This review presents literature that highlights saliva’s utility as a biofluid in the diagnosis and monitoring of COVID-19. A systematic search was performed in 5 electronic databases (PubMed, ...Embase, LILACS, Scopus, and Web of Science). Studies were eligible for inclusion if they assessed the potential diagnostic value and/or other discriminatory properties of biological markers in the saliva of patients with COVID-19. As of July 22, 2020, a total of 28 studies have investigated the presence of SARS-CoV-2 RNA in saliva. Several of those studies confirmed reliable detection of SARS-CoV-2 in the saliva of patients with COVID-19. Saliva offered sensitivity and specificity for SARS-CoV-2 detection comparable to that of the current standard of nasopharyngeal and throat swabs. However, the utility of saliva in diagnosing COVID-19 infection remains understudied. Clinical studies with larger patient populations that measure recordings at different stages during the disease are still necessary to confirm the accuracy of COVID-19 diagnosis with saliva. Nevertheless, the utility of saliva as a diagnostic tool opens the possibility of using rapid and less invasive diagnostic strategies by targeting bioanalytes rather than the pathogen.
Traumatic stress in early-life increases the risk for cognitive and neuropsychiatric disorders later in life. Such early stress can also impact the progeny even if not directly exposed, likely ...through epigenetic mechanisms. Here, we report in mice that the offspring of males subjected to postnatal traumatic stress have decreased gene expression in molecular pathways necessary for neuronal signaling, and altered synaptic plasticity when adult. Long-term potentiation is abolished and long-term depression is enhanced in the hippocampus, and these defects are associated with impaired long-term memory in both the exposed fathers and their offspring. The brain-specific gamma isoform of protein kinase C (Prkcc) is one of the affected signaling components in the hippocampus. Its expression is reduced in the offspring, and DNA methylation at its promoter is altered both in the hippocampus of the offspring and the sperm of fathers. These results suggest that postnatal traumatic stress in males can affect brain plasticity and cognitive functions in the adult progeny, possibly through epigenetic alterations in the male germline.
A common polymorphism (1245A>C) in the HSD3B1 gene is associated with increased de novo synthesis of androgens and worse outcomes in men treated with androgen-deprivation therapy for metastatic ...castration-sensitive prostate cancer. The objective of the study was to determine whether this polymorphism is associated with outcomes for metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide.
A total of 547 patients treated with abiraterone or enzalutamide from two prospective cohorts were evaluated. The HSD3B1 genotype was determined by targeted sequencing and/or TaqMan single-nucleotide polymorphism genotyping. In cohort 1, patients were randomized to receive abiraterone + prednisone or enzalutamide. In cohort 2, patients received either agent according to investigator's choice. Prostate-specific antigen (PSA) response rate, time to PSA progression (TTPP), time to progression (TTP) and overall survival were determined. Associations between HSD3B1 genotypes and outcomes were evaluated via univariate Cox regression. Multivariable Cox model was used to determine the independent association of each covariate.
The HSD3B1 variant genotype (CC) was present in 15% of patients and was associated with worse TTP hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.02–1.67, P = 0.032 and PSA response rates (48% for CC versus 62% and 65% for AA and AC, respectively P = 0.019), with no significant difference in TTPP (HR 1.28, 95% CI 0.99–1.66, P = 0.064). The effect of genotype was similar for treatment with abiraterone or enzalutamide with a negative test for interaction for TTPP (P = 0.997) and TTP (P = 0.749). Multivariable analysis did not show a significant association between genotype and TTP or TTPP.
The HSD3B1 (CC) genotype was associated with shorter TTP and lower PSA response rate in patients with mCRPC treated with abiraterone or enzalutamide. However, the CC genotype did not provide prognostic information beyond that conferred by standard clinical variables, suggesting that it may not be a suitable stand-alone biomarker in mCRPC.
•The HSD3B1 homozygous variant genotype CC was associated with shorter time to progression on abiraterone and enzalutamide.•The effect of the CC genotype on time to progression was the same for abiraterone and enzalutamide.•Patients who present the CC genotype were less likely to achieve a prostate-specific antigen response (≥50% decline).•The CC genotype was not confirmed as an independent prognosis factor and it may not be a suitable stand-alone biomarker in metastatic castration-resistant prostate cancer.
We evaluated the effects of supplementing bacterial direct-fed microbial (DFM) on performance, apparent total-tract digestibility, rumen fermentation, and immune parameters of lactating dairy cows. ...One hundred fourteen multiparous Holstein cows (41 ± 7 DIM) were used in a randomized complete block design with an experiment comprising 14 d of a covariate (pre-experimental sample and data collection) and 91 d of an experimental period. Cows were blocked based on energy-corrected milk (ECM) yield during the covariate period and the following treatments were randomly assigned within each block: (1) control (CON), corn silage-based total mixed ration without DFM; (2) PRO-A, basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 10
cfu/d; and 3) PRO-B, basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and Bacillus licheniformis at 11.8 × 10
cfu/d. Milk yield, dry matter intake (DMI), and body weight were measured daily, while milk samples for component analysis were taken on 2 consecutive days of each week of data collection. Feces, urine, rumen, and blood samples were taken during the covariate period, wk 4, 7, 10, and 13 for estimation of digestibility, N-partitioning, rumen fermentation, plasma nutrient status and immune parameters. Treatments had no effect on DMI and milk yield. Fat-corrected milk (3.5% FCM) and milk fat yield were improved with PRO-B, while milk fat percent and feed efficiency (ECM/DMI) tended to increase with PRO-B compared with PRO-A and CON. Crude fat digestibility was greater with PRO-B compared with CON. Feeding CON and PRO-A resulted in higher total volatile fatty acid concentration relative to PRO-B. Percentage of neutrophils tended to be reduced with PRO-A compared with CON and PRO-B. The mean fluorescence intensity (MFI) of anti-CD44 antibody on granulocytes tended to be higher in PRO-B compared with CON. The MFI of anti-CD62L antibody on CD8+ T cells was lower in PRO-A than PRO-B, with PRO-A also showing a tendency to be lower than CON. This study indicates the potential of DFM to improve fat digestibility with consequential improvement in fat corrected milk yield, feed efficiency and milk fat yield by lactating dairy cows. The study findings also indicate that dietary supplementation with DFM may augment immune parameters or activation of immune cells, including granulocytes and T cells; however, the overall effects on immune parameters are inconclusive.
Seasonal influenza virus infection is a significant cause of morbimortality in the elderly. However, there is poor vaccine efficacy in this population due to immunosenescence. We aimed to explore ...several homeostatic parameters in the elderly that could impact influenza vaccine responsiveness.
Subjects (> 60 years old) who were vaccinated against influenza virus were included, and the vaccine response was measured by a haemagglutination inhibition (HAI) test. At baseline, peripheral CD4 and CD8 T-cells were phenotypically characterized. Thymic function and the levels of different inflammation-related biomarkers, including Lipopolysaccharide Binding Protein (LBP) and anti-cytomegalovirus (CMV) IgG antibodies, were also measured.
Influenza vaccine non-responders showed a tendency of higher frequency of regulatory T-cells (Tregs) before vaccination than responders (1.49 1.08-1.85 vs. 1.12 0.94-1.63, respectively,
= 0.061), as well as higher expression of the proliferation marker Ki67 in Tregs and different CD4 and CD8 T-cell maturational subsets. The levels of inflammation-related biomarkers correlated with the frequencies of different proliferating T-cell subsets and with thymic function (e.g., thymic function with D-dimers, r = - 0.442,
= 0.001).
Age-related homeostatic dysregulation involving the proliferation of CD4 and CD8 T-cell subsets, including Tregs, was related to a limited responsiveness to influenza vaccination and a higher inflammatory status in a cohort of elderly people.
The essential oil (EO) composition of leaves of Campomanesia aurea was analyzed by GC-MS. The plant was collected in April (EOA) and October (EOO) in São Francisco de Assis/RS. The essential oils ...were obtained by hydrodistillation in a modified Clevenger apparatus. The yields were 4.44% in April, and 6.15%, in October. Thirty-one compounds were identified in EOA, accounting for 96.87% of the total, and twenty-eight compounds were identified in EOO, accounting for 99.46% of the total. For EOA, the major identified monoterpene was p-cymene (8.33%) and the major identified sesquiterpene was α-cadinol (10.72%), while regarding EOO the major identified monoterpene was repeatedly Terpinolene (3.43%), whereas the major identified sesquiterpene was α-cadinol (12.79%). The antibacterial activity of the essential oil was evaluated against the three Listeria monocytogenes from the American Type Culture Collection (strains ATCC 7644, 19114 and 13932). The essential oil showed a MIC of 10 mg/mL against the strains ATCC 7644 and 19114, with bacteriostatic effect of 20 mg/mL and a MIC of 20 mg/mL for ATCC 13932. Regarding the antibiofilm activity, o EOO showed the best results with an inhibition of 90% in the sessile growth with an applied concentration of 4.0 mg/mL.
The dual crop coefficient approach accounts separately for plant transpiration and soil evaporation by using the basal crop coefficient and the evaporation coefficient, respectively. The SIMDualKc ...model, which performs the soil water balance simulation with estimation of the actual crop evapotranspiration (ET) with the dual crop coefficient approach, was applied to a drip-irrigated peach orchard under Mediterranean conditions. Orchard ET was obtained with the eddy covariance technique, which was subsequently correlated with tree transpiration estimated from sap flow measurements and soil evaporation determined with microlysimeters, thus providing ET for the whole irrigation season. Two years of field observations were used for model calibration and validation using those ET measurements and taking into account the fraction of ground covered by trees through a density factor which adjusts the basal crop coefficient. Model fitting relative to ET observations during calibration and validation provided indices of agreement averaging 0.90, coefficients of regression close to 1.0, root mean square errors around 0.41 mm and average absolute errors of 0.32 mm. Model fitting relative to transpiration and to soil evaporation produced similar results, so showing the adequateness of modelling.
The objective of this work was to perform an integrative review of the inspection of peri-implant bone defects using cone beam computed tomography (CBCT). An electronic search was performed in the ...PubMed database using the following scientific terms: CBCT or Cone Beam computed tomography; dental implant; peri-implant; bone loss; defects. The survey identified 267 studies, of which 18 were considered relevant to this study. These studies provided important data taking into account the accuracy of cone beam computed tomography in the detection and measurement of peri-implant bone defects such as fenestrations, dehiscence and intraosseous circumferential defects. The effectiveness of CBCT in aiding in geometric bone calculations and in the diagnosis of peri-implant defects was influenced by factors such as artefacts, defect size, bone wall thickness, implant material, adjustment of acquisition parameters and observer experience. A not insignificant number of studies compared intraoral radiography to CBCT in the detection of peri-implant bone loss. CBCT was clearly superior to intraoral radiography in the detection of all peri-implant bone defects, except for defects located in the interproximal zone. In general, studies have shown that peri-implant bone measurements adjacent to the implant surface can be correctly determined, as well as the diagnosis of peri-implant bone defects with an average discrepancy of less than 1 mm from the actual measurement of the defect.
Background. Despite the relevance of monocytes as promoters of the inflammatory response, whether human immunodeficiency virus (HIV) infection induces premature age-related changes to the phenotype ...and function of monocytes or whether these alterations are different and/or specifically driven by HIV remains to be mechanistically determined. Methods. We assayed the activation phenotype and the responsiveness in vitro to Toll-like receptor (TLR) agonists in classical, intermediate, and nonclassical subsets of monocytes by assessing intracellular interleukin 1α (IL-1α), IL-1β, interleukin 6 (IL-6), interleukin 8, tumor necrosis factor α, and interleukin 10 (IL-10) production in 20 HIV-infected patients receiving combination antiretroviral therapy (cART) and 2 groups of uninfected controls (20 age-matched young individuals and 20 older individuals aged >65 years). Results. HIV-infected patients showed a more activated phenotype of monocytes than older controls. Regarding functionality, under unstimulated conditions HIV-infected patients showed a higher percentage of classical monocytes producing IL-6 and IL-10 than control subjects. The percentage of cells with production of multiple cytokines (polyfunctionality), including IL-10, in response to TLR agonists was greater among HIV-infected patients than among control subjects. Conclusions. Inflammatory alterations associated with monocytes during HIV infection are different from those in aging individuals. This monocyte dysfunction, mainly characterized by high levels of IL-6– and IL-10–producing monocytes, may have clinical implications in HIV-infected patients that are different from those in aging individuals.
Vertical transmission of human immunodeficiency virus (HIV) represents an important world-wide health problem although the incidence in developed countries has been drastically reduced by the ...extensive use of highly active antiretroviral therapy. Vertically HIV-infected subjects have been exposed to the virus during the maturation of their immune systems and have suffered a persistent chronic activation throughout their lifetime; the consequences of this situation for their immune system are not fully understood. The objective of this study was to analyse immunosenescence-related parameters in different CD4 T-cell subsets. Fifty-seven vertically HIV-infected subjects and 32 age-matched healthy subjects were studied. Activation (HLA– DR+), senescence (CD28– CD57+) and proliferation (Ki67+) were analysed on different CD4 T-cell subsets: naive (CD45RA+ CD27+), memory (CD45RO+ CD27+), effector memory (CD45RO+ CD27–) and effector memory RA (CD45RA+ CD27–). Compared with healthy subjects, vertically HIV-infected subjects showed increased naive and memory CD4 T-cell frequencies (p 0.035 and p 0.010, respectively) but similar frequencies of both effector subsets. Whereas naive CD4 T cells were not further altered, memory CD4 T cells presented increased levels of senescence and proliferation markers (p <0.001), effector memory CD4 T cells presented increased levels of activation, senescence and proliferation markers (p <0.001) and effector memory RA CD4 T cells presented increased levels of activation and senescence (p <0.001) compared with healthy subjects. Despite long periods of infection, vertically HIV-infected subjects show specific patterns of immunosenescence, revealing a preserved CD4 T-cell homeostasis for subset differentiation and distribution. Nevertheless, excepting the naive subpopulation, all subsets experienced some immunosenescence, pointing to uncertain consequences of the future aging process in these subjects.