Adaptive radiations play key roles in the generation of biodiversity and biological novelty, and therefore understanding the factors that drive them remains one of the most important challenges of ...evolutionary biology. Although both intrinsic innovations and extrinsic ecological opportunities contribute to diversification bursts, few studies have looked at the synergistic effect of such factors. Here we investigate the Teloschistales (Ascomycota), a group of >1,000 lichenized species with variation in species richness and phenotypic traits that hinted at a potential adaptive radiation. We found evidence for a dramatic increase in diversification rate for one of four families within this order—Teloschistaceae—which occurred ∼100 Mya (Late Cretaceous) and was associated with a switch from bark to rock and from shady to sun-exposed habitats. This adaptation to sunny habitats is likely to have been enabled by a contemporaneous key novel phenotypic innovation: the production in both vegetative structure (thallus) and fruiting body (apothecia) of anthraquinones, secondary metabolites known to protect against UV light. We found that the two ecological factors (sun exposure and rock substrate) and the phenotypic innovation (anthraquinones in the thallus) were all significant when testing for state-dependent shifts in diversification rates, and together they seem likely to be responsible for the success of the Teloschistaceae, one of the largest lichen-forming fungal lineages. Our results support the idea that adaptive radiations are driven not by a single factor or key innovation, but require a serendipitous combination of both intrinsic biotic and extrinsic abiotic and ecological factors.
La diabetes gestacional es una condición que se reconoce por primera vez en el embarazo y está asociada a serias complicaciones maternas, fetales y perinatales en el corto y largo plazo. El tema más ...controversial ha sido la forma para realizar el diagnóstico por la existencia de múltiples criterios diagnósticos. Esta situación se ha vuelto más compleja en los últimos años a partir de la implementación de la estrategia de un paso, propuesta por la International Association of Diabetes and Pregnancy Study Groups (IADPSG, por sus iniciales en inglés), cuya aplicación aumentó la incidencia de la enfermedad hasta un 17,8% en comparación con la estrategia tradicional de dos pasos (tamización y prueba confirmatoria), con la que la incidencia siempre se había estimado entre 6 y 7%. La evidencia actual no ha demostrado que el enfoque de un paso sea superior a la estrategia de dos pasos, en términos de complicaciones, costos y salud pública. Dados los beneficios de la intervención, por disminución de la incidencia de desenlaces adversos como macrosomía, distocia de hombros, recién nacidos grandes para la edad gestacional e hipertensión materna, se justifica la realización del tamizaje universal en las gestantes. Abstract Gestational diabetes is any glucose abnormality first recognized in pregnancy. It has been associated with maternal, fetal and newborn complications. Which diagnostic method to use has been a source of controversy (75 gram OGTT vs the two step approach 50 gram followed by 100 gram OGTT). Since the recommendations made by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) of using the 75 gram OGTT it has been argued that the incidence would rise from approximately 6-7% to 17,8%. There is no evidence that the one step strategy is superior to the two step approach in terms of reduction of complications or from an economical stand point. Regardless of the method used to make the diagnosis it has been shown that treatment of GDM (gestational diabetes) decreases the incidence of large for gestational age, shoulder distocia, macrosomia and maternal hypertension. Universal screening should be recommended to all pregnant patients.
Background
Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not ...been thoroughly demonstrated.
Objective
To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19.
Design
We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial.
Participants
We recruited 116 hospitalized patients with severe COVID-19 in Mexico.
Interventions
Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment.
Main Measures
The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients.
Key Results
Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35–1.93,
P
= 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66–3.88,
P
= 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A.
Conclusions
Colchicine is safe but not effective in the treatment of severe COVID-19.
Trial Registration
ClinicalTrials.gov Identifier: NCT04367168.
We identified the main changes in serum metabolites associated with severe (n = 46) and mild (n = 19) COVID-19 patients by gas chromatography coupled to mass spectrometry. The modified metabolic ...profiles were associated to an altered amino acid catabolism in hypoxic conditions. Noteworthy, three α-hydroxyl acids of amino acid origin increased with disease severity and correlated with altered oxygen saturation levels and clinical markers of lung damage. We hypothesize that the enzymatic conversion of α-keto-acids to α- hydroxyl-acids helps to maintain NAD recycling in patients with altered oxygen levels, highlighting the potential relevance of amino acid supplementation during SARS-CoV-2 infection.
SARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully ...elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.
Using a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.
The frequency of CD19
B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.
The severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.
Lupus nephritis (LN) is one of the most common manifestations of systemic lupus erythematosus (SLE), characterized by abnormal B cell activation and differentiation to memory or plasma effector ...cells. However, the role of these cells in the pathogenesis of LN is not fully understood, as well as the effect of induction therapy on B cell subsets, possibly associated with this manifestation, like aged-associated B cells (ABCs). Consequently, we analyzed the molecules defining the ABCs subpopulation (CD11c, T-bet, and CD21) through flow cytometry of blood samples from patients with lupus presenting or not LN, following up a small sub-cohort after six months of induction therapy. The frequency of ABCs resulted higher in LN patients compared to healthy subjects. Unexpectedly, we identified a robust reduction of a CD21
hi
subset that was almost specific to LN patients. Moreover, several clinical and laboratory lupus features showed strong and significant correlations with this undefined B cell subpopulation. Finally, it was observed that the induction therapy affected not only the frequencies of ABCs and CD21
hi
subsets but also the phenotype of the CD21
hi
subset that expressed a higher density of CXCR5. Collectively, our results suggest that ABCs, and more importantly the CD21
hi
subset, may work to assess therapeutic response since the reduced frequency of CD21
hi
cells could be associated with the onset of LN.
Background
Most of the explanatory and prognostic models of COVID-19 lack of a comprehensive assessment of the wide COVID-19 spectrum of abnormalities. The aim of this study was to unveil novel ...biological features to explain COVID-19 severity and prognosis (death and disease progression).
Methods
A predictive model for COVID-19 severity in 121 patients was constructed by ordinal logistic regression calculating odds ratio (OR) with 95% confidence intervals (95% CI) for a set of clinical, immunological, metabolomic, and other biological traits. The accuracy and calibration of the model was tested with the area under the curve (AUC), Somer’s D, and calibration plot. Hazard ratios with 95% CI for adverse outcomes were calculated with a Cox proportional-hazards model.
Results
The explanatory variables for COVID-19 severity were the body mass index (BMI), hemoglobin, albumin, 3-Hydroxyisovaleric acid, CD8+ effector memory T cells, Th1 cells, low-density granulocytes, monocyte chemoattractant protein-1, plasma TRIM63, and circulating neutrophil extracellular traps. The model showed an outstanding performance with an optimism-adjusted AUC of 0.999, and Somer’s D of 0.999. The predictive variables for adverse outcomes in COVID-19 were severe and critical disease diagnosis, BMI, lactate dehydrogenase, Troponin I, neutrophil/lymphocyte ratio, serum levels of IP-10, malic acid, 3, 4 di-hydroxybutanoic acid, citric acid, myoinositol, and cystine.
Conclusions
Herein, we unveil novel immunological and metabolomic features associated with COVID-19 severity and prognosis. Our models encompass the interplay among innate and adaptive immunity, inflammation-induced muscle atrophy and hypoxia as the main drivers of COVID-19 severity.
The results of a sliding wear tests on base and thermal treated gray cast iron (GCI) samples from internal combustion engine cylinder liner are reported here for dry and lubricated conditions. A ...thermal treatment was applied to samples of 10 x 10 mm to avoid the effect of residual stress and to obtain the microstructure of interest. Tribological tests were carried out up to 27000 cycles at room temperature. A frequency of 15 Hz, a stroke amplitude of 6 mm, and a maximum contact pressure of 1.12 GPa were selected. Under the unlubricated settings, a noticeable decrease in friction coefficient and specific wear rate are attributed to the appearance of irregular graphite nodules in the heating-quenching process. The significance of thermal treatment applied to low carbon cast iron in the derived self-lubricating function and its synergistic role with the oil lubricant is discussed. In this context, this work illustrates, for the first time, how the change in the morphology from flake graphite to irregular nodule graphite positively determines the reliability of gray casting irons.
Background
Different prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA ...index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD).
Aim
The aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT.
Methods
Out of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively.
Results
Minor PED was independently associated with a better iORR 78.8% vs. 50%, OR 3.71 (95% CI 1.26–10.99);
p
= 0.018 to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED 6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7–4.4);
p
< 0.001 independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS 18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4–3.3);
p
= 0.001.
Conclusion
Higher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.
Systematic review.
To provide current evidence on the efficacy of 4-aminopyridine (4-AP) to bring about functional improvement in individuals with chronic traumatic spinal cord injury (SCI).
The ...Medline (PubMed), Web of Science and SCOPUS databases were systematically searched for relevant articles on the efficacy of 4-AP to treat SCI, from the dates such articles were first published until May 2022. Full-text versions of all the articles selected were examined independently by two reviewers. Methodological quality was rated using the Modified Jadad Scale, and risk of bias was assessed with the RoB-2 test. Data extracted included human models/types, PRISMA assessment protocols, and the results of each study. Descriptive syntheses are provided.
In total, 28 articles were initially identified, 10 of which were included after screening. Most of the studies reviewed reported some degree of patient improvement in one or more of the following parameters: motor, sensitivity and sexual function, sphincter control, spasticity, ability to function independently, quality of life, central motor conduction, pain, and pulmonary function.
This review confirms the efficacy of 4-AP in improving several conditions resulting from SCI but further research on this topic is warranted. Additional randomized clinical trials with 4-AP involving larger sample sizes are needed, as are consistent outcome measures in order to obtain adequate data for analysis with a view to enhance treatment benefits.
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=334835, PROSPERO CRD42022334835.
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