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Aeromonas hydrophila is a Gram-negative bacterium that has been linked to serious illnesses in both humans and animals. The presence of hemolysin, a virulence factor, is critical in the development of A. hydrophila-related illnesses. As a result, precise and timely detection of the hemolysin gene is critical for efficient diagnosis and prevention of many illnesses. The PCR is used in this study to detect the hemolysin gene of A. hydrophila in a novel, fast, and highly sensitive one-step technique. Specific primers were constructed to amplify a conserved area within the hemolysin gene to achieve both specificity as well as sensitivity. The PCR assay was rigorously optimized, taking temperature, primer concentration, and reaction time into account, in order to maximize the efficiency and reliability of this method. In conclusion, this method’s simplicity, sensitivity, and specificity make it highly promising for regular diagnostic applications. Its application would allow for the early detection of A. hydrophila infections, allowing for more effective treatment and control methods.

Fiber Bragg Gratings (FBGs) in a sensor network have been widely used for structural health and process monitoring. The number of FBGs with distinct wavelength that can be used in such a sensor network is limited by the bandwidth of the laser used. FBGs, with overlapping spectra cannot be interrogated in a series sensor network since they shadow each other. Methods like time division multiplexing (TDM), code division multiplexing (CDM) have been used to interrogate overlapped FBGs. TDM is limited by the power budget system and CDM is limited by the number of FBGs can be used. We propose a neural network based Spectral Division Multiplexing (SPDM) scheme, to monitor overlapped FBGs in a series fiber sensor network.

In the present study, goldfish (Carassius auratus) were fed diets supplemented with different levels of methanolic crude extracts of Andrographis paniculata to assess their efficacy against Aeromonas hydrophila. The A. paniculata extract showed antibacterial activity against A. hydrophila at different concentrations and was characterised by FTIR and GC-MS analysis. The fishes (C. auratus) were divided into three groups, the control fishes were fed with a basel diet, the DI and DII group fishes were fed with a basel diet mixed with 0.1% and 1% of methanolic crude extracts of A. paniculata, respectively for 4 weeks. Then, haematological and immunological parameters were examined in each experimental and control group after the 2nd and 4th week. Finally, all group fish were challenged with A. hydrophila at the end of the 4th week, and their cytokine genes expression were investigated. The results showed that even at low concentrations (50 μg) of A. paniculata leaf extracts showed a potent antibacterial effect against A. hydrophila. GC-MS analysis revealed that the methanol precipitation contains Benzylamine, 2-hydroxy-N,N-DI-[2-aminoethyl]-, 18-Nonadecen-1-OL, and andrographolide. Similarly, FTIR analysis revealed aliphatic primary amine, conjugated ketone and alcohols, which are known antimicrobials. The extracts also changed the growth, haematological and immunological parameters of treated fishes by significantly increased the total RBC counts and haemoglobin level, along with the phagocytic, total immunoglobulin and myeloperoxidase activities when compared to the BD group. Moreover, fish fed with 1% of A. paniculata extract showed a higher survival rate (80%) against A. hydrophila. Furthermore, 1% of A. paniculata extract dietary was significantly up-regulated pro-anti-inflammatory cytokine gene expression, compared with the BD group. In conclusion, dietary A. paniculata extract supplementation beneficial for C. auratus, as it assesses their efficacy against A. hydrophila.

The study was to find out the effect of cadmium and mercury on levels of hemolymph glucose, crustacean hyperglycemic hormone (CHH) and hepatopancreas glycogen in the blue swimmer crab Portunus pelagicus. The experiments were performed in both intact and eyestalk ablated crabs. Quantification of CHH was done by the indirect ELISA with the aid of primary anti-Carcinus maenas-CHH antibody. Higher glucose concentration was observed on exposure to 8×10-6 of cadmium ((825.6±5.42) μg/mL) and 6×10-6 of mercury ((90.5±6.25) μg/mL) after 48 h and 24 h respectively. Higher level of hemolymph glucose was observed in eyestalk intact crabs on exposure to cadmium and mercury than eyestalk ablated crabs. Decrease in the levels of CHH was observed in both eyestalk intact and ablated crabs on heavy metal exposure. Decline of the hepatopancreas glycogen level was also witnessed with the exposure to heavy metal, which validated its utilization in the production of glucose. Thus this study brings to light, the variations in hemolymph glucose, CHH and hepatopancreas glycogen on heavy metal stress. These carbohydrate metabolites can be used as biomarkers in assessing heavy metal contamination in water bodies. [ABSTRACT FROM AUTHOR]

For the first time, we have a comprehensive database on usage of AYUSH (acronym for Ayurveda, naturopathy and Yoga, Unani, Siddha, and Homeopathy) in India at the household level. This article aims at exploring the spread of the traditional medical systems in India and the perceptions of people on the access and effectiveness of these medical systems using this database. The article uses the unit level data purchased from the National Sample Survey Organization, New Delhi. Household is the basic unit of survey and the data are the collective opinion of the household. This survey shows that less than 30% of Indian households use the traditional medical systems. There is also a regional pattern in the usage of particular type of traditional medicine, reflecting the regional aspects of the development of such medical systems. The strong faith in AYUSH is the main reason for its usage; lack of need for AYUSH and lack of awareness about AYUSH are the main reasons for not using it. With regard to source of medicines in the traditional medical systems, home is the main source in the Indian medical system and private sector is the main source in Homeopathy. This shows that there is need for creating awareness and improving access to traditional medical systems in India. By and large, the users of AYUSH are also convinced about the effectiveness of these traditional medicines. [ABSTRACT FROM AUTHOR]

Aquaculture is a fast-growing food sector but is plagued by a plethora of bacterial pathogens that infect fish. The rearing of fish at high population densities in aquaculture facilities makes them highly susceptible to disease outbreaks, which can cause significant economic loss. Thus, immunity development in fish through vaccination against various pathogens of economically important aquaculture species has been extensively studied and has been largely accepted as a reliable method for preventing infections. Vaccination studies in aquaculture systems are strategically associated with the economically and environmentally sustainable management of aquaculture production worldwide. Historically, most licensed fish vaccines have been developed as inactivated pathogens combined with adjuvants and provided via immersion or injection. In comparison, live vaccines can simulate a whole pathogenic illness and elicit a strong immune response, making them better suited for oral or immersion-based therapy methods to control diseases. Advanced approaches in vaccine development involve targeting specific pathogenic components, including the use of recombinant genes and proteins. Vaccines produced using these techniques, some of which are currently commercially available, appear to elicit and promote higher levels of immunity than conventional fish vaccines. These technological advancements are promising for developing sustainable production processes for commercially important aquatic species. In this review, we explore the multitude of studies on fish bacterial pathogens undertaken in the last decade as well as the recent advances in vaccine development for aquaculture.

Serotonin is one of the important neurotransmitter and neuromodulator so far studied in crustacean models. With its secretory sites well-studied in higher crustaceans, its function in controlling the release of metabolic hormones from their storage and release sites has been well proved. The present study attempts to localize serotonin-like immunoreactivity in Fenneropenaeus indicus, a commercially important shrimp species and a natural inhabitant of the Indian oceans. Histological studies were employed to visualize the different types of neurosecretory cells and their regions of occurrence in brain and optic ganglia on the basis of their size, shape, and tinctorial properties. Immunocytochemical studies were performed in the brain and optic ganglia with specific antisera against serotonin in combination with peroxidase anti-peroxidase to map the serotonin-like immunoreactive cells. Variations in the immunoreactivity were observed on comparing the cells of brain and optic ganglia. Medulla terminalis region had intense serotonin immunoreactivity suggesting it to be the primary source of the neurotransmitter. Microsc. Res. Tech., 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The temperature of habitat water has a drastic influence on the behavioral, physiological and biochemical mechanisms of crustaceans. Hyperglycemia is a typical response of many aquatic animals to harmful physical and chemical environmental changes. In crustaceans increased circulating crustacean hyperglycemic hormone (CHH) and hyperglycemia are reported to occur following exposure to several environmental stress. The biogenic amine, serotonin has been found to modulate the CHH levels and oxidation of serotonin into its metabolites is catalysed by monoamine oxidase. The blue swimmer crab, Portunus pelagicus is a dominant intertidal species utilized throughout the indo-pacific region and is a particularly important species of Palk bay. It has high nutritional value and delicious taste and hence their requirements of capture and cultivation of this species are constantly increasing. This species experiences varying and increasing temperature levels as it resides in an higher intertidal zone of Thondi coast. The present study examines the effect of thermal stress on the levels of serotonin and crustacean hyperglycemic hormone in the hemolymph of P. pelagicus and analyzes the effect of the monoamine oxidase inhibitor, pargyline on serotonin and CHH level after thermal stress. The results showed increased levels of glucose, CHH and serotonin on exposure to 26 °C in control animals. Pargyline injected crabs showed highly significant increase in the levels of CHH and serotonin on every 2 °C increase or decrease in temperature. A greater CHH level of 268.86±2.87 fmol/ml and a greater serotonin level of 177.69±10.10 ng/ml was observed at 24 °C. This could be due to the effect of in maintaining the level of serotonin in the hemolymph and preventing its oxidation, which in turn induces hyperglycemia by releasing CHH into hemolymph. Thus, the study demonstrates the effect of thermal stress on the hemolymph metabolites studied and the role of pargyline in elevating the levels of serotonin and CHH on thermal stress in the blue swimmer crab, P. pelagicus.

Purpose: Feedback seeking is an expected learner competency. Motivations to seek feedback are well explored, but we know little about how supervisors perceive such requests for feedback. These perceptions matter because how supervisors judge requests can affect the feedback they give. This study explores how supervisors perceive and attribute motivations behind feedback requests to better understand the benefits and hazards of feedback seeking., Method: Constructivist grounded theory was used to interview supervisors at the Temerty Faculty of Medicine, University of Toronto, from February 2020 to September 2022. Supervisors were asked to describe instances when they perceived feedback requests as being sincere or insincere, what led to their opinions, and how they responded. Transcripts were analyzed and coded in parallel with data collection; data analysis was guided by constant comparison., Results: Seventeen faculty were interviewed. Participants perceived 4 motivations when learners sought feedback: affirmation or praise; a desire to improve; an administrative requirement, such as getting forms filled out; and hidden purposes, such as making a good impression. These perceptions were based on assumptions regarding the framing of the initial request; timing; preexisting relationship with the learner; learner characteristics, such as insecurity; and learner reactions to feedback, particularly defensiveness. Although being asked for feedback was generally well received, some participants reported irritation at requests that were repetitive, were poorly timed, or did not appear sincere., Conclusions: Feedback seeking may prompt supervisors to consider learners' motivations, potentially resulting in a set of entangled attributions, assumptions, and reactions that shape the feedback conversation in invisible and potentially problematic ways. Learners should consider these implications as they frame their feedback requests and be explicit about what they want and why they want it. Supervisors should monitor their responses, ask questions to clarify requests, and err on the side of assuming feedback-seeking requests are sincere., (Copyright © 2024 the Association of American Medical Colleges.)

Citral (1a), a bioactive component of Cymbopogon citratus (lemongrass) could be isolated and semi-synthetic analogs synthesized with improved therapeutic properties. Herein we first report describes citral (1a) as a primary material for the synthesis of benzimidazole derivatives between various o-phenylenediamines (2a-l) in the presence of Diisopropylethylamine (DIPEA) as a commercially available environmentally benign base, ethanol as a green solvent and the yield of all benzimidazole derivatives (3a-l) was between 68-76 %; The semi-synthetically prepared benzimidazole derivatives (3a-l) were assessed for their anti-bacterial and anti-fungal properties. The benzimidazole compounds (3a-b, and 3g-j) exhibit good anti-microbial activity. In addition, in silico study was carried out to determine the specific binding affinity of the diamine halogen substituted benzimidazole derivatives to the specific target proteins. In silico analysis revealed a high correlation between docking results and experimental results. Finally, benzimidazole demonstrated significant antibacterial and antifungal activity. Zebrafish embryos were subjected to In vivo toxicological test found that all of the benzimidazole compounds (3a-l) were non-toxic and had low embryotoxicity after 96 h, with an LC 50 of 36.425 μg, which could facilitate the design of novel antimicrobial agents using a cost-effective method., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The use of the transdermal delivery system has recently gained ample recognition due to the ability to deliver drug molecules across the skin membrane, serving as an alternative to conventional oral or injectable routes. Subcutaneous insulin injection is the mainstay treatment for diabetes mellitus which often leads to non-compliance among patients, especially in younger patients. Apart from its invasiveness, the long-term consequences of insulin injection cause the development of physical trauma, which includes lipohypertrophy at the site of administration, scarring, infection, and sometimes nerve damage. Hence, there is a quest for a better alternative to drug delivery that is non-invasive and easily adaptable. One of the potential solutions is the transdermal delivery method. However, the stratum corneum (the top layer of skin) is the greatest barrier in transporting large molecules like insulin. Therefore, various chemical enhancers have been proposed to promote stratum corneum permeability, or they are designed to increase the permeability of the full epidermis, such as the use of ionic liquid, peptides, chemical pre-treatment as well as packaging insulin with carriers or nanoparticles. In this review, the recent progress in the development of chemical enhancers for transdermal insulin delivery is discussed along with the possible mechanistic of action and the potential outlook on the proposed permeation approaches in comparison to other therapeutical drugs.

Mosquito control is becoming more difficult as a result of the rise in resistance to toxic chemical insecticides. The insecticides of bio-fabrication sources may serve as a convenient alternative to environmentally acceptable methods in the future. The larvicidal and pupicidal activities of bio-fabricated zinc oxide nanoparticles (ZnO NPs) on the different instar larvae and pupae of Anopheles subpictus Grassi (Malaria vector) and Culex quinquefasciatus Say (lymphatic filariasis) were investigated in this study. The results recorded from XRD, FTIR, SEM-EDX, and TEM analyses confirmed the bio-fabrication of ZnO NPs. Such nanoparticles were nearly spherical and agglomerated with a size of 34.21 nm. GC-MS analysis of methanol extract revealed the compound, stigmasterol (C 29 H 48 O) as major one. Mosquito larvae and pupae of targeted mosquito were tested against varied concentrations of the bio-fabricated ZnO NPs and methanol extract of Vitex negundo for 24 h. The maximum activity was recorded from ZnO NPs against the larvae and pupae of A . subpictus LC 50 which were 1.70 (I), 1.66 (II), 1.93 (III), 2.48 (IV), and 3.63 mg/L (pupa) and C . quinquefasciatus LC 50 were 1.95 (I), 2.63 (II), 2.90 (III), 4.32 (IV), and 4.61 mg/L (pupa) respectively. ZnO NPs exhibited strong DPPH radical and FRAP scavengers compared to the aqueous extract of V. negundo . Also, V. negundo leaf methanol extract (VNLME) and ZnO NPs were evaluated for their cytotoxicity on HeLa cells, which exhibited the IC 50 values of 72.35 and 43.70μg/mL, respectively. The methylene blue (MB) dye, which is harmful to both aquatic and terrestrial life, was degraded using the biosynthesized ZnO nanoparticles. At 664 nm, 81.2% of the MB dye had degraded after 120 min of exposure to sunlight. Overall, our results revealed that ZnO NPs are the perfect biological agent and economical for the control of malaria, filariasis vectors, antioxidant, HeLa cells, and MB blue dye degradation under sunlight irradiation., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, 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.)

The year 2021 marks the 100th anniversary of the momentous discovery of insulin. Through years of research and discovery, insulin has evolved from poorly defined crude extracts of animal pancreas to recombinant human insulin and analogues that can be prescribed and administered with high accuracy and efficacy. However, there are still many challenges ahead in clinical settings, particularly with respect to maintaining optimal glycemic control whilst minimizing the treatment-related side effects of hypoglycemia and weight gain. In this review, the chronology of the development of rapid-acting, short-acting, intermediate-acting, and long-acting insulin analogues, as well as mixtures and concentrated formulations that offer the potential to meet this challenge, are summarized. In addition, we also summarize the latest advancements in insulin delivery methods, along with advancement to clinical trials. This review provides insights on the development of insulin treatment for diabetes mellitus that may be useful for clinicians in meeting the needs of their individual patients. However, it is important to note that as of now, none of the new technologies mentioned have superseded the existing method of subcutaneous administration of insulin.

Purpose: Small cell lung cancer (SCLC) is an aggressive disease with an overall 5-year survival rate of less than 10%. Treatment for SCLC with cisplatin/etoposide chemotherapy (C/E) ± radiotherapy has changed modestly over several decades. The ubiquitin-proteasome system is an underexplored therapeutic target for SCLC. We preclinically evaluated TAK-243, a first-in-class small molecule E1 inhibitor against UBA1., Experimental Design: We assessed TAK-243 in 26 SCLC cell-lines as monotherapy and combined with C/E, the PARP-inhibitor, olaparib, and with radiation using cell viability assays. We interrogated TAK-243 response with gene expression to identify candidate biomarkers. We evaluated TAK-243 alone and in combination with olaparib or radiotherapy with SCLC patient-derived xenografts (PDX)., Results: Most SCLC cell lines were sensitive to TAK-243 monotherapy (EC50 median 15.8 nmol/L; range 10.2 nmol/L-367.3 nmol/L). TAK-243 sensitivity was associated with gene-sets involving the cell cycle, DNA and chromatin organization, and DNA damage repair, while resistance associated with cellular respiration, translation, and neurodevelopment. These associations were also observed in SCLC PDXs. TAK-243 synergized with C/E and olaparib in vitro across sensitive and resistant SCLC cell lines. Considerable TAK-243-olaparib synergy was observed in an SCLC PDX resistant to both drugs individually. TAK-243 radiosensitization was also observed in an SCLC PDX., Conclusions: TAK-243 displays efficacy in SCLC preclinical models. Enrichment of gene sets is associated with TAK-243 sensitivity and resistance. TAK-243 exhibits synergy when combined with genotoxic therapies in cell lines and PDXs. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes, both as a single agent and in combination with existing therapies., (©2022 The Authors; Published by the American Association for Cancer Research.)

Five novel permanent cell lines have been established from gill, heart, kidney, eye and fin of snubnose pompano, Trachinotus blochii. They were designated as snubnose pompano gill (SPG), snubnose pompano heart (SPH), snubnose pompano kidney (SPK), snubnose pompano eye (SPE) and snubnose pompano fin (SPF), respectively. All these cell lines were characterized and cryopreserved successfully at different passage levels. Cell lines were passaged every alternate day; SPG, SPH, SPK, SPE and SPF cell lines attained passage levels of 68, 74, 82, 79 and 106, respectively, since the initiation of their development in 2019. The cell lines grew well in Leibovitz's 15 medium containing 15% foetal bovine serum at 28°C. Immunophenotyping of the cell lines revealed the presence of fibronectin and pancytokeratin. No mycoplasma contamination was found. The transfection study revealed the gene expression efficiency of these cell lines by expressing the green fluorescent protein (GFP). The authentication on origin of cell lines from T. blochii was confirmed by amplification of species-specific mitochondrial cytochrome oxidase I gene. The results showed the susceptibility of these cell lines to fish nodavirus (FNV) and tilapia lake virus (TiLV) and resistance to cyprinid herpesvirus 2 (CyHV-2). The FNV infection in the cell lines was confirmed by RT-PCR, Western blot, ELISA and immunocytochemistry, while TiLV infection was confirmed by RT-PCR assay. These results revealed that these cell lines are suitable for virological and foreign gene expression studies., (© 2021 John Wiley & Sons Ltd.)

Insight into cancer signaling pathways is vital in the development of new cancer treatments to improve treatment efficacy. A relatively new but essential developmental signaling pathway, namely Hedgehog (Hh), has recently emerged as a major mediator of cancer progression and chemoresistance. The evolutionary conserved Hh signaling pathway requires an in-depth understanding of the paradigm of Hh signaling transduction, which is fundamental to provide the necessary means for the design of novel tools for treating cancer related to aberrant Hh signaling. This review will focus substantially on the canonical Hh signaling and the treatment strategies employed in different studies, with special emphasis on the molecular mechanisms and combination treatment in regard to Hh inhibitors and chemotherapeutics. We discuss our views based on Hh signaling's role in regulating DNA repair machinery, autophagy, tumor microenvironment, drug inactivation, transporters, epithelial-to-mesenchymal transition, and cancer stem cells to promote chemoresistance. The understanding of this Achilles' Heel in cancer may improve the therapeutic outcome for cancer therapy.

The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. Hence, this review describes the various SMO-dependent and SMO-independent routes of GLI regulation in the tumorigenesis of multiple cancers in order to provide a holistic view of the paradigms of hedgehog signaling networks involving GLI regulation. An in-depth understanding of the complex interplay between GLI and various signaling elements could help inspire new therapeutic breakthroughs for the treatment of Hh-GLI-dependent cancers in the future. Lastly, we have presented an up-to-date summary of the latest findings concerning the use of Hh inhibitors in clinical developmental studies and discussed the challenges, perspectives, and possible directions regarding the use of SMO/GLI inhibitors in clinical settings.

Background & Purpose: Prophylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution's 20-year experience with this patient population and associated clinical outcomes., Materials & Methods: A retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution (1997-2018) was reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method, and significant covariates determined by the Cox proportional hazards model. Covariates predictive of PCI were determined using Fisher's exact test and the Mann-Whitney test. Brain failure risk (BFR) was calculated using the cumulative incidence method treating death as a competing event. Treatment cohorts (historic vs. contemporary) were stratified by the median year of diagnosis (2005)., Results: A total of 369 patients with LS-SCLC were identified, of which 278 patients were notionally PCI eligible. PCI was given to 196 patients (71%). Younger age was associated with PCI utilization (p < 0.001). PCI utilization rates did not change between the historic and contemporary treatment era (p = 0.11), whereas magnetic resonance imaging (MRI) use at baseline and follow-up became more prevalent in the contemporary era (p = <0.001). On multivariable analysis, PCI utilization was associated with improved OS (HR 1.88, 95% CI 1.32-2.69) and decreased BFR (HR 4.66, 95% CI 2.58-8.40). Patients who had MRI follow-up had a higher incidence of BFR (HR 0.35, 95% CI 0.18-0.66) in multivariable analyses., Conclusions: For LS-SCLC patients at our institution, PCI is more frequently utilized in younger patients, and the utilization rate did not change significantly over the past 20 years. PCI was independently associated with improved OS and lower BFR. Omission of PCI in LS-SCLC patients should not be routinely practiced in the absence of further prospective data., 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., (© 2021 The Author(s).)

Background:  In this pilot study, we perform a preliminary comparison of two targeted multiplex proteomics technologies for discerning serum protein concentration changes that may correlate to tumor burden in ovarian cancer (OC) patients. Methods : Using the proximity extension assay (PEA) and Quantibody® Kiloplex Array (QKA), we measured >1,000 proteins in the pre-surgical and post-surgical serum from nine OC patients (N=18 samples). We expect that proteins that have decreased significantly in the post-surgical serum concentration may correlate to tumor burden in each patient. Duplicate sera from two healthy individuals were used as controls (N=4 samples). We employed in-house ELISAs to measure five proteins with large serum concentration changes in pre- and post-surgical sera, from four of the original nine patients and the two original controls. Results:  Both platforms showed a weak correlation with clinical cancer antigen 125 (CA125) data. The two multiplexed platforms showed a significant correlation with each other for >400 overlapping proteins. PEA uncovered 15 proteins, while QKA revealed 11 proteins, with more than a two-fold post-surgical decrease in at least six of the nine patients. Validation using single enzyme-linked immunosorbent assays (ELISAs) showed at least a two-fold post-surgical decrease in serum concentration of the same patients, as indicated by the two multiplex assays. Conclusion:  Both methods identified proteins that had significantly decreased in post-surgical serum concentration, as well as recognizing proteins that had been implicated in OC patients. Our findings from a limited sample size suggest that novel targeted proteomics platforms are promising tools for identifying candidate serological tumor-related proteins.  However further studies are essential for the improvement of accuracy and avoidance of false results., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Ren A et al.)

Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.

Chebulinic acid (CA) is an ellagitannins isolated from the dried fruits of Terminalia chebula with diverse pharmacological activities. The present study focused on the acute toxicity of CA in normal Sprague Dawley (SD) rats. CA was administered via oral gavage to different groups in 300 and 2000 mg/kg body weight and vehicle respectively. All the animals were monitored carefully for any physiological or behavioral changes for 14 days. On day 15th animals were euthanized and blood was collected for hematological and biochemical analysis. Different tissues were collected for histopathological study using four different staining techniques (hematoxylin and eosin, Masson's trichrome, periodic acid Schiff and picro sirius red) to observe any pathological alterations. The results highlighted no morbidity and mortality after oral ingestion of CA (300 and 2000 mg/kg). Food and water consumption, body weight, relative organ weight, hematological and biochemical parameters were normal without any gross pathological lesions in harvested tissues. The outcome of the current study supported safety of CA even at high dose. However, further detailed study is required on experimentally disease model to unfold its therapeutic potential in laboratory animals., Competing Interests: Conflict of interestThe authors have no conflict of interest to disclose., (© Crown 2021.)

Mass spectrometry-based assays have been increasingly implemented in various disciplines in clinical diagnostic laboratories for their combined advantages in multiplexing capacity and high analytical specificity and sensitivity. It is now routinely used in areas including reference methods development, therapeutic drug monitoring, toxicology, endocrinology, paediatrics, immunology and microbiology to identify and quantify biomolecules in a variety of biological specimens. As new ionisation methods, instrumentation and techniques are continuously being improved and developed, novel mass spectrometry-based clinical applications will emerge for areas such as proteomics, metabolomics, haematology and anatomical pathology. This review will summarise the general principles of mass spectrometry and specifically highlight current and future clinical applications in anatomical pathology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: White spot disease (WSD), a major threat to sustainable aquaculture worldwide, is caused by White spot syndrome virus (WSSV). The diagnosis of WSD relies heavily on molecular detection of the virus by one-step PCR. These procedures are neither field-usable nor rapid enough considering the speed at which the virus spreads. Thus, development of a rapid, reliable and field-usable diagnostic method for the detection of WSSV infection is imperative to prevent huge economic losses., Methods/principal Findings: Here, we report on the development of a lateral flow immunoassay (LFIA) employing gold nanoparticles conjugated to a polyclonal antibody against VP28 (envelope protein of WSSV). The LFIA detected WSSV in ~20 min and showed no cross-reactivity with other shrimp viruses, viz. Monodon Baculovirus (MBV), Hepatopancreatic parvovirus (HPV) and Infectious Hypodermal and Hematopoietic Necrosis virus (IHHNV). The limit of detection (LOD) of the assay, as determined by real-time PCR, was 103 copies of WSSV. In a time course infectivity experiment, ~104 WSSV particles were injected in Litopenaeus vannamei. The LFIA could rapidly (~ 20 min) detect the virus in different tissues after 3 h (hemolymph), 6 h (gill tissue) and 12 h (head soft tissue, eye stalk, and pleopod) of infection. Based on these findings, a validation study was performed using 75 field samples collected from different geographical locations in India. The LFIA results obtained were compared with the conventional "gold standard test", viz. one-step PCR. The analysis of results in 2x2 matrix indicated very high sensitivity (100%) and specificity (96.77%) of LFIA. Similarly, Cohen's kappa coefficient of 0.983 suggested "very good agreement" between the developed LFIA and the conventional one-step PCR., Conclusion: The LFIA developed for the rapid detection of WSSV has an excellent potential for use in the field and could prove to be a boon to the aquaculture industry., Competing Interests: The authors have declared that no competing interests exist.