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This review provides a systematic analysis of advancements in biogas refining and biomethane purification, focusing on the application of biomass-derived activated carbon (AC) modified with metal oxides for the removal of hydrogen sulfide (H2S) and carbon dioxide (CO2). We explore technological innovations in biogas upgrading, including water scrubbing, pressure swing adsorption (PSA), membrane separation, and others, highlighting their operational efficiency, environmental impact, and cost-effectiveness. The removal of H2S and CO2is critical in converting raw biogas, primarily composed of methane (CH4) and CO2, into high-purity biomethane, making it suitable for integration into existing natural gas infrastructures. Our findings underscore the potential of these new composite materials to enhance biogas upgrading technologies, fostering the broader use of biomethane as a sustainable energy source. Furthermore, this review offers valuable insights for the future design and optimization of these refining processes, positioning biomass-derived AC modified with metal oxides as essential in advancing the field of biomethane purification.

Empirical evidence underscores an association between parental stress and emotional and behavioral problems in offspring. However, a comprehensive systematic review or meta-analysis on this topic is lacking. Thus, this study aims to address the scientific inquiry: Is there a relationship between parental stress and emotional/behavioral problems in children?

Atmospheric aerosol particles are essential for forming clouds and precipitation, thereby influencing Earth’s energy budget, water cycle and climate on regional and global scales. However, the origin of aerosol particles over the Amazon rainforest during the wet season is poorly understood. Earlier studies showed new particle formation in the outflow of deep convective clouds and suggested a downward flux of aerosol particles during precipitation events. Here we use comprehensive aerosol, trace gas and meteorological data from the Amazon Tall Tower Observatory to show that rainfall regularly induces bursts of nanoparticles in the nucleation size range. This can be attributed to rain-related scavenging of larger particles and a corresponding reduction of the condensation sink, along with an ozone injection into the forest canopy, which could increase the oxidation of biogenic volatile organic compounds, especially terpenes, and enhance new particle formation. During and after rainfall, the nucleation particle concentrations directly above the canopy are greater than those higher up. This gradient persists throughout the wet season for the nucleation size range, indicating continuous particle formation within the canopy, a net upward flux of newly formed particles and a paradigm shift in understanding aerosol–cloud–precipitation interactions in the Amazon. Particle bursts provide a plausible explanation for the formation of cloud condensation nuclei, leading to the local formation of green-ocean clouds and precipitation. Our findings suggest that an interplay of a rain-related reduction in the condensation sink, primary emissions of gases, mainly terpenes, and particles from the forest canopy, and convective cloud processing determines the population of cloud condensation nuclei in pristine rainforest air.

Purpose: Primary hypothyroidism is a main endocrine complication after allogeneic stem cells transplantation (allo-SCT) in children, but in adults data on post-SCT hypothyroidism are limited. The aims of this observational, cross-sectional study were to assess the prevalence of hypothyroidism in adult allo-SCT recipients according to time from transplantation, and to identify risk factors. Methods: One hundred and eighty-six patients (M 104; F 82; median age 53.4 years) who underwent allo-SCT between January 2010 and December 2017 were enrolled and divided into three groups, according to time from allo-SCT (1–3 years; 3–5 years; > 5 years). Pre-transplant TSH and fT4 levels were available for all patients. After transplantation, TSH, fT4 and anti-thyroperoxidase antibodies (TPO-Ab) were evaluated. Results: After a follow-up of 3.7 years, 34 (18.3%) patients developed hypothyroidism, with higher prevalence in females (p< 0.001) and in patients who received matched unrelated donor grafts (p< 0.05). No difference in prevalence was found at different time points. Patients who developed hypothyroidism showed higher rate of TPO-Ab positivity (p< 0.05) and higher pre-transplant TSH levels (median 2.34 µU/ml) compared to those with preserved thyroid function (median 1.53 µU/ml; p< 0.001). Multivariable analysis identified higher pre-transplant TSH levels as a positive predictor of hypothyroidism (p< 0.005). The ROC curve analysis identified a pre-SCT TSH cutoff of 1.84 µU/ml, which can predict hypothyroidism with sensitivity 74.1% and specificity 67.2%. Conclusions: About one out of four patients developed hypothyroidism after allo-SCT, with a greater incidence in females. Pre-transplant TSH levels seem to predict the onset of post-SCT hypothyroidism.

Ozone is a molecule that plays an important role in dentistry, specially for wound healing. The aim of the present study was to clinically and immunologically evaluate the effect of ozonated oil on the healing of palatal wounds. This is a prospective, longitudinal, triple‐blind, randomized, placebo‐controlled clinical trial. The groups were divided as follows: Test group (n= 14): after removal of the free gingival graft (FGG), the palatal wound was treated with ozonized seed sunflower oil with a peroxide index between 510 and 625 meq O2/kg; Control group (n= 14): after removal of the FGG, the palatal wound was treated with non‐ozonated sunflower oil (placebo). The treatments were applied three times a day, for 7 days. There were no significant differences in the measurements of wound area (mm2) between the test and control groups in the different periods evaluated (0, 3, 7, and 14 days; p> 0.05). The intra‐group analysis showed a significant decrease in wound size over the course of days (0, 3, 7, and 14 days; p< 0.05). Vascular endothelial growth factor (VEGF; pg/mL) presented a significant reduction at 7 days (p< 0.05) compared to day 3 in the test group (p< 0.05). There was a statistical difference for malondialdehyde (MDA; pg/mL) in the test group between 3 and 7 days post‐treatment (p< 0.05) and between test and control groups on the 7th day (p< 0.05). The application of highly ozonated sunflower oil did not improve the remaining scar area of the palate, decreasing the VEGF and increasing the oxidative stress marker MDA.

Understanding the mechanism of drug action in biological systems is facilitated by the interactions between small molecules and target chiral biomolecules. In this context, focusing on the enantiomeric recognition of carbohydrates in solution through steady-state fluorescence emission spectroscopy is noteworthy. To this end, we have developed a third generation of chiral optical sensors for carbohydrates, distinct from all of those previously presented, which interact with carbohydrates to form non-covalent probe-analyte interactions. The proposed sensor is based on 2-oxazolines bearing a fluorophoric benzothiazole unit. We evaluated their photophysical properties in the presence of enantiomeric pairs of arabinose, mannose, xylose, and glucose in solution. Our primary findings indicate that the compounds outlined in this study were able to distinguish between enantiomeric pairs in solution, demonstrating good to excellent enantioselectivity through simple intermolecular interactions. To achieve the best enantioselectivity results, theoretical calculations were performed to better understand the observed interactions between the sensors and the analytes.

Despite government efforts, tuberculosis (TB) remains a major public health threat in Brazil. In 2023, TB incidence was 39.8 cases per 100,000 population, far above the WHO’s target of 6.7 cases per 100,000. Using national-level datasets, we investigated and forecasted the potential impact of proposed public health interventions aimed at reducing TB incidence in Brazil.

The Aesculapian false coral snake, Erythrolamprus aesculapii, is reported here preying on two heterospecific snake species. An individual of E. aesculapiiwas observed preying an adult Atractuscf. majorin the municipality of Presidente Figueiredo, state of Amazonas, Brazil, and another on an adult Tropidodryas striacepsin the municipality of Divino de São Lourenço, state of Espírito Santo, also in Brazil. Both observations detail the predatory behavior of E. aesculapii, from chasing to immobilizing and ingesting the prey snakes. These findings expand knowledge of the predatory interactions of E. aesculapii, including the addition of two new prey species, reinforcing the ophiophagous nature of its feeding behavior.

Decisions are made with different degrees of consistency, and this consistency can be linked to the confidence that the best choice has been made. Theoretical work suggests that attractor dynamics in networks can account for choice consistency, but how this is implemented in the brain remains unclear. Here we provide evidence that the energy landscape around attractor basins in population neural activity in the prefrontal cortex reflects choice consistency. We trained two rhesus monkeys to make accept/reject decisions based on pretrained visual cues that signaled reward offers with different magnitudes and delays to reward. Monkeys made consistent decisions for very good and very bad offers, but decisions were less consistent for intermediate offers. Analysis of neural data showed that the attractor basins around patterns of activity reflecting decisions had steeper landscapes for offers that led to consistent decisions. Therefore, we provide neural evidence that energy landscapes predict decision consistency, which reflects decision confidence.

Cat domestication likely initiated as a symbiotic relationship between wildcats (Felis silvestrissubspecies) and the peoples of developing agrarian societies in the Fertile Crescent. As humans transitioned from hunter-gatherers to farmers ~12,000 years ago, bold wildcats likely capitalized on increased prey density (i.e., rodents). Humans benefited from the cats’ predation on these vermin. To refine the site(s) of cat domestication, over 1000 random-bred cats of primarily Eurasian descent were genotyped for single-nucleotide variants and short tandem repeats. The overall cat population structure suggested a single worldwide population with significant isolation by the distance of peripheral subpopulations. The cat population heterozygosity decreased as genetic distance from the proposed cat progenitor’s (F.s. lybica) natural habitat increased. Domestic cat origins are focused in the eastern Mediterranean Basin, spreading to nearby islands, and southernly via the Levantine coast into the Nile Valley. Cat population diversity supports the migration patterns of humans and other symbiotic species.

Accumulating evidence into the pathogenesis of COVID-19 highlights a hypercoagulability state with high risk of life-threatening thromboembolic complications. However, the mechanisms of hypercoagulability and their link to hyperinflammation remain poorly understood. Here, we investigate functions and mechanisms of platelet activation and platelet-monocyte interactions in inflammatory amplification during SARS-CoV-2 infection. We used a combination of immunophenotyping, single-cell analysis, functional assays, and pharmacological approaches to gain insights on mechanisms. Critically ill patients with COVID-19 exhibited increased platelet-monocyte aggregates formation. We identified a subset of inflammatory monocytes presenting high CD16 and low HLA-DR expression as the subset mainly interacting with platelets during severe COVID-19. Single-cell RNA-sequencing analysis indicated enhanced fibrinogen receptor Mac-1 in monocytes from patients with severe COVID-19. Monocytes from patients with severe COVID-19 displayed increased platelet binding and hyperresponsiveness to P-selectin and fibrinogen with respect to tumor necrosis factor-α and interleukin-1β secretion. Platelets were able to orchestrate monocyte responses driving tissue factor (TF) expression, inflammatory activation, and inflammatory cytokines secretion in SARS-CoV-2 infection. Platelet-monocyte interactions ex vivo and in SARS-CoV-2 infection model in vitro reciprocally activated monocytes and platelets, inducing the heightened secretion of a wide panel of inflammatory mediators. We identified platelet adhesion as a primary signaling mechanism inducing mediator secretion and TF expression, whereas TF signaling played major roles in amplifying inflammation by inducing proinflammatory cytokines, especially tumor necrosis factor-α and interleukin-1β. Our data identify platelet-induced TF expression and activity at the crossroad of coagulation and inflammation in severe COVID-19.

Tuberculosis (TB) remains a global challenge and disproportionately affecting vulnerable populations. This study analyses the economic burden of pulmonary TB in Brazil, focusing on direct healthcare costs. It also evaluates the cost-effectiveness of the Directly Observed Treatment (DOT) strategy and the economic effort required to achieve a 90% probability of cure.

The Amazon rainforest suffers increasing pressure from anthropogenic activities. A key aspect not fully understood is how anthropogenic atmospheric emissions within the basin interact with biogenic emissions and impact the forest’s atmosphere and biosphere. We combine a high-resolution atmospheric chemical transport model with an improved emissions inventory and in-situ measurements to investigate a surprisingly high concentration of ozone (O3) and secondary organic aerosol (SOA) 150–200 km downwind of Manaus city in an otherwise pristine forested region. We show that atmospheric dynamics and photochemistry determine a gross production of secondary pollutants seen in the simulation. After sunrise, the erosion of the nocturnal boundary layer mixes natural forest emissions, rich in biogenic volatile organic compounds, with a lofted pollution layer transported overnight, rich in nitrogen oxides and formaldehyde. As a result, O3and SOA concentrations greater than ∼47 ppbv and 1.8 μg m–3, respectively, were found, with maximum concentrations occurring at 2 pm LT, 150–200 km downwind of Manaus city. These high concentrations affect a large primary forested area of about 11,250 km2. These oxidative areas are under a NOx-limited regime so that changes in NOxemissions from Manaus have a significant impact on O3and SOA production.

The shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora.

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Purpose: Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. Methods: Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson’s trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. Results: Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p&lt; 0.05) and 1144 + ALPHA (p= 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. Conclusions: Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.

Background: Individuals with coronary artery disease (CAD) have worse executive function compared to the general population but the mechanisms are unknown.Objective: To investigate the role of acute mental stress (MS) on the executive function of patients with CAD.Methods: Participants with stable CAD underwent acute MS testing with simultaneous peripheral vascular function measurements and brain imaging using high resolution-positron emission tomography. Digital pulse wave amplitude was continuously measured using peripheral artery tonometry (PAT, Itamar Inc). Stress/rest PAT ratio (sPAT) of pulse wave amplitude during MS/baseline was calculated as a measure of microvascular constriction during MS. Plasma levels of catecholamine and interleukin-6 were assessed at baseline and after MS. Executive function was assessed both at baseline and at 2 years follow-up using the Trail Making Test parts A and B.Results: We studied 389 individuals with brain data available for 148 participants. Of this population follow-up cognitive assessments were performed in 226 individuals (121 with brain imaging). After multivariable adjustment for baseline demographics, risk factors, and medication use, a lower sPAT, indicating greater vasoconstriction, a higher inferior frontal lobe activation with MS, and increases in norepinephrine and IL-6 levels with MS were all independently associated with greater time to complete Trail B test.-38.4ptConclusion: In response to acute MS, greater peripheral vasoconstriction, higher inferior frontal lobe brain activation, and increases in the levels of norepinephrine and IL-6 are associated with worse executive function.

•Inference is a ubiquitous process in cognition and behavior.•State inference optimizes behavioral flexibility and stability under uncertainty.•The neural mechanisms underlie different aspects of hidden state inference.•Inference provides a framework for hierarchically organized decision making.

IMPORTANCE: Compared with older patients, young adults with a history of myocardial infarction (MI) tend to have a higher burden of psychosocial adversity. Exposure to early-life stressors may contribute to the risk of adverse outcomes in this patient population, potentially through inflammatory pathways. OBJECTIVE: To investigate the association of early-life trauma with adverse events and examine whether inflammation plays a role. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients aged 18 to 60 years with a verified history of MI in the past 8 months from a university-affiliated hospital network. Baseline data were collected from June 2011 to March 2016, and follow-up data were obtained through July 2019. Analysis began September 2019. EXPOSURES: Early-life trauma was assessed using the Early Trauma Inventory–Self Report short form (ETI-SR-SF), both as a continuous and as a binary variable at the threshold of a score of 7 or higher. Inflammatory biomarkers, interleukin 6, and C-reactive protein were obtained at baseline. MAIN OUTCOMES AND MEASURES: A composite end point of recurrent MI, stroke, heart failure hospitalization, and cardiovascular death over a median 3-year follow-up. RESULTS: Of 300 patients, the mean (SD) age was 51 (7) years, 198 (66%) were African American, and 150 (50%) were women. Compared with participants with MI with an ETI-SR-SF score less than 7, those with a score of 7 or higher had higher levels of interleukin 6 and C-reactive protein at baseline. Compared with participants with an ETI-SR-SF score less than 7, those with a score of 7 or higher were at a greater risk for adverse outcomes, with a hazards ratio of 2.3 (95% CI, 1.3-3.9). Results remained consistent in multivariable analysis. Further adjustment for C-reactive protein rendered the results no longer statistically significant. Early-life trauma displayed a dose-dependent response when analyzed as a continuous variable and by quartiles. CONCLUSIONS AND RELEVANCE: Early-life trauma is an independent risk factor for adverse outcomes in young and middle-aged individuals with a history of MI. Neurobiological mechanisms leading to lifetime activation of systemic inflammatory cascades may be implicated.

Mycobacterium tuberculosis(Mtb) infection induces pulmonary expression of the heme-degrading enzyme heme oxygenase-1 (HO-1). We have previously shown that pharmacological inhibition of HO-1 activity in experimental tuberculosis results in decreased bacterial loads and unexpectedly that this outcome depends on the presence of T lymphocytes. Here, we extend these findings by demonstrating that IFN? production by T lymphocytes and NOS2 expression underlie this T-cell requirement and that HO-1 inhibition potentiates IFN?-induced NOS2-dependent control of Mtb by macrophages in vitro. Among the products of heme degradation by HO-1 (biliverdin, carbon monoxide, and iron), only iron supplementation reverted the HO-1 inhibition-induced enhancement of bacterial control and this reversal was associated with decreased NOS2 expression and NO production. In addition, we found that HO-1 inhibition results in decreased labile iron levels in Mtb-infected macrophages in vitro and diminished iron accumulation in Mtb-infected lungs in vivo. Together these results suggest that the T-lymphocyte dependence of the therapeutic outcome of HO-1 inhibition on Mtb infection reflects the role of the enzyme in generating iron that suppresses T-cell-mediated IFN?/NOS2-dependent bacterial control. In broader terms, our findings highlight the importance of the crosstalk between iron metabolism and adaptive immunity in determining the outcome of infection.

It is largely known that low temperature stress can affect rice (Oryza sativa L.) development and yield. However, most studies have focussed on unique and uninterrupted cold treatment, which is not representative of cold conditions for early sowing in temperate and subtropical areas where cold nights are followed by warm days during early vegetative stages. In order to elucidate whether rice plants could recover from the damages caused by repetitive cold nights, we submitted a cold-tolerant (CT) and a cold-sensitive (CS) indica genotype to 28 cold nights (10°C) followed by warm days (26°C) and analysed the developmental and productivity traits of plants cultivated in greenhouse and field conditions. While CT plants were able to recover from cold damage without significant development and seed production penalties, CS plants were affected, presenting lower results in plant height, tiller number, number of seeds per plant, % of full seeds per plant, grain length and area, weight of 1000 full grains, and grain weight per plant, with a grain yield reduction of 82% and 30% when cultivated in greenhouse and field conditions, respectively. Such data on sowing period, night temperatures and the cold response of the rice cultivar used are important for the producer to consider.

We conducted a phase I–II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria.

A study was conducted to examine the dissimilarity amongst sexes in core cooling rates after exercise-induced hyperthermia. Findings concluded that males had heavier and lean body mass compared to females.

IMPORTANCE: Stem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown. OBJECTIVE: To investigate the association between the change in CPC counts during stress testing and the risk of adverse cardiovascular events in patients with stable coronary artery disease (CAD). DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included a population-based sample of 454 patients with stable CAD who were recruited between June 1, 2011, and August 15, 2014, at Emory University-affiliated hospitals and followed up for 3 years. Data were analyzed from September 15, 2018, to October 15, 2018. EXPOSURES: Myocardial perfusion imaging with technetium Tc 99m sestamibi at rest and 30 to 60 minutes after conventional stress testing. MAIN OUTCOMES AND MEASURES: Circulating progenitor cells were enumerated with flow cytometry as CD34-expressing mononuclear cells (CD45med/CD34+), with additional quantification of subsets coexpressing the chemokine (C-X-C motif) receptor 4 (CD34+/CXCR4+). Changes in CPC counts were calculated as poststress minus resting CPC counts. Cox proportional hazards regression models were used to identify factors associated with the combined end point of cardiovascular death and myocardial infarction after adjusting for clinical covariates, including age, sex, race, smoking history, body mass index, and history of heart failure, hypertension, dyslipidemia, and diabetes. RESULTS: Of the 454 patients (mean [SD] age, 63 [9] years; 76% men) with stable CAD enrolled in the study, 142 (31.3%) had stress-induced ischemia and 312 (68.7%) did not, as measured by single-photon emission computed tomography. During stress testing, patients with stress-induced ischemia had a mean decrease of 20.2% (interquartile range [IQR], −45.3 to 5.5; P &lt; .001) in their CD34+/CXCR4+ counts, and patients without stress-induced ischemia had a mean increase of 3.2% (IQR, −20.6 to 35.1; P &lt; .001) in their CD34+/CXCR4+ counts. Twenty-four patients (5.2%) experienced adverse events. After adjustment, baseline CPC counts were associated with worse adverse outcomes, but this association was not present after stress-induced ischemia was included in the model. However, the change in CPC counts during exercise remained significantly associated with adverse events (hazard ratio, 2.59; 95% CI, 1.15-5.32, per 50% CD34+/CXCR4+ count decrease), even after adjustment for clinical variables and the presence of ischemia. The discrimination of risk factors associated with incident adverse events improved (increase in C statistic from 0.72 to 0.77; P = .003) with the addition of the change in CD34+/CXCR4+ counts to a model that included clinical characteristics, baseline CPC count, and ischemia. CONCLUSIONS AND RELEVANCE: In this study of patients with CAD, a decrease in CPC counts during exercise is associated with a worse disease prognosis compared with the presence of stress-induced myocardial ischemia. Further studies are needed to evaluate whether strategies to improve CPC responses during exercise stress will be associated with improvements in the prognosis of patients with CAD.

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23–63 months). Overall survival (OS) at 3 years was 27% (95% CI 22–33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31–53) compared with 20% (95% CI 14–24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25–51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies.

IMPORTANCE: Acute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown. OBJECTIVE: To determine the association between mental stress–induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes among individuals with stable coronary artery disease. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at a university-affiliated hospital network between June 2011 and August 2014. A cohort of individuals with stable coronary artery disease were included. Data analysis took place from November 2018 to May 2019. EXPOSURES: Study participants were subjected to a laboratory mental stress task (public speaking). MAIN OUTCOMES AND MEASURES: Flow-mediated vasodilation was measured before and 30 minutes after a public-speaking mental stress task. We examined the association of the rest (prestress), poststress, and δ flow-mediated vasodilation (poststress minus prestress levels) with an adjudicated composite end point of adverse events, including cardiovascular death, myocardial infarction, unstable angina leading to revascularization, and heart failure hospitalization, after adjusting for sociodemographic factors, medical history, and depression. RESULTS: A total of 569 patients were included (mean [SD] age, 62.6 [9.3] years; 420 men [73.8%]). Flow-mediated vasodilation decreased from a mean (SD) of 4.8% (3.7%) before mental stress to 3.9% (3.6%) after mental stress (a 23% reduction; P &lt; .001), and 360 participants (63.3%) developed transient endothelial dysfunction (a decrease in flow-mediated vasodilation). During a median (interquartile range) follow-up period of 3.0 (2.9-3.1) years, 74 patients experienced a major adverse cardiovascular event. The presence of transient endothelial dysfunction with mental stress was associated with a 78% increase (subdistribution hazard ratio [sHR], 1.78 [95% CI, 1.15-2.76]) in the incidence of major adverse cardiovascular event. Both the δ flow-mediated vasodilation (sHR, 1.15 [95% CI, 1.03-1.27] for each 1% decline) and poststress flow-mediated vasodilation (sHR, 1.14 [95% CI, 1.04-1.24] for each 1% decline) were associated with major adverse cardiovascular event. Risk discrimination statistics demonstrated a significant model improvement after addition of either poststress flow-mediated vasodilation (change in the area under the curve, 0.05 [95% CI, 0.01-0.09]) or prestress plus δ flow-mediated vasodilation (change in the area under the curve, 0.04 [95% CI, 0.00-0.08]) compared with conventional risk factors. CONCLUSIONS AND RELEVANCE: In this study, transient endothelial dysfunction with mental stress was associated with adverse cardiovascular outcomes in patients with coronary artery disease. Endothelial responses to stress represent a possible mechanism through which psychological stress may affect outcomes in patients with coronary artery disease.

The study aims to evaluate the technical properties of the application of filler element for slab as a hollow ceramic blocks for non-load-bearing masonry. This ceramic product has dimensions of approximately 6.5x25x81.5 cm, and because it presents different geometries of the conventional ceramic block and characteristics different from those required by the norm, this product was submitted to the norms of non-load-bearing masonry and being carried out tests of geometry, water absorption and compressive strength, besides the visual characteristics according to the standard ABNT NBR 15270/2005. Thirteen samples were used for the geometry and compressive strength test, and six for the water absorption test. Some samples presented a great deviation from the square, besides not being within the established limits of the planes and septa. The water absorption is within the established limits and compressive strength is lower than that required by the standard.

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Necrotic cell death during Mycobacterium tuberculosis (Mtb) infection is considered host detrimental since it facilitates mycobacterial spread. Ferroptosis is a type of regulated necrosis induced by accumulation of free iron and toxic lipid peroxides. We observed that Mtb-induced macrophage necrosis is associated with reduced levels of glutathione and glutathione peroxidase-4 (Gpx4), along with increased free iron, mitochondrial superoxide, and lipid peroxidation, all of which are important hallmarks of ferroptosis. Moreover, necrotic cell death in Mtb-infected macrophage cultures was suppressed by ferrostatin-1 (Fer-1), a well-characterized ferroptosis inhibitor, as well as by iron chelation. Additional experiments in vivo revealed that pulmonary necrosis in acutely infected mice is associated with reduced Gpx4 expression as well as increased lipid peroxidation and is likewise suppressed by Fer-1 treatment. Importantly, Fer-1–treated infected animals also exhibited marked reductions in bacterial load. Together, these findings implicate ferroptosis as a major mechanism of necrosis in Mtb infection and as a target for host-directed therapy of tuberculosis.

Since 2014, Brazil has gradually implemented the Xpert MTB/RIF (Xpert) test to enhance early tuberculosis (TB) and drug-resistant (DR-TB) detection and control, yet its nationwide impact remains underexplored. Our study conducts an intervention time-series analysis (ITSA) to evaluate how the Xpert's implementation has improved TB and DR-TB detection nationwide.

AbstractThree-dimensional (3D) printing is a new method of creating anatomical models, which can enhance the training of students and health professionals. The large breed-variation in dogs means that interpretation of thoracic radiographs can be challenging for the inexperienced radiologist. The aim of this study was to develop digital and printed 3D cardiac models from six canine breeds and evaluate their use as a tool for studying breed variations in radiology. The printed and digital 3D cardiac models were used by postgraduate veterinary students in diagnostic imaging along with a theoretical class on the subject and students completed a pre- and post-test, assessing cardiac size on thoracic radiographs in order to verify the usefulness of the models. The students then completed a satisfaction questionnaire on a Likert scale. There was a significant difference between the pre-test and the post-test results, with greater accuracy after using the 3D models. More errors were made in pre-test interpretation of radiographs from English Cocker Spaniel, English Bulldog, and Yorkshire Terrier and there were a significantly higher number of correct answers after using the 3D models. The vast majority of responses to all questions in the satisfaction questionnaire were positive, with partial or total agreement of the participants. This study demonstrates that digitally printed cardiac models from different breeds of dogs are effective learning tools. They helped students to better understand the relevant spatial relationship and cardiac morphology and to compare this anatomy with the radiographic image. Models are provided in 3D PDF and STL files for download.

Shunts between the superior mesenteric vein (SMV) and the right renal vein (RRV) are very rare. Here, we describe and depict the rare case of a liver transplant (LT) in the setting of shunt between SMV and RRV. A 67-year-old white man presenting with Child C cirrhosis secondary to hemochromatosis and persistent encephalopathy was listed for LT. Preoperative abdominal angiotomography revealed the presence of a large spontaneous shunt between the SMV and the RRV. The patient underwent LT by receiving a liver from a 17-year-old brain-dead deceased donor victim of trauma. A large shunt between the SMV and the RRV was confirmed intraoperatively. Although there was no portal vein (PV) thrombosis, the PV was atrophic and had a reduced flow. PV pressure was 22mmHg (an arterial line was inserted inside the PV stump, and this line was connected to a common pressure transducer, the pressure readings was expressed in the anesthesia monitor). After shunt ligation PV pressure increased to 32mmHg. There were no post-transplant vascular complications, and the patient was discharged home in good health. Preoperative study of all LT candidates with angio CT scan is mandatory. Whenever there is PV thrombosis, an attempt to remove the entire thrombus is warranted. After thrombectomy or whenever there is not PV thrombosis, all large shunts should be ligated. PV pressure and flow should be measured before and after shunt ligation. In the absence of PV thrombosis, ligation of the shunt should enable an increase in PV flow and pressure, as reported herein.

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Background:Neurological disorders (NDs) are associated with high hospital mortality. We aimed to identify predictors of hospital mortality among elderly inpatients with NDs.Methods:Patients aged ≥60 years admitted to the hospital between January 1, 2009 and December 31, 2010 with acute NDs, chronic NDs as underpinnings of acute clinical disorders, and neurological complications of other diseases were studied. We analyzed demographic data, NDs, and comorbidities as independent predictors of hospital mortality. Logistic regression was performed for multivariable analysis.Results:Overall, 1540 NDs and 2679 comorbidities were identified among 798 inpatients aged ≥ 60 years (mean 75.8±9.1). Of these, 54.5% were female. Diagnostic frequency of NDs ranged between 0.3% and 50.8%. Diagnostic frequency of comorbidities ranged from 5.6% to 84.5%. Comorbidities varied from 0 to 9 per patient (90% of patients had ≥2 comorbidities), mean 3.2±1.47(CI, 3.1-3.3). Patients with multimorbidities presented with a mean of 4.7±1.7 morbidities per patient. Each ND and comorbidity were associated with high hospital mortality, producing narrow ranges between the lowest and highest incidences of death (hospital mortality = 18%) (95% CI, 15%-21%). After multivariable analysis, advanced age (P<0.001) and low socioeconomic status (P=0.003) were recognized as predictors of mortality, totaling 9% of the variables associated with hospital mortality.Conclusion:Neither a particular ND nor an individual comorbidity predicted hospital mortality. Age and low socioeconomic class accounted for 9% of predictors. We suggest evaluating whether functional, cognitive, or comorbidity scores will improve the risk model of hospital mortality in elderly patients admitted with ND.

Acute graft-vs-host disease (GVHD) is a serious complication after allografting. We carried out an exploratory study to investigate a potential correlation of surface antigens on extracellular vesicles (EVs) and acute GVHD. EVs were extracted from serum samples from 41 multiple myeloma patients who underwent allografting. EVs were characterized by flow cytometry using a panel of 13 antibodies against specific membrane proteins that were reported to be predictive of acute GVHD. We observed a correlation between three potential biomarkers expressed on EV surface and acute GVHD onset by both logistic regression analysis and Cox proportional hazard model. In our study, CD146 (MCAM-1) was correlated with an increased risk—by almost 60%—of developing GVHD, whereas CD31 and CD140-a (PECAM-1 and PDGFR-a) with a decreased risk—by almost 40 and 60%, respectively. These biomarkers also showed a significant change in signal level from baseline to the onset of acute GVHD. Our novel study encourages future investigations into the potential correlation between EVs and acute GVHD. Larger prospective multicenter studies are currently in progress.