BACKGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood products.In India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodefi...BACKGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood products.In India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV)-I/II,malaria,and syphilis is mandatory before blood transfusions.Worldwide,HCV,HBV,and HIV are the leading viruses causing mortality,affecting millions of people globally,including those with co-infections of HIV/HCV and HIV/HBV.Studies highlight the impact of TTIs on life expectancy and health risks,such as liver cirrhosis,cancer,and other diseases in individuals with chronic HBV.Globally,millions of blood donations take place annually,emphasizing the importance of maintaining blood safety.AIM To study the prevalence of TTIs,viz.,HBV,HCV,HIV I/II,syphilis,and malaria parasite(MP),among different blood donor groups.METHODS The study assessed the prevalence of TTIs among different blood donor groups in Delhi,India.Groups included total donors,in-house donors,total camp donors,institutional camp donors,and community camp donors.Tests for HIV,HBV,and HCV were done using enzyme-linked immunosorbent assay,while syphilis was tested with rapid plasma reagins and MP rapid card methods.The prevalence of HBV,HCV,HIV,and syphilis,expressed as percentages.Differences in infection rates between the groups were analyzed usingχ²tests and P-values(less than 0.05).RESULTS The study evaluated TTIs among 42158 blood donors in Delhi.The overall cumulative frequency of TTIs in total blood donors was 2.071%,and the frequencies of HBV,HCV,HIV-I/II,venereal disease research laboratory,and MP were 1.048%,0.425%,0.221%,0.377%,and 0.0024%,respectively.In-house donors,representing 37656 donors,had the highest transfusion transmissible infection(TTI)prevalence at 2.167%.Among total camp donors(4502 donors),TTIs were identified in 1.266%of donors,while community camp donors(2439 donors)exhibited a prevalence of 1.558%.Institutional camp donors(2063 donors)had the lowest TTI prevalence at 0.921%.Statistical analysis revealed significant differences in overall TTI prevalence,with total and in-house donors exhibiting higher rates compared to camp donors.CONCLUSION Ongoing monitoring and effective screening programs are essential for minimizing TTIs.Customizing blood safety measures for different donor groups and studying socio-economic-health factors is essential to improving blood safety.展开更多
Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous eff...Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous efforts have been devoted towards the development of such humanized mouse models. This review is focused on human lymphohematopoietic reconstitution and immune function in humanized mice by cotransplantation of human fetal thymic tissue and CD34＋ cells. The potential use of these humanized mice in translational biomedical research is also discussed.展开更多
AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected p...AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.展开更多
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
Background Interferon （IFN） can inhibit human immunodeficiency virus type 1 （HIV-1） replication in vitro and in clinic.However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its ...Background Interferon （IFN） can inhibit human immunodeficiency virus type 1 （HIV-1） replication in vitro and in clinic.However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon α （slFNα）.Methods We performed in vitro experiments with HIV-1 IIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of slFNα in severe combined immunodeficient （SClD） mice reconstituted with human peripheral blood leukocytes （hu-PBL-SClD mice）.Results We found that the 50% effective concentrations （EC5o） of slFNα against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed： with 0.45 μg and 1.35 μg slFNα daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 μg sIFNα daily treatments resulted in a terminally complete protection.Conclusions slFNα shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus （HCV）.展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
BACKGROUND Chronic diarrhoea in people living with human immunodeficiency virus(PLHIV)/acquired immunodeficiency syndrome presents a diagnostic challenge,often resulting from opportunistic infections(OIs),malignancies...BACKGROUND Chronic diarrhoea in people living with human immunodeficiency virus(PLHIV)/acquired immunodeficiency syndrome presents a diagnostic challenge,often resulting from opportunistic infections(OIs),malignancies,or disease progression itself.We present a case of an advanced human immunodeficiency virus(HIV)patient with chronic diarrhoea,significant weight loss,and antiretroviral therapy(ART)non-compliance,highlighting the diagnostic dilemma between HIV wasting syndrome,OIs,and malignancy.CASE SUMMARY A 36-year-old female,diagnosed with HIV five years ago on family screening,presented with three months of profuse watery diarrhoea,associated with crampy abdominal pain and weight loss(14 kg,30%in 3 months).She was non-compliant with ART.There was no history of recent travel,food contamination,or tuberculosis contact.Fever episodes were mild and transient.Physical examination revealed pallor and bilateral pedal oedema without lymphadenopathy or organomegaly.Genital examination was unremarkable.Routine investigations revealed severe anaemia and confirmed PLHIV status.CD4 count was<36 cells/μL.Empirical treatment with nitazoxanide was initiated for possible cryptosporidiosis.After ruling out OIs,ART was restarted.With treatment,her diarrhoea resolved,and she tolerated oral intake.Nutritional support was provided,and she was discharged in stable condition with ART,prophylactic antibiotics,and followup instructions for further evaluation.CONCLUSION In ART-noncompliant PLHIV with chronic diarrhoea,distinguishing between HIV wasting syndrome,OIs(Cryptosporidium,Mycobacterium avium complex,cytomegalovirus colitis)and malignancies(non-Hodgkin lymphoma and anal carcinoma)are critical.Gradual CD4 decline,systemic inflammation,and malnutrition favour progressive HIV/acquired immunodeficiency syndrome rather than an acute OI or malignancy.Early recognition and management,including ART reinitiation and nutritional support,are crucial for prognosis.展开更多
BACKGROUND Transition is a critical period for adolescents as they begin to assume responsibility for their own health.Similarly,the shift from pediatric to adult healthcare represents a vulnerable phase,marked by uni...BACKGROUND Transition is a critical period for adolescents as they begin to assume responsibility for their own health.Similarly,the shift from pediatric to adult healthcare represents a vulnerable phase,marked by unique challenges in adolescent health care.Despite its importance,only a few studies have explored healthcare transition among adolescents in Uganda.AIM To identify factors associated with the transition to adult human immunodeficiency virus(HIV)-centered care among adolescents attending HIV/AIDS clinics in Uganda.METHODS A cross-sectional mixed-methods study was conducted among 265 adolescents,randomly selected from three antiretroviral therapy(ART)clinics,using a structured questionnaire.Focus group discussions and key informant interviews were conducted.Individuals aged 10-20 years who were actively enrolled in the ART program between January 4,2022 and January 30,2023 were recruited.The primary outcome of interest was the transition to adult care.Bivariate and multivariate analyses were performed for quantitative data,while content analysis was used to analyze qualitative data.RESULTS The prevalence of transition to adult care was 40.6%.Most participants were male(53.6%)and fell within the 13-15 age group(35.6%).Multivariate logistic regression analysis identified several factors significantly associated with transition to adult care:Age group 10-12 years[prevalence ratio(PR)=2.525,95%CI:2.121-2.944,P=0.002],Age group 13-15 years(PR=1.900,95%CI:1.196-3.416,P=0.001),successful viral load suppression(PR=1.534,95%CI:1.173-1.648,P=0.016),disclosure of HIV status to relatives(PR=5.001,95%CI:3.411-3.611,P=0.000),being prepared for transitioning(PR=5.417,95%CI:3.468-7.135,P=0.041)and having skilled pediatric caregivers(PR=3.724,95%CI:2.084-4.105,P=0.005).CONCLUSION Transition to adult care among adolescents was low.Improving transition outcomes may require strengthening individual support within the family context and integrating transition-focused care into existing specialized clinical settings to enhance the delivery of adolescent-friendly services.展开更多
Human immunodeficiency virus continues to pose a severe global and national public health threat.In Pakistan,human immunodeficiency virus incidence has risen alarmingly,with over 9700 new cases reported in the first n...Human immunodeficiency virus continues to pose a severe global and national public health threat.In Pakistan,human immunodeficiency virus incidence has risen alarmingly,with over 9700 new cases reported in the first nine months of 2024 alone.Transmission is fueled by unsafe sex,needle-sharing,and systemic healthcare lapses,including unscreened transfusions and reused instruments.Sociocultural stigma,limited awareness,and poor treatment adherence especially in rural and underserved areas compound the crisis.Men,transgender individuals,and children represent increasingly affected groups.The role of international bodies such as World Health Organization,United Nations Development Programme,and United Nations Women has been critical in expanding community-based care and education programs.Effective biomedical tools like preexposure prophylaxis and post-exposure prophylaxis offer preventive pro-mise but remain underutilized.Pakistan urgently needs an integrated,multispectral response i.e.,enhancing surveillance,ensuring antiretroviral therapy access,improving healthcare worker training,and promoting harm reduction and eliminating certain stigmas to control the epidemic and prevent further escalation.展开更多
Objectives:This study aimed to describe the development process of the peer precision-matching and health management mobile platform"Aspark"for people living with human immunodeficiency virus(HIV)(PLWH)and t...Objectives:This study aimed to describe the development process of the peer precision-matching and health management mobile platform"Aspark"for people living with human immunodeficiency virus(HIV)(PLWH)and to evaluate its usability.Methods:The study assembled a multidisciplinary research and development team comprising researchers,software engineers,art designers,clinical nursing specialists,HIV peer volunteers,and psychological counselors.The team employed an agile development model to iteratively build the platform.Using the social determinants of health framework and the interpersonal circumplex,we identified 14 matching variables for the mobile platform.A video production team was formed to create peer training videos on health management for PLWH.We integrated relevant tools to provide PLWH with various types of support,including informational,instrumental,emotional,affiliational,and appraisal assistance.From March to May 2024,the research team used convenience sampling to select 130 platform users.It administered an electronic questionnaire based on the System Usability Scale to evaluate the platform's overall usability.Results:The platform incorporates multiple functional modules,including"Precision Matching,""Drug Interaction Query,""Medication Reminder,""Health Management,""Mood Diary,""Community Discussion,"and"Activity Center,"achieving comprehensive coverage across informational,emotional,instrumental,social,and appraisal support.The precision matching module facilitates intelligent pairing between patients and peer volunteers;the health management module allows for the entry of test results and trend analysis;medication reminders and check-in features enhance medication adherence;the mood diary supports emotional recording and expressive writing;while the community module offers functions such as topic discussions,appointment scheduling,and organization of offline activities.Among the 130 valid questionnaires,more than 83%of users scored above 68 on the System Usability Scale,indicating that the platform demonstrates favourable usability.Conclusions:The"Aspark"platform offers a feasible and promising digital solution for precision matching in HIV peer support and health management,enabling healthcare providers to deliver personalized and continuous health support to patients through its functions.Well-designed clinical trials should be conducted in the future to evaluate the effectiveness of this tool.展开更多
Treatment adherence among people living with human immunodeficiency virus(PLWH)is a critical determinant of viral suppression and improved quality of life.Medication literacy,as a key factor influencing adherence,is i...Treatment adherence among people living with human immunodeficiency virus(PLWH)is a critical determinant of viral suppression and improved quality of life.Medication literacy,as a key factor influencing adherence,is itself shaped by various psychosocial variables.Existing studies suggest that human immunodeficiency virus(HIV)-related stigma,self-efficacy,and trust in healthcare providers serve as significant mediators in the relationship between health literacy and treatment adherence.This review systematically explores how medication literacy affects treatment adherence in PLWH through intermediary psychosocial mechanisms such as depression,anxiety,and social support.By synthesizing current evidence,we aim to inform the development of targeted psychosocial interventions to enhance treatment outcomes and quality of life for this population.Our findings provide an evidence-based foundation for nursing practice and support innovative strategies in comprehensive HIV care.展开更多
Leukocyte adhesion deficiency type-1 is frequently associated with otorhinolaryngological manifestations,most notably a high prevalence of otitis media.Although multiple case reports have documented an increased preva...Leukocyte adhesion deficiency type-1 is frequently associated with otorhinolaryngological manifestations,most notably a high prevalence of otitis media.Although multiple case reports have documented an increased prevalence of acute otitis media and mastoiditis in patients with LAD-1,no clinical or experimental studies have fully elucidated the pathophysiological mechanisms underlying this association.Despite guideline recommendations for urgent antibiotic therapy in immunocompromised patients with acute otitis media,a standardized treatment protocol for its complications remains lacking.Moreover,no established consensus exists regarding the optimal therapeutic approach for Leukocyte adhesion deficiency type-1associated cases.This report contributes to the scarce literature on acute mastoiditis in LAD-1 and underscores the need for a tailored,multidisciplinary approach.In the absence of standardized treatment protocols,further research is crucial to refine management strategies and improve outcomes in immunocompromised patients with acute otitis media complications.展开更多
Severe combined immunodeficiency disease(SCID),characterized by profound immune system dysfunction,can lead to life-threatening infections and death.Animal models play a pivotal role in elucidating biological processe...Severe combined immunodeficiency disease(SCID),characterized by profound immune system dysfunction,can lead to life-threatening infections and death.Animal models play a pivotal role in elucidating biological processes and advancing therapeutic strategies.Recent advances in gene-editing technologies,including zincfinger nucleases(ZFNs),transcription activator-like effector nucleases(TALENs),CRISPR/Cas9,and base editing,have significantly enhanced the generation of SCID models.These models have not only deepened our understanding of disease pathophysiology but have also driven progress in cancer therapy,stem cell transplantation,organ transplantation,and infectious diseasemanagement.Thisreviewprovidesa comprehensive overview of current SCID models generated using novel gene-editing approaches,highlighting their potential applications in translational medicine and their role in advancing biomedical research.展开更多
The long-term effects of combined antiretroviral therapy(ART)on liver fibrosis patterns in adults living with human immunodeficiency virus(HIV)and chronic hepatitis B virus(HBV)are not well understood.Therefore,this s...The long-term effects of combined antiretroviral therapy(ART)on liver fibrosis patterns in adults living with human immunodeficiency virus(HIV)and chronic hepatitis B virus(HBV)are not well understood.Therefore,this study aimed to investigate the trajectories of liver fibrosis and identify the associations of baseline variables with different patterns of liver fibrosis evolution.A total of 333 individuals with HIV/HBV co-infection and undergoing long-term ART were enrolled in this study.Demographic,clinical,and biochemical data were collected at baseline and during annual visits.Group-based trajectory models(GBTMs)were used to detect the patterns of liver fibrosis evolution based on longitudinal data of fibrosis-4(Fib-4)and aspartate aminotransferase to platelet ratio index(APRI)scores.Logistic regression analysis was performed to identify baseline predictors of liver fibrosis evolution.The median age of all participants was 33 years.Among them,89.5%initially received TDF-containing ART.GBTMs identified two distinct patterns of liver fibrosis evolution using either APRI or Fib-4 scores.The majority of individuals(78.5%for APRI and 75.3%for Fib-4;pattern A)showed stable or low fibrosis with no progression,while the remaining participants showed regression from high fibrosis levels(21.5%for APRI and 24.7%for Fib-4;pattern B).Pattern A participants were younger and had higher CD4^(+)cell counts,higher lymphocyte cell counts,higher white blood cell counts,and lower platelet counts at baseline compared to pattern B participants.For HIV/HBV co-infected patients with varying degrees of initial liver fibrosis,long-term ART has shown distinct patterns of alleviating liver fibrosis.展开更多
BACKGROUND The World Health Organization(WHO)recommends lumbar puncture(LP)procedures to assess the diagnosis of cryptococcal meningitis(CM)among patients with advanced human immunodeficiency virus(HIV)disease(AHD)wit...BACKGROUND The World Health Organization(WHO)recommends lumbar puncture(LP)procedures to assess the diagnosis of cryptococcal meningitis(CM)among patients with advanced human immunodeficiency virus(HIV)disease(AHD)with positive serum cryptococcal antigen(CrAg)and do not have evidence of CM.AIM To estimate pooled prevalence of uptake of LP,CM and mortality among patients with AHD.METHODS PubMed,Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024.LP uptake was defined as percentage of people who underwent LP procedures among those with AHD(CD4≤200 cells/mm3 or WHO stage III/IV)and positive serum CrAg.Using random effects models,we computed the pooled estimate of LP uptake,CM and mortality and 95%CI.Stratified analyses were used to compare uptake of LP between studies that involved multiple vs single sites,and mortality analyses between patients with positive and negative serum CrAg were performed.Sensitivity analysis on LP uptake was done by excluding prospective cohort studies that reported 100%uptake.RESULTS A total of 32 studies with 46890 people with AHD screened for serum CrAg and 2730(5.8%)had positive serum CrAg.Overall,pooled prevalence of LP uptake was 67.7%(95%CI:54.0-81.5).The overall pooled prevalence of CM was 54.3%(95%CI:39.7-69.0),and mortality was 6.2%(95%CI:4.5-8.0).There is disparities in the pooled prevalence of LP uptake with studies involving multiple sites having lower prevalence compared to those that involved single sites(54.8%vs 84.7%,P=0.004).By excluding prospective cohort studies that reported 100%uptake,the overall LP uptake was 54.5%(95%CI:38.8-70.1).The pooled prevalence of CM was significantly lower among studies that involved multiple sites compared to those that involved single sites(6.8%vs 8.1%,P≤0.001).Mortality was significantly twice as high among patients who had positive serum CrAg compared to those who had negative serum CrAg[risk ratio=2.0(95%CI:1.6-2.5),P≤0.001].CONCLUSION Nearly three to five in 10 people with AHD with positive serum CrAg did not have LP procedures done,indicating significant gaps in identifying patients with CM.Establishing a confirmed diagnosis of CM is critical to avoid exposing patients to subtherapeutic levels of antifungals preemptively.Capacity to perform LP and patient refusals are among the reasons for not performing the procedure.Capacity building in training health care providers to perform LP procedures and professional counselling to obtain patient consent are critical for appropriate treatment to reduce mortality associated with CM infection.展开更多
BACKGROUND Common variable immunodeficiency(CVID)is a primary antibody immunodeficiency disorder characterized by diminished IgG levels.Despite ongoing research,the precise pathogenesis of CVID remains unclear.Genetic...BACKGROUND Common variable immunodeficiency(CVID)is a primary antibody immunodeficiency disorder characterized by diminished IgG levels.Despite ongoing research,the precise pathogenesis of CVID remains unclear.Genetic factors account for only 10%-20%of cases,with an estimated incidence of 1 in 10000 to 1 in 100000,affecting individuals across all age groups.CASE SUMMARY We report the case of a 32-year-old man with CVID who presented with a chief complaint of“recurrent diarrhea and significant weight loss over the past 2 years”.Laboratory tests on admission showed fat droplets in stool,while other parameters were within normal ranges.Gastroscopy revealed a smooth gastric mucosa without bile retention or signs of Helicobacter pylori infection;however,the mucosa of the descending segment of the duodenum appeared rough.Further evaluation of the small intestine using computed tomography indicated no abnormalities.Finally,the whole-small bowel double-balloon enteroscopy(DBE)was performed,which revealed various phenotypic changes in the small intestinal mucosa.The patient was diagnosed with CVID,which improved after immunoglobulin therapy,with favorable follow-up outcomes.CONCLUSION Non-infectious enteropathy in CVID is rare.Therefore,DBE is essential for diagnosing small intestinal involvement in such cases.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and poor sleep are common among people with human immunodeficiency virus(PWH)and may mediate the impaired health-related quality of life(HRQoL)...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and poor sleep are common among people with human immunodeficiency virus(PWH)and may mediate the impaired health-related quality of life(HRQoL)seen in PWH and in people with MASLD.However,the prevalence and burden of poor sleep in PWH and MASLD is not well described.AIM To study the prevalence and multi-faceted relationship between MASLD,poor sleep,and HRQoL in PWH.METHODS In this cross-sectional,observational study,adult PWH and no other known cause of liver disease underwent controlled attenuated parameter(for hepatic fat)and liver stiffness measurement via vibration-controlled transient elastography at eight United States.centers(July 2021 to November 2024).Sleep quality was assessed by Pittsburgh Sleep Quality Index(PSQI)and HRQoL by Rand 36-Item Short Form Health Survey.Outcomes were compared using standard methods.Multivariate regression examined associations between sleep quality,HRQoL,and clinical factors.RESULTS PWH(n=1005)on suppressive antiretroviral therapy had mean age 55 years and were 65%non-White and 27%cisgender female;77%had body mass index(BMI)>25 kg/m2,44%had MASLD(controlled attenuated parameter≥263 dB/minute),13%liver fibrosis(liver stiffness measurement≥8 kPa)and 64%poor sleep quality(PSQI>5).The mean±SD of PSQI was 6.6±4.1,with no differences by MASLD status;MASLD+fibrosis was associated with poorer sleep.HRQoL was low(<50)overall:A step-wise decline in physical component summary(PCS)scores was associated with worse liver disease,from no MASLD to MASLD+fibrosis.Among poor sleepers,a similar step-wise PCS worsening occurred.In multivariate analysis,MASLD+fibrosis was associated with lower PCS and poor sleep was associated with worse physical and mental HRQoL.CONCLUSION In this cohort of PWH,there was no association between MASLD and sleep quality.Poor sleep,MASLD and liver fibrosis were independently associated with poor HRQoL.展开更多
Naf1(Nef-associated factor 1)is a host protein that interacts with human immunodeficiency virus type 1(HIV-1)Nef protein.We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes....Naf1(Nef-associated factor 1)is a host protein that interacts with human immunodeficiency virus type 1(HIV-1)Nef protein.We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes.Myeloid cells are targets for HIV infection,but Naf1 expression in myeloid cells and whether it also regulates HIV infection in these cells are not yet identified.In this study,we found that Naf1 had a higher expression in CD14þmonocytes than in monocyte-derived dendritic cells(MDDCs),and its expression in both types of cells could be induced by HIV-1 gp120 glycoproteins or viral particles.Importantly,the expression of Naf1 restricted HIV-1 infection in monocytes and MDDCs.Functional investigation showed that both the constitutive and the induced expression of Naf1 inhibited NF-κB signaling in MDDCs and reduced the basal level or LPS(Lipopolysaccharide)-stimulated production of cytokines.Moreover,Naf1 reduced the expression of ICAM-1(intercellular cell adhesion molecule-1)on MDDCs and compromised their capacity to prime the activation of resting CD4^(+)T cells in co-culture.In light of the essential role of NF-κB signaling for HIV-1 transcription,Naf1-mediated inhibition of NF-κB signaling may hinder a robust viral replication in MDDCs and help maintain viral persistence.Furthermore,virus-induced Naf1 expression in MDDCs may diminish the cross-talk between DC(dendritic cell)and T cells,hence suppressing the activation of antiviral immune responses.Taken together,we identified the new function of Naf1 in myeloid cells.Those findings may facilitate the understanding for the host restriction of HIV-1 infection in myeloid cells.展开更多
Inflammatory bowel disease(IBD)is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract(GIT).It results either from gene-environment interactions or as a monogenic disease result...Inflammatory bowel disease(IBD)is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract(GIT).It results either from gene-environment interactions or as a monogenic disease resulting from pa-thogenic mutations causing impairment in the protective mechanism of the GIT.Around 10%-15%of patients with very early onset IBDs may have an underlying monogenic condition.Monogenic IBD is very different from complex forms of polygenic IBD in the underlying molecular basis of uncontrolled intestinal inflam-mation,age of onset,extraintestinal comorbidities as well as treatment modality.An in-depth understanding of this distinct form of IBD is essential for deciding an appropriate therapeutic approach as well as prognostication.In this review,we aim to discuss about the epidemiology,clinical presentation,diagnostic approach,therapeutic challenges and latest advances in patients with monogenic IBD.展开更多
Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
文摘BACKGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood products.In India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV)-I/II,malaria,and syphilis is mandatory before blood transfusions.Worldwide,HCV,HBV,and HIV are the leading viruses causing mortality,affecting millions of people globally,including those with co-infections of HIV/HCV and HIV/HBV.Studies highlight the impact of TTIs on life expectancy and health risks,such as liver cirrhosis,cancer,and other diseases in individuals with chronic HBV.Globally,millions of blood donations take place annually,emphasizing the importance of maintaining blood safety.AIM To study the prevalence of TTIs,viz.,HBV,HCV,HIV I/II,syphilis,and malaria parasite(MP),among different blood donor groups.METHODS The study assessed the prevalence of TTIs among different blood donor groups in Delhi,India.Groups included total donors,in-house donors,total camp donors,institutional camp donors,and community camp donors.Tests for HIV,HBV,and HCV were done using enzyme-linked immunosorbent assay,while syphilis was tested with rapid plasma reagins and MP rapid card methods.The prevalence of HBV,HCV,HIV,and syphilis,expressed as percentages.Differences in infection rates between the groups were analyzed usingχ²tests and P-values(less than 0.05).RESULTS The study evaluated TTIs among 42158 blood donors in Delhi.The overall cumulative frequency of TTIs in total blood donors was 2.071%,and the frequencies of HBV,HCV,HIV-I/II,venereal disease research laboratory,and MP were 1.048%,0.425%,0.221%,0.377%,and 0.0024%,respectively.In-house donors,representing 37656 donors,had the highest transfusion transmissible infection(TTI)prevalence at 2.167%.Among total camp donors(4502 donors),TTIs were identified in 1.266%of donors,while community camp donors(2439 donors)exhibited a prevalence of 1.558%.Institutional camp donors(2063 donors)had the lowest TTI prevalence at 0.921%.Statistical analysis revealed significant differences in overall TTI prevalence,with total and in-house donors exhibiting higher rates compared to camp donors.CONCLUSION Ongoing monitoring and effective screening programs are essential for minimizing TTIs.Customizing blood safety measures for different donor groups and studying socio-economic-health factors is essential to improving blood safety.
文摘Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous efforts have been devoted towards the development of such humanized mouse models. This review is focused on human lymphohematopoietic reconstitution and immune function in humanized mice by cotransplantation of human fetal thymic tissue and CD34＋ cells. The potential use of these humanized mice in translational biomedical research is also discussed.
基金Supported by the Self-funded Research Project of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z2016325).
文摘AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.
文摘Background Interferon （IFN） can inhibit human immunodeficiency virus type 1 （HIV-1） replication in vitro and in clinic.However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon α （slFNα）.Methods We performed in vitro experiments with HIV-1 IIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of slFNα in severe combined immunodeficient （SClD） mice reconstituted with human peripheral blood leukocytes （hu-PBL-SClD mice）.Results We found that the 50% effective concentrations （EC5o） of slFNα against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-α in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed： with 0.45 μg and 1.35 μg slFNα daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 μg sIFNα daily treatments resulted in a terminally complete protection.Conclusions slFNα shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-α to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus （HCV）.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
文摘BACKGROUND Chronic diarrhoea in people living with human immunodeficiency virus(PLHIV)/acquired immunodeficiency syndrome presents a diagnostic challenge,often resulting from opportunistic infections(OIs),malignancies,or disease progression itself.We present a case of an advanced human immunodeficiency virus(HIV)patient with chronic diarrhoea,significant weight loss,and antiretroviral therapy(ART)non-compliance,highlighting the diagnostic dilemma between HIV wasting syndrome,OIs,and malignancy.CASE SUMMARY A 36-year-old female,diagnosed with HIV five years ago on family screening,presented with three months of profuse watery diarrhoea,associated with crampy abdominal pain and weight loss(14 kg,30%in 3 months).She was non-compliant with ART.There was no history of recent travel,food contamination,or tuberculosis contact.Fever episodes were mild and transient.Physical examination revealed pallor and bilateral pedal oedema without lymphadenopathy or organomegaly.Genital examination was unremarkable.Routine investigations revealed severe anaemia and confirmed PLHIV status.CD4 count was<36 cells/μL.Empirical treatment with nitazoxanide was initiated for possible cryptosporidiosis.After ruling out OIs,ART was restarted.With treatment,her diarrhoea resolved,and she tolerated oral intake.Nutritional support was provided,and she was discharged in stable condition with ART,prophylactic antibiotics,and followup instructions for further evaluation.CONCLUSION In ART-noncompliant PLHIV with chronic diarrhoea,distinguishing between HIV wasting syndrome,OIs(Cryptosporidium,Mycobacterium avium complex,cytomegalovirus colitis)and malignancies(non-Hodgkin lymphoma and anal carcinoma)are critical.Gradual CD4 decline,systemic inflammation,and malnutrition favour progressive HIV/acquired immunodeficiency syndrome rather than an acute OI or malignancy.Early recognition and management,including ART reinitiation and nutritional support,are crucial for prognosis.
文摘BACKGROUND Transition is a critical period for adolescents as they begin to assume responsibility for their own health.Similarly,the shift from pediatric to adult healthcare represents a vulnerable phase,marked by unique challenges in adolescent health care.Despite its importance,only a few studies have explored healthcare transition among adolescents in Uganda.AIM To identify factors associated with the transition to adult human immunodeficiency virus(HIV)-centered care among adolescents attending HIV/AIDS clinics in Uganda.METHODS A cross-sectional mixed-methods study was conducted among 265 adolescents,randomly selected from three antiretroviral therapy(ART)clinics,using a structured questionnaire.Focus group discussions and key informant interviews were conducted.Individuals aged 10-20 years who were actively enrolled in the ART program between January 4,2022 and January 30,2023 were recruited.The primary outcome of interest was the transition to adult care.Bivariate and multivariate analyses were performed for quantitative data,while content analysis was used to analyze qualitative data.RESULTS The prevalence of transition to adult care was 40.6%.Most participants were male(53.6%)and fell within the 13-15 age group(35.6%).Multivariate logistic regression analysis identified several factors significantly associated with transition to adult care:Age group 10-12 years[prevalence ratio(PR)=2.525,95%CI:2.121-2.944,P=0.002],Age group 13-15 years(PR=1.900,95%CI:1.196-3.416,P=0.001),successful viral load suppression(PR=1.534,95%CI:1.173-1.648,P=0.016),disclosure of HIV status to relatives(PR=5.001,95%CI:3.411-3.611,P=0.000),being prepared for transitioning(PR=5.417,95%CI:3.468-7.135,P=0.041)and having skilled pediatric caregivers(PR=3.724,95%CI:2.084-4.105,P=0.005).CONCLUSION Transition to adult care among adolescents was low.Improving transition outcomes may require strengthening individual support within the family context and integrating transition-focused care into existing specialized clinical settings to enhance the delivery of adolescent-friendly services.
文摘Human immunodeficiency virus continues to pose a severe global and national public health threat.In Pakistan,human immunodeficiency virus incidence has risen alarmingly,with over 9700 new cases reported in the first nine months of 2024 alone.Transmission is fueled by unsafe sex,needle-sharing,and systemic healthcare lapses,including unscreened transfusions and reused instruments.Sociocultural stigma,limited awareness,and poor treatment adherence especially in rural and underserved areas compound the crisis.Men,transgender individuals,and children represent increasingly affected groups.The role of international bodies such as World Health Organization,United Nations Development Programme,and United Nations Women has been critical in expanding community-based care and education programs.Effective biomedical tools like preexposure prophylaxis and post-exposure prophylaxis offer preventive pro-mise but remain underutilized.Pakistan urgently needs an integrated,multispectral response i.e.,enhancing surveillance,ensuring antiretroviral therapy access,improving healthcare worker training,and promoting harm reduction and eliminating certain stigmas to control the epidemic and prevent further escalation.
基金funded by the National Natural Science Foundation of China(72204006).
文摘Objectives:This study aimed to describe the development process of the peer precision-matching and health management mobile platform"Aspark"for people living with human immunodeficiency virus(HIV)(PLWH)and to evaluate its usability.Methods:The study assembled a multidisciplinary research and development team comprising researchers,software engineers,art designers,clinical nursing specialists,HIV peer volunteers,and psychological counselors.The team employed an agile development model to iteratively build the platform.Using the social determinants of health framework and the interpersonal circumplex,we identified 14 matching variables for the mobile platform.A video production team was formed to create peer training videos on health management for PLWH.We integrated relevant tools to provide PLWH with various types of support,including informational,instrumental,emotional,affiliational,and appraisal assistance.From March to May 2024,the research team used convenience sampling to select 130 platform users.It administered an electronic questionnaire based on the System Usability Scale to evaluate the platform's overall usability.Results:The platform incorporates multiple functional modules,including"Precision Matching,""Drug Interaction Query,""Medication Reminder,""Health Management,""Mood Diary,""Community Discussion,"and"Activity Center,"achieving comprehensive coverage across informational,emotional,instrumental,social,and appraisal support.The precision matching module facilitates intelligent pairing between patients and peer volunteers;the health management module allows for the entry of test results and trend analysis;medication reminders and check-in features enhance medication adherence;the mood diary supports emotional recording and expressive writing;while the community module offers functions such as topic discussions,appointment scheduling,and organization of offline activities.Among the 130 valid questionnaires,more than 83%of users scored above 68 on the System Usability Scale,indicating that the platform demonstrates favourable usability.Conclusions:The"Aspark"platform offers a feasible and promising digital solution for precision matching in HIV peer support and health management,enabling healthcare providers to deliver personalized and continuous health support to patients through its functions.Well-designed clinical trials should be conducted in the future to evaluate the effectiveness of this tool.
基金Supported by Taizhou Municipal Hospital,No.2025JK317 and No.2025JK318.
文摘Treatment adherence among people living with human immunodeficiency virus(PLWH)is a critical determinant of viral suppression and improved quality of life.Medication literacy,as a key factor influencing adherence,is itself shaped by various psychosocial variables.Existing studies suggest that human immunodeficiency virus(HIV)-related stigma,self-efficacy,and trust in healthcare providers serve as significant mediators in the relationship between health literacy and treatment adherence.This review systematically explores how medication literacy affects treatment adherence in PLWH through intermediary psychosocial mechanisms such as depression,anxiety,and social support.By synthesizing current evidence,we aim to inform the development of targeted psychosocial interventions to enhance treatment outcomes and quality of life for this population.Our findings provide an evidence-based foundation for nursing practice and support innovative strategies in comprehensive HIV care.
文摘Leukocyte adhesion deficiency type-1 is frequently associated with otorhinolaryngological manifestations,most notably a high prevalence of otitis media.Although multiple case reports have documented an increased prevalence of acute otitis media and mastoiditis in patients with LAD-1,no clinical or experimental studies have fully elucidated the pathophysiological mechanisms underlying this association.Despite guideline recommendations for urgent antibiotic therapy in immunocompromised patients with acute otitis media,a standardized treatment protocol for its complications remains lacking.Moreover,no established consensus exists regarding the optimal therapeutic approach for Leukocyte adhesion deficiency type-1associated cases.This report contributes to the scarce literature on acute mastoiditis in LAD-1 and underscores the need for a tailored,multidisciplinary approach.In the absence of standardized treatment protocols,further research is crucial to refine management strategies and improve outcomes in immunocompromised patients with acute otitis media complications.
基金supported by the Postdoctoral Fellowship Program of CPSF (GZC20231064)China Postdoctoral Science Foundation (2024M761345)+3 种基金Guangzhou Basic and Applied Basic Research Foundation (2024A04J6615)Scientific Research Project of Southern Medical University Stomatological Hospital (PY2023004)National Key Research and Development Program of China (2021YFA0805300)National Natural Science Foundation of China (82171244,32470564)。
文摘Severe combined immunodeficiency disease(SCID),characterized by profound immune system dysfunction,can lead to life-threatening infections and death.Animal models play a pivotal role in elucidating biological processes and advancing therapeutic strategies.Recent advances in gene-editing technologies,including zincfinger nucleases(ZFNs),transcription activator-like effector nucleases(TALENs),CRISPR/Cas9,and base editing,have significantly enhanced the generation of SCID models.These models have not only deepened our understanding of disease pathophysiology but have also driven progress in cancer therapy,stem cell transplantation,organ transplantation,and infectious diseasemanagement.Thisreviewprovidesa comprehensive overview of current SCID models generated using novel gene-editing approaches,highlighting their potential applications in translational medicine and their role in advancing biomedical research.
基金financially supported by the National Natural Science Foundation of China(NSFC,82272312,82241072,82072271,and 82272319)the Shenzhen-Hong Kong-Macao Science and Technology Project(Category C project)(SGDX20220530111403024)+5 种基金the National Key R&D Program of China(2023YFC2307004,2021YFC2301900,and 2021YFC2301905)the 100 Top Talent Programs of Sun Yat-sen University(58000-12230029)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018 and 2022-1-007)Beijing Health Technologies Promotion Program(BHTPP202002)the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(DFL20191701)Beijing Key Laboratory for HIV/AIDS Research(BZ0089).
文摘The long-term effects of combined antiretroviral therapy(ART)on liver fibrosis patterns in adults living with human immunodeficiency virus(HIV)and chronic hepatitis B virus(HBV)are not well understood.Therefore,this study aimed to investigate the trajectories of liver fibrosis and identify the associations of baseline variables with different patterns of liver fibrosis evolution.A total of 333 individuals with HIV/HBV co-infection and undergoing long-term ART were enrolled in this study.Demographic,clinical,and biochemical data were collected at baseline and during annual visits.Group-based trajectory models(GBTMs)were used to detect the patterns of liver fibrosis evolution based on longitudinal data of fibrosis-4(Fib-4)and aspartate aminotransferase to platelet ratio index(APRI)scores.Logistic regression analysis was performed to identify baseline predictors of liver fibrosis evolution.The median age of all participants was 33 years.Among them,89.5%initially received TDF-containing ART.GBTMs identified two distinct patterns of liver fibrosis evolution using either APRI or Fib-4 scores.The majority of individuals(78.5%for APRI and 75.3%for Fib-4;pattern A)showed stable or low fibrosis with no progression,while the remaining participants showed regression from high fibrosis levels(21.5%for APRI and 24.7%for Fib-4;pattern B).Pattern A participants were younger and had higher CD4^(+)cell counts,higher lymphocyte cell counts,higher white blood cell counts,and lower platelet counts at baseline compared to pattern B participants.For HIV/HBV co-infected patients with varying degrees of initial liver fibrosis,long-term ART has shown distinct patterns of alleviating liver fibrosis.
文摘BACKGROUND The World Health Organization(WHO)recommends lumbar puncture(LP)procedures to assess the diagnosis of cryptococcal meningitis(CM)among patients with advanced human immunodeficiency virus(HIV)disease(AHD)with positive serum cryptococcal antigen(CrAg)and do not have evidence of CM.AIM To estimate pooled prevalence of uptake of LP,CM and mortality among patients with AHD.METHODS PubMed,Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024.LP uptake was defined as percentage of people who underwent LP procedures among those with AHD(CD4≤200 cells/mm3 or WHO stage III/IV)and positive serum CrAg.Using random effects models,we computed the pooled estimate of LP uptake,CM and mortality and 95%CI.Stratified analyses were used to compare uptake of LP between studies that involved multiple vs single sites,and mortality analyses between patients with positive and negative serum CrAg were performed.Sensitivity analysis on LP uptake was done by excluding prospective cohort studies that reported 100%uptake.RESULTS A total of 32 studies with 46890 people with AHD screened for serum CrAg and 2730(5.8%)had positive serum CrAg.Overall,pooled prevalence of LP uptake was 67.7%(95%CI:54.0-81.5).The overall pooled prevalence of CM was 54.3%(95%CI:39.7-69.0),and mortality was 6.2%(95%CI:4.5-8.0).There is disparities in the pooled prevalence of LP uptake with studies involving multiple sites having lower prevalence compared to those that involved single sites(54.8%vs 84.7%,P=0.004).By excluding prospective cohort studies that reported 100%uptake,the overall LP uptake was 54.5%(95%CI:38.8-70.1).The pooled prevalence of CM was significantly lower among studies that involved multiple sites compared to those that involved single sites(6.8%vs 8.1%,P≤0.001).Mortality was significantly twice as high among patients who had positive serum CrAg compared to those who had negative serum CrAg[risk ratio=2.0(95%CI:1.6-2.5),P≤0.001].CONCLUSION Nearly three to five in 10 people with AHD with positive serum CrAg did not have LP procedures done,indicating significant gaps in identifying patients with CM.Establishing a confirmed diagnosis of CM is critical to avoid exposing patients to subtherapeutic levels of antifungals preemptively.Capacity to perform LP and patient refusals are among the reasons for not performing the procedure.Capacity building in training health care providers to perform LP procedures and professional counselling to obtain patient consent are critical for appropriate treatment to reduce mortality associated with CM infection.
基金Supported by National Natural Science Foundation of China,No.82360120Ten Thousand Doctor Plan in Yunnan Province,No.YNWRMY-2018-020Yunnan Provincial Key Laboratory of Clinical Virology,No.202205AG070053-07.
文摘BACKGROUND Common variable immunodeficiency(CVID)is a primary antibody immunodeficiency disorder characterized by diminished IgG levels.Despite ongoing research,the precise pathogenesis of CVID remains unclear.Genetic factors account for only 10%-20%of cases,with an estimated incidence of 1 in 10000 to 1 in 100000,affecting individuals across all age groups.CASE SUMMARY We report the case of a 32-year-old man with CVID who presented with a chief complaint of“recurrent diarrhea and significant weight loss over the past 2 years”.Laboratory tests on admission showed fat droplets in stool,while other parameters were within normal ranges.Gastroscopy revealed a smooth gastric mucosa without bile retention or signs of Helicobacter pylori infection;however,the mucosa of the descending segment of the duodenum appeared rough.Further evaluation of the small intestine using computed tomography indicated no abnormalities.Finally,the whole-small bowel double-balloon enteroscopy(DBE)was performed,which revealed various phenotypic changes in the small intestinal mucosa.The patient was diagnosed with CVID,which improved after immunoglobulin therapy,with favorable follow-up outcomes.CONCLUSION Non-infectious enteropathy in CVID is rare.Therefore,DBE is essential for diagnosing small intestinal involvement in such cases.
基金Supported by National Institutes of Health,No.R01DK121378,No.R01DK126042,and No.P30DK120515.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and poor sleep are common among people with human immunodeficiency virus(PWH)and may mediate the impaired health-related quality of life(HRQoL)seen in PWH and in people with MASLD.However,the prevalence and burden of poor sleep in PWH and MASLD is not well described.AIM To study the prevalence and multi-faceted relationship between MASLD,poor sleep,and HRQoL in PWH.METHODS In this cross-sectional,observational study,adult PWH and no other known cause of liver disease underwent controlled attenuated parameter(for hepatic fat)and liver stiffness measurement via vibration-controlled transient elastography at eight United States.centers(July 2021 to November 2024).Sleep quality was assessed by Pittsburgh Sleep Quality Index(PSQI)and HRQoL by Rand 36-Item Short Form Health Survey.Outcomes were compared using standard methods.Multivariate regression examined associations between sleep quality,HRQoL,and clinical factors.RESULTS PWH(n=1005)on suppressive antiretroviral therapy had mean age 55 years and were 65%non-White and 27%cisgender female;77%had body mass index(BMI)>25 kg/m2,44%had MASLD(controlled attenuated parameter≥263 dB/minute),13%liver fibrosis(liver stiffness measurement≥8 kPa)and 64%poor sleep quality(PSQI>5).The mean±SD of PSQI was 6.6±4.1,with no differences by MASLD status;MASLD+fibrosis was associated with poorer sleep.HRQoL was low(<50)overall:A step-wise decline in physical component summary(PCS)scores was associated with worse liver disease,from no MASLD to MASLD+fibrosis.Among poor sleepers,a similar step-wise PCS worsening occurred.In multivariate analysis,MASLD+fibrosis was associated with lower PCS and poor sleep was associated with worse physical and mental HRQoL.CONCLUSION In this cohort of PWH,there was no association between MASLD and sleep quality.Poor sleep,MASLD and liver fibrosis were independently associated with poor HRQoL.
基金supported by the National Natural Science Foundation of China(82172242)the Natural Science Foundation of Guangdong(2022A1515012053)the projects from Guangzhou Municipal Science and Technology Bureau(2023A04J1075).
文摘Naf1(Nef-associated factor 1)is a host protein that interacts with human immunodeficiency virus type 1(HIV-1)Nef protein.We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes.Myeloid cells are targets for HIV infection,but Naf1 expression in myeloid cells and whether it also regulates HIV infection in these cells are not yet identified.In this study,we found that Naf1 had a higher expression in CD14þmonocytes than in monocyte-derived dendritic cells(MDDCs),and its expression in both types of cells could be induced by HIV-1 gp120 glycoproteins or viral particles.Importantly,the expression of Naf1 restricted HIV-1 infection in monocytes and MDDCs.Functional investigation showed that both the constitutive and the induced expression of Naf1 inhibited NF-κB signaling in MDDCs and reduced the basal level or LPS(Lipopolysaccharide)-stimulated production of cytokines.Moreover,Naf1 reduced the expression of ICAM-1(intercellular cell adhesion molecule-1)on MDDCs and compromised their capacity to prime the activation of resting CD4^(+)T cells in co-culture.In light of the essential role of NF-κB signaling for HIV-1 transcription,Naf1-mediated inhibition of NF-κB signaling may hinder a robust viral replication in MDDCs and help maintain viral persistence.Furthermore,virus-induced Naf1 expression in MDDCs may diminish the cross-talk between DC(dendritic cell)and T cells,hence suppressing the activation of antiviral immune responses.Taken together,we identified the new function of Naf1 in myeloid cells.Those findings may facilitate the understanding for the host restriction of HIV-1 infection in myeloid cells.
文摘Inflammatory bowel disease(IBD)is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract(GIT).It results either from gene-environment interactions or as a monogenic disease resulting from pa-thogenic mutations causing impairment in the protective mechanism of the GIT.Around 10%-15%of patients with very early onset IBDs may have an underlying monogenic condition.Monogenic IBD is very different from complex forms of polygenic IBD in the underlying molecular basis of uncontrolled intestinal inflam-mation,age of onset,extraintestinal comorbidities as well as treatment modality.An in-depth understanding of this distinct form of IBD is essential for deciding an appropriate therapeutic approach as well as prognostication.In this review,we aim to discuss about the epidemiology,clinical presentation,diagnostic approach,therapeutic challenges and latest advances in patients with monogenic IBD.
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
