Dermatophytoses are the most common dermatological conditions but they are however not life threatening or debilitating hence medical care is sought usually due to aesthetic reasons and chronicity of the lesions despi...Dermatophytoses are the most common dermatological conditions but they are however not life threatening or debilitating hence medical care is sought usually due to aesthetic reasons and chronicity of the lesions despite several self-medications. The purpose of this study was to determine the distribution pattern of dermatophytes isolated in the medical microbiology laboratory of University of Port Harcourt teaching hospital (UPTH). This is a 5-year desk review of the Dermatophytes isolated in the medical microbiology laboratory of UPTH. Relevant Patients’ data were retrieved and analyzed. A total of seventy (70) dermatophytes were isolated over the five-year period as follows: Trichophyton species accounted for 55 (79%), Epidermophyton species were 8 (11%) and Microsporum species 7 (10%). The peak age range of patients from which dermatophytes were isolated was 31 - 40 years with a male to female ratio of 1:1.7. The majority of patients being 49 (70%) were referred from the dermatology outpatient clinic (DOPC) and the most frequent clinical diagnosis was Tinea corporis. Trichophyton species were the commonest cause of dermatophytoses in adult patients in Port Harcourt where the most common clinical presentation was Tinea corporis.展开更多
Often time people love the title medical,if you ask most children while growing up,most wanted to be medical doctors.Whether they are from rich background or poor background,whether they are from educational backgroun...Often time people love the title medical,if you ask most children while growing up,most wanted to be medical doctors.Whether they are from rich background or poor background,whether they are from educational background or disadvantaged background,most wanted to be doctors.展开更多
Microbiology Research Laboratory(MRL)is a biosafety level-2(BSL-2)research laboratory located at the main campus of Faculty of Medicine,Ain Shams University(ASU)in Cairo.With the objective of strengthening the departm...Microbiology Research Laboratory(MRL)is a biosafety level-2(BSL-2)research laboratory located at the main campus of Faculty of Medicine,Ain Shams University(ASU)in Cairo.With the objective of strengthening the departmental capacities of biosafety,a series of activities were carried out between October 2019,and January 2020 to raise awareness,along with instilling standard biosafety practices and procedures among laboratory staff including non-health professions.MRL staff were categorized according to their biosafety knowledge into three tiers:tier(1):with zero to minimal knowledge,tier(2):with basic knowledge,tier(3):with satisfactory knowledge.Tier based activities were designed to align with their job responsibilities.Results:44 selected laboratory staff were trained on biosafety practices:12 from tier(1),19 from tier(2)and 13 constituted tier(3).Through regular follow-ups,the impact of the implemnted training plan was reflected on the practices and knowledge of all laboratory staff.Knowledge among health professions has increased by 60%.Furthermore,6 staff members have granted a biosafety certification by International Federation of Biosafety Association(IFBSA).Conclusion:establishing a culture of biosafety within microbiology research laboratories is integral to safe research practices.Together with developing local and national biosafety regulations and policies will ensure research advancement without compromising public health or environmental safety.展开更多
Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study...Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.展开更多
During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increase...During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.展开更多
Inflammatory bowel diseases(IBDs)are classified into two distinct types based on the area and severity of inflammation:Crohn's disease(CD)and ulcerative colitis.In CD,gut bacteria can infiltrate mesenteric fat,cau...Inflammatory bowel diseases(IBDs)are classified into two distinct types based on the area and severity of inflammation:Crohn's disease(CD)and ulcerative colitis.In CD,gut bacteria can infiltrate mesenteric fat,causing expansion known as creeping fat,which may limit bacterial spread and inflammation but can promote fibrosis.The gut bacteria composition varies depending on whether the colon or ileum is affected.Fecal microbiota transplantation(FMT)transfers feces from a healthy donor to restore gut microbiota balance,often used in IBD patients to reduce inflammation and promote mucosal repair.The use of FMT for CD rema-ins uncertain,with insufficient evidence to fully endorse it as a definitive treat-ment.While some studies suggest it may improve symptoms,questions about the duration of these improvements and the need for repeated treatments persist.There is a pressing need for methods that provide long-term benefits,as high-lighted by Wu et al's research.展开更多
Background:The German Military Medical Service contributed to the medical screening of unaccompanied minor refugees(UMRs)coming to Germany in 2014 and 2015.In this study,a broad range of diagnostic procedures was appl...Background:The German Military Medical Service contributed to the medical screening of unaccompanied minor refugees(UMRs)coming to Germany in 2014 and 2015.In this study,a broad range of diagnostic procedures was applied to identify microorganisms with clinical or public health significance.Previously,those tests had only been used to screen soldiers returning from tropical deployments.This instance is the first time the approach has been studied in a humanitarian context.Methods:The offered screenings included blood cell counts,hepatitis B serology and microscopy of the stool to look for protozoa and worm eggs as well as PCR from stool samples targeting pathogenic bacteria,protozoa and helminths.If individuals refused certain assessments,their decision to do so was accepted.A total of 219 apparently healthy male UMRs coming from Afghanistan,Egypt,Somalia,Eritrea,Syria,Ghana,Guinea,Iran,Algeria,Iraq,Benin,Gambia,Libya,Morocco,Pakistan,and Palestine were assessed.All UMRs who were examined at the study department were included in the assessment.Results:We detected decreasing frequencies of pathogens that included diarrhoea-associated bacteria[Campylobacter(C.)jejuni,enteropathogenic Escherichia(E.)coli(EPEC),enterotoxic E.coli(ETEC),enteroaggregative E.coli(EAEC),enteroinvasive E.coli(EIEC)/Shigella spp.),Giardia(G.)duodenalis,helminths(comprising Schistosoma spp.,Hymenolepis(H.)nana,Strongyloides(S.)stercoralis]as well as hepatitis B virus.Pathogenic microorganisms dominated the samples by far.While G.duodenalis was detected in 11.4%of the assessed UMRs,the incidence of newly identified cases in the German population was 4.5 cases per 100,000 inhabitants.Conclusion:We conclude that the applied in-house PCR screening systems,which have proven to be useful for screening military returnees from tropical deployments,can also be used for health assessment of immigrants from the respective sites.Apparently healthy UMRs may be enterically colonized with a broad variety of pathogenic and apathogenic microorganisms.Increased colonization rates,as shown for G.duodenalis,can pose a hygiene problem in centralized homes for asylum seekers.展开更多
To our knowledge,this is the first study to conduct an objective assessment of the routine decontamination practices at a medical microbiology research laboratory(MRL)a year after a biosafety training was provided to ...To our knowledge,this is the first study to conduct an objective assessment of the routine decontamination practices at a medical microbiology research laboratory(MRL)a year after a biosafety training was provided to all laboratory staff.Between March 28th and June 28th,2021,unobtrusive observations were carried out to identify-three high-touch surfaces at the MRL during different working hours.Swabbing was used to evaluate the effectiveness of the disinfectant used in the laboratory.All three high-touch surfaces were sampled before and after decontamination with 200 ppm of 5%sodium hypochlorite(household bleach)to quantify the microbial load and identify the types of organisms residing on the laboratory surfaces.A higher concentration(500 ppm)of 5%sodium hypochlorite was employed after refresher training was provided to housekeeping staff,and resampling of the three surfaces was carried out during a 4-week follow-up period using the same procedure.The three high-touch surfaces identified were the two sides of the workbench(22%–24%)and the front surface of one incubator(14%).Anthracoid bacilli and Staphylococcus aureus were the most commonly found organisms on laboratory surfaces preintervention(100%and 89%,respectively)and post-intervention(56%and 44%,respectively).Other microorganisms detected included Salmonella spp.(27.7%),Proteus spp.(5.6%),Escherichia coli(5.6%),and Klebsiella spp.(33.3%).Employing a higher concentration(500 ppm)of sodium hypochlorite significantly(p<0.000)reduced the total aerobic colony count from an average of 15–250 cfu/cm2 to 10–60 cfu/cm^(2).This study demonstrated suboptimal decontamination practices at the MRL and the need to apply a higher concentration(500 ppm)of sodium hypochlorite to reduce the overall microbial load.It also demonstrated the importance of quantitative assessment to monitor decontamination practices and ensure staff compliance.More studies are needed to identify bacterial communities within the laboratory,which will help provide guidance regarding the types,proper concentrations,and appropriateness of the in-use disinfectants.Furthermore,large-scale studies on the acceptable level of residual contamination following any decontamination process are urgently recommended.展开更多
In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR)...In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR), University of Ghana. The ARL which hitherto was used for routine clinical research in viral, bacteria and immunological studies has since been the facility of choice for testing for all suspected cases of COVID-19 submitted from across Ghana and beyond. The success of testing at the ARL hinged on the availability of several laboratory spaces furnished with state-of-the-art diagnostic equipment and working aids. During the “peak season” where overwhelming numbers of clinical specimens were received, the ARL processed and got results for close to four thousand samples daily. After general disinfection and re-bagging into smaller numbers, at the entrance of the ARL, the samples are taken to a central receiving laboratory, where they are received and entered in a database with accompanying case investigation forms. All samples that are successfully sorted and matched are sent to general laboratories for nucleic acid extraction and then referred to the Instrumentation laboratory for real time reverse-transcription polymerase chain reaction (RT-PCR). When the RT-PCRs were completed, results were analysed and transmitted via email and/or local network to the data reporting office. The data managers then reported results to the investigators and the Ghana Health Service (GHS). Additionally, the ARL provided a next-generation Genome Sequencing platform in partnership with the West African Centre for Cell Biology of Infectious Pathogens at the University of Ghana, which was essential in reporting the genome data of the circulating variants of SARS-CoV-2 in Ghana. Conclusively, it is worth noting, that the NMIMR fulfilled its mandate of supporting the country with specialized diagnostics through the judicious use of the ARL for SARS-CoV-2 testing, from sample receipt to data reporting. The ARL facility and the research faculty have trained and continue to train budding laboratories on biosafety, biosecurity, best practices and testing protocols. It is obvious that the success story of SARS-CoV-2 testing in Ghana, cannot be complete without the mention of the ARL at NMIMR.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most count...Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.展开更多
Objective:To investigate the role of CRX-527,a Toll-like receptor 4 agonist,as the possible adjuvant for recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing merozoite surface protein 1C(BCG-MSP-1C).Met...Objective:To investigate the role of CRX-527,a Toll-like receptor 4 agonist,as the possible adjuvant for recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing merozoite surface protein 1C(BCG-MSP-1C).Methods:The mice were immunized with BCG and BCG-MSP-1C in the presence and absence of CRX-527.The untreated mice(injected with PBS-T80 only)were the negative control.The ability of CRX-527 to enhance IgG and its subclasses,as well as IL-4 and IFN-γproduction in the serum and spleen supernatant was evaluated using ELISA.Results:Mice immunized with BCG-MSP-1C exhibited the highest production of IgGs,IL-4 and IFN-γafter third immunization.In addition,CRX-527 further promoted the production of total IgG and IgG subclasses as well as IFN-γand IL-4 in the serum and splenocytes of immunized mice.Conclusions:CRX-527 has the potential as an adjuvant candidate for the candidate vaccines.Further study is needed to verify appropriate dosage for immunization and its efficacy.展开更多
Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples receiv...Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,2023.The results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and socio-demographics.Data was analyzed using descriptive statistics.Results:A total of 2141 stool samples from 1644 cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)surveillance.Both polioviruses(19/1644,1.15%)and non-polio enteroviruses(73/1644,4.44%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus isolated.Wild polioviruses or circulating VDPVs were not detected among the cases.During all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14 days of receipt,ensuring timely reporting as per global guidelines.Conclusions:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance indicators.Non-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understandi...BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.展开更多
Vector-borne diseases caused by arthropod-borne viruses(arboviruses) are a considerable challenge to public health globally. Mosquito-borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of ...Vector-borne diseases caused by arthropod-borne viruses(arboviruses) are a considerable challenge to public health globally. Mosquito-borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of human illnesses and may be fatal. Currently, efforts to control these diseases still face challenges due to growing vector resistance towards insecticides, urbanization, and limited effective antiviral treatments and vaccines. Animal models are crucial in antiviral research on mosquito-borne arboviruses, playing a role in understanding disease mechanisms,vaccine development, and toxicity testing, but the application of animal models still faces the challenges of ethical considerations and animal-to-human translational success. Genetically engineered mouse models, hamster models and non-human primate(NHP) are currently used in arbovirus research, but new models such as tree shrews and novel humanized mice are emerging. In the context of Malaysian research, the use of long-tailed macaques as potential NHP models for arbovirus research is possible;however, it faces the ethical dilemma of using an endangered species for scientific purposes. Overall, animal models play a crucial role in advancing infectious disease research, but a balance between medical research and species conservation must be upheld.展开更多
In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid...In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF.展开更多
Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the out...Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the outbreak.Methods:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri Lanka.According to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,respectively.Selected RNA positive samples were sequenced at reference laboratory,India.Analysis of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella Laboratory.Data was analyzed using descriptive statistics.Results:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or both.Males(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive patients.All provinces reported measles positive cases.All samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing Victoria.Australia origin.Conclusions:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating globally.Further,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.展开更多
Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selecte...Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selected hospitals in Malaysia.Methods:A total of 192 K.pneumoniae isolates were collected and subjected to antibiotic susceptibility,hypermucoviscosity test and multiplex PCR to detect the presence of K1-and K2-serotype associated genes.Multilocus sequence typing(MLST)was performed on ESBL-producing K.pneumoniae isolates presented with K1 and K2 serotypes,followed by phylogenetic analysis.Results:A total of 87 out of 192(45.3%)of the K.pneumoniae isolates collected were ESBL producers.However,only 8.3%(16/192)and 10.9%(21/192)of the total isolates were detected to carry K1-and K2-serotype associated genes,respectively.Statistical analysis showed that K1 and K2 capsular serotypes were not significantly associated with ESBL phenotype(P=0.196).However,they were significantly associated with hypervirulent,as demonstrated by the positive string test(P<0.001).MLST analysis revealed that ST23 as the predominant sequence type(ST)in the K1 serotype,while the ST in the K2 serotype is more diverse.Conclusions:Although the occurrence of ESBL-producing isolates among the hypervirulent strains was low,their coexistence warrants the need for continuous surveillance.MLST showed that these isolates were genetically heterogeneous.展开更多
Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals ...Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.展开更多
This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spect...This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method.The frequency of resistance(FoR)to MEM combined with InC58 was investigated.Mutants were sequenced and tested for cross resistance,fitness,and the stability of the resistance phenotype.Compared with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(P.aeruginosa)and OXA-23-carrying Acinetobacter baumannii(A.baumannii).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,respectively.The mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.展开更多
Objective:To address the lack of research on invasive group B Streptococcus(GBS)infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals.Methods:Medical record...Objective:To address the lack of research on invasive group B Streptococcus(GBS)infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals.Methods:Medical records from patients with GBS infection isolated from the sterile site,such as blood and cerebrospinal fluid from 14 July 2019 to 15 December 2020,were reviewed from six major hospitals in Peninsular Malaysia.Inclusion criteria were invasive GBS,sterile sites and non-repeated GBS isolated from the same patients in the same admission.Viable isolates were re-identified for GBS and serotyped.Results:A total of 118 patients were eligible,with a majority of non-pregnant adults(76.3%).Over half of the patients(62.7%)had underlying medical conditions,with diabetes as the most common disease,followed by respiratory disease,renal disease,cardiovascular disease and skin and soft tissue disease.The most common manifestations were sepsis,followed by soft tissue abscess,diabetic foot ulcer,wet gangrene and cellulitis.The overall mortality was 7.6%.The most common serotype was serotype桋.Conclusions:Invasive GBS infection among non-pregnant adults showed a rising trend,particularly among diabetic individuals.The study underscores the importance of reducing risk factors and highlights the necessity of developing GBS vaccination as a preventive strategy for both infants and adults.展开更多
文摘Dermatophytoses are the most common dermatological conditions but they are however not life threatening or debilitating hence medical care is sought usually due to aesthetic reasons and chronicity of the lesions despite several self-medications. The purpose of this study was to determine the distribution pattern of dermatophytes isolated in the medical microbiology laboratory of University of Port Harcourt teaching hospital (UPTH). This is a 5-year desk review of the Dermatophytes isolated in the medical microbiology laboratory of UPTH. Relevant Patients’ data were retrieved and analyzed. A total of seventy (70) dermatophytes were isolated over the five-year period as follows: Trichophyton species accounted for 55 (79%), Epidermophyton species were 8 (11%) and Microsporum species 7 (10%). The peak age range of patients from which dermatophytes were isolated was 31 - 40 years with a male to female ratio of 1:1.7. The majority of patients being 49 (70%) were referred from the dermatology outpatient clinic (DOPC) and the most frequent clinical diagnosis was Tinea corporis. Trichophyton species were the commonest cause of dermatophytoses in adult patients in Port Harcourt where the most common clinical presentation was Tinea corporis.
文摘Often time people love the title medical,if you ask most children while growing up,most wanted to be medical doctors.Whether they are from rich background or poor background,whether they are from educational background or disadvantaged background,most wanted to be doctors.
文摘Microbiology Research Laboratory(MRL)is a biosafety level-2(BSL-2)research laboratory located at the main campus of Faculty of Medicine,Ain Shams University(ASU)in Cairo.With the objective of strengthening the departmental capacities of biosafety,a series of activities were carried out between October 2019,and January 2020 to raise awareness,along with instilling standard biosafety practices and procedures among laboratory staff including non-health professions.MRL staff were categorized according to their biosafety knowledge into three tiers:tier(1):with zero to minimal knowledge,tier(2):with basic knowledge,tier(3):with satisfactory knowledge.Tier based activities were designed to align with their job responsibilities.Results:44 selected laboratory staff were trained on biosafety practices:12 from tier(1),19 from tier(2)and 13 constituted tier(3).Through regular follow-ups,the impact of the implemnted training plan was reflected on the practices and knowledge of all laboratory staff.Knowledge among health professions has increased by 60%.Furthermore,6 staff members have granted a biosafety certification by International Federation of Biosafety Association(IFBSA).Conclusion:establishing a culture of biosafety within microbiology research laboratories is integral to safe research practices.Together with developing local and national biosafety regulations and policies will ensure research advancement without compromising public health or environmental safety.
文摘Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.
基金supported by the National Institute of Environmental Health Sciences(R21ES035492,R21ES035969)National Institutes of Child Health(R01HD090214)(to PA).
文摘During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.
文摘Inflammatory bowel diseases(IBDs)are classified into two distinct types based on the area and severity of inflammation:Crohn's disease(CD)and ulcerative colitis.In CD,gut bacteria can infiltrate mesenteric fat,causing expansion known as creeping fat,which may limit bacterial spread and inflammation but can promote fibrosis.The gut bacteria composition varies depending on whether the colon or ileum is affected.Fecal microbiota transplantation(FMT)transfers feces from a healthy donor to restore gut microbiota balance,often used in IBD patients to reduce inflammation and promote mucosal repair.The use of FMT for CD rema-ins uncertain,with insufficient evidence to fully endorse it as a definitive treat-ment.While some studies suggest it may improve symptoms,questions about the duration of these improvements and the need for repeated treatments persist.There is a pressing need for methods that provide long-term benefits,as high-lighted by Wu et al's research.
文摘Background:The German Military Medical Service contributed to the medical screening of unaccompanied minor refugees(UMRs)coming to Germany in 2014 and 2015.In this study,a broad range of diagnostic procedures was applied to identify microorganisms with clinical or public health significance.Previously,those tests had only been used to screen soldiers returning from tropical deployments.This instance is the first time the approach has been studied in a humanitarian context.Methods:The offered screenings included blood cell counts,hepatitis B serology and microscopy of the stool to look for protozoa and worm eggs as well as PCR from stool samples targeting pathogenic bacteria,protozoa and helminths.If individuals refused certain assessments,their decision to do so was accepted.A total of 219 apparently healthy male UMRs coming from Afghanistan,Egypt,Somalia,Eritrea,Syria,Ghana,Guinea,Iran,Algeria,Iraq,Benin,Gambia,Libya,Morocco,Pakistan,and Palestine were assessed.All UMRs who were examined at the study department were included in the assessment.Results:We detected decreasing frequencies of pathogens that included diarrhoea-associated bacteria[Campylobacter(C.)jejuni,enteropathogenic Escherichia(E.)coli(EPEC),enterotoxic E.coli(ETEC),enteroaggregative E.coli(EAEC),enteroinvasive E.coli(EIEC)/Shigella spp.),Giardia(G.)duodenalis,helminths(comprising Schistosoma spp.,Hymenolepis(H.)nana,Strongyloides(S.)stercoralis]as well as hepatitis B virus.Pathogenic microorganisms dominated the samples by far.While G.duodenalis was detected in 11.4%of the assessed UMRs,the incidence of newly identified cases in the German population was 4.5 cases per 100,000 inhabitants.Conclusion:We conclude that the applied in-house PCR screening systems,which have proven to be useful for screening military returnees from tropical deployments,can also be used for health assessment of immigrants from the respective sites.Apparently healthy UMRs may be enterically colonized with a broad variety of pathogenic and apathogenic microorganisms.Increased colonization rates,as shown for G.duodenalis,can pose a hygiene problem in centralized homes for asylum seekers.
基金This study was approved by the Ethical and Moral Committee of the Faculty of Medicine,Ain Shams University,Cairo,Egypt(No.:FMASU M S).
文摘To our knowledge,this is the first study to conduct an objective assessment of the routine decontamination practices at a medical microbiology research laboratory(MRL)a year after a biosafety training was provided to all laboratory staff.Between March 28th and June 28th,2021,unobtrusive observations were carried out to identify-three high-touch surfaces at the MRL during different working hours.Swabbing was used to evaluate the effectiveness of the disinfectant used in the laboratory.All three high-touch surfaces were sampled before and after decontamination with 200 ppm of 5%sodium hypochlorite(household bleach)to quantify the microbial load and identify the types of organisms residing on the laboratory surfaces.A higher concentration(500 ppm)of 5%sodium hypochlorite was employed after refresher training was provided to housekeeping staff,and resampling of the three surfaces was carried out during a 4-week follow-up period using the same procedure.The three high-touch surfaces identified were the two sides of the workbench(22%–24%)and the front surface of one incubator(14%).Anthracoid bacilli and Staphylococcus aureus were the most commonly found organisms on laboratory surfaces preintervention(100%and 89%,respectively)and post-intervention(56%and 44%,respectively).Other microorganisms detected included Salmonella spp.(27.7%),Proteus spp.(5.6%),Escherichia coli(5.6%),and Klebsiella spp.(33.3%).Employing a higher concentration(500 ppm)of sodium hypochlorite significantly(p<0.000)reduced the total aerobic colony count from an average of 15–250 cfu/cm2 to 10–60 cfu/cm^(2).This study demonstrated suboptimal decontamination practices at the MRL and the need to apply a higher concentration(500 ppm)of sodium hypochlorite to reduce the overall microbial load.It also demonstrated the importance of quantitative assessment to monitor decontamination practices and ensure staff compliance.More studies are needed to identify bacterial communities within the laboratory,which will help provide guidance regarding the types,proper concentrations,and appropriateness of the in-use disinfectants.Furthermore,large-scale studies on the acceptable level of residual contamination following any decontamination process are urgently recommended.
文摘In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR), University of Ghana. The ARL which hitherto was used for routine clinical research in viral, bacteria and immunological studies has since been the facility of choice for testing for all suspected cases of COVID-19 submitted from across Ghana and beyond. The success of testing at the ARL hinged on the availability of several laboratory spaces furnished with state-of-the-art diagnostic equipment and working aids. During the “peak season” where overwhelming numbers of clinical specimens were received, the ARL processed and got results for close to four thousand samples daily. After general disinfection and re-bagging into smaller numbers, at the entrance of the ARL, the samples are taken to a central receiving laboratory, where they are received and entered in a database with accompanying case investigation forms. All samples that are successfully sorted and matched are sent to general laboratories for nucleic acid extraction and then referred to the Instrumentation laboratory for real time reverse-transcription polymerase chain reaction (RT-PCR). When the RT-PCRs were completed, results were analysed and transmitted via email and/or local network to the data reporting office. The data managers then reported results to the investigators and the Ghana Health Service (GHS). Additionally, the ARL provided a next-generation Genome Sequencing platform in partnership with the West African Centre for Cell Biology of Infectious Pathogens at the University of Ghana, which was essential in reporting the genome data of the circulating variants of SARS-CoV-2 in Ghana. Conclusively, it is worth noting, that the NMIMR fulfilled its mandate of supporting the country with specialized diagnostics through the judicious use of the ARL for SARS-CoV-2 testing, from sample receipt to data reporting. The ARL facility and the research faculty have trained and continue to train budding laboratories on biosafety, biosecurity, best practices and testing protocols. It is obvious that the success story of SARS-CoV-2 testing in Ghana, cannot be complete without the mention of the ARL at NMIMR.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
基金supported by the Ministry of Higher Education Malaysia for Fundamental Research Grant Scheme with Project Code:FRGS/1/2021/SKK06/USM/002/4.
文摘Objective:To investigate the role of CRX-527,a Toll-like receptor 4 agonist,as the possible adjuvant for recombinant Mycobacterium bovis Bacillus Calmette-Guerin expressing merozoite surface protein 1C(BCG-MSP-1C).Methods:The mice were immunized with BCG and BCG-MSP-1C in the presence and absence of CRX-527.The untreated mice(injected with PBS-T80 only)were the negative control.The ability of CRX-527 to enhance IgG and its subclasses,as well as IL-4 and IFN-γproduction in the serum and spleen supernatant was evaluated using ELISA.Results:Mice immunized with BCG-MSP-1C exhibited the highest production of IgGs,IL-4 and IFN-γafter third immunization.In addition,CRX-527 further promoted the production of total IgG and IgG subclasses as well as IFN-γand IL-4 in the serum and splenocytes of immunized mice.Conclusions:CRX-527 has the potential as an adjuvant candidate for the candidate vaccines.Further study is needed to verify appropriate dosage for immunization and its efficacy.
文摘Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,2023.The results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and socio-demographics.Data was analyzed using descriptive statistics.Results:A total of 2141 stool samples from 1644 cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)surveillance.Both polioviruses(19/1644,1.15%)and non-polio enteroviruses(73/1644,4.44%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus isolated.Wild polioviruses or circulating VDPVs were not detected among the cases.During all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14 days of receipt,ensuring timely reporting as per global guidelines.Conclusions:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance indicators.Non-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.
文摘BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.
文摘Vector-borne diseases caused by arthropod-borne viruses(arboviruses) are a considerable challenge to public health globally. Mosquito-borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of human illnesses and may be fatal. Currently, efforts to control these diseases still face challenges due to growing vector resistance towards insecticides, urbanization, and limited effective antiviral treatments and vaccines. Animal models are crucial in antiviral research on mosquito-borne arboviruses, playing a role in understanding disease mechanisms,vaccine development, and toxicity testing, but the application of animal models still faces the challenges of ethical considerations and animal-to-human translational success. Genetically engineered mouse models, hamster models and non-human primate(NHP) are currently used in arbovirus research, but new models such as tree shrews and novel humanized mice are emerging. In the context of Malaysian research, the use of long-tailed macaques as potential NHP models for arbovirus research is possible;however, it faces the ethical dilemma of using an endangered species for scientific purposes. Overall, animal models play a crucial role in advancing infectious disease research, but a balance between medical research and species conservation must be upheld.
基金Supported by The Hubei Provincial Natural Science Foundation of China,No.2020CFB656.
文摘In this editorial,we comment on the article published in the recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function.Ferroptosis and pyroptosis,cell death forms that can be initiated or blocked concurrently,can play significant roles in developing inflammation and various malignancies.However,their roles in ALF remain unclear.The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF,and revealed that the silent information regulator sirtuin 1(SIRT1)inhibits both pathways through p53,dramatically reducing inflammation and protecting hepatocytes.This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF.Thus,we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms.Additionally,we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways,as well as examples of SIRT1 activators being used as disease treatment strategies,providing new insights into the therapy of ALF.
文摘Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the outbreak.Methods:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri Lanka.According to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,respectively.Selected RNA positive samples were sequenced at reference laboratory,India.Analysis of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella Laboratory.Data was analyzed using descriptive statistics.Results:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or both.Males(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive patients.All provinces reported measles positive cases.All samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing Victoria.Australia origin.Conclusions:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating globally.Further,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.
基金supported by the Ministry of Higher Education under the Fundamental Research Grant Scheme(FRGS/1/2021/SKK0/UPM/02/8)the Universiti Putra Malaysia Research University Grant Scheme(GP/IPS/2021/9702000).
文摘Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selected hospitals in Malaysia.Methods:A total of 192 K.pneumoniae isolates were collected and subjected to antibiotic susceptibility,hypermucoviscosity test and multiplex PCR to detect the presence of K1-and K2-serotype associated genes.Multilocus sequence typing(MLST)was performed on ESBL-producing K.pneumoniae isolates presented with K1 and K2 serotypes,followed by phylogenetic analysis.Results:A total of 87 out of 192(45.3%)of the K.pneumoniae isolates collected were ESBL producers.However,only 8.3%(16/192)and 10.9%(21/192)of the total isolates were detected to carry K1-and K2-serotype associated genes,respectively.Statistical analysis showed that K1 and K2 capsular serotypes were not significantly associated with ESBL phenotype(P=0.196).However,they were significantly associated with hypervirulent,as demonstrated by the positive string test(P<0.001).MLST analysis revealed that ST23 as the predominant sequence type(ST)in the K1 serotype,while the ST in the K2 serotype is more diverse.Conclusions:Although the occurrence of ESBL-producing isolates among the hypervirulent strains was low,their coexistence warrants the need for continuous surveillance.MLST showed that these isolates were genetically heterogeneous.
基金funded by the grant National Key R&D Program of China(2017ZX10103011-004 and 2018YFC1603804)the Science and Technology Program of Guangdong Province(2018B020207013 and 2019B030316013).
文摘Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China.Methods This study included individuals aged 28 days–85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA.Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0–1 year,and RVA is the key pathogen circulating in patients 6–10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains.Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.
基金supported by the Ineos Oxford Institute for Antimicrobial Research,the Biotechnology and Biological Sciences Research Council(BB/V003291/1)the WellcomeTrust(106244/Z/14/Z).
文摘This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution method.The frequency of resistance(FoR)to MEM combined with InC58 was investigated.Mutants were sequenced and tested for cross resistance,fitness,and the stability of the resistance phenotype.Compared with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(P.aeruginosa)and OXA-23-carrying Acinetobacter baumannii(A.baumannii).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,respectively.The mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.
基金the Research Grants from Universiti Putra Malaysia(UPM/800-3/3/1/GPB/2020/9683800)Ministry of Higher Education under the Fundamental Research Grant Scheme(FRGS/1/2023/WAB04/UPM/01/4).
文摘Objective:To address the lack of research on invasive group B Streptococcus(GBS)infections in Malaysia and Southeast Asia through a comprehensive analysis of GBS isolates obtained from hospitals.Methods:Medical records from patients with GBS infection isolated from the sterile site,such as blood and cerebrospinal fluid from 14 July 2019 to 15 December 2020,were reviewed from six major hospitals in Peninsular Malaysia.Inclusion criteria were invasive GBS,sterile sites and non-repeated GBS isolated from the same patients in the same admission.Viable isolates were re-identified for GBS and serotyped.Results:A total of 118 patients were eligible,with a majority of non-pregnant adults(76.3%).Over half of the patients(62.7%)had underlying medical conditions,with diabetes as the most common disease,followed by respiratory disease,renal disease,cardiovascular disease and skin and soft tissue disease.The most common manifestations were sepsis,followed by soft tissue abscess,diabetic foot ulcer,wet gangrene and cellulitis.The overall mortality was 7.6%.The most common serotype was serotype桋.Conclusions:Invasive GBS infection among non-pregnant adults showed a rising trend,particularly among diabetic individuals.The study underscores the importance of reducing risk factors and highlights the necessity of developing GBS vaccination as a preventive strategy for both infants and adults.