Interaction of MMP-9 in the active phase of Graves' disease with and without ophthalmopathy.

Thyroid eye disease (TED) is expressed as orbital inflammation, and serum levels of several proinflammatory cytokines have been studied among patients with Graves' disease (GD) with and without TED; however, a more sensitive and specific marker for the different phases of GD and TED is still lacking. Seventeen active TED, 16 inactive TED, 16 GD without TED, and 16 healthy controls were recruited. Serum IL-17A, MMP-2, MMP-3, and MMP-9 were measured by multiplex bead assay. TED hormone and eye parameters were evaluated, and their relationship with cytokine levels was analyzed. Serum MMP-9 was higher in active TED than healthy controls, whereas IL-17A was lower among these patients than in GD without TED and healthy controls. No differences were found in MMP-3 and MMP-2 concentrations. MMP-9 levels were lower in patients with inactive TED who underwent radioactive iodine (RAI) therapy and those on levothyroxine replacement. MMP-9 levels were elevated in patients on methimazole. A negative correlation was found between age at assessment and time of follow-up with MMP-9 levels in inactive TED. Free T3 and ophthalmometry values were positively correlated with MMP-9 in the GD without TED and inactive TED groups, respectively. In conclusion, serum MMP-9 was increased in patients with active TED and was related to the RAI treatment, longer follow-up time, and higher ophthalmometry in patients with inactive TED, as well as thyroid function in GD without TED. MMP-9 may be involved in both the active phase of TED and the active phase of inflammation related to GD.NEW & NOTEWORTHY Our study addresses clinical aspects of specific ophthalmological examination and serum cytokine concentrations of patients with Graves' disease (GD) with and without ophthalmopathy. Our findings suggest that MMP-9 may be involved in the active phase of ophthalmopathy and in the active phase of GD. The central question is whether MMP-9 is a potential target for future treatments.

EUS- versus ERCP-guided biliary drainage for malignant biliary obstruction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Increasing evidence supports EUS-guided biliary drainage (EUS-BD) as a potential alternative to ERCP-guided biliary drainage (ERCP-BD) in the primary treatment of malignant biliary obstruction (MBO). This systematic review and meta-analysis aimed to compare the efficacy and safety of both techniques as the initial approach for MBO. METHODS: We systematically searched in MEDLINE, Embase, and Cochrane databases for randomized controlled trials comparing both techniques and reporting at least one of the outcomes of interest. The pooled estimates were calculated using the random-effects model, and I2 statistics were used to evaluate heterogeneity. RESULTS: We included 6 randomized controlled trials (577 patients). There were no significant differences between both groups in terms of stent patency (mean difference [MD], 8.18 days; 95% confidence interval [CI], -22.55 to 38.91), procedure time (MD, -6.31 minutes; 95% CI, -12.68 to 0.06), and survival (MD, 4.59 days; 95% CI, -34.23 to 43.40). Technical success (risk ratio [RR], 1.04; 95% CI, 0.96-1.13), clinical success (RR, 1.02; 95% CI, 0.96-1.08), overall adverse events (RR, 0.58; 95% CI, 0.24-1.43), and cholangitis (RR, 1.19; 95% CI, 0.39-3.61) were also similar between groups. However, the hospital stay was significantly shorter (MD, -1.03 days; 95% CI, -1.53 to -0.53), and the risk of reintervention (RR, 0.57; 95% CI, 0.37-0.88), postprocedure pancreatitis (RR, 0.15; 95% CI, 0.03-0.66), and tumor ingrowth/overgrowth (RR, 0.28; 95% CI, 0.11-0.70) were significantly lower with EUS-BD. CONCLUSIONS: EUS-BD and ERCP-BD had similar efficacy and safety as the initial approach for MBO. However, EUS-BD had a significantly lower risk of reintervention, postprocedure pancreatitis, tumor ingrowth/overgrowth, and reduced hospital stay.

Cold endoscopic mucosal resection versus cold snare polypectomy for colorectal lesions: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cold resection of colorectal lesions is widely performed because of its safety and effectiveness; however, it remains uncertain whether adding submucosal injection could improve the efficacy and safety. We aimed to compare cold endoscopic mucosal resection (C-EMR) versus cold snare polypectomy (CSP) for colorectal lesions. METHODS: We performed a systematic review of randomized controlled trials (RCTs) identified from PubMed, Cochrane Library, and Embase. The primary outcome was complete resection. Secondary outcomes were procedure time, en bloc resection, and adverse events (AEs). Prespecified subgroup analyses based on the size and morphology of the polyps were performed. The random-effects model was used to calculate the pooled risk ratio (RR) and mean difference, with corresponding 95%CIs, for dichotomous and continuous variables, respectively. Heterogeneity was assessed using the Cochran Q test and I 2 statistics. RESULTS: 7 RCTs were included, comprising 1556 patients, with 2287 polyps analyzed. C-EMR and CSP had similar risk ratios for complete resection (RR 1.02, 95%CI 0.98-1.07), en bloc resection (RR 1.08, 95%CI 0.82-1.41), and AEs (RR 0.74, 95%CI 0.41-1.32). C-EMR had a longer procedure time (mean difference 42.1 seconds, 95%CI 14.5-69.7 seconds). In stratified subgroup analyses, the risk was not statistically different between C-EMR and CSP for complete resection in polyps<10 mm or ≥10 mm, or for complete resection, en bloc resection, and AEs in the two groups among nonpedunculated polyps. CONCLUSIONS: The findings of this meta-analysis suggest that C-EMR has similar efficacy and safety to CSP, but significantly increases the procedure time. PROSPERO: CRD42023439605.

Endoscopic ultrasound-guided versus percutaneous liver biopsy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Percutaneous liver biopsy (PC-LB) has long been the usual method for acquisition of liver tissue. Recently, endoscopic ultrasound-guided liver biopsy (EUS-LB) has gained popularity as an alternative modality. We aimed to compare the efficacy and safety of EUS-LB versus PC-LB. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library databases for randomized controlled trials (RCTs) comparing EUS-LB with PC-LB published until October 20, 2023. The primary outcome was diagnostic adequacy. Secondary outcomes were: the number of complete portal tracts (CPTs), longest sample length (LSL), total sample length (TSL), post-procedure pain scores, and adverse events (AEs), including overall AEs and AEs excluding minor post-procedure symptoms. We compared binary outcomes using risk ratios (RRs) and continuous outcomes using the mean difference (MD) or standardized mean difference (SMD), with 95%CIs. RESULTS: Four RCTs (258 patients) were included. The EUS-LB group presented lower post-procedure pain scores (SMD -0.58, 95%CI -0.95 to -0.22) than the PC-LB group. Both groups performed similarly in terms of diagnostic adequacy (RR 1.0, 95%CI 0.96 to 1.04), number of CPTs (MD 2.57, 95%CI -4.09 to 9.22), LSL (MD -2.91 mm, 95%CI -5.86 to 0.03), TSL (MD 4.16 mm, 95%CI -10.12 to 18.45), overall AEs (RR 0.54, 95%CI 0.20 to 1.46), and AEs excluding minor post-procedure symptoms (RR 1.65, 95%CI 0.21 to 13.02). CONCLUSIONS: This meta-analysis suggests that EUS-LB is as safe and effective as PC-LB and is associated with lower post-procedure pain scores.Registration on PROSPERO: CRD42023469469.

Remimazolam versus propofol for sedation in gastrointestinal endoscopic procedures: a systematic review and meta-analysis.

BACKGROUND: Propofol has a favourable efficacy profile in gastrointestinal endoscopic procedures, however adverse events remain frequent. Emerging evidence supports remimazolam use in gastrointestinal endoscopy. This systematic review and meta-analysis compares remimazolam and propofol, both combined with a short-acting opioid, for sedation of adults in gastrointestinal endoscopy. METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomised controlled trials comparing efficacy-, safety-, and satisfaction-related outcomes between remimazolam and propofol, both combined with short-acting opioids, for sedation of adults undergoing gastrointestinal endoscopy. We performed sensitivity analyses, subgroup assessments by type of short-acting opioid used and age range, and meta-regression analysis using mean patient age as a covariate. We used R statistical software for statistical analyses. RESULTS: We included 15 trials (4516 subjects). Remimazolam was associated with a significantly lower sedation success rate (risk ratio [RR] 0.991; 95% confidence interval [CI] 0.984-0.998; high-quality evidence) and a slightly longer induction time (mean difference [MD] 9 s; 95% CI 4-13; moderate-quality evidence), whereas there was no significant difference between the sedatives in other time-related outcomes. Remimazolam was associated with significantly lower rates of respiratory depression (RR 0.41; 95% CI 0.30-0.56; high-quality evidence), hypotension (RR 0.43; 95% CI 0.35-0.51; moderate-quality evidence), hypotension requiring treatment (RR 0.25; 95% CI 0.12-0.52; high-quality evidence), and bradycardia (RR 0.42; 95% CI 0.30-0.58; high-quality evidence). There was no difference in patient (MD 0.41; 95% CI -0.07 to 0.89; moderate-quality evidence) and endoscopist satisfaction (MD -0.31; 95% CI -0.65 to 0.04; high-quality evidence) between both drugs. CONCLUSIONS: Remimazolam has clinically similar efficacy and greater safety when compared with propofol for sedation in gastrointestinal endoscopies.

Refractive error and ocular alignment in school-aged children from low-income areas of São Paulo, Brazil.

BACKGROUND: Uncorrected refractive errors and amblyopia are reported as the two main causes of childhood visual impairment and blindness worldwide. Our purpose was to evaluate refractive status, ocular alignment and effective refractive error coverage (eREC) of school-aged children from low-income areas of Sao Paulo city, Brazil. METHODS: Data from the "Ver na Escola" Project were used for the current study. Children enrolled in the selected schools had an ophthalmic exam including eye alignment assessed by cover test, automatized and subjective dynamic and static refraction. The associations of demographic variables with occurrence and magnitude of refractive errors and eREC were investigated by multiple logistic regressions and multilevel mixed effect models. RESULTS: A total of 17,973 children (51.12% females) with mean ± sd age 8.24 ± 3.54 years old examined from July 2018 to July 2019, were included in the study. Most of the participants (73%) showed orthoposition of the visual axis for both distance and near. Heterophoria was found in about 25% of participants (N = 4,498), with 71.7% of them (N= 3,222) classified as exophoria. Less than 2% (N = 232) showed strabismus, most of them (N = 160) esotropia. Overall, 1,370 (7.70%) of participants had myopia and 577 (3.24%) had hyperopia. Age was found to be significantly associated with increasing static subjective refraction spherical equivalent (Coefficient: -0.18; 95% Confidence Interval (CI): -0.21 to -0.16; p < 0.001). Female sex (Odds Ratio (OR) = 1.13; 95%CI: 1.01-1.27; p = 0.027) and older age (OR = 1.17; 95%CI: 1.16-1.19; p < 0,001) were significantly associated with myopia diagnosis. Older age decreased the odds of hyperopia (OR = 0.95; 95%CI: 0.93-0.98; p < 0.001). The overall effective refractive coverage was 51.76% and was significantly associated with age group, ranging from 32.25% in children aged 3 to 7 years to 61.35% in children aged 8 to 12 years. CONCLUSIONS: Most children have shown eye alignment for both distance and near assessments and no refractive error. Myopia was observed in 7.70% of the population and it was associated with older age and female sex. Hyperopia was observed in 3.24% and was associated with younger age. The overall eREC was 51.76%, significantly associated with age.

TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular Level.

This work aims to develop and validate a framework for the multiscale simulation of the biological response to ionizing radiation in a population of cells forming a tissue. We present TOPAS-Tissue, a framework to allow coupling two Monte Carlo (MC) codes: TOPAS with the TOPAS-nBio extension, capable of handling the track-structure simulation and subsequent chemistry, and CompuCell3D, an agent-based model simulator for biological and environmental behavior of a population of cells. We verified the implementation by simulating the experimental conditions for a clonogenic survival assay of a 2-D PC-3 cell culture model (10 cells in 10,000 µm2) irradiated by MV X-rays at several absorbed dose values from 0-8 Gy. The simulation considered cell growth and division, irradiation, DSB induction, DNA repair, and cellular response. The survival was obtained by counting the number of colonies, defined as a surviving primary (or seeded) cell with progeny, at 2.7 simulated days after irradiation. DNA repair was simulated with an MC implementation of the two-lesion kinetic model and the cell response with a p53 protein-pulse model. The simulated survival curve followed the theoretical linear-quadratic response with dose. The fitted coefficients α = 0.280 ± 0.025/Gy and ß = 0.042 ± 0.006/Gy2 agreed with published experimental data within two standard deviations. TOPAS-Tissue extends previous works by simulating in an end-to-end way the effects of radiation in a cell population, from irradiation and DNA damage leading to the cell fate. In conclusion, TOPAS-Tissue offers an extensible all-in-one simulation framework that successfully couples Compucell3D and TOPAS for multiscale simulation of the biological response to radiation.

Global DNA methylation changes in adults with attention deficit-hyperactivity disorder and its comorbidity with bipolar disorder: links with polygenic scores.

Genetic and environmental factors contribute to the etiology of Attention Deficit-Hyperactivity Disorder (ADHD). In this sense, the study of epigenetic mechanisms could contribute to the understanding of the disorder's neurobiology. Global DNA methylation (GMe) evaluated through 5-methylcytosine levels could be a promising epigenetic biomarker to capture long-lasting biological effects in response to environmental and hormonal changes. We conducted the first assessment of GMe levels in subjects with ADHD (n = 394) and its main comorbidities in comparison to populational controls (n = 390). Furthermore, given the high genetic contribution to ADHD (heritability of 80%), polygenic risk scores (PRS) were calculated to verify the genetic contribution to GMe levels in ADHD and the comorbidities associated with GMe levels. The GMe levels observed in patients were lower than controls (P = 1.1e-8), with women being significantly less globally methylated than men (P = 0.002). Regarding comorbidities, the presence of bipolar disorder (BD) among patients with ADHD was associated with higher methylation levels compared to patients with ADHD without BD (P = 0.031). The results did not change when pharmacological treatment was accounted for in the analyses. The ADHD and BD most predictive PRSs were negatively (P = 0.0064) and positively (P = 0.0042) correlated with GMe, respectively. This study is the first to report an association between GMe, ADHD, and its comorbidity with BD and associations between PRSs for specific psychiatric disorders and GMe. Our findings add to previous evidence that GMe may be a relevant piece in the psychiatric disorders' etiological landscape.

Competition for water and rapid exclusion of an island endemic by a pantropical species in a tropical climate.

Water availability has major effects on community structure and dynamics globally, yet our understanding of competition for water in the tropics is limited. On the tropical Trindade Island, we explored competition for water in the context of the rapid exclusion of an endemic sedge, Cyperus atlanticus (Cyperaceae), by a pantropical, N-fixing shrub, Guilandina bonduc (Fabaceae). Guilandina patches were generally surrounded by rings of bare soil, and dead Cyperus halos commonly surrounded these bare zones. With geo-referenced measurements, we showed that Guilandina patches and bare soil zones rapidly expanded and replaced adjacent Cyperus populations. We found that soil water potentials were much lower in bare soils than soils under Guilandina or Cyperus, and that leaf water potentials of Cyperus plants were lower when co-occurring with Guilandina than when alone. When Guilandina was removed experimentally, Cyperus populations expanded and largely covered the bare soil zones. Our results indicate that when Guilandina establishes, its root systems expand beyond its canopies and these roots pull water from soils beneath Cyperus and kill it, creating bare zone halos, and then Guilandina expands and repeats the process. This scenario indicates rapid competitive exclusion and displacement of an endemic by a common pantropical species, at least in part through competition for water.

Dietary intake of anthocyanins improves arterial stiffness, but not endothelial function, in volunteers with excess weight: A randomized clinical trial.

Excess body weight has been associated with endothelial dysfunction and increased arterial stiffness. Foods rich in polyphenols and anthocyanins such as açaí-juçara (Euterpe edulis Martius) fruit may have protective vascular effects. Thus, we examined the effect of dietary intake of anthocyanins (açaí-juçara fruit) on endothelial function (flow-mediated dilation [FMD]) and arterial stiffness (pulse wave velocity [PWV]) in individuals with excess body weight. Fifty-five individuals with BMI ≥25 kg/m2 were randomized into non-anthocyanin (N-ATH, n = 25) or anthocyanin (ATH, n = 30) intake groups. A 12-week individualized diet plan (20% reduction in total energy intake) was prescribed and included daily intake of açaí-juçara 200 g (anthocyanins 293.6 mg) in the ATH diet plan. We evaluated anthropometric and biochemical parameters, FMD, PWV, and peripheral vascular resistance (PVR). A GEE (Bonferroni post-hoc) was used (p ≤ 0.05). No change in FMD was observed. However, PWV showed a reduction from baseline in the ATH (p = 0.002) and vs. N-ATH (p = 0.036). Both groups showed reduced peripheral vascular resistance (N-ATH, p = 0.005; ATH, p = 0.040) with no significant differences between them. In conclusion, dietary intake of anthocyanins proved effective in protecting against arterial stiffness (by PWV) in individuals with excess weight. PVR was reduced in both diet groups regardless of dietary intake of anthocyanins.

HIV self-test: a tool to expand test uptake among men who have sex with men who have never been tested for HIV in São Paulo, Brazil.

OBJECTIVES: HIV self-testing is an effective tool to improve diagnostic coverage in key populations, enabling linkage to care and access to antiretroviral therapy. Its implementation requires better understanding of patients' perspectives on this novel strategy. The aim of the study was to investigate the perception of men who have sex with men (MSM) regarding the HIV oral fluid self-test (HIVST) in São Paulo, Brazil, and to analyse the sociodemographic characteristics and testing strategy preferences of individuals registered to undertake HIVST. METHODS: Preceding the implementation of HIVST use as public policy in 2019, we recruited MSM living in São Paulo to undertake HIVST using a digital platform, and investigated their sociodemographic profiles, testing experiences and testing preferences. Results were compared according to reported lifetime HIV testing. RESULTS: A total of 6477 MSM (median age 28 years) were recruited to the study from April 9th to December 31st, 2018. Seventy-eight per cent reported previous HIV testing. The opening hours of health facilities (53%), concern about disclosing intimate personal information to health care providers (34%) and fear of stigma (21%) were reported as the main barriers to testing. Older age, higher education, illicit drug use and self-identifying as gay were associated with prior HIV testing (P < 0.001). Most participants (67%) were unaware that HIVST was available before enrolling in the study. Preference for HIVST over other testing technologies was higher among those never tested (71%) than among participants with previous HIV testing (61%; P < 0.001). CONCLUSIONS: HIVST was found to be an effective tool to improve testing uptake among MSM, particularly those who had never been tested before. Characterization of the most likely users of HIVST among MSM will help to inform implementation and scaling up of this novel testing method in the Brazilian public health system.

Phylogenetic systematics of Yphthimoides Forster, 1964 and related taxa, with notes on the biogeographical history of Yphthimoides species.

Species losses are increasing and may have an impact on our understanding of patterns of evolutionary pathways and phylogenetic relationships among the groups being lost. The knowledge of such patterns can contribute to preventing future losses by identifying which lineages have higher or lower diversification rates, thus informing conservation strategies. Recent years have seen a significant growth in studies of butterfly systematics, allowing a better understanding of evolutionary relationships among most groups and revealing significant taxonomic chaos in several groups. One of the latter groups is the nymphalid subtribe Euptychiina (Satyrinae), which has been shown to include a number of non-monophyletic genera based on recent molecular phylogenetic analyses. Among others, these genera include Yphthimoides, which is widespread throughout the Neotropical region but particularly diverse in the southeastern Neotropics, and a pair of related genera, Pharneuptychia Forster, 1964 and Moneuptychia Forster, 1964. Using molecular data, this study scope and aims were to provide a phylogenetic hypothesis that corroborates Yphthimoides as presently conceived being non-monophyletic, a result reinforced by a comparative study of the male genitalic morphology. Our results also show that Pharneuptychia and Moneuptychia, plus a species misplaced elsewhere in the Euptychiina, Euptychoides castrensis (Schaus, 1902), form a well supported clade, and that the latter 'species' is a complex of cryptic species. We therefore propose a number of taxonomic rearrangements in the present work to resolve these issues: Yphthimoides eriphule (A. Butler, 1867) will be moved to a new genus; Y. affinis (A. Butler, 1867), Y. maepius (Godart, [1824]), Y. mimula (Hayward, 1954), Y. neomaenas (Hayward, 1967) and Y. mythra (Weymer, 1911) are being transferred to Malaveria Viloria & Benmesbah, 2021; Pharneuptychia innocentia (Godart, [1824]) will be moved to another genus to be described; and Euptychoides castrensis, Pharneuptychia romanina (Bryk, 1953) and Yphthimoides viviana (Romieux, 1927) are being moved to Moneuptychia. The dating of divergences points to a split between the ancestral lineage of Yphthimoides and its sister group, Carminda Ebert and Dias, inDias 1998, during the last half of the Miocene, around 11.86 Mya, and to the diversification of the Pharneuptychia during the same time 11.35 (±3.52) Mya. Biogeographic analysis showed that the most recent common ancestor of Yphthimoides started to diversify either in the the Brazilian Cerrado savannas or in a combined area of Cerrado and South Atlantic Forest, with a possible change in the ancestral habitat of Carminda. Furthermore, ancestral character mapping favors a savanna origin hypothesis over a forest origin hypothesis.

Arterial stiffness: a possible predictor of atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 0.5%-1% of people worldwide. Hemodynamic changes due to stiffening of the arteries may cause cardiac structural and electrical remodeling that induces AF.Pulse wave velocity (PWV) is a direct non-invasive method to measure arterial stiffness (AS). Central pulse pressure (PPc) describes oscillations around the mean arterial pressure and is increased in more rigid arteries. These two central variables can be considered markers of AF. Sympathetic activity has been reported to be directly relatedto PWV even in patients without comorbidities. Therefore, in patients with more rigid arteries, sudden changes in pressure could affect the activation of arterial baroreceptors, leading to an acute imbalance between the sympathetic and parasympathetic responses in the heart. The coexistence of AF and AS is common. This critical review aims to bring information about the role of AS in the pathophysiology of AF and discuss results of clinical studies on this topic. Althuogh discussed in the literature, further studies are needed to confirm the predictive role of these variables in AF, and their use in clinical practice.

COVID-19 mortality prediction in the intensive care unit with deep learning based on longitudinal chest X-rays and clinical data.

OBJECTIVES: We aimed to develop deep learning models using longitudinal chest X-rays (CXRs) and clinical data to predict in-hospital mortality of COVID-19 patients in the intensive care unit (ICU). METHODS: Six hundred fifty-four patients (212 deceased, 442 alive, 5645 total CXRs) were identified across two institutions. Imaging and clinical data from one institution were used to train five longitudinal transformer-based networks applying five-fold cross-validation. The models were tested on data from the other institution, and pairwise comparisons were used to determine the best-performing models. RESULTS: A higher proportion of deceased patients had elevated white blood cell count, decreased absolute lymphocyte count, elevated creatine concentration, and incidence of cardiovascular and chronic kidney disease. A model based on pre-ICU CXRs achieved an AUC of 0.632 and an accuracy of 0.593, and a model based on ICU CXRs achieved an AUC of 0.697 and an accuracy of 0.657. A model based on all longitudinal CXRs (both pre-ICU and ICU) achieved an AUC of 0.702 and an accuracy of 0.694. A model based on clinical data alone achieved an AUC of 0.653 and an accuracy of 0.657. The addition of longitudinal imaging to clinical data in a combined model significantly improved performance, reaching an AUC of 0.727 (p = 0.039) and an accuracy of 0.732. CONCLUSIONS: The addition of longitudinal CXRs to clinical data significantly improves mortality prediction with deep learning for COVID-19 patients in the ICU. KEY POINTS: • Deep learning was used to predict mortality in COVID-19 ICU patients. • Serial radiographs and clinical data were used. • The models could inform clinical decision-making and resource allocation.

Germination of grass species from dry and wet grasslands in response to osmotic stress under present and future temperatures.

PREMISE: Seed germination is controlled by the soil microclimate, which is expected to change with the temperature increase and rainfall irregularity predicted for the future. Because changes in soil characteristics directly affect species recruitment, vegetation dynamics and resilience, we investigated how caryopses of native grasses from dry and wet grasslands respond to water stress under current and future temperature regimes. METHODS: Caryopses were collected from 10 grass species in dry and wet grasslands, subjected or not to a fire event, and tested for germination at increasing osmotic potential (0 to -1.0 MPa) at current (17°/27°C night/day) and future (23°/33°C) simulated temperatures. RESULTS: The viability and germination percentages of caryopses from both dry and wet grassland species were progressively reduced as osmotic stress increased, irrespective of temperature regime. The viability of caryopses from wet grassland species was reduced under the future temperature regime, irrespective of osmotic potential. The slow germination of caryopses of dry grassland species at the present temperature regime was absent when they were incubated in the future temperature regime. CONCLUSIONS: More intense water stress reduced the survival of caryopses for both dry and wet grassland grass species. The predicted future temperature regime reduced the viability of wet grassland species and altered the germination strategy of dry grassland species. These results indicate that increasing water stress and temperature predicted for the future may compromise the recruitment potential of dry and wet grassland species and directly impact the dynamics and resilience of these ecosystems.

Formaldehyde toxicity reports from in vitro and in vivo studies: a review and updated data.

Formaldehyde (FA) is a xenobiotic air pollutant and its universal distribution causes a widespread exposure to humans. This review aimed to bring updated information concerning FA toxicity in humans and animals based on in vitro and in vivo studies from 2013 to 2019. Researches were carried out in Pubmed, Scopus, and Science Direct databases to determine the effects of FA exposure on inflammation, oxidative stress and genotoxicity in experimental studies with animals (rats and mice) and humans. Besides, in vitro studies assessing FA cytotoxicity focusing on cell viability and apoptosis in different cell line cultures were reviewed. Studies with humans gave evidence regarding significant deleterious effects on health associated to chronic FA occupational exposure. Evaluations carried out in experimental studies showed toxic effects on different organs as lung, upper respiratory tract, bone marrow and brain as well as in cells. In summary, this study demonstrates that knowing the mechanisms underlying FA toxicity is essential to understand the deleterious effects that this xenobiotic causes on biological systems.

Identification and Prognosis of Patients With Interstitial Pneumonia With Autoimmune Features.

BACKGROUND/OBJECTIVE: Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF. METHODS: We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models. RESULTS: We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77-11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome. CONCLUSION: Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

Machine learning automatically detects COVID-19 using chest CTs in a large multicenter cohort.

OBJECTIVES: To investigate machine learning classifiers and interpretable models using chest CT for detection of COVID-19 and differentiation from other pneumonias, interstitial lung disease (ILD) and normal CTs. METHODS: Our retrospective multi-institutional study obtained 2446 chest CTs from 16 institutions (including 1161 COVID-19 patients). Training/validation/testing cohorts included 1011/50/100 COVID-19, 388/16/33 ILD, 189/16/33 other pneumonias, and 559/17/34 normal (no pathologies) CTs. A metric-based approach for the classification of COVID-19 used interpretable features, relying on logistic regression and random forests. A deep learning-based classifier differentiated COVID-19 via 3D features extracted directly from CT attenuation and probability distribution of airspace opacities. RESULTS: Most discriminative features of COVID-19 are the percentage of airspace opacity and peripheral and basal predominant opacities, concordant with the typical characterization of COVID-19 in the literature. Unsupervised hierarchical clustering compares feature distribution across COVID-19 and control cohorts. The metrics-based classifier achieved AUC = 0.83, sensitivity = 0.74, and specificity = 0.79 versus respectively 0.93, 0.90, and 0.83 for the DL-based classifier. Most of ambiguity comes from non-COVID-19 pneumonia with manifestations that overlap with COVID-19, as well as mild COVID-19 cases. Non-COVID-19 classification performance is 91% for ILD, 64% for other pneumonias, and 94% for no pathologies, which demonstrates the robustness of our method against different compositions of control groups. CONCLUSIONS: Our new method accurately discriminates COVID-19 from other types of pneumonia, ILD, and CTs with no pathologies, using quantitative imaging features derived from chest CT, while balancing interpretability of results and classification performance and, therefore, may be useful to facilitate diagnosis of COVID-19. KEY POINTS: • Unsupervised clustering reveals the key tomographic features including percent airspace opacity and peripheral and basal opacities most typical of COVID-19 relative to control groups. • COVID-19-positive CTs were compared with COVID-19-negative chest CTs (including a balanced distribution of non-COVID-19 pneumonia, ILD, and no pathologies). Classification accuracies for COVID-19, pneumonia, ILD, and CT scans with no pathologies are respectively 90%, 64%, 91%, and 94%. • Our deep learning (DL)-based classification method demonstrates an AUC of 0.93 (sensitivity 90%, specificity 83%). Machine learning methods applied to quantitative chest CT metrics can therefore improve diagnostic accuracy in suspected COVID-19, particularly in resource-constrained environments.

Real-World Lung Cancer CT Screening Performance, Smoking Behavior, and Adherence to Recommendations: Lung-RADS Category and Smoking Status Predict Adherence.

BACKGROUND. Low-dose CT (LDCT) lung cancer screening (LCS) has been shown to decrease mortality in persons with a significant smoking history. However, adherence in real-world LCS programs is significantly lower than in randomized controlled trials. OBJECTIVE. The purpose of this article is to assess real-world LDCT LCS performance and factors predictive of adherence to LCS recommendations. METHODS. We retrospectively identified all persons who underwent at least two LCS examinations from 2014 to 2019. Patient demographics, smoking history and behavior changes, Lung-RADS category, PPV, NPV, and adherence to screening recommendations were recorded. Predictors of adherence were assessed via univariate comparisons and multivariate logistic regression. RESULTS. A total of 260 persons returned for follow-up LDCT (57.7% had two, 34.2% had three, 7.7% had four, and 0.4% had five LDCT examinations). A total of 43 of 260 (16.5%) had positive (Lung-RADS category 3 or above) scans, of which 27 of 260 persons (10.3%) were graded as Lung-RADS category 3, eight of 260 (3.1%) were category 4A, six of 260 (2.3%) were category 4B, and two of 260 (0.8%) were category 4X. Cancer was diagnosed in four of the 260 (three with lung cancer and one with metastatic melanoma). A total of 143 of 260 (55.0%) persons were current smokers at baseline and 121 of 260 (46.5%) were current smokers at the last round of LCS. LCS had sensitivity of 100.0%, specificity of 84.8%, PPV of 9.3%, and NPV of 100%. Overall adherence was 43.0% but increased progressively with higher Lung-RADS category (Lung-RADS 1: 33.2%; Lung-RADS 2: 46.3%; Lung-RADS 3: 53.8%; Lung-RADS 4A: 77.8%; Lung-RADS 4B: 83.3%; Lung-RADS 4X: 100%; p < .001). was also higher in former versus current smokers (50.0% vs 36.2%; p < .001). Being a former smoker and having a nodule that is Lung-RADS category 3 or greater were the only significant independent predictors of adherence. CONCLUSION. Our real-world LCS program showed very high sensitivity and NPV, but moderate specificity and very low PPV. Adherence to LCS recommendations increased with former versus current smokers and in those with positive (Lung-RADS categories 3, 4A, 4B, or 4X) LCS examinations. Adherence was less than 50.0% in current smokers and persons with negative (Lung-RADS categories 1 or 2) LCS examinations. CLINICAL IMPACT. Our results offer a road map for targeted performance improvement by focusing on LCS subjects less likely to remain in the program, such as persons with negative LCS examinations and persons who continue to smoke, potentially improving LCS cost effectiveness and maximizing its societal benefits.

Aerobic exercise, but not isometric handgrip exercise, improves endothelial function and arterial stiffness in patients with myocardial infarction undergoing coronary intervention: a randomized pilot study.

BACKGROUND: Aerobic exercise improves endothelial function and arterial stiffness after myocardial infarction (MI), but the effects of isometric exercise on cardiovascular parameters are still uncertain. We aimed to assess the effects of one session of aerobic or isometric exercise on flow-mediated dilation (FMD) and pulse wave velocity (PWV) in post-MI volunteers undergoing percutaneous coronary intervention (PCI). METHODS: Twenty post-MI patients undergoing PCI were randomized to aerobic (AE, n = 10) or isometric (IE, n = 10) exercise groups. We evaluated cardiac structure and function (echocardiographic); carotid plaque presence (ultrasound). FMD and PWV were measured 10 min before and 10 min after the intervention: a single session of moderate-intensity AE (30 min; ratings 12-14 on Borg's scale or 50-60% HRreserve) or handgrip IE (four two-minute bilateral contractions; 30% maximal voluntary contraction; 1-min rest). Generalized estimating equations (Bonferroni post-hoc) was used to assess differences (p ≤ 0.050). RESULTS: FMD improved only in the AE group (Δ = 4.9%; p = 0.034), with no difference between groups after exercise. Even after adjustment (for baseline brachial artery diameter) the effectiveness of AE remained (p = 0.025) with no change in the IE group. PWV was slightly reduced from baseline in the AE group (Δ = 0.61 m/s; p = 0.044), and no difference when compared to the IE group. Peripheral vascular resistance decreased in AE versus IE (p = 0.050) and from baseline (p = 0.014). CONCLUSIONS: Vascular measurements (FMD and PWV) improved after a single session of AE. There are apparently no benefits following a session of IE. TRIAL REGISTRATION: http://www.clinicaltrials.gov and ID number NCT04000893.