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Monitoring mortality is an essential strategy for fish health management. Commercial marine finfish sites in British Columbia, Canada, are required to report mortality events (MEs) to Fisheries and Oceans Canada (DFO), which makes these data publicly available. This study aimed to analyze the spatial and temporal patterns of ME composition and total MEs. Between June 2011 and June 2022, 561 MEs were reported. The annual incidence ranged from 1.36 (95% CI: 0.55-2.81) MEs per 100 active site-months in 2013 to 17.98 (95% CI: 13.26-23.84) MEs per 100 active site-months in 2022, with a broadly increasing trend over the period under consideration. The primary causes of MEs were low levels of dissolved oxygen, fish health treatments, and harmful algal blooms (HABs). Both HABs and low dissolved oxygen followed similar patterns, increasing from 2014, peaking in 2019, and declining thereafter. Treatment-related MEs were first reported in 2017 and saw a sharp increase in subsequent years, becoming the leading cause of MEs by 2020. Nearly all treatment-related MEs were linked to sea lice treatments, highlighting the urgent need for adaptive strategies to mitigate these impacts. Sites on the west coast of Vancouver Island demonstrated a higher risk of reporting MEs compared to Mainland sites, likely due to their higher levels of exposure to fluctuating oceanographic conditions. Long-term climate change and persistent periods of warming events, such as marine heat waves, are warming the oceans, altering water parameters, and likely increasing the occurrence and severity of HABs and low dissolved oxygen-related MEs. Further studies are needed to quantify the effects of ocean warming on salmon aquaculture and the resulting increase in fish mortalities., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Atlantic salmon aquaculture companies in British Columbia (BC) must report fish health events to Fisheries and Oceans Canada (DFO) as part of their licensing conditions. Our study aimed to summarize these fish health events reported by Atlantic salmon sites in BC to identify spatial and spatio-temporal clusters. We conducted descriptive, retrospective global, and local cluster analyses using Moran's I and scan statistics. Between 2016 and 2022, 265 fish health events were reported. The annual incidence ranged from 5.60 (95% CI: 3.90-7.80) to 6.86 (95% CI: 4.70-9.60) health events per 100 active site-months. The most common events were yellow mouth (60.75%; 161/265) and salmonid rickettsial septicaemia (SRS) (15.47%; 41/265). The Moran's I index was positive and significant for yellow mouth, SRS, and overall fish health events at different distance bands. Most of the spatial and spatio-temporal clusters were identified in the west-central and southwestern parts of Vancouver Island. Our study hypothesizes that management practices, environmental conditions, and water quality parameters may have influenced the increased reporting of fish health events in these regions. Overall, the study highlights the potential of publicly available data for practical risk mapping in understanding the patterns of farmed Atlantic salmon diseases in BC., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

The oyster aquaculture sector plays a major role in food security, providing a sustainable way to obtain food and livelihood for coastal and Island nations. Oysters are one of the preferred choices by aquaculturists because of their resilience to harsh climatic conditions. Nonetheless, climate change will continue to pose threats to its culture. Climate-induced hazards such as floods, storms, disease, and invasive species are some of the key factors limiting oyster production globally. A thriving aquaculture industry needs optimal conditions to maximize exploitation. Here, we continue with the review of the impacts of climate change on oyster aquaculture at the global scale, highlighting climate vulnerability assessment. We also propose a framework for modeling oyster responses to future climate scenarios. Furthermore, we explore the health implications of infected oysters on consumer's health. We also identify knowledge gaps and challenges for sustainable oyster production. Additionally, we document mitigation and adaptation measures and future research directions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pheochromocytoma is a rare neuroendocrine tumor arising from adrenal medulla. Patients usually show classic triad of headache, palpitations and diaphoresis along with persistent or paroxysmal hypertension. Majority of the tumors are solid or mixed solid and cystic. But purely cystic variant is extremely rare with few cases reports available in the published literature. We report a case of purely cystic pheochromocytoma in a male in 30s who presented to our hospital for unrelated symptom of recurrent burning micturition. He was evaluated for causes of recurrent UTI which revealed incidental right adrenal cyst. The patient's blood pressure was raised on clinical examination and imaging showed simple adrenal cyst without solid component or septations. Suspecting possibility of pheochromocytoma, biochemical analysis was done which revealed elevated 24-hour urinary metanephrine. The diagnosis of cystic pheochromocytoma was made. Adrenalectomy was performed showing cystic lesion in the right adrenal region. Histopathology and immunohistochemistry revealed pheochromocytoma with cystic degeneration. Patient's hypertension resolved during the follow up. In conclusion, purely cystic pheochromocytoma must be considered as differential for adrenal cystic lesions, especially when atypical features are present., (© 2024 Published by Elsevier Inc. on behalf of University of Washington.)

Aim: This study aimed to summarize the frequency and the antimicrobial susceptibility profiles of the Salmonella serotypes identified from the specimens of companion animals, livestock, avian, wildlife and exotic species within Atlantic Canada., Materials and Methods: The retrospective electronic laboratory data of microbiological analyses of a selected subset of samples from 03 January 2012 to 29 December 2021 submitted from various animal species were retrieved. The frequency of Salmonella serotypes identified, and their antimicrobial susceptibility results obtained using the disk diffusion or broth method were analysed. The test results were interpreted according to the Clinical and Laboratory Standards Institute standard. The Salmonella serotypes were identified by slide agglutination (Kauffman-White-Le-Minor Scheme) and/or the Whole Genome Sequencing for the Salmonella in silico Serovar Typing Resource-based identification., Results: Of the cases included in this study, 4.6% (n = 154) had at least one Salmonella isolate, corresponding to 55 different serovars. Salmonella isolation was highest from exotic animal species (n = 40, 1.20%), followed by porcine (n = 26, 0.78%), and canine (n = 23, 0.69%). Salmonella subsp. enterica serovar Typhimurium was predominant among exotic mammals, porcine and caprine samples, whereas S. Enteritidis was mostly identified in bovine and canine samples. S. Typhimurium of porcine origin was frequently resistant (>70.0%) to ampicillin. In contrast, S. Typhimurium isolates from porcine and caprine samples were susceptible (>70.0%) to florfenicol. S. Oranienburg from equine samples was susceptible to chloramphenicol, but frequently resistant (>90.0%) to azithromycin. In avian samples, S. Copenhagen was susceptible (>90.0%) to florfenicol, whereas Muenchen was frequently resistant (>90.0%) to florfenicol. S. subsp. diarizonae serovar IIIb:61:k:1,5 of ovine origin was resistant (50.0% isolates) to sulfadimethoxine. No significant changes were observed in the antibiotic resistance profiles across the study years., Conclusions: This report provides data for surveillance studies, distribution of Salmonella serotypes and their antimicrobial resistance among veterinary specimens of Atlantic Canada., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Oysters are enriched with high-quality protein and are widely known for their exquisite taste. The production of oysters plays an important role in the local economies of coastal communities in many countries, including Atlantic Canada, because of their high economic value. However, because of the changing climatic conditions in recent years, oyster aquaculture faces potentially negative impacts, such as increasing water acidification, rising water temperatures, high salinity, invasive species, algal blooms, and other environmental factors. Although a few isolated effects of climate change on oyster aquaculture have been reported in recent years, it is not well understood how climate change will affect oyster aquaculture from a systematic perspective. In the first part of this study, we present a systematic review of the impacts of climate change and some key environmental factors affecting oyster production on a global scale. The study also identifies knowledge gaps and challenges. In addition, we present key research directions that will facilitate future investigations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The sustainable utilization of resources motivate us to create eco-friendly processes for synthesizing novel carbon nanomaterials from waste biomass by minimizing chemical usage and reducing energy demands. By keeping sustainability as a prime focus in the present work, we have made the effective management of Parthenium weeds by converting them into carbon-based nanomaterial through hydrothermal treatment followed by heating in a tube furnace under the nitrogen atmosphere. The XPS studies confirm the natural presence of nitrogen and oxygen-containing functional groups in the biomass-derived carbon. The nanostructure has adopted a layered two-dimensional structure, clearly indicated through HRTEM images. Further, the nanomaterials are analyzed for their ability towards the electrochemical detection of mercury, with a detection limit of 6.17 μM, while the limit of quantification and sensitivity was found to be 18.7 μM and 0.4723 μM μA -1 cm -2 , respectively. The obtained two-dimensional architecture has increased the surface area, while the nitrogen and oxygen functional groups act as an active site for sensing the mercury ions. This study will open a new door for developing metal-free catalysts through a green and sustainable approach by recycling and utilization of waste biomass., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Host-microbe dynamics are of increasing interest in marine research due to their role in host health and productivity. Changes in the shell microbiome of American lobsters have been associated with epizootic shell disease, a syndrome that is spreading northwards across the eastern U.S. and Canadian Atlantic coast. This study analyzed differences in alpha and beta diversity, as well as differentially abundant taxa, in the shell-associated bacterial community of apparently healthy lobsters from four lobster fishing areas (LFAs) in Atlantic Canada. Over 180 lobsters from New Brunswick, Nova Scotia and Prince Edward Island (PEI) were sampled during seven sampling events over four sampling months. The bacterial community was identified using novel PacBio long-read sequencing, while alpha and beta diversity parameters were analyzed using linear regression models and weighted UniFrac distances. The bacterial richness, diversity and evenness differed by sampling location, sampling month, and molt stage, but not by lobster sex or size, nor sampling depth. Similarly, based on LFA, sampling month, year and lobster molt stage, the shell microbiome differed in microbial community composition with up to 34 out of 162 taxa differing significantly in abundance between sampling groups. This large-scale microbial survey suggests that the shell microbial diversity of apparently healthy lobsters is influenced by spatial and temporal factors such as geographic location, as well as the length of time the carapace is exposed to the surrounding seawater., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Koepper, Clark, McClure, Revie, Stryhn and Thakur.)

Size distribution and size frequency information of American lobsters (Homarus americanus) are often used to help estimate the age distributions, and reproductive output for the species and to guide the determination of appropriate minimum legal sizes for the fishery. This study used truncated linear regression models to estimate the effects of sampling year, sampling month, lobster sex and water depth on the lobster size. A dataset of almost 130,000 trap-caught lobsters from the two most important lobster fishing areas of Atlantic Canada collected over a 12-year period (2004-2015) was analyzed. It was shown that truncated models can help to account for biases due to the trap sampling method from vessels and from wharf samplings. There were significant annual and seasonal changes in size distribution, and data collected outside the fishing season showed a significant increase in carapace length in 2014 and 2015, potentially reflecting a northward shift of the range of lobster populations due to more favourable settlement and recruitment habitats. Size also increased in late summer, likely due to moult. Our results demonstrated that landed lobsters, especially females, were smaller than the predicted size-at-maturity in the region (96.5 mm carapace length), which could have long-term repercussions for the stock's reproductive potential., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Koepper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The objectives of this study were to describe spatiotemporal patterns of infectious salmon anemia virus (ISAV) detections in marine salmonid production sites in the province of Newfoundland and Labrador in Canada., Methods: Infectious salmon anemia virus surveillance data between 2012 and 2020 from the province of Newfoundland and Labrador were used. Data comprised a total of 94 sampling events from 20 Atlantic Salmon Salmo salar production sites in which ISAV was detected. Using linear regression models, factors influencing time to detection (days from stocking to first ISAV detection) and time to depopulation (days from first detection to production site depopulation) were investigated., Result: Based on 28 unique cases, site-level annual incidence risk of ISAV detection ranged from 3% to 29%. The proportion of ISAV detection by PCR in fish samples ranged from 2% to 45% annually. Overall, ISAV variants from the European clade were more common than variants from the North American clade. The type of ISAV clade, detections of ISAV in nearest production sites based on seaway distances, and year of infectious salmon anemia cases were not associated with time to first ISAV detection. Time to depopulation for sites infected with the ISAV-HPRΔ variant was not associated with ISAV North American or European clades., Conclusion: Our results contribute to the further understanding of the changing dynamics of infectious salmon anemia detections in Newfoundland and Labrador since its first detection in 2012 and will likely assist in the design of improved disease surveillance and control programs in the province., (© 2023 The Authors. Journal of Aquatic Animal Health published by Wiley Periodicals LLC on behalf of American Fisheries Society.)

The shell microbial community of lobsters-a key factor in the development of epizootic shell disease (ESD)-is still insufficiently researched in Atlantic Canada and many knowledge gaps remain. This study aimed to establish a baseline description and analysis of the shell microbiome of apparently healthy lobsters from four locations in the region. More than 180 lobster shell swab samples were collected from New Brunswick, Nova Scotia and Prince Edward Island (PEI). PacBio long-read 16S rDNA sequencing and bioinformatic analyses in QIIME2 identified the shell-associated bacteria. The shell microbiome of healthy lobsters consisted mainly of the bacterial classes Gammaproteobacteria , Saprospiria , Verrucomicrobiae , Alphaproteobacteria , Flavobacteriia , Acidimicrobiia and Planctomycetia . The microbial composition differed regionally and seasonally, with some classes showing decreased or increased relative abundances in the PEI samples as well as in the winter and spring samples in Nova Scotia. The core shell microbiome included potentially pathogenic as well as beneficial bacterial taxa, of which some were present only in certain regions. Bacterial taxa that have previously been associated with ESD were present on healthy lobsters in Atlantic Canada, but their frequency differed by location, sampling time, and moult stage. This study indicated that geographical and seasonal factors influenced the shell microbiome of apparently healthy lobsters more than host factors such as sex, size, and moult stage. Our results provide valuable reference microbial data from lobsters in a disease-free state., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koepper, Clark, McClure, Revie, Stryhn and Thakur.)

Purpose: 3D bioprinting is capable of rapidly producing small-scale human-based tissue models, or organoids, for pathology modeling, diagnostics, and drug development. With the use of 3D bioprinting technology, 3D functional complex tissue can be created by combining biocompatible materials, cells, and growth factor. In today's world, 3D bioprinting may be the best solution for meeting the demand for organ transplantation. It is essential to examine the existing literature with the objective to identify the future trend in terms of application of 3D bioprinting, different bioprinting techniques, and selected tissues by the researchers, it is very important to examine the existing literature. To find trends in 3D bioprinting research, this work conducted an systematic literature review of 3D bioprinting., Methodology: This literature provides a thorough study and analysis of research articles on bioprinting from 2000 to 2022 that were extracted from the Scopus database. The articles selected for analysis were classified according to the year of publication, articles and publishers, nation, authors who are working in bioprinting area, universities, biomaterial used, and targeted applications., Findings: The top nations, universities, journals, publishers, and writers in this field were picked out after analyzing research publications on bioprinting. During this study, the research themes and research trends were also identified. Furthermore, it has been observed that there is a need for additional research in this domain for the development of bioink and their properties that can guide practitioners and researchers while selecting appropriate combinations of biomaterials to obtain bioink suitable for mimicking human tissue., Significance of the Research: This research includes research findings, recommendations, and observations for bioprinting researchers and practitioners. This article lists significant research gaps, future research directions, and potential application areas for bioprinting., Novelty: The review conducted here is mainly focused on the process of collecting, organizing, capturing, evaluating, and analyzing data to give a deeper understanding of bioprinting and to identify potential future research trends., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows rapid and reliable identification of microorganisms. The accuracy of bacterial identification using MALDI-TOF MS depends on main spectral profiles (MSPs) provided in a quality-assured commercial reference library, which requires ongoing improvement. This study aimed to develop and validate an in-house MALDI-TOF MS MSP to rapidly identify Yersinia ruckeri isolated from Atlantic salmon ( Salmo salar ). The novel MSP was prepared using an isolate of Y. ruckeri recovered from Atlantic salmon and confirmed by 16S rRNA gene sequencing. Subsequently, a validation set which comprises 29 isolates of Y. ruckeri were examined from three fishes: Atlantic salmon ( Salmo salar ) ( n = 26), American eel ( Anguilla rostrata ) ( n = 1), and Atlantic cod ( Gadus morhua ) ( n = 2). These isolates were randomly selected from the Atlantic Veterinary College, Aquatic Diagnostic Services Bacteriology Laboratory's culture collection to validate the novel MSP. Analytical sensitivity of MALDI-TOF MS using the novel MSP to identify the validation set was 86.2%. Repeatability was assessed by acquiring spectra from 30 different spots of a randomly-selected isolate of Y. ruckeri , and analyzed spectra from each spot were compared against the novel MSP. The coefficient of variation was 3.3%. The novel MSP clustered with Bruker MSPs ( n = 3) of Y. ruckeri in the reference library and did not falsely identify any closely related bacteria to Y. ruckeri . This study reports the development of a novel MSP of high analytical sensitivity and specificity for rapid identification of Y. ruckeri using MALDI-TOF MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ojasanya, Gardner, Groman, Saksida, Saab and Thakur.)

Monitoring the moulting phenology of American lobsters (Homarus americanus) is important for maintaining sustainable lobster stocks. Changes in lobster landings can affect reproduction and disease susceptibility. Data on lobster moult indicators and on life-history traits (sex, size) were collated from a twelve-year monitoring program (2004-2015) in six lobster fishing areas in Atlantic Canada. A total of 141,659 lobsters were sampled over 1,195 sampling events using a standardized protocol and commercial lobster fishing traps. The dataset contains pleopod stages, estimated hemolymph protein levels (°Brix values) and shell hardness as well as lobster sex and size. Evaluation of sex ratio dynamics is also possible but existing biases in sampling males and females needs to be noted. This dataset is valuable in terms of inferring spatio-temporal trends in the life history of lobsters, as well as in the analysis of their moult cycle, and hence more generally for fisheries science and marine ecology., (© 2022. The Author(s).)

Despite significant advancements made in the treatment of cancer during the past several decades, it remains one of the leading causes of death worldwide killing approximately 9.6 million people annually. The major challenge for therapeutic success is the development of chemoresistance in cancer cells against conventional chemotherapeutic agents via modulation of numerous survival and oncogenic signaling pathways. Therefore, sensitization of cancer cells to conventional drugs using multitargeted agents that suppress the survival and oncogenic pathways, in single or in combination, is an emerging strategy to overcome drug-resistance. During the last couple of decades, phytochemicals such as curcumin, resveratrol, tocotrienol and quercetin have emerged as potential chemosensitizing agents in cancer cells due to their less toxic and multitargeted properties. Numerous preclinical and clinical studies enumerated their potential to prevent drug resistance and sensitize cancer cells to chemotherapeutic agents by modulating several genes/proteins or pathways that regulate the key factors during the growth and progression of tumors such as inhibition of anti-apoptotic proteins, activation of pro-apoptotic proteins, reduced expression of different transcription factors, chemokines, enzymes, cell adhesion molecules, protein tyrosine kinases and cell cycle regulators. Therefore, natural chemosensitizing agents will have a special place in cancer treatment in the near future. This comprehensive review summarizes data obtained from various in vitro, in vivo and clinical studies to provide a new perspective for the application of agents obtained from "Mother Nature" as potential chemosensitizers for further cancer drug research and development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The medicinal plant Scutellaria baicalensis, commonly known as Chinese skullcap or Huang-Qin, has been used as a traditional medicine for several thousand years. The roots of this plant contain bioactive compounds, such as wogonin (WOG), wogonoside, baicalein, and baicalin. The aim of this article is to evaluate the therapeutic potential and mechanisms of action of WOG against different cancers. Numerous in vitro and in vivo studies have revealed that WOG exerts immense therapeutic potential against bladder cancer, breast cancer, cholangiocarcinoma, cervical cancer, colorectal cancer, gallbladder cancer, gastric cancer, glioblastoma, head and neck cancer, hepatic cancer, leukemia, lung cancer, lymphoma, melanoma, multiple myeloma, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, and renal cancer by regulating various cell signaling pathways. WOG, in combination with established chemotherapeutic drugs, improves the efficacy of treatment and lowers toxicity. Nevertheless, human trials are warranted to validate these findings. Numerous preclinical studies, combined with an extensive margin of safety and no severe side effects, underscore WOG's therapeutic potential as an anticancer drug. These studies propound the use of WOG as a potential anticancer candidate; however, further high-quality studies are required to firmly establish the clinical efficacy of WOG for the prevention and treatment of human malignancies., (© 2022 John Wiley & Sons Ltd.)

Bacterial infection and antimicrobial resistance are important constraints in the production and sustainability of farmed salmonids. This retrospective study aimed to describe the frequency of bacterial isolates and antimicrobial resistance profiles in salmonid aquaculture in Atlantic Canada. Bacterial isolates and antimicrobial susceptibility testing (AST) results assessed by disk diffusion testing were summarized for 18,776 Atlantic salmon ( Salmo salar ) and rainbow trout ( Oncorhynchus mykiss ) samples from 2291 unique cases submitted to the Atlantic Veterinary College, Aquatic Diagnostic Services Bacteriology Laboratory from 2000 to 2021. Kidney was the most commonly submitted tissue (60.29%, n = 11,320), and these specimens were mostly submitted as swabs (63.68%, n = 11,957). The most prevalent pathogens detected in these cases were Yersinia ruckeri type 1 (5.54%, n = 127), Renibacterium salmoninarum (2.10%, n = 48), Aeromonas salmonicida (atypical) (1.66%, n = 38), and Pseudomonas fluorescens (1.22%, n = 28). Most bacterial isolates tested (n = 918) showed resistance to florfenicol, oxytetracycline, ormetoprim-sulfadimethoxine, and trimethoprim-sulfamethoxazole, but not to enrofloxacin. This report provides baseline data for antimicrobial surveillance programs that investigate emerging antimicrobial resistance trends in salmonid aquaculture in Atlantic Canada.

The hydrogels responding to pH synthesized by graft copolymerization only and then concurrent grafting and crosslinking of monomer N-isopropyl acrylamide (NIPAAM) and binary comonomers acrylamide, acrylic acid and acrylonitrile (AAm, AA and AN) onto chitosan support were explored for the percent upload and release study for anti-inflammatory diclofenac sodium drug (DS), w.r.t. time and pH. Diclofenac sodium DS was seized in polymeric matrices by the equilibration process. The crosslinked-graft copolymers showed the highest percent uptake than graft copolymers (without crosslinker) and chitosan itself. The sustainable release of the loaded drug was studied with respect to time at pH 2.2, 7.0, 7.4 and 9.4. Among graft copolymers (without crosslinking), Chit-g-polymer (NIPAAM-co-AA) and Chit-g-polymer (NIPAAM-co-AN) exhibited worthy results for sustainable drug deliverance, whereas Crosslink-Chit-g-polymer (NIPAAM-co-AA) and Crosslink-Chit-g-polymer (NIPAAM-co-AAm) presented the best results for controlled/sustained release of diclofenac sodium DS with 93.86 % and 96.30 % percent release, respectively, in 6 h contact time. Therefore, the grafted and the crosslinked graft copolymers of the chitosan showed excellent delivery devices for the DS with sustainable/prolonged release in response to pH. Drug release kinetics was studied using Fick’s law. The kinetic study revealed that polymeric matrices showed the value of n as n > 1.0, hence drug release took place by non-Fickian diffusion. Hence, the present novel findings showed the multidirectional drug release rate. The morphological changes due to interwoven network structure of the crosslinked are evident by the Scanning electron microscopy (SEM) analysis.

Lung cancer is the foremost cause of cancer related mortality among men and one of the most fatal cancers among women. Notably, the 5-year survival rate of lung cancer is very low; 5% in developing countries. This low survival rate can be attributed to factors like late stage diagnosis, rapid postoperative recurrences in the patients undergoing treatment and development of chemoresistance against different agents used for treating lung cancer. Therefore, in this study we evaluated the potential of a recently identified protein namely TIPE3 which is known as a transfer protein of lipid second messengers as a lung cancer biomarker. TIPE3 was found to be significantly upregulated in lung cancer tissues indicating its role in the positive regulation of lung cancer. Supporting this finding, knockout of TIPE3 was also found to reduce the proliferation, survival and migration of lung cancer cells and arrested the G2 phase of cell cycle through inactivation of Akt/mTOR, NF-κB, STAT-3 signaling. It is well evinced that tobacco is the major risk factor of lung cancer which affects both males and females. Therefore, this study also evaluated the involvement of TIPE3 in tobacco mediated lung carcinogenesis. Notably, this study shows for the first time that TIPE3 positively regulates tobacco induced proliferation, survival and migration of lung cancer through modulation of Akt/mTOR signaling. Thus, TIPE3 plays critical role in the pathogenesis of lung cancer and hence it can be specifically targeted to develop novel therapeutic strategies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

An approximate 1:1 sex ratio of American lobsters can be skewed due to environmental factors or fisheries management. Substantial skewness can impact mating behaviour and lower reproduction which could have far-reaching ecological and economic consequences. The aim was to investigate the sex ratio patterns of lobsters in two lobster fishing areas (LFAs) in southwestern Nova Scotia, Canada and identify factors associated with skewed sex ratios. This study analyzed biological data from more than 270,000 lobsters sampled over ten years (2010-2019) by the Fishermen and Scientists Research Society. A mixed effect logistic regression model evaluated the effect of spatial, temporal and environmental factors as well as size on the sex ratio of lobsters. There were significant temporal patterns in sex ratios that differed by LFA. After the effects of sampling month, year and LFA were accounted for, lower bottom temperature and deeper water depth were associated with a higher prevalence of females, especially in larger lobsters. We present the first long term analyses of sex ratio patterns in H. americanus in Atlantic Canada's most commercially important region for this species and provide evidence that these patterns are influenced by environmental factors and fisheries. In view of future climate change scenarios, monitoring the population dynamics of this iconic fishery species is crucial to ensure sustainable fisheries and healthy lobster stocks., (© 2021. The Author(s).)

Background: Chronic diseases or non-communicable diseases are a major burden worldwide due to the lack of highly efficacious treatment modalities and the serious side effects associated with the available therapies., Purpose/study Design: A novel self-emulsifying formulation of curcumin with fenugreek galactomannan hydrogel scaffold as a water-dispersible non-covalent curcumin-galactomannan molecular complex (curcumagalactomannosides, CGM) has shown better bioavailability than curcumin and can be used for the prevention and treatment of chronic diseases. However, the exact potential of this formulation has not been studied, which would pave the way for its use for the prevention and treatment of multiple chronic diseases., Methods: The whole transcriptome analysis (RNAseq) was used to identify differentially expressed genes (DEGs) in the liver tissues of mice treated with LPS to investigate the potential of CGM on the prevention and treatment of chronic diseases. Expression analysis using DESeq2 package, GO, and pathway analysis of the differentially expressed transcripts was performed using UniProtKB and KEGG-KAAS server., Results: The results showed that 559 genes differentially expressed between the liver tissue of control mice and CGM treated mice (100 mg/kg b.wt. for 14 days), with adjusted p-value below 0.05, of which 318 genes were significantly upregulated and 241 were downregulated. Further analysis showed that 33 genes which were upregulated (log2FC > 8) in the disease conditions were significantly downregulated, and 32 genes which were downregulated (log2FC < -8) in the disease conditions were significantly upregulated after the treatment with CGM., Conclusion: Overall, our study showed CGM has high potential in the prevention and treatment of multiple chronic diseases., (Copyright © 2021. Published by Elsevier Inc.)

In recent years, triple-negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%-24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease-free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms., (© 2021 Wiley Periodicals LLC.)

Free-roaming dogs have been identified as an important reservoir of rabies in many countries including Thailand. There is a need for novel insights to improve current rabies control strategies in these countries. Network analysis is commonly used to study the interactions between individuals or organizations and has been applied in preventive veterinary medicine. However, contact networks of domestic free-roaming dogs are mostly unexplored. The objective of this study was to explore the contact network of free-roaming dogs residing on a university campus. Three one-mode networks were created using co-appearances of dogs as edges. A two-mode network was created by associating the dog with the pre-defined area it was seen in. The average number of contacts a dog had was 6.74. The normalized degree for the weekend network was significantly higher compared to the weekday network. All one-mode networks displayed small-world network characteristics. Most dogs were observed in only one area. The average number of dogs which shared an area was 8.67. In this study, we demonstrated the potential of observational methods to create networks of contacts. The network information acquired can be further used in network modeling and designing targeted disease control programs.

Background: Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties., Aim: To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm., Method: A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm., Key Findings: The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation., Significance: As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Porcine Reproductive and Respiratory Syndrome (PRRS) is a viral swine disease that causes reproductive failure in breeding sows and respiratory distress in growing pigs. The main objectives were to simulate the transmission patterns of PRRS in Uganda using North American Animal Disease Spread Model (NAADSM) and to evaluate the potential effect of prevention and control options such as vaccination and movement control. The median number of infectious farms at the end of 52 weeks for the baseline scenario was 735 (36.75% of the 2,000 farms). The best effects of vaccination were observed in scenarios 60% farm coverage and 80% farm coverage, which resulted in 82 and 98.2% reduction in the median number of infectious farms at the end of the simulation, respectively. Vaccination of all medium and large farms only (33% of the farms) resulted in a 71.2% decrease in the median number of infectious farms at the end of 52 weeks. Movement control (MC) results showed that the median number of infectious farms at the end of 52 weeks decreased by 21.6, 52.3, 79.4, and 92.4% for scenarios MC 20, MC 40, MC 60, and MC 80%, respectively. This study provides new insights to the government of Uganda on how PRRS can be controlled. The large and medium farms need to be prioritized for vaccination, which would be a feasible and effective way to limit the spread of PRRS in Uganda. Scavenging pigs should be confined at all times, whether in the presence or absence of any disease outbreaks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hasahya, Thakur, Dione, Wieland, Oba, Kungu and Lee.)

The main objectives of this study were to model various scenarios of African swine fever (ASF) virus transmission among farms in Vietnam and to evaluate the impact of control strategies using North American Animal Disease Spread Model (NAADSM). A total of 7,882 pig farms in the Red River Delta (RRD) region were obtained from the General Statistics Office, and then, random points corresponding to the number of farms in each province were generated as exact farm locations were not available. A total of 10 models were developed, including movement control scenarios. In addition, we conducted sensitivity analysis to assess the impact of indirect contact transmission probability (TP). Overall, the indirect contact exhibited an important role in transmitting the ASF virus. In order to minimize ASF transmission between farms, we found that movement restriction needed to reach a certain level (approximately between 50% and 75%) and that the restriction had to be applied in a timely manner. This study offers valuable insight into how ASF virus can be transmitted via direct and indirect contact and controlled among farms under the various simulation scenarios. Our results suggest that the enforcement of movement restriction was an effective control measure as soon as the outbreaks were reported. In addition, this study provided evidence that high standards of biosecurity can contribute to the reduction of disease spread., (© 2020 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

Diabetes Ketoacidosis in association with acute myocardial infarction is quite frequent but is also associated with higher morbidity and mortality. These two can trigger each other, different hypothesis have been proposed to explain this phenomenon but still it is difficult to know which one appears first. We report a referred case to our centre with acute Myocardial Infarction and diabetic ketoacidosis promptly initiated treatment of diabetic ketoacidosis along with primary PCI. Keywords: Cardiogenic shock; diabetic ketoacidosis; metabolic acidosis; myocardial Infarction.

African swine fever virus is highly contagious, and mortality rates reach up to 100% depending on the host, virus dose, and the transmission routes. The main objective of this study was to develop a network-based simulation model for the farm-level transmission of ASF virus to evaluate the impact of changes in farm connectivity on ASF spread in Vietnam. A hypothetical population of 1,000 pig farms was created and used for the network-based simulation, where each farm represented a node, and the connection between farms represented an edge. The three scenarios modelled in this way (baseline, low, and high) evaluated the impact of connectivity on disease transmission. The median number of infected farms was higher as the connectivity increased (low: 659, baseline: 968 and high: 993). In addition, we evaluated the impact of the culling strategy on the number of infected farms. A total of four scenarios were simulated depending on the timing of culling after a farm was infected. We found that the timing of culling at 16, 12, 8, and 6 weeks had resulted in a reduction of the number of median infected farms by 81.92%, 91.63%, 100%, and 100%, respectively. Finally, our evaluation of the implication of stability of ties between farms indicated that if the farms were to have the same trading partners for at least six months could significantly reduce the median number of infected farms to two (95th percentile: 413) than in the basic model. Our study showed that pig movements among farms had a significant influence on the transmission dynamics of ASF virus. In addition, we found that the either timing of culling, reduction in the number of trading partners each farm had, or decreased mean contact rate during the outbreaks were essential to prevent or stop further outbreaks., Competing Interests: NO authors have competing interests Enter: The authors have declared that no competing interests exist.

In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn., which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, nuclear factor-kappa B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies., Competing Interests: The authors express no conflict of interest., (© The Author(s) 2021.)

Lung cancer is the leading cause of cancer-related death across the globe. Despite the marked advances in detection and therapeutic approaches, management of lung cancer patients remains a major challenge to oncologists which can be mainly attributed to late stage diagnosis, tumor recurrence and chemoresistance. Therefore, to overthrow these limitations, there arises a vital need to develop effective biomarkers for the successful management of this aggressive cancer type. Notably, TNF-alpha induced protein 8 (TIPE), a nuclear factor-kappa B (NF-κB)-inducible, oncogenic molecule and cytoplasmic protein which is involved in the regulation of T lymphocyte-mediated immunity and different processes in tumor cells such as proliferation, cell death and evasion of growth suppressors, might serve as one such biomarker which would facilitate effective management of lung cancer. Expression studies revealed this protein to be significantly upregulated in different lung cancer types, pathological conditions, stages and grades of lung tumor compared to normal human lung tissues. In addition, knockout of TIPE led to the reduced proliferation, survival, invasion and migration of lung cancer cells. Furthermore, TIPE was found to function through modulation of Akt/mTOR/STAT-3 signaling cascade. This is the first report which shows the involvement of TIPE in tobacco induced lung carcinogenesis. It positively regulated nicotine, NNK, NNN, and BaP induced proliferation, survival and migration of lung cancer cells possibly via Akt/STAT-3 signaling. Thus, this protein possesses important role in the pathogenesis of lung tumor and hence it can be targeted for developing newer therapeutic interventions for the clinico-management of lung cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Chronic diseases are a major cause of mortality worldwide, and despite the recent development in treatment modalities, synthetic drugs have continued to show toxic side effects and development of chemoresistance, thereby limiting their application. The use of phytochemicals has gained attention as they show minimal side effects. Diosgenin is one such phytochemical which has gained importance for its efficacy against the life-threatening diseases, such as cardiovascular diseases, cancer, nervous system disorders, asthma, arthritis, diabetes, and many more., Aim: To evaluate the literature available on the potential of diosgenin and its analogs in modulating different molecular targets leading to the prevention and treatment of chronic diseases., Method: A detailed literature search has been carried out on PubMed for gathering information related to the sources, biosynthesis, physicochemical properties, biological activities, pharmacokinetics, bioavailability and toxicity of diosgenin and its analogs., Key Findings: The literature search resulted in many in vitro, in vivo and clinical trials that reported the efficacy of diosgenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK, etc., which play a crucial role in the development of most of the diseases. Reports have also revealed the safety of the compound and the adaptation of nanotechnological approaches for enhancing its bioavailability and pharmacokinetic properties., Significance: Thus, the review summarizes the efficacy of diosgenin and its analogs for developing as a potent drug against several chronic diseases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tenacibaculosis remains a major health issue for a number of important aquaculture species globally. On the west coast of Canada, yellow mouth (YM) disease is responsible for significant economic loss to the Atlantic salmon industry. While Tenacibaculum maritimum is considered to be the primary agent of clinical YM, the impact of YM on the resident microbial community and their influence on the oral cavity is poorly understood. Using a 16s rRNA amplicon sequencing analysis, the present study demonstrates a significant dysbiosis and a reduction in diversity of the microbial community in the YM affected Atlantic salmon. The microbial community of YM affected fish was dominated by two amplicon sequence variants (ASVs) of T. maritimum , although other less abundant ASVs were also found. Interestingly clinically unaffected (healthy) and YM surviving fish also had a high relative abundance of T. maritimum , suggesting that the presence of T. maritimum is not solely responsible for YM. A statistically significant association was observed between the abundance of T. maritimum and increased abundance of Vibrio spp. within fish displaying clinical signs of YM. Findings from our study provide further evidence that YM is a complex multifactorial disease, characterized by a profound dysbiosis of the microbial community which is dominated by distinct ASVs of T. maritimum . Opportunistic taxa, including Vibrio spp., may also play a role in clinical disease progression., (Copyright © 2020 Wynne, Thakur, Slinger, Samsing, Milligan, Powell, McKinnon, Nekouei, New, Richmond, Gardner and Siah.)

Background: Hepatitis E virus (HEV) is a zoonotic disease and has been reported around the world. The main objective of this study was to evaluate the sero-prevalence and phylogenetic analysis of HEV in Vietnam. Pig blood and fecal pooled samples were collected to assess the prevalence of HEV. We assessed the true prevalence (TP) of HEV from apparent prevalence (AP) by taking into account the sensitivity and specificity of diagnostic tests using a Bayesian approach. For phylogenetic analysis, the data compared with worldwide HEV reference strains including all eight genotypes (G1-G8) which were identified in previous study., Results: A total of 475 sera and 250 fecal pooled samples were collected at slaughterhouses and pig farms from five provinces, in Viet Nam. Overall, the sero-AP of HEV was 58.53% (95% confidence interval: 53.95-62.70) while the sero-TP was slightly higher (65.43, 95% credible interval: 47.19-84.70). In terms of pooled samples, overall, the RNA-AP was 6.80% (95% confidence interval: 4.01-10.66). One strain in Hanoi, two strains in Dak Lak, seven strains in An Giang, four strains in Son La and two strains in Nghe An were isolated. The phylogenetic tree demonstrated that 19 Vietnamese strains were clustered into HEV 3 and 4., Conclusions: This study provided evidence that HEV is circulating in domestic pigs in Vietnam. From a public health perspective, it is very important to raise public awareness for high-risk groups (e.g. slaughterhouse workers, pig traders, farmers and market sellers) who have more opportunities to come in contact with pig and contaminated meats.

Most chronic diseases, caused by lifestyle factors, appear to be linked to inflammation. Inflammation is activated mechanistically, and nuclear factor-κB (NF-κB) is a significant mediator. NF-κB, one of the most studied transcription factors, was first identified in the nucleus of B lymphocytes almost three decades ago. This protein has a key function in regulating the human immune system, and its dysregulation has been linked to many chronic diseases including asthma, cancer, diabetes, rheumatoid arthritis, inflammation, and neurological disorders. Physiologically, many cytokines have been discovered that activate NF-κB. Pathologically, environmental carcinogens such as cigarette smoke, radiation, bacteria, and viruses can also activate this transcription factor. NF-κB activation controls expression of more than 500 genes, and most are deleterious to the human body when dysregulated. More than 70,000 articles have been published regarding NF-κB. This review emphasizes the upside and downside of NF-κB in normal and disease conditions and the ways in which we can control this critical transcription factor in patients.

The main objective of this study was to develop various models using North American Animal Disease Spread Model (NAADSM) to simulate the transmission of Porcine reproductive and respiratory syndrome (PRRS) virus between farms in Nghe An Province in Vietnam in order to inform the prevention and control of this important disease. Using real data from the household survey, credible parameters for direct/indirect mean contact rates between different farms were estimated. A total of eleven models were developed, including immunization scenarios. In addition, we conducted sensitive analysis on how the mean contact rates influenced the results. The immunization scenarios showed that a high proportion of pigs in medium size farms needs to be vaccinated in order to reduce the transmission to pigs in small farms under the Vietnamese pig production system. In order to promote the use of vaccinations, incentives (such as a vaccine subsidy) for medium size farms may be needed. It could be the most cost-effective control and prevention strategy for pig diseases in Vietnam. Our study provides insights on how pig diseases can be spread between pig farms via direct and indirect contact in Nghe An under the various hypothetical scenarios. Our results suggest that medium/large farms may play an important role in the transmission of pig diseases., (© 2019 The Authors Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.)

Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri . It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson's disease, Alzheimer's, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases.

Background: Leptospirosis is an important zoonotic disease with a global distribution, affecting a wide range of mammalian animals and humans. Japanese encephalitis (JE) virus is the major vector-borne zoonotic disease in the Asia-Pacific region. The main objective of this study was to evaluate the seroprevalence of serovar-specific Leptospira and JE in swine from 10 provinces in Vietnam., Methods: Samples were initially collected for swine influenza surveillance from March to April 2017 at large-scale farms (with at least 50 sows and/or 250 fattening pigs) with pigs that tested positive for influenza in the previous surveillance period (2015-16)., Findings: A total of 2,000 sera samples were analyzed from 10 provinces. Overall, the seroprevalence of leptospirosis was 21.05% (95% CI: 19.28-22.90) using a cut-off titer of ≥ 1:100. The apparent prevalence of JE was 73.45% (95% CI: 71.46-75.37) while the true prevalence was slightly higher (74.46%, 95% credible interval: 73.73-86.41). We found a relatively high presence of leptospirosis and JE in pigs kept on large farms. Prevalence was comparable with other studies suggesting opportunistic testing of samples collected for other surveillance purposes can be a valuable tool to better understand and prevent the potential transmission of these zoonotic diseases from pigs to people in Vietnam., Conclusion: Our study provides evidence to veterinarians and animal health professionals for evidence-based practice such as diagnosis, vaccination and zoonotic control. Further investigation into the possible role of different domestic animals, wildlife species or environmental factors is needed to identify the potential risk factors and transmission routes in Vietnam., Competing Interests: The authors have declared that no competing interests exist.

Impact Statement: The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

In response to concerns that novel infectious agents were introduced through the movement of eggs as Atlantic salmon aquaculture developed in British Columbia (BC), Canada, we estimated the prevalence of infectious agents in archived return-migrating Sockeye salmon, from before and during aquaculture expansion in BC (1985-94). Of 45 infectious agents assessed through molecular assays in 652 samples, 23 (7 bacterial, 2 viral and 14 parasitic) were detected in liver tissue from six regions in BC. Prevalence ranged from 0.005 to 0.83 and varied significantly by region and year. Agent diversity ranged from 0 to 12 per fish (median 4), with the lowest diversity observed in fish from the Trans-Boundary and Central Coast regions. Agents known to be endemic in Sockeye salmon in BC, including Flavobacterium psychrophilum, Infectious haematopoietic necrosis virus, Ceratonova shasta and Parvicapsula minibicornis, were commonly observed. Others, such as Kudoa thyrsites and Piscirikettsia salmonis, were also detected. Surprisingly, infectious agents described only recently in BC salmon, Ca. Branchiomonas cysticola, Parvicapsula pseudobranchicola and Paranucleospora theridion, were also detected, indicating their potential presence prior to the expansion of the aquaculture industry. In general, our data suggest that agent distributions may not have substantially changed because of the salmon aquaculture industry., (© 2019 The Authors. Journal of Fish Diseases Published by John Wiley & Sons Ltd.)

Tumor necrosis factor (TNF)-α, the most potent proinflammatory cytokine discovered to date, was first isolated in 1984 from human macrophage cells. Initially, it was thought to be a protein that was cytotoxic to tumor cells. But later, it was regarded as an agent that promotes inflammation and other chronic diseases found in humans. Currently, we know that the TNF superfamily (TNFS) has 19 members that perform a wide variety of functions via > 40 TNF receptors. Of TNFS members, TNF-α has been studied extensively and was found to be implicated in numerous autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, juvenile idiopathic arthritis, and diabetes. Thus, agents that can inhibit TNF-α have great potential for prevention and treatment of chronic diseases. To date, the U.S. Food and Drug Administration has approved many TNF-α blockers, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab. These agents can block TNF-α actions and be used to treat different diseases. However, the uses of TNF-α blockers are not without serious adverse effects. Therefore, natural TNF-α blockers are best for developing safe, efficacious, and affordable agents for prevention and treatment of chronic diseases. The current review details the TNFS, functions of TNF-α in normal and disease conditions, roles of TNF-α blockers, and advantages and disadvantages.

The intake of fruits has proven to reduce the risk and incidence of cancer worldwide and plays a crucial role in cancer prevention. Pomegranate (Punica granatum), which belongs to the Punicaceae family, is one such plant that contains beneficial nutrients as well as many bioactive components and important phytochemicals that can be attributed to cancer-related therapeutic purposes. Pomegranate possesses antioxidant, anti-inflammatory, anti-proliferative, anti-angiogenic, anti-invasive, and anti-metastatic properties, and induces apoptosis. It also down-regulates various signaling pathways such as NF-κB, PI3K/AKT/mTOR, and Wnt, and down-regulates the expression of genes that are responsible in cancer development, such as anti-apoptotic genes, MMPs, VEGF, c-met, cyclins, Cdks, and pro-inflammatory cytokines. Therefore, inclusion of the fruit in one's diet would assist in a healthy life protected from cancer and also act as an effective chemotherapeutic with no toxic side effects., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Breast cancer is the most prevalent cancer among women worldwide. Among the different breast cancer subtypes, triple-negative breast cancer (TNBC), which is more prevalent among younger age women, is the most aggressive form. Numerous clinicopathologic studies performed throughout the world strongly support the utterly poor prognoses and high recurrence rate of TNBC. The present report details a thorough data survey from Google and PubMed on the burden of TNBC worldwide and other associated factors, with special emphasis on its ever increasing incidence among Indian women. Our analysis revealed that the proportion of TNBC ranges from 6.7% to 27.9% in different countries, with the highest reported percentage in India among all, followed by Indonesia, Algeria, and Pakistan. Most of the other countries (Netherlands, Italy, London, Germany) had a TNBC incidence less than the mean level (ie, 15%). The high incidence of TNBC in the Indian population is associated with vivid risk factors, which primarily include lifestyle, deprivation status, obesity, family history, high mitotic indexes, and BRCA1 mutations. The treatment of TNBC is greatly hampered due to the lack of targeted therapies. Hence, it requires earnest attention towards extensive research for the prevention and development of treatment modalities with high efficacy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Design and reporting quality of diagnostic accuracy studies (DAS) are important metrics for assessing utility of tests used in animal and human health. Following standards for designing DAS will assist in appropriate test selection for specific testing purposes and minimize the risk of reporting biased sensitivity and specificity estimates. To examine the benefits of recommending standards, design information from published DAS literature was assessed for 10 finfish, seven mollusc, nine crustacean and two amphibian diseases listed in the 2017 OIE Manual of Diagnostic Tests for Aquatic Animals. Of the 56 DAS identified, 41 were based on field testing, eight on experimental challenge studies and seven on both. Also, we adapted human and terrestrial-animal standards and guidelines for DAS structure for use in aquatic animal diagnostic research. Through this process, we identified and addressed important metrics for consideration at the design phase: study purpose, targeted disease state, selection of appropriate samples and specimens, laboratory analytical methods, statistical methods and data interpretation. These recommended design standards for DAS are presented as a checklist including risk-of-failure points and actions to mitigate bias at each critical step. Adherence to standards when designing DAS will also facilitate future systematic review and meta-analyses of DAS research literature., (© 2018 John Wiley & Sons Ltd.)

Transfusion of blood and blood products is a double edged sword, so it should be used judiciously. The primary aim of the centralized Haemovigilance Program is to improve transfusion safety. To determine the incidence of adverse transfusion reactions (ATRs) in recipients of blood and blood components. Prospective study from January 2014 till April 2015 was done. ATRs reported to the Department of Transfusion Medicine were recorded and analyzed on the basis of their clinical features and lab tests. During the study period 25,099 units of blood and blood components were transfused and 100 ATRs (0.40 %) were reported. The incidence of febrile nonhemolytic transfusion reactions (FNHTR) was maximum (73 %) followed by allergic reactions (24 %), bacterial sepsis (1 %), hypotension due to ACE inhibitors (1 %) and acute hemolytic transfusion reaction (AHTR) (1 %). Of all the reported ATRs, 76 % occurred with packed red cells, 15 % occurred with whole blood, while platelets and Fresh Frozen Plasma transfusions were responsible for 8 % and 1 %, respectively. The majority of the reactions were FNHTRs followed by allergic reactions. Reporting of all adverse events and continuous medical education to medical and paramedical staff will help in strengthening hemovigilance system.

Neuropathic pain is a state of chronic pain arising after peripheral or central nerve injury. These injuries can be mediated through the activation of various cells (astrocytes, microglia and Schwann cells), as well as the dissolution of distal axons. Recent studies have suggested that after nerve injury, Toll-like receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes and microglia that can cause induction of the proinflammatory mediators and cytokines in the spinal cord, thereby leading to the generation and maintenance of neuropathic pain. Indeed considering the prevalence of neuropathic pain and suffering of the affected patients, insights into the diverse mechanism(s) of activation of TLR signaling cascades may open novel avenues for the management of this chronic condition. Moreover, existing therapies like antidepressants, anticonvulsants, opiates and other analgesic are not sufficiently effective in reducing the pain. In this review, we present substantial evidences highlighting the diverse roles of TLRs and their signaling pathways involved in the progression of neuropathic pain. Furthermore, an elaborate discussion on various existing treatment regimens and future targets involving TLRs has also been included., (Copyright © 2016 Elsevier Ltd. All rights reserved.)