Historically,influenza pandemics have arisen from avian influenza viruses.Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates.Infection of humans with the highly pathogenic avian influenza H5N1 vir...Historically,influenza pandemics have arisen from avian influenza viruses.Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates.Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%,which has been attributed to dysregulation of the cytokine system.Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus.The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated.In the present study,we demonstrate that autophagy,a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents,plays a role in cytokine induction.Autophagy is induced to a greater extent by H9N2/G1,in association with cytokine hyperinduction,compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses.Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene,Atg5,we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-a expression in primary human blood macrophages.Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.展开更多
Natural killer （NK） cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitte...Natural killer （NK） cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitted in the early phase of virus infection. Evasion of host innate immunity including NK cells is critical for the virus to expand and establish a successful acute infection. Previously, we showed that human influenza HIN1 virus infects NK cells and induces cell apoptosis, as well as inhibits NK cell activity. In this study, we further demonstrated that avian influenza virus also directly targeted NK cells as an immunoevasion strategy. The avian virus infected human NK cells and induced cell apoptosis. In addition, avian influenza virion and HA protein inhibited NK cell cytotoxicity. This novel strategy has obvious advantages for avian influenza virus, allowing the virus sufficient time to expand and subsequent spread before the onset of the specific immune response. Our findings provide an important clue for the immunopathogenesis of avian influenza, and also suggest that direct targeting NK cells may be a common strategy used by both human and avian influenza viruses to evade NK cell immunity.展开更多
<strong>Objective: </strong>The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment o...<strong>Objective: </strong>The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment of severity and thrombocytopenia in dengue. <strong>Methods:</strong> A cross-sectional analytical study was carried out on diagnosed dengue patients admitted to Nawaloka Hospital, Sri Lanka. Blood samples were taken from patients (n = 50) on the day of admission, 3<sup>rd</sup> and 5<sup>th</sup> day from admission for analysis of GR, aspartate transaminase, alanine transaminase, platelets, white blood cells, and Atypical Lymphocytes (AL). <strong>Results:</strong> GR level of all three measured stages had a higher area under the curve (>88%), high sensitivity and specificity compared to liver transaminases. A significant regression model represents on admission GR and AL levels as predictive variables to platelet levels in day 03 from admission (Day 3 Platelet level = 127155.3 - 383 * GR - 0.431 * AL). <strong>Conclusion:</strong> Liver transaminases, GR, and AL% can be considered as a profile of predictive biomarkers in early diagnosis of severity of dengue infection. The degree of thrombocytopenia can be predicted using on admission GR and AL% level in acute dengue viral infection.展开更多
Apart from the conventional factors, recent evidences have suggested that lumbar disc herniation (LDH) is also associated with microbes, which is completely ignored in the management of patients with disc prolapse and...Apart from the conventional factors, recent evidences have suggested that lumbar disc herniation (LDH) is also associated with microbes, which is completely ignored in the management of patients with disc prolapse and disc degeneration. Therefore, the present study was carried out to identify the different microorganisms in subjects with LDH. Subjects (n = 101) who were confirmed for LDH with Magnetic Resonance Imaging and undergoing lumbar discectomy, were recruited in this study. Standard protocols for disinfection of the skin and surgical instruments were adhered. Skin scrapings, muscle biopsies and portion of the inter-vertebral disc were transferred into individually labeled Robertson’s cooked meat enrichment broth for anaerobic identification. Remaining portions of the excised disc material and muscle biopsy were taken for aerobic identification. Anaerobic isolates were identified using Gram stain and catalase test while the species identification was done by RapID ANA II ID kit. Gram stain, catalase test, DNase test and coagulase tests were used for identification of aerobic bacteria. Study confirmed 6/101 disc cultures (6%) with positive anaerobes and 12 disc cultures with coagulase negative Staphylococci spp. Among the anaerobes, two disc cultures were identified as Propionibacterium acnes and one as Gemella morbillorum. Due to slow growth, other three anaerobic cultures were not confirmed. However, they resembled the colony morphology of Gram positive bacilli. None of the control samples (skin and muscles) had any positive growth. The present study adds to the literature confirming the role of microorganisms in LDH. Present study newly identified Gemella morbillorum in the intervertebral tissue in addition to the previously reported microorganisms associated with LDH.展开更多
Wearable health-monitoring devices are novel and integral developments based on smart-textiles.Conventional wearable technology consists of micro-controllers and a variety of electronic devices embedded on the skin,or...Wearable health-monitoring devices are novel and integral developments based on smart-textiles.Conventional wearable technology consists of micro-controllers and a variety of electronic devices embedded on the skin,or incorporated into the apparels,where they act as signal receptors,analytical devices and transmitters of the signals generated from the human body.Invasive methods are currently more commonly practiced where biofluids are obtained by penetrating the body by incision or injection,while in non-invasive methods no such penetrations take place.A critical review of current non-invasive wearable technology,including colorimetric,enzymatic,pH based,electrochemical and conductivity sensors,is presented in this paper along with the challenges and limitations they pose.Additionally,novel techniques of analysis have been explored concluding that a textile-based medium offers higher compatibility for integration of such sensors in comparison to other existing substrates.展开更多
AIMTo assess the impact of multi-disciplinary teams (MDTs) management in optimising the outcome for rectal cancers. METHODSWe undertook a retrospective review of a prospectively maintained database of patients with re...AIMTo assess the impact of multi-disciplinary teams (MDTs) management in optimising the outcome for rectal cancers. METHODSWe undertook a retrospective review of a prospectively maintained database of patients with rectal cancers (defined as tumours ≤ 15 cm from anal verge) discussed at our MDT between Jan 2008 and Jan 2011. The data was validated against the national database to ensure completeness of dataset. The clinical course and follow-up data was validated using the institution’s electronic patient records. The data was analysed in terms of frequencies and percentages. Significance of any differences were analysed using χ<sup>2</sup> test. A Kaplan-Meier analysis was performed for overall survival and disease free survival. RESULTSFollowing appropriate staging, one hundred and thirty-three patients were suitable for potentially curative resections. Seventy two (54%) were upper rectal cancer (URC) - tumour was > 6 cm from the anal verge and 61 (46%) were lower rectal cancers (LRC) - lower extent of the tumour was palpable ≤ 6 cm. Circumferential resection margin (CRM) appeared threatened on pre-operative MRI in 19/61 (31%) patients with LRC requiring neo-adjuvant therapy (NAT). Of the 133 resections, 118 (89%) were attempted laparoscopically (5% conversion rate). CRM was positive in 9 (6.7%) patients; Median lymph node harvest was 12 (2-37). Major complications occurred in 8 (6%) patients. Median follow-up was 53 mo (0-82). The 90-d mortality was 2 (1.5%). Over the follow-up period, disease related mortality was 11 (8.2%) and overall mortality was 39 (29.3%). Four (3%) patients had local recurrence and 22 (16.5%) patients had distant metastases. CONCLUSIONManagement of rectal cancers can be optimized with multi-disciplinary input to attain acceptable long-term oncological outcomes even when incorporating a laparoscopic approach to rectal cancer resection.展开更多
Identification of redox markers may be of clinical significance in the management of dengue patients. This study is to identify the association between antioxidant enzymes, hematological parameters and liver transamin...Identification of redox markers may be of clinical significance in the management of dengue patients. This study is to identify the association between antioxidant enzymes, hematological parameters and liver transaminases in patients with acute dengue infection. Blood samples were taken from patients on the day of admission, day 05 and 07 from admission for analysis of glutathione peroxidase (GPX), glutathione reductase (GR), aspartate transaminase (AST), alanine transaminase (ALT) and hematological parameters. AST and ALT levels were significantly elevated (p < 0.05) on day 05 in dengue patients. In contrast, GPX and GR showed significantly low levels on day 05 compared to on the day of admission and day 07. Although there was a decline in the trend of platelets towards day 05, values were not significantly different. Dengue associated with liver injury appears to peak around day 05 when the GPX and GR enzymes levels in patients were the lowest suggesting that increased viral load in the acute phase of dengue infection has initiated an antioxidant imbalance. Thus, timely investigation of antioxidant enzymes (GR and GPX) and liver transaminases around day 05 of admission may be of value in the management of patients with dengue infection similar to as seen in platelet counts.展开更多
The Middle East respiratory syndrome(MERS)is a lethal zoonosis caused by MERS coronavirus(MERS-CoV)and poses a significant threat to public health worldwide.Therefore,a rapid,sensitive,and specific serologic test for ...The Middle East respiratory syndrome(MERS)is a lethal zoonosis caused by MERS coronavirus(MERS-CoV)and poses a significant threat to public health worldwide.Therefore,a rapid,sensitive,and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness.Here,we evaluated various novel luciferase immunosorbent assays(LISA)based on nucleocapsid protein(NP)as well as fragments derived from spike protein(S)including subunit 1(S1),N terminal domain(NTD),receptorbinding domain(RBD)and subunit 2(S2)of S for the detection of MERS-CoV-specific IgG.Fusion proteins,including nanoluciferase(NLuc)and various fragments derived from the NP or S protein of MERS-CoV,were expressed in human embryonic kidney 293 T cells.LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins.Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR,commercial S1-based ELISA,and pseudovirus particle neutralization test(ppNT).Our results showed that the S1-,RBD-,and NP-LISAs were more sensitive than the NTD-and S2-LISAs for the detection of anti-MERS-CoV IgG.Furthermore,the S1-,RBD-,and NP-LISAs were more sensitive(by at least 16-fold)than the commercially available S1-ELISA.Moreover,the S1-,RBD-,and NPLISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV(OC43,229E,HKU1,NL63)-infected patients.More importantly,these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels,monkeys,and mice,among which the RBD-LISA exhibited excellent performance.The results of this study suggest that the novel MERS-CoV RBD-and S1-LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples.These assays have the potential to be used as serologic tests for 展开更多
AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative col...AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative colitis(UC) or Crohn's disease(CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12 B :rs1045431, IL23 R :rs11805303, ARPC2 :rs12612347, IRGM :rs13361189, IL26/IL22 :rs1558744, CDH1 :rs1728785, IL10 :rs3024505, FCGR2 A :rs3737240, PTGER4 :rs4613763, IL17 REL/PIM3 :rs5771069, HNF4 a :rs6017342, STAT3 :rs744166, SMURF1 :rs7809799, LAMB1 :rs886774, HLA-DRB5, DQA1, DRB1, DRA :rs9268853, MST1, UBA7, and APEH :rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium(P > 10^(-3)). To account for multiple hypothesis testing, P-values < 0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms(SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774(LAMB1-gene) and UC(odds ratio(OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease(OR = 1.66, P < 0.001) and remained in remission(OR = 1.48, P < 0.001). A positive association was noted between rs10045431(IL 12 B gene) and upper gastrointestinal involvement in CD(OR = 4.76, P = 0.002). CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.展开更多
Objective: To describe the symptoms of dengue at acute and post-infection stage and to identify preventive strategies adopted by the patients in the Western Province, Sri Lanka.Methods: This was a descriptive cross-se...Objective: To describe the symptoms of dengue at acute and post-infection stage and to identify preventive strategies adopted by the patients in the Western Province, Sri Lanka.Methods: This was a descriptive cross-sectional study conducted in the Western Province of Sri Lanka in November 2017. The study population consisted of 473 confirmed dengue patients aged from 18 to 64 years who were hospitalized between June and August 2017. A stratified random sampling technique was applied to select the participants. Data collection was done by trained interviewers, using a structured, pre-tested interviewer-administered questionnaire. Results: The most common symptoms of dengue fever at the acute stage was body ache(81.81%, n=387), followed by headache(71.67%, n=339), loss of appetite(66.80%, n=316), tiredness(53.06 %, n=251) and vomiting(41.86%, n=198). The most common symptom during the post-infection stage was body ache(48.62%, n=230), followed by fatigue(39.74%, n=188), and loss of appetite(28.75%, n=136). Adding sand to the water in places where water accumulates(41.64%, n=197) was the most common method used to prevent transmission of dengue followed by removing/draining stagnant water regularly(36.15%, n=177). Use of mosquito nets(83.08%, n=393) was the most common method in preventing mosquito bites followed by the use of fans among dengue patients(56.02%, n=265).Conclusions: The study shows a prolonged persistence of clinical symptoms during the postinfection period.展开更多
A 66-year-old female with cryptogenic cirrhosis complicated by ascites,hepatic encephalopathy,variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with...A 66-year-old female with cryptogenic cirrhosis complicated by ascites,hepatic encephalopathy,variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique.Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow.The liver graft was recirculated without any hemodynamic instability.Subsequently,the patient became hypotensive progressing to asystole.She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle.The patient was noted to be coagulopathic at the time.She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.展开更多
Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronavir...Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses,which can be found from a wide range of mammals,were recently detected in bats. Strikingly,these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families,but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health.展开更多
Atherosclerosis is the most important contributor to increasing burden of coronary artery disease (CAD). Growing evidence suggests that the ratios of Apo B/Apo A-I and Lp(a) are better indexes for risk assessment of C...Atherosclerosis is the most important contributor to increasing burden of coronary artery disease (CAD). Growing evidence suggests that the ratios of Apo B/Apo A-I and Lp(a) are better indexes for risk assessment of CAD. Elevated plasma levels of lipoprotein(a) in humans represent a major in-herited risk factor for atherosclerosis. Thus, a study was performed to determine the association betwwen serum Apo B, Apo A-I, and lipoprotein(a) levels, and severity of CAD in patients with CAD confirmed on coronary angiography findings. An analytical case control study was carried out with 85 patients (58 males and 27 females) 40 - 60 years of age confirmed as having CAD on coronary angiography and 85 age and sex matched healthy volunteers as controls. Serum samples were an-alyzed for Apo A-1 LDL, Apo B, Apo A-I, and lipoprotein(a) concentration and the severity of CAD was assessed using coronary angiography scoring method. Patients with CAD had significantly high serum LDL-C, Apo B and Lp(a) levels compared to control subjects. However, serum Apo A-I level did not show a significant difference between two groups. Subjects with a positive family history of CAD with increased serum Lp(a) ≥ 17.3 mg/dL have high risk for development of CAD. Present study suggests that serum Lp(a) cut-off value of 17.3 mg/dL may be an important predictor in ruling out major vessel disease and luminal narrowing by atheroma.展开更多
Religion makes individuals more social friendly as its teachings mainly focus on social responsibilities.So,it is clear that practical aspects of the religions are common and social friendly.Yet in the modern world,co...Religion makes individuals more social friendly as its teachings mainly focus on social responsibilities.So,it is clear that practical aspects of the religions are common and social friendly.Yet in the modern world,conflict among the devotees of different religions can be seen very commonly.Purpose of this research is to understand the Buddhist approach on other religious believes and believers.Documentary study on Pali Tipitaka is the method of data collecting and content analysis is used for data analysing in this research.Religion of a person can be defined as ones’point of view on self and the world.Buddhist teachings name these views as“Dhitthi”-viewpoints.Buddhist literature shows that Buddha and his disciples followed a unique approach on other religious believes and believers.This approach is having characteristics,such as:understanding how that believes occur,identifying the similarities and differences between other believes and Buddhist teachings,not to be emotional even being criticized,giving freedom to explain their point of view,encouraging to be open-minded,giving freedom to decide,and giving interpretations to the concepts other believer knows.Buddhist approach on other religious believes and believers is having a unique characteristics.It never discriminates the other religious believes and believers,and condemns them.It has a clear vision.That is helping individuals to overcome suffering.For that identity is not needed.展开更多
Back pain associated with lumbar disc herniation is a common musculoskeletal disorder that leads to absence at work place worldwide. Studies have proven in addition to the traditional factors, microbes play a role in ...Back pain associated with lumbar disc herniation is a common musculoskeletal disorder that leads to absence at work place worldwide. Studies have proven in addition to the traditional factors, microbes play a role in disc herniation causing chronic back pain. A 34-year-old male who has not involved in any traumatic work but has a family history of disc herniation presented with lower back pain and numbness in his right leg. He had previously undergone lumbar discectomy at L4/L5 ten years back. Magnetic Resonance Imaging (MRI) showed L5/S1 right para central disc herniation impinging on the right S1 and S2 nerve roots. Standard protocols for disinfection of instruments, external skin and all transport media were adhered. Skin scrapings, muscle biopsy and excised disc tissue were obtained for anaerobic and aerobic bacterial cultures. Anaerobic microbial cultures of excised disc tissue following lumbar discectomy showed Gram positive growth. Further anaerobic isolation carried out using RapID ANA ID kit confirmed the growth as Gemella morbillorum. In addition, neither of the control samples (muscle nor skin) had any anaerobic growth indicating the absence of contamination. Aerobic bacterial growth was not present in the skin, muscles and disc cultures. The study findings add to the available literature, on the role of microorganisms in lumbar disc herniation and future treatment regimens with antibiotics.展开更多
This study presents a novel approach to evaluate the rate of aggregate risk of Invasive Alien Plant Species. Using risk values and grade of importance of weights of risk factors which may reflect invasiveness of plant...This study presents a novel approach to evaluate the rate of aggregate risk of Invasive Alien Plant Species. Using risk values and grade of importance of weights of risk factors which may reflect invasiveness of plant species are considered. We use Linguistic Ordered Weighted Averaging operator to evaluate the grade of important of weights. Since the risk values and important weights are identified from two different linguistic term sets, fuzzy set theory techniques were used to combine the two sets. The rates obtained from the model were compared with NRA risk levels and the model was validated with data from known and non-invasive species. The model is improved by weighting the risk values of risk factors. The improved model produced significant results and resulted a better tracking system for identifying potential invaders than the conventional risk assessment.展开更多
A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian ...A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses(compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.展开更多
基金supported by Area of Excellence grants to Malik Peiris,K.Y.Yuen and Allan S.Lau(Grant AoE/M-12/06)from the Research Grants Council of Hong Kong and the Research Fund for Control of Infectious Disease(09080832),as well as grants to Allan S.Lau and Malik Peiris from the Research Grants Council Central Allocation(HKU 1/05C).
文摘Historically,influenza pandemics have arisen from avian influenza viruses.Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates.Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%,which has been attributed to dysregulation of the cytokine system.Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus.The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated.In the present study,we demonstrate that autophagy,a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents,plays a role in cytokine induction.Autophagy is induced to a greater extent by H9N2/G1,in association with cytokine hyperinduction,compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses.Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene,Atg5,we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-a expression in primary human blood macrophages.Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.
基金supported in part by Theme-based Research Scheme (Project No. T11-705/14N)the General Research Fund (HKU 780113M,17121214 and 17115015)+1 种基金Research Grants Council of the Hong Kong SARShenzhen Science and Technology Innovation Committee (JCYJ20140411175241066),China
文摘Natural killer （NK） cell is a key component of innate immunity and plays an important role in host defense against virus infection by directly destroying infected cells. Influenza is a respiratory disease transmitted in the early phase of virus infection. Evasion of host innate immunity including NK cells is critical for the virus to expand and establish a successful acute infection. Previously, we showed that human influenza HIN1 virus infects NK cells and induces cell apoptosis, as well as inhibits NK cell activity. In this study, we further demonstrated that avian influenza virus also directly targeted NK cells as an immunoevasion strategy. The avian virus infected human NK cells and induced cell apoptosis. In addition, avian influenza virion and HA protein inhibited NK cell cytotoxicity. This novel strategy has obvious advantages for avian influenza virus, allowing the virus sufficient time to expand and subsequent spread before the onset of the specific immune response. Our findings provide an important clue for the immunopathogenesis of avian influenza, and also suggest that direct targeting NK cells may be a common strategy used by both human and avian influenza viruses to evade NK cell immunity.
文摘<strong>Objective: </strong>The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment of severity and thrombocytopenia in dengue. <strong>Methods:</strong> A cross-sectional analytical study was carried out on diagnosed dengue patients admitted to Nawaloka Hospital, Sri Lanka. Blood samples were taken from patients (n = 50) on the day of admission, 3<sup>rd</sup> and 5<sup>th</sup> day from admission for analysis of GR, aspartate transaminase, alanine transaminase, platelets, white blood cells, and Atypical Lymphocytes (AL). <strong>Results:</strong> GR level of all three measured stages had a higher area under the curve (>88%), high sensitivity and specificity compared to liver transaminases. A significant regression model represents on admission GR and AL levels as predictive variables to platelet levels in day 03 from admission (Day 3 Platelet level = 127155.3 - 383 * GR - 0.431 * AL). <strong>Conclusion:</strong> Liver transaminases, GR, and AL% can be considered as a profile of predictive biomarkers in early diagnosis of severity of dengue infection. The degree of thrombocytopenia can be predicted using on admission GR and AL% level in acute dengue viral infection.
文摘Apart from the conventional factors, recent evidences have suggested that lumbar disc herniation (LDH) is also associated with microbes, which is completely ignored in the management of patients with disc prolapse and disc degeneration. Therefore, the present study was carried out to identify the different microorganisms in subjects with LDH. Subjects (n = 101) who were confirmed for LDH with Magnetic Resonance Imaging and undergoing lumbar discectomy, were recruited in this study. Standard protocols for disinfection of the skin and surgical instruments were adhered. Skin scrapings, muscle biopsies and portion of the inter-vertebral disc were transferred into individually labeled Robertson’s cooked meat enrichment broth for anaerobic identification. Remaining portions of the excised disc material and muscle biopsy were taken for aerobic identification. Anaerobic isolates were identified using Gram stain and catalase test while the species identification was done by RapID ANA II ID kit. Gram stain, catalase test, DNase test and coagulase tests were used for identification of aerobic bacteria. Study confirmed 6/101 disc cultures (6%) with positive anaerobes and 12 disc cultures with coagulase negative Staphylococci spp. Among the anaerobes, two disc cultures were identified as Propionibacterium acnes and one as Gemella morbillorum. Due to slow growth, other three anaerobic cultures were not confirmed. However, they resembled the colony morphology of Gram positive bacilli. None of the control samples (skin and muscles) had any positive growth. The present study adds to the literature confirming the role of microorganisms in LDH. Present study newly identified Gemella morbillorum in the intervertebral tissue in addition to the previously reported microorganisms associated with LDH.
文摘Wearable health-monitoring devices are novel and integral developments based on smart-textiles.Conventional wearable technology consists of micro-controllers and a variety of electronic devices embedded on the skin,or incorporated into the apparels,where they act as signal receptors,analytical devices and transmitters of the signals generated from the human body.Invasive methods are currently more commonly practiced where biofluids are obtained by penetrating the body by incision or injection,while in non-invasive methods no such penetrations take place.A critical review of current non-invasive wearable technology,including colorimetric,enzymatic,pH based,electrochemical and conductivity sensors,is presented in this paper along with the challenges and limitations they pose.Additionally,novel techniques of analysis have been explored concluding that a textile-based medium offers higher compatibility for integration of such sensors in comparison to other existing substrates.
文摘AIMTo assess the impact of multi-disciplinary teams (MDTs) management in optimising the outcome for rectal cancers. METHODSWe undertook a retrospective review of a prospectively maintained database of patients with rectal cancers (defined as tumours ≤ 15 cm from anal verge) discussed at our MDT between Jan 2008 and Jan 2011. The data was validated against the national database to ensure completeness of dataset. The clinical course and follow-up data was validated using the institution’s electronic patient records. The data was analysed in terms of frequencies and percentages. Significance of any differences were analysed using χ<sup>2</sup> test. A Kaplan-Meier analysis was performed for overall survival and disease free survival. RESULTSFollowing appropriate staging, one hundred and thirty-three patients were suitable for potentially curative resections. Seventy two (54%) were upper rectal cancer (URC) - tumour was > 6 cm from the anal verge and 61 (46%) were lower rectal cancers (LRC) - lower extent of the tumour was palpable ≤ 6 cm. Circumferential resection margin (CRM) appeared threatened on pre-operative MRI in 19/61 (31%) patients with LRC requiring neo-adjuvant therapy (NAT). Of the 133 resections, 118 (89%) were attempted laparoscopically (5% conversion rate). CRM was positive in 9 (6.7%) patients; Median lymph node harvest was 12 (2-37). Major complications occurred in 8 (6%) patients. Median follow-up was 53 mo (0-82). The 90-d mortality was 2 (1.5%). Over the follow-up period, disease related mortality was 11 (8.2%) and overall mortality was 39 (29.3%). Four (3%) patients had local recurrence and 22 (16.5%) patients had distant metastases. CONCLUSIONManagement of rectal cancers can be optimized with multi-disciplinary input to attain acceptable long-term oncological outcomes even when incorporating a laparoscopic approach to rectal cancer resection.
文摘Identification of redox markers may be of clinical significance in the management of dengue patients. This study is to identify the association between antioxidant enzymes, hematological parameters and liver transaminases in patients with acute dengue infection. Blood samples were taken from patients on the day of admission, day 05 and 07 from admission for analysis of glutathione peroxidase (GPX), glutathione reductase (GR), aspartate transaminase (AST), alanine transaminase (ALT) and hematological parameters. AST and ALT levels were significantly elevated (p < 0.05) on day 05 in dengue patients. In contrast, GPX and GR showed significantly low levels on day 05 compared to on the day of admission and day 07. Although there was a decline in the trend of platelets towards day 05, values were not significantly different. Dengue associated with liver injury appears to peak around day 05 when the GPX and GR enzymes levels in patients were the lowest suggesting that increased viral load in the acute phase of dengue infection has initiated an antioxidant imbalance. Thus, timely investigation of antioxidant enzymes (GR and GPX) and liver transaminases around day 05 of admission may be of value in the management of patients with dengue infection similar to as seen in platelet counts.
基金This work was supported by the following grants:the National Major Project for Control and Prevention of Infectious Disease in China(No.2018ZX10101002 and 2018ZX10732401)the National Key Research and Development Program of China(No.2016YFD0500301 and 2017YFC1200503)。
文摘The Middle East respiratory syndrome(MERS)is a lethal zoonosis caused by MERS coronavirus(MERS-CoV)and poses a significant threat to public health worldwide.Therefore,a rapid,sensitive,and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness.Here,we evaluated various novel luciferase immunosorbent assays(LISA)based on nucleocapsid protein(NP)as well as fragments derived from spike protein(S)including subunit 1(S1),N terminal domain(NTD),receptorbinding domain(RBD)and subunit 2(S2)of S for the detection of MERS-CoV-specific IgG.Fusion proteins,including nanoluciferase(NLuc)and various fragments derived from the NP or S protein of MERS-CoV,were expressed in human embryonic kidney 293 T cells.LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins.Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR,commercial S1-based ELISA,and pseudovirus particle neutralization test(ppNT).Our results showed that the S1-,RBD-,and NP-LISAs were more sensitive than the NTD-and S2-LISAs for the detection of anti-MERS-CoV IgG.Furthermore,the S1-,RBD-,and NP-LISAs were more sensitive(by at least 16-fold)than the commercially available S1-ELISA.Moreover,the S1-,RBD-,and NPLISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV(OC43,229E,HKU1,NL63)-infected patients.More importantly,these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels,monkeys,and mice,among which the RBD-LISA exhibited excellent performance.The results of this study suggest that the novel MERS-CoV RBD-and S1-LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples.These assays have the potential to be used as serologic tests for
基金Supported by National Research Council,Sri Lanka,Grant No.NRC 13-108
文摘AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative colitis(UC) or Crohn's disease(CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12 B :rs1045431, IL23 R :rs11805303, ARPC2 :rs12612347, IRGM :rs13361189, IL26/IL22 :rs1558744, CDH1 :rs1728785, IL10 :rs3024505, FCGR2 A :rs3737240, PTGER4 :rs4613763, IL17 REL/PIM3 :rs5771069, HNF4 a :rs6017342, STAT3 :rs744166, SMURF1 :rs7809799, LAMB1 :rs886774, HLA-DRB5, DQA1, DRB1, DRA :rs9268853, MST1, UBA7, and APEH :rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium(P > 10^(-3)). To account for multiple hypothesis testing, P-values < 0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms(SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774(LAMB1-gene) and UC(odds ratio(OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease(OR = 1.66, P < 0.001) and remained in remission(OR = 1.48, P < 0.001). A positive association was noted between rs10045431(IL 12 B gene) and upper gastrointestinal involvement in CD(OR = 4.76, P = 0.002). CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.
基金Funding support was provided by the Government of Canada
文摘Objective: To describe the symptoms of dengue at acute and post-infection stage and to identify preventive strategies adopted by the patients in the Western Province, Sri Lanka.Methods: This was a descriptive cross-sectional study conducted in the Western Province of Sri Lanka in November 2017. The study population consisted of 473 confirmed dengue patients aged from 18 to 64 years who were hospitalized between June and August 2017. A stratified random sampling technique was applied to select the participants. Data collection was done by trained interviewers, using a structured, pre-tested interviewer-administered questionnaire. Results: The most common symptoms of dengue fever at the acute stage was body ache(81.81%, n=387), followed by headache(71.67%, n=339), loss of appetite(66.80%, n=316), tiredness(53.06 %, n=251) and vomiting(41.86%, n=198). The most common symptom during the post-infection stage was body ache(48.62%, n=230), followed by fatigue(39.74%, n=188), and loss of appetite(28.75%, n=136). Adding sand to the water in places where water accumulates(41.64%, n=197) was the most common method used to prevent transmission of dengue followed by removing/draining stagnant water regularly(36.15%, n=177). Use of mosquito nets(83.08%, n=393) was the most common method in preventing mosquito bites followed by the use of fans among dengue patients(56.02%, n=265).Conclusions: The study shows a prolonged persistence of clinical symptoms during the postinfection period.
文摘A 66-year-old female with cryptogenic cirrhosis complicated by ascites,hepatic encephalopathy,variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique.Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow.The liver graft was recirculated without any hemodynamic instability.Subsequently,the patient became hypotensive progressing to asystole.She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle.The patient was noted to be coagulopathic at the time.She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.
基金supported by the National Institute of Allergy and Infectious Diseases (NIAID contract HHSN266200700005C)European Research Project SARS-DTV (contract no: SP22-CT-2004)
文摘Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses,which can be found from a wide range of mammals,were recently detected in bats. Strikingly,these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families,but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health.
文摘Atherosclerosis is the most important contributor to increasing burden of coronary artery disease (CAD). Growing evidence suggests that the ratios of Apo B/Apo A-I and Lp(a) are better indexes for risk assessment of CAD. Elevated plasma levels of lipoprotein(a) in humans represent a major in-herited risk factor for atherosclerosis. Thus, a study was performed to determine the association betwwen serum Apo B, Apo A-I, and lipoprotein(a) levels, and severity of CAD in patients with CAD confirmed on coronary angiography findings. An analytical case control study was carried out with 85 patients (58 males and 27 females) 40 - 60 years of age confirmed as having CAD on coronary angiography and 85 age and sex matched healthy volunteers as controls. Serum samples were an-alyzed for Apo A-1 LDL, Apo B, Apo A-I, and lipoprotein(a) concentration and the severity of CAD was assessed using coronary angiography scoring method. Patients with CAD had significantly high serum LDL-C, Apo B and Lp(a) levels compared to control subjects. However, serum Apo A-I level did not show a significant difference between two groups. Subjects with a positive family history of CAD with increased serum Lp(a) ≥ 17.3 mg/dL have high risk for development of CAD. Present study suggests that serum Lp(a) cut-off value of 17.3 mg/dL may be an important predictor in ruling out major vessel disease and luminal narrowing by atheroma.
文摘Religion makes individuals more social friendly as its teachings mainly focus on social responsibilities.So,it is clear that practical aspects of the religions are common and social friendly.Yet in the modern world,conflict among the devotees of different religions can be seen very commonly.Purpose of this research is to understand the Buddhist approach on other religious believes and believers.Documentary study on Pali Tipitaka is the method of data collecting and content analysis is used for data analysing in this research.Religion of a person can be defined as ones’point of view on self and the world.Buddhist teachings name these views as“Dhitthi”-viewpoints.Buddhist literature shows that Buddha and his disciples followed a unique approach on other religious believes and believers.This approach is having characteristics,such as:understanding how that believes occur,identifying the similarities and differences between other believes and Buddhist teachings,not to be emotional even being criticized,giving freedom to explain their point of view,encouraging to be open-minded,giving freedom to decide,and giving interpretations to the concepts other believer knows.Buddhist approach on other religious believes and believers is having a unique characteristics.It never discriminates the other religious believes and believers,and condemns them.It has a clear vision.That is helping individuals to overcome suffering.For that identity is not needed.
文摘Back pain associated with lumbar disc herniation is a common musculoskeletal disorder that leads to absence at work place worldwide. Studies have proven in addition to the traditional factors, microbes play a role in disc herniation causing chronic back pain. A 34-year-old male who has not involved in any traumatic work but has a family history of disc herniation presented with lower back pain and numbness in his right leg. He had previously undergone lumbar discectomy at L4/L5 ten years back. Magnetic Resonance Imaging (MRI) showed L5/S1 right para central disc herniation impinging on the right S1 and S2 nerve roots. Standard protocols for disinfection of instruments, external skin and all transport media were adhered. Skin scrapings, muscle biopsy and excised disc tissue were obtained for anaerobic and aerobic bacterial cultures. Anaerobic microbial cultures of excised disc tissue following lumbar discectomy showed Gram positive growth. Further anaerobic isolation carried out using RapID ANA ID kit confirmed the growth as Gemella morbillorum. In addition, neither of the control samples (muscle nor skin) had any anaerobic growth indicating the absence of contamination. Aerobic bacterial growth was not present in the skin, muscles and disc cultures. The study findings add to the available literature, on the role of microorganisms in lumbar disc herniation and future treatment regimens with antibiotics.
文摘This study presents a novel approach to evaluate the rate of aggregate risk of Invasive Alien Plant Species. Using risk values and grade of importance of weights of risk factors which may reflect invasiveness of plant species are considered. We use Linguistic Ordered Weighted Averaging operator to evaluate the grade of important of weights. Since the risk values and important weights are identified from two different linguistic term sets, fuzzy set theory techniques were used to combine the two sets. The rates obtained from the model were compared with NRA risk levels and the model was validated with data from known and non-invasive species. The model is improved by weighting the risk values of risk factors. The improved model produced significant results and resulted a better tracking system for identifying potential invaders than the conventional risk assessment.
基金supported in part by General Research Fund, Research Grants Council of Hong Kong (HKU 780113M)Area of Excellence program (AoE/M-12/06)+1 种基金University Grants Committee of Hong Kong SARResearch Fund for the Control of Infectious Diseases, Hong Kong SAR government (11100742)
文摘A novel avian influenza A(H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses(compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.
