Antibodies against the HPV16 oncoprotein E6 are promising biomarkers for HPV16-driven oropharyngeal cancer (HPV16-OPC) due to their high sensitivity and specificity, and prospective manifestation. In previous studies, 0•7% of controls without HPV-associated malignancies were HPV16 E6 seropositive of which only a minority is expected to develop HPV16-driven cancer. We aimed to characterise HPV16 E6 antibodies in individuals without HPV-associated malignancies.
We analysed serum antibodies against HPV16 E6, E7, L1 and HPV18 L1 in a random sample (n=9,695) of the prospective UK Biobank cohort (UKB). Excluding individuals with potentially HPV-associated malignancies (n=192), we assessed risk factors for seropositivity by logistic regression.
In individuals without potentially HPV-associated malignancies (n=9,503), the HPV16 E6 seroprevalence was 0•8%. Seropositivity against HPV16 E6 and all other HPV antigens was strongly associated with sexual behaviour. The seroprevalence of HPV16 E6, L1 and HPV18 L1 increr, additional risk stratification will be required to identify individuals at highest risk to develop HPV16-OPC.
Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.
We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.
After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.
Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.
ANRS and Paris-Saclay University.
ANRS and Paris-Saclay University.Shear wave elastography (SWE) estimates shear modulus in muscle. This is interpreted as an index of muscle stiffness, but depends on muscle characteristics. This study evaluated relationship between shear modulus and myoelectric activity of lumbar multifidus and longissimus muscles to assess its validity. Intramuscular electromyography (EMG) of multifidus (deep [DM], superficial [SM] fibres) at L4/5, longissimus [LG] at L2, were recorded in nine healthy participants. Participants performed isometric trunk extension in side-lying from 0 to 30% maximal voluntary contraction (MVC) with EMG amplitude feedback. Using SWE, two regions of interest (ROI) were investigated in each muscle. Generally, shear modulus was moderately correlated with root mean squared (RMS) EMG (r = 0.50-0.78). Univariate and multiple regression analyses showed ultrasound/SWE features of 'B-mode quality' (24.5%), '%Void pixels' (17.9%) and 'Connective tissue' (16.2%) explained most variation in the shear modulus/EMG relationship. Regression prediction scores generated using imaging features were correlated with r-coefficients of shear modulus/EMG relationship. When analysis was restricted to high quality data (i.e., regression prediction score above an a priori defined threshold), the shear modulus/EMG relationship increased to r = 0.70-0.96. Although a linear relationship between shear modulus/EMG was confirmed, supporting validity of SWE measures in anatomically distinct **** muscles, this depends on image quality.The quadriceps-intermittent-fatigue (QIF) test assesses knee extensors strength, endurance and performance fatigability in isometric condition. We aimed to assess reliability and agreement for this test in dynamic conditions and with the use of transcranial magnetic stimulation. On two separate sessions, 20 young adults (25 ± 4 yr, 10 women) performed stages of 100 knee extensors concentric contractions at 120°/s (60° range-of-motion) with 10% increments of the initial maximal concentric torque until exhaustion. Performance fatigability across the test was quantified as maximal isometric and concentric torque loss, and its mechanisms were investigated through the responses to transcranial magnetic and electrical stimulations. Reliability and agreement were assessed using ANOVAs, coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) with 95% CI. Good inter-session reliability and high agreement were found for number of contractions [489 ± 75 vs. 503 ± 95; P = 0.20; ICC = 0.85 (0.66; 0.94); CV = 5% (3; 7)] and total work [11,285 ± 4,932 vs. 11,792 ± 5838 Nm.s; P = 0.20; ICC = 0.95 (0.87; 0.98); CV = 8% (5; 11)]. Poor reliability but high agreement were observed for isometric [-33 ± 6 vs. -31 ± 7%; P = 0.13; ICC = 0.47 (0.05; 0.75); CV = 6% (4;8)] and concentric [-20 ± 11% vs. https://www.selleckchem.com/products/talabostat.html -19 ± 9%; P = 0.82; ICC = 0.26 (-0.22; 0.63); CV = 9% (6; 12)] torque loss. The dynamic QIF test represents a promising tool for neuromuscular evaluation in isokinetic mode.Oral antigen administration to induce regulatory T cells (Treg) takes advantage of regulatory mechanisms that the gastrointestinal tract utilizes to promote unresponsiveness against food antigens or commensal microorganisms. Recently, antigen-based oral immunotherapies (OITs) have shown efficacy as treatment for food allergy and autoimmune diseases. Similarly, OITs appear to prevent anti-drug antibody responses in replacement therapy for genetic diseases. Intestinal epithelial cells and microbiota possibly condition dendritic cells (DC) toward a tolerogenic phenotype that induces Treg via expression of several mediators, e.g. IL-10, transforming growth factor-β, retinoic acid. Several factors, such as metabolites derived from microbiota or diet, impact the stability and expansion of these induced Treg, which include, but are not limited to, FoxP3+ Treg, LAP+ Treg, and/or Tr1 cells. Here, we review various orally induced Treg, their plasticity and cooperation between the Treg subsets, as well as underlying mechanisms controlling their induction and role in oral tolerance.
Antibodies against the HPV16 oncoprotein E6 are promising biomarkers for HPV16-driven oropharyngeal cancer (HPV16-OPC) due to their high sensitivity and specificity, and prospective manifestation. In previous studies, 0•7% of controls without HPV-associated malignancies were HPV16 E6 seropositive of which only a minority is expected to develop HPV16-driven cancer. We aimed to characterise HPV16 E6 antibodies in individuals without HPV-associated malignancies.
We analysed serum antibodies against HPV16 E6, E7, L1 and HPV18 L1 in a random sample (n=9,695) of the prospective UK Biobank cohort (UKB). Excluding individuals with potentially HPV-associated malignancies (n=192), we assessed risk factors for seropositivity by logistic regression.
In individuals without potentially HPV-associated malignancies (n=9,503), the HPV16 E6 seroprevalence was 0•8%. Seropositivity against HPV16 E6 and all other HPV antigens was strongly associated with sexual behaviour. The seroprevalence of HPV16 E6, L1 and HPV18 L1 increr, additional risk stratification will be required to identify individuals at highest risk to develop HPV16-OPC.
Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.
We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.
After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.
Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.
ANRS and Paris-Saclay University.
ANRS and Paris-Saclay University.Shear wave elastography (SWE) estimates shear modulus in muscle. This is interpreted as an index of muscle stiffness, but depends on muscle characteristics. This study evaluated relationship between shear modulus and myoelectric activity of lumbar multifidus and longissimus muscles to assess its validity. Intramuscular electromyography (EMG) of multifidus (deep [DM], superficial [SM] fibres) at L4/5, longissimus [LG] at L2, were recorded in nine healthy participants. Participants performed isometric trunk extension in side-lying from 0 to 30% maximal voluntary contraction (MVC) with EMG amplitude feedback. Using SWE, two regions of interest (ROI) were investigated in each muscle. Generally, shear modulus was moderately correlated with root mean squared (RMS) EMG (r = 0.50-0.78). Univariate and multiple regression analyses showed ultrasound/SWE features of 'B-mode quality' (24.5%), '%Void pixels' (17.9%) and 'Connective tissue' (16.2%) explained most variation in the shear modulus/EMG relationship. Regression prediction scores generated using imaging features were correlated with r-coefficients of shear modulus/EMG relationship. When analysis was restricted to high quality data (i.e., regression prediction score above an a priori defined threshold), the shear modulus/EMG relationship increased to r = 0.70-0.96. Although a linear relationship between shear modulus/EMG was confirmed, supporting validity of SWE measures in anatomically distinct back muscles, this depends on image quality.The quadriceps-intermittent-fatigue (QIF) test assesses knee extensors strength, endurance and performance fatigability in isometric condition. We aimed to assess reliability and agreement for this test in dynamic conditions and with the use of transcranial magnetic stimulation. On two separate sessions, 20 young adults (25 ± 4 yr, 10 women) performed stages of 100 knee extensors concentric contractions at 120°/s (60° range-of-motion) with 10% increments of the initial maximal concentric torque until exhaustion. Performance fatigability across the test was quantified as maximal isometric and concentric torque loss, and its mechanisms were investigated through the responses to transcranial magnetic and electrical stimulations. Reliability and agreement were assessed using ANOVAs, coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) with 95% CI. Good inter-session reliability and high agreement were found for number of contractions [489 ± 75 vs. 503 ± 95; P = 0.20; ICC = 0.85 (0.66; 0.94); CV = 5% (3; 7)] and total work [11,285 ± 4,932 vs. 11,792 ± 5838 Nm.s; P = 0.20; ICC = 0.95 (0.87; 0.98); CV = 8% (5; 11)]. Poor reliability but high agreement were observed for isometric [-33 ± 6 vs. -31 ± 7%; P = 0.13; ICC = 0.47 (0.05; 0.75); CV = 6% (4;8)] and concentric [-20 ± 11% vs. https://www.selleckchem.com/products/talabostat.html -19 ± 9%; P = 0.82; ICC = 0.26 (-0.22; 0.63); CV = 9% (6; 12)] torque loss. The dynamic QIF test represents a promising tool for neuromuscular evaluation in isokinetic mode.Oral antigen administration to induce regulatory T cells (Treg) takes advantage of regulatory mechanisms that the gastrointestinal tract utilizes to promote unresponsiveness against food antigens or commensal microorganisms. Recently, antigen-based oral immunotherapies (OITs) have shown efficacy as treatment for food allergy and autoimmune diseases. Similarly, OITs appear to prevent anti-drug antibody responses in replacement therapy for genetic diseases. Intestinal epithelial cells and microbiota possibly condition dendritic cells (DC) toward a tolerogenic phenotype that induces Treg via expression of several mediators, e.g. IL-10, transforming growth factor-β, retinoic acid. Several factors, such as metabolites derived from microbiota or diet, impact the stability and expansion of these induced Treg, which include, but are not limited to, FoxP3+ Treg, LAP+ Treg, and/or Tr1 cells. Here, we review various orally induced Treg, their plasticity and cooperation between the Treg subsets, as well as underlying mechanisms controlling their induction and role in oral tolerance.
0 Commenti
0 condivisioni
67 Views
0 Anteprima
