Fat mass: a novel digital biomarker for remote monitoring that may indicate risk for malnutrition and new complications in decompensated cirrhosis.

BACKGROUND: Cirrhosis is associated with sarcopaenia and fat wasting, which drive decompensation and mortality. Currently, nutritional status, through body composition assessment, is not routinely monitored in outpatients. Given the deleterious outcomes associated with poor nutrition in decompensated cirrhosis, there is a need for remotely monitoring this to optimise community care. METHODS: A retrospective analysis was conducted on patients monitored remotely with digital sensors post hospital discharge, to assess outcomes and indicators of new cirrhosis complications. 15 patients had daily fat mass measurements as part of monitoring over a median 10 weeks, using a Withing's bioimpedance scale. The Clinical Frailty Score (CFS) was used to assess frailty and several liver disease severity scores were assessed. RESULTS: 73.3% (11/15) patients were male with a median age of 63 (52-68). There was a trend towards more severe liver disease based on CLIF-Consortium Acute Decompensation (CLIF-C AD) scores in frail patients vs. those not frail (53 vs 46, p = 0.072). When the cohort was split into patients who gained fat mass over 8 weeks vs. those that lost fat mass, the baseline CLIF-C AD scores and WBC were significantly higher in those that lost fat (58 vs 48, p = 0.048 and 11.2 × 109 vs 4.7 × 109, p = 0.031). CONCLUSIONS: This proof-of-principle study shows feasibility for remote monitoring of fat mass and nutritional reserve in decompensated cirrhosis. Our results suggest fat mass is associated with greater severity of acute decompensation and may serve as an indicator of systemic inflammatory response. Further prospective studies are required to validate this digital biomarker.

Identification of Clostridium innocuum hypothetical protein that is cross-reactive with C. difficile anti-toxin antibodies.

OBJECTIVES: Previously considered solely an opportunistic pathogen, Clostridium innocuum (CI) was recently reported in Taiwan to be an emerging cause of antibiotic-associated diarrhea and clinically indistinguishable from Clostridioides difficile (CD) infection. We previously identified CI culture supernatant being cross-reactive with commercial CD toxin enzyme immunoassays. We aimed to identify and characterize the cross-reacting protein and determine whether it functioned as a human toxin. METHODS: We performed western blots using CI culture supernatants and CD anti-toxin antibodies and identified interacting bands. We identified protein(s) using tandem mass spectrometry and evaluated them by cytotoxicity assays. RESULTS: CI, but not CD, was isolated from stool of 12 children and adults with diarrhea. Culture supernatant from 6/12 CI isolates, and an ATCC reference strain, tested positive for CD toxins (total 7/13 isolates) by commercial EIA. Using two of these isolates, we identified two ∼40 kDa hypothetical proteins, CI_01447 and CI_01448, and confirmed cross-reactivity with CD anti-toxin antibodies by enzyme immunoassay and Western blot. Whole-genome sequencing confirmed all 13 isolates contained both genes, which were highly conserved. We observed no cytopathic or cytotoxic effects to HeLa cells when treated with these proteins. We identified amino acid sequence similarity to the NlpC/P60 family of proteins. CONCLUSIONS: Our findings do not suggest CI proteins CI_01448 and CI_01447, which cross-react with antibodies against CD toxins A and B, are toxic to HeLa cells. Further studies are needed to determine the function of these cross-reacting proteins and the potential virulence factors that could be responsible for CI diarrheal disease.

Transcriptome landscaping for gene mining and SSR marker development in Coriander (Coriandrum sativum L.).

Coriander (Coriandrum sativum L.) is an aromatic herb, widely used as a spice and is of great pharmaceutical interest. Despite high medicinal and economic value, there is a dearth of genomic information about profiling as well as the expressed sequence-based genic markers. In this study, transcriptome was sequenced from seeds, leaves, and flower for gene mining and identification of SSR markers. A total of 9746 SSR containing loci were identified, the most abundant type of SSR identified were the di-nucleotide repeat motifs (45.5%), followed by tri- (34.6%), tetra- (4.5%), penta- (1.5%) and hexanucleotide repeats (1%). A total of 3795 primers were designed, out of which 120 randomly selected were validated in 14 accessions of coriander cultivated in India. The current study provides useful information about preliminary transcriptome sketch and genic markers, which can be useful in breeding and genetic diversity estimation of coriander.

Stability of nano-sized permethrin in its colloidal state and its effect on the physiological and biochemical profile of Culex tritaeniorhynchus larvae.

The occurrence of pesticidal pollution in the environment and the resistance in the mosquito species makes an urge for the safer and an effective pesticide. Permethrin, a poorly water-soluble pyrethroid pesticide, was formulated into a hydrodispersible nanopowder through rapid solvent evaporation of pesticide-loaded oil in water microemulsion. Stability studies confirmed that the nanopermethrin dispersion was stable in paddy field water for 5 days with the mean particle sizes of 175.3 ± 0.75 nm and zeta potential of -30.6 ± 0.62 mV. The instability rate of the nanopermethrin particles was greater in alkaline (pH 10) medium when compared with the neutral (pH 7) and acidic (pH 4) dispersion medium. The colloidal dispersion at 45°C was found to be less stable compared with the dispersions at 25 and 5°C. The 12- and 24-h lethal indices (LC50) for nanopermethrin were found to be 0.057 and 0.014 mg l-1, respectively. These results were corroborative with the severity of damages observed in the mosquito larvae manifested in epithelial cells and the evacuation of the midgut contents. Further, the results were substantiated by the decrease in cellular biomolecules and biomarker enzyme activity in nanopermethrin treated larvae when compared to bulk and control treatment.

The Environmentally Benign form of Pesticide in Hydrodispersive Nanometric form with Improved Efficacy Against Adult Mosquitoes at Low Exposure Concentrations.

Permethrin, a poorly water-soluble synthetic pesticide belonging to the pyrethroid family, was formulated into water-dispersive nanometric form by rapid evaporation of pesticide loaded oil-in-water microemulsion. The mean hydrodynamic diameter of Nanopermethrin was found to be 199.01 ± 1.4 nm. The efficacy of the Nanopermethrin was comparatively investigated with its bulk form against 2-3 days old adult mosquitoes by WHO cone bioassay for 60 min. The median knockdown concentration of Culex tritaeniorhynchus, Culex quinquefasciatus and Aedes albopictus were found to be 7.20 × 10(4), 7.53 × 10(4), 0.42 × 10(3) mg/L for Bulk permethrin, and 0.98 × 10(4), 1.17 × 10(4), 0.05 × 10(3) mg/L for Nanopermethrin, respectively. The obtained results extrapolate the improved efficacy of Nanopermethrin even at low-level concentrations. Hence, the formulated Nanopermethrin will serve as an effective alternative pesticide in controlling the mosquito population with reduced environmental toxicity.

Design, synthesis, cytotoxic, and anti-inflammatory activities of some novel analogues of aloe-emodin isolated from the rhizomes of Rheum emodi.

In connection with our continuous efforts in the synthesis of derivatives from major compounds isolated from traditional medicinal plants, in the present study we have attempted to synthesize the furan-conjugated aloe-emodin derivatives (5a-j) using a three-component reaction. The synthesized derivatives were assessed for anticancer activity against five different cancer cell lines using the in vitro MTT assay and the results showed that most of the derivatives are potent against cancer cells comparing with the control. Compounds 5a and 5e showed excellent activity against all the cancer cells with less than 12.5 µM and arrested the cell cycle at the G0/G1 phase in both CAL27 and SCC9 cells. Compound 5e induces the early apoptosis in CAL27 cells and compounds 5a and 5e induce early and late apoptosis, respectively, in SCC9 cells. Moreover, compounds 5b, 5c, 5i, and 5j showed excellent anti-inflammatory activity in LPS-stimulated RAW 264.7 cells by inhibiting IL-6 production. The molecular docking studies revealed that compound 5e has strong interaction with the CLK kinase and protein kinase II through hydrogen binding Asp325 and Lys290.

Non-surgical organ preservation in laryngeal and hypopharyngeal cancers: an audit from the clinic.

BACKGROUND: There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. METHOD: This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). RESULTS: Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. CONCLUSION: Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.

Nuclear envelope, chromatin organizers, histones, and DNA: The many achilles heels exploited across cancers.

In eukaryotic cells, the genome is organized in the form of chromatin composed of DNA and histones that organize and regulate gene expression. The dysregulation of chromatin remodeling, including the aberrant incorporation of histone variants and their consequent post-translational modifications, is prevalent across cancers. Additionally, nuclear envelope proteins are often deregulated in cancers, which impacts the 3D organization of the genome. Altered nuclear morphology, genome organization, and gene expression are defining features of cancers. With advances in single-cell sequencing, imaging technologies, and high-end data mining approaches, we are now at the forefront of designing appropriate small molecules to selectively inhibit the growth and proliferation of cancer cells in a genome- and epigenome-specific manner. Here, we review recent advances and the emerging significance of aberrations in nuclear envelope proteins, histone variants, and oncohistones in deregulating chromatin organization and gene expression in oncogenesis.

Current status and prospects of herbicide-resistant grain sorghum (Sorghum bicolor).

Grain sorghum is a versatile crop, which can thrive under limited water and other inputs. However, crop loss from weed infestation continues to be a major constraint in grain sorghum production. Particularly, post-emergence grass weed control is a great challenge in grain sorghum due to the lack of herbicide options. Unlike in other major crops, such as maize or soybean, herbicide-resistant sorghum technology that can facilitate weed control throughout crop growing season is not available to growers yet. The development of herbicide-resistant sorghum can have potential to improve weed management, including post-emergence grass weed control. One of the major concerns in the development of such technology in sorghum is escape of resistance traits into weedy relatives of sorghum (e.g. shattercane and johnsongrass). This review focuses on sources of herbicide resistance in sorghum, the status of the development of herbicide-resistant sorghum technologies, overview of breeding methods, and limitations in the development of such sorghum technology as well as economic benefits for sorghum growers. © 2021 Society of Chemical Industry.

A pharmacokinetic and bioequivalence study of Contiflo ICON 400 µg tablets in healthy Indian subjects.

INTRODUCTION: Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in human prostate. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of benign prostatic hypertrophy. A new formulation Contiflo ICON 400 µg has been developed by Ranbaxy Laboratories Limited, India similar to Flomaxtra XL 400 µg of Astellas Pharma Limited, United Kingdom. This product is specifically designed to achieve a more consistent plasma concentration over a period of 24-h, a lower maximum plasma concentration (Cmax) and an independence of pharmacokinetics (PKs) on food intake. METHODS: The objective of the present study was to evaluate the pharmacokinetics and bioequivalence of the new formulation Contiflo ICON 400 µg of Ranbaxy Laboratories Limited, India and Flomaxtra XL 400 µg prolonged release tablets (containing tamsulosin hydrochloride prolonged release 400 µg) of Astellas Pharma Limited, United Kingdom. Study was conducted as an open label, balanced, randomized, two-treatment, two-period, two-sequence, cross over, single-dose bioequivalence study in 32 adult male human subjects under fed conditions. The mean (range) age, weight and height of the study subjects were 27.03 years (19 - 40 years), 57.19 kg (48 - 72 kg) and 166.81 cm (154 - 181 cm) respectively. Blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 20, 24, 36, 48, 72, and 96 h post dose in each period. Plasma samples were analyzed for tamsulosin by using validated liquid chromatographic mass spectrometry (LC-MS/MS) method. RESULTS: The Mean ± SD of pharmacokinetic parameters tmax, Cmax, AUC24, AUClast and AUCinf for Tamsulosin were 11.741 ± 4.7201 and 12.155 ± 6.3077 h, 10.7614 ± 4.76709 and 10.4954 ± 5.08979 ng/ml, 171.4674 ± 77.39695 and 160.6738 ± 77.98628 ng.h/ml, 262.7771 ± 150.21432 and 250.6854 ± 156.75581 ng.h/ml, 280.0702 ± 152.14253 and 273.5078 ± 156.85910 ng.h/ml for test and reference formulations respectively. The ratios of least square means and the 90% confidence interval of log transformed pharmacokinetic parameter Cmax, AUC24, AUClast and AUCinf were within 80 - 125% acceptance range. CONCLUSION: In conclusion, Contiflo ICON 400 µg tablets developed by Ranbaxy Laboratories Limited is bioequivalent to the reference formulation in healthy adult male volunteers under fed condition.

Preparation of bio-eco based cellulose nanomaterials from used disposal paper cups through citric acid hydrolysis.

The Used Disposal Paper Cups (UDPCs) have become a concern to the solid waste management sector as scientists triggered the problems in recent years, to proceed forward in developing the process for this issue. Based on this concern, the present study emphasizes on the isolation of a novel bio-eco based Cellulose NanoCrystals (CNCs) from UDPCs through citric acid hydrolysis. The effect of acid concentration on microstructure and yield of CNCs are highlighted. The optimized yield (55 wt.%) has an appearance of rod-like structure with a width of 13.7 ±â€¯0.6 nm which results due to 76 wt.% of acid hydrolyzed CNCs. The colloidal stability, crystallinity index, presence of functional groups and elemental composition in CNCs (76 wt.%) were identified by employing zeta potential, XRD, conductometric test and FTIR techniques. Finally, the thermal stability of CNCs (76 wt.%) was investigated by thermo-gravimetric analysis.

Effect of agro waste α-cellulosic micro filler on mechanical and thermal behavior of epoxy composites.

Of late, measures are being undertaken to curtail deforestation thereby to save the environment. In this venture, agro waste products are utilized for structural applications instead of wood. By this way, the α-cellulosic micro filler, which are isolated from Cocos nucifera var Aurantiaca Peduncle (CAP) through chemical treatment process, are systematically utilized as a reinforcing material in thermo set epoxy polymers as a replacement by manmade carbon, ceramic fillers and wood derived products. The results on mechanical properties such as tensile, flexural, impact test revealed that these properties of the α-cellulosic micro filler reinforced epoxy composites increased in linear nature for 3 wt% to 15 wt% of filler loading and 15 wt% shows the superior behaviour in their mechanical properties. The internal structure of the fractured mechanical test specimens are investigated through Field Emission Scanning Electron Microscopy (FE-SEM). In addition to that, visco-elastic behaviour, thermal stability of the 15 wt% of α-cellulosic micro filler reinforced epoxy composite were analyzed through dynamic mechanical and thermo gravimetric analysis and compare with pristine epoxy.

Controlled delivery of ranitidine in the stomach using magnetic field.

An attempt has been made to localize ranitidine loaded microspheres in the stomach by magnetic means. Since ranitidine undergoes metabolism by microbial enzymes in the intestine, it is ideal to localize the controlled drug delivery system within the stomach to get uniform release and absorption of the drug for the desired period. Gelatin magnetic microspheres loaded with 9.1, 17.9, 26.3 and 33.3% w/w of ranitidine hydrochloride were prepared by emulsification-cross linking technique. The formulated microspheres were characterized by magnetite content, particle size and in vitro drug release. The efficiency of microspheres to be localized in the stomach is tested in vivo in rats. The prepared microspheres were spherical and had a size distribution from 10 to 105 microm. The in vitro study revealed the capability of microspheres to release the drug over a period of 8 to 12 hours, depending on drug loading. The release was found to be diffusion controlled and followed fickian diffusion principle. The in vivo study showed the efficiency of microspheres to be retained in the stomach over a period of 8 hours.

Cystic renal oncocytoma mimicking renal cell carcinoma.

Cystic renal lesions are one of the commonly encountered urological conditions. They can be either benign or malignant. The Bosniak classification is employed to differentiate benign cysts from the malignant ones and to recommend treatment options. Bosniak type 4 cysts are mostly malignant. Rarely, benign tumors can be encountered in Bosniak type 4 cysts. We present a 59-year-old female who presented with a hilar Bosniak type 4 cyst in the right kidney. She underwent open exploration of the right renal tumor. The tumor was infiltrating into the renal vessels and could not be separated from the renal vein. In view of preoperative and intraoperative suspicion of malignancy, radical nephrectomy was done. Postoperative histopathological examination revealed the tumor to be an oncocytoma. The benign nature of the cyst could not be conclusively determined by preoperative investigations and intraoperative findings. Postoperative histological examination uncovered the rare cystic presentation of this benign tumor.

Extraction of cellulose nanofibers from cocos nucifera var aurantiaca peduncle by ball milling combined with chemical treatment.

The development of bio-degradable, renewable and low-cost material is critical to meet the growing environmental concerns and energy demands. The present study emphasizes on the extraction of a new kind of Cellulose NanoFibers (CNFs) from peduncles which are a bio-waste product of Cocos nucifera var-Aurantiaca through ball milling combined with chemical treatment. The crystallinity index, presence of functional groups and elemental composition in CNFs were identified by employing XRD, FT-IR and EDX techniques. The thermal stability of CNFs was investigated by thermo-gravimetric analysis. The morphological analysis was performed by electron microscopy and the results showed the appearance of CNFs in web-like structure with a width of 55-64 nm. The effect of reinforcement of CNFs in epoxy matrix was performed, whose tensile strength increased by 37% when 2 wt% of CNFs was loaded into the matrix.

Transcriptome profiling and cataloging differential gene expression in floral buds of fertile and sterile lines of cotton (Gossypium hirsutum L.).

Cytoplasmic Male Sterility is maternally inherited trait in plants, characterized by failure to produce functional pollen during anther development. Anther development is modulated through the interaction of nuclear and mitochondrial genes. In the present study, differential gene expression of floral buds at the sporogenous stage (SS) and microsporocyte stage (MS) between CGMS and its fertile maintainer line of cotton plants was studied. A total of 320 significantly differentially expressed genes, including 20 down-regulated and 37 up-regulated in CGMS comparing with its maintainer line at the SS stage, as well as and 89 down-regulated and 4 up-regulated in CGMS compared to the fertile line at MS stage. Comparing the two stages in the same line, there were 6 down-regulated differentially expressed genes only induced in CGMS and 9 up-regulated differentially expressed gene only induced in its maintainer. GO analysis revealed essential genes responsible for pollen development, and cytoskeleton category show differential expression between the fertile and CGMS lines. Validation studies by qRT-PCR shows concordance with RNA-seq result. A set of novel SSRs identified in this study can be used in evaluating genetic relationships among cultivars, QTL mapping, and marker-assisted breeding. We reported aberrant expression of genes related to pollen exine formation, and synthesis of pectin lyase, myosine heavy chain, tubulin, actin-beta, heat shock protein and myeloblastosis (MYB) protein as targets for CMS in cotton. The results of this study contribute to basic information for future screening of genes and identification of molecular portraits responsible for CMS as well as to elucidate molecular mechanisms that lead to CMS in cotton.

Environmental benignity of a pesticide in soft colloidal hydrodispersive nanometric form with improved toxic precision towards the target organisms than non-target organisms.

Mosquito-borne diseases are of major concern as they cause devastating health effects, morbidity, and mortality in the human population. Conventional pesticides have failed to curb the mosquito population due to the development of insensitivity in mosquitoes. Hence, higher dosages of pesticides along with their toxic solubilizers have been employed, which have led to raise in pesticide pollution load, environmental toxicity, and human health concerns. As a realisation for the requirement of alternative pesticides, the present study has involved in the formulation of a hydrodispersive nanometric colloidal form of deltamethrin (NDM), a type-II pyrethroid pesticide, from its hydroimmisicible parental form (PDM). The mean hydrodynamic diameter of the droplets was found to be 30.6±4.6nm by dynamic light scattering study (DLS). High-resolution transmission electron micrographs have revealed the spherical structure of the droplets with a size range of 35-40nm. The NDM was found to possess sedimentation resistance, intrinsic and hydrodispersive stability. The toxicity of NDM and PDM was comparatively investigated on target organisms (Culex tritaeniorhynchus and Culex quinquefasciatus mosquitoes) and non-target organisms (Allium cepa - Bioindicator of toxicants and Rhizobium sp. - Soil bacteria). As comparative to PDM, NDM has exerted higher efficacy on adult mosquito and larval population, even at low-level concentrations. However, in the case of non-target organisms, the NDM toxicity was lower than PDM. Comprehensively, the study has concluded the potential advantage of formulating conventional pesticides into nanometric soft colloidal form for the improved toxic precision on target organisms (mosquitoes). This ensures the ability of NDM to combat against the mosquito population even at lower concentrations, thereby reducing the pesticide exposure load towards the environment and human population.

Comparative cytotoxic and genotoxic effects of permethrin and its nanometric form on human erythrocytes and lymphocytes in vitro.

The research on the novel pesticides such as nanopesticides has become inevitable to control the mosquito population. Nanopermethrin (NP), one of such kind was formulated in pesticide loaded oil-in-water (o/w) microemulsion by rapid evaporation. Even though NP possess improved efficacy against the target pests, the toxicological investigation on the human or mammalian system remains unexplored. So, the present study focused on a comparative investigation of the cytotoxic and genotoxic effects of NP in vitro and its commercial parental bulk form of permethrin (BP) on human peripheral erythrocyte/lymphocyte by erythrocyte morphology analysis, cell viability assay, and cytokinesis-block micronucleus (CBMN) assay. The NP and BP concentrations (10, 25, 50 and 100 µg/ml) interacted with human blood cells, and the morphological changes were observed using a phase contrast microscope. The drastic increase of echinocyte was observed at 24, 48 and 72 h treatment as compared with the control. The cell viability studies have shown the significant decrease with increase in NP and BP concentration. CBMN study showed a series correlation in the number of micronuclei, bridge, bud, trinucleated and tetranucleated when interacted with different levels of NP and BP, as comparative to control *p < 0.05, **p < 0.001, ***p < 0.0001.