ANALYSIS OF RELIABILITY AND CONDUCTION MECHANISMS IN EMBEDDED PLANAR CAPACITORS

An embedded planar capacitor is a thin laminate embedded in a multilayered printed wiring board (PWB) that functions both as a power-ground plane and as a parallel plate capacitor. The capacitor laminate consists of a dielectric material (epoxy-BaTiO3 composite dielectric is widely used) sandwiched between two Cu layers. These capacitors have gained importance with an increase in the operating frequency and a decrease in the supply voltage in electronic circuits since it can lead to PWB miniaturization. Further, the use of embedded planar capacitor leads to better electrical performance of the PWB. Although embedded planar capacitors have various advantages there are some issues such as lack of reliability information and a high leakage current in the epoxy-BaTiO3 composite dielectric. This dissertation aims in investigating these issues that needs to be investigated for wide scale commercialization of these capacitors. The reliability of embedded planar capacitors is critical since these capacitors are not reworkable and its failure can lead to PWB failure. In this work the reliability of an embedded planar capacitor (with epoxy-BaTiO3 composite dielectric) is investigated under environmental stress conditions in the presence of an applied bias. Temperature-humidity-bias (THB) tests and highly accelerated life test (HALT) was performed at multiple stress levels to investigate the reliability under these conditions. The failure modes and mechanisms during THB and HALT are investigated. Further, during HALT the life time is also modeled using the Prokopowicz model and regression of the in-situ capacitor data. The loading of BaTiO3 in the epoxy-BaTiO3 composite dielectric should be as high as possible (until the theoretical maximum packing density is achieved) to maximize the effective dielectric constant of the composite. But as the loading of BaTiO3 in the composite dielectric increases, the undesirable leakage current also increases. The mechanism of current conduction in this composite dielectric is investigated in this work. The effect of various factors such as BaTiO3 loading, BaTiO3 particle diameter, temperature, and voltage on the resulting leakage current has been modeled. Measurements of leakage current were performed on embedded capacitors with varying BaTiO3 loading and varying particle diameters over a range of temperature and voltage. The consistence of the leakage current data with standard conduction models is compared to investigate the conduction mechanism

Systems Biology of Immunomodulation for Post-Stroke Neuroplasticity: Multimodal Implications of Pharmacotherapy and Neurorehabilitation.

AIMS: Recent studies indicate that anti-inflammatory drugs, act as a double-edged sword, not only exacerbating secondary brain injury but also contributing to neurological recovery after stroke. Our aim is to explore whether there is a beneficial role for neuroprotection and functional recovery using anti-inflammatory drug along with neurorehabilitation therapy using transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), so as to improve functional recovery after ischemic stroke. METHODS: We develop a computational systems biology approach from preclinical data, using ordinary differential equations, to study the behavior of both phenotypes of microglia, such as M1 type (pro-inflammatory) vis-à-vis M2 type (anti-inflammatory) under anti-inflammatory drug action (minocycline). We explore whether pharmacological treatment along with cerebral stimulation using tDCS and rTMS is beneficial or not. We utilize the systems pathway analysis of minocycline in nuclear factor kappa beta (NF-κB) signaling and neurorehabilitation therapy using tDCS and rTMS that act through brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) signaling pathways. RESULTS: We demarcate the role of neuroinflammation and immunomodulation in post-stroke recovery, under minocycline activated-microglia and neuroprotection together with improved neurogenesis, synaptogenesis, and functional recovery under the action of rTMS or tDCS. We elucidate the feasibility of utilizing rTMS/tDCS to increase neuroprotection across the reperfusion stage during minocycline administration. We delineate that the signaling pathways of minocycline by modulation of inflammatory genes in NF-κB and proteins activated by tDCS and rTMS through BDNF, TrkB, and calmodulin kinase (CaMK) signaling. Utilizing systems biology approach, we show that the activation pathways for pharmacotherapy (minocycline) and neurorehabilitation (rTMS applied to ipsilesional cortex and tDCS) results into increased neuronal and synaptic activity that commonly occur through activation of N-methyl-d-aspartate receptors. We construe that considerable additive neuroprotection effect would be obtained and delayed reperfusion injury can be remedied, if one uses multimodal intervention of minocycline together with tDCS and rTMS. CONCLUSION: Additive beneficial effect is, thus, noticed for pharmacotherapy along with neurorehabilitation therapy, by maneuvering the dynamics of immunomodulation using anti-inflammatory drug and cerebral stimulation for augmenting the functional recovery after stroke, which may engender clinical applicability for enhancing plasticity, rehabilitation, and neurorestoration

Microwave-assisted green synthesis and antimicrobial activity of silver nanoparticles derived from a supercritical carbon dioxide extract of the fresh aerial parts of Phyllanthus niruri L

Purpose: To synthesize and evaluate the antimicrobial activity of silver nanoparticles (AgNPs) derived from a supercritical carbon dioxide extract of the fresh aerial parts of Phyllanthus niruri. Methods: The synthesis of AgNPs of a P. niruri extract was carried out in a microwave oven. The extraction was carried out using a supercritical fluid extractor. The AgNPs were characterized by the Ultraviolet-visible (UV-vis) spectral analysis, Dynamic Light Scattering (DLS) zetasizer analysis, Transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis and Fourier transform infrared (FT-IR) spectroscopy. The antimicrobial assays of AgNPs were carried out against different bacterial and fungal strains. Results: Results of various analytical techniques confirmed the synthesis of AgNPs of a P. niruri extract. The UV–vis spectroscopy showed an intense silver surface plasmon resonance band at 415 NM. The AgNPs had a mean size of 110 nm in the Zetasizer analysis. TEM images illustrated spherical AgNPs having a mean particle size of 110 nm. The X-ray diffractograms showed peaks at 38.17°, 44.28°, and 64.52°. The average crystallite size of Ag-NPs was found to be 110 nm. FT-IR spectra confirmed the stability of the AgNPs. The AgNPs demonstrated good antimicrobial effects against several tested pathogenic microbes. Conclusion: An efficiently synthesized AgNPs of P. niruri (SC-CO2) extract has been prepared by a simple, eco-friendly, cost-effective, rapid green chemistry methodology. The AgNPs of P. niruri extract possesses significant antimicrobial properties against the tested bacterial and fungal strains. Keywords: Nanoparticles, Phyllanthus niruri, Supercritical fluid extraction, Microwave, Antimicrobial activit

COMPARATIVE ANTI-INFLAMMATORY AND HEPATOPROTECTIVE ACTIVITIES OF ASTRAGALUS GUMMIFER LABILL HERB AND ROOTS IN RATS

Background: The Astragalus gummifer (F. Fabaceae), herb and roots were studied for anti-inflammatory and hepatoprotective activities. Materials and method: The alcoholic extracts of Astragalus gummifer (F. Fabaceae), herb (AGHE), and roots (AGRE), were used for anti-inflammatory and hepatoprotective activities in Wister rats. The effects of AGHE and AGRE were compared with the standard drugs Phenylbutazone and silymarin, for anti-inflammatory and hepatoprotective activities respectively. Result: Both extracts showed significant anti-inflammatory activity (P< 0.001). AGRE showed comparatively more significant hepatoprotective activity (P< 0.001), than AGHE (P< 0.05); at doses of 250 and 500 mg/kg body weight as manifested by lowering the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin. The hepatoprotective activity was, also, supported by total protein (TP), malondialdehyde (MDA), nonprotein sulfhydryls (NP-SH), and histo-pathological studies of liver tissue. Discussion: To the best of our knowledge, this is the first report of the anti-inflammatory and hepatoprotective activities of Astragalus gummifer. The results of present studies indicated that both AGHE and AGRE can be used in inflammatory conditions, while investigation supports the use of AGRE in cases that hepatoprotection are required in the hepatotoxic conditions. More supportive studies are required before clinical recommendation

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Theoretical and experimental study on lipophilicity and wound healing activity of ginger compounds

Objective: To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing. Methods: Mixtures of acetonitrile and water with acetonitrile content between 95% and 50% v/v in 5% increments were kept separately in 10 different chromatographic chambers, saturated with solvent for 2 h. Spots were observed under UV light at λ=254 nm p-anisaldehyde used as a spraying reagent. Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps. For percentage wound contraction, five groups of animal (mice) (25-30 g) of either sex were selected. Wound were created on dorsal surface of animals using toothed forceps, scalpel and pointed scissors. The wound areas were calculated using vernier caliper. After making wound mice were orally administered 35 mg/kg 6-shogoal, 6-gingerol, 8-gingerol and 10-gingerol respectively. Group E as the control group received tap water. Results: The lipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis. Significant correlations were found between log P values calculated by software program and the experimental reversed-phase thin-layer chromatography data. Order of wound healing property of ginger compounds is directly dependent on lipophilicity i.e. more lipophilic compound has highest activity. Conclusions: Experimentally determined lipophilicity (RMO) values were correlated with log P determined by software's and found satisfactory. Lipophilicity (RMO) is a useful parameter for the determination and prediction of biological activity of ginger compounds

QbD-Optimized, Phospholipid-Based Elastic Nanovesicles for the Effective Delivery of 6-Gingerol: A Promising Topical Option for Pain-Related Disorders

In this study, elastic nanovesicles, constructed of phospholipids optimized by Quality by Design (QbD), release 6-gingerol (6-G), a natural chemical that may alleviate osteoporosis and musculoskeletal-related pain. A 6-gingerol-loaded transfersome (6-GTF) formulation was developed using a thin film and sonication approach. 6-GTFs were optimized using BBD. Vesicle size, PDI, zeta potential, TEM, in vitro drug release, and antioxidant activity were evaluated for the 6-GTF formulation. The optimized 6-GTF formulation had a 160.42 nm vesicle size, a 0.259 PDI, and a −32.12 mV zeta potential. TEM showed sphericity. The 6-GTF formulation’s in vitro drug release was 69.21%, compared to 47.71% for the pure drug suspension. The Higuchi model best described 6-G release from transfersomes, while the Korsmeyer–Peppas model supported non-Fickian diffusion. 6-GTF had more antioxidant activity than the pure 6-G suspension. The optimized transfersome formulation was converted into a gel to improve skin retention and efficacy. The optimized gel had a spreadability of 13.46 ± 4.42 g·cm/s and an extrudability of 15.19 ± 2.01 g/cm2. The suspension gel had a 1.5 μg/cm2/h ex vivo skin penetration flux, while the 6-GTF gel had 2.71 μg/cm2/h. Rhodamine B-loaded TF gel reached deeper skin layers (25 μm) compared to the control solution in the CLSM study. The gel formulation’s pH, drug concentration, and texture were assessed. This study developed QbD-optimized 6-gingerol-loaded transfersomes. 6-GTF gel improved skin absorption, drug release, and antioxidant activity. These results show that the 6-GTF gel formulation has the ability to treat pain-related illnesses effectively. Hence, this study offers a possible topical treatment for conditions connected to pain

Formulation, In Vitro and In Silico Evaluations of Anise (<i>Pimpinella anisum</i> L.) Essential Oil Emulgel with Improved Antimicrobial Effects

Over the past decade, researchers have made several efforts to develop gel-based formulations that provide an alternative to traditional hydrogels and emulgel. Due to its excellent antibacterial properties, anise, the main constituent of Pimpinella anisum L., widely used in pharmaceuticals, was selected as the active ingredient in this study. Since many bacteria have developed considerable antibiotic resistance, this research aimed to develop an herbal emulgel for treating skin infections caused by bacteria. Given these obstacles, we developed and evaluated a new, cost-effective topical emulgel solution containing anise essential oil against Escherichia coli (E. coli). Anise-based emulgels, potential drug delivery platforms, have been evaluated for various parameters, including physical properties, viscosity, pH, rheology, encapsulation efficiency, and in vitro release research. The AEOs emulgel demonstrated remarkable colloidal stability, with a zeta potential of 29 mV, a size of 149.05 nm, and considerable polydispersity. The efficacy of anise-loaded emulgels as antibacterial formulations was evaluated in vitro. E. coli was used as a model microbial organism for the antibacterial study. Human keratinocytes (HaCaT) were used to examine the biocompatibility of the emulgel. Molecular docking revealed that the essential oil components of Pimpinella anisum L. possess a high affinity for the bacterial adhesin protein FimH of E. coli. These findings indicate that the developed AEOs have the potential to be analyzed using E. coli as a model organism