Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats.

Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration. Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport. Results: Mean ± SD ivacaftor oral bioavailability was 18.4 ± 3.2% and 16.2 ± 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 ± 1.61% and 4.35 ± 1.84%, respectively. Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.

Isolated Trochlear Fracture in an Elderly Lady : A Rare and Interesting Case Treated in a Rural Coal Mines Hospital.

Introduction: Isolated trochlear fractures are very rarely reported in the orthopedic literature; moreover, most of the cases reported are of patients in the younger age group. Due to its anatomical position, trochlear fractures are usually associated with other bony injuries around the distal humerus and with elbow dislocation, and so, its extremely rare to find an isolated trochlear fracture reported in postmenopausal lady with osteoporotic bone. Case Report: Here, we report a postmenopausal elderly lady suffering from isolated trochlear fracture of humerus trochlea. She was having pain and discomfort around her right elbow with restricted motion in elbow following a blunt trauma. After necessary investigation, we treated the patient with open reduction through posterior approach to elbow with olecranon osteotomy and fixed the fracture under direct vision with headless titanium screws. Post-operative physiotherapy was initiated after 2 weeks as pain subsided. Conclusion: Isolated trochlear fractures are rare clinical entity specially in postmenopausal women and it should be properly managed for a good clinical and functional outcome.

Effect of non surgical periodontal therapy and vitamin C supplementation on total antioxidant capacity in patients with chronic generalised periodontitis - A randomised controlled trial.

Background: Periodontal inflammation are inflammation of supporting tissues of periodontium. The microbial factor can cause infection which is polymicrobial in origin and causes dysbiosis and shift in oxidative stress with compromised antioxidant capacity. This study focused at determination of the effect of nonsurgical periodontal therapy (NSPT) and vitamin C supplementation on total antioxidant capacity (TAOC) in chronic periodontitis patients (ChP). Material & method: A total of 70 ChPand 35 periodontally healthy subjects (control) were recruited in this study. Further, ChP group was subdivided into ChP1 group (n = 35) which received NSPT only and ChP 2 group (n = 35) which received NSPT with vitamin C 500 mg once daily for 3 months. Serum and saliva samples were taken at baseline and at 3 months postNSPT for measurement of TAOC. Clinical parameters measured were measured at 1-, 3-, 6- and 12-month interval. Results: Lower levels of serum and salivary TAOC levels were observed in ChP patients than healthy subjects (p < 0.05). Improvement in Clinical parameters was observed in both the groups ChP1 and ChP 2 group post therapy (p < 0.05). The periodontal treatment showed insignificant changes in serum and salivary TAOC levels (p > 0.05). The supplemental dose of vitamin C didn't have any additional benefits (p > 0.05). Conclusion: There lies an association of oxidative stress with periodontitis, low serum and salivary TAOC levels were seen in chronic periodontitis patients. NSPT improved the periodontal inflammatory status. However, benefits of vitamin C as an adjunct to NSPT remains inconclusive and needs to be further explored by multicentre longitudinal studies.

Simultaneous Anodic and Cathodic Formate Production in a Paired Electrolyzer by CO2 Reduction and Glycerol Oxidation.

Electrochemical CO2 conversion is a key technology to promote the production of carbon-containing molecules, alongside reducing CO2 emissions leading to a closed carbon cycle economy. Over the past decade, the interest to develop selective and active electrochemical devices for electrochemical CO2 reduction emerged. However, most reports employ oxygen evolution reaction as an anodic half-cell reaction causing the system to suffer from sluggish kinetics with no production of value-added chemicals. Therefore, this study reports a conceptualized paired electrolyzer for simultaneous anodic and cathodic formate production at high currents. To achieve this, CO2 reduction was coupled with glycerol oxidation: a BiOBr-modified gas-diffusion cathode and a Nix B on Ni foam anode keep their selectivity for formate in the paired electrolyzer compared to the half-cell measurements. The paired reactor here reaches a combined Faradaic efficiency for formate of 141 % (45 % anode and 96 % cathode) at a current density of 200 mA cm-2 .

Ag-induced Phase Transition of Bi2 O3 Nanofibers for Enhanced Energy Conversion Efficiency towards Formate in CO2 Electroreduction.

Bi-based electrocatalysts have been widely investigated in the CO2 reduction reaction (CO2 RR) for the formation of formate. However, it remains a challenge to achieve high Faradaic efficiency (FE) and industrial current densities at low overpotentials for obtaining both high formate productivity and energy efficiency (EE). Herein, we report an Ag-Bi2 O3 hybrid nanofiber (Ag-Bi2 O3 ) for highly efficient electrochemical reduction of CO2 to formate. Ag-Bi2 O3 exhibits a formate FE of >90% for current densities from -10 to -250 mA ⋅ cm-2 and attains a yield rate of 11.7 mmol ⋅ s-1 ⋅ m-2 at -250 mA ⋅ cm-2 . Moreover, Ag-Bi2 O3 increased the EE (52.7%) by nearly 10% compared to a Bi2 O3 only counterpart. Structural characterization and in-situ Raman results suggest that the presence of Ag induced the conversion of Bi2 O3 from a monoclinic phase (α-Bi2 O3 ) to a metastable tetragonal phase (ß-Bi2 O3 ) and accelerated the formation of active metallic Bi at low overpotentials (at > -0.3 V), which together contributes to the highly efficient formate formation.

Cellular Landscaping of COVID-19 and Gynaecological Cancers: An Infrequent Correlation.

COVID-19 resulted in a mortality rate of 3-6% caused by SARS-CoV-2 and its variant leading to unprecedented consequences of acute respiratory distress septic shock and multiorgan failure. In such a situation, evaluation, diagnosis, treatment, and care for cancer patients are difficult tasks faced by medical staff. Moreover, patients with gynaecological cancer appear to be more prone to severe infection and mortality from COVID-19 due to immunosuppression by chemotherapy and coexisting medical disorders. To deal with such a circumtances oncologists have been obliged to reconsider the entire diagnostic, treatment, and management approach. This review will provide and discuss the molecular link with gynaecological cancer under COVID-19 infection, providing a novel bilateral relationship between the two infections. Moreover, the authors have provided insights to discuss the pathobiology of COVID-19 in gynaecological cancer and their risks associated with such comorbidity. Furthermore, we have depicted the overall impact of host immunity along with guidelines for the treatment of patients with gynaecological cancer under COVID-19 infection. We have also discussed the feasible scope for the management of COVID-19 and gynaecological cancer.

Charge storage mechanism in vanadium telluride/carbon nanobelts as electroactive material in an aqueous asymmetric supercapacitor.

A novel one-step method for fabricating vanadium telluride nanobelt composites for high-performance supercapacitor applications is reported. The nanobelts are realized by direct tellurization of vanadium oxide in-situ formed via decomposition of ammonium metavanadate in argon atmosphere. Use of melamine as precursor helps in forming graphitic carbon layers during pyrolization on which the nanobelts are grafted. Morphological analysis suggests interconnected nanobelts of ∼23.0 nm width coming out of carbon structure. As pseudocapacitive electrode, vanadium telluride/carbon (C) composite exhibits interesting electrochemical performance within a potential window of 0-1.0 V in 1.0 M sodium sulfate electrolyte along with excellent capacitance retention during 5000 cycles. In-depth analysis suggests that the charge storage mechanism in the composite is governed by both diffusion-controlled and diffusion-independent processes with the former dominating at slower scan rates and later at faster scan rates. The asymmetric supercapacitor assembled using vanadium telluride/C and activated charcoal (AC) as respective positive and negative electrodes exhibited an energy/power combination of 19.3 Wh/kg and 1.8 kW/kg within a potential window of 0-1.8 V in aqueous electrolyte. This strategy to improve capacitance along with potential window in an aqueous electrolyte would facilitate development of high-performance energy storage devices with metal chalcogenides.

CoviLearn: A Machine Learning Integrated Smart X-Ray Device in Healthcare Cyber-Physical System for Automatic Initial Screening of COVID-19.

The pandemic of novel Coronavirus Disease 2019 (COVID-19) is widespread all over the world causing serious health problems as well as serious impact on the global economy. Reliable and fast testing of the COVID-19 has been a challenge for researchers and healthcare practitioners. In this work, we present a novel machine learning (ML) integrated X-ray device in Healthcare Cyber-Physical System (H-CPS) or smart healthcare framework (called "CoviLearn") to allow healthcare practitioners to perform automatic initial screening of COVID-19 patients. We propose convolutional neural network (CNN) models of X-ray images integrated into an X-ray device for automatic COVID-19 detection. The proposed CoviLearn device will be useful in detecting if a person is COVID-19 positive or negative by considering the chest X-ray image of individuals. CoviLearn will be useful tool doctors to detect potential COVID-19 infections instantaneously without taking more intrusive healthcare data samples, such as saliva and blood. COVID-19 attacks the endothelium tissues that support respiratory tract, and X-rays images can be used to analyze the health of a patient's lungs. As all healthcare centers have X-ray machines, it could be possible to use proposed CoviLearn X-rays to test for COVID-19 without the especial test kits. Our proposed automated analysis system CoviLearn which has 98.98% accuracy will be able to save valuable time of medical professionals as the X-ray machines come with a drawback as it needed a radiology expert.

Interfacial Electron Transfer Strategy to Improve the Hydrogen Evolution Catalysis of CrP Heterostructure.

Though several Pt-free hydrogen evolution reaction (HER) catalysts have been reported, their employment for industry is challenging. Here, a facile pyrolysis method to obtain phase-pure CrP nanoparticles supported on N, P dual-doped carbon (CrP/NPC) is reported to be tuned toward industrial HER. Interestingly, CrP/NPC exhibits excellent HER activity that requires an overpotential of 34 mV to attain a current density of 10 mA cm-2 , which is only 1 mV positive to commercial Pt/C and a potential of 55 mV to achieve a current density of 200 mA cm-2 which is better than Pt/C. In addition, the long-term durability of CrP/NPC is far superior to Pt/C due to the strong interaction between CrP and C support, restricting any agglomeration or leaching. Density functional theory (DFT) calculations suggest that electronic modulation at the interface (CrP/NPC) optimizes the hydrogen adsorption energy. The Cr-Cr bridge site with required density of states near the Fermi level is found to be the active site. Overall, this report provides a practical scheme to synthesize rarely investigated CrP based materials along with a computational mechanistic guideline for electrocatalysis that can be utilized to explore other phosphides for various applications.

Robust Visible-Blind Wearable Infrared Sensor Based on IrP2 Nanoparticle-Embedded Few-Layer Graphene and the Effect of Photogating.

It is challenging to realize a visible-blind infrared photodetector as the materials that absorb infrared light also absorb visible light. Here, we report the synthesis of IrP2 nanoparticle-embedded few-layer graphene by one-step solid-state pyrolysis and its application in visible-blind infrared sensing. A linear photodetector device was fabricated by drop casting IrP2 nanoparticle-embedded few-layer graphene onto a flexible PET substrate with two gold electrodes separated by ∼16 µm. The photoconductive gain was found to be as high as ∼145% with response and decay times of ∼0.4 and ∼2.8 s, respectively, under 1550 nm irradiation of 800 mW cm-2. The room-temperature responsivity was ∼1.81 A W-1 at 80 mW cm-2 and ∼0.54 A W-1 at a high incident power of ∼2200 mW cm-2 under a bias of 1 V. Interestingly, the device showed response even in the long-wavelength infrared region, but no response was found under visible light. The embedded IrP2 nanoparticles act as trap centers inducing photogating in the device, and the average trap state energy was estimated to be ∼16.5 ± 1.5 meV from the temperature-dependent photocurrent studies. The device was found to be immune to air exposure and bending, suggestive of use a a wearable sensor.

Hand-drawn electrode based disposable paper chip for artificial sweat analysis using impedance spectroscopy.

Low cost, disposable paper based electrical sensor to examine the analyte concentration in an extremely small volume of sample solution is essential for environmental and healthcare applications. For the development of paper based devices, sophisticated instruments are essential to pattern electrode on the top surface of the paper. In most cases, such fabricated device results in direct contact with the analyte solution on the surface of the electrode during electrical detection and leads to high electrical double layer capacitance. In this work, we have focused to reduce the double layer capacitance by fabricating hand drawn electrode paper sensor utilising the reverse side of the paper. This design acts as a sample storage and facilitate impedimetric sensing of ionic concentration of analyte solution using a few microlitre. Droplet formation at the bottom of the paper in the confined area is visually monitored to reduce sample wastage. The interaction between two different electrode materials (graphite and silver) on the paper substrate with the different volume and concentration of the electrolyte is analysed to improve the robustness and sensitivity of the measurement. Simultaneously, we observed a reduction in the electrical double layer effect on the low sample volumes. The proposed paper based sensor shows the enhanced impedance stability on silver electrode patterned paper chip than graphite electrode paper chip to detect the different ionic concentration of artificial sweat sample. Finally, it demonstrates that paper chip has great potential as a disposable diagnostics sensor in healthcare applications.

Cobalt phosphide (Co2P) encapsulated in nitrogen-rich hollow carbon nanocages with fast rate potassium ion storage.

We synthesized Co2P nanoparticle encapsulated N-doped carbon nanocages through one-step carbonization-phosphidation of ZIF-67. As potassium ion battery (KIB, PIB) anodes, the Co2P@NCCs display state-of-the-art electrochemical performance, including the most favorable fast charge characteristics reported. The single-nanometer thick carbon cage yields rapid solid-state K-ion diffusion and prevents aggregation/pulverization of 40 nm cobalt phosphide.

Clinical guideline and treatment planning decisions of single-tooth implants versus preserving natural teeth with nonsurgical endodontic therapy.

The outcomes of both dental implants and endodontically treated teeth have been extensively studied. An assessment of whether to rehabilitate a tooth requiring endodontic treatment or to replace it with a dental implant can often involve a challenging and complex decision making process for clinicians now a days. This review describes practical criteria and a systematic process to aid the treatment planning decision of whether to preserve teeth by root canal treatment (RCT) or extract and provide an implant. This article reviews the benefits and disadvantages of both treatment options and discusses success vs. survival outcomes.

dMole: A Novel Transreceiver for Mobile Molecular Communication Using Robust Differential Detection Techniques.

This paper proposes two differential detection techniques for signal detection in mobile molecular communication (MMC) for targeted drug delivery (TDD) application. In MMC, a nano-transmitter and a nano-receiver are considered to be in Brownian motion in an extracellular fluid medium. Transmitter uses calcium molecules to communicate with the receiver. Detection is performed using concentration difference based detector (CDD) at the receiver which calculates the maximum absolute concentration difference of the received signal within the same bit interval to detect the bit. This improves the bit error rate (BER) performance in MMC. The performance is further enhanced using manchester coded transmission with differential detection (MCD). In MCD, Bit-1 is coded by the symbol [1 0] and Bit-0 is coded by the symbol [0 1] and the difference between peaks of signals received in consecutive bit duration is taken to detect the bit. Simulation results prove that the MCD technique is 3 dB less sensitive to inter symbol interference (ISI) than the CDD technique. The detection threshold is selected using maximum a posteriori probability (MAP) rule. The performance of these detectors is compared with other existing detection techniques. Results reveal that BER performance of the CDD and MCD better by at least 3 dB and 6 dB, respectively. The proposed CDD and MCD techniques perform better in different bit-sequence length, various initial distance and different bit duration than other existing techniques.

Author Correction: Metabolomics reveals perturbations in endometrium and serum of minimal and mild endometriosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Imbalanced insulin substrate-1 and insulin substrate-2 signaling trigger hepatic steatosis in vitamin D deficient rats: 8-methoxypsoralen, a vitamin D receptor ligand with a promising anti-steatotic action.

The exact role of VD deficiency in the development of non-alcoholic fatty liver disease (NAFLD) remains unknown. In this study, we induced VD deficiency by feeding Female Sprague-Dawley rats a VD deficient (VDD) Diet and studied the hepatic changes associated with VD deficiency. Simultaneously, we provided the VDD rats with VD or 8-methoxy psoralen (8-MOP), a suggested vitamin D receptor agonist, to test the reversibility of the hepatic changes. VDD Rats developed borderline non-alcoholic steatohepatitis (NASH) with considerable elevation in hepatic triglycerides, total cholesterol, and malondialdehyde. Furthermore, VD deficiency induced the expression of crucial enzymes and transcription factors involved in denovo lipogenesis, which justified the hepatic lipid accumulation. Insulin receptor signaling was affected by VD deficiency, demonstrated by the elevation in insulin substrate-1 (IRS1) and reduction in insulin substrate-2 (IRS2) signaling. Treatment with VD or 8-MOP attenuated IRS1 signaling and its downstream targets, leading to a decline in de novo lipogenesis, while the elevation in IRS2 expression resulted in the nuclear exclusion of forkhead box O1 (FoxO1) and diminished gluconeogenesis, a vital source of acetyl-CoA for de novo lipogenesis. Moreover, 8-MOP and Calcipotriol modulated insulin signaling in human hepatocyte cell line L02, which highlighted the crucial role of VD in the regulation of hepatic lipid contents in rats and humans. Silencing of the vitamin D receptor expression in L02 diminished the inhibitory effect of Calcipotriol and 8-MOP on fatty acid synthase and acetyl- CoA carboxylase 1 and provided the evidence that 8-MOP actions mediated via vitamin D receptor.

Adaptive homeostasis of the vitamin D-vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity.

8-methoxypsoralen (8-MOP) with ultraviolet A radiation therapy (PUVA) is the standard therapy for patients with psoriasis, despite the reported potential risks of 8-MOP-induced cholestatic liver injury in both humans and animals. Usually, patients with chronic cholestasis exhibit lower serum 25-hydroxy vitamin D (25(OH)D) levels. But those patients receiving PUVA for psoriasis showed an increase in serum 25(OH)D levels, probably highlighting that the vitamin D-vitamin D nuclear receptor (VD-VDR) axis play a protective role in 8-MOP-induced hepatotoxicity. The present study confirmed 8-MOP could increase serum 25(OH)D levels in conventional lighting and diet (CLD) and vitamin D deficient (VDD) Sprague-Dawley rats. Potential liver risks were also found in CLD and VDD rats after 8-MOP treatment. We proved that 8-MOP could be a potent ligand for VDR using molecular docking and luciferase report assay. Effect of 8-MOP on VDR subcellular distribution was determined using human liver cell line L02. We found 8-MOP could increase VDR protein expression in the nuclear and cytosol extracts and also total cell extracts in L02. siRNAs for VDR were used to determine the role of VDR in protecting 8-MOP-induced cholestasis and potential cellular mechanisms. The results showed 8-MOP could affect the CYP7A1, SHP and MRP3 expression via VDR, and such effects could be reversed by knockdown of VDR expression, suggesting a vital role of VDR involved in 8-MOP-regulated bile acid synthesis and transportation. In conclusion, these results revealed activation of VD-VDR axis may play a beneficial role in 8-MOP-mediated regulation of bile acid synthesis and transportation.

In Situ Fabrication of a Nickel/Molybdenum Carbide-Anchored N-Doped Graphene/CNT Hybrid: An Efficient (Pre)catalyst for OER and HER.

Despite the recent promise of transition metal carbides as nonprecious catalysts for the hydrogen evolution reaction (HER), their extension to the oxygen evolution reaction (OER) to achieve the goal of overall water splitting remains a significant challenge. Herein, a new Ni/Mo xC (MoC, Mo2C) nanoparticle-supported N-doped graphene/carbon nanotube hybrid (NC) catalyst is developed via a facile, one-step integrated strategy, which can catalyze both the HER and OER in an efficient and robust manner. The catalyst affords low overpotentials of 162 and 328 mV to achieve a current density of 10 mA/cm2 for HER and OER, respectively, in alkaline medium, which either compares favorably or exceeds most of the Mo-based catalysts documented in the literature. It is believed that there is an electronic synergistic effect among Mo xC, Ni, and NC, wherein a tandem electron transfer process (Ni → Mo xC → NC) may be responsible for promoting the HER as well as OER activity. This work opens a new avenue toward the development of multicomponent, highly efficient but inexpensive electrocatalysts for overall water splitting.

Metabolomics reveals perturbations in endometrium and serum of minimal and mild endometriosis.

Endometriosis is a common benign gynecological disease, characterized by growth and proliferation of endometrial glands and stroma outside the uterus. With studies showing metabolic changes in various biofluids of endometriosis women, we have set upon to investigate whether endometrial tissue show differences in their metabolic profiles. 1H NMR analysis was performed on eutopic endometrial tissue of women with endometriosis and controls. Analysis was performed on spectral data and on relative concentrations of metabolites obtained from spectra using multivariate and univariate data analysis. Analysis shows that various energy, ketogenic and glucogenic metabolites have significant altered concentrations in various stages of endometriosis. In addition, altered tissue metabolites in minimal and mild stages of endometriosis were explored in serum of these patients to assess their role in disease diagnosis. For Stage I diagnosis alanine was found to have 90% sensitivity (true positives) and 58% specificity (true negatives). For Stage II diagnosis alanine, leucine, lysine, proline and phenylalanine showed significant altered levels in serum. While sensitivity of these serum metabolites varied between 69.2-100% the specificity values ranged between 58.3-91.7%. Further, a regression model generated with this panel of serum markers showed an improved sensitivity and specificity of 100% and 83%, respectively for Stage II diagnosis.

Bioimpedimetric analysis in conjunction with growth dynamics to differentiate aggressiveness of cancer cells.

Determination of cancer aggressiveness is mainly assessed in tissues by looking at the grade of cancer. There is a lack of specific method to determine aggressiveness of cancer cells in vitro. In our present work, we have proposed a bio-impedance based non-invasive method to differentiate aggressive property of two breast cancer cell lines. Real-time impedance analysis of MCF-7 (less aggressive) and MDA-MB-231 cells (more aggressive) demonstrated unique growth pattern. Detailed slope-analysis of impedance curves at different growth phases showed that MDA-MB-231 had higher proliferation rate and intrinsic resistance to cell death, when allowed to grow in nutrient and space limiting conditions. This intrinsic nature of death resistance of MDA-MB-231 was due to modulation and elongation of filopodia, which was also observed during scanning electron microscopy. Results were also similar when validated by cell cycle analysis. Additionally, wavelet based analysis was used to demonstrate that MCF-7 had lesser micromotion based cellular activity, when compared with MDA-MB-231. Combined together, we hypothesize that analysis of growth rate, death resistance and cellular energy, through bioimpedance based analysis can be used to determine and compare aggressiveness of multiple cancer cell lines. This further opens avenues for extrapolation of present work to human tumor tissue samples.