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In this paper, we introduce a new approach, based on a unified framework incorporating Data Envelopment Analysis (DEA) and Ordered Weighted Averaging (OWA), for assessing water quality in contextual settings that involve a large number of hydrochemical parameters. In order to enhance discrimination among water sources, the DEA model is adopted with data-driven input variables, called “surrogate optimistic closeness values,” computed through an aggregation procedure that includes the observed values of the hydrochemical parameters with OWA weights. The proposed DEA-OWA methodology has been employed to assess the quality of 51 water samples, collected from irrigation wells in Sereflikochisar Basin, Turkey, by means of 19 hydrochemical parameters. Using different subjectivity levels, the Surrogate Water Quality Indices (SWQIs) that are produced are proven effective in enhancing discrimination among the water sources while enabling a more robust water quality-based ranking. The k-means analysis has been used for clustering the water quality of the wells into Excellent, Good, Permissible, and Unsuitable rather than using pre-set boundaries. Only one water source has been identified as Excellent, whereas 17.65%, 45.10%, and 35.29% of the sampled wells, respectively, are categorized with Good, Permissible, and Unsuitable water quality. Inferred from wells’ location, the results suggest that the groundwater might be drastically affected by saline water intrusion from Lake Tuz. The latter conclusion has been corroborated through a Tobit regression analysis.

The engagement of programmed death 1 (PD-1) to its ligands, PD-L1 and PD-L2 1 , 2 , 3 , 4 , inhibits proliferation and cytokine production mediated by antibodies to CD3 (refs. 5 , 6 , 7 ). Blocking the PD-1–PD-L1 pathway in mice chronically infected with lymphocytic choriomeningitis virus restores the capacity of exhausted CD8 + T cells to undergo proliferation, cytokine production and cytotoxic activity and, consequently, results in reduced viral load 8 . During chronic HIV infection, HIV-specific CD8 + T cells are functionally impaired 9 , 10 , 11 , showing a reduced capacity to produce cytokines and effector molecules as well as an impaired capacity to proliferate 12 , 13 , 14 , 15 . Here, we found that PD-1 was upregulated on HIV-specific CD8 + T cells; PD-1 expression levels were significantly correlated both with viral load and with the reduced capacity for cytokine production and proliferation of HIV-specific CD8 + T cells. Notably, cytomegalovirus (CMV)-specific CD8 + T cells from the same donors did not upregulate PD-1 and maintained the production of high levels of cytokines. Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8 + T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen. The accumulation of HIV-specific dysfunctional CD8 + T cells in the infected host could prevent the renewal of a functionally competent HIV-specific CD8 + repertoire.

Background: The implication and clinical significance of low-level viremia (LLV) in HIV patients are still not clear. This study aimed to characterize the clinical outcomes and to evaluate whether LLV could predict future virological failure in a well-defined cohort of HIV-infected Omani patients attending a large HIV clinic. Methods: Patients on regular antiretroviral therapy (ART) for at least 12 months, and had at least 2 HIV RNA measurements 1 year after starting ART, were prospectively enrolled in a cohort study. LLV was defined as plasma HIV RNA between 50-200 copies/mL that persists after at least 2 consecutive measurements after 12 months of ART. Multivariate Cox proportional hazards regression model was used to measure the association among virological failure, LLV and potential predictors. Results: After 12 months of starting ART, 60 patients (40%) had undetectable viral load (UVL) < 50 copies/mL, while 37 patients (24%) had LLV and 53 patients (35%) had primary virological failure > 200 copies/mL. The incidence rates of subsequent secondary virological failure for UVL and LLV groups, were 3 and 7 cases per 1000 patient-months, respectively. Compared to UVL group, LLV group had increased risk of subsequent secondary virological failure with hazard ratio of (4.437 [95% CI, 1.26-15.55]; p = 0.02). Age, duration of HIV infection, pretreatment HIV RNA level, pretreatment CD4+ cell count, and ART adherent were associated with subsequent secondary virological failure. Conclusion: Collectively, Omani HIV patients with LLV were at a higher risk for HIV virological failure, and should be monitored closely. Further studies are need to assess whether ART modification in LLV patients would lower the risk of virological failure.

Purpose As treatment options for children with sickle cell anemia (SCA) continue to expand survival, evaluation of factors associated with health-related quality of life (HRQoL) is becoming an important aspect for further improving clinical management. Although the general features of SCA are similar, factors influencing HRQoL within a country may differ from those of other countries, therefore this study aimed to explore factors affecting HRQoL in children with SCA living in the Sultanate of Oman. Methods This was a cross-sectional study in which the PedsQL™ Sickle Cell Disease Module was used to evaluate the overall HRQoL in children with SCA. The socio-demographic data, clinical, and treatment outcomes were collected. Univariate and multivariate linear regression analyses were used to identify predictors of HRQoL. Results A total of 123 children with SCA, aged from 2 to 16 years were enrolled. The mean total HRQoL score was 52 ± 15% (9–94), where Worry II scale recorded the highest score. The multiple regression analysis revealed that the only predictors of total HRQoL score were hemoglobin F ( B  = 0.64, 95% confidence interval [CI] 0.149–1.118, P  = 0.009) and to a lesser degree white blood cell count ( B  = − 0.99, 95% CI − 1.761 to − 0.198, P  = 0.01), independently of other study parameters such as age, gender, spleen status, and hydroxyurea therapy. Conclusions Collectively, these findings indicated that hemoglobin F out-weighted white blood cell count in predicting HRQoL in Omani children with SCA. Recognition of these factors could help health professionals to develop effective strategies to improve the overall HRQoL in these young patients.

Background: Antiretroviral therapy (ART) adherence is crucial to achieve HIV suppression and to prolong survival of HIV-infected patients. Although monitoring of ART adherence is standard of HIV care, there is yet no optimal method to measure ART adherence. Therefore, it is essential to compare the effectiveness of different adherence measurement tools to predict HIV suppression. Methods: In this study, we measured ART adherence using pharmacy refill prescription and self-reported adherence questionnaire. Both the methods were compared for predicting HIV suppression in adult Omani HIV-infected patients attending the outpatient clinics at Sultan Qaboos University Hospital. Results: A total of 141 HIV-infected patients were included. The pharmacy refill–based measure showed a median adherence rate of 98.90% (interquartile range [IQR]: 86%-99.45%). The self-report adherence questionnaire revealed a median adherence rate of 100% (IQR: 75-100). A significant positive correlation was found between the adherence rates measured by the 2 methods (r = 0.32, P = .01). The pharmacy refill and self-report questionnaire adherence measures were both negatively correlated with plasma HIV RNA levels (r = −0.20, P = .01 and r = −0.26, P = .04, respectively). Conclusion: Collectively, these findings suggest that pharmacy refill measure could serve as a valid and practical tool of ART adherence in routine clinical practice.

Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control (HIV-) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B cell survival in ST subjects was significantly enhanced by the addition of exogenous IL-2 in a Foxo3a-dependent manner. We further showed that Foxo3a silencing by siRNA resulted in decreased expression of TRAIL and apoptosis levels in memory B cells from ST subjects. Our results thus establish a direct role for Foxo3a/TRAIL signaling in the persistence of memory B cells and provide a mechanism for the reduced survival of memory B cells during HIV infection. This knowledge could be exploited for the development of therapeutic and preventative HIV vaccines.

Background: Despite sustained viral control by antiretroviral therapy (ART), some HIV-infected patients do not recover normal CD4+ T cell counts. This Discordant Immune Response (DIR) increases the risk of opportunistic infections. Objective: To evaluate the factors associated with DIR in HIV-infected Omani patients attending public sector clinics. Methods: All HIV-infected patients receiving ART with regular follow-up visits were eligible for this study. The DIR group comprised patients on ART for at least two years with plasma HIV viral load < 50 copies/mL and helper CD4+ T cell counts below 350 cells/μl. The Concordant Immune Responses (CIR) group was similar to DIR but with CD4+ T cell counts above 350 cells/μl. Univariate and multivariate analyses using logistic regression models were used to assess the impact of demographic characteristics, clinical, immunological and virological parameters, type of ART regimens, tuberculosis and other opportunistic co-infections on DIR. Results: Among 153 enrolled participants, 28 and 76 patients were identified as having DIR and CIR, respectively. The multivariate analysis revealed that the only factors independently associated with DIR after adjustment were age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.04-1.23), baseline CD4+ T cell count (OR: 0.98; CI: 0.97-0.99) and baseline CD56+ cell count (OR: 0.97; CI: 0.96-0.99). Conclusion: Collectively, these findings suggest that a significant proportion of HIV-infected Omani patients develop DIR totaling 27%, and efforts should be made to improve early identification of these patients who tend to experience poor clinical outcomes.

Background. Concentrations of interleukin (IL)-18 increase in the circulation of human immunodeficiency virus (HIV)-infected persons. However, nothing is known concerning the regulation of IL-18-binding protein (IL-18BP), which neutralizes IL-18 in vivo. This issue is addressed in the present study. Methods. Serum samples obtained from healthy subjects and HIV-infected patients were analyzed by enzymelinked immunosorbent assay to determine their IL-18 and IL-18BP contents. Human monocyte-derived macrophages (MDMs) were infected in vitro with HIV type 1 (HIV-1), and the production of these 2 cytokines by these cells was measured. Finally, we determined the effect of IL-18 on HIV-1 replication in human cells. Results. In contrast to IL-18 levels, IL-18BP levels decreased in the serum of HIV-infected patients. This decrease resulted in enhanced levels of free IL-18 in the serum of such patients. The infection increased production of IL-18 but decreased that of IL-18BP in MDMs. IL-10 and transforming growth factor-β, concentrations of which are increased in HIV-infected persons, also decreased production of IL-18BP by human MDMs. Finally, recombinant human IL-18 enhanced HIV-1 replication in human CD4+ T cells. Conclusions. Production of IL-18 and its antagonist becomes imbalanced in HIV-1-infected persons. The infection and the cytokine milieu play a role in this decreased production. The increased biological activities of IL-18 may enhance viral replication in human CD4+ T cells.

Highly active antiretroviral therapy is unable to eliminate HIV infection, because the virus persists in latently infected CD4 + T cells—a so-called virus reservoir. Rafick-Pierre Sekaly and his colleagues have shown that central memory CD4 + T cells and transitional memory CD4 + T cells are the main cellular reservoirs for HIV, and they suggest a mechanism that ensures the stability of this reservoir of virus. HIV persists in a reservoir of latently infected CD4 + T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (T CM ) and transitional memory (T TM ) CD4 + T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in T CM cells in subjects showing reconstitution of the CD4 + compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in T TM cells from aviremic individuals with low CD4 + counts and higher amounts of interleukin-7–mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.

The authors describe a rare case of a 27-year old previously healthy male presenting with high grade fever, pancytopenia, hepatosplenomegaly, high levels of ferritin and triglyceride, suggesting a diagnosis of hemophagocytic lymphohistiocytosis (HLH) syndrome. Other investigations showed a positive Leishmania infantum serology and high Epstein-Barr virus (EBV) viremia. The diagnosis of a visceral leishmaniasis was confirmed by bone morrow biopsy, which showed Leishman-Donovan bodies and evidence of HLH. The patient received liposomal amphotericin B and he had a complete resolution of his symptoms and clearance of EBV viremia. This case of HLH associated with visceral leishmaniasis and EBV co-infection raises the question about the significance of EBV in patients with HLH. The treatment of actual etiological agent can lead to complete cure while using current recommend chemotherapy for HLH-related EBV in a patient with hidden infection may have deleterious effects.