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A practical and effective photoredox propargylation of aldehydes promoted by 10 mol % of [Cp2TiCl2] is presented. No stoichiometric metals or scavengers are used for the process. A catalytic amount of the cheap and simply prepared organic dye 3DPAFIPN is used as the reductant for titanium. The reaction displayed a broad scope, and no traces of allenyl isomers were detected for simple propargyl bromide, whereas mixtures of propargyl and allenyl isomers were observed for substituted propargyl bromides.

Kinetics of hepatitis A virus (HAV) accumulation and depuration from mussels (Mytilus galloprovincialis) was studied in an experimental depuration system. Different parameters likely to influence the rate of virus accumulation and elimination were evaluated. Analyses were carried out by both real-time RT-qPCR and digital PCR. Results demonstrated that the animals start to concentrate the virus already after one hour and reach the maximum level of contamination in 6 h of experiment. With respect to depuration, HAV showed a rapid reduction of the concentration (89%) during the first 24-48 h of experiment and a very slow virus decrement in the following days with a 1% residual RNA at the ninth day of depuration. When process parameters likely to increase the depuration rate (presence of ozone, microalgal feeding, presence of lactic bacteria, pre-treatment with digestive enzymes) were tested, no significant differences in the kinetics were observed. Only treatment with pancreatin seemed to positively affect depuration in the first two days of the experiment.

PURPOSE To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

BODIPYs are renowned fluorescent dyes with strong and tunable absorption in the visible region, high thermal and photo-stability and exceptional fluorescence quantum yields. Transition metal complexes are the most commonly used triplet photosensitisers, but, recently, the use of organic dyes has emerged as a viable and more sustainable alternative. By proper design, BODIPY dyes have been turned from highly fluorescent labels into efficient triplet photosensitizers with strong absorption in the visible region (from green to orange). In this perspective, we report three design strategies: (i) halogenation of the dye skeleton, (ii) donor–acceptor dyads and (iii) BODIPY dimers. We compare pros and cons of these approaches in terms of optical and electrochemical properties and synthetic viability. The potential applications of these systems span from energy conversion to medicine and key examples are presented., BODIPYs offer a versatile platform to build organic triplet photosensitisers for PDT, TTA upconversion and photocatalysis. Tuning their properties provides the opportunity of replacing heavy-metal complexes and can lead to improved sustainability.

The preparation of homoallylic alcohols by addition of organometallic allyl compounds to carbonyls is an important strategy in organic chemistry. Allylating organometallic cobalt species can be generated employing stoichiometric quantities of Zn acting as reductant. To avoid the employment of stoichiometric amount of Zn, we have developed an allylation reaction of aromatic and aliphatic aldehydes promoted by photoredox catalysis in the presence of a cobalt complex, and we present herein a full account of our research. In the presence of the abundant CoBr2 (10 mol %), 4,4′-di-tert-butyl-2,2′-dipyridyl (dtbbpy, 10 mol %), allyl acetate (3 equiv.), [Ir(dtbbpy)(ppy)2]PF6 (ppy=2-phenylpyridine, 2 mol %), and N,N-diisopropylethylamine (4 equiv.), an allylation of aldehydes is taking place, in moderate to good yields. Substrates scope, limitations, and photophysical investigations of this new process are reported. (Figure presented.).

High level time-dependent density functional theory (TD-DFT) computational modeling of coumarin dyes has been exploited for guiding the design of effective photocatalysts (PCs). A library of coumarins were investigated from the theoretical point of view and photophysical/electrochemical properties (absorption and emission spectra, E00, oxidation and reduction potentials) were evaluated. Comparison with literature values reported for a few candidates has been used for assessing the level of theory. On the basis of the results obtained, new strongly reducing PCs [Eox(PC.+/PC*)=−2.1 – −2.0 V vs SCE] were discovered. Through the computational study of structure-properties relationships, a number of coumarins derivatives have been synthesized and evaluated in the pinacol coupling of aldehydes as the model reaction. The new organic photoredox catalysts show experimental photophysical and electrochemical data in accordance with the ones predicted by calculation, with excited state reduction potentials surpassing those of highly reducing transition metal-based PCs. A careful investigation of their behavior as PC has revealed crucial issues that need to be taken into consideration in the general photoredox catalysis, shedding light on the use of these PC in the pinacol, as well as, in other photoredox reactions.

Long-term time-series are a fundamental prerequisite to understand and detect climate shifts and trends. Understanding the complex interplay of changing ocean variables and the biological implication for marine ecosystems requires extensive data collection for monitoring and hypothesis testing and validation of modelling products. In marginal seas, such as Mediterranean Sea, there are still monitoring gaps, both in time and in space. To contribute filling these gaps, an extensive dataset of dissolved inorganic nutrients profiles (nitrate, NO3; phosphate, PO43−; and silicate, SiO2) have been collected between 2004 and 2017 in the Western Mediterranean Sea and subjected to quality control techniques to provide to the scientific community a publicly available, long-term, quality controlled, internally consistent biogeochemical data product. The database includes 870 stations of dissolved inorganic nutrients sampled during 24 cruises, including temperature and salinity. Details of the quality control (primary and secondary quality control) applied are reported. The data are available in PANGAEA (https://doi.org/10.1594/PANGAEA.904172, Belgacem et al. 2019).

Background: Functional imaging with 68Ga-DOTATATE PET-CT is widely employed to detect both primary and metastatic pheochromocytomas and paragangliomas (PGL), but its results may be occasionally misleading as in the case here reported. Case Presentation: We report here a 75-year-old woman with an interaortocaval PGL that was diagnosed after a hypertensive crisis occurring during the resection of a kidney tumor. 68Ga-DOTATATE PET-CT disclosed pathologic uptake in the abdomen and at the iliac crest. After the resection of the abdominal tumor, with the histological confirmation of PGL, arterial blood pressure and metanephrine levels were normalized. Genetic testing was negative. Thereafter, the bone lesion increased in size and became painful, requiring multiple medications. A selective biopsy disclosed a metastatic lesion arising from the renal tumor. Conclusion: The false-positive result of 68Ga-DOTATATE PET-CT is discussed.

A gas chromatography-tandem mass spectrometry (GC-MS/MS) method was developed for the simultaneous detection and quantification of five phytogenic compounds (carvone, menthol, thymol, carvacrol and methyl salicylate) in chicken breast. Chicken breast samples were analyzed using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach using acetonitrile as extraction solvent, followed by a d-SPE (dispersive-solid phase extraction) clean up step. The linearities for the 5 substances were studied in the range between 2 and 100 μg/L and the coefficients of determination (R2) were always0.995. Matrix effects were also assessed by comparing the slopes obtained in solvent and chicken breast matrix. The recoveries for all the substances at 3 different spike levels (5, 10 and 50 μg/kg) were in the range 80-102% with RSDs15%. The instrumental limits of quantification were in the range 2.7-4.8 μg/kg, while the reporting level of the method was 5 μg/kg for all the aforementioned compounds. The method was successfully applied to 10 chicken breasts samples from the local market.

HCV infection has been hypothesized as a contributor of poor CD4+ recovery in patients living with HIV (PLWHIV). Aim of this study was to evaluate CD4+, CD8+ cells and CD4/CD8 ratio trends before and after HCV treatment with direct acting agents (DAA) in PLWHIV. HIV/HCV patients enrolled in ICONA and HepaICONA cohorts with HIV-RNA≤50copies/ml who achieved a sustained viral response after DAA treatment were studied. A linear regression model was used to investigate CD4+, CD8+ and CD4/CD8 changes 12months before and after DAA treatment. A total of 939 HIV/HCV patients were included, 225 (24.0%) female, median age: 53years (IQR 50–56). At DAA initiation, CD4+ T cell count was 12.5kPa. Trends of CD4+ and CD4/CD8 ratio were similar before and after DAA in all study populations (CD4+ change +17.6 cells/mm3 (95%CI −33.5; 69.4, p=0.494); CD4/CD8 change 0.013 (95%CI −0.061; 0.036, p=0.611). However, patients treated with ribavirin (RBV)-free DAA showed a significant decrease in CD8+ cells (−204.3 cells/mm3, 95%CI −375.0;-33.4, p=0.019), while patients treated with RBV experienced CD8+ cell increase (+141.2 cells/mm3, 95%CI 40.3; 242.1, p=0.006). In conclusion, HCV eradication following DAA treatment does not seem to have an impact on CD4+ T cell recovery in PLWHIV. However, a fast decline of CD8+T cells has been observed in patients treated without RBV, suggesting a favourable effect of HCV clearance on the general state of immune activation.

4-Fluoro-threonine, the only fluoro amino acid of natural origin discovered so far, is an interesting target for both synthetic and theoretical investigations. In this work, we lay the foundation for spectroscopic characterization of 4-fluoro-threonine. First, we report a diastereoselective synthetic route, which is suitable to produce synthetic material for experimental characterization. The addition of the commercially available ethyl isocyanoacetate to benzyloxyacetaldehyde led to the corresponding benzyloxy-oxazoline, which was hydrolyzed and transformed into ethyl (4S*,5S*)-5-hydroxymethyl-2-oxo-4-oxazolidinecarboxylate in a few steps. Fluorination with diethylamino sulfur trifluoride (DAST) afforded ethyl (4S*,5S*)-5-fluoromethyl-2-oxo-4-oxazolidinecarboxylate, which was deprotected to give the desired diastereomerically pure 4-fluoro-threonine, in 8-10% overall yield. With the synthetic material in our hands, acid-base titrations have been carried out to determine acid dissociation constants and the isoelectric point, which is the testing ground for the theoretical analysis. We have used machine learning coupled with quantum chemistry at the state-of-the-art to analyze the conformational space of 4-fluoro-threonine, with the aim of gaining insights from the comparison of computational and experimental results. Indeed, we have demonstrated that our approach, which couples a last-generation double-hybrid density functional including empirical dispersion contributions with a model combining explicit first-shell molecules and a polarizable continuum for describing solvent effects, provides results and trends in remarkable agreement with experiments. Finally, the conformational analysis applied to fluoro amino acids represents an interesting study for the effect of fluorine on the stability and population of conformers. 4-Fluoro-threonine, the only fluoro amino acid of natural origin discovered so far, is an interesting target for both synthetic and theoretical investigations. In this work, we lay the foundation for spectroscopic characterization of 4-fluoro-threonine. First, we report a diastereoselective synthetic route, which is suitable to produce synthetic material for experimental characterization. The addition of the commercially available ethyl isocyanoacetate to benzyloxyacetaldehyde led to the corresponding benzyloxy-oxazoline, which was hydrolyzed and transformed into ethyl (4S*,5S*)-5-hydroxymethyl-2-oxo-4-oxazolidinecarboxylate in a few steps. Fluorination with diethylamino sulfur trifluoride (DAST) afforded ethyl (4S*,5S*)-5-fluoromethyl-2-oxo-4-oxazolidinecarboxylate, which was deprotected to give the desired diastereomerically pure 4-fluoro-threonine, in 8-10% overall yield. With the synthetic material in our hands, acid-base titrations have been carried out to determine acid dissociation constants and the isoelectric point, which is the testing ground for the theoretical analysis. We have used machine learning coupled with quantum chemistry at the state-of-the-art to analyze the conformational space of 4-fluoro-threonine, with the aim of gaining insights from the comparison of computational and experimental results. Indeed, we have demonstrated that our approach, which couples a last-generation double-hybrid density functional including empirical dispersion contributions with a model combining explicit first-shell molecules and a polarizable continuum for describing solvent effects, provides results and trends in remarkable agreement with experiments. Finally, the conformational analysis applied to fluoro amino acids represents an interesting study for the effect of fluorine on the stability and population of conformers.

To investigate the influence of age on the thickness of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex and the quantitative autofluorescence (qAF) and to study the possible correlation existing between these 2 parameters in a healthy White population.Cross-sectional, observational study.Healthy White volunteers aged 18 to 65 years.All subjects underwent spectral domain OCT (SD-OCT) and qAF imaging with the Heidelberg HRA-Spectralis (Heidelberg Engineering, Heidelberg, Germany). Spectral domain OCT images were analyzed using the in-built graph-based automatic segmentation algorithm for single retinal layer identification to assess RPE/BM complex thickness in vivo. The thickness values of both inner and outer rings of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, generated by the software using the "RPE" segmentation, were averaged to obtain a single RPE/BM complex thickness value in each eye. Quantitative autofluorescence images were also evaluated using a dedicated software. The qAF values of 8 subfields forming a ring centered onto the fovea were collected and averaged to obtain a single qAF value (qAFThe in vivo correlation between RPE/BM complex thickness and qAF.A total of 105 eyes from 105 subjects (mean age, 42.1 ± 13.9 years; range, 18-65) were included in the analysis. The mean RPE/BM complex thickness significantly increased with age (r = 0.33, P = 0.0006). The values of qAF also positively increased with age (P0.0001). A significant correlation was found between qAF and RPE/BM complex thickness (r = 0.27, P = 0.004). After adjusting for age, iris color, and gender, the correlation remained significant only for subjects aged less than 40 years (P = 0.009).BM complex thickness was significantly co/BM complex thickness increased with age in a healthy White population. A similar increase was found for qAF values. After adjusting for age and iris color, qAF and RPE/BM complex thickness were still correlated in subjects aged less than 40 years. The RPE/BM complex thickness could reflect the lipofuscin/melanolipofuscin accumulation in normal subjects, adding great interest in RPE cell biology.

Objectives: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. Methods: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. Results: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p &lt, 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). Conclusions: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.

Blood samples from 260 unrelated cattle (132 animals affected by papillomavirus-associated bladder tumors and 128 healthy) were genotyped using the classic polymerase chain reaction/restriction fragment length polymorphism method to screen MHC class II bovine leukocyte antigen-DRB3. 2 polymorphism. The DRB3*22 allele was significantly (p ≤ 0.01) detected in healthy cattle, thus appearing to have a negative association (protective effect) with virus infection of the urinary bladder known to represent a bladder tumor risk for cattle living free at pasture. Considering the two sequence alleles identified in animals carrying DRB3*22, DRB3*011:01 allele from samples of animals harboring the unexpressed bovine papillomaviruses (BPV)-2 E5 gene was characterized by amino acid residues believed to have a protective effect against BPV infection such as arginine at position 71 (R71) in pocket 4, histidine at position 11 (H11) in pocket 6, and both glutamine at position 9 (Q9) and serine at position 57 (S57) in pocket 9 of the antigen-binding groove. The DRB3*011:02v allele from affected animals was characterized by amino acids believed to be susceptibility residues such as lysine (K71), tyrosine (Y11), glutamic acid (E9), and aspartic acid (D57) in these pockets. These results suggest that animals harboring the DRB3*011:01 allele may have a lower risk of BPV infection and, consequently, a reduced risk of bladder tumors.

One of the most detrimental loss mechanisms in Luminescent Solar Concentrators (LSCs) is reabsorption of emitted light from the luminophore. Silicon Nanocrystals (SiNCs) offer a solution due to the high apparent Stokes shift, but the poor absorption properties limit their performance as LSC luminophores. Coupling an organic dye to SiNCs represents a smart approach to obtain sensitization of SiNC luminescence by the organic dyes, thus, resulting in tunable and improved optical properties of LSCs. In particular, 9,10-diphenylanthracene was employed as a UV sensitizer for SiNCs in order to produce LSCs with an aesthetic appearance suitable to smart window application and optical efficiency as high as 4.25%. In addition, the role of the energy transfer process on LSC performance was elucidated by a thorough optical and photovoltaic characterization.

Here we report the application of dual nickel/photoredox catalysis to the allylation of aliphatic, aromatic and heteroaromatic aldehydes by using commercially available reagents. The process utilizes the combination of a Ni(ii) complex, [Ru(bpy)3]2+ as a photoredox catalyst, and allylacetate under blue LED irradiation, and allows the synthesis of a large variety of homoallylic alcohols.

According to the drug label, linezolid dosage adjustments are not needed in geriatric patients. Nevertheless, clinical evidence suggests that elderly patients may benefit from the use of reduced linezolid doses to limit drug overexposure. Here, we aimed to describe the results of the last 5 years of therapeutic drug monitoring of linezolid in our institution with a special focus on elderly patients.Linezolid therapeutic drug monitoring requests collected between January 2016 and June 2020 were considered. Linezolid trough concentrations were considered both as a continuous variable and as a categorical variable, clustering data according to the therapeutic range proposed by available literature (2, 2-8, and8 mg/L, respectively). Patients' age and sex were considered as categorical variables. Comparisons of linezolid trough concentrations between groups of patients stratified according to age were performed using an analysis of variance; comparisons in the frequency distributions were performed using the chi-squared test.From 2016 to 2020, we collected 3250 linezolid TDM requests. A highly significant, progressive increment in the linezolid trough concentrations was observed moving from patients aged50 years (5.8 ± 5.6 mg/L) to those aged90 years (16.6 ± 10.0 mg/L), with an overall increment of 30% per decade of age. Nearly 30%, 50%, and 65% of patients aged65 years, 65-80 years, and80 years, respectively, had supra-therapeutic linezolid trough concentrations at the first therapeutic drug monitoring assessment. This trend did not change significantly moving from 2016 to 2020.Elderly patients given linezolid at the conventional 600-mg twice-daily dose might be at a high risk of being overexposed to treatment, eventually increasing their risk to experience drug-related hematological toxicity. Reduced linezolid dosing schemes should be potentially considered in elderly patients at a low risk of treatment failure, ideally guided by therapeutic drug monitoring.

A second-generation kilogram-scale synthesis of the psychedelic tryptamine psilocybin has been developed. The synthesis was designed to address several challenges first encountered with the scale-up of previously described literature procedures, which were not optimized for providing consistent yield and purity of products, atom economy, or being run in pilot plant-scale reactors. These challenges were addressed and circumvented with the design of the second-generation route, which featured an optimized cGMP large-scale Speeter-Anthony tryptamine synthesis to the intermediate psilocin with improved in-process control and impurity removal over the three steps. Psilocin was subsequently phosphorylated directly with phosphorous oxychloride for the first time, avoiding a tedious and poor atom economy benzyl-protecting group strategy common to all previously described methods for producing psilocybin. In this report, the challenges encountered in a 100 g scale first-generation literature-based synthesis are highlighted, followed by a detailed description of the newly developed second-generation synthesis to provide over one kilogram of high-purity psilocybin under cGMP.

Background Modular dual-mobility (MDM) total hip arthroplasty (THA) is designed with a cobalt-chromium liner inserted into a titanium acetabular component. The purpose of this study is to investigate the potential risks for fretting corrosion at this junction, by measuring serum metal ions, after MDM acetabular revision. Methods Thirty-seven patients with well-functioning revision THAs participated in a cross-sectional study at mean 5.1 (2-10) years after surgery. All received a trabecular titanium MDM acetabular component. The serum levels of cobalt and chromium were measured using mass spectrometry. Results The mean values of chromium and cobalt were 2.08 μg/L (95% confidence interval 0.9-3.2, range 0.02-11.8) and 1.99 μg/L (95% confidence interval 0.81-3.17, range 0.07-16.05), respectively. Eleven patients (29, 7%) had ion levels above the normal range, with 6 (16.2%) above 5 μg/L and 5 (13.5%) between 1 and 5 μg/L. A significant correlation was found between an elevated serum metal ion level and University of California Los Angeles score (P = .016). Conclusion We conclude that serum metal level elevation may occur secondary to metal debris resulting from corrosion of the index MDM THA. This potential risk should be included in the decision-making process when dealing with revision arthroplasty in young and active patients.

BACKGROUND Carbamazepine and oxcarbazepine are potent modulators of metabolic enzymes. Hence, potential drug-drug interactions (DDIs) may occur between these 2 drugs and antiretrovirals. Here, we aimed to assess the relevance of these drug-drug interactions in real-life clinical settings. METHODS Patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months were considered. Data on therapeutic drug monitoring (TDM) of both antiepileptic and antiretrovirals as trough concentrations were collected. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. RESULTS Eleven HIV-positive patients prescribed carbamazepine or oxcarbazepine were identified. All the TDM evaluations for carbamazepine and oxcarbazepine that resulted were within the therapeutic ranges. TDM results of darunavir measured in these patients were comparable with values usually measured in the control group. Conversely, the trough concentrations for atazanavir and dolutegravir demonstrated significantly lower values when compared with values usually measured in HIV-infected patients not treated with antiepileptic drugs (190 ± 91 versus 546 ± 380 ng/mL; -65%, P < 0.001; 191 ± 78 versus 1096 ± 510 ng/mL; -83%, P < 0.001, respectively). CONCLUSIONS Co-administration of carbamazepine or oxcarbazepine with atazanavir or dolutegravir should be avoided owing to the potential risk of virological failure; in case of these 2 drugs, the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.

OBJECTIVE. The purpose of this article is to describe the risk-benefit balance of contrast-enhanced breast MRI (CE-BMRI) screening. CONCLUSION. CE-BMRI confers risk of effects associated with administration of gadolinium-based contrast agents (GBCAs), including nephrogenic systemic fibrosis and gadolinium retention. The risk-benefit balance of CE-BMRI screening is favorable for carriers of BRCA, TP53, or other deleterious mutations women who have undergone thoracic irradiation; and women at 20% or greater lifetime risk of breast cancer. The balance is uncertain, however, for women at intermediate to average risk. Women must always receive detailed information regarding possible GBCA-associated effects.

Simple Summary The gastrointestinal tract of the bottlenose dolphin (Tursiops truncatus) differs structurally and functionally from that of terrestrial mammals. In particular, the intestine does not show any macroscopic subdivision and lacks a caecum. In addition, the histological aspect of the intestine is relatively constant, without marked differences between the anterior and posterior parts. Although the intestine of these cetaceans presents differences in comparison with terrestrial mammals, little information is currently available on their enteric nervous system. The aim of the present study was to investigate the morphological and quantitative aspects of neurons immunoreactive (IR) for the neuronal nitric oxide synthase (nNOS) and Substance P (SP) in the intestine of bottlenose dolphins (Tursiops truncatus). In these dolphin specimens, a smaller number of nNOS-IR neurons in the submucosal plexus and a larger number of SP-IR neurons in the myenteric plexus were observed compared to other mammals. Interestingly, no co-localization between nNOS- and SP-IR neurons was detected in either of the plexuses, suggesting the existence of two completely distinct functional classes of neurons in the intestine of the bottlenose dolphin. Abstract Compared with other mammals, the digestive system of cetaceans presents some remarkable anatomical and physiological differences. However, the neurochemical features of the enteric nervous system (ENS) in these animals have only been described in part. The present study gives a description of the nitrergic and selected peptidergic systems in the myenteric plexus (MP) and submucosal plexus (SMP) of the intestine of the bottlenose dolphin (Tursiops truncatus). The distribution and morphology of neurons immunoreactive (IR) for the neuronal nitric oxide synthase (nNOS) and Substance P (SP) were immunohistochemically studied in formalin-fixed specimens from the healthy intestine of three animals, and the data were compared with those described in the literature on other mammals (human and non-human). In bottlenose dolphins, the percentages of nitrergic neurons (expressed as median and interquartile range—IQR) were 28% (IQR = 19–29) in the MP and 1% (IQR = 0–2) in the SMP, while the percentages of SP-IR neurons were 31% (IQR = 22–37) in the MP and 41% (IQR = 24–63) in the SMP. Although morphological features of nNOS- and SP-IR neurons were similar to those reported in other mammals, we found some noticeable differences in the percentages of enteric neurons. In fact, we detected a lower proportion of nNOS-IR neurons in the SMP and a higher proportion of SP-IR neurons in the MP compared to other mammals. To the best of the authors’ knowledge, this study represents the first description and quantification of nNOS-IR neurons and the first quantification of SP-IR neurons in the intestine of a cetacean species. As nNOS and SP are important mediators of intestinal functions and the nitrergic population is an important target for many neuroenteropathies, data obtained from a healthy intestine provide a necessary basis to further investigate and understand possible functional differences and motor intestinal dysfunctions/alterations in these special mammals.

Weight loss is one of the most frequent adverse events during treatment with multikinase inhibitors, but scanty data are available on its extent and characteristics. This is the first assessment of the body composition by bioelectrical impedance analysis and of circulating leptin and ghrelin levels, in patients with advanced thyroid cancer before and at regular intervals during treatment with the tyrosine kinase inhibitor lenvatinib. Body mass index (BMI) decreased in all patients, with an average ∆ reduction of –6.4, –9.8, and –15.3% at 3, 6, and 12 months of treatment, respectively. Interestingly, in most patients, after the first year of treatment, BMI remained stable. In all patients, fat mass (FM) reduced more than fat-free mass, the highest decrement being of –60 and –16%, respectively. A decrease in the body cell mass, a parameter mainly due to muscle tissue, was observed only in patients with a vast baseline muscular mass. Total body water decreased in parallel to BMI. During treatment, leptin tightly paralleled the decrease of BMI values, consistent with the decrease in FM, whereas ghrelin levels increased upon BMI decrease. The loss of the FM accounts for the largest portion of BMI reduction during lenvatinib treatment. The increase in ghrelin could account for the BMI stabilization observed after 1 year of treatment. Nevertheless, oral nutritional supplements should be given as early as possible and athletic patients should be encouraged to maintain physical activity. In some circumstances, parenteral nutrition is required for the rehabilitation of these patients.

Organometallic allylic reagents are widely used in the construction of C−C bonds by Barbier-type reactions. In this communication, we have described a photoredox Barbier allylation of aldehydes mediated by bismuth, in absence of other metals as co-reductants. Mild reaction conditions, tolerance of oxygen, and use of aqueous solvent make this photoredox methodology attractive for green and sustainable synthesis of homoallylic alcohols.

The change in feeding regime of dairy herds using summer grazing in mountainous areas has several implications on cows’ productivity and milk composition. The present study quantified the effect of summer grazing on the milk fatty acids (FA) profile of Simmental and crossbred cows in an alpine holding. A total of 616 milk samples of 71 cows were collected 3 days before the onset of the grazing season until 91 days of grazing. Individual and groups of FA were quantified through mid-infrared spectroscopy. Data were analysed using a linear mixed model including the fixed effects of breed, stage of lactation, parity, sampling period, and the random effects of cows nested within breed and the residual. The stage of lactation and the sampling period were the most significant factors associated with milk FA. The variance explained by the random cow effect ranged from 15.10% (C18:1) to 25.31% (medium-chain FA). The concentration of C14:0, C16:0, and short- and medium-chain FA decreased across the summer season. Long-chain FA and polyunsaturated FA concentrations were greater in milk obtained at pasture compared with milk obtained indoors. Given these outcomes, the present study demonstrated the positive effect of grazing on milk FA composition from a nutraceutical point of view.

The use of organic dyes to promote organic reactions by photoredox catalysis is continuously expanding and was recently reviewed by Nicewicz. The synthesis of new dyes, their application in flow photoredox reactions, and their use in stereoselective and multicomponent transformations have considerably expanded the repertoire of application of organic dyes in photoredox mediated reactions. The low costs of these dyes, their tailored synthesis and availability in combination with the development of new concepts and careful catalytic cycle design (made possible by the application of fine theoretical investigations and deep understanding) are guiding the widespread application of organic dyes in the metallaphotoredox catalysis area. Developments and recent applications of different metal catalyzed processes mediated by organic dyes are covered by this review. This journal is

Objectives: Comparisons between rilpivirine (RPV) and integrase strand transfer inhibitors (INSTIs) in antiretroviral therapy (ART)-naïve HIV-infected individuals are currently lacking. This study aimed to compare, in an observational cohort setting, the durability of treatment with RPV-based and INSTI-based first-line regimens. Methods: Patients who started first-line ARTs based on RPV or INSTIs, with HIV­RNA < 100 000 copies/mL and CD4 cell count > 200 cells/μL were included. The primary endpoint was the cumulative probability of treatment failure (TF = virological failure [confirmed HIV-RNA > 50 copies/mL] or discontinuation of the anchor drug in the regimen), as assessed by the Kaplan-Meier method. A multivariable Cox regression was used to control for potential confounding. Results: Of the 1991 included patients, 986 started ART with an RPV-based regimen and 1005 with an INSTIs-based regimen. The median (IQR) follow-up was 20 (10, 35) months. The cumulative 2-year probability of TF with RPV (9.1% [95% 7.2, 11.1]) was lower than that observed in the INSTIs group (16.6% [13.8, 19.4], P = 0.0002) but not when compared with dolutegravir (DTG) alone. Starting ART with an INSTIs-based regimen vs. RPV was associated with a higher risk of TF after controlling for potential confounding factors (adjusted hazard ratio, AHR [95% CI]: 1.64 [1.28, 2.10]; P < 0.001). The results were similar when restricting the analysis to single-tablet regimens, although the probability of virological success was higher for INSTIs and DTG. Conclusions: In ART-naïve patients with low viral loads and high CD4 counts, the risk of treatment failure was lower in those who started RPV-based vs. INSTIs-based regimens other than DTG-based ones.