Determination of biogeochemical properties in sea waters using the inversion of the three-stream irradiance model.

Inversion models, in the context of oceanography, relate the observed ocean color to the concentrations of the different biogeochemical components present in the water of the ocean. However, building accurate inversion models can be quite complex due to the many factors that can influence the observed ocean color, such as variations in the composition or the optical properties of biogeochemical products. Here we assess the feasibility of the inversion approach, by implementing the three-stream light inversion model in a one-dimensional water column configuration, represented at the BOUSSOLE site in the northwestern Mediterranean Sea.

Incorporation of Edited MRS into Clinical Practice May Improve Care of Patients with -Mutant Glioma.

Background And Purpose: Isocitrate dehydrogenase () mutation and 1p/19q codeletion classify adult-type diffuse gliomas into 3 tumor subtypes with distinct prognoses. We aimed to evaluate the performance of edited MR spectroscopy for glioma subtyping in a clinical setting, via the quantification of D-2-hydroxyglutarate (2HG) and cystathionine. The delay between this noninvasive classification and the integrated histomolecular analysis was also quantified.

Coronary calcifications as a new prognostic marker in COVID-19 patients: role of CT.

Objective: COVID-19 pneumonia, caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic by the WHO on 11th March 2020. While Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) represents the diagnostic gold standard of infection, computed tomography (CT) has been shown to have an important role in supporting the diagnosis, quantifying the severity, and assessing the efficacy of treatment and its response. Coronary artery calcification (CAC) is a CT finding that estimates atherosclerosis and can be quantified using the coronary artery calcium score (CACS).

Radiative Transfer Modeling With Biogeochemical-Argo Float Data in the Mediterranean Sea.

A radiative transfer model was parameterized and validated using Biogeochemical Argo float data acquired between 2012 and 2017 across the Mediterranean Sea. Fluorescence-derived chlorophyll concentration, particulate optical backscattering at 700 nm, and fluorescence of chromophoric dissolved organic matter (CDOM) were used to parametrize the light absorption and scattering coefficients of the optically significant water constituents (such as pure water, non-algal particles, CDOM, and phytoplankton). The model was validated with in situ downwelling irradiance profiles and apparent optical properties derived both from irradiance profiles and satellite data, such as the diffuse attenuation coefficients and remote sensing reflectance.

Effects of solar irradiance noise on a complex marine trophic web.

The analysis of experimental data of the solar irradiance, collected on the marine surface, clearly highlights the intrinsic stochasticity of such an environmental parameter. Given this result, effects of randomly fluctuating irradiance on the population dynamics of a marine ecosystem are studied on the basis of the stochastic 0-dimensional biogeochemical flux model. The noisy fluctuations of the irradiance are formally described as a multiplicative Ornstein-Uhlenbeck process, that is a self-correlated Gaussian noise.

Imaging-based indices combining disease severity and time from disease onset to predict COVID-19 mortality: A cohort study.

Background: COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care.

Purpose: The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED).

Materials And Methods: All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included.

Low complexity model to study scale dependence of phytoplankton dynamics in the tropical Pacific.

We demonstrate that a simple model based on reaction-diffusion-advection (RDA) equation forced by realistic surface velocities and nutrients is skilled in reproducing the distributions of the surface phytoplankton chlorophyll in the tropical Pacific. We use the low-complexity RDA model to investigate the scale relationships in the impact of different drivers (turbulent diffusion, mean and eddy advection, primary productivity) on the phytoplankton chlorophyll concentrations. We find that in the 1/4^{∘} (∼25 km) model, advection has a substantial impact on the rate of primary productivity, while the turbulent diffusion term has a fairly negligible impact.

bFGF blockade reduces intraplaque angiogenesis and macrophage infiltration in atherosclerotic vein graft lesions in ApoE3*Leiden mice.

Intraplaque angiogenesis increases the chance of unstable atherosclerotic plaque rupture and thrombus formation leading to myocardial infarction. Basic Fibroblast Growth Factor (bFGF) plays a key role in angiogenesis and inflammation and is involved in the pathogenesis of atherosclerosis. Therefore, we aim to test K5, a small molecule bFGF-inhibitor, on remodelling of accelerated atherosclerotic vein grafts lesions in ApoE3*Leiden mice.

Development of Oxygen-Bridged Pyrazole-Based Structures as Cannabinoid Receptor 1 Ligands.

In this work, the synthesis of the cannabinoid receptor 1 neutral antagonists 8-chloro-1-(2,4-dichlorophenyl)--piperidin-1-yl-4,5-dihydrobenzo-1-6-oxa-cyclohepta[1,2-]pyrazole-3-carboxamide and its deaza cyclohexyl analogue has led to a deepening of the structure-activity studies of this class of compounds. A series of novel 4,5-dihydrobenzo-oxa-cycloheptapyrazoles analogues of ,, derivatives -, was synthesized, and their affinity towards cannabinoid receptors was determined. Representative terms were evaluated using in vitro tests and isolated organ assays.

Cumulative Impact Index for the Adriatic Sea: Accounting for interactions among climate and anthropogenic pressures.

Assessing and managing cumulative impacts produced by interactive anthropogenic and natural drivers is a major challenge to achieve the sustainable use of marine spaces in line with the objectives of relevant EU acquis. However, the complexity of the marine environment and the uncertainty linked to future climate and socio-economic scenarios, represent major obstacles for understanding the multiplicity of impacts on the marine ecosystems and to identify appropriate management strategies to be implemented. Going beyond the traditional additive approach for cumulative impact appraisal, the Cumulative Impact Index (CI-Index) proposed in this paper applies advanced Multi-Criteria Decision Analysis techniques to spatially model relationships between interactive climate and anthropogenic pressures, the environmental exposure and vulnerability patterns and the potential cumulative impacts for the marine ecosystems at risk.

Frequency and Significance of Promoter, and Mutations in Cytologically Indeterminate Thyroid Nodules: A Monocentric Case Series at a Tertiary-Level Endocrinology Unit.

Purpose: The management of thyroid nodules of indeterminate cytology is controversial. Our study aimed to establish the frequency and significance of promoter, and gene mutations in thyroid nodes of indeterminate cytology and to assess their potential usefulness in clinical practice.

Methods: -,-, promoter and gene mutations were examined in a series of 199 consecutive nodes of indeterminate cytology referred for surgical excision.

Novel pyrrolocycloalkylpyrazole analogues as CB ligands.

Novel 1,4-dihydropyrazolo[3,4-a]pyrrolizine-, 4,5-dihydro-1H-pyrazolo[4,3-g]indolizine- and 1,4,5,6-tetrahydropyrazolo[3,4-c]pyrrolo[1,2-a]azepine-3-carboxamide-based compounds were designed and synthesized for cannabinoid CB and CB receptor interactions. Any of the new synthesized compounds showed high affinity for CB receptor with K values superior to 314 nm, whereas some of them showed moderate affinity for CB receptor with K values inferior to 400 nm. 7-Chloro-1-(2,4-dichlorophenyl)-N-(homopiperidin-1-yl)-4,5-dihydro-1H-pyrazolo[4,3-g]indolizine-3-carboxamide (2j) exhibited good affinity for CB receptor (K CB  = 81 nm) and the highest CB /CB selectively ratio (>12).

Efficacy of carboxymethyl beta-glucan in cervical intraepithelial neoplasia: a retrospective, case-control study.

Background: Persistent human papillomavirus (HPV) infection constitutes the principal risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. For this reason, new drugs have been studied to support the host immune system against the HPV infection. The aim of this retrospective, case-control study was to detect the efficacy and safety of carboxymethyl β-glucan (Colpofix®) gel as adjuvant therapy in HPV infection.

Differences in biomarkers of crack-cocaine adolescent users before/after abstinence.

Aims: To measure the variation in Brain-Derived Neurotrophic Factor (BDNF), Thiobarbituric Acid Reactive Substances (TBARS) and interleukin (IL) levels in crack-cocaine dependent adolescents after 21days of abstinence, comparing to levels found in a group of healthy controls.

Design: Cross-sectional nested on a short follow-up study.

Setting: Two inpatient treatment units for adolescents, and a low-income neighborhood.

KEMTUB012-NI2, a novel potent tubulysin analog that selectively targets hypoxic cancer cells and is potentiated by cytochrome p450 reductase downregulation.

Purpose: There is an urgent need to develop effective therapies and treatment strategies to treat hypoxic tumors, which have a very poor prognosis and do not respond well to existing therapies.

Methods: A novel hypoxia-targeting agent, KEMTUB012-NI2, was synthesized by conjugating a 2-nitroimidazole hypoxia-targeting moiety to a synthetic tubulysin, a very potent antimitotic. Its hypoxic selectivity and mode of action were studied in breast cancer cell lines.

Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats.

Weight gain is an important side effect of most atypical antipsychotic drugs such as olanzapine. Moreover, although many animal models with metabolic side effects have been well defined, the interaction with other pathways has to be considered. The endocannabinoid system and the CB1 receptor (CB1R) are among the most promising central and peripheral targets involved in weight and energy balance.

Synthesis and Superpotent Anticancer Activity of Tubulysins Carrying Non-hydrolysable N-Substituents on Tubuvaline.

Synthetic tubulysins 24 a-m, containing non-hydrolysable N-substituents on tubuvaline (Tuv), were obtained in high purity and good overall yields using a multistep synthesis. A key step was the formation of differently N-substituted Ile-Tuv fragments 10 by using an aza-Michael reaction of azido-Ile derivatives 8 with the α,β-unsaturated oxo-thiazole 5. A structure-activity relationship study using a panel of human tumour cell lines showed strong anti-proliferative activity for all compounds 24 a-m, with IC values in the sub-nanomolar range, which were distinctly lower than those of tubulysin A, vinorelbine and paclitaxel.

A critical review of both the synthesis approach and the receptor profile of the 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and analogue derivatives.

8-Chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 9a was discovered as potent and selective CB1 antagonist by part of our group few years ago. In particular it was reported to have an affinity towards the CB1 cannabinoid receptor (CB1R), expressed as Ki, of 0.00035 nM.

Design of novel 3,6-diazabicyclo[3.1.1]heptane derivatives with potent and selective affinities for α4β2 neuronal nicotinic acetylcholine receptors.

New analogues (3a-l) of the previously described α4β2 selective ligand 3-(6-halopyridin-3-yl)-3,6-diazabicyclo[3.1.1]heptanes (2a,b) have been synthesized and their binding activity for neuronal acetylcholine receptor subtypes α4β2 and α7 were assayed.

Novel diazabicycloalkane delta opioid agonists.

Here we report the investigation of diazabicycloalkane cores as potential new scaffolds for the development of novel analogues of the previously reported diazatricyclodecane selective delta (δ) opioid agonists, as conformationally constrained homologues of the reference δ agonist (+)-4-[(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80). In particular, we have simplified the diazatricyclodecane motif of δ opioid agonist prototype 1a with bridged bicyclic cores. 3,6-diazabicyclo[3.

Age and the metabolic syndrome affect salivary cortisol rhythm: data from a community sample.

Objective: Measurement of cortisol levels in saliva is a marker of free hormone. How salivary cortisol rhythm is affected by age, gender, the metabolic syndrome and estrogen-progestin therapy was evaluated in a community sample of adults.

Subjects And Methods: One hundred twenty volunteers recruited from the Hospital staff and family members of the Endocrinology Unit were instructed to collect 7 salivary samples: the first on awakening (F(0)) and 6 more (F(1.

The tubulysin analogue KEMTUB10 induces apoptosis in breast cancer cells via p53, Bim and Bcl-2.

Purpose: Tubulysins are natural tetrapeptides that inhibit tubulin polymerisation. Tubulysins are very potent inhibitors of mammalian cancer cell growth, but restricted availability has limited their characterisation and development as anti-cancer compounds. KEMTUB10 was recently developed as a synthetic analogue of natural tubulysins.

Development of novel ADCs: conjugation of tubulysin analogues to trastuzumab monitored by dual radiolabeling.

Tubulysins are highly toxic tubulin-targeting agents with a narrow therapeutic window that are interesting for application in antibody-drug conjugates (ADC). For full control over drug-antibody ratio (DAR) and the effect thereof on pharmacokinetics and tumor targeting, a dual-labeling approach was developed, wherein the drug, tubulysin variants, and the antibody, the anti-HER2 monoclonal antibody (mAb) trastuzumab, are radiolabeled. (131)I-radioiodination of two synthetic tubulysin A analogues, the less potent TUB-OH (IC50 > 100 nmol/L) and the potent TUB-OMOM (IC50, ~1 nmol/L), and their direct covalent conjugation to (89)Zr-trastuzumab were established.

Tricyclic pyrazoles part 7. Discovery of potent and selective dihydrothienocyclopentapyrazole derived CB2 ligands.

A series of dihydrothienocyclopentapyrazole-based derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The major term, the 6-methyl-1-(1,4-dichlorophenyl)-N-piperidinyl)-1,4-dihydrothieno[2',3'-4,5]cyclopenta[1,2-c]pyrazole-3-carboxamide (6a), displayed a high affinity and good selectivity for CB2 receptors (Ki values of 2.30 nM for CB2 receptor and 440 nM for CB1 receptors respectively).