Real-World Effectiveness of the Varicella Vaccine among Children and Adolescents in Qatar: A Case-Control Study.

BACKGROUND: Despite the availability of a highly efficacious vaccine, varicella outbreaks are still being reported globally. In this study, we evaluated the real-world effectiveness of varicella vaccination among children between the ages of 1 and 18 years old during the period 2017 to 2019 in Qatar. METHODS: A matched case-control study was conducted that included all reported varicella-infected children who visited the primary healthcare system in Qatar from January 2017 to December 2019. The cases were children under the age of 18 years who were clinically diagnosed with varicella. The controls were of the same age, who visited the Primary Health Care Corporation (PHCC) during 2017-2019 with a skin rash where varicella infection was ruled out. The data on varicella vaccination for each participant were obtained from the electronic database in the PHCC during the study period. RESULTS: We included 862 cases of varicella and 5454 matched controls, with a median age of 8 years (IQR 3-12); 47.4% were female and almost 50% were of Qatari nationality. The year 2019 had the highest varicella infection count with a total of 416 cases. The cases were less likely to be vaccinated against varicella, with approximately a quarter (25.6%) of cases and 36.7% of the controls having either one or two doses of the vaccine (p < 0.001). Compared to not being vaccinated, a single dose vaccination showed a 56% reduction in the odds of varicella infection [OR 0.44, 95% CI: 0.34-0.55; p < 0.000], and a two-dose vaccination showed an 86% reduction in the odds of varicella infection [OR 0.13, 95% CI: 0.06-0.29; p < 0.000]. CONCLUSION: In this multicultural setting, a two-dose varicella vaccination shows reasonable protection against varicella infection.

Activation and Inactivation of Nicotinic Receptnors in the Dorsal Hippocampal Region Restored Negative Effects of Total (TSD) and REM Sleep Deprivation (RSD) on Memory Acquisition, Locomotor Activity and Pain Perception.

Sleep deprivation (SD) is a common issue in today's society. Sleep is essential for proper cognitive functions, including learning and memory. Furthermore, sleep disorders can alter pain information processing. Meanwhile, hippocampal nicotinic receptors have a role in modulating pain and memory. The goal of this study is to investigate the effect of dorsal hippocampal (CA1) nicotinic receptors on behavioral changes induced by Total (TSD) and REM Sleep Deprivation (RSD). A modified water box and multi-platform apparatus were used to induce TSD and RSD, respectively. To investigate the interaction between nicotinic receptors and hippocampus-dependent memory, nicotinic receptor agonist (nicotine) or antagonist (mecamylamine) was injected into the CA1 region. The results showed, nicotine at the doses of 0.001 and 0.1 µg/rat and mecamylamine at the doses of 0.01 and 0.1 µg/rat decreased memory acquisition, while both at the doses of 0.01 and 0.1 µg/rat enhanced locomotor activity. Additionally, all doses used for both drugs did not alter pain perception. Also, 24 h TSD or RSD attenuated memory acquisition with no effect on locomotor activity and only TSD induced an analgesic effect. Intra-CA1 administration of subthreshold dose of nicotine (0.0001 µg/rat) and mecamylamine (0.001 µg/rat) did not alter memory acquisition, pain perception and locomotor activity in sham of TSD/RSD rats. Both drugs reversed all behavioral changes induced by TSD. Furthermore, both drugs reversed the effect of RSD on memory acquisition, while only mecamylamine reversed the effect of RSD on locomotor activity. In conclusion, CA1 nicotinic receptors play a significant role in TSD/RSD-induced behavioral changes.

Chemical composition and antibacterial properties of Peganum harmala L.

OBJECTIVE: The present study was conducted to investigate antibacterial properties of fruit and flower of Peganum harmala. MATERIAL AND METHODS: Column chromatography, followed by preparative thin layer chromatography (TLC) was used for final purification. The structure of pure alkaloids was determined using spectroscopic methods (1H-NMR, 13C-NMR, UV and MS). Smoke and extract of total alkaloids were investigated for antimicrobial activity against five different microorganisms (standards and hospital isolates). The antibacterial activity was evaluated using disc diffusion assay and minimum inhibitory concentration (MIC) was determined by serial dilution methods. RESULTS: Chemical investigation of the chloroform extract of ripe fruit and flower of P. harmala led to identification of three alkaloids in ripe fruit and two alkaloids in the flower and leaves of this plant. Alkaloids identified in ripe fruit were harmine, peganine (vasicine) and harmaline. Two alkaloids, harmine and peganine, were detected in the flower of P. harmala, while harmaline was only found in the ripe fruit. The total alkaloids of flower were compared with total alkaloids of ripe fruit by TLC method. Fruits and flowers had 3.12 and 3.27% alkaloid contents, respectively. CONCLUSION: Our results showed that the alkaloids and smoke were specifically more effective on Candida albicans and Gram- positive bacteria (Micrococcus luteus and Staphylococcus aureus), while Gram- negative bacteria, especially Pseudomonas aeruginosa, were less sensitive.

Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD).

AIM: Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). METHOD: A modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to determine the effects of SD and its changes by physostigmine (as cholinesterase inhibitor) or scopolamine (muscarinic receptor antagonist) on memory formation. Because locomotor activity and pain perception induce critical roles in passive avoidance memory formation, we also measured these factors by open field and hot-plate instruments, respectively. RESULTS: The results showed that TSD and RSD for 24 hours impaired memory formation but they did not alter locomotor activity. TSD also induced analgesia effect, but RSD did not alter it. Intra-CA1 injection of physostigmine (0.0001µg/rat) and scopolamine (0.01µg/rat) did not alter memory acquisition in the sham-TSD or sham-RSD, by themselves. Moreover, intra-CA1 injection of sub-threshold dose of physostigmine (0.0001µg/rat) and scopolamine (0.01µg/rat) could restore the memory acquisition deficit induced by RSD, while scopolamine could restore TSD-induced amnesia. Both drugs reversed analgesia induced by TSD. None of previous interventions altered locomotor activity. CONCLUSION: According to this study, CA1 cholinergic muscarinic receptors play an important role in amnesia induced by both TSD and RSD. However further studies are needed for showing cellular and molecular mechanisms of surprising result of similar pharmacological effects using compounds with opposite profiles.

Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents.

Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec). We evaluated their inhibitory activities against pan HDAC and HDAC1 isoform. Four compounds (8f, 8q, 8r and 8u) showed significant cytotoxicity with IC50 in the range of 0.53-57.59 µM on cancer cells and potent pan-HDAC inhibitory activity (consists of HDAC isoenzymes) (IC50 = 0.80-14.81 µM) and HDAC1 inhibitory activity (IC50 = 0.47-0.87 µM and also, had no effect on Huvec (human normal cell line) viability (IC50 > 100 µM). Among them, 8u displayed a higher potency for HDAC1 inhibition with IC50 value of 0.47 ± 0.02 µM near equal to the reference drug Entinostat (IC50 = 0.41 ± 0.06 µM). Molecular docking studies and Molecular dynamics simulation of compound 8a displayed possible mode of interaction between this compound and HDAC1enzyme.

Self-assembled supramolecular hydrogel based on PCL-PEG-PCL triblock copolymer and γ-cyclodextrin inclusion complex for sustained delivery of dexamethasone.

In this study, thermosensitive, water-soluble, and biodegradable triblock copolymer PCL600-PEG6000-PCL600 was used to form supramolecular hydrogel (SMGel) by inclusion complexation with γ-cyclodextrin (γ-CD). The prepared SMGel was investigated as a carrier for sustained release of dexamethasone. The triblock copolymer PCL-PEG-PCL [where PCL = polycaprolactone, PEG = poly(ethylene glycol)] was synthesized by the ring-opening polymerization method using microwave irradiation. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). SMGel was prepared in aqueous solution by blending an aqueous γ-CD solution with aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. The sol-to-gel transition time was measured at various concentrations of copolymer and γ-CD. As-prepared SMGel was used to prepare a sustained, controllable drug delivery system of dexamethasone sodium phosphate. The SMGel was also characterized in terms of rheological, morphological, and structural properties. Results obtained from proton nuclear magnetic resonance ( (1)H-NMR) and GPC demonstrated that microwave irradiation is a simple and reliable method for synthesis of PEG-PCL copolymer. The SMGel with excellent syringability was prepared by mixing of 20% wt γ-CD and 10% wt of copolymer within 4 s. The SMGel containing 10% wt copolymer, 20% wt γ-CD, and 0.5% or 0.1% wt dexamethasone released approximately 100% and 45% of drug over up to 23 days, respectively. It could be concluded that SMGel based on self-assembly of inclusion complexes between PCL-PEG-PCL copolymer and γ-CD could be used as a basis for injectable drug delivery systems that provide sustained and controlled release of macromolecular drugs such as dexamethasone.

Preparation of a sustained release drug delivery system for dexamethasone by a thermosensitive, in situ forming hydrogel for use in differentiation of dental pulp.

In situ forming delivery systems composed of block copolymers are attracting substantial attention due to their ease of use, biocompatibility, and biodegradability. In this study, the thermoresponsive triblock copolymer PLGA-PEG-PLGA was studied as a dexamethasone delivery system. Dexamethasone, a synthetic glucocorticoid, is used clinically to improve inflammation, pain, and the hyperemesis of chemotherapy, and it is applied experimentally as a differentiation factor in tissue engineering. PLGA-PEG-PLGA was synthesised under microwave irradiation for 5 min. The obtained copolymer was characterised to determine its structure and phase transition temperature. An in vitro release study was conducted for various copolymer structures and drug concentrations. The yield of the reaction and HNMR analysis confirmed the appropriateness of the microwave-assisted method for PLGA-PEG-PLGA synthesis. Phase transition temperature was affected by the drug molecule as well as by the copolymer concentration and structure. An in vitro release study demonstrated that release occurs mainly by diffusion and does not depend on the copolymer structure or dexamethasone concentration.