Association of Vitamin D Prescribing and Clinical Outcomes in Adults Hospitalized with COVID-19.

It is unclear whether vitamin D benefits inpatients with COVID-19. Objective: To examine the relationship between vitamin D and COVID-19 outcomes. Design: Cohort study. Setting: National COVID Cohort Collaborative (N3C) database. Patients: 158,835 patients with confirmed COVID-19 and a sub-cohort with severe disease (n = 81,381) hospitalized between 1 January 2020 and 31 July 2021. Methods: We identified vitamin D prescribing using codes for vitamin D and its derivatives. We created a sub-cohort defined as having severe disease as those who required mechanical ventilation or extracorporeal membrane oxygenation (ECMO), had hospitalization >5 days, or hospitalization ending in death or hospice. Using logistic regression, we adjusted for age, sex, race, BMI, Charlson Comorbidity Index, and urban/rural residence, time period, and study site. Outcomes of interest were death or transfer to hospice, longer length of stay, and mechanical ventilation/ECMO. Results: Patients treated with vitamin D were older, had more comorbidities, and higher BMI compared with patients who did not receive vitamin D. Vitamin D treatment was associated with an increased odds of death or referral for hospice (adjusted odds ratio (AOR) 1.10: 95% CI 1.05−1.14), hospital stay >5 days (AOR 1.78: 95% CI 1.74−1.83), and increased odds of mechanical ventilation/ECMO (AOR 1.49: 95% CI 1.44−1.55). In the sub-cohort of severe COVID-19, vitamin D decreased the odds of death or hospice (AOR 0.90, 95% CI 0.86−0.94), but increased the odds of hospital stay longer >5 days (AOR 2.03, 95% CI 1.87−2.21) and mechanical ventilation/ECMO (AOR 1.16, 95% CI 1.12−1.21). Limitations: Our findings could reflect more aggressive treatment due to higher severity. Conclusion: Vitamin D treatment was associated with greater odds of extended hospitalization, mechanical ventilation/ECMO, and death or hospice referral.

A case of proliferative nodule arising within blue nevus.

Abstract: Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical , dermoscopic and histolopathologic features of a case of proliferative nodule arising within blue nevus is discussed. Running title: Blue nevi are an heterogeneous group of melanocytic lesions blue tinctorial properties. Proliferative nodules are rare benign lesions often present at birth as a component of a large congenital melanocytic nevi, congenital or acquired nevi. We first report a case of proliferative nodule arising within blue nevus.

A Review of the EUSO-Balloon Pathfinder for the JEM-EUSO Program.

EUSO-Balloon is a pathfinder for JEM-EUSO, the mission concept of a spaceborne observatory which is designed to observe Ultra-High Energy Cosmic Ray (UHECR)-induced Extensive Air Showers (EAS) by detecting their UltraViolet (UV) light tracks "from above." On August 25, 2014, EUSO-Balloon was launched from Timmins Stratospheric Balloon Base (Ontario, Canada) by the balloon division of the French Space Agency CNES. After reaching a floating altitude of 38 km, EUSO-Balloon imaged the UV light in the wavelength range ∼290-500 nm for more than 5 hours using the key technologies of JEM-EUSO. The flight allowed a good understanding of the performance of the detector to be developed, giving insights into possible improvements to be applied to future missions. A detailed measurement of the photoelectron counts in different atmospheric and ground conditions was achieved. By means of the simulation of the instrument response and by assuming atmospheric models, the absolute intensity of diffuse light was estimated. The instrument detected hundreds of laser tracks with similar characteristics to EASs shot by a helicopter flying underneath. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. The reconstruction of the direction of the laser tracks was performed. In this work, a review of the main results obtained by EUSO-Balloon is presented as well as implications for future space-based observations of UHECRs.

A case of hidradenitis suppurativa linked to trisomy 1q.

Hidradenitis suppurativa (HS) is a chronic relapsing disorder of the apocrine gland affecting mainly areas subjected to friction (e.g. the axillae, groin, perineum and medial aspects of the thighs). This condition can be linked to different comorbidities: autoimmune and inflammatory disease, hormone-related disorders, obesity and the metabolic syndrome, as well as rare syndromes such as Bazex-Dupré-Christol, Down's, KID, PAPASH, PASS, PASH, and SAPHO syndromes, or Dowling-Degos disease. We report a case of severe HS in a patient with Trisomy 1q;13, a very rare cytogenetic anomaly characterized by severe anomalies including dysmorphisms, multiple congenital malformations, heart defects and intellectual disability.

Dermoscopy and methyl aminolevulinate: A study for detection and evaluation of field cancerization.

Actinic keratosis (AK) is a keratinocyte intraepidermal neoplasia UV light-induced that frequently appears in sun-exposed areas of the skin. Although historically AK was defined as "precancerous", actually it is considered as the earliest stage of squamous cell carcinoma (SCC) in situ. Since AKs can progress into invasive SCC, their treatment is recommended. AKs rarely develop as a single lesion; usually multiple lesions commonly affect an entire area of chronically actinic damaged skin. This has led to the concept of "field cancerization", an area chronically sun-exposed that surrounds peripherally visible lesions, in which are individualized subclinical alterations. One of the main principles endpoint in the management of AKs is the evaluation and the treatment of field cancerization. In this view, in order to detect and quantify field cancerization, we employed a method based on the topical application of methyl aminolevulinate (MAL) and the detection of the fluorescence emitted by its metabolite Protoporphyrin IX (PpIX); then, considering the extension and the intensity of measured fluorescence, we create a score of field cancerization. The results show that patients underwent to daylight PDT had a reduction of total score, from T0 to T2. Whereas in the group untreated we observed a stability of total score or a slightly worse. So, the method and the score used allows to evaluate with a good approximation the dimension of field cancerization and show the modification of it after treatment.

Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits.

Alterations of the dopaminergic system are associated with the cognitive and functional dysfunctions that characterize complex neuropsychiatric disorders. We modeled a dysfunctional dopaminergic system using mice with targeted ablation of dopamine (DA) D2 autoreceptors in mesencephalic dopaminergic neurons. Loss of D2 autoreceptors abolishes D2-mediated control of DA synthesis and release. Here, we show that this mutation leads to a profound alteration of the genomic landscape of neurons receiving dopaminergic afferents at distal sites, specifically in the prefrontal cortex. Indeed, we observed a remarkable downregulation of gene expression in this area of ~2000 genes, which involves a widespread increase in the histone repressive mark H3K9me2/3. This reprogramming process is coupled to psychotic-like behaviors in the mutant mice. Importantly, chronic treatment with a DA agonist can revert the genomic phenotype. Thus, cortical neurons undergo a profound epigenetic reprogramming in response to dysfunctional D2 autoreceptor signaling leading to altered DA levels, a process that may underlie a number of neuropsychiatric disorders.

Measurement of the depth of maximum of extensive air showers above 10{18} eV.

We describe the measurement of the depth of maximum, X{max}, of the longitudinal development of air showers induced by cosmic rays. Almost 4000 events above 10;{18} eV observed by the fluorescence detector of the Pierre Auger Observatory in coincidence with at least one surface detector station are selected for the analysis. The average shower maximum was found to evolve with energy at a rate of (106{-21}{+35}) g/cm{2}/decade below 10{18.24+/-0.05} eV, and (24+/-3) g/cm{2}/decade above this energy. The measured shower-to-shower fluctuations decrease from about 55 to 26 g/cm{2}. The interpretation of these results in terms of the cosmic ray mass composition is briefly discussed.

Comment on "Observation of neutronless fusion reactions in picosecond laser plasmas".

The paper by Belyaev [Phys. Rev. E 72, 026406 (2005)] reported the first experimental observation of alpha particles produced in the thermonuclear reaction 11B(p,alpha)8Be induced by laser irradiation on a 11B polyethylene (CH2) composite target. The laser used in the experiment is characterized by a picosecond pulse duration and a peak of intensity of 2x10(18) W/cm(2). We suggest that both the background-reduction method adopted in their detection system and the choice of the detection energy region of the reaction products are possibly inadequate. Consequently the total yield reported underestimates the true yield. Based on their observation, we give an estimation of the total yield to be higher than their conclusion, i.e., of the order of 10(5)alpha per shot.

Isospin dependence of incomplete fusion reactions at 25 MeV/nucleon.

40Ca+;{40,48}Ca,46Ti reactions at 25 MeV/nucleon have been studied using the 4pi CHIMERA detector. An isospin effect on the competition between fusionlike and binarylike reaction mechanisms has been observed. The probability of producing a heavy residue is lower in the case of N approximately Z colliding systems as compared to the case of reactions induced on the neutron rich 48Ca target. Predictions based on constrained molecular dynamics II calculations show that the competition between fusionlike and binary reactions in the selected centrality bins can constrain the parametrization of the symmetry energy and its density dependence in the nuclear equation of state.

Observation of the suppression of the flux of cosmic rays above 4 x 10 (19) eV.

The energy spectrum of cosmic rays above 2.5 x 10;{18} eV, derived from 20,000 events recorded at the Pierre Auger Observatory, is described. The spectral index gamma of the particle flux, J proportional, variantE;{-gamma}, at energies between 4 x 10;{18} eV and 4 x 10;{19} eV is 2.69+/-0.02(stat)+/-0.06(syst), steepening to 4.2+/-0.4(stat)+/-0.06(syst) at higher energies. The hypothesis of a single power law is rejected with a significance greater than 6 standard deviations. The data are consistent with the prediction by Greisen and by Zatsepin and Kuz'min.

Upper limit on the diffuse flux of ultrahigh energy tau neutrinos from the Pierre Auger Observatory.

The surface detector array of the Pierre Auger Observatory is sensitive to Earth-skimming tau neutrinos that interact in Earth's crust. Tau leptons from nu(tau) charged-current interactions can emerge and decay in the atmosphere to produce a nearly horizontal shower with a significant electromagnetic component. The data collected between 1 January 2004 and 31 August 2007 are used to place an upper limit on the diffuse flux of nu(tau) at EeV energies. Assuming an E(nu)(-2) differential energy spectrum the limit set at 90% C.L. is E(nu)(2)dN(nu)(tau)/dE(nu)<1.3 x 10(-7) GeV cm(-2) s(-1) sr(-1) in the energy range 2 x 10(17) eV< E(nu)< 2 x 10(19) eV.

Fast ternary and quaternary breakup of the 197Au + 197Au system in collisions at 15 MeV/nucleon.

A new reaction mechanism of violent reseparation of a heavy nucleus-nucleus system, 197Au + 197Au, into three or four massive fragments in collisions at 15 MeV/nucleon has been observed. After reseparation, the fragments are almost exactly aligned, thus showing a very short time scale of the reseparation process, of about 70-80 fm/c.

Correlation of the highest-energy cosmic rays with nearby extragalactic objects.

Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrated a correlation between the arrival directions of cosmic rays with energy above 6 x 10(19) electron volts and the positions of active galactic nuclei (AGN) lying within approximately 75 megaparsecs. We rejected the hypothesis of an isotropic distribution of these cosmic rays with at least a 99% confidence level from a prescribed a priori test. The correlation we observed is compatible with the hypothesis that the highest-energy particles originate from nearby extragalactic sources whose flux has not been substantially reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

Possibility to deduce the emission time sequence of neutrons and protons from the neutron-proton correlation function.

Experimental information has been derived from the neutron-proton correlation function in order to deduce the time sequence of neutrons and protons emitted at 45 degrees in the E/A = 45 MeV 58Ni + 27Al reaction.

Non-steroidal glucocorticoid-like substances: receptor binding and in vivo activity.

Compounds of general structure I, prepared by a Diels-Alder reaction with diene 3, are relatives of the known potent glucocorticoid II but possess a markedly modified C- and D-ring environment. Despite these structural changes, 4, 5, 9, 10, 12a, 13, and 14 bound to the glucocorticoid receptor with an affinity which approximated that of the reference standard, 6-alpha-methylprednisolone. Four of these compounds not only exhibited antiinflammatory activity in the alpha-tocopherol pouch test but also exhibited marked adrenal suppression and other typical glucocorticoid properties at doses in the same range as the effective antiinflammatory doses.

Clastogenic and aneuploidizing effects of antiblastic busulphan revealed by kinetochore immunofluorescence in CHO cells.

We utilized, in CHO cells, the cytoplasm preservation technique to evaluate the micronucleus frequency at different busulphan concentrations, and the indirect immunofluorescence technique, using sera obtained from patients with scleroderma (CREST variant), to analyze if busulphan-induced micronuclei have kinetochores. Results show that this alkylating agent is capable of causing a significant increase of micronuclei in vitro, a great part (40%) of them having CREST-positive kinetochores. These findings confirm the clastogenic effect of busulphan and reveal a considerable capability of this agent to induce aneuploidy. These results are examined taking into account the high incidence of secondary neoplasias induced by chemotherapy with alkylating agents utilized against primary neoplasias.

Steroidogenesis inhibitors. 1. Adrenal inhibitory and interceptive activity of trilostane and related compounds.

Several methylated derivatives of trilostane were prepared. Methylation of C-4 or C-4 and C-17 changes this relatively selective adrenal inhibitor to compounds with increased ovarian/placental inhibitory activity with decreased adrenal inhibitory activity.

Win 32,729, a new, potent interceptive agent in rats and rhesus monkeys.

Win 32,729 [(2 alpha, 4 alpha, 5 alpha, 17 beta)-4,5-epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane-2-carbonitrile] is an orally active interceptive agent in rats and rhesus monkeys (M mulatta). A single oral dose of 48 mg/kg terminated gestation when given on Day 10 of pregnancy. When given orally for up to 5 days to pregnant monkeys, it terminated pregnancy in 26 of 34 animals at a dose of 50 mg/monkey (ca 7 mg/kg), in 18 of 24 at a dose of 100 mg/monkey (ca 14 mg/kg) and in all 6 at 250 mg/monkey (ca 35 mg/kg). It did not inhibit ACTH-stimulated glucocorticoid production at 50 mg/monkey but did at a dose of 250 mg/monkey. This preferential gonadal inhibition was not evident in rodents. While in most cases five oral medications of 50-100 mg were required to terminate gestation in 50-day pregnant monkeys, a single subcutaneous medication with 250 mg was also effective, terminating pregnancy in 7 of 7 monkeys.

Interceptive activity of azastene in rhesus monkeys.

Azastene is an orally effective "luteolytic" agent in rhesus monkeys. In nonpregnant monkeys it reverses the human chorionic gonadotropin-stimulated increase in progesterone production and delay in the onset of menstruation, and, in inseminated monkeys, it prevents pregnancy if given for 5 days beginning on day 24 of the menstrual cycle. The drug is also effective in terminating pregnancy if given for 5 days beginning on approximately day 26, day 50, or day 80 of gestation. Concurrent progesterone administration prevents the interceptive action of the drug. Although azastene inhibits gonadal and placental progesterone production, it has no effect on cortisol production in monkeys and is devoid of apparent hormonal activity.