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The repercussions of the industrial and digital revolutions on the world's social and economic landscapes are only now becoming apparent. Every element of a society's economy is affected by this collision and the AI Revolution, from little businesses to large communities to entire nations. This breakthrough in AI will lead to seismic shifts in society and pose grave threats to human civilization. Many have tried, and failed, to establish ethical guidelines for AI that benefit humankind. The goal is for these standards to help individuals out. Concepts that are too complex may leave the audience baffled. These developments provide the chance to enhance tools, solutions, and services in an effort to address some of the world's most pressing issues and advance progress towards the United Nations' Sustainable Development Goals. These targets were set to help usher in a more fair and sustainable society (SDGs). The results of a 2017 World Economic Forum (WEF) research on AI and robotics suggest that the world's economy is not ready for "Automation and Robotization," which might lead to high levels of unemployment. Artificial intelligence and robots were the subjects of the study. Most pressing issues for contemporary society and businesses are related to the implementation of AI technology, the expansion of opportunities and productivity, the elimination of unemployment, and the reduction of economic disparity. This study delves at the positive and negative aspects of artificial intelligence as well as current views, its prevalence in society, and the many methods in which it has been implemented.

Objective: To determine the correlation of platelet indices; platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW) and platelet large cell ratio (P-LCR) with mortality in patients admitted to PICU. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pediatric Intensive Care Unit (PICU) of CMH Lahore from Jun 2019 to May 2020. Methodology: Cases (mortality group) were the 81 consecutive patients who died in the PICU during the study period and fulfilled inclusion criteria. The control group comprised 81 surviving patients admitted to PICU contemporarily. Both groups' mean values of platelet indices (PC, MPV, PDW and P-LCR) were compared. Results: The mortality rate was 10.42%. Infants were the largest sub-group (45.68%) in the mortality group. Mean platelet counts were significantly low, while mean MPV, PDW and P-LCR were significantly higher in children in the mortality group compared to the control group (p-value

Objective: To find out the frequency of chemotherapy-induced febrile neutropenia (FN) in children diagnosed with Acute Lymphoblastic Leukemia (ALL) and its response to empirical antibiotic therapy. Study Design: Cross-sectional study. Place and Duration of Study: Department of Peadiatric Oncology, Combined Military Hospital, Rawalpindi Pakistan, from Nov 2017 to Oct 2018. Methodology: Newly diagnosed pediatric patients suffering from acute lymphoblastic leukemia between 1 to 15 years of age were included. All patients were treated with chemotherapy according to the United Kingdom National Randomized Trial for Children and Young adults with Acute Lymphoblastic Leukemia (UKALL) 2011 protocol. Patients with febrile neutropenic (FN) episodes were treated with empirical antimicrobial therapy as per hospital guidelines. Patients ‘response to antimicrobial therapy, blood culture results and related complications were noted. Results: Out of a total 77 patients, 45 (58.4%) had 69 episodes of febrile neutropenia (FN), 62 (78.5%) episodes of febrile neutropenia (FN) were started empirical treatment with first-line antibiotics (piperacillin-tazobactam and amikacin) whereas 15 (21.7%) episodes of febrile neutropenia (FN) not responding to the 1st line were shifted to second-line antibiotics (meropenem and amikacin). Mean duration of fever was 4.1 ± 2.8 days on 1st line antibiotic regimen, 2.6 ± 1 days on 2nd line antibiotics and 6.3 ± 3.3 days on combination with antifungal drug. Ten patients received antifungal therapy empirically. Efficacy of the 1st line and the 2nd line was 72.5% and 77% respectively. Staphylococcus aureus was the most frequent organism isolated from blood culture results. During the induction phase, 10 (12.9%) patients..............

Aim/Purpose: The present study examines the effect of perceived organisational and co-worker support on the adjustment of repatriates and its impact on their intention to transfer knowledge in multinational companies (MNCs). It also examines the relationship between perceived organisational support, co-worker support, and knowledge transfer through the mediating role of repatriate adjustment. Background: The ability of acquiring and utilising international knowledge is one of the core competitive advantages of MNCs. This knowledge is transferred by MNCs across their subsidiaries efficiently through repatriates, which will result in superior performance when compared to their local competitors. But in MNCs the expatriation process has been given more emphasis than the repatriation process; therefore, there is limited knowledge about repatriation knowledge transfer. Practically, the knowledge transferred by repatriates is not managed properly by the MNCs. Methodology: The proposed model was supported by Uncertainty Reduction Theory, Organisational Socialisation Theory, Organisational Support Theory, and Socialisation Resource Theory. The data were gathered from 246 repatriates working in Indian MNCs in the manufacturing and information technology sectors who had been on an international assignment for at least one year. The data obtained were analysed using Structural Equation Modeling (SEM) using AMOS 21 software. Contribution: The present study expands prior research on repatriate knowledge transfer by empirically investigating the mediating role of repatriate adjustment between perceived support and repatriate knowledge transfer in MNCs. The present study also highlights that organisational and co-worker support during repatriation is beneficial for repatriate knowledge transfer. It is important that MNCs initiate support practices during repatriation to motivate repatriates to transfer international knowledge. Findings: The results revealed that both perceived organisational and co-worker support had a significant role in predicting repatriate adjustment in MNCs. Furthermore, the results also revealed that perceived organisational and co-worker support increases repatriate knowledge transfer through repatriate adjustment in MNCs. Recommendations for Practitioners: This study indicates the role of management in motivating repatriates to transfer their knowledge to the organisation. The management of MNCs develop HR policies and strategies leading to high perceived organisational support, co-worker support, and repatriate adjustment. They need to pay particular attention to the factors that affect the repatriates’ intention to share knowledge with others in the organisation. Recommendation for Researchers: Researchers can use the validated measurement instrument which could be essential for the advancement of future empirical research on repatriate knowledge transfer. Impact on Society: The present study will assist MNCs in managing their repatriates during the repatriation process by developing an appropriate repatriation support system. This will help the repatriates to better adjust to their repatriation process which will motivate them to transfer the acquired knowledge. Future Research: Future research can adopt a longitudinal style to test the different levels of the adjustment process which will help in better understanding the repatriate adjustment process. Additionally, this model can be tested with the repatriates of other countries and in diverse cultures to confirm its external validity. Furthermore, future research can be done with the repatriates who go on an international assignment through their own initiative (self-initiated expatriates).

Up to now, no vaccine has been developed for COVID-19 treatment. Although many scientists are working for the rapid development of a vaccine to control this pandemic, nonetheless, it will take time. If the vaccine will be developed soon, it will not be available to the entire world instantly since the mass production of the vaccine will take time. In this scenario, we will have to take alternative measures to control the COVID-19 pandemic. These alternative approaches include the stimulation of the immune system to fight against viral infections. Among the different approaches to strengthen the immune system, the use of probiotics is the best one. Probiotics can help the body to fight against COVID-19 directly and indirectly. In this review, we comprehensively discuss the use of probiotics for the prevention and control of COVID-19.

ObjectivesTo assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs).MethodsThis prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score.ResultsAfter vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (pConclusionPatients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses.

Introduction Intense livestock farming practices enforcing the farmers to use antibiotics as food supplements on a routine basis. Aberrant use of antibiotics is associated with the emergence of antibiotics resistance and resistant superbugs. Keeping in view the current scenario, the present study was designed for the first time from Pakistan with a specific aim to estimate the prevalence of the carbapenem-resistant Klebsiella pneumoniae in veterinary settings and the waste in Pakistan. Methods A total of 138 samples from various veterinary sources were collected by employing a nonprobability sampling technique. Isolation and phenotypic identification of carbapenem-resistant K. pneumoniae were performed according to the CLSI standard. Molecular detection of various antibiotic resistance genes (ARGs) was done through PCR by using specific primers against each ARG. According to the pasture scheme, the multilocus sequence typing (MLST) was performed to characterize the K. pneumoniae sequence types (STs). Results According to the results of the study, overall 9.4% (13/138) isolates were confirmed carbapenem-resistant K. pneumoniae. Among various carbapenem ARGs particularly, the bla NDM-1 was found in 92.3% (12/13) isolates followed by bla OXA-48 84.6% (11/13). MLST results revealed that overall 3 STs were found in the study which includes ST29, ST11, and ST258. Taking together, this is the first study to our best knowledge which demonstrated the prevalence of carbapenem-resistant K. pneumoniae and its various STs prevalent in veterinary settings and the waste of Pakistan. Conclusion Based on the above-mentioned facts, we suggested that veterinary settings and waste are the potential source and reservoir of carbapenem-resistant K. pneumoniae, which may be disseminated to the environment and ultimately can affect the public and companion livestock health.

Quorum sensing (QS) is a major controller of virulence and biofilm formation in pathogenic bacteria. The aim of the research was to screen novel synthetic compounds (18) from 2 series (Pyrazole and Diene dione) for quorum sensing and biofilm inhibitory potential against resistant pathogens isolated from patients with chronic sinusitis. Most of the compounds have documented zone of inhibition against Gram positive strains Staphylococcus aureus, Enterococcus faecalis and moderate activity against Gram negative Klebseilla pneumoniae and Proteus mirabilis in comparison with standard antibiotic. Compounds Q1 and Q7 have given the maximum zone of inhibition 18 and 20 mm with MICs 0.312 mg/mL and .156 mg/mL against S aureus and E faecalis, respectively. Some compounds were equally potent at inhibiting the formation of biofilm which later established by phase contrast microscopy. Regarding quorum sensing inhibition, the tested concentration of synthetic compound UA3 0.313 mg/mL inhibited violacein production without decreasing Chromobacterium pseudoviolaceum count which was significantly lower than determined MIC’s. It was depicted from the results that selected compounds exhibited low level of cytotoxicity toward human red blood cells. Hence, these findings revealed that most novel compounds were effective antibacterial, whereas compound UA3 has shared significant anti-quorum sensing potential against Chromobacterium pseudoviolaceum.

Aim: This study aimed at detecting and quantifying Merkel cell polyomavirus (MCPyV) viral loads in the peripheral blood of healthy Pakistani individuals. Patients & methods: A total of 221 whole blood samples obtained from healthy individuals were examined by qPCR. Results & conclusion: MCPyV was detected in the peripheral blood of 31.2% healthy individuals. The rate of MCPyV positivity decreased from young (36%), to middle (33.7%) and elder (25.3%) age groups. Our data revealed higher prevalence of MCPyV in women (43.93%) than men (25.80%). The MCPyV viral load was calculated in the range of 0.06 –11 copies/ng of isolated DNA. The MCPyV viral load increased from young (median = 3.35) to elder (median = 5.66) age groups. The MCPyV circulate at a higher frequency by residing dormant in certain blood cells, which might act as potential vehicles for the spread of MCPyV infection among general population.

Background/Aims Time-to-relapse after rituximab for ANCA vasculitis is variable and optimal retreatment strategy is unclear. We previously showed that repopulation of naïve B-cells at 6 months predicts sustained response. Our objective was to evaluate clinical and B-cell predictors for relapse in multivariable analysis to develop a retreatment algorithm. Methods An observational study was conducted in 60 rituximab-treated AAV patients over 10-years. Complete response was defined as a Birmingham Vasculitis Activity Score (BVAS) v3.0=0. Repeat rituximab cycles were given on clinical relapse. Naïve, memory B-cells and plasmablasts were measured using highly sensitive flow cytometry. Clinical and B cell predictors were analysed in multivariable analysis (MVA) to develop a retreatment algorithm. Results Patients were: 33/60 (55%) male, mean(SD) age 51(19), 39/60 (65%) received concomitant immunosuppressants and 54/60 (90%) had prior therapy with cyclophosphamide. Median times to retreatment for cycles 1-5 were 87, 71, 65, 59 and 86 weeks. Over 417 patient-years follow up, 137 relapses occurred in 50 patients; 16 (in 14 patients) were major (renal=7, neurological=4, ENT=3 and lungs=2). The major-relapse rate was 3.8/100 patient-years. Results of MVA are shown in the table. With naïve B-cell repopulation at 6 months, relapse rates at 12 and 18 months were 5% and 16%, versus 45% and 59% without naïve repopulation (p < 0.001). Relapse rates at 18 and 24 months were 17% and 54% with naïve repopulation at 12 months versus and 29% and 71% without (p = 0.045). AUROC for time-to-relapse was greater if retreatment was guided by naïve B-cell repopulation than if ANCA and/or CD19+ return was used at 6 months, 0.82 and 0.52 respectively. Conclusion These results suggest the following: (i) all patients should receive an oral immunosuppressant; (ii) patients with incomplete remission should be retreated at 6 months; (iii) patients with complete remission but absent naïve B cells at 6 months should be retreated at 6 months; (iv) patients with complete remission and naïve B-cell return may not be appropriate for fixed retreatment. For this last group monitoring of clinical symptoms and B-cells may be effective and future work will address this further. This algorithm could avoid hypogammaglobulinaemia due to unnecessary retreatment. P207 Table 1:Factors associated with time-to-relapse to first cycle rituximabRisk FactorsUnivariable analysisHR (95% CI); p-values(with multiple imputation)Multivariable analysis (MVA)HR (95% CI); p-values(with multiple imputation)Age, per 10 years (BL)1.01 (0.86 – 1.17); p = 0.954Not included in MVAFemale (BL)1.15 (0.65 – 2.02); p = 0.629Not included in MVADisease duration, years (BL)1.06 (0.98 – 1.15); p = 0.160Included in MVA but removed from final model as p < 0.20Concomitant immunosuppressant (BL)0.69 (0.39 – 1.22); p = 0.2050.48 (0.24 – 0.94); p = 0.034Positive ANCA immunofluorescence (BL)0.89 (0.46 – 1.71); p = 0.725Not included in MVAPositive anti-PR3/anti-MPO (BL)0.57 (0.31 – 1.06); p = 0.077Included in MVA but removed from final model as p < 0.20CRP, mg/L (BL)1.00 (0.99 – 1.01); p = 0.456Not included in MVABVAS 3.0 per point score (BL)0.99 (0.94 – 1.05); p = 0.763Included in MVA but removed from final model as p < 0.20VDI per point score (BL)1.14 (0.87 – 1.50); p = 0.353Not included in MVANaïve B-cells, x 10 9/L* (BL)1.00 (1.00 – 1.01); p = 0.797Not included in MVAMemory B-cells, x 10 9/L* (BL)1.01 (1.00 – 1.02); p = 0.0401.01 (1.00 – 1.02); p = 0.045Plasmablasts, x 10 9/L* (BL)1.04 (0.94 – 1.16); p = 0.459Not included in MVAComplete depletion at 6 Weeks post-RTX0.90 (0.50 – 1.61); p = 0.721Not included in MVAComplete Response (26Wk)0.34 (0.19 – 0.61); p < 0.0010.24 (0.12 – 0.50); p < 0.001Positive ANCA immunofluorescence (26Wk)0.99 (0.56 – 1.75); p = 0.962Not included in MVAPositive anti-PR3/anti-MPO (26Wk)0.79 (0.44 – 1.42); p = 0.426Not included in MVACRP, mg/L (26Wk)0.99 (0.97 – 1.02); p = 0.618Not included in MVANaïve B-cell repopulation (26Wk)0.38 (0.19 – 0.76); p = 0.0060.43 (0.22 – 0.84); p = 0.013Memory B-cell repopulation (26Wk)0.45 (0.20 – 0.99); p = 0.046Included in MVA but removed from final model as p < 0.20Plasmablast cell repopulation (26Wk)1.14 (0.61 – 2.13); p = 0.675Not included in MVABL = baseline, 26Wk = 26 weeks. Disclosure J.E. Arnold: None. E.M.J. Vital: Honoraria; Roche, GSK, AstraZeneca. S. Dass: Honoraria; Roche, GSK. A. Aslam: None. A.C. Rawstron: None. S. Savic: Honoraria; Novartis, Swedish Orphan Biovitrum, Sire. Grants/research support; Novartis, Swedish Orphan Biovitrum, Octapharma, CSL Behring. P. Emery: Consultancies; BMS, Abbott, Pfizer, MSD, Novartis, Roche, UCB. Grants/research support; Abbott, BMS, Pfizer, MSD, Roche. M. Md Yusof: None.

Introduction The mounting incidence of multidrug-resistant bacterial strains and the dearth of novel antibiotics demand alternate therapies to manage the infections caused by resistant superbugs. Bacteriophages and phage=derived proteins are considered as potential alternates to treat such infections, and have several applications in health care systems. The aim of this review is to explore the hidden potential of bacteriophage proteins which may be a practical alternative approach to manage the threat of antibiotic resistance. Results Clinical trials are in progress for the use of phage therapy as a tool for routine medical use; however, the existing regulations may hamper their development of routine antimicrobial agents. The advancement of molecular techniques and the advent of sequencing have opened new potentials for the design of engineered bacteriophages as well as recombinant bacteriophage proteins. The phage enzymes and proteins encoded by the lysis cassette genes, especially endolysins, holins, and spanins, have shown plausible potentials as therapeutic candidates. Conclusion This review offers an integrated viewpoint that aims to decipher the insights and abilities of bacteriophages and their derived proteins as potential alternatives to antibiotics.

Newcastle disease (ND) is an economically important contagious disease of wild and domestic birds worldwide. The disease causes severe economic losses in terms of production due to high mortality and morbidity in nonvaccinated chickens. Despite extensive vaccination approaches, Newcastle disease (ND) remains a permanent threat to the poultry industry worldwide. In the current study, we used natural chicken IFN-α as an innate immune modulator to counteract ND in chickens. We report that chIFN-α is effective in protecting the chickens against ND and also prevents shedding of the virus, which can then prevent further spread of the disease. We propose that in addition to vaccination, chIFN-α therapy could be an effective option for controlling ND in areas of endemicity., Despite extensive vaccination approaches, Newcastle disease (ND) remains a permanent threat to the poultry industry worldwide. Besides vaccination, there is a burgeoning demand for new antivirals for use in interventions to control ND. One strategy is to strengthen the host innate immunity via host-derived innate immune proteins. Type I interferons define one of the first lines of innate immune defense against viral infections. Chicken interferon alpha (chIFN-α) is one of the potent cytokines that trigger antiviral responses. In the current study, we investigated the therapeutic effect of natural chIFN-α administered via oral and intramuscular (i.m.) routes against ND in broiler chickens. Our results showed that the level of protection against ND in response to chIFN-α therapy was dependent on the route and dose of IFN administration. A better therapeutic effect was observed in chickens treated with chIFN-α via the oral route than in those treated via the i.m. route. Regardless of the administration route, double-dose chIFN-α (2,000-U) treatments provided better protection than single-dose (1,000-U) treatments. However, complete protection against ND was achieved in birds treated with repeated doses of chIFN-α via the oral route. Histopathology of trachea, proventriculus, spleen, and liver showed a significant improvement in ND-induced degenerative changes in double-dose IFN-treatment groups compared to single-dose groups. Results of the hemagglutination test demonstrated a decrease in ND virus (NDV) titer in IFN-treated groups. Also, double doses of chIFN-α via oral route resulted in early recovery in weight gain. We propose that chIFN-α therapy via oral route could be an important therapeutic tool to control NDV infection in chicken. IMPORTANCE Newcastle disease (ND) is an economically important contagious disease of wild and domestic birds worldwide. The disease causes severe economic losses in terms of production due to high mortality and morbidity in nonvaccinated chickens. Despite extensive vaccination approaches, Newcastle disease (ND) remains a permanent threat to the poultry industry worldwide. In the current study, we used natural chicken IFN-α as an innate immune modulator to counteract ND in chickens. We report that chIFN-α is effective in protecting the chickens against ND and also prevents shedding of the virus, which can then prevent further spread of the disease. We propose that in addition to vaccination, chIFN-α therapy could be an effective option for controlling ND in areas of endemicity.

The IL-33/ST2 axis is known to be involved in liver pathologies and IL-33 is over-expressed in mouse hepatitis models. We aimed to investigate the proposed protective effect of IL-33 in murine fulminant hepatitis induced by a Toll like receptor 3 (TLR3) viral mimetic, Poly I:C or by Concanavalin-A (ConA). The Balb/C mice were administered intravenously with ConA (15 mg/kg) or Poly I:C (30 μg/mouse) to induce acute hepatitis along with vehicle control. The recombinant mouse IL-33 (rIL-33) was injected (0.2 μg/mouse) to mice 2 h prior to ConA or Poly I:C injection to check its hepato-protective effects. The gross lesions, level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), histopathology (H&E staining) and levels of IFNγ and TNFα were measured by ELISA. The gross pathological liver injury induced by Poly I:C or ConA was reduced by rIL-33 administration in mice. The levels of AST and ALT were significantly (P ≤ 0.05) higher in mice challenged with Poly I:C or ConA in comparison to control mice. The rIL-33 pre-treated mice in both Poly I:C and ConA challenge groups showed significantly (P ≤ 0.05) lower levels of AST and ALT, and decreased liver injury (parenchymal and per-vascular necrotic areas) in histological liver sections. The soluble levels of TNFα and IFNγ were significantly (P ≤ 0.05) raised in Poly I:C or ConA challenged mice than control mice. The levels of TNFα and IFNγ were significantly reduced (P ≤ 0.05) in rIL-33 pre-treated mice. In conclusion, the exogenous IL-33 administration mitigated liver injury and inflammation (decreased levels of IFNγ and TNFα) in Poly I:C and ConA-induced acute hepatitis in mice.

Background Myositis is an autoimmune disease which can cause a decrease in quality of life and increased mortality, presenting with muscle weakness, raised muscle enzymes and myalgia. Diagnosis is reliant on subjective clinical examinations, blood tests, conventional MRI and invasive muscle biopsies. Quantitative T2 MRI offers a non-invasive measurement of muscle oedema which could help improve the understanding of muscle pathology and potentially inform diagnosis. The aim of this study was to evaluate whether quantitative T2 MRI of muscles is sensitive enough to detect differences in myositis patients compared to healthy controls, and how it compares with current radiologist scoring methods. Methods 16 myositis patients were recruited (10/16 female, 10 polymyositis, 6 dermatomyositis, mean age 50 ± 26), median CK 1000IU/L ± 3100IU/L, and 16 age and gender matched healthy controls were recruited. MRI of the dominant thigh were performed. Imaging was performed using a fat-suppressed turbo-spin echo sequence. Quantitative T2 measurements were obtained from regions of interest (ROI) drawn manually within the individual muscles that make up the quadriceps and hamstrings with no distinction made between affected and unaffected muscles. A mono-exponential fit was used to obtain an estimate of the T2 from each ROI. Two radiologists blinded to the diagnosis, semi-quantitatively scored by consensus the muscles on a 4-point visual scale as either no oedema (0), mild oedema (1), moderate oedema (2) or severe oedema (3). Muscle strength was assessed using an isokinetic dynamometer. Results T2 values were higher in myositis patients compared to healthy controls [mean (SD) hamstring myositis 47.8ms (7.7ms), healthy 39.9ms (1.5ms), p < 0.001; quadriceps myositis 53.8ms (12.1ms), healthy 42.1ms (2.1ms), p < 0.001]. Quantitative T2 correlated with the radiologists’ oedema scores with rs=0.7 in the hamstrings (p < 0.001) and rs=0.6 in the quadriceps (p < 0.001), with an upward trend in T2 as radiologist scored visible oedema increased. Patients who had been classified as normal by the radiologists were compared with matched healthy controls (n = 8), T2 values for patients with ‘normal muscle’ were still higher than those for healthy controls: mean T2 in the hamstrings (myositis 42.2ms, healthy controls 38.7ms, p = 0.004); mean T2 in the quadriceps (myositis 43.9ms, healthy controls 40.1ms, p = 0.001). T2 was inversely correlated with muscle strength in all participants. Conclusion Quantitative T2 measurements can detect muscle differences between myositis patients and healthy control groups, which suggests that this measurement could be used as an objective method to monitor muscles. They are also sensitive to differences that may not be detected by radiologists. This suggests that subtle systemic changes in muscle in myositis patients, which go undetected in semi-quantitative visual scoring, can be detected using quantitative T2 measurements. This shows the potential for T2 measurements to be a diagnostic measure in the diagnosis and management of myositis. Disclosures M. Farrow None. J. Biglands None. A. Grainger None. E. Hensor None. P. O'Connor None. A. Ladas None. S. Tanner None. A. Aslam None. P. Emery None. A. Tan None.

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken innate immune system and are considered potent antiviral agents against avian viral pathogens. Chicken type I IFNs are divided into three subtypes namely, chIFN-α, chIFN-β, and chIFN-κ. Viral pathogen-associated molecular patterns (PAMPs) recognized by their corresponding specific PRRs (pattern recognition receptors) induce the expression of chicken type I IFNs. Interaction of chicken type I IFNs with their subsequent IFN receptors results in the activation of the JAK-STAT pathway, which in turn activates hundreds of chicken interferon-stimulated genes (chISGs). These chISGs establish an antiviral state in neighboring cells and prevent the replication and dissemination of viruses within chicken cells. Chicken type I IFNs activate different pathways that constitute major antiviral innate defense mechanisms in chickens. However, evolutionary mechanisms in viruses have made them resistant to these antiviral players by manipulating host innate immune pathways. This review focuses on the underlying molecular mechanisms employed by avian RNA viruses to counteract chicken type I IFNs and chISGs through different viral proteins. This may help to understand host-pathogen interactions and the development of novel therapeutic strategies to control viral infections in poultry.

Introduction Intense livestock farming practices enforcing the farmers to use antibiotics as food supplements on a routine basis. Aberrant use of antibiotics is associated with the emergence of antibiotics resistance and resistant superbugs. Keeping in view the current scenario, the present study was designed for the first time from Pakistan with a specific aim to estimate the prevalence of the carbapenem-resistant Klebsiella pneumoniae in veterinary settings and the waste in Pakistan. Methods A total of 138 samples from various veterinary sources were collected by employing a nonprobability sampling technique. Isolation and phenotypic identification of carbapenem-resistant K. pneumoniae were performed according to the CLSI standard. Molecular detection of various antibiotic resistance genes (ARGs) was done through PCR by using specific primers against each ARG. According to the pasture scheme, the multilocus sequence typing (MLST) was performed to characterize the K. pneumoniae sequence types (STs). Results According to the results of the study, overall 9.4% (13/138) isolates were confirmed carbapenem-resistant K. pneumoniae. Among various carbapenem ARGs particularly, the blaNDM-1 was found in 92.3% (12/13) isolates followed by blaOXA-48 84.6% (11/13). MLST results revealed that overall 3 STs were found in the study which includes ST29, ST11, and ST258. Taking together, this is the first study to our best knowledge which demonstrated the prevalence of carbapenem-resistant K. pneumoniae and its various STs prevalent in veterinary settings and the waste of Pakistan. Conclusion Based on the above-mentioned facts, we suggested that veterinary settings and waste are the potential source and reservoir of carbapenem-resistant K. pneumoniae, which may be disseminated to the environment and ultimately can affect the public and companion livestock health.

The emergence of carbapenem-resistant bacterial pathogens is a significant and mounting health concern across the globe. At present, carbapenem resistance (CR) is considered as one of the most concerning resistance mechanisms and mainly found in gram-negative bacteria of the Enterobacteriaceae family. Although carbapenem resistance has been recognized in Enterobacteriaceae from last 20 years or so, recently it emerged as a global health issue as CR clonal dissemination of various Enterobacteriaceae members especially E. coli, and Klebsiella pneumoniae are reported from across the globe at an alarming rate. Phenotypically, carbapenems resistance is in due to the two key mechanisms, like structural mutation coupled with β-lactamase production and the ability of the pathogen to produce carbapenemases which ultimately hydrolyze the carbapenem. Additionally, penicillin-binding protein modification and efflux pumps are also responsible for the development of carbapenem resistance. Carbapenemases are classified into different classes which include Ambler classes A, B, and D. Several mobile genetic elements (MGEs) have their potential role in carbapenem resistance like Tn4401, Class I integrons, IncFIIK2, IncF1A, and IncI2. Taking together, resistance against carbapenems is continuously evolving and posing a significant health threat to the community. Variable mechanisms that are associated with carbapenem resistance, different MGEs, and supplementary mechanisms of antibiotic resistance in association with virulence factors are expanding day by day. Timely demonstration of this global health concern by using molecular tools, epidemiological investigations, and screening may permit the suitable measures to control this public health menace.

Brucellosis is reportedly endemic in ruminants in Pakistan. Both Brucella abortus and B. melitensis infections have been decumented in domestic animals and humans in the country. This study aimed to identify the burden of anti-Brucella antibodies in small ruminants as well as associated potential risk factors with its occurrence at nine institutional livestock farms in Punjab, Pakistan. The sera collected from equal number of sheep and goats (500 from each species) were screened by indirect-ELISA for anti-smooth-Brucella antibodies followed by a serial detection by real-time PCR. Overall, 5.1% (51/1000) seropositivity was registered corresponding to 5% (25/500) prevalence in goats and 5.2% (26/500) in sheep. Brucella-DNA could not be detected in any of the tested sera by real-time PCR. Multiple logistic regression model indicated that farm location (OR 34.05), >4 years of age (OR 2.88), with history of reproductive disorders (OR 2.69), and with BCS of ≤ 3 (OR 12.37) were more likely to test positive for brucellosis at these farms. A routine screening, stringent biosecurity, and quarantine measures are warranted for monitoring and eradication of the infection. Similarly, isolation and molecular investigation of the etiologic agent(s) are needed to understand the relationship of epidemiology and out-breaks of brucellosis in the country.

The advent of multidrug resistance among pathogenic bacteria is imperiling the worth of antibiotics, which have previously transformed medical sciences. The crisis of antimicrobial resistance has been ascribed to the misuse of these agents and due to unavailability of newer drugs attributable to exigent regulatory requirements and reduced financial inducements. Comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms, resistance mechanisms, and antimicrobial agents. Multidisciplinary approaches are required across health care settings as well as environment and agriculture sectors. Progressive alternate approaches including probiotics, antibodies, and vaccines have shown promising results in trials that suggest the role of these alternatives as preventive or adjunct therapies in future.

Background:Time-to-relapse after rituximab for ANCA-associated vasculitis (AAV) is variable and optimal retreatment strategy has been unclear. We previously showed that repopulation of naïve B-cells at 6 months predicts sustained response [1].Objectives:In AAV following rituximab induction, to evaluate clinical and B-cell predictors of relapse in order to develop a retreatment algorithm.Methods:An observational study was conducted in 60 rituximab-treated AAV patients followed for over 10 years. Complete response (CR) was defined as Birmingham Vasculitis Activity Score v3.0 = 0. Retreatment was given on clinical relapse, defined as new features or worsening of persistent disease (not by biomarker status). Peripheral B-cell subsets were measured using highly sensitive flow cytometry. Predictors were tested using multivariable Cox-Regression.Results:Median times-to-retreatment for rituximab cycles 1-5 were 87, 71, 65, 59 and 86 weeks. Over 417 patient-years follow-up, 137 relapses occurred in 50 patients; 16 (in 14 patients) were major (renal=7, neurological=4, ENT=3 and respiratory=2). The major-relapse rate was 3.8/100 patient-years. In multivariable analysis, concomitant immunosuppressant [HR 0.48 (95% CI 0.24–0.94)], achieving CR [0.24 (0.12–0.50)] and naïve B-cell repopulation at 6 months [0.43 (0.22–0.84)] were associated with longer time-to-relapse. Higher baseline memory B-cells [1.01 (1.00–1.02)] were associated with a shorter time-to-relapse. AUROC for prediction of time-to-relapse was greater if guided by naïve B-cell repopulation than if ANCA and/or CD19+ return at 6 months had been used, 0.82 and 0.52 respectively.Conclusion:These data suggest that all patients should receive concomitant oral immunosuppressant. Those with incomplete response or with absent naïve B-cells should be retreated at 6 months. Patients with complete response and naïve repopulation at 6 months should not receive fixed retreatment. This algorithm could reduce hypogammaglobulinaemia due to unnecessary retreatment.Figure 1.A personalised retreatment algorithm for rituximab in ANCA-associated vasculitisReferences:[1]Md Yusof et al. Annals of rheumatic diseases (2015) PMID: 25854586.Disclosure of Interests:Jack Arnold: None declared, Edward Vital Speakers bureau: Roche, GSK and AstraZeneca, Consultant of: Roche, GSK and AstraZeneca, Grant/research support from: Roche, GSK and AstraZeneca, Shouvik Dass Speakers bureau: Roche and GSK, Aamir Aslam: None declared, Andrew Rawstron: None declared, Sinisa Savic: None declared, Paul Emery Speakers bureau: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB, Consultant of: BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB, Grant/research support from: Abbott, BMS, Pfizer, MSD and Roche., Md Yuzaiful Md Yusof: None declared

2D transition metal dichalcogenides (TMDs) have received widespread interest by virtue of their excellent electrical, optical, and electrochemical characteristics. Recent studies on TMDs have revealed their versatile utilization as electrocatalysts, supercapacitors, battery materials, and sensors, etc. In this study, MoS

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken immune system and mediate the first line of defense against viral pathogens infecting the avian species. Recognition of viral pathogens by specific pattern recognition receptors (PRRs) induce chicken type I IFNs expression followed by their subsequent interaction to IFN receptors and induction of a variety of IFN stimulated antiviral proteins. These antiviral effectors establish the antiviral state in neighboring cells and thus protect the host from infection. Three subtypes of chicken type I IFNs; chIFN-α, chIFN-β, and a recently discovered chIFN-κ have been identified and characterized in chicken. Chicken type I IFNs are activated by various host cell pathways and constitute a major antiviral innate defense in chicken. This review will help to understand the chicken type 1 IFNs, host cellular pathways that are involved in activation of chicken type I IFNs and IFN stimulated antiviral effectors along with the gaps in knowledge which will be important for future investigation. These findings will help us to comprehend the role of chicken type I IFNs and to develop different strategies for controlling viral infection in poultry.