors that have a similar mechanism of action to niacin and are not metabolized by the cytochrome P450 enzymes.^25,26,27Experiments were undertaken to elucidate how an LA-phospholipid stimulation in apoA-I secretion may involve membrane ATPases. We show that increased apoA-I secretion is inversely related to cell membrane ATPase protein levels. Compounds that inhibit ATPase activity significantly stimulate apoA-I secretion and those that increase ABC transporter levels in HepG2 cells inhibit apoA-I secretion. The data suggests that hepatic apoA-I secretion is closely linked to the expression and function of membrane-bound ATP metabolizing proteins.     

Phenolic content and anti-hyperglycemic activity of pecan cultivars from Egypt

Context: Pecans are commonly used nuts with important health benefits such as anti-hyperglycemic and anti-hyperlipidemic effects.

Objective: A comparative investigation of the antihyperglycemic and total phenolic content of the leaves and shells of four pecan cultivars growing in Egypt was carried out. The selected cultivars (cv.) were Carya illinoinensis Wangneh. K. Koch. cv. Wichita, cv. WesternSchely, cv. Cherokee, and cv. Sioux family Juglandaceae.

Materials and methods: Total phenolic and flavonoid contents of the leaves and shells of pecan cultivars were carried out using Folin–Ciocalteu’s and aluminum chloride assays, respectively. Moreover, HPLC profiling of phenolic and flavonoid contents was carried out using RP-HPLC-UV. In addition, in vivo anti-hyperglycemic activity of the ethanolic extracts (125?mg/kg bw, p.o.) of C. illinoinensis cultivars was carried out using streptozotocin (STZ)-induced diabetes in Sprague–Dawley rats for 4 weeks.

Results and discussion: Phenolic contents were higher in shells than leaves in all studied cultivars, while flavonoids were higher in leaves. Leaves and shells of cv. Sioux showed the highest phenolics (251.7?µg gallic acid equivalent (GAE)/g), and flavonoid contents (103.27?µg rutin equivalent (RE)/g and 210.67?µg quercetin equivalent (QE)/g), respectively. The HPLC profiling of C. illinoinensis cultivars resulted in the identification of eight flavonoids (five of these compounds are identified for the first time from pecan), and 15 phenolic acids (six are identified for the first time from pecan). Leaves of cv. Sioux revealed the most potent decrease in blood glucose and glycated hemoglobin (HbA_1c%) (194.9?mg/dl and 6.52%, respectively), among other tested cultivars. Moreover, leaves of cv. Sioux significantly elevated serum total antioxidant capacity (TAC) and reduced glutathione (GSH) (0.33?mMol/l and 30.68?mg/dl, respectively), and significantly suppressed the markers of both lipid peroxidation (malondialdehyde, MDA) and protein oxidation (protein carbonyl, PC) (14.25?µmol/ml and 3.18?nmol/mg protein, respectively).

Conclusion: Different pecan cultivars showed significant variation in its phenolic and flavonoid contents and consequently their antioxidant and anti-hyperglycemic effects.     

Study of P53 in peripheral blood and synovial mononuclear cells of rheumatoid arthritis and osteoarthritis patients and its relation to the degree of disease activity

Over expression of P53 has been described in many inflammatory conditions including rheumatoid arthritis (RA) and osteoarthritis (OA) as a protective mechanism to induce apoptosis of synovial cells. Lack of P53 function through mutation in human synoviocytes increases the development of normal synovial fibroblasts into transformed aggressive synovial fibroblasts. P53 levels were determined in supernatant of cultured mononuclear cells (MCs) isolated from peripheral blood (PBMCs) of patients with RA (n = 10) and OA (n = 10) as well as 10 normal healthy controls (C). P53 levels were also determined in supernatants of MCs isolated from synovial fluid (SFMCs) of RA and OA patients. Results of this work revealed that P53 level was significantly higher in PBMCs supernatant of RA group than those of both (C) and (OA) groups (P = 0.022). P53 level was non-significantly higher in SFMCs supernatant of RA than OA group. Significantly higher levels of P53 was detected in SFMCs culture supernatant than that of PBMCs within each RA (P = 0.003) and OA (P = 0.001) group. Results also showed a significantly positive correlation between P53 levels (in both PBMCs and SFMCs) and the disease activity score (DAS) in RA group (P = 0.01, P = 0.02 respectively) while insignificantly positive correlations between P53 level (in both PBMCs and SFMCs) and radiological grading of OA group were obtained. These results indicate that mutations and consequent dysfunction of P53 gene may result in chronic inflammation and hyperplasia in RA patients. In conclusion, gene therapy targeting P53-dependent pathway could be a promising therapy for RA and OA diseases.     

A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial

Timely participant recruitment remains a significant challenge for most clinical trials. We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial. The effects of communication were determined in a single-blind randomised controlled trial involving 167 clinical sites in 19 countries. Clinical sites were randomised to either additional or usual communication strategies - the additional communication group received a communication package based on additional, individually-tailored feedback about recruitment, in addition to the usual correspondence from the central trial coordinators that was provided to the control group. The two study outcomes were the median time to half randomisation target and the median total number of participants randomised per clinical site. Eighty-five clinical centres were randomised to receive additional communication and 82 to receive usual communication. At the conclusion of recruitment, there was no significant difference in the median number of participants randomised per centre between the additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half randomisation target was lower in the additional communication group compared to the usual group, however this difference did not achieve conventional levels of statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner.     

Metabolic syndrome in the Middle East

Metabolic syndrome (MS) is a combination of medical disorders that, in concert, increase the risk of developing cardiovascular disease and diabetes. It affects about one in four people in the Middle East, and prevalence increases with age. The aim of current review is to discuss the prevalence of MS and its component in different regions in the Middle East. The recorded high prevalence of the MS and its key cardiovascular risk factors (15-60%) among Middle East population mandates the need for a national and international prevention programs to combat obesity, diabetes, hypertension, dyslipidemia, smoking and related comorbidities. Consideration of early prevention and control is of utmost importance.