A Comparative Study of Effect of Oral Melatonin Versus Oral Midazolam as Premedicant in Children Undergoing Surgery Under General Anesthesia

Background: Preoperative anxiety in children is associated with multiple post-operative outcomes like post-operative regressive behavioral disturbances, prolonged distress in the recovery phase, eating disorders, and bedwetting. The present study was designed to use low-dose oral melatonin versus oral midazolam in relieving pre-operative anxiety in children in the Indian population. Materials and Methods: A prospective randomized comparative study was conducted on children aged between 2 to 10 years of age scheduled for elective surgeries under general anesthesia are included in the study. This study was conducted with a sample size of 70. Patients were randomly distributed into two groups of 35 content. Group A (received 0.2mg/kg melatonin as premedical) and group B (received 0.5mg/kg midazolam as premedical). Results: Mean induction dose of propofol in the melatonin group was 52.143+ 18.36 mg and in the midazolam, the group was 48.714 + 16.6 mg. In our study, 90 minutes after premedication, the anxiety score was less in the midazolam group. There was no statistically significant difference between the sedation scores in melatonin and midazolam. Conclusion: Low-dose melatonin (0.2mg/kg) is not an effective alternative premedicant in children to alleviate preoperative anxiety compared to midazolam

Falls and Physical Activity in Persons with Multiple Sclerosis

Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P \u3c .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P \u3e.05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Superconducting ground state study of valence skip compound AgSnSe2_2

The valence-skipped superconductors are natural candidates for unconventional superconductivity, as they can exhibit a negative effective, attractive interaction for electron-pairing. This work reports comprehensive XRD, magnetization, specific heat and muon spin rotation and relaxation measurements ($\mu$SR) on a valence-skipped compound: AgSnSe$_2$. The temperature dependence of the electronic specific heat ($C_{el}(T)$) and of the upper critical field ($H_{c2}(T)$) provide evidence of two-gap superconductivity, which is also confirmed by our transverse-field $\mu$SR measurements. Our zero-field $\mu$SR measurements suggest preserved time-reversal symmetry in the superconducting ground state of AgSnSe$_2$.Comment: 8 pages, 6 figure

Role of spin orbital coupling in unconventional superconductivity

We have studied the superconducting properties of the ternary noncentrosymmetric superconductors TaXSi (X = Re, Ru), with the help of muon spin rotation/relaxation ({\mu}SR) and density functional theory calculations. Our transverse-field {\mu}SR measurements reveal isotropic s-wave superconductivity in TaReSi and multi-gap superconductivity with gap nodes in TaRuSi. Zero-field {\mu}SR measurements, highly sensitive to very small magnetic fields find no evidence for spontaneous fields in the superconducting state of TaReSi, whereas we observe spontaneous fields which onset with superconductivity indicating broken time reversal symmetry (TRS) superconductivity in TaRuSi. Broken TRS in weakly coupled TaRuSi can be attributed to a non-unitary triplet pairing state, while in TaReSi, this state is suppressed due to strong anti-symmetric spin orbital coupling. Our results in TaXSi demonstrate that the strength of spin orbit coupling can be responsible for stabilizing unconventional superconductivity.Comment: 10 Pages, 5 Figure

Falls and physical activity in persons with multiple sclerosis

Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P < .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P > .05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis

Delineation of the movement disorders associated with FOXG1 mutations

Objective: The primary objective of this research was to characterize the movement disorders associated with FOXG1 mutations. Methods: We identified patients with FOXG1 mutations who were referred to either a tertiary movement disorder clinic or tertiary epilepsy service and retrospectively reviewed medical records, clinical investigations, neuroimaging, and available video footage. We administered a telephone-based questionnaire regarding the functional impact of the movement disorders and perceived efficacy of treatment to the caregivers of one cohort of participants. Results: We identified 28 patients with FOXG1 mutations, of whom 6 had previously unreported mutations. A wide variety of movement disorders were identified, with dystonia, choreoathetosis, and orolingual/facial dyskinesias most commonly present. Ninety-three percent of patients had a mixed movement disorder phenotype. In contrast to the phenotype classically described with FOXG1 mutations, 4 patients with missense mutations had a milder phenotype, with independent ambulation, spoken language, and normocephaly. Hyperkinetic involuntary movements were a major clinical feature in these patients. Of the symptomatic treatments targeted to control abnormal involuntary movements, most did not emerge as clearly beneficial, although 4 patients had a caregiver-reported response to levodopa. Conclusions: Abnormal involuntary movements are a major feature of FOXG1 mutations. Our study delineates the spectrum of movement disorders and confirms an expanding clinical phenotype. Symptomatic treatment may be considered for severe or disabling cases, although further research regarding potential treatment strategies is necessary

Differential Roles of the PKC Novel Isoforms, PKCδ and PKCε, in Mouse and Human Platelets

Background Increasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation. Methodology/Principal Findings In this study, we focus on the role of two novel PKC isoforms, PKCδ and PKCε, in both mouse and human platelets. PKCδ is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCδ undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCε, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCε in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRγ-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor. Conclusions These results demonstrate a reciprocal relationship in levels of the novel PKC isoforms δ and ε in human and mouse platelets and a selective role for PKCε in signalling through GPVI