Formulation and In Vitro Assessment of Polymeric pH-Responsive Nanogels of Chitosan for Sustained Delivery of Madecassoside.

Madecassoside, a triterpenoid saponin compound mainly isolated from the gotu kola herb (Centella asiatica), shows an extensive range of biological activities, including antiapoptotic, antioxidant, anti-inflammatory, moisturizing, neuroprotective, and wound healing effects. It has been highly used in the management of eczema, skin wounds, and other diseases. Due to poor oral bioavailability, membrane permeability, and intestinal absorption, the clinical application of the madecassoside is limited. Hence, a drug carrier system is needed that not only sustains the release of the madecassoside but also overcomes the drawbacks associated with its administration. Therefore, the authors prepared novel pH-responsive chitosan-based nanogels for the sustained release of madecassoside. Free radical polymerization technique was used for cross-linking of polymer chitosan and monomer methacrylic acid in the presence of cross-linker N',N'-methylene bis(acrylamide). The decrease in polymer crystallinity after polymerization and development of nanogels was demonstrated by XRD and FTIR analysis. The effects of nanogel contents on polymer volume, sol-gel analysis, swelling, drug loading, and release were investigated. Results indicated that high swelling and maximum release of the drug occurred at pH 7.4 compared to pH 1.2 and 4.6, indicating the excellent pH-sensitive nature of the engineered nanogels. High swelling and drug release were perceived with the integration of a high quantity of chitosan, while a decline was observed with the high integration of N',N'-methylene bis(acrylamide) and methacrylic acid contents. The same effects of nanogel contents were shown for drug loading too. Sol fraction was reduced, while gel fraction was enhanced by increasing the chitosan load, N',N'-methylene bis(acrylamide), and methacrylic acid. The Korsmeyer-Peppas model of kinetics was trailed by all nanogel formulations with non-Fickian diffusion. The results demonstrated that prepared nanogels can be employed for sustained release of the madecassoside.

A Novel Approach of Polyvinyl Alcohol/Acrylic Acid Based Hydrogels for Controlled Delivery of Diclofenac Sodium.

AIM AND OBJECTIVE: The aim of this study was to prepare polyvinyl alcohol/acrylic acid (PVA/AA) hydrogels for the controlled release of diclofenac sodium and to develop PVA/AA hydrogels as controlled release carriers to overcome not only the side effects of diclofenac sodium but also sustain its release for an extended period. BACKGROUND: Diclofenac sodium is employed for relieving pain and fever. The half-life of diclofenac sodium is very short (1-2 h). Hence, multiple intakes of diclofenac sodium are required to maintain a constant pharmacological action. Multiple GI adverse effects are produced as a result of diclofenac sodium intake. METHOD: A free radical polymerization technique was used for crosslinking PVA with AA in the presence of APS. EGDMA was used as a cross-linker. FTIR and XRD confirmed the preparation and loading of the drug by prepared hydrogels. An increase in the thermal stability of PVA was shown by TGA and DSC analysis. Surface morphology was investigated by SEM. Similarly, water penetration and drug loading were demonstrated by porosity and drug loading studies. The pH-sensitive nature of PVA/AA hydrogels was investigated at different pH values by swelling and drug release studies. RESULTS: The development and drug loading of PVA/AA hydrogels were confirmed by FTIR and XRD analysis. TGA and DSC indicated high thermal stability of prepared hydrogels as compared to unreacted PVA. SEM indicated a hard and compact network of developed hydrogels. The swelling and drug release studies indicated maximum swelling and drug release at high pH as compared to low pH values, indicating the pH-sensitive nature of prepared hydrogels. Moreover, we demonstrated that drug release was sustained for a prolonged time in a controlled pattern by prepared hydrogels by comparing the drug release of the developed hydrogels with the commercial product Cataflam. CONCLUSION: The results indicated that prepared PVA/AA hydrogels can be used as an alternative approach for the controlled delivery of diclofenac sodium.

Efficacy of Endoscopic Therapy in Symptomatic Pancreatic Divisum: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Pancreas divisum (PD) is a congenital malformation of the pancreas and is implicated as a cause of pancreatitis. The role of endotherapy has been variable in symptomatic PD indicated by recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), or chronic pancreatic-type abdominal pain (PP). The aim of this study was to analyze the pooled data to determine the success of endoscopic intervention for pancreas divisum. METHODS: We conducted a comprehensive search of several databases (inception to July 2023) to identify studies reporting on the use of endoscopic therapy in symptomatic pancreatic divisum. The random-effects model was used to calculate the pooled rates and I2% values were used to assess the heterogeneity. RESULTS: A total of 27 studies were retrieved that reported endoscopic intervention in pancreatic divisum. The calculated pooled rate of technical success was 92% (95% CI: 87-95; I2=63%). The calculated pooled rate of clinical success was 65% (95% CI: 60-70; I2=60%). The rate of clinical success by PD subtypes was highest in RAP at 71% (95% CI: 65-76; I2=24%). Available studies had significant heterogeneity in defining clinical success. The rate of adverse events was 71% (95% CI: 65-76; I2=24%). CONCLUSIONS: The role of endoscopic therapy in pancreatic divisum is variable with the highest success rate in recurrent acute pancreatitis. Endoscopic intervention is associated with a higher-than-usual rate of adverse events, including post-ERCP pancreatitis.

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride.

BACKGROUND: Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects. AIM: This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers. OBJECTIVE: The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality. METHODS: Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels. RESULTS: FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone. CONCLUSION: The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

Elucidating the effects of heavy metals contamination on vital organ of fish and migratory birds found at fresh water ecosystem.

Heavy metal pollution in aquatic environments threatens marine life and lowers the quality of freshwater supplies. This research aimed to quantify the heavy metal concentration in fish, avian tissue, and water of the Mangla reservoir. Concentrations of heavy metals such as Cu, Cd, Cr, and Pb were determined in five vital organs of six species of fishes (Cirrhinus cirrhosis, Catla catla, Hypophthalmichthys molitrix, Wallagu attu, Cyprinus carpio, Sperata seenghala) and five species of migratory birds (Anas strepera, Aythya ferina, Anas platyrhynchos, Anas crecca, Anas clypeata) and water of Mangla dam. Heavy metal concentration was observed with AAS' help after the samples' complete chemical digestion. The average concentration of these metals in water samples was higher than the mean values in fish and birds. Heavy metals damaged fish and birds in the same order: Cd > Cu > Cr > Pb. The results of this research will hopefully prompt further consideration on the dangers of heavy metal contamination in freshwater ecosystem.

Fabrication and In vitro Evaluation of Carbopol/Polyvinyl Alcohol-based pH-sensitive Hydrogels for Controlled Drug Delivery.

BACKGROUND: Diclofenac sodium has a short half-life (about 1.5 hours), requiring repeated administration, and as a result, serious complications, such as GI bleeding, peptic ulcer, and kidney and liver dysfunction, are generated. Hence, a sustained/controlled drug delivery system is needed to overcome the complications caused by the administration of diclofenac sodium. AIMS: This study aimed to fabricate and evaluate carbopol/polyvinyl alcohol-based pH-sensitive hydrogels for controlled drug delivery. OBJECTIVE: pH-sensitive carbopol/polyvinyl alcohol graft-poly(acrylic acid) hydrogels (Cp/PVA-g-PAa hydrogels) were developed for the controlled delivery of diclofenac sodium. METHODS: The combination of carbopol/polyvinyl alcohol, acrylic acid, and ethylene glycol dimethacrylate was used as polymer, monomer, and cross-linker, respectively. The effects of the formulation's composition on porosity, swelling index, and release pattern of diclofenac sodium from the developed hydrogels were investigated. RESULTS: An increase in porosity and swelling was observed with the increasing amounts of carbopol and acrylic acid, whereas polyvinyl alcohol showed the opposite effect. Due to the formation of a highly viscous system, the drug release decreased with the increasing concentrations of carbopol and polyvinyl alcohol while increased with increasing acrylic acid concentration. The pH-responsive properties of the fabricated hydrogels were demonstrated by dynamic swelling and drug release studies at three different pH values. Higher dynamic swelling and diclofenac sodium (model drug) release were found at high pH values compared to low pH values, i.e., pH 7.4 > 4.6 > 1.2, respectively. Cytotoxicity studies reported no toxic effect of the prepared hydrogels, thus indicating that the prepared hydrogels are safe to be used on clinical basis. CONCLUSION: The prepared carbopol/polyvinyl alcohol crosslinked hydrogel can be used as a promising carrier for the controlled release of drugs.

Enhanced Photocatalytic Degradation of Malachite Green Dye Using Silver-Manganese Oxide Nanoparticles.

Efficient and excellent nanoparticles are required for the degradation of organic dyes in photocatalysis. In this study, silver-manganese oxide nanoparticles (Ag-Mn-NPs) were synthesized through a wet chemical precipitation method and characterized as an advanced catalyst that has enhanced photocatalytic activity under sunlight irradiation. The nanoparticles were characterized using scanning electron microscopy (SEM), XRD, UV-vis light spectra, and energy-dispersive X-ray (EDX) spectroscopy, revealing their spherical and agglomerated form. The EDX spectra confirmed the composition of the nanoparticles, indicating their presence in oxide form. These bimetallic oxide nanoparticles were employed as photocatalysts for the degradation of malachite green (MG) dye under sunlight irradiation in an aqueous medium. The study investigated the effects of various parameters, such as irradiation time, catalyst dosage, recovered catalyst dosage, dye concentration, and pH, on the dye's photodegradation. The results showed that Ag-Mn oxide nanoparticles exhibited high photocatalytic activity, degrading 92% of the dye in 100 min. A longer irradiation time led to increased dye degradation. Moreover, a higher catalyst dosage resulted in a higher dye degradation percentage, with 91% degradation achieved using 0.0017 g of the photocatalyst in 60 min. Increasing the pH of the medium also enhanced the dye degradation, with 99% degradation achieved at pH 10 in 60 min. However, the photodegradation rate decreased with increasing dye concentration. The Ag-Mn oxide nanoparticles demonstrate excellent potential as a reliable visible-light-responsive photocatalyst for the efficient degradation of organic pollutants in wastewater treatment.

Xanthan-Gum/Pluronic-F-127-Based-Drug-Loaded Polymeric Hydrogels Synthesized by Free Radical Polymerization Technique for Management of Attention-Deficit/Hyperactivity Disorder.

Smart and intelligent xanthan gum/pluronic F-127 hydrogels were fabricated for the controlled delivery of atomoxetine HCl. Different parameters such as DSC, TGA, FTIR, XRD, SEM, drug loading, porosity, swelling index, drug release, and kinetics modeling were appraised for the prepared matrices of hydrogels. FTIR confirmed the successful synthesis of the hydrogel, while TGA and DSC analysis indicated that the thermal stability of the reagents was improved after the polymerization technique. SEM revealed the hard surface of the hydrogel, while XRD indicated a reduction in crystallinity of the reagents. High gel fraction was achieved with high incorporated contents of the polymers and the monomer. An increase in porosity, drug loading, swelling, and drug release was observed with the increase in the concentrations of xanthan gum and acrylic acid, whereas Pluronic F-127 showed the opposite effect. A negligible swelling index was shown at pH 1.2 and 4.6 while greater swelling was observed at pH 7.4, indicating a pH-responsive nature of the designed hydrogels. Furthermore, a higher drug release was found at pH 7.4 compared to pH 1.2 and 4.6, respectively. The first kinetics order was followed by the prepared hydrogel formulations. Thus, it is signified from the discussion that smart xanthan gum/pluronic F-127 hydrogels have the potential to control the release of the atomoxetine HCl in the colon for an extended period of time.

Isolation and Bioassay of a New Terminalone A from Terminalia arjuna.

Terminalia arjuna possesses significant cardioprotective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna. Spectroscopic characterization identified one of them as a new flavonoid "Terminalone A (1)" and two known flavonoids i.e., 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (2) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (3). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH radical scavenging) potential for all the three compounds 1-3 where the compound 1 showed strong antibacterial and antioxidant activity.

Intergenerational trauma: A silent contributor to mental health deterioration in Afghanistan.

Multiple theories, including family systems, epigenetics, attachments, and many others, have proposed mechanisms for trauma transmission from generation to generation. Intergenerational trauma is today one of the most important psychosocial issues affecting Afghans' mental health and psychology, with the potential to affect subsequent generations. A variety of factors have impacted the mental health of the Afghan population over the years, including years of conflict, socioeconomic instability, natural disasters, chronic drought conditions, economic turmoil, and food insecurity, all of which have been exacerbated by recent political turbulence and the The Coronavirus pandemic COVID-19 pandemic that has further increased the susceptibility to intergenerational trauma among the Afghan population. International bodies must play a role in addressing intergenerational trauma among Afghans. Breaking the chain in future generations will be possible by resolving political issues, providing adequate health facilities, financial support, and eliminating stigmas associated with mental health issues.

The impact of COVID-19 followed by extreme flooding on vector borne diseases in Pakistan: A mini narrative review.

While the Coronavirus pandemic continues to spread havoc across the world, countries like Pakistan are faced with another challenge: the steady rise of vector borne diseases alongside a spike in COVID-19 cases. Moreover, signs and clinical manifestations of multiple arbovirus infections mimic those experienced in COVID-19, causing further complications in management and diagnosis. Without urgent adequate management and testing equipment, the recent surge of COVID-19 along with the steady rise in Vector Borne Diseases (VBDs) could collapse the exhausted Pakistani healthcare system. This article explores the impact of COVID-19 on the management, diagnosis, and treatment of the common arbovirus infections of Pakistan, including dengue (DENV), malaria, chikungunya (CHIKV), and other foreign infections that are on a hazardous rise.

Natural Products as Bioactive Agents in the Prevention of Dementia.

Dementia is a complex syndrome of neurological disorders which is associated with cognitive functions of the body. The present review focuses on the role and application of natural products in the treatment of dementia and related diseases. The studies highlight that there exist some potent synthetic/semisynthetic drugs that can effectively target dementia and related diseases. In contrast, despite the existence of a large library of natural products, only a few of them (galantamine, huperzine A, etc.) have been approved as drugs against dementia. This fact is not discouraging because a large number of natural products, including classes of polyphenols, alkaloids, isothiocyanates, phytocannabinoids, and terpenoids, are in the process of drug development stages against dementia and related diseases. It is because they display some promising and diverse biological activities, including antioxidant, acetylcholinesterase inhibitory activity, and anti-amyloidogenic properties, which are significantly associated with the prevention of dementia syndrome. The studies reported in the literature reveal that bioactive natural products particularly target Alzheimer's and Parkinson's diseases by suppressing the risks responsible for dementia. Huperzine A has been identified as a potent natural product against Alzheimer's disease. Despite the efficient role of natural products in preventing dementia, their direct application as drugs is still limited due to some controversial results obtained from their clinical trials; however, bioassay-guided drug development studies can prove them potential drugs against dementia and related diseases. This review provides useful information for researchers, pharmacologists, and medical doctors.

Three new α-glucosidase inhibitor benzo-isochromenes from Datura stramonium.

Three new α-glucosidase inhibitory benzo-isochromenes were isolated from the chloroform fraction of Datura stramonium. Their structures were established with the help of modern spectroscopic techniques and were assigned the names as 1,6,8-triimethoxy-2-methyl-3,4-dihydrobenzoisochromene-5,10-diol, 3,6-dimethoxy-5-hydroxy-4-methylbenzoisochromene-9,11-dione and demethylflavasperon for compounds 1-3 respectively. The α-glucosidase inhibiting activity of compound 2 showed strong inhibition with an IC50 value of 27.5 µM, while compound 1 exhibited moderate activity with IC50 value of 60.2 µM compared to positive control (acarbose).

Compliance with best practice recommendations for colonoscopy bowel preparation among hospitalized patients at a tertiary adult hospital.

INTRODUCTION: Proper bowel preparation is essential to successful colonoscopies. The quality of bowel preparation is often poorer in the inpatient settings compared with outpatient settings. This can result in repeat procedures and increased hospital length of stay. OBJECTIVE: The aim of this evidence implementation project was to assess and improve compliance with best practice recommendations for bowel preparation prior to colonoscopy. METHODS: The project was done in three phases for patients hospitalized at a tertiary adult hospital: the initial audit; clinical practice change that included providing patients with both oral and written education about bowel preparation; and a follow-up audit. RESULTS: The baseline audit showed that the hospital was already fully compliant with two out of four best practice criteria. For two criteria with poor compliance rates at baseline, we improved compliance for criterion 1 (giving patients both oral and written education about bowel preparation) from 8 to 40%, while compliance rate for criterion 4 [using 2 l polyethylene glycol - (PEG) or adding ascorbic acid to 4 l PEG] remained at 0% at the end of the intervention. CONCLUSION: The JBI evidence implementation program provided a structured approach to analyze colonoscopy bowel preparation practices and develop strategies to align policies with the best practice recommendation of providing written education about bowel preparation. However, there is need for more conclusive evidence to identify the most ideal inpatient bowel preparation formulation.

Preparation of pH-Responsive Hydrogels Based on Chondroitin Sulfate/Alginate for Oral Drug Delivery.

This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in various mixing ratios of chondroitin sulfate, alginate and acrylic acid in the presence of ammonium persulfate and N',N'-Methylene bisacrylamide. Crosslinking and loading of drug were confirmed by Fourier transform infrared spectroscopy. Thermal stability of both polymers was enhanced after crosslinking as indicated by thermogravimetric analysis and differential scanning calorimeter thermogram of developed hydrogel. Similarly, surface morphology was evaluated by scanning electron microscopy, whereas crystallinity of the polymers and developed hydrogel was investigated by powder X-ray diffraction. Furthermore, swelling and drug-release studies were investigated in acidic and basic medium of pH 1.2 and 7.4 at 37 °C, respectively. Maximum swelling and drug release were detected at pH 7.4 as compared to pH 1.2. Increased incorporation of hydrogel contents led to an increase in porosity, drug loading, and gel fraction while a reduction in sol fraction was seen. The polymer volume fraction was found to be low at pH 7.4 compared to pH 1.2, indicating a prominent and greater swelling of the prepared hydrogels at pH 7.4. Likewise, a biodegradation study revealed a slow degradation rate of the developed hydrogel. Hence, we can conclude from the results that a fabricated system of hydrogel could be used as a suitable carrier for the controlled delivery of ketorolac tromethamine.

Structural, electronic, magnetic and elastic properties of xenon-based fluoroperovskites XeMF3 (M = Ti, V, Zr, Nb) via DFT studies.

In this work, the structural, electronic, magnetic and elastic properties of the xenon-based fluoroperovskites XeMF3 (M = Ti, V, Zr, Nb) have been studied using density functional theory. The structural study reveals that all the perovskites have stable structures. A half-metallic nature is observed due to the presence of a band gap in only the spin-down channel. The result indicates that the considered compounds are ferromagnetic materials with integer magnetic moments. The elastic parameters were studied to obtain their elastic properties. It is noted that all compounds have an anisotropic nature and show ductility. The optical characteristics show that these compounds are good optical absorbers at high energy. Furthermore, we suggest that these compounds could be good candidates for spintronic and optoelectronic devices.

Investigating structural, electronic, magnetic, and optical properties of Co-doped and Co-X (X = Fe, Mn) co-doped MoS2 for optoelectronic applications.

We employ first-principle calculations to investigate structural, electronic, magnetic, and optical properties of cobalt and Co-X (X = Fe, Mn) co-doped MoS2. Result demonstrates that pure MoS2 is nonmagnetic, while Co and Co-Fe/Mn co-doping brings magnetism into MoS2 with magnetic moment values of 0 [Formula: see text], 2.022 [Formula: see text], 3.906 [Formula: see text], and 3.643 [Formula: see text] respectively. d states of dopants and p-d hybridization bring significant improvements in electronic properties of MoS2. Novelty of current work lies not only in origin of magnetism in the proposed materials but also in absorption spectra which show blueshift. We notice reduction in optical band gap with Co and Co-Fe/Mn co-doping. Enhanced absorption and conductivity with decrease in reflectivity illustrate potential uses of these materials for revolutionizing future of optoelectronics, spintronics, magneto-optics, and photonics devices. Moreover, crossroads of MoS2 and allied materials may further explore new avenues in sensing, artificial intelligence, and miniaturization of existing technology.

Morphometric and Myelin Basic Protein Expression Changes in Arcuate Nucleus Kisspeptin Neurons Underlie Activation of Hypothalamic Pituitary Gonadal-axis in Monkeys (Macaca Mulatta) during the Breeding Season.

INTRODUCTION: Kisspeptin is involved in the hypothalamic pituitary gonadal-axis' seasonal regulation in rodents and sheep. Studies of kisspeptin signaling in regulating the transition between breeding and nonbreeding seasons have focused on kisspeptin expression, myelin basic protein (MBP) expression around kisspeptin-ir cells, and quantifying the synaptic connections between kisspeptin and gonadotropin-releasing hormone (GnRH) neurons in various animal models; however, the role of kisspeptin in regulating the seasonal breeding of primates has not been explored yet. OBJECTIVE: This study investigated changes in kisspeptin signaling during breeding and a non-breeding season in a non-human primate model, the rhesus monkey. METHODS: Three adult male monkeys (n = 3) from the breeding season and two monkeys (n = 2) from the non-breeding season were used in this study. After measuring the testicular volume and collecting a single blood sample, all animals were humanely euthanized under controlled conditions, and their hypothalami were collected and processed. Two 20 µm thick hypothalamic sections (mediobasal hypothalamus) from each animal were processed for kisspeptin-MBP and kisspeptin-GnRH immunohistochemistry (IHC). One section from each animal was used as a primary antibody omitted control to check the nonspecific binding in each IHC. RESULTS: Compared to the non-breeding season, plasma testosterone levels and testicular volumes were significantly higher in monkeys during the breeding season. Furthermore, compared to the non-breeding season, increased kisspeptin expression and a higher number of synaptic contacts between kisspeptin fibers and GnRH cell bodies were observed in the arcuate nucleus of the breeding season monkeys. In contrast, enlarged kisspeptin soma and higher MBP expression were observed in non-breeding monkeys. CONCLUSION: Our results indicated enhanced kisspeptin signaling in primate hypothalamus during the breeding season. These findings support the idea that kisspeptin acts as a mediator for the seasonal regulation of the reproductive axis in higher primates.

A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis.

The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single-arm open-label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per-protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug-related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC.

Structural, Electronic and Optical Properties of Titanium Based Fluoro-Perovskites MTiF3 (M = Rb and Cs) via Density Functional Theory Computation.

This study reports the theoretical investigations on the structural, electronic, and optical properties of titanium-based fluoro-perovskites MTiF3 (M = Cs and Rb) using density functional theory. The impact of on-site Coulomb interactions is considered, and calculations are performed in generalized gradient approximation with the Hubbard U term (GGA + U). The ground state parameters, such as lattice constants, bulk modulus, and pressure derivatives of bulk modulus, were found. These compounds are found stable in cubic perovskite structures having lattice constants of 4.30 and 4.38 Å for RbTiF3 and CsTiF3, respectively. Analysis of elastic properties shows that both of the compounds are ductile in nature. According to the band structure profile, the examined compounds have a half-metallic character, exhibiting conducting behavior in the spin-up configuration and nonconducting behavior in the spin-down configuration. The ferromagnetic nature is conformed from the study of its magnetic moments. The optical behaviors such as reflectivity, absorption, refraction, and conductivity of the cubic phase of MTiF3 (M = Rb and Cs) are studied in the energy range of 0-40 eV.