Superhorizon isocurvature fluctuations relax tensions

We present a new class of models that have potential to alleviate tensions present in the cosmological data today. We postulate variation in the sound horizon scale on super-horizon scales, i.e. on scales that are larger than that of the present observable low-redshift universe ($\gtrsim 1\,$Gpc) while at the same time smaller than the largest scales probed by the cosmic microwave background (CMB) ($\lesssim10\,$Gpc). In this scenario, CMB peaks are naturally smoothed as preferred by the Planck data, while at the same time the low-redshift baryon acoustic oscillation calibration is partially decoupled from the CMB. Taking super-horizon variations in baryon fraction as an example and using approximate modeling, we find improvement in the best fit Planck power spectrum model $\Delta \chi^2 \sim 6$ for one extra degree of freedom with the relevant extension parameter $10^3 \sigma_b = 2.12 \pm 0.50$, implying about $10\%$ variations in baryon fraction across the universe. At the same time, $S_8$ drops by about 1 sigma, easing tension with weak lensing surveys. While $H_0$ increases in this model by about 1 sigma, this is insufficient to explain the Hubble tension in $\Lambda$CDM. Since the power of low redshift BAO is relaxed, we find that the combination of Planck 2018 data, eBOSS BAO data and Riess et al distance ladder Hubble parameter determination produces a satisfactory fit in the model with free dark energy equation of state. Such a fit, however, favors a phantom dark energy equation of state $w<-1$ at 2-3 sigma.Comment: 14 pages, 7 figure

A selective alpha1D-adrenoreceptor antagonist inhibits human prostate cancer cell proliferation and motility "in vitro"

The progression of prostate cancer (PC) to a metastatic hormone refractory disease is the major contributor to the overall cancer mortality in men, mainly because the conventional therapies are generally ineffective at this stage. Thus, other therapeutic options are needed as alternatives or in addition to the classic approaches to prevent or delay tumor progression. Catecholamines participate to the control of prostate cell functions by the activation of alpha1-adrenoreceptors (alpha1-AR) and increased sympathetic activity has been linked to PC development and evolution. Molecular and pharmacological studies identified three alpha1-AR subtypes (A, B and D), which differ in tissue distribution, cell signaling, pharmacology and physiological role. Within the prostate, alpha1A-ARs mainly control stromal cell functions, while alpha1B- and alpha1D- subtypes seem to modulate glandular epithelial cell growth. The possible direct contribution of alpha1D-ARs in tumor biology is supported by their overexpression in PC. The studies here presented investigate the "in vitro" antitumor action of A175, a selective alpha1D-AR antagonist we have recently obtained by modifying the potent, but not subtype-selective alpha1-AR antagonist (S)-WB4101, in the hormone-refractory PC3 and DU145 PC cell lines. The results indicate that A175 has an alpha1D-AR-mediated significant and dose-dependent antiproliferative action that possibly involves the induction of G0/G1 cell cycle arrest, but not apoptosis. In addition, A175 reduces cell migration and adhesiveness to culture plates. In conclusion, our work clarified some cellular aspects promoted by alpha1D-AR activity modulation and supports a further pharmacological approach in the cure of hormone-refractory PC, by targeting specifically this AR subtype

Cosmological constraints from abundance, weak-lensing and clustering of galaxy clusters: application to the SDSS

The clustering of galaxy clusters is a powerful cosmological tool, which can help to break degeneracies between parameters when combined with other cosmological observables. We aim to demonstrate its potential in constraining cosmological parameters and scaling relations when combined with cluster counts and weak lensing mass information, using as a case study the redMaPPer cluster catalog derived from the Sloan Digital Sky Survey (SDSS). We extend the analysis of number counts and weak lensing signal performed by Costanzi et al. 2019a, with the addition of the real-space 2-point correlation function. We derive cosmological and scaling relation posteriors for all the possible combinations of the three observables to assess their constraining power, parameter degeneracies, and possible internal tensions. We find no evidence for tensions between the three data set analyzed. We demonstrate that the inclusion of the cluster clustering statistic can greatly enhance the constraining power of the sample thanks to its capability of breaking the $\Omega_{\rm m} - \sigma_8$ degeneracy characteristic of cluster abundance studies. In particular, for a flat $\Lambda$CDM model with massive neutrinos, we obtain $\Omega_{\rm m}=0.28 \pm 0.03$ and $\sigma_8 = 0.82 \pm 0.05$, a 33% and 50% improvement compared to the posteriors derived combining cluster abundance and weak lensing analyses. Our results are consistent with cosmological posteriors from other cluster surveys, as well as with Planck CMB results and DES-Y3 galaxy clustering and weak-lensing analysis.Comment: 15 pages, 10 figure

The rotation of white lupin (Lupinus albus L.) with metal-accumulating plant crops: A strategy to increase the benefits of soil phytoremediation

Most of the plants employed to remove metals from contaminated soils are annuals and have a seed-to- seed life cycle of a few months, usually over spring and summer. Consequently, for most of the year, fields are not actively cleaned but are completely bare and subject to erosion by water and wind. The objective of this study was to evaluate the benefits of using Lupinus albus as a winter crop in a rotation sequence with a summer crop ideally selected for phytoextraction, such as industrial hemp. Lupin plants were grown in two alkaline soil plots (heavy metal-contaminated and uncontaminated) of approximately 400 m 2 each after the cultivation and harvest of industrial hemp. A smaller-scale parallel pot experiment was also performed to better understand the lupin behavior in increasing concentrations of Cd, Cu, Ni and Zn. White lupin grew well in alkaline conditions, covering the soil during the winter season. In few months plants were approximately 40e50 cm high in both control and contaminated plots. In fields where the bioavailable fraction of metals was low (less than 12%), plants showed a high tolerance to these contaminants. However, their growth was affected in some pot treatments in which the concen- trations of assimilable Cu, Zn and Ni were higher, ranging from approximately 40e70% of the total concentrations. The lupin's ability to absorb heavy metals and translocate them to shoots was negligible with respect to the magnitude of contamination, suggesting that this plant is not suitable for extending the period of phytoextraction. However, it is entirely exploitable as green manure, avoiding the appli- cation of chemical amendments during phytoremediation. In addition, in polluted fields, white lupin cultivation increased the soil concentration of live bacteria and the bioavailable percentage of metals. On average live bacteria counts per gram of soil were 65 10 6 ± 18 10 6 and 99 10 6 ± 22*10 6 before and after cultivation, respectively. The percentages of bioavailable Cu, Pb, Ni, Zn and Cr, which were 5.7 ± 0.7, 5.3 ± 1.7, 1.2 ± 0.1, 12 ± 1.5 and 0.1 ± 0.02%, respectively, before lupin growth, increased to 9.6 ± 1.6, 7 ± 2, 2 ± 0.3, 14 ± 1.5 and 0.1 ± 0.02% after lupin harvest. On the whole, our results indicate that the winter cultivation of white lupin in sequence with a metal- accumulator summer crop can improve the recovery of soil quality during the phytoextraction period. It improves the safety of the area, limiting additional ecological and human health problems, and enhances soil health by avoiding the use of chemical amendments and by increasing the levels of viable microorganism

Changes in Pain Perception following Psychotherapy: The Mediating Role of Psychological Components

Chronic pain is frequently associated with significant psychological issues, such as depression or anxiety. Psychological treatments, such as psychotherapy, can often alleviate both psychological and pain symptoms. However, there is limited research about the association between psychological symptoms and perceived pain in the context of psychotherapeutic interventions. We conducted a retrospective study that analyzed, in a hospital context, how changes in psychological functioning and well-being were associated with pain reduction. Thirty-seven records of patients with chronic pain attending psychotherapy in a public hospital were included. All patients were assessed before psychotherapy, as well as after 6 and 10 months, with self-reported questionnaires about pain, anxiety, depression, and psychological functioning. Results indicate that reductions in anxiety, depression, psychological problems, risk factors, and well-being are strongly related with a reduction in pain, further confirming the hypothesis that psychological morbidity is associated with pain severity

DAPT plus anticoagulant therapy: The difficult coexistence post-ACS in older patients with atrial fibrillation

Atrial fibrillation (AF) and coronary artery disease requiring percutaneous coronary intervention (PCI) and stenting often coexist in older patients. This poses the difficult problem of concurrent anticoagulant and double antiplatelet therapy (triple therapy). Current treatment guidelines do recommend triple therapy, especially in the course of acute coronary syndrome (ACS), with limitations due to an excessive risk of bleeding associated with this therapeutic regimen. This review summarizes randomized clinical trials and observational studies that compared triple therapy with a variety of different therapeutic options. Although the available evidence is not completely satisfactory and other studies are urgently needed, alternative regimens to triple therapy in AF patients undergoing PCI and stenting are promising, at least in terms of safety

Therapeutic Induction of Energy Metabolism Reduces Neural Tissue Damage and Increases Microglia Activation in Severe Spinal Cord Injury

: Neural tissue has high metabolic requirements. Following spinal cord injury (SCI), the damaged, tissue suffers from a severe metabolic impairment, which aggravates axonal degeneration and, neuronal loss. Impaired cellular energetic, tricarboxylic acid (TCA) cycle and oxidative, phosphorylation metabolism in neuronal cells has been demonstrated to be a major cause of neural tissue death and regeneration failure following SCI. Therefore, rewiring the spinal cord cell metabolism may be an innovative therapeutic strategy for the treatment of SCI. In this study, we evaluated the therapeutic effect of the recovery of oxidative metabolism in a mouse model of severe contusive SCI. Oral administration of TCA cycle intermediates, co-factors, essential amino acids, and branched-chain amino acids was started 3 days post-injury and continued until the end of the experimental procedures. Metabolomic, immunohistological, and biochemical analyses were performed on the injured spinal cord sections. Administration of metabolic precursors enhanced spinal cord oxidative metabolism. In line with this metabolic shift, we observed the activation of the mTORC1 anabolic pathway, the increase in mitochondrial mass, and ROS defense which effectively prevented the injury-induced neural cell apoptosis in treated animals. Consistently, we found more choline acetyltransferase (ChAT)-expressing motor neurons and increased neurofilament positive corticospinal axons in the spinal cord parenchyma of the treated mice. Interestingly, oral administration of the metabolic precursors increased the number of activated microglia expressing the CD206 marker suggestive of a, pro-resolutive, M2-like phenotype. These molecular and histological modifications observed in treated animals ultimately led to a significant, although partial, improvement of the motor functions. Our data demonstrate that rewiring the cellular metabolism can represent an effective strategy to treat SCI

Critical issues for the proper diagnosis of Metachromatic Leukodystrophy

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Computed tomography findings and prognosis in older COVID-19 patients

Background: In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. Methods: Hospitalized COVID-19 patients aged 60&nbsp;years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. Results: 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24-3.06) for pleural effusion and 13 (95%CI 6.41-27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion ("LH"), respectively. Out of the three CT based clusters, "LH" was the only independent predictor in the multivariable model. Conclusions: Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. Trial registration: ClinicalTrials.gov:&nbsp;NCT04379440

Testing the 2018 NIA-AA research framework in a retrospective large cohort of patients with cognitive impairment: From biological biomarkers to clinical syndromes

Background According to the 2018 NIA-AA research framework, Alzheimer's disease (AD) is not defined by the clinical consequences of the disease, but by its underlying pathology, measured by biomarkers. Evidence of both amyloid-beta (A beta) and phosphorylated tau protein (p-tau) deposition-assessed interchangeably with amyloid-positron emission tomography (PET) and/or cerebrospinal fluid (CSF) analysis-is needed to diagnose AD in a living person. Our aim was to test the new NIA-AA research framework in a large cohort of cognitively impaired patients to evaluate correspondence between the clinical syndromes and the underlying pathologic process testified by biomarkers. Methods We retrospectively analysed 628 subjects referred to our centre in suspicion of dementia, who underwent CSF analysis, together with neuropsychological assessment and neuroimaging, and were diagnosed with different neurodegenerative dementias according to current criteria, or as cognitively unimpaired. Subjects were classified considering CSF biomarkers, and the prevalence of normal, AD-continuum and non-AD profiles in each clinical syndrome was calculated. The positivity threshold of each CSF biomarker was first assessed by receiver operating characteristic analysis, using A beta-positive/negative status as determined by amyloid-PET visual reads. The agreement between CSF and amyloid-PET data was also evaluated. Results Among patients with a clinical diagnosis of AD, 94.1% were in the AD-continuum, whereas 5.5% were classified as non-AD and 0.4% were normal. The AD-continuum profile was found also in 26.2% of frontotemporal dementia, 48.6% of Lewy body dementia, 25% of atypical parkinsonism and 44.7% of vascular dementia. Biomarkers' profile did not differ in amnestic and not amnestic mild cognitive impairment. CSF A beta levels and amyloid-PET tracer binding negatively correlated, and the concordance between the two A beta biomarkers was 89%. Conclusions The examination of the 2018 NIA-AA research framework in our clinical setting revealed a good, but incomplete, correspondence between the clinical syndromes and the underlying pathologic process measured by CSF biomarkers. The AD-continuum profile resulted to be a sensitive, but non-specific biomarker with regard to the clinical AD diagnosis. CSF and PET A beta biomarkers were found to be not perfectly interchangeable to quantify the A beta burden, possibly because they measure different aspects of AD pathology