The interplay of soft-hard substituents in photochromic diarylethenes

A series of diarylethenes with substituents of different size and chemical nature was synthesised showing that beside some intermolecular interactions involving the central diarylethene core, lateral groups clearly play a key role in the crystal packing arrangements. These structural features were further analyzed in relation to the thermal data obtained by differential scanning calorimetry (DSC) and monitored using FT-IR spectroscopy, thus providing a rationalization of the observed thermal transitions processes. The role of van der Waals interactions is crucial in driving crystal packing formation towards loosely packed arrangements characterized by large hydrophobic contact areas. Interestingly, some functional substituents favour an amorphous state after thermal treatment, a peculiar feature that can be exploited to design uniform photochromic layers

Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury

The liver is susceptible to such oxidative and metabolic stresses as ischemia-reperfusion (I/R) and fatty acid accumulation. Probiotics are viable microorganisms that restore the gut microbiota and exert a beneficial effect on the liver by inhibiting bacterial enzymes, stimulating immunity, and protecting intestinal permeability. We evaluated Lactobacillus paracasei F19 (LP-F19), for its potential protective effect, in an experimental model of I/R (30 min ischemia and 60 min reperfusion) in rats fed a standard diet or a steatogen [methionine/choline-deficient (MCD)] diet. Both groups consisted of 7 sham-operated rats, 10 rats that underwent I/R, and 10 that underwent I/R plus 8 wk of probiotic dietary supplementation. In rats fed a standard diet, I/R induced a decrease in sinusoid perfusion (P < 0.001), severe liver inflammation, and necrosis besides an increase of tissue levels of malondialdehyde (P < 0.001), tumor necrosis factor-alpha (P < 0.001), interleukin (IL)-1beta (P < 0.001), and IL-6 (P < 0.001) and of serum levels of transaminase (P < 0.001) and lipopolysaccharides (P < 0.001) vs. sham-operated rats. I/R also induced a decrease in Bacterioides, Bifidobacterium, and Lactobacillus spps (P < 0.01, P < 0.001, and P < 0.001, respectively) and an increase in Enterococcus and Enterobacteriaceae (P < 0.01 and P < 0.001, respectively) on intestinal mucosa. The severity of liver and gut microbiota alterations induced by I/R was even greater in rats with liver inflammation and steatosis, i.e., MCD-fed animals. LP-F19 supplementation significantly reduced the harmful effects of I/R on the liver and on gut microbiota in both groups of rats, although the effect was slightly less in MCD-fed animals. In conclusion, LP-F19 supplementation, by restoring gut microbiota, attenuated I/R-related liver injury, particularly in the absence of steatosis

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation.

BACKGROUND: In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain. METHODS: In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs. FINDINGS: Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex. INTERPRETATION: This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised. FUNDING: National Institute for Health Research

Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development

Sociality influences thermoregulation and roost switching in a forest bat using ephemeral roosts

In summer, many temperate bat species use daytime torpor, but breeding females do so less to avoid interferences with reproduction. In forest-roosting bats, deep tree cavities buffer roost microclimate from abrupt temperature oscillations and facilitate thermoregulation. Forest bats also switch roosts frequently, so thermally suitable cavities may be limiting. We tested how barbastelle bats (Barbastella barbastellus), often roosting beneath flaking bark in snags, may thermoregulate successfully despite the unstable microclimate of their preferred cavities. We assessed thermoregulation patterns of bats roosting in trees in a beech forest of central Italy. Although all bats used torpor, females were more often normothermic. Cavities were poorly insulated, but social thermoregulation probably overcomes this problem. A model incorporating the presence of roost mates and group size explained thermoregulation patterns better than others based, respectively, on the location and structural characteristics of tree roosts and cavities, weather, or sex, reproductive or body condition. Homeothermy was recorded for all subjects, including nonreproductive females: This probably ensures availability of a warm roosting environment for nonvolant juveniles. Homeothermy may also represent a lifesaver for bats roosting beneath loose bark, very exposed to predators, because homeothermic bats may react quickly in case of emergency. We also found that barbastelle bats maintain group cohesion when switching roosts: This may accelerate roost occupation at the end of a night, quickly securing a stable microclimate in the newly occupied cavity. Overall, both thermoregulation and roost-switching patterns were satisfactorily explained as adaptations to a structurally and thermally labile roosting environment

A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer

Introduction: For unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort. Methods: Two hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS). Results: One hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 83.5% (95%CI: 77.6–89.7) and 97.2% (95%CI: 94.6–99.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%). Conclusions: Durvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice

Diffusion-weighted imaging and apparent diffusion coefficient mapping of head and neck lymph node metastasis: a systematic review

Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck lymph node (LN) status is the major indicator of prognosis in all head and neck cancers, and the early detection of LN involvement is crucial in terms of therapy and prognosis. Diffusion-weighted imaging (DWI) is a non- invasive imaging technique used in magnetic resonance imaging (MRI) to characterize tissues based on the displacement motion of water molecules. This review aims to provide an overview of the current literature concerning quantitative diffusion imaging for LN staging in patients with HNSCC. Methods: This systematic review performed a literature search on the PubMed database (https://pubmed.ncbi.nlm.nih.gov/) for all relevant, peer-reviewed literature on the subject following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria, using the keywords: DWI, MRI, head and neck, staging, lymph node. Results: After excluding reviews, meta-analyses, case reports, and bibliometric studies, 18 relevant papers out of the 567 retrieved were selected for analysis. Conclusions: DWI improves the diagnosis, treatment planning, treatment response evaluation, and overall management of patients affected by HNSCC. More robust data to clarify the role of apparent diffusion coefficient (ADC) and DWI parameters are needed to develop models for prognosis and prediction in HNSCC cancer using MRI

Socioeconomic differences in food habits among 6- to 9-year-old children from 23 countries-WHO European Childhood Obesity Surveillance Initiative (COSI 2015/2017)

Background: Socioeconomic differences in children's food habits are a key public health concern. In order to inform policy makers, cross-country surveillance studies of dietary patterns across socioeconomic groups are required. The purpose of this study was to examine associations between socioeconomic status (SES) and children's food habits. Methods: The study was based on nationally representative data from children aged 6-9 years (n = 129,164) in 23 countries in the World Health Organization (WHO) European Region. Multivariate multilevel analyses were used to explore associations between children's food habits (consumption of fruit, vegetables, and sugar-containing soft drinks) and parental education, perceived family wealth and parental employment status. Results: Overall, the present study suggests that unhealthy food habits are associated with lower SES, particularly as assessed by parental education and family perceived wealth, but not parental employment status. We found cross-national and regional variation in associations between SES and food habits and differences in the extent to which the respective indicators of SES were related to children's diet. Conclusion: Socioeconomic differences in children's food habits exist in the majority of European and Asian countries examined in this study. The results are of relevance when addressing strategies, policy actions, and interventions targeting social inequalities in children's diets.The authors gratefully acknowledge support from a grant from the Russian Government in the context of the WHO European Office for the Prevention and Control of NCDs. Data collection in the countries was made possible through funding from Albania: WHO through the Joint Programme on Children, Food Security and Nutrition “Reducing Malnutrition in Children,” funded by the Millennium Development Goals Achievement Fund, and the Institute of Public Health; Bulgaria: Ministry of Health, National Center of Public Health and Analyses, WHO Regional Office for Europe; Croatia: Ministry of Health, Croatian Institute of Public Health and WHO Regional Office for Europe; Czechia: Ministry of Health of the Czech Republic, grant nr. AZV MZČR 17-31670 A and MZČ–VO EÚ 00023761; Denmark: Danish Ministry of Health; Georgia: WHO; Ireland: Health Service Executive; Italy: Ministry of Health and Italian National Institute of Health; Kazakhstan: Ministry of Health of the Republic of Kazakhstan and WHO Country Office; Kyrgyzstan: World Health Organization; Latvia: Ministry of Health, Centre for Disease Prevention and Control; Lithuania: Science Foundation of Lithuanian University of Health Sciences and Lithuanian Science Council and WHO; Malta: Ministry of Health; Montenegro: WHO and Institute of Public Health of Montenegro; Norway: Ministry of Health and Norwegian Institute of Public Health; Poland: National Health Programme, Ministry of Health; Portugal: Ministry of Health Institutions, the National Institute of Health, Directorate General of Health, Regional Health Directorates and the kind technical support from the Center for Studies and Research on Social Dynamics and Health (CEIDSS); Romania: Ministry of Health; Russian Federation: WHO; San Marino: Health Ministry, Educational Ministry; Serbia: This study was supported by the World Health Organization (Ref. File 2015-540940); Spain: Spanish Agency for Food Safety and Nutrition (AESAN); Tajikistan: WHO Country Office in Tajikistan and Ministry of Health and Social Protection; Turkmenistan: WHO Country Office in Turkmenistan and Ministry of Health; Turkey: Turkish Ministry of Health and World Bank. The CO-CREATE project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 774210.info:eu-repo/semantics/publishedVersio

The STRATOB study: design of a randomized controlled clinical trial of Cognitive Behavioral Therapy and Brief Strategic Therapy with telecare in patients with obesity and binge-eating disorder referred to residential nutritional rehabilitation

bstract BACKGROUND: Overweight and obesity are linked with binge eating disorder (BED). Effective interventions to significantly reduce weight, maintain weight loss and manage associated pathologies like BED are typically combined treatment options (dietetic, nutritional, physical, behavioral, cognitive-behavioral, pharmacological, surgical). Significant difficulties with regard to availability, costs, treatment adherence and long-term efficacy are present. Particularly Cognitive Behavioral Therapy (CBT) is the therapeutic approach indicated both in in-patient and in out-patient settings for BED. In recent years systemic and systemic-strategic psychotherapies have been implemented to treat patients with obesity and BED involved in familiar problems. Particularly a brief protocol for the systemic-strategic treatment of BED, using overall the strategic dialogue, has been recently developed. Moreover telemedicine, a new promising low cost method, has been used for obesity with BED in out-patient settings in order to avoid relapse after the in-patient step of treatment and to keep on a continuity of care with the involvement of the same clinical in-patient team. METHODS: The comparison between CBT and Brief Strategic Therapy (BST) will be assessed in a two-arm randomized controlled clinical trial. Due to the novelty of the application of BST in BED treatment (no other RCTs including BST have been carried out), a pilot study will be carried out before conducting a large scale randomized controlled clinical trial (RCT). Both CBT and BST group will follow an in-hospital treatment (diet, physical activity, dietitian counseling, 8 psychological sessions) plus 8 out-patient telephone-based sessions of psychological support and monitoring with the same in-patient psychotherapists. Primary outcome measure of the randomized trial will be the change in the Global Index of the Outcome Questionnaire (OQ-45.2). Secondary outcome measures will be the percentage of BED patients remitted considering the number of weekly binge episodes and the weight loss. Data will be collected at baseline, at discharge from the hospital (c.a. 1 month after) and after 6-12-24 months from the end of the in-hospital treatment. Data at follow-up time points will be collected through tele-sessions. DISCUSSION: The STRATOB (Systemic and STRATegic psychotherapy for OBesity), a comprehensive two-phase stepped down program enhanced by telepsychology for the medium-term treatment of obese people with BED seeking intervention for weight loss, will shed light about the comparison of the effectiveness of the BST with the gold standard CBT and about the continuity of care at home using a low-level of telecare (mobile phones). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0109625