Cluster Of Differentiation 4 Research Articles

Short-term mortality from HIV-infected persons diagnosed from 2012 to 2016: Impact of late diagnosis of HIV infection.

We investigated the temporal trends of short-term mortality (death within 1 year of diagnosis) and cause-specific deaths in human immunodeficiency virus (HIV)-infected persons by stage of HIV infection at diagnosis. We also assessed the impact of late diagnosis (LD) on short-term mortality.Epidemiological records of HIV-infected Singapore residents from the National HIV Registry were linked to death records from the Registry of Births and Deaths for observational analyses. Newly-diagnosed HIV cases with available cluster of differentiation 4 count at time of diagnosis in a 5-year period from 2012 to 2016 were included in the study. Hazard ratios (HRs) and 95% confidence interval (CI) of LD for all deaths excluding suicides and self-inflicted or accidental injuries, and HIV/ acquired immunodeficiency syndrome (AIDS)-related deaths occurring within 1 year post-diagnosis were calculated using Cox proportional hazards regression models with adjustment for age at HIV/AIDS diagnosis. Population attributable risk proportions (PARPs) were then calculated using the adjusted HRs.Of the 1990 newly-diagnosed HIV cases included in the study, 7.2% had died by end of 2017, giving an overall mortality rate of 2.16 per 100 person-years (PY) (95% CI 1.82–2.54). The mortality rate was 3.81 per 100 PY (95% CI 3.15–4.56) in HIV cases with LD, compared with 0.71 (95% CI 0.46–1.05) in non-LD (nLD) cases. Short-term mortality was significantly higher in LD (9.1%) than nLD cases (1.1%). Of the 143 deaths reported between 2012 and 2017, 58.0% were HIV/AIDS-related (nLD 28.0% vs LD 64.4%). HIV/AIDS-related causes represented 70.4% of all deaths which occurred during the first year of diagnosis (nLD 36.4% vs LD 74.7%). The PARP of short-term mortality due to LD was 77.8% for all deaths by natural causes, and 87.8% for HIV/AIDS-related deaths.The mortality rate of HIV-infected persons with LD was higher than nLD, especially within 1 year of diagnosis, and HIV/AIDS-related causes constituted majority of these deaths. To reduce short-term mortality, persons at high risk of late-stage HIV infection should be targeted in outreach efforts to promote health screening and remove barriers to HIV testing and treatment.

A Retrospective Analysis on Risk Factors for 30-day Readmission Rates in Patients Living With HIV and Severe Major Depression Disorder.

BackgroundMajor depression disorder (MDD) is the most common psychiatric comorbidity in patients living with HIV (PLWHIV). The prevalence rate of MDD is higher in PLWHIV in comparison to the general population. In our study, we focus specifically on the 30-day readmission rate of PLWHIV and severe major depression.MethodsThe Health Care Agency (HCA) databank was used to conduct a retrospective study on PLWHIV and severe MDD. Keywords such as HIV, severe MDD, CD4, viral load were used to identify the data. 30-day readmission rate is studied in PLWHIV and severe MDD (N=143). Variables such as age, sex, gender, adherence to antiretroviral medications, cluster of differentiation 4 (CD4), and viral load were studied in this population. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria were used to diagnose severe MDD in PLWHIV. An antiretroviral therapy (ART) medication list was used to analyze adherence in this population group. Geographical locations were identified using urbanization codes.ResultsLogistic regression analysis for the 30-day readmission rate in PLWHIV was found to be higher in the older age group (p<0.01). Caucasian population (p<0.01) and rural areas (p<0.01), ART non-adherence (p<0.05), and severe major depression were also found to be significant in this population (p<0.01).ConclusionAs more patients live longer with HIV/AIDS, it gives rise to illnesses such as anxiety, depression, and cognitive impairment. Thus, it is important to identify severe depression in PLWHIV since it can have an impact on rates of hospitalization, morbidity/mortality, and the financial burden, specifically within 30-days of discharge.

Immune-related gene ANGPT1 is an adverse biomarker for endometrial carcinoma.

BackgroundImmunotherapy has made great strides in cancer treatment. Endometrial carcinoma (EC) has been 1 of the most common tumors among women. This study aimed to screen immune-related prognosis biomarkers for EC.MethodsThe transcriptome profiling and clinical data of EC were downloaded from The Carcinoma Genome Atlas (TCGA) public database, and differentially expressed genes (DEGs) were obtained through the limma package in R software. An immune-related genes (IRGs) list was collected from the ImmPort database. We constructed a free-scale gene co-expression network via weighted gene co-expression network analysis (WGCNA). Then, the intersection genes of the module genes which significantly related to EC, along with IRGs and DEGs were screened as the candidate genes for further analysis. We identified the hub gene via Venn analysis of the protein-protein interaction (PPI) network genes and the prognostic genes, and verified expression of the hub gene through Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) databases which provided the GSE17025 dataset. Furthermore, we used the CIBERSORT deconvolution algorithm to explore tumor immune cells infiltration in EC, and investigated correlations between the hub gene and immune cells.ResultsThe differential expression analysis demonstrated that there were 900 up-regulated genes and 1,008 down-regulated genes in TCGA-UCEC (Uterine Corpus Endometrial Carcinoma) cohort. There were 74 candidate intersection genes in blue module genes, IRGs, and DEGs. Finally, angiopoietin 1 (ANGPT1) was identified as the hub gene in EC. Low expression of ANGPT1 was associated with better overall survival (OS) in EC patients. The expression of ANGPT1 was negatively correlated with regulatory T cells (Tregs), but positively correlated with resting memory cluster of differentiation 4 (CD4) T cells, activated dendritic cells (DCs), activated natural killer (NK) cells, and activated memory CD4 T cells (P<0.05, Spearman). A high-infiltrating regulatory T cell would improve the prognosis for EC patients.ConclusionsThe gene ANGPT1 can increase the infiltration of T cells and improve the prognosis of EC patients.

A Meta-analysis of Antimicrobial Peptide Effects on Intestinal Bacteria, Immune Response, and Antioxidant Activity of Broilers

This study used a meta-analysis to systematically assess the effect of antimicrobial peptide (AMP) addition on the number of bacteria, immune responses, and antioxidant activity of broilers. The database was compiled from 29 post evaluation articles that were found in search engines consisted of 36 experiments and 111 data. The mixed model method was used to assess the effect of AMP, with AMP addition level as a fixed effect and experiment as a random effect. The fixed effect was tested for linear and quadratic models. The quadratic model was retained when significant at p&lt;0.05 but turned into its corresponding linear model when insignificant. In the starter phase, AMP addition decreased the number of bacteria in the ileum (coliform and total aerobic bacteria (TAB); (p&lt;0.05), the caecum (Clostridium spp., Escherichia coli, coliform, and lactic acid bacteria (LAB); p&lt;0.05), and excreta (Clostridium spp.; p&lt;0.1). Similarly, the number of bacteria also declined in the ileum (Escherichia coli, p&lt;0.05; TAB, p&lt;0.1), the caecum (LAB; p&lt;0.1), and excreta (Clostridium spp.; p&lt;0.05) of broilers in the finisher phase. There were significant improvements in immune response and antioxidant activity in starter broiler, as indicated by the titer of Newcastle disease (ND) antibody, bursal index, spleen index, and thymus index (p&lt;0.05) due to AMP addition. Variables of immunoglobulin M (IgM), cluster of differentiation 4 (CD4), ND antibody titer, bursal index, spleen index, and thymus index were also significantly increased (p&lt;0.05) while superoxide dismutase activity (SOD activity) tended to increase (p&lt;0.1) in finisher broiler following the AMP addition. In short, AMP addition is able to suppress the number of pathogenic bacteria and increase the immune response and antioxidant activity of broilers.

HIV Stigma and Discrimination: Perspectives and Personal Experiences of Healthcare Providers in Yogyakarta and Belu, Indonesia.

Stigma and discrimination are major challenges facing People Living with HIV/AIDS (PLWHA) globally due to their HIV status. As part of a larger qualitative study in Yogyakarta and Belu, Indonesia, using in-depth interviews with 92 PLWHA (52 women, 40 men) and 20 healthcare providers, this paper describes perspectives and personal experiences of the 20 healthcare providers, relating to HIV stigma and discrimination toward PLWHA in both study settings. The healthcare providers were recruited from healthcare facilities providing HIV-related healthcare services, using a snowball sampling technique. A qualitative framework analysis was used to guide data analysis. Health stigma and discrimination framework guided the conceptualisation and discussion of the findings. The findings presented the views and perspectives of healthcare providers that HIV stigma and discrimination toward PLWHA still occurred within families, communities and healthcare settings. These were reflected in negative labelling, separation of personal belongings, avoidance, denial of treatment and rejection of PLWHA by healthcare providers, family and community members. Some healthcare providers reported that they had personally stigmatised and discriminated against PLWHA. A lack of knowledge about HIV, fear of contracting HIV, personal values, religious thoughts and sociocultural values and norms, were reported as drivers or facilitators behind this HIV-related stigma and discrimination. The findings indicate the importance of continued HIV/AIDS education for families, community members and healthcare providers, to raise awareness and to ensure that healthy and professional support systems are in place for PLWHA. The findings indicate the need to enhance improvement within the healthcare or HIV care system to adequately address the needs of PLWHA, which may facilitate their early initiation of HIV treatment and better treatment adherence and retention to increase Cluster of Differentiation 4 (CD4) count and suppress viral load. Future studies are also needed to explore the role that government and non-government institutions can play in improving health service delivery for people newly diagnosed with HIV and those living with HIV/AIDS.

Ex Vivo High Salt Activated Tumor-Primed CD4+T Lymphocytes Exert a Potent Anti-Cancer Response.

Simple SummaryCell based immunotherapy is rapidly emerging as a promising cancer treatment. Salt (sodium chloride) treatment to immune cell cultures is known to induce inflammatory activation. In our current study, we analyzed the anti-cancer ability of salt treatment on immune cells outside the host followed by reinfusion into the host. Using a pre-clinical breast cancer model, we demonstrated that external salt treatment on T-cell subset of immune cells produced a viable anti-cancer response, which may have future human clinical application.Cell based immunotherapy is rapidly emerging as a promising cancer treatment. A modest increase in salt (sodium chloride) concentration in immune cell cultures is known to induce inflammatory phenotypic differentiation. In our current study, we analyzed the ability of salt treatment to induce ex vivo expansion of tumor-primed CD4 (cluster of differentiation 4)+T cells to an effector phenotype. CD4+T cells were isolated using immunomagnetic beads from draining lymph nodes and spleens from tumor bearing C57Bl/6 mice, 28 days post-injection of Py230 syngeneic breast cancer cells. CD4+T cells from non-tumor bearing mice were isolated from splenocytes of 12-week-old C57Bl/6 mice. These CD4+T cells were expanded ex vivo with five stimulation cycles, and each cycle comprised of treatment with high salt (Δ0.035 M NaCl) or equimolar mannitol controls along with anti-CD3/CD28 monoclonal antibodies for the first 3 days, followed by the addition of interleukin (IL)-2/IL-7 cytokines and heat killed Py230 for 4 days. Ex vivo high salt treatment induced a two-fold higher Th1 (T helper type 1) expansion and four-fold higher Th17 expansion compared to equimolar mannitol treatment. Importantly, the high salt expanded CD4+T cells retained tumor-specificity, as demonstrated by higher in vitro cytotoxicity against Py230 breast cancer cells and reduced in vivo syngeneic tumor growth. Metabolic studies revealed that high salt treatment enhanced the glycolytic reserve and basal mitochondrial oxidation of CD4+T cells, suggesting a role of high salt in enhanced pro-growth anabolic metabolism needed for inflammatory differentiation. Mechanistic studies demonstrated that the high salt induced switch to the effector phenotype was mediated by tonicity-dependent transcription factor, TonEBP/NFAT5. Using a transgenic murine model, we demonstrated that CD4 specific TonEBP/NFAT5 knock out (CD4cre/creNFAT5flox/flox) abrogated the induction of the effector phenotype and anti-tumor efficiency of CD4+T cells following high salt treatment. Taken together, our data suggest that high salt-mediated ex vivo expansion of tumor-primed CD4+T cells could induce effective tumor specific anti-cancer responses, which may have a novel cell-based cancer immunotherapeutic application.

Characteristics of immune function in the acute phase of Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is still diagnosed using symptoms and signs together with some histopathological findings. The purpose of this study was to summarize the characteristics and roles of cellular and humoral immunity in children with Henoch-Schönlein purpura (HSP). A total of 502 cases of patients with acute HSP were diagnosed and observed. The levels of T lymphocyte subsets, natural killer cells (NK cells), and B cells were analyzed by flow cytometry. The serum immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), and complement C3 (C3) and complement C4 (C4) levels were detected by velocity scatter turbidimetry. Compared with the healthy groups, the levels of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), B cells, and NK cells and ratio of CD4/CD8 in patients with HSP were decreased (P < 0.05). The levels of IgG, IgA, IgM, and C3 were increased (P < 0.05). Compared with the Kawasaki disease (KD) group, the levels of CD3, CD4, CD8, B cells, NK cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM, C3, and C4 was decreased (P < 0.05). Compared with the pneumonia group, the levels of CD3, CD4, B cells, and IgA in patients with HSP were increased (P < 0.05), and the ratio of CD4/CD8 and levels of IgM and C4 was decreased (P < 0.05). Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. The decline of NK cells, B lymphocyte cells, CD3, CD4 the increased secretion of immunoglobulin, and the abnormal appearance of IgA and C3 may exist during the progression. It may indicate a worse prognosis and increasing the risk of dedifferentiation. Cellular immunity was lower, which lead to increased production of inflammatory mediators and increased secretion of immunoglobulin, which then mediated systemic small-vessel vasculitis. Key Points • The pathogenesis of Henoch-Schönlein purpura (HSP) was not completely illuminated. • There was a lack of disease-specific laboratory abnormalities that can be used in the clinical diagnosis of HSP. • We compared the laboratory abnormalities in the immune system of HSP with KD and pneumonia. • Cellular immunity and humoral immunity were all involved in the pathogenesis of HSP. Cellular immunity was lower, which lead to the following pathological changes.

Dual engineered gold nanoparticle based synergistic prophylaxis delivery system for HIV/AIDS

HIV is a pandemic and continuously raises problem across the world. This disease puts an immense pressure on treatment modalities. There are only few clinically accepted drugs available for the treatment and few molecules under clinical development. Although, the antiretroviral drugs give reliable and positive response on control of virus replication but during the long treatment, it has been affirmed that there are number of side effects. With recent advancements in biotechnology, nanomaterials such as gold and silver etc. are proving to be a game changer in targeted drug delivery treatment. As gold nanoparticles (AuNPs) are biocompatible natural excipients, a lot of scientists are very eager to investigate more about the immune effects of AuNPs to create a safe and cost effective treatment that could potentially help in the reduction of numerous toxic effects present in the existing treatments of various critical diseases like cancer and HIV etc. In this context, the present hypothesis recommends the use of combination drug delivery strategy based on gold nanoparticles that could pave the way to overcome adverse results of existing delivery techniques of antiretroviral drugs to treat HIV. This review also highlights the fact that a proper development of this gold nanoparticle combination antiretroviral drug delivery approach will not only help to suppress the virus multiplication but also target the viral entry area by attaching with gp120 (glycoprotein 120), and inhibit the binding with CD4 (Cluster of differentiation 4) T cells.

Prevalence of Hepatitis B Virus coinfection among Human Immunodeficiency Virus positive patients in Yola, Adamawa State, Nigeria

Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) confection has been reported to impair negatively on the health of the patients because it impacts directly on the outcome of HBV infection, considerably complicating its natural history, diagnosis and management. This study was aimed at determining the incidence and distribution of HBV/HIV coinfection in the study area. Methods: The sera people living with HIV/AIDS were screened for hepatitis B surface antigen (HBsAg) and cluster of differentiation 4 (CD4) cell counts using the Becton Dickinson Fluorescence Activated Cell Sorter procedure. Results: The prevalence of HBV co-infection among people living with HIV/AIDS in this study was 11% with the coinfection being higher in males (14.3%) compared to the 9.7% among females. The coinfection was highest among people ages 25-39 yr. (12.9%) while least occurrence of coinfection was observed in ages above 53 yr. (8.3%). The CD4 counts of HBV and HIV coinfected persons showed that 18.2% of coinfected persons had CD4 counts above 700-1000 cells/mm3 while 12.1% had CD4 counts between 501-700 cells/mm3. Conclusion: The relatively high prevalence of HBV infection in HIV patients confirms the need for baseline screening for these markers in HIV-infected patients, as this could affect the choice of highly active antiretroviral therapy (HAART) regimen for the patients.

Evaluation of virologic suppression rates during the COVID-19 pandemic with outpatient interdisciplinary HIV care.

IntroductionThe Coronavirus Disease 2019 (COVID‐19) pandemic has presented social distancing challenges leading healthcare systems to adapt and utilize telemedicine platforms more than ever before. Reducing patient exposure to COVID‐19 became a primary concern, especially for populations at an increased risk for severe illness, such as human immunodeficiency virus (HIV) positive patients.ObjectivesThe primary objective of this study was to measure the impact of pharmacy services including telehealth through the percentage of virologically suppressed patients (HIV ribonucleic acid [RNA] < 200 copies/mL) during the pre‐COVID and post‐COVID time periods. Secondary objectives included the percentage of patients with undetectable viral loads (HIV RNA < 20 copies/mL), percentage of patients with cluster of differentiation 4 (CD4) cell counts greater than 200 cells/mm3, and changes in CD4 cell counts and percentages pre‐COVID and post‐COVID.MethodsThis was a retrospective chart review at a single center HIV primary care clinic in Brooklyn, NY evaluating electronic medical records (EMRs) of 211 HIV‐positive patients. Pre‐COVID was defined as 1 year prior to March 13, 2020, and post‐COVID was defined as March 13 to July 20, 2020.ResultsViral load suppression rates for pre and post‐COVID were 88.6% and 85.3%, respectively (P = .28). Undetectable viral load rates for pre and post‐COVID were approximately 81.5% and 74.4% (P = .096). Mean CD4 cell counts and percentages were 617 cells/mm3 and 29% for pre‐COVID, and 460 cells/mm3 and 22% for post‐COVID. CD4 cell counts greater than 200 cells/mm3 pre‐COVID and post‐COVID was 92.6% and 78.3%, respectively (P = .001).ConclusionUtilization of pharmacy services including telehealth, may allow clinical pharmacists to collaboratively provide remote services without jeopardizing patient outcomes. Larger studies are needed to confirm these findings, and display the long‐term impact and satisfaction of these services.

Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells.

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

Sudden Cardiac Death and Sudden Cardiac Arrest in Patients with Human Immunodeficiency Virus: A Systematic Review.

The importance of this review lies in its study of the risk of sudden cardiac death (SCD) and sudden cardiac arrest (SCA) in people living with the human immunodeficiency virus (PLWH). To the best of our knowledge, this is the first review investigating the effect of the human immunodeficiency virus (HIV) on SCD and SCA.The review's objective was to determine the risk of SCD and SCA in PLWH. To do this, the electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Scopus, and Google Scholar were systematically searched to identify eligible studies published before January 31, 2021. Reference lists of the included studies were searched for further identification of relevant studies. The search terms included: "Sudden Cardiac Death," "Sudden Cardiac Arrest," "Human Immunodeficiency virus," "HIV," "Acquired immunodeficiency syndrome," and "AIDS." Only observational studies that assessed the association between SCD and SCA in PWLH were selected. Data were extracted by two independent authors who screened titles, abstracts, and articles to meet the inclusion criterion. Quality assessment was done by using modified Downs and Black checklist.A total of seven studies were included in this review. Five studies revealed a higher incidence of SCD in PLWH, two of which focused on patients with HIV and low left ventricular ejection fraction (LVEF). The other two studies were about the association of HIV and SCA. Studies reported that PLWH had a three- to five-fold higher incidence of SCD as compared to non-HIV patients. HIV patients with low LVEF had a higher incidence of SCD than HIV patients with normal LVEF. PLWH had a higher incidence of SCA and less successful cardiopulmonary resuscitation (CPR) as compared to patients without HIV. After adjusting for various confounders in multiple studies, all the studies reported a higher incidence of SCD in PLWH.To conclude, PLWH is at an increased risk of SCD and SCA. Some risk factors for this include LVEF, viral load (VL), and the cluster of differentiation 4 (CD4) count. There is a paucity of data on the mechanisms involved, although a higher prevalence of cardiac fibrosis and interstitial fibrosis in PLWH may play a role. Because of the general suboptimal quality of the heterogeneous nature of the current evidence, further, rigorous studies are needed to determine the association of increased risk of SCD and SCA in PLWH.

DNA-double strand breaks enhance the expression of major histocompatibility complex class II through the ATM-NF-κΒ-IRF1-CIITA pathway.

Major histocompatibility complex class II (MHC II) is important for the adaptive immune response because MHC II presents processed antigens to a cluster of differentiation 4 (CD4)-positive T-cells. Conventional doses of chemotherapeutic agents induce tumor cell death by causing DNA double-strand breaks (DSBs). However, cellular responses caused by sub-lethal doses of chemotherapeutic agents are poorly understood. In this study, using low doses of chemotherapeutic agents, we showed that DSBs enhanced the expression of MHC II on cells that originate from antigen-presenting cells (APCs). These agents induced the MHC class II transactivator (CIITA), the master regulator of MHC II, and interferon regulatory factor 1 (IRF1), a transcription factor for CIITA. Short hairpin RNA against IRF1 suppressed chemotherapeutic agent-induced CIITA expression, whereas exogenous expression of IRF1 induced CIITA. Inhibition of ataxia-telangiectasia mutated (ATM), a DSB-activated kinase, suppressed induction of IRF1, CIITA, and MHC II. Similar results were observed by inhibiting NF-κB, a downstream target of ATM. These results suggest that DSBs induce MHC II activity via the ATM-NF-κB-IRF1-CIITA pathway in cells that intrinsically present antigens. Additionally, chemotherapeutic agents induced T-cell regulatory molecules. Our findings suggest that chemotherapeutic agents enhance the antigen presentation activity of APCs for T-cell activation.

A deep learning-based quantitative computed tomography model for predicting the severity of COVID-19: a retrospective study of 196 patients.

BackgroundThe assessment of the severity of coronavirus disease 2019 (COVID-19) by clinical presentation has not met the urgent clinical need so far. We aimed to establish a deep learning (DL) model based on quantitative computed tomography (CT) and initial clinical features to predict the severity of COVID-19.MethodsOne hundred ninety-six hospitalized patients with confirmed COVID-19 were enrolled from January 20 to February 10, 2020 in our centre, and were divided into severe and non-severe groups. The clinico-radiological data on admission were retrospectively collected and compared between the two groups. The optimal clinico-radiological features were determined based on least absolute shrinkage and selection operator (LASSO) logistic regression analysis, and a predictive nomogram model was established by five-fold cross-validation. Receiver operating characteristic (ROC) analyses were conducted, and the areas under the receiver operating characteristic curve (AUCs) of the nomogram model, quantitative CT parameters that were significant in univariate analysis, and pneumonia severity index (PSI) were compared.ResultsIn comparison with the non-severe group (151 patients), the severe group (45 patients) had a higher PSI (P<0.001). DL-based quantitative CT indicated that the mass of infection (MOICT) and the percentage of infection (POICT) in the whole lung were higher in the severe group (both P<0.001). The nomogram model was based on MOICT and clinical features, including age, cluster of differentiation 4 (CD4)+ T cell count, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP). The AUC values of the model, MOICT, POICT, and PSI scores were 0.900, 0.813, 0.805, and 0.751, respectively. The nomogram model performed significantly better than the other three parameters in predicting severity (P=0.003, P=0.001, and P<0.001, respectively).ConclusionsAlthough quantitative CT parameters and the PSI can well predict the severity of COVID-19, the DL-based quantitative CT model is more efficient.

Cell Culture-Derived Tilapia Lake Virus-Inactivated Vaccine Containing Montanide Adjuvant Provides High Protection against Viral Challenge for Tilapia.

Tilapia lake virus (TiLV) is a newly emerging pathogen responsible for high mortality and economic losses in the global tilapia industry. Currently, no antiviral therapy or vaccines are available for the control of this disease. The goal of the present study was to evaluate the immunological effects and protective efficacy of formaldehyde- and β-propiolactone-inactivated vaccines against TiLV in the presence and absence of the Montanide IMS 1312 VG adjuvant in tilapia. We found that β-propiolactone inactivation of viral particles generated a vaccine with a higher protection efficacy against virus challenge than did formaldehyde. The relative percent survivals of vaccinated fish at doses of 108, 107, and 106 50% tissue culture infectious dose (TCID50)/mL were 42.9%, 28.5%, and 14.3% in the absence of the adjuvant and 85.7%, 64.3%, and 32.1% in its presence, respectively. The vaccine generated specific IgM and neutralizing antibodies against TiLV at 3 weeks following immunization that were significantly increased after a second booster immunization. The steady state mRNA levels of the genes tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon γ (IFN-γ), cluster of differentiation 4 (CD4), major histocompatibility complex (MHC)-Ia, and MHC-II were all increased and indicated successful immune stimulation against TiLV. The vaccine also significantly lowered the viral loads and resulted in significant increases in survival, indicating that the vaccine may also inhibit viral proliferation as well as stimulate a protective antibody response. The β-propiolactone-inactivated TiLV vaccine coupled with the adjuvant Montanide IMS 1312 VG and booster immunizations can provide a high level of protection from virus challenge in tilapia.

A Comparison of Postoperative Surgical Outcomes among Women Undergoing Obstetric Fistula Repair with and without HIV.

Background and Objective:Obstetric fistula affects approximately 2 million women worldwide, predominantly in places with a high Human Immunodeficiency Virus (HIV) burden. In Malawi, where thousands of women live with fistulas, HIV prevalence is 11-13%. Although repair is usually successful, surgical outcomes among immunocompromised women are poorly understood. Inconsistent guidelines regarding the Cluster of Differentiation 4 (CD4) threshold necessary for repair make it difficult for surgeons to make informed decisions. This study compares the postoperative outcomes of women undergoing obstetric fistula repair with and without HIV, stratified by CD4 count.Methods:This is a retrospective case-control study using a database of women who underwent vesicovaginal fistula repair at the Fistula Care Center from 2010-2018. HIV-positive participants, stratified by CD4<350 and CD4>350, were matched to HIV-negative controls by age within 5 years and Goh classification. Controls were matched to cases in a 3:1 ratio. Bivariate analysis and logistic regression were conducted on indicators based on HIV status and CD4 count stratification. Outcomes included dye test results, pad weights, and continence status at 2 weeks post-repair.Results:54 seropositive women were matched to 135 seronegative women. Of the 54 HIV positive women, 22.2% (n=12) had a CD4 count < 350. We found no statistically significant difference in surgical outcomes between HIV-positive and negative patients. 93.5% of HIV positive and 90% of HIV negative women healed completely. In our sub-analysis of 12 seropositive women with CD4<350, we found a statically significant difference in successful closure, with 25% of women with CD4<350 having a positive dye test indicating incomplete closure, compared to 2.8% of women with CD4>350 (p=0.024).Conclusion and Global Health Implications:Our analysis confirms previous research indicating that seropositive women with a CD4>350 can safely undergo obstetric fistula repair. Further research is needed to evaluate postoperative outcomes among women with CD4<350.

Conserved broad HIV-1 Gag-specific responses associated with low viral load and high CD4+ T cell nadir and preserved HAART regimen.

Broad human immunodeficiency virus type 1 (HIV-1) Gag-specific cellular responses can control viremia and provide slow progression to Acquired immunodeficiency syndrome (AIDS). In this study, we evaluate multiple HIV-1 Gag-specific lymphoproliferative responses and find their connection with cluster of differentiation 4 (CD4)+ T cell count and viral load from chronically HIV-1-infected patients. We further search for the correlation between multiple Gag-specific lymphoproliferative responses and changes in highly active antiretroviral therapy (HAART) regimen. We found correlation between Gag-specific responses and higher CD4+ T cells nadir and low HIV-1 viral load. Additionally, we observed that HIV-1-infected subjects did not need to change HAART regimen, when multiple Gag responses are present. We concluded that the start of HAART when CD4+ T cell nadir is the highest as possible may promote Gag-specific cellular responses conservation. Multiple Gag responses must be important to suppress HIV-1 replication. Preserved Gag-specific responses reduce HIV-1 viral load and are associated with stability of HAART regimen. Keywords: HIV-1; Gag; lymphoproliferation; viral load; HAART.

Evaluation of Chlamydia trachomatis and HR-HPV infection in women living with HIV: a cross-sectional study

Introduction: Infections caused by Chlamydia trachomatis (CT) and Human Papilloma Virus (HPV) are among the most prevalent sexually transmitted infections (STIs) worldwide. CT infection in women living with the human immunodeficiency virus (HIV) can facilitate HIV transmission by increasing HIV shedding in cervicovaginal secretions. The prevalence of Human papillomavirus (HPV) infection is higher in women living with HIV when compared to HIV-negative women, even when comparing those with the same sociodemographic characteristics. Generally, they have a high viral load and a higher persistence of viral infection, which increases the risk of developing premalignant and malignant lesions in the lower genital tract. Objective: To evaluate the frequency of CT and High-Risk HPV (HR-HPV) infection among women living with HIV and the association with sociodemographic, behavioral and clinical characteristics. Methods: Cross-sectional study carried out with a population of 66 non-pregnant women aged between 18 and 70 years living with HIV and/or acquired immunodeficiency syndrome (AIDS) at the Hospital Universitário Antônio Pedro, Universidade Federal Fluminense (UFF), Niterói (RJ), Brazil, between the period of March 1, 2018 and October 31, 2018. A standardized questionnaire was applied including sociodemographic and behavioral characteristics, and clinical information (use of oral contraceptives, Antiretroviral Therapy (ART), cluster of differentiation 4 (CD4) cell count, and viral load). Endocervical samples were collected for CT (COBAS 4800® system, Roche) and HPV (COBAS® HPV test, Roche) detection. Fisher's Exact Test was used to assess the association between variables. Regression analyses were performed using the logistic model in order to identify the factors associated with the outcomes of interest. Results: A frequency of 1.5% for CT and 21.2% for HR-HPV was found. Age was the single factor that presented statistical significance associated with HR-HPV infection. Conclusion: Our study showed that some women living with HIV promote risky behavior which could facilitate the acquisition of other STIs, such as HPV and CT infection. Some of them, with detected viral load, were not using condoms even with HIV-negative partners. These results may suggest that in addition to treatment and follow-up of women living with HIV, STIs counseling and guidance may play an important role in the control of STIs in this population.

Chemical Compounds and Computational Prediction of Their Inhibitory Effects on the HIV-1 gp120 Receptor by Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), with Antler-Like Morphology of Fruiting Bodies.

In this study, crude extracts of Ganoderma lucidum (NGCs) were compared to the crude extracts of G. lucidum that has antler-like fruiting bodies (AGCs) for their cytotoxicity, inhibitory effects on the attachment of human immunodeficiency virus (HIV)-1 glycoprotein 120 (gp120) to cluster of differentiation 4 (CD4), identification and molecular docking simulations of chemical compounds to predict the best ligand inhibitor and the binding mechanism. Results showed that AGCs had a higher percentage of inhibition (54.3% ± 6.2%) at 150 ppm and higher cytotoxicity (half maximal cytotoxic concentration [CC50] < 300 ppm) than NGCs (CC50 < 400 ppm). Quadrupole time-of-flight (QTOF) liquid chromatography- mass spectrometry (LC-MS) results successfully identified 32 chemical compounds in AGCs and NGCs, comprising mostly ganoderic acids (62%) and their derivatives. Molecular docking simulations of ganolucidic acid A/D and ganoderic acid A/B predicted the strongest binding affinity via hydrogen bonding, suggesting the inhibition of HIV-1 gp120 attachment to CD4. The highest and lowest occupied molecular orbital (HOMO and LUMO, respectively) gap energies of ganoderic acids tended to have less negative HOMO energy and smaller HOMO-LUMO gap energy, implying increased interactions of ligands to the gp120 protein receptor. AGCs showed higher inhibition against HIV-1 gp120 than NGCs due to a higher abundance of ganoderic and ganolucidic acids, whereby both acids contributed the highest number of hydrogen bonds and polar interactions from the hydroxyl and carboxylic functional groups.

Immune-associated molecular occurrence and prognosis predictor of hepatocellular carcinoma: an integrated analysis of GEO datasets

ABSTRACT Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of cancer-related deaths worldwide. As immune response failure is the main factor in the occurrence and poor prognosis of HCC, our study aimed to develop an immune-associated molecular occurrence and prognosis predictor (IMOPP) of HCC. To that end, we discovered a 4-gene immune-associated gene signature: C–C motif chemokine ligand 14 (CCL14), kallikrein B1 (KLKB1), vasoactive intestinal peptide receptor 1 (VIPR1), and cluster of differentiation 4 (CD4). When tested on three cohorts as an immune-associated molecular occurrence predictor (IMOP), it had high sensitivity, specificity, and area under the receiver operating characteristics curve. When tested as an immune-associated molecular prognosis predictor (IMPP), it stratified the HCC prognosis for overall survival (Kaplan–Meier analysis, log rank P = 0.0016; Cox regression, HR = 1.832, 95% CI = 1.173–2.859, P = 0.008) and disease-free survival (Kaplan-Meier analysis, log rank P = 0.0227). IMPP also significantly correlated with the clinicopathological characteristics of HCC; integrating it with clinicopathological characteristics improved the accuracy of a nomogram for overall survival prediction (C-index: 0.7097 vs. 0.6631). In HCC tumor microenviroments, the proportion of CD8+ T cells significantly differed between IMOP-stratified groups. We conclude that IMOPP can potentially predict the occurrence of HCC in high-risk populations and improve prognostic accuracy by providing new biomarkers for risk stratification. In addition, we believe that the IMOP mechanism may be related to its effect on the proportion of CD8+ T cells in tumor-infiltrating lymphocytes.