Weight loss in nonalcoholic fatty liver disease patients in an ambulatory care setting is largely unsuccessful but correlates with frequency of clinic visits

Background and Aims: Nonalcoholic fatty liver disease (NALFD) is a leading cause of liver disease. Weight loss improves clinical features of NAFLD; however, maintenance of weight loss outside of investigational protocols is poor. The goals of this study were to characterize patterns and clinical predictors of long-term weight loss in ambulatory patients with NAFLD

Incidental papillary carcinoma of thyroid in Graves’ disease

Traditionally Grave's disease was considered as protection against thyroid cancer. The incidence of papillary carcinoma thyroid in grave’s disease is 2.4%. Thyroid cancer occurring in grave’s disease has higher frequency of persisting or relapsing disease than thyroid cancers occurring in matched euthyroid control patients. Here we present a case of papillary carcinoma in a Grave’s disease patient presented with nodular goiter

Study on rationality of different fixed dose drug combinations in tertiary care hospital: an evaluation study

Background: The fixed dose drug combinations (FDCs) of drugs is defined as product of two or more active ingredients in a defined composition. There is a need to study the pattern of prescription from time to time to evaluate their rationality. In this context we undertook this study to know the prescription pattern of FDC in our setting. To study the rationality of different prescribed FDCs.Methods: This is a prospective study which is carried out in NIMRA Institute of medical sciences which is a tertiary care teaching private hospital. For this study we have collected one thousand prescriptions of patients for 3 months that is from 10th March 2017 to 25th of June 2017 including both in-patients as well as outpatients. Selection criteria of patients mainly basing on their willingness to give prescriptions. Institutional ethical committee permission was taken for the study. The prescribed FDCs were compared with the essential drug list of FDCs approved by Drugs Controller General of India, July 2018.  we have used descriptive statistics to analyze data. The percentage of FDCs used in each class and their contribution to overall FDCs were calculated.Results: In a total of 2952 drugs were prescribed, of this 747 were FDCs and 2205 were non FDCs. In the prescribed FDCs 89.2% drugs were rational and 10.8% drugs were irrational.Conclusions: From this study, we can conclude that 10.8% of irrational prescription of fixed dose drug combinations are prescribed in Nimra Institute of Medical Sciences which is a tertiary care teaching private hospital

First-Time Investigation of Bombax ceiba Stem Crude Extract’s Role for Autoclave-assisted Silver Nanoparticle Synthesis from Silver Sulphate and Silver Nitrate: Multifaceted Characterization, Catalytic and Antibacterial Investigations

The Bombax ceiba plant stem extract is selected for the first time in synthesis of silver nanoparticles from silver sulphate and silver nitrate. The pH 6.5 and autoclave conditions facilitated the synthesis of low sized stable SBAN-AgNP and SBAS-AgNP in presence of 3% and 2% v/v SB (Stem extract of Bombax) from silver nitrate (AN) and silver sulphate (AS) at 0.6 and 0.4mM concentrations respectively. The formation and characterization of nanoparticles are performed by employing UV-Vis spec, XRD, FTIR, DLS and FESEM-EDS. These studies revealed that the nanoparticles are crystalline in nature with capping of functional groups from plant crude extract. The FESEM results ensured that the nanoparticles formed are spherical in shape with average particle size of obtained using silver nitrate (SBAN-AgNP) and silver sulphate (SBAS-AgNP) salts are 20.6 nm and 19.4 nm respectively. Both the SBAN-AgNP and SBAS-AgNP showed 94.6% and 87.3% catalytic reduction efficiency of 4-nitrophenol within 11 and 12 mins and are completely eliminated the synthetic dye methylene blue from water in presence of NaBH4 as reducing agent within 10 and 12 mins respectively. The synthesized SBAS-AgNP showed significant MIC, MBC, anti-biofilm and TKK activities with 31.27 ± 2.04 µg/ml MIC value against Bacillus megaterium

Synthesis, and biological screening of chloropyrazine conjugated benzothiazepine derivatives as potential antimicrobial, antitubercular and cytotoxic agents

A series of twenty new chloropyrazine conjugated benzothiazepines (22-41) have been synthesized with 58%–95% yields. The compounds were characterized by using different spectroscopic techniques including FT-IR, ¹H NMR, ¹³C NMR spectroscopy and mass spectrometry. The synthesized compounds (22-41) and their precursor chalcones (2-21) were evaluated for antitubercular and cytotoxic activities. Additionally, compounds 22-41 were also tested for antimicrobial activity. Among the chalcone series (2-21), compounds 7 and 14 showed significant antitubercular activities (MICs 25.51 and 23.89 µM, respectively), whereas among benzothiazepines (22-41), compounds 27 and 34 displayed significant antimicrobial (MICs 38.02 µM, 19.01 µM) and antitubercular (MIC 18.10 µM) activities. Compounds 7 and 41 displayed cytotoxic activities with IC₅₀ of 46.03 ± 1 and 35.10 ± 2 µM respectively. All the compounds were evaluated for cytotoxic activity on normal human liver cell lines (L02) and found to be relatively less selective towards this cell line. The most active compounds identified through this study could be considered as potential leads for the development of drugs with possible antimicrobial, antitubercular, and cytotoxic activities

Staggered-flux state for rectangular-lattice spin 1/2 Heisenberg antiferromagnet

We investigate the spin-1/2 Heisenberg model on a rectangular lattice, using the Gutzwiller projected variational wave function known as the staggered flux state. Using Monte Carlo techniques, the variational parameters and static spin-structure factor for different coupling anisotropies $\gamma=J_y/J_x$ are calculated. We observe a gradual evolution of the ground state energy towards a value which is very close to the 1D estimate provided by the Bethe ansatz and a good agreement between the finite size scaling of the energies. The spin-spin correlation functions exhibit a power-law decay with varying exponents for different anisotropies. Though the lack of N\'eel order makes the staggered flux state energetically unfavorable in the symmetric case $\gamma=1$, it appears to capture the essence of the system close to 1D. Hence we believe that the staggered flux state provides an interesting starting point to explore the crossover from quantum disordered chains to the N\'eel ordered 2D square lattices

Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis

Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC₅₀ value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities

Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC~16–18 μM). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs