High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

<p>Abstract</p> <p>Background</p> <p>Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function.</p> <p>Methods</p> <p>To address this issue we analyzed CD4⁺T absolute counts and the proportion of CD8⁺T cells expressing CD38 in <it>Leishmania</it>/HIV co-infected patients that recovered after anti-leishmanial therapy.</p> <p>Results</p> <p>We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4⁺T cell counts under 200 cells/mm³, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm³). Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4⁺T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8⁺T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects.</p> <p>Conclusions</p> <p><it>Leishmania </it>infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4⁺T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.</p

Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS during the adult life

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Diversidad de avispas parasitoides de la familia Encyrtidae (Hymenoptera: Chalcidoidea) del bosque tropical caducifolio en San Buenaventura, Jalisco, México Diversity of parasitoid wasps of the family Encyrtidae (Hymenoptera: Chalcidoidea) in the tropical dry forest of San Buenaventura, Jalisco, Mexico

Se presentan los resultados del estudio de la fauna de avispas parasitoides de la familia Encyrtidae en el bosque tropical caducifolio de San Buenaventura, Jalisco, México. El estudio se llevó a cabo de noviembre de 1996 a octubre de 1997. La recolección se realizó con trampas Malaise durante 5 días de cada mes. Se registró un total de 61 especies, 30 géneros, 13 tribus y 2 subfamilias. El mayor número de géneros y especies fue de la subfamilia Encyrtinae, con 22 géneros y 44 especies, seguida por Tetracneminae con 8 géneros y 17 especies. El género con mayor número de especies fue Metaphycus con 11. Las especies recolectadas no fueron abundantes, y su riqueza y abundancia varió estacionalmente, registrándose los valores más altos durante la temporada de lluvias. La similitud de la fauna de San Buenaventura, Jalisco con la de Huautla, Morelos fue mayor que la encontrada en otras regiones previamente estudiadas de bosque tropical caducifolio (San Javier, Sonora y Huatulco, Oaxaca).<br>Results of a faunistic study of the parasitoid wasps of the family Encyrtidae of the tropical dry forest of San Buenaventura, Jalisco, Mexico are presented. The study was carried out from November 1996 to October 1997. Collecting technique was Malaise trapping. Collections were carried out during 5 days of every month. A total of 61 species, 30 genera, 13 tribes and 2 subfamilies were recorded. The subfamily with the largest number of species was Encyrtinae with 22 genera and 44 species, followed by Tetracneminae with 8 genera and 17 species. The genus with the largest number of species was Metaphycus with 11. Species had low abundance. Species richness and abundance varied with time, with the highest values recorded in the rainy season. The fauna of San Buenaventura, Jalisco was most similar to that of Huautla, Morelos, than to that of San Javier, Sonora and Huatulco, Oaxaca, all of them previously studied

Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients

Background: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. Methods: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. Results: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = &minus;0.36, p = 0.0027). Conclusion: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests

RNU6-1 in circulating exosomes differentiates GBM from non-neoplastic brain lesions and PCNSL but not from brain metastases.

Background. Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Circulating biomarkers may assist in the processes of differential diagnosis and response assessment. GBM cells release extracellular vesicles containing a subset of proteins and nucleic acids. We previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to healthy subjects. In this exploratory study, we investigated the role of this small noncoding RNA as a diagnostic biomarker for GBM versus other brain lesions with some potential radiological similarities. Methods. We analyzed the expression of RNU6-1 in circulating exosomes of GBM patients (n = 18), healthy controls (n = 30), and patients with subacute stroke (n = 30), acute/subacute hemorrhage (n = 30), acute demyelinating lesions (n = 18), brain metastases (n = 21), and primary central nervous system lymphoma (PCNSL; n = 12) using digital droplet PCR. Results. Expression of RNU6-1 was significantly higher in GBM patients than in healthy controls (P = .002). RNU6-1 levels were also significantly higher in exosomes from GBM patients than from patients with nonneoplastic lesions (stroke [P = .05], hemorrhage [P = .01], demyelinating lesions [P = .019]) and PCNSL (P = .004). In contrast, no significant differences were found between patients with GBM and brain metastases (P = .573). Receiver operator characteristic curve analyses supported the role of this biomarker in differentiating GBM from subacute stroke, acute/subacute hemorrhage, acute demyelinating lesions, and PCNSL (P < .05), but again not from brain metastases (P = .575)

RNU6-1 in circulating exosomes differentiates GBM from non-neoplastic brain lesions and PCNSL but not from brain metastases.

Background. Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Circulating biomarkers may assist in the processes of differential diagnosis and response assessment. GBM cells release extracellular vesicles containing a subset of proteins and nucleic acids. We previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to healthy subjects. In this exploratory study, we investigated the role of this small noncoding RNA as a diagnostic biomarker for GBM versus other brain lesions with some potential radiological similarities. Methods. We analyzed the expression of RNU6-1 in circulating exosomes of GBM patients (n = 18), healthy controls (n = 30), and patients with subacute stroke (n = 30), acute/subacute hemorrhage (n = 30), acute demyelinating lesions (n = 18), brain metastases (n = 21), and primary central nervous system lymphoma (PCNSL; n = 12) using digital droplet PCR. Results. Expression of RNU6-1 was significantly higher in GBM patients than in healthy controls (P = .002). RNU6-1 levels were also significantly higher in exosomes from GBM patients than from patients with nonneoplastic lesions (stroke [P = .05], hemorrhage [P = .01], demyelinating lesions [P = .019]) and PCNSL (P = .004). In contrast, no significant differences were found between patients with GBM and brain metastases (P = .573). Receiver operator characteristic curve analyses supported the role of this biomarker in differentiating GBM from subacute stroke, acute/subacute hemorrhage, acute demyelinating lesions, and PCNSL (P < .05), but again not from brain metastases (P = .575)