ABSTRACT
AIM: In-depth 'One Health' risk assessment of extraintestinal pathogenic Escherichia coli (ExPEC) strains carrying the traits of urinary tract infection, sepsis, meningitis and avian colibacillosis in poultry of India. METHODS AND RESULTS: A total of 230 E. coli isolates were recovered from chicken samples representing the different sources (faeces vs caeca), stages (poultry farms vs retails butcher shop) or environments (rural vs urban) of poultry in India. Among all poultry-origin E. coli isolates, 49 (21·1%) strains were identified as ExPEC possessing multiple virulence determinants regardless of their association with any specific phylogenetic lineages. Of particular, potentially virulent ExPEC pathotypes, that is, uropathogenic E.coli (UPEC, 20·4%), avian pathogenic E. coli (APEC, 34·6%), septicaemia-associated E. coli (SEPEC, 47·0%) and neonatal meningitis-causing E.39 coli (NMEC, 2·0%) were also detected among all ExPEC strains. CONCLUSIONS: Our study is the first to assess ExPEC strains circulating in the different settings of poultry in India and significantly demonstrates their potential ability to cause multiple extraintestinal infections both in humans and animals. SIGNIFICANCE AND IMPACT OF THE STUDY: The data of our study are in favour of the possibility that poultry-origin putative virulent ExPEC pathotypes consequently constitute a threat risk to 'One Health' or for food safety and a great concern for poultry production of India.
Subject(s)
Bird Diseases/microbiology , Escherichia coli Infections/microbiology , Escherichia coli Infections/veterinary , Extraintestinal Pathogenic Escherichia coli/classification , Extraintestinal Pathogenic Escherichia coli/pathogenicity , Animals , Biofilms/growth & development , Cecum/microbiology , DNA, Bacterial , Escherichia coli Proteins/genetics , Extraintestinal Pathogenic Escherichia coli/isolation & purification , Feces/microbiology , Genetic Association Studies , Genotyping Techniques , Humans , India , Meningitis/microbiology , Phylogeny , Polymerase Chain Reaction , Sepsis/microbiology , Urinary Tract Infections/microbiology , Virulence Factors/geneticsABSTRACT
BACKGROUND: Vitrification is an ultra-rapid freezing technique for germplasm preservation under high salt concentration with very short exposure time. OBJECTIVE: To assess the post-thawed developmental potential of in vitro-produced buffalo embryos vitrified by solid surface technique using different concentrations of cryoprotectants. MATERIALS AND METHODS: The slaughterhouse derived oocytes were in vitro matured and fertilized with epididymal sperm. IVF embryos at the morula stage were vitrified under two protocols; (i) Protocol-1: ethylene glycol (35%) (ii) Protocol-2: ethylene glycol (15%) and dimethyl sulfoxide (15%). The vitrified-thawed embryos were in vitro cultured up to the blastocyst stage. RESULTS: Post-thawed development of embryos vitrified under Protocol-1 was significantly higher in terms of compact morula formation as compared to Protocol-2. However, blastocyst developmental rates were not significantly different between the two protocols. The developmental rates of the non-vitrified control were significantly higher than embryos vitrified by either protocols. CONCLUSION: The process of cryopreservation, under both protocols, significantly affected the developmental potential of pre-implant embryos as compared to fresh embryos. Hence the nature and concentrations of cryoprotectants needs to be optimized for efficient, viable embryonic development.
Subject(s)
Buffaloes , Cryopreservation/veterinary , Embryo, Mammalian/physiology , Animals , Blastocyst , Cryoprotective Agents/pharmacology , Female , Fertilization in Vitro , Oocytes , Pregnancy , VitrificationABSTRACT
Objective: The purpose of present research was to develop and statistically optimize nitrendipine nanoemulsion gel for transdermal delivery using box-behnken statistical design.Method: The nanoemulsion formulations bearing nitrendipine were prepared by application of ternary phase diagram and spontaneous emulsification method. Box-behnken design was employed for the optimization of nitrendipine loaded nanoemulsion. The independent variables were oil, surfactant and co-surfactant while globule size, drug content and zeta potential were dependent variables. The optimized nanoemulsion formulation was incorporated into gel and evaluated for in-vitro release, ex-vivo permeation studies, confocal laser scanning microscopy, skin irritation and histopathological studies.Results: The optimized formulation through box-behnken statistical design showed globule size of 20.43 ± 1.50 nm, drug content of 97.05 ± 1.77% and zeta potential of -15.45 ± 0.35 mV. The ex-vivo study confirmed the enhanced delivery of nitrendipine from nanoemulsion gel than compare to drug solution by virtue of better permeation and solubility. Nanoemulsion gel was proved significantly superior by confocal laser scanning microscopy for satisfactory permeation and distribution of gel, deep into the rat skin. The optimized gel was found with no allergic dermal effects and was proved safe by histopathological studies for transdermal application.Conclusions: Results reveals that developed nitrendipine nanoemulsion gel overcomes the limitation of low penetration and accentuate permeation through albino Wistar rat skin. It was concluded that nanoemulsion gel could be utilized as a potential carrier for transdermal delivery of nitrendipine.
Subject(s)
Emulsions/chemistry , Gels/chemistry , Nanoparticles/chemistry , Nitrendipine/administration & dosage , Nitrendipine/chemistry , Administration, Cutaneous , Animals , Chemistry, Pharmaceutical/methods , Drug Carriers/chemistry , Drug Compounding/methods , Drug Delivery Systems/methods , Male , Particle Size , Permeability/drug effects , Rats , Rats, Wistar , Skin/metabolism , Skin Absorption/drug effects , Solubility/drug effects , Surface-Active Agents/chemistryABSTRACT
AIMS: The present study was designed to assess the phenotypic traits and virulence determinants of vegetable-/fruit-origin Escherichia coli and Salmonella strains. METHODS AND RESULTS: A total of 520 fresh vegetables/fruits samples were analysed for the presence of E. coli, including Shiga toxin-producing E. coli (STEC), and Salmonella. The vegetable-/fruit-origin E. coli and Salmonella strains were further assessed for antimicrobial resistance, biofilm formation, extracellular matrix production and in vitro invasion/intracellular survivability assays. A total of 73 E. coli, including four STEC, and 26 Salmonella strains were recovered from vegetables/fruits in the present study. Most of the E. coli and Salmonella isolates were able to form biofilm with higher production of cellulose/curli-fimbriae. Furthermore, more resistance was observed in E. coli isolates (61·6%) than in Salmonella isolates (38·5%) against tested antimicrobials. Additionally, invasion/intracellular survival results showed that majority of the E. coli and Salmonella isolates were able to efficiently invade/replicate intracellularly in the human epithelial cells. CONCLUSIONS: Our results demonstrate that vegetable-/fruit-origin E. coli and Salmonella significantly exhibited distinct phenotypic/virulence traits which could be linked to their plant-associated lifestyle with food safety issues. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study provides valuable baseline information that E. coli and Salmonella may use plants as an alternative host with significant clinical importance.
Subject(s)
Escherichia coli , Fruit/microbiology , Salmonella , Vegetables/microbiology , Escherichia coli/pathogenicity , Escherichia coli/physiology , India , Phenotype , Salmonella/pathogenicity , Salmonella/physiology , VirulenceABSTRACT
Current status of resistance to benzimidazole (BZ) group of anthelmintic drugs against caprine nematodes in Central India at Amanala goat farm, Jabalpur, Madhya Pradesh (M. P.), was systematically investigated using faecal egg count reduction (FECR) test and egg hatch test (EHT). Besides, allele-specific PCR (AS-PCR) was deployed to ascertain the susceptible genotype (alleles) especially of the Haemonchus contortus. Randomly selected 30 goats, irrespective of age and sex, were divided into three groups of 10 each, to serve as treated and untreated controls. It was ensured that the animals were not administered with an anthelmintic drug for the past 3 months prior to undertaking the study, and faecal egg counts were estimated. FECR test evidenced fenbendazole resistance by partial elimination (24.90%) copro-egg counts in the treated group of animals vis-à-vis controls with a lower confidence interval of -26%. Further, EHT revealed ED-50 value of 0.335 µg of thiabendazole/ml, confirming benzimidazole resistance in the animals of that farm. AS-PCR showed that 62% of H. contortus larvae were homozygous resistant (rr), 24% heterozygous (rS) and 14% homozygous susceptible (SS). The genotypic frequencies of three genotypes (rr, rS and SS) were significantly (P < 0.01) different. The prevalence of benzimidazole resistance allele (r) was also significantly (P < 0.01) higher (74%) as compared to susceptible allele (S) (26%). The resistance to benzimidazole has been discussed while emphasizing improved managemental practices designed to reduce exposure of the goat population to parasites, minimize frequency of anthelmintic use at optimum dose and rotational use of different chemical groups of medicines with different mode of action, so as to overcome and combat the upcoming problem in the field.
Subject(s)
Antinematodal Agents/pharmacology , Benzimidazoles/pharmacology , Drug Resistance , Goat Diseases/prevention & control , Haemonchus/drug effects , Helminthiasis, Animal/prevention & control , Animals , Female , Goat Diseases/parasitology , Goats , Helminthiasis, Animal/parasitology , India , Male , Nematoda/drug effects , Parasite Egg Count/veterinary , Polymerase Chain Reaction/veterinaryABSTRACT
BACKGROUND: FKBP51 is overexpressed in melanoma and impacts tumour cell properties. However, its comprehensive role in melanoma pathogenesis and underlying mechanism(s) remain elusive. METHODS: FKBP51 was stably silenced in aggressive melanoma cell lines and its effect examined in vitro and in mouse model. Histological/immunohistochemical analyses were performed to confirm metastasis, angiogenesis and neutrophil infiltration. Gene expression was analyzed by qRT-PCR, immunoblot and/or ELISA. NF-κB transcriptional activity and promoter binding were monitored by luciferase-based promoter-reporter and ChIP assays, respectively. Interleukin (IL)-8 inhibition was achieved by gene silencing or neutralising-antibody treatment. RESULTS: FKBP51 silencing reduced melanoma growth, metastasis, angiogenesis and neutrophil infiltration and led to IL-8 downregulation through NF-κB suppression in cell lines and tumour xenografts. IL-8 inhibition drastically decreased growth, migration and invasiveness of FKPB51-overexpressing cells; whereas its treatment partially restored the suppressed phenotypes of FKBP51-silenced melanoma cells. Interleukin-8 depletion in conditioned medium (CM) of FKBP51-overexpressing melanoma cells inhibited endothelial cell proliferation and capillary-like structure formation, whereas its treatment promoted these effects in endothelial cells cultured in CM of FKBP51-silenced melanoma cells. CONCLUSIONS: FKBP51 promotes melanoma growth, metastasis and angiogenesis, and IL-8 plays a key role in these processes. Thus, targeting of FKBP51 or its upstream or downstream regulatory pathways could lead to effective therapeutic strategies against melanoma.
Subject(s)
Interleukin-8/genetics , Melanoma/genetics , Neovascularization, Pathologic/genetics , Tacrolimus Binding Proteins/biosynthesis , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , Interleukin-8/metabolism , Melanoma/pathology , Mice , NF-kappa B/genetics , Neoplasm Metastasis , Neovascularization, Pathologic/pathology , Promoter Regions, Genetic , Tacrolimus Binding Proteins/geneticsABSTRACT
Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.
Subject(s)
Aspergillus flavus , Brain/pathology , Cytokines/metabolism , Granuloma/immunology , Granuloma/pathology , Neuroaspergillosis/immunology , Neuroaspergillosis/pathology , Animals , Aspergillus flavus/isolation & purification , Brain/immunology , Cytokines/immunology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-12/immunology , Interleukin-12/metabolism , Interleukin-12 Subunit p40/immunology , Interleukin-12 Subunit p40/metabolism , Interleukin-17/immunology , Interleukin-17/metabolism , Interleukin-23/immunology , Interleukin-4/immunology , Interleukin-4/metabolism , Interleukin-6/immunology , Interleukin-6/metabolism , Kinetics , Mice , Mice, Inbred BALB C/metabolism , Neurons/pathology , Tumor Necrosis Factor-alpha/immunologyABSTRACT
Strong magnetoresistance effects are often observed in ferromagnet-nonmagnet multilayers, which are exploited in state-of-the-art magnetic field sensing and data storage technologies. In this work we report a novel current-perpendicular-to-plane magnetoresistance effect in multilayer graphene as grown on a catalytic nickel surface by chemical vapor deposition. A negative magnetoresistance effect of â¼10(4)% has been observed, which persists even at room temperature. This effect is correlated with the shape of the 2D peak as well as with the occurrence of D peak in the Raman spectrum of the as-grown multilayer graphene. The observed magnetoresistance is extremely high as compared to other known materials systems for similar temperature and field range and can be qualitatively explained within the framework of "interlayer magnetoresistance" (ILMR).
ABSTRACT
BACKGROUND: Emergence of castration-resistance in prostate cancer (PCa) is invariably associated with aggressive and metastatic disease. Previously, we reported promotion of castration-resistance upon downregulation of PPP2CA (encoding catalytic subunit of protein phosphatase 2A (PP2A), α-isoform); however, its role in PCa growth and metastasis remained undetermined. METHODS: PPP2CA was overexpressed/silenced in PCa cells by stable transfection. Gene expression was examined by reverse transcription polymerase chain reaction, immunoblot and immunofluorescence analyses, and transcriptional activity measured by luciferase-based promoter-reporter assay. Effect on PCa phenotype was studied in vitro and in orthotopic mouse model, and immunohistochemical/histological analyses performed to assess proliferation/apoptosis and confirm metastatic lesions. RESULTS: An inverse association of PPP2CA expression was observed with epithelial-to-mesenchymal transition (EMT) and aggressive PCa phenotype. PPP2CA restoration resulted in decreased nuclear accumulation and transcriptional activity of ß-catenin/NF-κB, and restitution of their activity abrogated PPP2CA-induced EMT reversal and suppression of PCa invasiveness. Akt mediated PPP2CA loss-induced nuclear accumulation of ß-catenin/NF-κB through inactivation of Gsk3-ß and IκB-α, respectively. Animal studies revealed a suppressive effect of PPP2CA expression on PCa growth and metastasis. CONCLUSIONS: Our findings suggest that PPP2CA downregulation serves as a molecular link between gain of castration-resistance and aggressive PCa phenotype, and its restoration could be an effective preventive/therapeutic approach against the advanced disease.
Subject(s)
Epithelial-Mesenchymal Transition/genetics , Molecular Targeted Therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Protein Phosphatase 2/genetics , Animals , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Male , Mice , Neoplasm Metastasis/genetics , Neoplasm Metastasis/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Protein Phosphatase 2/antagonists & inhibitors , Protein Phosphatase 2/biosynthesis , Signal TransductionABSTRACT
The present study evaluated the effects of omega-3 (ω-3) fatty acid-rich linseed supplementation on the reproductive performance, endocrine profile, and biochemical profile of ewes reared in subtropical climates. Forty-eight acyclic and clinically healthy Marwari sheep, aged 1.5-2.5 years with no parity, were divided into four groups (n = n = 12 in each). Ewes in the control group (group I) were fed only a basal feed, whereas ewes in the treatment groups II, III, and IV were fed the basal diet along with 10%, 15%, and 20% linseed, respectively, daily on a dry matter basis. The experiment was conducted during the typical breeding season (October-November) of the sheep. The estrus induction rate was significantly higher (p < 0.05) in all treatment groups than in the control group. The estrus induction interval was significantly lower (p < 0.05) in group III. The conception rate in group I was significantly lower (p < 0.05). In addition, ewes in the control group had a significantly lower (p < 0.05) lambing rate than all treatment groups. Serum progesterone concentrations differed significantly (p < 0.05) between the control and the treatment groups on days 15, 30, 45, and 60 of supplementation. On treatment days 15 and 30, the serum estrogen concentrations were significantly higher (p < 0.05) in all treatment groups compared to that in group I. In all treatment groups, monounsaturated fatty acid (MUFA) decreased significantly (p < 0.05), whereas polyunsaturated fatty acid (PUFA) increased significantly (p < 0.05) from day 15 onward. In conclusion, by providing 15% dietary linseed supplementation to ewes, their reproductive performance can be improved in subtropical climates. Future studies are recommended to further elucidate the role of linseed supplementation in sheep reproduction in subtropical climates.
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We performed temperature dependent x-ray linear dichroism (XLD) experiments on an iron pnictide system, Ba(Fe(1-x)Co(x))2As2 with x=0.00, 0.05, 0.08, and 0.10 to experimentally verify the existence of orbital ordering (OO). Substantial XLD was observed in polarization dependent x-ray absorption spectra of Fe L edges. By exploiting the difference in the temperature dependent behaviors, OO, and structure contributions to XLD could be clearly separated. The observed OO signal indicates different occupation numbers for d(yz) and d(zx) orbitals and supports the existence of ferro-OO. The results are also consistent with the theoretical prediction. Moreover, we find substantial OO signal well above the structural and magnetic transition temperatures, which suggests the existence of strong OO fluctuations up to high temperatures.
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In 2018, the Government of Madhya Pradesh initiated the feasibility testing of integrating an algorithmic approach (assess, give, counsel, treat) to strengthen antenatal nutrition services in routine government-funded programmes coupled with a health system thinking approach to strengthen the health service delivery platform. Implementation phases included (1) an evidence review and stakeholder consultations (April 2018) and (2) a health systems strengthening preparedness phase (May-December 2018), including pilot testing in Vidisha district (January-December 2019) covering â¼54 100 pregnant women with 237 antenatal contact points through 241 government auxiliary nurse midwives/staff nurses. During 2020-21, feasibility testing was expanded to an additional 7 districts. We used programme registers of the Auxiliary Nurse Midwives Registers (2019-21) and National Family Health Survey data for 2016 and 2021 to show changes in the Vidisha district and 7 expansion districts. We compare the performance of Vidisha district with Ashok Nagar district, where no such intervention occurred. Comparing 2016 and 2021 data, the Vidisha district showed improvements in receipt of antenatal care in the first trimester (29 to 85%) and in four antenatal visits (17 to 54%). Using the difference-in-difference approach, a 42% net increase in first-trimester antenatal check-ups in Vidisha as compared to Ashok Nagar is observed. There was also an improvement in the maternal nutrition budget of the state from USD 8.5 million to USD 17.8 million during this period. The Vidisha initiative offers several lessons in time-effective workflow to deliver all constituents of nutrition services at various antenatal contact points through and via routine government health systems. Continued execution of the algorithm for screening, with longitudinal data on the management of all nutrition risks, will be critical to show its long-term impact on maternal morbidities and birth outcomes.
Subject(s)
Health Services Accessibility , Prenatal Care , Female , Pregnancy , Humans , Prenatal Nutritional Physiological Phenomena , Government , Systems AnalysisABSTRACT
Land-use conversion affects soil organic carbon (SOC) dynamics. Therefore, an in-depth study of change in SOC, SOC pool, fractions of SOC and enzymatic activities of soil microbial biomass carbon (SMBC) and dehydrogenase (DHA) with the conversion of forest land to jhum, fallow jhum and settle cultivation use has been undertaken on the hills of Arunachal Pradesh of India. Geo-referenced soil samples from eight different locations, each from different land uses were collected at three depth. One part of the soil sample had been used for the analysis of SOC and its carbon fraction. The second portion was kept in a deep freezer for determining SMBC and DHA. The third part was used for the analysis of bulk density. The result revealed that the highest loss of SOC pool was recorded in jhum land (41.8 to 13.4%), and the labile carbon was also found to decrease in jhum land. The highest SMBC was observed on the surface soil of the natural forest; the highest DHA was found in the natural forest; and the lowest DHA was recorded in jhum land. This study found that the converting natural forest to jhum reduces SOC storage, enzymatic activities and C fractions significantly whereas fallow jhum shows sign of recovery because all of these parameters improved when compared to the jhum land-use system. This study also confirms that the fallow period helps restore the initial situation.
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Nano-particle embedded system plays an importance in developing of future terahertz (THz) radiation source for real-world applications. The laser interactions with nanoparticle embedded system can produce a wide range of THz radiation due to plasma oscillations excitation. We investigate THz field generation from the laser-beat wave interaction with a mixture of spherical and cylindrical graphite nanoparticles in argon gas. Different laser intensity distributions such as Gaussian, cosh-Gaussian, flat-top and ring shape laser pulses have been studied in this work. The relevant plasmon resonance conditions with appropriate symmetry of spherical nanoparticles and cylindrical nanoparticles are discussed. THz field is enhanced upto the order of 10 2 when the laser intensity redistributes along the polarization direction for a ring shape field envelope.
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Our detailed 3-D seismic tomographic assimilation using high-quality phase arrival time data recorded by the local seismographic network demonstrated that heterogeneities in the crustal faults have contributed significantly to the pop-up tectonics beneath the Shillong Plateau, characterized by high-V and low-σ. The major seismogenic faults, namely, the north-dipping Dapsi thrust in association with Dauki fault in the south and south dipping Brahmaputra fault in the north, located either side of the Shillong Plateau that acted as the causative factors for the pop-up, which attributed to the lithostatic (high-V, low-σ) and sedimentary (low-V, high-σ) load, respectively. Seismicity is found confined to a depth ≤ 60 km. Uneven distribution of structural heterogeneities in the upper crust is responsible for earthquake genesis of varying strengths. It is intriguing to note that high-velocity anomalies and low-Ï in the uppermost crust, interpreted as the Shillong Plateau that acted as a geometric asperity and the juxtaposition of high-V and low-V became the source zone of the 1897 Shillong earthquake (Ms 8.7) as a novel observation for the region. Structural heterogeneities are distinctly distributed between low-V, high-σ and high-V, low-σ in the lower crust plays a major role for future intense seismogenesis due to differential strain accumulation.
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Caprine intestinal diseases associated with clostridia are generally caused by Cpa and Etx encoded alpha (α) and epsilon (ε) toxinotypes of Clostridium perfringens type D respectively. A recent study on goat enterocolitis, demonstrated that the incidence of Clostridium perfringens type-D toxinotype and beta 2 toxins is high, suggesting its role in enterocolitis and many other diseases of goats affecting intestinal tract. Considering this scenario, the present prevalence study was planned to screen the goat intestinal tissues for the presence of the epsilon toxin and beta 2 toxin. Tissue sections from enterotoxaemia suspected cases in 189 goats were collected and epsilon-toxin was demonstrated by immuno-histochemically and toxinotyping multiplex polymerase reaction in 19 animals and beta 2 toxin in 19 animals by multiplex polymerase reaction. Immuno-reactivity to epsilon toxin was detected maximum in distal ileum of goat intestine and this toxin was produced by Clostridium perfringens type D. It suggests that immunohistochemistry is a confirmatory tool for detection of bacterial toxin especially epsilon toxin where isolation and characterisation of bacteria is not possible. Here, we have reported a strong association between ε-toxin (epsilon) and beta-2 toxin in causing disorders of intestine in goats. In addition, we have explored the possible role of cpb2 positive isolates of C. perfringens and their pathogenic effects in causing enterotoxaemia. These determinants help in the understanding of the pathogenesis of enterotoxaemia in goats which needs to be further investigated.
Subject(s)
Bacterial Toxins , Clostridium Infections , Enterocolitis , Goat Diseases , Animals , Clostridium Infections/veterinary , Clostridium perfringens , Enterocolitis/veterinary , Enterotoxemia/epidemiology , Enterotoxemia/microbiology , Goat Diseases/microbiology , GoatsABSTRACT
AIM: To compare the efficacy of oxygen-ozone therapy and the combined use of oxygen-ozone therapy with percutaneous intradiscal radiofrequency thermocoagulation (PIRFT) for the treatment of contained lumbar disc herniation. METHODS: Ninety-one adult patients with low back pain secondary to contained lumbar disc herniation were randomly assigned into two groups. Ozone group received intradiscal oxygen-ozone therapy (4 to 7 mL of oxygen ozone mixture); ozone-PIRFT group received a combination of oxygen-ozone therapy with PIRFT (radiofrequency lesioning at 80°C for 360 s). OUTCOME MEASURES: Primary outcome measures included a visual analog scale (VAS) for pain and the Oswestry disability index (ODI). Secondary outcome measures included pain relief, reduction of analgesic consumption, and patient's satisfaction. Clinical assessment of these outcome measures was performed at 2 weeks, 1 month, 3 months, 6 months, and 1 year after the procedure. RESULTS: VAS scores and ODI were significantly decreased by both ozone and ozone-PIRFT when compared with the baseline values at all points of follow-up; however, ozone-PIRFT produced a significant reduction in the VAS scores and ODI when compared to ozone at 2 weeks, 1 month, 3 months, 6 months, and 1 year follow-up. Ozone-PIRFT also resulted in a significant change in all secondary measures at all points of follow-up, as compared with the ozone group. CONCLUSION: Ozone-PIRFT is more efficacious than ozone alone in reducing pain scores, analgesic consumption, improving functional outcome, and satisfaction of patients with contained lumbar disc herniation.
Subject(s)
Intervertebral Disc Displacement/therapy , Low Back Pain/therapy , Oxygen/therapeutic use , Ozone/therapeutic use , Spondylosis/therapy , Adolescent , Adult , Double-Blind Method , Female , Humans , Low Back Pain/etiology , Male , Middle Aged , Oxygen/administration & dosage , Ozone/administration & dosage , Prospective Studies , Young AdultABSTRACT
BACKGROUND AND AIMS: When the world was frantically searching for a drug effective against the coronavirus disease (COVID)-19, remdesivir, a broad-spectrum anti-viral medication, became a part of the COVID treatment. We planned a study to evaluate improvement in clinical outcomes with remdesivir treatment for five days. METHODS: Participants more than 40-years old and with moderate to severe COVID-19 but not on mechanical ventilation were randomly assigned into two groups-remdesivir group (34 cases) to receive the study drug intravenous (IV) remdesivir for five days plus the standard care (SC) and non-remdesivir group (36 cases) to receive the SC but not to receive the study drug. Follow-up was continued for 12 days after the beginning of treatment or until discharge/death. Patient's clinical status was assessed by laboratory investigations and physical examination (from day 1 to day 12 on a 4-point ordinal scale and from day 12 to 24 on a 6-point ordinal scale). Oxygen support requirements and adverse events were recorded. The data were entered and analysed using Statistical Package for the Social Sciences (SPSS) version 22.0. RESULTS: High-flow oxygen support and non-invasive ventilation was required at baseline by lesser patients in the remdesivir group. In the end, both groups had similar outcomes after adjustment for baseline clinical status. There was no statistical difference in mortality between the two groups (p = 0.749). Patients in both groups had an equal time to recovery. There was no difference in the occurrence of adverse effects of remdesivir between the two groups. CONCLUSION: Remdesivir therapy for five days did not produce improvement in clinical outcomes in moderate to severe COVID-19 cases.
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OBJECTIVES: No reflow during percutaneous coronary intervention (PCI) is a complex issue with serious outcomes. Multiple studies have studied predictors of no-reflow during primary PCI, but data on patients with the late presentation is sparse, which constitutes the majority of patients in peripheral centers. This study aimed to determine predictors of no-reflow during PCI in patients with ST-segment elevation myocardial infarction (STEMI) in 7 days. METHODS: It was a single-center prospective case-control study performed at a tertiary care center and included 958 patients with STEMI who underwent PCI within 7 days of symptom onset. Baseline and angiographic data of patients undergoing PCI were recorded and patients divided into reflow and no-reflow group. RESULTS: Of 958 who underwent PCI, 182 (18.9%) showed no-reflow by myocardial blush grade (MBG)<2. No-reflow group had a higher mean age (66.46±10.71 vs. 61.36±9.94 years), lower systolic blood pressure (SBP) on admission (100.61±26.66 vs. 112.23±24.35, P<0.0001), a higher level of peak Troponin I level (9.37±2.81 vs. 7.66±3.11ng/dL, P<0.0001), low left ventricular ejection fraction (36.71±3.89 vs. 39.58±4.28% respectively P<0.0001). Among angiographic data and procedural features, multivariable logistic regression analysis identified that advanced age, reperfusion time>6hours, SBP<100mmHg on admission, functional status of Killip class for heart failure≥3, lower EF (≤35%), low initial myocardial blush grade (≤1) before PCI, long target lesion length, larger reference diameter of vessel (>3.5mm) and high thrombus burden on angiography were found to be independent predictors of no-reflow (P<0.05). CONCLUSION: No-reflow phenomenon after PCI for STEMI is complex and multifactorial and can be identified by simple clinical, angiographic, and procedural features. Preprocedural characters of the lesion and early perfusion decides the fate of the outcome.
Subject(s)
No-Reflow Phenomenon/etiology , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction/therapy , Age Factors , Aged , Blood Pressure , Case-Control Studies , Coronary Angiography , Female , Humans , Logistic Models , Male , Middle Aged , No-Reflow Phenomenon/blood , No-Reflow Phenomenon/diagnostic imaging , No-Reflow Phenomenon/epidemiology , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/statistics & numerical data , Predictive Value of Tests , Prospective Studies , Risk Factors , ST Elevation Myocardial Infarction/surgery , Stroke Volume , Thrombosis/diagnostic imaging , Time Factors , Troponin I/blood , Ventricular Dysfunction, Left/physiopathologyABSTRACT
BACKGROUND: Pancreatic cancer cells are highly resistant to drug therapy; however, underlying causes remain largely unknown. We hypothesised that the activation of CXCL12-CXCR4 signalling confers drug resistance to pancreatic cancer cells by potentiating survival. CXCR4 is overexpressed in precancerous/malignant pancreatic lesions and cancer stem cells, and implicated in its pathogenesis. METHODS: Effect of CXCR4 activation by CXCL12 on restricting the gemcitabine-induced cytotoxicity and stimulating the survival signalling was examined in pancreatic cancer cells by MTT, DNA laddering, caspase activity, immunoblot, and promoter-reporter assays. Subsequently, we examined the effect of CXCR4 antagonist, AMD3100, in abrogating the rescue effect of activated CXCL12-CXCR4 signalling. RESULTS: The pancreatic cancer cells treated with gemcitabine exhibited reduced cytotoxicity in the presence of CXCL12 as compared with the cells treated with drug alone. CXCL12 induced the activation of FAK, ERK, and Akt signalling pathways, enhanced transcriptional activities of ß-catenin and NF-κB, and expression of survival proteins. AMD3100 arrested the CXCL12-induced pancreatic cancer cell growth and drug resistance. CONCLUSION: Our findings demonstrate, for the first time, a role of CXCL12-CXCR4 signalling axis in conferring drug resistance to pancreatic cancer cells and suggest that it could serve as a novel therapeutic target for pancreatic cancer therapy, alone and in combination with the cytotoxic drug.