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Background: However, disturbances in cellular energy demarcate neuronal hyperexcitability in essential tremor (ET); nevertheless, no available data relates energy sensors and GABAergic neurotransmission in ET. Noteworthy, reports have asserted dapagliflozin's (DAPA) role in enhancing autophagic sensors in other disorders. Herein, this study aims to investigate DAPA's impact on the GABA B receptor subunit (GABA B R2), notwithstanding the GABA A involvement, in an ET model., Methods: ET was induced by a single dose of harmaline (30 mg/kg; i.p.), while DAPA (1 mg/kg/day; p.o.) was given for 5 days before ET induction. The autophagic sensors were examined by injecting a single dose of dorsomorphin (DORSO) AMPK inhibitor (0.2 mg/kg; i.p.) on the 5 th day before ET induction., Results: DAPA decreased the HAR-induced tremor score and alleviated motor disabilities observed in the open field, rotarod, wire grip strength, and gait kinematics confirmed by reduced electrical activity in electroencephalogram. In the cerebella, DAPA curbed HAR-evoked inflammatory cytokines, apoptotic markers, and glutamate while restoring the disturbed GABA, BDNF, LKB1, p-AMPK, and GABA B R2 levels. DAPA's effect was mostly obliterated by DORSO., Conclusion: DAPA offers a potential neuroprotective effect in ET by augmenting the neuronal inhibitory machinery via suppressing the inflammatory and excitotoxicity systems through LKB1/p-AMPK/GABA B R2 signaling.

Aim: To adapt and validate an Arabic version of the short form of physical function measure (PF-10a), a generic questionnaire for physical function, in Egyptian patients with rheumatoid arthritis (RA)., Methods: After standardized linguistic validation of the Arabic version of PF-10a, with forward and backward translation, the questionnaire was completed by 70 Egyptian RA patients who were diagnosed according to American College of Rheumatology/European League Against Rheumatism 2010 classification criteria, on two occasions 3-5 days apart. The internal consistency and test-retest reliability were evaluated using Cronbach's alpha and intra-class correlation. The content validity of the Arabic PF-10a was tested against Health Assessment Questionnaire Disability Index (HAQ-DI), Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). In addition, serology results, hand radiographs, and treatments received were all recorded., Results: Most of our patients were female (88.6%) with a mean age of 49.2 ± 10.5 years. They had a mean disease duration of 7.3 ± 7 years and an active disease with a mean CDAI of 33.1 ± 12.6. The mean value of PF-10a was 34.6 ± 6.2. The Cronbach's alpha for Arabic PF-10a was 0.904. Intra-CLASS CORRELATION was 0.897. Arabic PF-10a correlated strongly with HAQ-DI (-0.746), moderately with CDAI, patient global assessment, and pain (-0.457, -0.417, and -0.371 respectively)., Conclusion: The validation study showed that the Arabic PF-10a had acceptable psychometric characteristics, in terms of internal consistency and construct validity. The Arabic PF-10a is a reliable and valid instrument to be used by Arabic RA patients., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Aims: Statins are the most widely used to lower elevated low-density lipoprotein levels and preventing cardiovascular diseases in humans. However, about 20% of patients treated with this medication suffer from statin-related myalgia. To this end, this study investigated the potential effect of nano-particulate formulation in alleviating the muscles and liver damage either alone or when co-administered with nano coenzyme Q10 and nano vitamin E., Materials and Methods: Male Wistar rats were fed normal diet or high-fat diet for 12 weeks, following which rats were treated with either (i) atorvastatin (5 or 20 mg/kg/day, p.o.) or (ii) atorvastatin with CoQ10 (10 mg/kg/day, p.o.) (iii) and/or vitamin E (30 mg/kg/day, p.o.) in free particle or nanoparticle forms for another 4 weeks. In all rats, serum total cholesterol (CH), triglycerides (TGs), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), creatine kinase (CK), albumin (ALB), as well as hepatic malondialdehyde (MDA) and antioxidants "reduced glutathione (GSH) and superoxide dismutase (SOD)" were measured. Additionally quadriceps muscles and liver tissues were used for histopathological examination., Key Findings: The antihyperlipidemic effect of statins was not altered when formulated as nanoparticles; albeit the former showed a prominent reduction in the liver and muscle enzymes and histopathological alterations together with a marked decline in the oxidative stress as compared to the free particulate form. These results were augmented when atorvastatin was combined with CoQ10 and/or Vit.E., Significance: Nanoparticulate formulation alleviated the statins induced liver and muscle damage especially when combined with CoQ10 and/or Vit.E., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Ischemic acute kidney injury (AKI) is usually accompanied by neuroinflammation-induced encephalopathy. However, the specific mechanism remains unclear. Toll-like receptors (TLR), specifically TLR-4 has been linked to ischemic reperfusion injury in different organs like kidney, brain and liver. Here, we induced an ischemic reperfusion kidney injury in Sprague Dawley rats. All animals were evaluated using behavioral tests which revealed locomotor activity and motor disturbances in the AKI group. The brains were then examined by immunostaining with ionized calcium binding adaptor molecule 1 (microglial marker) and TLR-4 antibodies. The histological analysis revealed significant up-regulation of TLR-4 in the hippocampus and striatum in the AKI group. These data demonstrate for the first time, the triggering effect of TLR-4 on AKI-induced neuroinflammation in the brain that may lead to AKI-induced encephalopathy. This would also generate a novel hypothesis that using TLR blockers may have a role in preventing AKI effects on the brain.