When coronavirus infectious disease-2019 (COVID-19) blew up, ill-fated auguries on the collision between COVID-19 and the human immunodeficiency virus (HIV) epidemics loomed.
Data from observational ...studies suggest similar incidence attacks of SARS-CoV-2 infection in people living with HIV (PLWH) and HIV-uninfected populations. The mortality rate of COVID-19 is similar in both populations too. The authors discuss the role of combination antiretroviral therapy (cART) in preventing infection or reducing COVID-19 severity. They also discuss the pharmacological interventions for COVID-19 in PLWH.
Management of COVID-19 in PLWH is no different from the general population. It should be based on careful supportive care, emphasizing lung-protective ventilation, and wise pharmacological interventions. The antiviral drug remdesivir and dexamethasone are the only pharmacological interventions with clinical benefit for COVID-19, whereas anticoagulation may prevent thrombotic complications. The experience with using these drugs in PLWH is limited, which prevents from rendering well-founded conclusions. Until more data on COVID-19 in PLWH become available, the best weapons within our reach are sound supportive care and sensible use of RDV and dexamethasone, bearing in mind the potential for drug-drug interactions of most corticosteroids and antiretroviral drugs.
Dry rivers are a type of non-perennial river characterized by extreme dry conditions and dominance of terrestrial habitats. They are present in all continents, being especially abundant in arid and ...semiarid regions. Recent studies have shown their capacity to provide ecosystem services, although they are often undervalued and altered. This study is a literature review on the ecosystem services provided by dry rivers to human well-being. We apply the conceptual framework for the Millennium Ecosystem Assessment. First, we describe and exemplify the services provided by the natural system and its biodiversity. Second, we present the contributions of the local social system to service provision through co-production processes. Finally, the main drivers of ecosystem change that alter service provision are listed and discussed. We found that dry rivers and their biodiversity contribute to local human well-being. The ecological knowledge and culture of local human communities acquired over generations contribute to service provision maintaining the socio-ecological system’s sustainability and its resilience to disturbances. Among drivers of change, those of a social-cultural (e.g., sedentarization) and economic (e.g., globalization) nature affect dry rivers’ capacity to provide ecosystem services the most. Reconciling people and dry rivers requires a great deal of research and education.
Chimeric antigen receptor–based therapies beyond cancer Velasco‐de Andrés, María; Muñoz‐Sánchez, Guillermo; Carrillo‐Serradell, Laura ...
European journal of immunology,
March 2023, 2023-03-00, 20230301, Letnik:
53, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Adoptive cell transfer (ACT) therapies have gained renewed interest in the field of immunotherapy following the advent of chimeric antigen receptor (CAR) technology. This immunological breakthrough ...requires immune cell engineering with an artificial surface protein receptor for antigen‐specific recognition coupled to an intracellular protein domain for cell activating functions. CAR‐based ACT has successfully solved some hematological malignancies, and it is expected that other tumors may soon benefit from this approach. However, the potential of CAR technology is such that other immune‐mediated disorders are beginning to profit from it. This review will focus on CAR‐based ACT therapeutic areas other than oncology such as infection, allergy, autoimmunity, transplantation, and fibrotic repair. Herein, we discuss the results and limitations of preclinical and clinical studies in that regard.
Engineering immune cells with chimeric antigen receptors (CARs) for adoptive cell immunotherapy has captivated the interest of oncologists to combat hematological cancer. Novel applications of CAR‐based technology are beginning to be implemented in a myriad of medical conditions as diverse as autoimmunity, infection, asthma, transplantation, hemophilia, or cardiac fibrosis.
To assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human ...immunodeficiency virus (PLWH), on human adipose cells.
Drugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays.
Overall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir.
The INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH.
•Integrase inhibitors do not affect human adipose cell differentiation in culture.•Integrase inhibitors have different effects on adipokine and cytokine expression in human adipocytes.•Dolutegravir, but not bictegravir or raltegravir, represses gene expression and release of adiponectin and leptin.
Diagnostic and therapeutic caveats in Griscelli syndrome Castaño‐Jaramillo, Lina‐Maria; Lugo‐Reyes, Saul O.; Cruz Muñoz, Mario E. ...
Scandinavian journal of immunology,
June 2021, 2021-Jun, 2021-06-00, 20210601, Letnik:
93, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Griscelli syndrome (GS) is a rare autosomal recessive disease with characteristic pigment distribution, and there are currently 3 types according to the underlying genetic defect and clinical ...features. We present the case of a girl born from consanguineous parents who presented with predominant neurologic symptoms, silvery hair and granulomatous skin lesions. Cerebral magnetic resonance revealed diffuse white matter lesions, and central nervous system (CNS) lymphocytic infiltration was suspected. The patient underwent haematopoietic stem cell transplantation with graft failure and autologous reconstitution. She developed elevated liver enzyme with a cholestatic pattern. Multiple liver biopsies revealed centrilobular cholestasis and unspecific portal inflammation that improved with immunomodulatory treatment. She was revealed to have an impaired cytotoxicity in NK cells and a decreased expression of RAB27A. However, no variants were found in the gene. All types of GS present with pigment dilution and irregular pigment clumps that can be seen through light microscopy in hair and skin biopsy. Dermic granulomas and immunodeficiency with infectious and HLH predisposition have been described in GS type 2 (GS2). Neurologic alterations might be seen in GS type 1 (GS1) and GS type 2 (GS2), due to different mechanisms. GS1 presents with neurologic impairment secondary to myosin Va role in neuronal development and synapsis. Meanwhile, GS2 can present with neurologic impairment secondary to SNC HLH. Clinical features and cytotoxicity might aid in differentiating GS1 and GS2, especially since treatment differs.
Elvitegravir is a recently developed integrase inhibitor used for antiretroviral treatment of HIV infection. Secondary effects, including disturbances in lipid metabolism and, ultimately, in adipose ...tissue distribution and function, are common concerns associated with antiretroviral treatments. Here, we provide the first study of the effects of elvitegravir (in comparison with efavirenz, a non-nucleoside analog inhibitor of reverse transcriptase; and raltegravir, another integrase inhibitor) on human adipocyte differentiation, gene expression and secretion of adipokines and cytokines. Elvitegravir impaired adipogenesis and adipocyte metabolism in human SGBS adipocytes in a concentration-dependent manner (delaying acquisition of adipocyte morphology and reducing the expression of adipogenesis marker genes such as PPARγ, glucose transporter GLUT4, lipoprotein lipase, and the adipokines adiponectin and leptin). Compared with efavirenz, the effects of elvitegravir were similar but tended to occur at higher concentrations than those elicited by efavirenz, or were somewhat less intense than those caused by efavirenz at similar concentration. Elvitegravir tended to cause a more moderate induction of pro-inflammatory cytokines than efavirenz. Efavirenz induced a marked concentration-dependent increase in interleukin-8 expression and release whereas elvitregravir had little effect. Raltegravir had totally neutral actions of adipogenesis, adipocyte metabolism-related gene expression and release of adipokines and cytokines. In conclusion, elvitegravir alters adipocyte differentiation and function and promotes induction of pro-inflammatory cytokines similarly to efavirenz, but several effects were less intense. Further assessment of lipid metabolism and adipose tissue function in patients administered elvitegravir-based regimes is advisable considering that totally neutral effects of elvitegravir on lipid homeostasis cannot be anticipated from the current study in vitro.
•We determined the effects of elvitegravir on human adipocytes in culture.•Elvitegravir impairs adipogenesis and adipocyte metabolism in adipocytes.•Elvitegravir induces the expression and release of pro-inflammatory cytokines.•The effects of elvitegravir were similar to efavirenz, but less intense.
Background
Long-term antiviral therapy has resulted in viral suppression and biochemical response in chronic hepatitis B, although the risk of hepatocellular carcinoma has not been abolished. The ...Page-B score could be useful to estimate the probability of HCC.
Aims
To analyze the effectiveness and safety of entecavir or tenofovir for more than 4 years and the usefulness of Page-B score in the real-world setting.
Methods
Analysis of Caucasian chronic hepatitis B subjects treated with entecavir or tenofovir from the prospective, multicenter database CIBERHEP.
Results
A total of 611 patients were enrolled: 187 received entecavir and 424 tenofovir. Most were men, mean age 50 years, 32% cirrhotic and 16.5% HBeAg-positive. Mean follow-up was 55 (entecavir) and 49 (tenofovir) months. >90% achieved HBV DNA <69 IU/mL and biochemical normalization by months 12 and 36, respectively. Cumulative HBeAg loss and anti-HBe seroconversion were achieved by 33.7 and 23.8%. Four patients lost HBsAg; three HBeAg-positive. Renal function remained stable on long-term follow-up. Fourteen (2.29%) developed HCC during follow-up all of them with baseline Page-B ≥10. Nine were diagnosed within the first 5 years of therapy. This contrasts with the 27 estimated by Page-B, a difference that highlights the importance of regular HCC surveillance even in patients with virological suppression.
Conclusions
Entecavir and tenofovir achieved high biochemical and virological response. Renal function remained stable with both drugs. A Page-B cut-off ≥10 selected all patients at risk of HCC development.
Emotional intelligence (EI), or the ability to perceive, use, understand and regulate emotions, appears to be helpful in the performance of "hot" (i.e., emotionally laden) cognitive tasks when using ...performance-based ability models, but not when using self-report EI models. The aim of this study is to analyze the relationship between EI (as measured through a performance-based ability test, a self-report mixed test and a self-report ability test) and cognitive control ability during the performance of hot and "cool" (i.e., non-emotionally laden) "go/no-go" tasks. An experimental design was used for this study in which 187 undergraduate students (25% men) with a mean age of 21.93 years (standard deviation SD = 3.8) completed the three EI tests of interest (Mayer-Salovey-Caruso Emotional Intelligence Test MSCEIT, Trait Meta-Mood Scale TMMS and Emotional Quotient Inventory-Short Form EQi:S) as well as go/no-go tasks using faces and geometric figures as stimuli. The results provide evidence for negative associations between the "managing" branch of EI measured through the performance-based ability test of EI and the cognitive control index of the hot go/no-go task, although similar evidence was not found when using the cool task. Further, the present study failed to observe consistent results when using the self-report EI instruments. These findings are discussed in terms of both the validity and implications of the various EI models.
During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, ...768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.
Abstract
Background
Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine ...estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.
Methods
Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient’s characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.
Results
The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR adjusted median difference (±SD) –3.5 ± 1.6 (95% CI –6.6 to –0.3), P = 0.047, and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent adjusted OR 3.233 (95% CI 1.343–7.782), P = 0.009, with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).
Conclusions
Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
PDF
