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Gastric cancer (GC) is recognized as one of the most common deadly malignancies worldwide and about 40-50% of patients present at diagnosis with an unresectable disease due to a locally advanced or already metastatic condition. Recently, therapeutic options for management of metastatic GC (mGC) have been approved allowing a potential improvement of patient cancer treatment response and also an establishment of a continuum of care for this aggressive disease. This report is the result of a literature review by an expert panel. The aim of this document is to provide evidence, wherever it is lacking, to provide expert opinion directed at strategic management of mGC, and in particular aspect at practical management where appropriate guidelines are not available. Treatment landscape with new therapeutic strategies for third line and beyond, role of imaging, prognostic factors, symptoms, and markers as well as the importance of multidisciplinary approach particularly the nutritional aspects are discussed., Competing Interests: SC: consultant or advisory board: Lilly, Servier, MSD, and BMS. LF: consultant or advisory board: Lilly, Servier; MSD, BMS, and AstraZeneca. FD: consultant or advisory board: Celgene, BMS, MSD, Lilly, and Servier. MD: consultant: Lilly SpA, Servier, MSD, and BMS. SL: honoraria or advisory board: Roche, Eli Lilly, BMS, Servier, Merck Serono, Pierre Fabre, GlaxoSmithKline, Amgen, AstraZeneca, Incyte, Daiichi-Sankyo, Servier, and Merck Sharp & Dohme. GB: honoraria or advisory board: Roche, Lilly, Eisai, Incyte, Servier, ClovisOncology, Ipsen, Eli Lilly, Merck Serono, Amgen, Novartis, and BMS., (Copyright © 2022 Cascinu, Di Bartolomeo, Lonardi, Beretta, Fornaro and De Vita.)

(1) Cases of cancer are expected to increase in the next years and the risk of cancer increases with age. Data 2016-2019 from the Italian population-based surveillance PASSI d'Argento (PdA) allow the description of the physical and psychosocial well-being of people aged ≥65 years diagnosed with cancer (Ca), and the comparison with elderly suffering from other chronic conditions (Ch) and healthy older individuals (H). (2) Data are collected by Local Health Units' professionals using a standardized questionnaire during telephone interviews. (3) A total of 8051 out of the 56,352 interviewees reported a previous diagnosis of cancer: an annual average cancer prevalence of 12.8% (95% CI 12.4-13.3%) corresponding to 1.725 million elderly residing in Italy. In comparison to the H, Ca were more likely to refer bad health (aPR = 4.21; 95% CI: 3.70-4.79), suffer from depressive symptoms (aPR = 2.65; 95% CI: 2.35-2.99), disability (aPR = 2.50; 95% CI: 2.22-2.81) or sensory problems (aPR = 1.51; 95% CI: 1.40-1.63), be frail (aPR = 1.45; 95% CI: 1.30-1.61). Ca are often current smokers (aPR = 1.26; 95% CI: 1.11-1.45) and sedentary (aPR = 1.10; 95% CI: 1.03-1.18). (4) PdA provides valuable information to researchers and policy-makers by showing the difficulties for older people with cancer in contributing socially and accessing basic social and health services, which amplifies the risk of cognitive decline, isolation, and psychological deterioration.

Activation of T cells relies on the availability of intracellular cholesterol for an effective response after stimulation. We investigated the contribution of cholesterol derived from extracellular uptake by the low-density lipoprotein (LDL) receptor in the immunometabolic response of T cells. By combining proteomics, gene expression profiling, and immunophenotyping, we described a unique role for cholesterol provided by the LDLR pathway in CD8+ T cell activation. mRNA and protein expression of LDLR was significantly increased in activated CD8+ compared to CD4+ WT T cells, and this resulted in a significant reduction of proliferation and cytokine production (IFNγ, Granzyme B, and Perforin) of CD8+ but not CD4+ T cells from Ldlr -/- mice after in vitro and in vivo stimulation. This effect was the consequence of altered cholesterol routing to the lysosome resulting in a lower mTORC1 activation. Similarly, CD8+ T cells from humans affected by familial hypercholesterolemia (FH) carrying a mutation on the LDLR gene showed reduced activation after an immune challenge., (© 2022 Bonacina et al.)

Cocaine (COC) and its main metabolite, the benzoylecgonine (BE), are the main illicit drugs measured in aquatic system worldwide, with concentrations up to hundreds of ng/L. Although their current environmental concentrations are low these molecules can induce adverse effects at sub-individual level in non-target organisms. In contrast, the information at individual and behavioral level are still scant. The present study aimed at investigating biochemical and behavioral effects induced by 14-days exposure to environmentally relevant concentrations (50 ng/L and 500 ng/L) of COC and BE towards Procambarus clarkii. At sub-individual level, the activity of antioxidant and detoxifying (superoxide dismutase - SOD, catalase - CAT, glutathione peroxidase - GPx and glutathione S-transferases - GST) enzymes, as well as the levels of lipid peroxidation (LPO), were measured as oxidative stress-related endpoints. We also measured the acetylcholinesterase (AChE) activity to check for neurotoxic effect of COC and BE. At individual level, the modulation of some behavioral tasks (i.e., response to external stimuli, changes in feeding activity and exploration of a new environment) were assessed. Although both COC and BE exposure did not induce an oxidative stress situation, a significant inhibition of AChE activity was noted, resulting in behavioral changes in crayfish exposed to COC only. Crayfish exposed to the higher COC concentration showed an increase in the boldness and a decrease in the feeding activity, suggesting that COC may act according to its psychotropic mode of action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In a recent communication, Maselli and colleagues [...].

Metabolic syndrome is a complex condition associated with a series of pathologies featuring glucose intolerance, diabetes, high blood pressure, dyslipidemia, microalbuminuria, overweight, and obesity. It is also related to nonalcoholic fatty liver disease (NAFLD), recognized as the most familiar cause of chronic liver disease worldwide. The overall prevalence of metabolic syndrome and, consequently, the one of NAFLD is constantly increasing worldwide. The initial management of these diseases involves lifestyle modifications, including changes in diet and physical exercise. In addition to conventional drugs like orlistat, botanicals are traditionally used to counteract these disorders, and some of them are currently under evaluation. The present work evaluated the in vivo beneficial effects of hydroalcoholic extracts of two Cameroonian spices, focusing on obesity-related hepatic lipid injury in high-fat-fed C57BL/6 mice. Hydroethanolic extracts were prepared and characterized by reverse phase-high-performance liquid chromatography (HPLC)-photodiode array detection and ultra performance liquid chromatography-triple time-of-flight electrospray ionization tandem mass spectroscopy (TOF-ESI-MS/MS) analysis. Plant extracts were orally administered for 30 days at different dose levels (100 and 200 mg kg -1 body weight (BW)) to obese C57BL/6 mice. Food intake (FI) and BW were recorded daily. Plasma biochemical parameters and lipid content were estimated at the beginning and at the end of the experiment. Liver tissues were subjected to histological examinations, lipid content, as well as oxidative stress markers, and FAME (fatty acid methyl esters) were estimated. Oral administration of extracts at 200 mg kg -1 BW significantly reduced FI and prevented BW gain. A decrease in the weight of the liver and a decrease in the hepatic and plasma lipid content were observed. Plasma enzyme (serum glutamic-oxaloacetic transaminase, SGOT; serum glutamic pyruvic transaminase, SGPT; alkaline phosphatase, ALP) activities were not indicative of any organ damage. Chemical analysis suggested that phenolic acids (4-caffeoylquinic acid, p-coumaric acid 4-O-glucoside, 5-caffeoylshikimic acid, caffeic acid hexose, and 4-O-methyl gallic acid) and flavonoids (morusin derivatives, naringenin-7-O-glucoside, and homoisoflavanone) identified in the extracts could potentially justify the biological properties observed. The main findings of this study showed that Xylopia parviflora (A. Rich.) Benth and Aframomum citratum (Pereira ex Oliv. et Hanb.) K. Shum decreased hepatic lipid accumulation in high-fat-diet (HFD)-induced obese C57BL/6 mice and confirmed, at least in part, our previous in vitro and ex vivo studies. The molecular mechanisms underlying these effects are still unclear and will be explored in the future., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objective: To determine the impact on perinatal health of changes in social policies and obstetric care implemented to curb SARS-CoV-2 transmission. However, robust data on the topic are lacking since most of the studies has examined only the first few months of the outbreak., Methods: A retrospective analysis of prospectively collected data on uninfected and asymptomatically infected women giving birth between March and November 2020 and in the same time frame of 2019 at our tertiary care center in Lombardy, northern Italy. Perinatal outcomes were compared according to the year (2019 versus 2020) and to the trimester (March-May, June-August, September-November) of childbirth, corresponding to the three phases of the pandemic (first wave, deceleration, second wave) and covering a 9-month period., Results: We identified increased rates of gestational diabetes mellitus, spontaneous preterm birth, and neuraxial analgesia in 2020 versus 2019, with different temporal distributions: gestational diabetes mellitus and spontaneous preterm birth were more prevalent during the deceleration and the second wave phase, whereas epidural analgesia was more prevalent during the first wave., Conclusion: By assessing a prolonged time frame of the pandemic, we show that pandemic-related control measures, as applied in Lombardy, impacted relevant perinatal outcomes of women giving birth at our center., (© 2021 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

The development of innovative technologies and the advances in the genetics and genomics, have offered new opportunities for personalized treatment in oncology. Although the selection of the patient based on the molecular characteristics of the neoplasm has the potential to revolutionize the therapeutic scenario of oncology, this approach is extremely challenging. The access, homogeneity, and economic sustainability of the required genomic tests should be warranted in the clinical practice, as well as the specific scientific and clinical expertise for the choice of medical therapies. All these elements make essential the collaboration of different specialists within the Molecular Tumor Boards (MTBs). In this position paper, based on experts' opinion, the AIOM-SIAPEC/IAP-SIBioC-SIC-SIF-SIGU-SIRM Italian Scientific Societies critically discuss the available molecular profiling technologies, the proposed criteria for the selection of patients candidate for evaluation by the MTB, the criteria for the selection and analysis of biological samples, and the regulatory and pharmaco-economic issues., (Copyright © 2021. Published by Elsevier B.V.)

Background: Human neurodegenerative diseases occur as a result of various factors. Regardless of the variety in the etiology of development, many of these diseases are characterized by the accumulation of pathological, misfolded proteins; hence, such diseases are considered as proteinopathies. While plenty of research study has been conducted in order to identify the pathophysiology of these proteinopathies, there is still a lack of understanding in terms of potential therapeutic targets., Summary: Molecular chaperones present the main workforce for cellular protection and stress response. Therefore, considering these functions, molecular chaperones present a promising target for research within the field of conformational diseases that arise from proteinopathies. Since the association between neurodegenerative disorders and their long-term consequences is well documented, the need for the development of new therapeutic strategies becomes even more critical., Key Message: In this review, we summarized the molecular function of heat shock proteins and recent progress on their role, involvement, and other mechanisms related to neurodegeneration caused by different etiological factors. Based on the relevant scientific data, we will highlight the functional classification of heat shock proteins, regulation, and their therapeutic potential for neurodegenerative disorders., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 Indian Academy of Neurosciences (IAN).)

Introduction: Cardiac rehabilitation (CR) is an effective tool for secondary prevention after acute coronary syndrome (ACS)., Aim: Aim of our study was to find the significant determinants of exercise capacity (evaluated with the six-minute walking test-6-MWT) and functional improvement in patients undergoing CR after an ACS., Methods: The study group included 298 patients (mean age 61.6 ± 10.2 years; males 80.2%) who, after ACS, were enrolled in CR program at Niguarda Hospital in Milan from 2015 to 2018. For all patients, we collected anamnestic, clinical and instrumental cardiological data. All patients performed a 6-MWT at the beginning (6-MWT-1) and at the end (6-MWT-2) of CR program. Δ meters were used to represent functional improvement., Results: Multiple linear regression models were carried out for 6-MWT-1, 6-MWT-2, Δ meters and % Δ meters. Standardized regression coefficients showed that age (β = - 0.237; p < 0.001), BMI (β = - 0.116; p = 0.006) and heart rate (β = - 0.082; p = 0.040) were determinants of exercise capacity (6MWT-1 and 2), whereas age (β = -.231; p = 0.004), sex (β = - 0.187; p = 0.008) and BMI (β = - 0.164; p = 0.022) were determinants of functional improvement (Δ meters)., Conclusions: Our data showed that functional improvement after CR in ACS patients is mainly related to non-cardiological variables. Instead it is related to intrinsic factors, both modifiable (BMI) and non-modifiable (age, sex)., (© 2021. The Author(s).)

Hydroalcoholic extracts (HE) and essential oils (EO) of branches, leaves and fruits of Rhus typhina L ., were characterized by GC-MS. HE (yealds: branches 68.30 mg/g, leaves 35.82 mg/g and fruits 257.76 mg/g), showed different compositions dominated by gallic acid (33.46%) in branches, its precursor 1-cyclohexane-3,4,5-hydroxy-carboxylic acid (20.55%) in leaves and malic acid (89.15%) in fruits. EO yields were 210 µg/g for branches (main component δ -cadinene, 22.00%), followed by fruits with 132 µg/g ( β -pinene 32.2%) and by leaves with 54 µg/g and phenylacetaldehyde as major component (40.13%). Total phenolic content (TPC) was highest in branches HE (5.87 µg GAE /mL) and in EO leaves (17.71 µg GAE /mL). The highest value of radical scavenging activity (DPPH test) was detected in leaves HE and EO. The branches EO antimicrobial activity was strong against C. albicans and negligible against E. coli . Leaves and fruits EO showed strong activity against C. albicans and intermediate activity against Escherichia coli .

Background and Objectives : The aim of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios and to compare them with other biomarkers and clinical scores of sepsis outside the intensive care unit. Materials and methods : In this retrospective study, 251 patients with sepsis and 126 patients with infection other than sepsis were enrolled. NLR and PLR were calculated as the ratio between absolute values of neutrophils, lymphocytes, and platelets by complete blood counts performed on whole blood by Sysmex XE-9000 (Dasit, Italy) following the manufacturer's instruction. Results : The best NLR value in diagnosis of sepsis was 7.97 with sensibility, specificity, AUC, PPV, and NPV of 64.26%, 80.16%, 0.74 ( p < 0.001), 86.49%, and 53.18%, respectively. The diagnostic role of NLR significantly increases when PLR, C-reactive protein (PCR), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) values, as well as systemic inflammatory re-sponse syndrome (SIRS), sequential organ failure assessment (SOFA), and quick-sequential organ failure assessment (qSOFA) scores, were added to the model. The best value of NLR in predicting 90-day mortality was 9.05 with sensibility, specificity, AUC, PPV, and NPV of 69.57%, 61.44%, 0.66 ( p < 0.0001), 28.9%, and 89.9%, respectively. Sensibility, specificity, AUC, PPV, and NPV of NLR increase if PLR, PCR, PCT, MR-proADM, SIRS, qSOFA, and SOFA scores are added to NLR. Conclusions : NLR and PLR represent a widely useful and cheap tool in diagnosis and in predict-ing 90-day mortality in patients with sepsis.

In this study we investigated the performance of a computational pipeline for protein identification and label free quantification (LFQ) of LC-MS/MS data sets from experimental animal tissue samples, as well as the impact of its specific peptide search combinatorial approach. The full pipeline workflow was composed of peptide search engine adapters based on different identification algorithms, in the frame of the open-source OpenMS software running within the KNIME analytics platform. Two different in silico tryptic digestion, database-search assisted approaches (X!Tandem and MS-GF+), de novo peptide sequencing based on Novor and consensus library search (SpectraST), were tested for the processing of LC-MS/MS raw data files obtained from proteomic LC-MS experiments done on proteolytic extracts from mouse ex vivo liver samples. The results from proteomic LFQ were compared to those based on the application of the two software tools MaxQuant and Proteome Discoverer for protein inference and label-free data analysis in shotgun proteomics. Data are available via ProteomeXchange with identifier PXD025097., (© 2021 The Authors. Proteomics published by Wiley-VCH GmbH.)

Aim: Loss of immunosuppressive response supports inflammation during atherosclerosis. We tested whether adoptive cell therapy (ACT) with Tregulatory cells (Tregs), engineered to selectively migrate in the atherosclerotic plaque, would dampen the immune-inflammatory response in the arterial wall in animal models of familial hypercholesterolaemia (FH)., Methods and Results: FH patients presented a decreased Treg suppressive function associated to an increased inflammatory burden. A similar phenotype was observed in Ldlr -/- mice accompanied by a selective increased expression of the chemokine CX3CL1 in the aorta but not in other districts (lymph nodes, spleen, and liver). Treg overexpressing CX3CR1 were thus generated (CX3CR1+-Tregs) to drive Tregs selectively to the plaque. CX3CR1+-Tregs were injected (i.v.) in Ldlr -/- fed high-cholesterol diet (western type diet, WTD) for 8 weeks. CX3CR1+-Tregs were detected in the aorta, but not in other tissues, of Ldlr -/- mice 24 h after ACT, corroborating the efficacy of this approach. After 4 additional weeks of WTD, ACT with CX3CR1+-Tregs resulted in reduced plaque progression and lipid deposition, ameliorated plaque stability by increasing collagen and smooth muscle cells content, while decreasing the number of pro-inflammatory macrophages. Shotgun proteomics of the aorta showed a metabolic rewiring in CX3CR1+-Tregs treated Ldlr -/- mice compared to controls that was associated with the improvement of inflammation-resolving pathways and disease progression., Conclusion: ACT with vasculotropic Tregs appears as a promising strategy to selectively target immune activation in the atherosclerotic plaque., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: Thyroid ultrasound (US) is crucial for clinical decision in the management of thyroid nodules. In this cross-sectional study, we aimed to test if the evaluation of thyroid nodules' vascularization could improve the risk stratification ability of the American College of Radiology (ACR) TI-RADS classification system., Methods: A total of 873 thyroid nodules undergoing fine-needle aspiration were classified according to ACR TI-RADS US classification. Three types of vascularization were identified: type 0, no vascular signals; type 1, peripheral vascular signals; type 2, peripheral and intralesional vascular signals. Cytology specimens were evaluated conforming to the Italian Reporting System for Thyroid Cytology, and TIR3b, TIR4, and TIR5 were defined as high risk for malignancy. Odds ratios (ORs) with 95% confidence intervals (CI) and the areas under the receiver operating characteristic curves (ROC-AUC) for high-risk cytology categories were calculated., Results: The 3 vascular patterns were differently distributed within the cytology categories: 52.4% of TIR1c, 15.9% of TIR2, 5.9% of TIR3a, 6.7% of TIR3b, 12.5% of TIR4, and 28.9% of TIR5 nodules had no vascular signals ( p < 0.001). Nodule vascularity alone was not associated with a higher risk of malignant cytology (OR [95% CI] 0.75 [0.43-1.32], p = 0.32), without differences between peripheral (OR [95% CI] 0.65 [0.35-1.20]) and intranodular (OR [95% CI] 0.88 [0.48-1.62]) vascularization ( p = 0.22). The ROC-AUC (95% CI) for the diagnosis of malignant cytology was similar when considering TI-RADS classification alone (0.736 [0.684-0.786]) and when considering TI-RADS classification plus the presence/absence of vascular signals (0.736 [0.683-0.789], p value for differences between the ROC-AUCs: 0.91). Among TR1, TR2, and TR3 TI-RADS classes, no nodules without vascular signals showed a malignant cytology, allowing the identification of nodules with benign cytology with 100% specificity within these US classes., Conclusions: Color Doppler study of thyroid nodules does not improve the risk stratification ability of the ACR TI-RADS US classification system., Competing Interests: The authors have nothing to disclose., (Copyright © 2020 by European Thyroid Association Published by S. Karger AG, Basel.)

Introduction: Gender equity and gender medicine are opportunities not to be missed, and this Expert Group Opinion Paper on pain in women aims to review the treatment of pain conditions mainly affecting women, as well as the fundamental aspects of the different clinical response to drug treatment between the genders, and what can be done for gender-specific rehabilitation., Methods: Perspective review., Results: Genotypic and phenotypic differences in pain between the sexes are conditioned by anatomical, physiological, neural, hormonal, psychological, social, and cultural factors, such as the response to pharmacological treatment to control pain. The examination of these factors shows that women are affected by pain diseases more frequently and severely than men and that they report pain more frequently and with a lower pain threshold than men. Some forms of pain are inherently related to gender differences, such as pain related to the genitourinary system. However, other forms of chronic pain are seen more frequently in women than men, such as migraine, rheumatological, and musculoskeletal pain, in particular fibromyalgia., Discussion: Research is needed into the pathophysiological basis for gender differences in the generation of acute pain and maintenance of chronic pain, including the factors that put women at higher risk for developing chronic pain. In addition, different specialties need to collaborate to develop gender-related diagnostic and therapeutic guidelines, and healthcare professionals need to upskill themselves in the appropriate management of pain using existing diagnostic tools and therapeutic options.

Melanoma is an aggressive tumor with still poor therapy outcomes. δ-tocotrienol (δ-TT) is a vitamin E derivative displaying potent anti-cancer properties. Previously, we demonstrated that δ-TT triggers apoptosis in human melanoma cells. Here, we investigated whether it might also activate paraptosis, a non-canonical programmed cell death. In accordance with the main paraptotic features, δ-TT was shown to promote cytoplasmic vacuolization, associated with endoplasmic reticulum/mitochondrial dilation and protein synthesis, as well as MAPK activation in A375 and BLM cell lines. Moreover, treated cells exhibited a significant reduced expression of OXPHOS complex I and a marked decrease in oxygen consumption and mitochondrial membrane potential, culminating in decreased ATP synthesis and AMPK phosphorylation. This mitochondrial dysfunction resulted in ROS overproduction, found to be responsible for paraptosis induction. Additionally, δ-TT caused Ca 2+ homeostasis disruption, with endoplasmic reticulum-derived ions accumulating in mitochondria and activating the paraptotic signaling. Interestingly, by using both IP3R and VDAC inhibitors, a close cause-effect relationship between mitochondrial Ca 2+ overload and ROS generation was evidenced. Collectively, these results provide novel insights into δ-TT anti-melanoma activity, highlighting its ability to induce mitochondrial dysfunction-mediated paraptosis. δ-tocotrienol induces paraptotic cell death in human melanoma cells, causing endoplasmic reticulum dilation and mitochondrial swelling. These alterations induce an impairment of mitochondrial function, ROS production and calcium overload.

Prostate cancer (PCa) is the most common malignancy in men and represents the second leading cause of cancer deaths in Western countries. PCa is initially androgen-dependent, however, this tumor inevitably progresses as castration-resistant prostate cancer (CRPC), which represents the most aggressive phase of the pathology. In this work, in two CRPC cell lines (DU145 and PC3), we studied the in vitro inhibitory properties of the tryptophan-derived endogenous metabolite kynurenic acid (KYNA) and of the lactam form of 3-2'-pyrrilonidinyl-kynurenic acid (3-PKA-L), alkaloids usually present in combination in chestnut honey. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell colony formation assay, and Western blot analysis of the major mediator proteins involved in apoptotic processes. In all experiments, KYNA was scarcely or not active while 3-PKA-L showed anticancer activity in the high concentration range (0.01 mM - 1 mM) from 24 to 72 h. The results obtained showed that cell death was induced by extrinsic apoptotic pathway, by cell morphological changes and reduction of cell colonies number. These novel results represent the first promising step to the accurate description of 3-PKA-L cytotoxic effect, not observed with KYNA, paving the way to the search of new anticancer agents, as well as to the better understanding of the physiopathological role of this interesting natural product.

The study was performed on the dichloromethane (DCM), ethyl acetate (EAc) and n -butanol (Bu) fractions (F) obtained from the 80% ethanol extract of Linaria scariosa Desf. aerial parts, collected in the North Eastern region of Algeria. Remarkable total phenolic and flavonoid contents were obtained, mainly for EAcF. These results were in accordance with the antioxidant activity of EAcF against DPPH, ABTS, CUPRAC and reducing power tests. DCMF and BuF exhibited significant cholinesterase activity inhibition of BChE and AChE. Moreover, EAcF displayed only moderate antibacterial activities, especially against S. aureus . The biological results were correlated to the chemical components, deduced by both GC-MS analysis of the fractions and the isolation of hemipholin, pectolinarigenin, antirride, antirrinoside, pectolinarin and linariosise, some of which known to exhibit potent effects on the tested biological activities. The study provides the first biological and chemical investigation on Linaria scariosa Desf (unresolved name).

Oncological patients increasingly require second medical opinions to feel more likely confident with their oncologists and treatments, although this could lead to wrong opinions and delay in the start of treatments. Second opinions can be required also by physicians to obtain advices, especially in case of rare tumors. The request of new opinions is documented in radiology and pathology settings too, with not negligible discrepancy rate. Conversely, the role in general medical/surgical conditions has not been well established. Literature is poor of studies relative to second opinions or they are more focused on patient's motivations. For these reasons, AIOM (Italian Association of Medical Oncology) and AIOM Foundation faced this topic during the 7th Annual Meeting on Ethics in Oncology (Ragusa, 4-5 t h May 2018). In this position paper we report reasons, limits, advantages and outcomes of second medical opinion and the respective Decalogue in the oncological setting., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 c ases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12-218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32-2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11-0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Nitric oxide seems to be involved in the altitude acclimatization process due to its ability to regulate pulmonary, cardiovascular and muscular responses to hypoxia. In this study, we investigated the plasma nitrate (NO 3 - ) and nitrite (NO 2 - ) response to hypobaric hypoxia in two groups of lowlanders exposed at different altitudes. For seven days, fourteen subjects were evaluated at Casati Hut (3269 m a.s.l. M.CEVEDALE) and eleven individuals were studied at Capanna Regina Margherita (4554 m a.s.l. M.ROSA). Before expeditions and at different time points during high-altitude sojourn, plasma NO 3 - and NO 2 - concentrations were measured by chemiluminescence. Resting peripheral arterial oxygen saturation (SpO 2 ), heart rate (HR) and mean arterial blood pressure (MAP) were monitored during the experimental period. Possible confounding factors such as dietary NO 3 - intake, physical activity and altitude changes were controlled. Sea level plasma NO 3 - and NO 2 - concentrations significantly increased at altitude in both M.CEVEDALE group (+26.2 μM, p ≤ 0.0001, 95% CI [+17.6, +34.8] and +559.2 nM, p ≤ 0.0001, [+332.8, +785.6]) and M.ROSA group (+18.7 μM, p ≤ 0.0001, [+10.8, +26.5] and +463.7 nM, p ≤ 0.0001, [+314.3, +613.0]). Average peak value in NO metabolites concentration occurred earlier in M.CEVEDALE group vs M.ROSA group (NO 3 - , day 3 vs day 5, p = 0.007; NO 2 - , day 3 vs day 5, p = 0.019). In both groups, resting SpO 2 , HR and MAP values changed according to altitude levels. This study shows that exposure to hypobaric hypoxia affects nitric oxide metabolites, resulting in a significant increase in plasma NO 3 - and NO 2 - concentrations from sea level values. Interestingly, the higher the altitude reached, the longer the time taken to reach a peak in plasma concentrations of nitric oxide metabolites., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Among the top five human infections requiring medical treatment is dermatitis. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains. The aim of this study was to compare the antimicrobial activity of essential oils (EOs) and hydrolates (Hys) extracted from six aromatic plants grown in Italy ( Lavandula angustifolia, Lavandula intermedia, Origanum hirtum, Satureja montana, Monarda didyma, and Monarda fistulosa ) towards fungal ( Candida albicans , Candida parapsilosis , Candida glabrata and Candida tropicalis ; Trichophyton soudanense , Trichophyton tonsurans , Trichophyton rubrum , Trichophyton violaceum and Microsporum canis ) and bacterial strains ( Staphylococcus aureus MRSA, Staphylococcus aureus MSSA, Streptococcus pyogenes , E. faecalis, Enterococcus faecalis VRE, and Enterococcus faecium ) potentially pathogenic for human skin. The composition and antimicrobial activity of EOs and Hys were evaluated using the Gas-chromatography mass spectrometry and micro dilution-broth test, respectively. The volatiles' conversion factors (CFs) were calculated to compare the activity of Hys with that of the corresponding EOs. Data show that, although the minimum inhibitory concentration values of EOs are lower than the corresponding Hys, the volatiles contained in Hys are more effective at inhibiting microbial growth because they are active at lower concentrations.

Nano- and microsized extracellular vesicles (EVs) are naturally occurring cargo-bearing packages of regulatory macromolecules, and recent studies are increasingly showing that EVs are responsible for physiological intercellular communication. Nanoparticles encapsulating anti-tumor theranostics represent an attractive "exosome-interfering" strategy for cancer therapy. Methods : Herein, by labeling plasma-derived EVs with indocyanine green (ICG) and following their biodistribution by in vivo and ex vivo imaging, we demonstrate the existence of nanoparticles with a highly selective cancer tropism in the blood of colorectal cancer (CRC) patients but not in that of healthy volunteers. Results : In CRC patient-derived xenograft (PDX) mouse models, we show that transplanted EVs recognize tumors from the cognate nanoparticle-generating individual, suggesting the theranostic potential of autologous EVs encapsulating tumor-interfering molecules. In large canine breeds bearing spontaneous malignant skin and breast tumors, the same autologous EV transplantation protocol shows comparable safety and efficacy profiles. Conclusions : Our data show the existence of an untapped resource of intercellular communication present in the blood of cancer patients, which represents an efficient and highly biocompatible way to deliver molecules directly to the tumor with great precision. The novel EV-interfering approach proposed by our study may become a new research direction in the complex interplay of modern personalized cancer therapy., Competing Interests: Competing Interests: Al.V., M.G., V.M. and P.C. are coinventors of the patent n. IT 102019000007785 filed on May 5th 2019, at the Italian patent office: UIBM., (© The author(s).)

In Cameroon, local plants are traditionally used as remedies for a variety of ailments. In this regard, several papers report health benefits of Cameroonian spices, which include antioxidant and anti-microbial properties, whereas gastric anti-inflammatory activities have never been previously considered. The present study investigates the antioxidant and anti-inflammatory activities of hydro-alcoholic extracts of eleven Cameroonian spices in gastric epithelial cells (AGS and GES-1 cells). The extracts showed antioxidant properties in a cell-free system and reduced H 2 O 2 -induced ROS generation in gastric epithelial cells. After preliminary screening on TNFα-induced NF-κB driven transcription, six extracts from Xylopia parviflora , Xylopia aethiopica , Tetrapleura tetraptera , Dichrostachys glomerata , Aframomum melegueta , and Aframomum citratum were selected for further studies focusing on the anti-inflammatory activity. The extracts reduced the expression of some NF-κB-dependent pro-inflammatory mediators strictly involved in the gastric inflammatory process, such as IL-8, IL-6, and enzymes such as PTGS2 (COX-2), without affecting PTGS1 (COX-1). In conclusion, the selected extracts decreased pro-inflammatory markers by inhibiting the NF-κB signaling in gastric cells, justifying, in part, the traditional use of these spices. Other molecular mechanisms cannot be excluded, and further studies are needed to better clarify their biological activities at the gastric level.

The therapeutic options for castration-resistant prostate cancer (CRPC) are still limited. Natural bioactive compounds were shown to possess pro-death properties in different tumors. We previously reported that δ-tocotrienol (δ-TT) induces apoptosis, paraptosis and autophagy in CRPC cells. Here, we investigated whether δ-TT might exert its activity by impairing mitochondrial functions. We demonstrated that, in PC3 and DU145 cells, δ-TT impairs mitochondrial respiration and structural dynamics. In both cell lines, δ-TT triggers mitochondrial Ca 2+ and ROS overload. In PC3 cells, both Ca 2+ and ROS mediate the δ-TT-related anticancer activities (decrease of cell viability, apoptosis, paraptosis, autophagy and mitophagy). As expected, in autophagy-defective DU145 cells, Ca 2+ overload was involved in δ-TT-induced pro-death effects but not in autophagy and mitophagy. In this cell line, we also demonstrated that ROS overload is not involved in the anticancer activities of δ-TT, supporting a low susceptibility of these cells to ROS-related oxidative stress. Taken together, these data demonstrate that, in CRPC cells, δ-TT triggers cell death by inducing mitochondrial functional and structural impairments, providing novel mechanistic insights in its antitumor activity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: An increase in the incidence of OHCA during the COVID-19 pandemic has been recently demonstrated. However, there are no data about how the COVID-19 epidemic influenced the treatment of OHCA victims., Methods: We performed an analysis of the Lombardia Cardiac Arrest Registry comparing all the OHCAs occurred in the Provinces of Lodi, Cremona, Pavia and Mantua (northern Italy) in the first 100 days of the epidemic with those occurred in the same period in 2019., Results: The OHCAs occurred were 694 in 2020 and 520 in 2019. Bystander cardiopulmonary resuscitation (CPR) rate was lower in 2020 (20% vs 31%, p<0.001), whilst the rate of bystander automated external defibrillator (AED) use was similar (2% vs 4%, p = 0.11). Resuscitation was attempted by EMS in 64.5% of patients in 2020 and in 72% in 2019, whereof 45% in 2020 and 64% in 2019 received ALS. At univariable analysis, the presence of suspected/confirmed COVID-19 was not a predictor of resuscitation attempt. Age, unwitnessed status, non-shockable presenting rhythm, absence of bystander CPR and EMS arrival time were independent predictors of ALS attempt. No difference regarding resuscitation duration, epinephrine and amiodarone administration, and mechanical compression device use were highlighted. The return of spontaneous circulation (ROSC) rate at hospital admission was lower in the general population in 2020 [11% vs 20%, p = 0.001], but was similar in patients with ALS initiated [19% vs 26%, p = 0.15]. Suspected/confirmed COVID-19 was not a predictor of ROSC at hospital admission., Conclusion: Compared to 2019, during the 2020 COVID-19 outbreak we observed a lower attitude of laypeople to start CPR, while resuscitation attempts by BLS and ALS staff were not influenced by suspected/confirmed infection, even at univariable analysis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The correctness of the results of automated platelet analysis is still highly debated. The aim of this multicenter study, conducted according to international guidelines, was to verify the analytical performance of nine different types of hematology analyzers (HAs) in the automated platelet analysis., Methods: Four hundred eighty-six peripheral blood samples (PB), collected in K 3 EDTA tubes, were analyzed by ABX Pentra, ADVIA2120i, BC-6800, BC-6800 Plus, Cell-DYN Sapphire, DxH800, XE-2100, XE-5000, XN-20 with PLT-F App. Within-run imprecision and between-run imprecision were carried out using PB and material control, respectively. The carryover, low limit of quantification (LoQ), and the PB stability were evaluated., Results: The carryover was absent for all HAs. The LoQ of PLT ranged between 2.0 (Cell-Dyn Sapphire) and 25.0 × 10 9 /L (ADVIA 2120i), while immature platelet fraction (IPF) ranged between 1.0 (XN-20) and 12.0 × 10 9 /L (XE-5000). The imprecision (%CV) increases as the platelet count decreases. No HAs showed desirable CV APS for PLT counts less than 50.0 × 10 9 /L, with the exception of Cell-DYN Sapphire (CV 3.0% with PLT-O mean value of 26.7 × 10 9 /L), XN-20 (CV 2.4% with PLT-F mean value of 21.5 × 10 9 /L), and BC-6800 Plus (CV 1.9% with PLT-O mean value of 26.5 × 10 9 /L). The sample stability ranged between under two hours for MPV by ADVIA2120i and 8 hours for other PLT parameters and HAs., Conclusion: The findings of this study may provide useful information regarding carryover, precision, and stability of platelet counts and parameters, especially in thrombocytopenic samples. Moreover, the stability of sample for platelet analysis is conditioned by the HA and by temperature and storage time., (© 2020 John Wiley & Sons Ltd.)

The Mg 2+ -dependent Mycobacterium tuberculosis salicylate synthase (MbtI) is a key enzyme involved in the biosynthesis of siderophores. Because iron is essential for the survival and pathogenicity of the microorganism, this protein constitutes an attractive target for antitubercular therapy, also considering the absence of homologous enzymes in mammals. An extension of the structure-activity relationships of our furan-based candidates allowed us to disclose the most potent competitive inhibitor known to date ( 10 , K i = 4 μM), which also proved effective on mycobacterial cultures. By structural studies, we characterized its unexpected Mg 2+ -independent binding mode. We also investigated the role of the Mg 2+ cofactor in catalysis, analyzing the first crystal structure of the MbtI-Mg 2+ -salicylate ternary complex. Overall, these results pave the way for the development of novel antituberculars through the rational design of improved MbtI inhibitors.

Introduction: Cardiac rehabilitation (CR) improves the functional capacity and the prognosis of patients with coronary artery disease., Aim: Our study was aimed at assessing the relationship between functional improvement (evaluated with 6-min Walk Test-6MWT) and the improvement in left ventricular ejection fraction (LVEF) after CR., Methods: We collected data from 249 patients (age 66.79 ± 11.06 years; males 81.52%) with a recent history of Acute Coronary Syndrome that performed CR. The functional improvement after CR was expressed as the Δ between distance covered at the final versus the initial 6-min Walking Test (6-MWT), while LVEF was calculated with transthoracic echocardiogram at the beginning and at the end of the CR., Results: Patients were divided accordingly to their pre-rehab LVEF (≥ 55% vs < 55%). With superimposable age and baseline 6MWT distance covered (434.58 vs 405.12 m, p = 0.08), the latter group presented higher Δ meter values at 6MWT (167.93 vs 193.97 m, p = 0.018). However, no statistically significant positive correlation between Δ meters and Δ LVEF was found. Moreover, linear regression analyses found that nor baseline LVEF nor Δ LVEF were significant determinants of Δ meters when considering the whole group, with age, basal 6MWT and peak CK-MB as additional covariates in the model., Conclusion: Although it could be expected that an increase in LVEF is related to the functional improvement after CR, no significant correlation was found in our population.

Aims: An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve., Methods and Results: We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001)., Conclusion: The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Oxidative stress plays a relevant role in the progression of chronic conditions, including cardiometabolic diseases. Several Cameroonian plants, including spices, are traditionally used as herbal medicines for the treatment of diseases where oxidative stress contributes to insulin resistance, like type 2 diabetes mellitus. This study evaluated the antioxidant capacity and the effects on oxidative-stress-induced impairment of glucose uptake of 11 Cameroonian spice extracts. H 2 O 2 -induced reactive oxygen species (ROS) production by human HepG2 cells was significantly reduced by 8/11 extracts. The most effective extracts, Xylopia parviflora , Echinops giganteus , and Dichrostachys glomerata , showed a concentration-dependent ROS-scavenging activity, which involved Nrf2 translocation into the nucleus. Xylopia parviflora , Tetrapleura tetraptera , Dichrostachys glomerata , Aframomum melegueta , and Aframomum citratum extracts showed the highest antioxidant capacity, according to oxygen radical absorbance capacity (ORAC) (2.52-88 μM Trolox Eq/g of extract), ferric-reducing antioxidant power (FRAP) (40.23-233.84 mg gallic acid Eq/g of extract), and total phenol (8.96-32.96% mg gallic acid Eq/g of extract) assays. In HepG2 cells, glucose uptake was stimulated by 4/11 extracts, similarly to insulin and metformin. H 2 O 2 -induced oxidative stress reduced glucose uptake, which was rescued by pretreatment with Xylopia aethiopica , Xylopia parviflora , Scorodophloeus zenkeri , Monodora myristica , and Dichrostachys glomerata extracts. The ROS-scavenging ability of the spice extracts may reside in some secondary metabolites observed by phytochemical profiling (reverse-phase high-performance liquid chromatography coupled to a diode array detector (HPLC-UV-DAD)). Further studies are needed to better clarify their biological activities and potential use to control oxidative stress and promote insulin sensitivity.

Background and Purpose: The number of people suffering from stroke is strongly increasing, giving rise to multiple cognitive deficits which frequently prevent a full recovery. The identification of both spared and impaired cognitive domains has a key role to plan adequate interventions. However, the existing standard tests are either too expensive in terms of time and efforts for patients in acute stage or they derived from instruments addressing different pathologies such as dementia., Methods: We developed a brief neuropsychological battery (mental performance in acute stroke, MEPS) to assess different cognitive domains (language, memory, praxis, visual perception) in acute stroke patients. MEPS was validated by enrolling a sample of 204 patients suffering from stroke in acute stage, and 263 healthy controls participants., Results: The results indicated an adequate construct validity and a high ability in discriminating patients from healthy controls., Conclusions: MEPS can be considered a simple and highly valuable bedside battery, easy to administer, with values of sensitivity and specificity suitable to be proposed as a screening tool for patients with acute stroke.

Italy is the European country that was hit first and hardest by the COVID-19 epidemic. Since February 2020, the outbreak of the epidemic disease in Italy, with fatal outcomes in up to 10% of cases, made it urgent to implement extraordinary measures to avoid a breakdown of the universal Italian national health system. The update for April 1, 2020, in Italy recorded 102,669 confirmed COVID-19 cases, with a median patient age of 63 years. The deceased patients were older people (median age 80 years) and often had a cancer diagnosis (about 20%). Thus, in the extraordinary epidemiological scenario of the COVID-19 pandemic in Italy, older persons in cancer treatment are at particularly high risk of being severely affected by COVID-19. These people face a health- and economics-related emergency that also carries cultural and ethical implications. In accordance with the measures adopted by the Italian government to limit viral transmission, several associations of Italian oncologists have taken action to update Elderly Cancer Care programs. In view of the newly emerging needs, we herein outline practical suggestions aimed at guaranteeing the best continuity to elderly cancer patients., (Copyright © 2020 Fratino, Procopio, Di Maio, Cinieri, Leo and Beretta.)

In this study, a sensitive quantitative method based on high performance liquid chromatography combined with high-resolution mass spectrometry, Q Exactive TM -Orbitrap ® was set up and applied for the determination of the immunosuppressor agents cyclosporine A and tacrolimus in novel ethanol-free ophthalmic formulations for the treatment of Vernal keratoconjunctivitis. Different storage parameters in terms of storage temperatures and practical usage conditions were investigated to assess the stability of all formulations during shelf life simulating the real conditions as well to confirm the feasibility of use of ethanol-free products. The methodology was linear (r 2 = 0.995) over the concentration range 0-200 ng/mL, and its selectivity, precision, accuracy and recovery were all within the required limits. Under different conditions (storage period 0-90 days, 5-25 °C, unopened/usage simulated conditions), our results revealed that both active pharmaceutical ingredients (API) show satisfactory stability up to 30 days of storage/usage, with a significant and consistent concentration decline of cyclosporine A after this time point when its hydroalcoholic formulation was kept at 25 °C.

Background: Hydrolates, complex mixtures containing traces of essential oils (EOs), are inexpensive, easy to make and less toxic than their corresponding EOs. The antibacterial and antifungal activity of the hydrolate of Coridothymus capitatus (L.) Reichenb. fil. (Lamiaceae) alone and in combination with antimicrobial drugs, such as tetracycline and itraconazole, were evaluated., Methods: The chemical composition was analysed by gas-chromatography-mass spectrometry (GC-MS). Standard methods were performed to evaluate the susceptibility of some Gram-positive and Gram-negative bacteria, and Candida spp. to the hydrolate, in comparison with its EO. The hydrolate mechanism of action was assayed by propidium iodide and MitoTracker staining. Checkerboard tests were carried out for combinations studies., Results: GC-MS identified 0.14% (v/v) of total EO content into hydrolate and carvacrol as a dominant component. The hydrolate showed a good antimicrobial activity against bacteria and yeasts. It exhibited a synergistic effect with itraconazole against Candida krusei, and an additive effect with tetracycline against methicillin-resistant Staphylococcus aureus strains. Hydrolate changed the membranes permeability of bacteria and yeasts and altered mitochondrial function of yeasts., Conclusions: Our study extends the knowledge by exploiting non-conventional antimicrobial agents to fight the emergence of antibiotic resistance.

Background: The Informative System of Nursing Performance was developed to measure complexity of nursing care based on the actual interventions performed by nurses at the point of care. The association of this score with in-hospital mortality was not investigated before. Having this information is relevant to define evidence-based criteria that hospital administrators can use to allocate nursing workforce according to the real and current patients' need for nursing care. The aim of this study is to assess the association between complexity of nursing care and in-hospital mortality., Methods: Register-based cohort study on all patients admitted to acute medical wards of a middle-large hospital in the North of Italy between January 1, 2014, to December 31, 2015 and followed up to discharge. Out of all the eligible 7247 records identified in the Hospital Discharge Register, 6872 records from 5129 patients have been included. A multivariable frailty Cox model was adopted to estimate the association between the Informative System of Nursing Performance score, both as continuous variable and dichotomized as low (score < 50) or high (score ≥ 50), and in-hospital mortality adjusting for several factors recorded at admission (age, gender, type of admission unit, type of access and Charlson Comorbidity Index)., Results: The median age of the 5129 included patients was 76 [first-third quartiles 64-84] and 2657(52%) patients were males. Over the 6872 admissions, there were 395 in-hospital deaths among 2922 patients at high complexity of nursing care (13.5%) and 74/3950 (1.9%) among those at low complexity leading to a difference of 11.6% (95% CI: 10.3-13.0%). Adjusting by relevant confounders, the hazard rate of mortality in the first 10 days from admission resulted 6 times significantly higher in patients at high complexity of nursing care with respect to patients at low complexity (hazard ratio, HR 6.58, 95%CI: 4.50;9.62, p < 0.001). The HR was lower after 10 days from admission but still significantly higher than 1. By considering the continuous score, the association was confirmed., Conclusion: Complexity of nursing care is strongly associated to in-hospital mortality of acute patients admitted to medical departments. It predicts in-hospital mortality better than widely used indicators, such as comorbidity.

Background: Dependency in older ages is increasing. Many older persons receive care while living in the community. We aimed to identify the predictive value of four clinical measurements to predict home care intensity in older patients following discharge from hospital to home care over 90 days., Methods: We included 425 inpatients from the "Frailty Department-Local Palliative Care Network" of the local social health authority (ASST) Lecco, Italy (mean age 75.4 years, SD 14.5; female 75.5%). Changes in Health, End-stage disease, and Signs and Symptoms, light version (CHESS-Lite), activities of daily living (ADL), frailty, and the Service Urgency Algorithm. Receiver operative curves were used to calculate the area under the curve (AUC) for predicting Home Care Intensity coefficient (ratio of the number of days when any home care was provided 90 days post-discharge). The interRAI Contact Assessment Instrument was used to calculate these measures., Results: Analysis was stratified using six different home care intensity score cut-offs. CHESS-Lite had a higher AUC for predicting home care intensity at all cut-off levels but was best for predicting the highest level of home care intensity (≥ 0.8) where the AUC was 0.71 (0.64-0.79). The frailty index also had an acceptable AUC. ADL had the lowest AUC., Conclusions: Health instability measured with CHESS-Lite has a high predictive value for identifying home care intensity in geriatric patients after discharge from hospital to home, especially in persons with higher home care intensity scores. Geriatric patients with high health instability should be focused on at discharge to prioritize assessment and initiate timely services for home care support.

The ability of an organism to adapt to short-term environmental changes within its lifetime is of fundamental importance. This adaptation may occur through phenotypic plasticity. Insects and mites, in particular, are sensitive to changes in temperature and humidity, especially during the juvenile stages. We studied the role of phenotypic plasticity in the adaptation of eggs to different relative humidity conditions, in the predatory mite Phytoseiulus persimilis, used worldwide as a biological control agent of the spider mite Tetranychus urticae. The biocontrol efficacy of P. persimilis decreases under dry conditions, partly because P. persimilis eggs are sensitive to drought. We exposed P. persimilis adult females from two different strains to constant and variable humidity regimes and evaluated the hatching rate of their eggs in dry conditions, as well as the survival and oviposition rates of these females. Whereas the eggs laid by P. persimilis females exposed to constant high humidity did not survive in dry conditions, females exposed to constant low humidity started laying drought-resistant eggs after 24 h of exposure. Survival and oviposition rates of the females were affected by humidity: females laid fewer eggs under constant low humidity and had a shorter lifespan under constant high and constant low humidity. The humidity regimes tested had similar effects across the two P. persimilis strains. Our results demonstrate that transgenerational phenotypic plasticity, called maternal effect, allows P. persimilis females to prepare their offspring for dry conditions.

Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K i of 8.8 µM and its antimycobacterial activity (MIC 99  = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic derivatives are a promising class of MbtI inhibitors.

Under drought stress, Phytoseiulus persimilis females are able to lay drought-resistant eggs through an adaptive maternal effect. The mechanisms making these eggs drought resistant still remain to be investigated. For this purpose, we studied the physiological differences between drought-resistant and drought-sensitive eggs. We compared the volume and the surface-area-to-volume ratio (SA:V) of the eggs, their sex ratio, their chemical composition (by gas chromatography-mass spectrometry), their internal and external structure [by scanning electron microscope (SEM) and transmission electron microscope (TEM) images], and their developmental time. Our results show that drought-resistant and drought-sensitive eggs have a different chemical composition: drought-resistant eggs contain more compatible solutes (free amino acids and sugar alcohols) and saturated hydrocarbons than drought-sensitive eggs. This difference may contribute to reducing water loss in drought-resistant eggs. Moreover, drought-resistant eggs are on average 8.4% larger in volume, and have a 2.4% smaller SA:V than drought-sensitive eggs. This larger volume and smaller SA:V, probably the result of a higher water content, may make drought-resistant eggs less vulnerable to water loss. We did not find any difference in sex ratio, internal or external structure nor developmental time between drought-resistant and drought-sensitive eggs. These results mark the first step in the understanding of the strategies and the energetic costs involved in the production of drought-resistant eggs in P. persimilis females.

Cardiovascular diseases are the greatest cause of death globally and are frequently associated with type 2 diabetes mellitus and metabolic syndrome, a condition including visceral obesity, hypertension, elevated triglycerides and low HDL cholesterol and hyperglycaemia. Several medicinal plants, including spices, are used in Cameroon as herbal medicines and are traditionally employed for the treatment of several ailments such as diabetes and related diseases. In this study, we chemically characterized eleven Cameroonian spice extracts and evaluated their effects on some enzyme activities relevant to carbohydrate and lipid digestion and cardio-metabolic diseases. Hydroethanolic spice extracts were characterized by GC-MS analysis and screened for their ability to modulate the activity of α-glucosidase, α-amylase, pancreatic lipase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and angiotensin-converting enzyme (ACE). Among the spice extracts tested, those from Xylopia parviflora showed the widest inhibitory spectrum, with a relevant effect on all enzyme activities. Dichrostachys glomerata and Aframomum citratum extracts were more selective. The selected and strong activity of some plants, such as that of Aframomum citratum on pancreatic lipase and that of Xylopia aethiopica on ACE, suggests their specific use in obesity and hypertension, respectively. Chemical analysis indicated that for some spice extracts such as Xylopia parviflora and Aframomum citratum their secondary metabolites (chlorogenic acid, pimaric acid, and catechin and its derivatives) could potentially justify the biological properties observed. Our findings clearly show significant inhibition of cardio-metabolic enzymes by hydroethanolic Cameroonian spice extracts, suggesting the potential usefulness of nutraceuticals derived from these plants to develop novel management strategies for obesity and diabetes complications.