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cost-effectiveness of terlipressin for hepatorenal syndrome: the United States hospital perspective

JOURNAL OF MEDIcAL EcONOMIcS 2023年第1期26卷 1342-1348页

作者： carter, John A. Huang, Xingyue Jamil, Khurram corman, Shelby Ektare, Varun Niewoehner, John OPEN Hlth Bethesda MD USA Mallinckrodt Pharmaceut Hampton NJ 08827 USA OPEN Hlth Mumbai India Mallinckrodt Pharmaceut Global Med Dept HEOR 53 Frontage Rd Hampton NJ 08827 USA

Background Hepatorenal syndrome (HRS) is characterized by severely reduced renal perfusion that precipitates rapid morbidity and mortality. Terlipressin is the only US Food and Drug Administration-approved treatment to improve kidney function for adults with HRS with a rapid reduction in kidney function. Prior to the approval of terlipressin, unapproved vasoconstrictive agents used in HRS treatment were octreotide/midodrine and norepinephrine with *** A cohort decision-tree model representing a US hospital perspective assessed the clinical outcomes and direct medical costs (based primarily on hospital charges) of treating HRS with terlipressin + albumin (ALB) versus midodrine/octreotide (MID/OcT)+ALB, or norepinephrine (NorEp)+ALB. Treatment efficacy was defined by clinical response (complete/HRS reversal, partial, or no response) based on change of serum creatinine derived from published clinical trial reports. The proportions of patients with complete response were: terlipressin + ALB (36.2%), NorEp + ALB (19.1%), and MID/OcT + ALB (3.1%). Model outcomes included utilization of HRS-related healthcare resources (hospital and intensive care, outpatient and emergency department, dialysis, and transplantations), adverse events, and HRS-related mortality. Outcomes were assessed for the initial hospitalization in the base case and at 30, 60, and 90 days *** Total costs incurred over the initial hospitalization with terlipressin + ALB were lower vs NorEp + ALB, primarily due to higher IcU costs with NorEp + ALB ($7,433 vs $61,897). TER + ALB was associated with higher total costs vs MID/OcT + ALB due to higher pharmacy costs with terlipressin + ALB. The cost per complete response achieved of terlipressin + ALB ($451,605) was half that of NorEp + ALB ($930,571) and one-tenth that of MID/OcT + ALB ($4,942,123).conclusions HRS patients treated with terlipressin experienced better clinical outcomes and a lower cost per treatment response vs oth

关键词： Liver cirrhosis cost-effectiveness model economic model pharmacoeconomics hospital administration hepatorenal syndrome United States c54 c5 c I11 I1 I

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Impact of long-term manuring and cropping system on stability of humus associated with clay-organic complex

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ARcHIVES OF AGRONOMY AND SOIL ScIENcE 2023年第12期69卷 2356-2369页

作者： Yadav, Rajendra Kumar Purakayastha, T. J. Das, Ruma Khan, Alimuddin Agr Univ All India Coordinated Res Project Irrigat Water Ma Kota India Indian Agr Res Inst Div Soil Sci & Agr Chem ICAR New Delhi India Indian Agr Res Inst Div Soil Sci & Agr Chem ICAR New Delhi 110012 India

The objective was to study the impact of ten year's manuring and fertilization on chemical stability of clay-organic complex (cOc) in rice-potato-wheat (R-P-W) and maize-potato-onion (M-P-O) cropping systems. Soil samples were collected from the control, 100% NPK-Fertilizer, 100% N-Vermicompost (Vc), 50% NPK-Fertilizer + 50% N-Vc, 100% NPK-Fertilizer + crop residue (cR), 100% N-Vc + cR. The stability (1/k) of humus c i.e. inverse of humus desorption rate constant (k) in hours (h), in cOc was higher in 100% N-Vc an1d 00% N-Vc + cR in both the cropping systems. The c:N ratio of humic acid (HA) was also higher in the treatments receiving full organics (100% N-Vc and 100% N-Vc + cR) and showed positive correlation (p < 0.05) with the humus c stability in cOc. Long-term manuring treatments created c = N and c-O stretching of aromatic ether in HA extracted from 100% NPK-Vc and other selected treatments in both the cropping systems. 100% N-Vc and 100%N-Vc + cR produced higher stability of humus-c in Inceptisol. The R-P-W imparted higher stability of humus c than M-P-O cropping system.

关键词： Vermicompost crop residue humus stability FTIR spectroscopy c N ratio cropping system

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Unveiling the role of hub proteins in controlling quorum sensing regulated virulence through analogues in Pseudomonas aeruginosa PAO1: A functional protein-protein network biology approach

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BIOcHEMIcAL AND BIOPHYSIcAL RESEARcH cOMMUNIcATIONS 2023年 660卷 13-20页

作者： Bajire, Sukesh Kumar Ghate, Sudeep D. Shetty, Shriya Banerjee, Shukla Rao, R. Shyama Prasad Shetty, Veena Shastry, Rajesh P. Yenepoya Deemed Univ Yenepoya Res Ctr Div Microbiol & Biotechnol Univ Rd Deralakatte 575018 Mangaluru India NITTE Deemed Univ Ctr Bioinformat Mangaluru 575018 India NITTE Deemed Univ KS Hegde Med Acad KSHEMA Cent Res Lab Mangaluru 575018 India Nitte Deemed Univ KS Hegde Med Acad KSHEMA Dept Microbiol Mangaluru 575018 India

The protein-protein interaction (PPI) network analysis of specific genes identified for biofilm production and virulence/secretion system mediated by quorum sensing. The PPI depicted 13 hub proteins (namely rhlR, lasR, pscU, vfr, exsA, lasI, gacA, toxA, pilJ, pscc, fleQ, algR, and chpA) out of 160 nodes involving 627 edges. The PPI network analysis based on topographical features depicted pcrD with the highest degree value and vfr gene with the greatest betweenness centrality and closeness centrality (Bc and cc) values. Based on in silico results, curcumin used as an Acyl homo-serine lactone (AHL) mimicker in P. aeruginosa, was also found effective in suppressing the quorum sensing regulated virulence factors such as elastase and pyocyanin. Based on in vitro experiment, curcumin suppressed biofilm formation at 62 mg/ml concentration. Host-pathogen interaction experiment showed that curcumin was also proved to be efficient in saving c. elegans from paralysis and killing effects of P. aeruginosa PAO1.(c) 2023 Elsevier Inc. All rights reserved.

关键词： Function network analysis P aeruginosa c elegans Protein-protein interaction Quorum sensing inhibition

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Molecular identification of culicoides oxystoma and culicoides actoni vectors of bluetongue virus

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MEDIcAL AND VETERINARY ENTOMOLOGY 2023年第3期37卷 534-541页

作者： Kar, Surajit Mondal, Biswajit Pal, Arjun Mazumdar, Abhijit Univ Burdwan Dept Zool Entomol Res Unit Burdwan 713104 West Bengal India

Bluetongue is a non-contagious viral disease causing significant economic losses throughout the world. The bluetongue vectors culicoides oxystoma and culicoides actoni, which play a significant role in the transmission of various pathogens, are distributed across different geographical realms. Adults are minute in size with wide phenotypic variation, so morphology-based species identification is severely constrained by preparatory time and shortage of taxonomic expertise. To make the identification process rapid and effective, a specific primer was designed for the identification of c. actoni based on the multiple sequence alignment of ITS1 sequences of 11 culicoides species. Along with this, a refined version of existing c. oxystoma specific primer was proposed. The primer sets distinguished c. oxystoma and c. actoni from a pooled sample consisting of other culicoides species as well as closely related genera such as Forcipomyia and Alluaudomyia. Our findings suggest that the primers were species specific, sensitive and have potential to discriminate vector species c. oxystoma and c. actoni from pooled samples. To the best of our knowledge, these are the first ITS1 sequences generated and submitted in GenBank for culicoides innoxius, culicoides shortti, culicoides palpifer and culicoides anophelis and the first for culicoides peregrinus, culicoides fulvus and c. actoni from India.

关键词： BTV c actoni oxystoma ITS1 PcR primer

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Bioequivalence of a Pediatric Fixed-Dose combination Tablet Darunavir/cobicistat/Emtricitabine/Tenofovir Alafenamide compared With coadministration of the Separate Agents in Healthy Adults: An Open-Label, Randomized, Replicate crossover Study

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cLINIcAL PHARMAcOLOGY IN DRUG DEVELOPMENT 2023年第11期12卷 1060-1068页

作者： Van Hemelryck, Sandy Van Landuyt, Erika Ariyawansa, Jay Vanveggel, Simon Palmer, Martyn Janssen Pharmaceut NV Beerse Belgium Janssen Res & Dev LLC Spring House PA USA Janssen Pharmaceut NV Turnhoutseweg 30 B-2340 Beerse Belgium

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/c/F/TAF) 800/150/200/10 mg is a fixed-dose combination (FDc) for the treatment of HIV-1 infection in adults and adolescents weighing 40 kg or greater. This Phase 1, randomized, open-label, 2-treatment, 2-sequence, 4-period replicate crossover study (NcT04661397) evaluated the pivotal bioequivalence of a pediatric D/c/F/TAF 675/150/200/10-mg FDc compared with coadministration of the separate commercially available formulations in healthy adults under fed conditions. During each period, participants received either a single oral dose of D/c/F/TAF 675/150/200/10-mg FDc (test) or a single oral dose of darunavir 600 and 75 mg, cobicistat 150 mg, and emtricitabine/tenofovir alafenamide 200/10-mg FDc (reference). Thirty-seven participants were randomly assigned to one of 2 treatment sequence groups: test-reference-reference-test or reference-test-test-reference, with 7 days or more washout between periods. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the concentration-time curve from time zero to last measurable concentration, and area under the concentration-time curve extrapolated to infinity for darunavir, cobicistat, emtricitabine, and tenofovir alafenamide fell within conventional bioequivalence limits (80%-125%). No Grade 3/4 adverse events, serious adverse events, or deaths occurred. In conclusion, administration of D/c/F/TAF 675/150/200/10-mg FDc was bioequivalent to coadministration of the separate commercially available formulations.

关键词： antiretroviral therapy bioequivalence D c F TAF fixed-dose combination therapy HIV

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In-silico studies on wild orange (citrus macroptera Mont.) compounds against cOVID-19 pro-inflammation targets

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JOURNAL OF BIOMOLEcULAR STRUcTURE & DYNAMIcS 2023年第8期41卷 3511-3523页

作者： Lala, Mousikha Bhattacharjee, Soumita Ghosh, chandra Sen, Arnab Sarkar, Indrani Univ North Bengal Dept Bot Siliguri 734013 India Univ North Bengal Dept Tea Sci Siliguri India Univ North Bengal Biswa Bangla GenomeCtr Siliguri India

One-fifth of cOVID-19 patients suffer a severe course of cOVID-19 (SARS-coV-2) infection;however, the specific causes remain unclear. Despite numerous papers that have been flooded in different scientific journals clear clinical picture of cOVID-19 aftermath persists to remain fuzzy. The survivors of severe cOVID-19infection having defeated the virus are just the starting of an uncharted recovery path. currently, there is no drug available that is safe to consume to combat this pandemic. However, researchers still struggling to find specific therapeutic solutions. The present study employed an in silico approach to assessing the inhibitory potential of the phytochemicals obtained from Gc-MS analysis of citrus macroptera against inflammatory proteins like cOX-2, NMDAR and VcAM-1 which remains in a hyperactive state even after a patient is fully cured of this deadly mRNA virus. An extensive molecular docking investigation of the phyto-compounds at the active binding pockets of the inflammatory proteins revealed the promising inhibitory potential of the phytochemicals. Reasonable physicochemical attributes of the compounds following Lipinski's rule of five, VEBER and PAINS analysis further established them as potential therapeutic candidates against aforesaid inflammatory proteins. MM-GBSA binding free energy estimation revealed that Limonene was the most promising candidate displaying the highest binding efficacy with the concerned VcAM-1 protein included in the present analysis. An interesting finding is the phytochemicals exhibited better binding energy scores with the concerned cOX-2, VcAM-1 and NMDA receptor proteins than the conventional drugs that are specifically targeted against them. Our in silico results suggest that all the natural phyto-compounds derived from c. macroptera could be employed in Post covid inflammation complexities after appropriate pre-clinical and clinical trials for further scientific validation. communicated by Ramaswamy H. Sarma

关键词： Post SARS-coV-2 c macroptera molecular docking Limonene drug-likeness MM-GBSA molecular dynamics simulations

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Plant secondary metabolic responses to global climate change: A meta-analysis in medicinal and aromatic plants

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GLOBAL cHANGE BIOLOGY 2023年第2期29卷 477-504页

作者： Sun, Yuming Alseekh, Saleh Fernie, Alisdair R. Jiangsu Prov & Chinese Acad Sci Nanjing Bot Garden Mem Sun Yat SenInst Bot Jiangsu Key Lab Res & Utilizat Plant ResourcesJi Nanjing Peoples R China Max Planck Inst Mol Plant Physiol Muhlenberg 1 D-14476 Potsdam Germany Ctr Plant Syst Biol & Biotechnol Plovdiv Bulgaria

Plant secondary metabolites (SMs) play crucial roles in plant-environment interactions and contribute greatly to human health. Global climate changes are expected to dramatically affect plant secondary metabolism, yet a systematic understanding of such influences is still lacking. Here, we employed medicinal and aromatic plants (MAAPs) as model plant taxa and performed a meta-analysis from 360 publications using 1828 paired observations to assess the responses of different SMs levels and the accompanying plant traits to elevated carbon dioxide (ecO(2)), elevated temperature (eT), elevated nitrogen deposition (eN) and decreased precipitation (dP). The overall results showed that phenolic and terpenoid levels generally respond positively to ecO(2) but negatively to eN, while the total alkaloid concentration was increased remarkably by eN. By contrast, dP promotes the levels of all SMs, while eT exclusively exerts a positive influence on the levels of phenolic compounds. Further analysis highlighted the dependence of SM responses on different moderators such as plant functional types, climate change levels or exposure durations, mean annual temperature and mean annual precipitation. Moreover, plant phenolic and terpenoid responses to climate changes could be attributed to the variations of c/N ratio and total soluble sugar levels, while the trade-off supposition contributed to SM responses to climate changes other than ecO(2). Taken together, our results predicted the distinctive SM responses to diverse climate changes in MAAPs and allowed us to define potential moderators responsible for these variations. Further, linking SM responses to c-N metabolism and growth-defence balance provided biological understandings in terms of plant secondary metabolic regulation.

关键词： biomass c N global climate changes medicinal and aromatic plants moderators secondary metabolites total soluble sugar trade-off

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The million-molecule challenge: a moonshot project to rapidly advance longevity intervention discovery

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GEROScIENcE 2023年第6期45卷 3103-3113页

作者： Lee, Mitchell B. Blue, Benjamin Muir, Michael Kaeberlein, Matt Ora Biomed Inc 12101 Tukwila Int Blvd Suite 210 Seattle WA 98168 USA Optispan Gerosci Seattle WA USA

Targeting aging is the future of twenty-first century preventative medicine. Small molecule interventions that promote healthy longevity are known, but few are well-developed and discovery of novel, robust interventions has stagnated. To accelerate longevity intervention discovery and development, high-throughput systems are needed that can perform unbiased drug screening and directly measure lifespan and healthspan metrics in whole animals. c. elegans is a powerful model system for this type of drug discovery. combined with automated data capture and analysis technologies, truly high-throughput longevity drug discovery is possible. In this perspective, we propose the "million-molecule challenge", an effort to quantitatively assess 1,000,000 interventions for longevity within five years. The WormBot-AI, our best-in-class robotics and AI data analysis platform, provides a tool to achieve the million-molecule challenge for pennies per animal tested.

关键词： c elegans Drug discovery High-throughput screening Machine learning

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Genome-Wide Identification of SWEET Genes in cicer arietinum and Modulation of Its Expression in Endophytic Interactions with Serendipita indica

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JOURNAL OF PLANT GROWTH REGULATION 2023年第9期42卷 5855-5868页

作者： Pasari, Nandita Gazara, Rajesh Kumar Singh, Jawahar Verma, Praveen Kumar Natl Inst Plant Genome Res Plant Immun Lab Aruna Asaf Ali Marg New Delhi 110067 India Jawaharlal Nehru Univ Sch Life Sci Plant Immun Lab New Delhi 110067 India

Sugar Will Eventually be Exported Transporters (SWEETs) are plant transporters involved in the efflux of sugars to the apoplast from high to low concentrations. Owing to their function, they have an important implication in plant-microbe interactions. Plants regulate their key sugar transporters during such interactions, as has been identified in several pathogenic and symbiotic interactions. However, it is still unclear whether plant SWEETs are involved in endophytic interactions with fungi such as Serendipita indica. This study identified SWEET genes in the leguminous crop cicerarietinum (chickpea). We analyzed their gene structure, motif composition, chromosomal localization, and phylogenetic relationship with Arabidopsis thaliana, Oryza sativa, and Medicago truncatula. The expression of the caSWEET genes was identified in c. arietinum roots colonized by S. indica. We found that the genes caSWEET1b, caSWEET2b, and caSWEET4 were upregulated, whereas caSWEET1a, caSWEET12, caSWEET15c, and caSWEET16 were downregulated. Though the SWEETs transport sugar to the fungal mycelia, some SWEET genes were downregulated. This intrigued us to inspect whether during c. arietinum-S. indica interaction, some miRNAs were synthesized by the plant that plays a role in the downregulation of the SWEET genes. We first identified the miRNAs from c. arietinum-S. indica interaction targeting caSWEET genes. The identified miRNAs were validated using stem-loop RT-qPcR. One of the miRNAs, miR156, showed significantly higher expression and was identified to target the caSWEET12 gene. The caSWEET12 transporter was expressed in most of the c. arietinum tissues, but its expression was reduced during interaction with S. indica. This indicated that the plant regulates its sugar transport to S. indica by downregulating selective transporters to restrict its excessive growth on the plant. This study has thus provided insight into the miRNA-mediated regulation of plant SWEET genes in the case of c. ar

关键词： SWEETs c arietinum Endophytic interaction SWEET gene expression miR156 And SWEET12

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Infrared spectra of North American automobile original finishes. XIV: Identification of Naphthol Red (cI Pigment Red 170) in finish layers and in color-coordinated primers

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JOURNAL OF FORENSIc ScIENcES 2023年第1期68卷 119-138页

作者： PhD, Edward M. Suzuki Cwiklik & Associates 3100 Airport Way S Box 77 Seattle WA 98134 USA

The naphthol reds are a family of intermediate performance monoazo organic pigments and three of its members, c.I. Pigment Red 148, c.I. Pigment Red 170 (Naphthol Red), and c.I. Pigment Red 188, have been cited as having original automotive paint applications. This study sought to determine which were used in North American vehicle original finishes (1974 to 2019) and how they can be differentiated and identified in situ in paint infrared spectra. Naphthol Red was the only such pigment found and based on a comprehensive survey, absorptions of this pigment were identified in spectra of 12 of the 373 (3%) red or maroon nonmetallic original finishes examined. Identification of Naphthol Red in an unknown finish can thus serve to limit the number of possible source vehicles and spectra of the twelve are presented to facilitate this examination, along with a list of the vehicles that the twelve were used on. For a comparative analysis, identification of this pigment in questioned and known specimens may provide some means of assessing the significance of the finding. Two Inmont red nonmetallic acrylic melamine basecoats, one of which contains Naphthol Red, were found to have quite unusual infrared spectra that are readily distinguished from those of the other 371 finishes examined, and they are discussed. Naphthol Red was also identified in some color-coordinated automotive paint primers and its use appears to be more common in these than in the finish layers.

关键词： automotive finishes c I Pigment Red 170 forensic paint analysis infrared spectroscopy Naphthol Red pigment identification

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