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IntroductionThe emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains has underscored the urgent need for novel therapeutic approaches. Carbon-based nanomaterials, such as graphene oxide (GO), have shown potential in anti-TB activities but suffer from significant toxicity issues.MethodsThis study explores the anti-TB potential of differently functionalized graphene quantum dots (GQDs) – non-functionalized, L-GQDs, aminated (NH2-GQDs), and carboxylated (COOH-GQDs) – alone and in combination with standard TB drugs (isoniazid, amikacin, and linezolid). Their effects were assessed in both axenic cultures and in vitro infection models.ResultsGQDs alone did not demonstrate direct mycobactericidal effects nor trapping activity. However, the combination of NH2-GQDs with amikacin significantly reduced CFUs in in vitro models. NH2-GQDs and COOH-GQDs also enhanced the antimicrobial activity of amikacin in infected macrophages, although L-GQDs and COOH-GQDs alone showed no significant activity.DiscussionThe results suggest that specific types of GQDs, particularly NH2-GQDs, can enhance the efficacy of existing anti-TB drugs. These nanoparticles might serve as effective adjuvants in anti-TB therapy by boosting drug performance and reducing bacterial counts in host cells, highlighting their potential as part of advanced drug delivery systems in tuberculosis treatment. Further investigations are needed to better understand their mechanisms and optimize their use in clinical settings.

The purpose of this review is to describe the impact of endurance and strength physical training on the cardiovascular system by reviewing the molecular signaling pathways, which plays a key role in different muscle adaptations, and the cardiac changes in terms of metabolic and cardiac remodeling, and hemodynamics. In response to endurance-exercise, multiple signaling pathways, including Ca2+-dependent pathways, reactive oxygen species (ROS), AMP-dependent protein kinase (AMPK), and mitogen activated protein kinases (p38 MAPK), are involved in the regulation of peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α), which controls the mitochondrial biogenesis. Strength training increases the insulin-like growth factor (IGF-1) which initiates the phosphatidylinositol 3-kinase (PI3-k)-(AKT)-(mTOR) signaling cascade, resulting in the synthesis of proteins and the muscle hypertrophy. In addition to the well-documented changes in skeletal muscle, a critical component of the response to exercise training is the dynamic cardiac remodeling, which is classified as either pathological or physiological depending on triggers.

Abstract Background Physical activity contributes to changes in cardiac morphology, which are known as “athlete’s heart”. Therefore, these modifications can be characterized using different imaging modalities such as echocardiography, including Doppler (flow Doppler and Doppler myocardial imaging) and speckle-tracking, along with cardiac magnetic resonance, and cardiac computed tomography. Main text Echocardiography is the most common method for assessing cardiac structure and function in athletes due to its availability, repeatability, versatility, and low cost. It allows the measurement of parameters like left ventricular wall thickness, cavity dimensions, and mass. Left ventricular myocardial strain can be measured by tissue Doppler (using the pulse wave Doppler principle) or speckle tracking echocardiography (using the two-dimensional grayscale B-mode images), which provide information on the deformation of the myocardium. Cardiac magnetic resonance provides a comprehensive evaluation of cardiac morphology and function with superior accuracy compared to echocardiography. With the addition of contrast agents, myocardial state can be characterized. Thus, it is particularly effective in differentiating an athlete’s heart from pathological conditions, however, is less accessible and more expensive compared to other techniques. Coronary computed tomography is used to assess coronary artery anatomy and identify anomalies or diseases, but its use is limited due to radiation exposure and cost, making it less suitable for young athletes. A novel approach, hemodynamic forces analysis, uses feature tracking to quantify intraventricular pressure gradients responsible for blood flow. Hemodynamic forces analysis has the potential for studying blood flow within the heart and assessing cardiac function. Conclusions In conclusion, each diagnostic technique has its own advantages and limitations for assessing cardiac adaptations in athletes. Examining and comparing the cardiac adaptations resulting from physical activity with the structural cardiac changes identified through different diagnostic modalities is a pivotal focus in the field of sports medicine. Graphical Abstract

Taking the recent changes introduced in the Italian Constitution as a starting point, which for the first time have included the environmental protection in our fundamental Charter, the essay aims to offer an analytical perspective on environmental education. We’ll try to answer two questions: what does environmental citizenship mean today and how is this type of citizenship built in relation to the new constitutional provision, keeping together the conservation of the environment, its resources and sustainable development thanks to environmental education.

BackgroundHemodynamic forces (HDF) analysis has been proposed as a method to quantify intraventricular pressure gradients, however data on its reliability are still scanty. Thus, the aim of this study is to assess the reliability of HDF parameters derived from cardiac magnetic resonance (CMR).MethodsCMR studies of 25 athletes were analysed by two independent observers and then re-analysed by the same observer one week apart. Intraclass Correlation Coefficient (ICC [95% CI]) and Bland-Altman plots were used to assess association, agreement, and bias of the longitudinal (A-B) HDF, transverse (L-S) HDF, and Impulse Angle. The sample size required to detect a relative change in the HDF parameters was also calculated.ResultsIn terms of inter-observer variability, there was a good correlation for the A-B and L-S (ICC 0.85 [0.67-0.93] and 0.86 [0.69-0.94]; pConclusionsThe results of this study showed a low inter- and intra-observer variability of HDF parameters derived from feature-tracking CMR. This provides the fundamental basis for their use both in research and clinical practice, which could eventually lead to the detection of significant changes at follow-up studies.

The aim of this study is to analyze the well-being of young music teachers working in Trentino Music Schools (TMS). Specifically, we assess (i) the extent to which the interaction between teaching and playing affects the well-being of young musicians using a satisfaction measure for their overall professional path as teachers and musicians, and (ii) what extrinsic and intrinsic drivers may guide their involvement in teaching activities in the early stages of their careers. To this end, we analyze original survey data on young musicians teaching in TMS to estimate their relative satisfaction and identify their motivational drivers. Specifically, we estimate from elementary items six constructs concerning material work conditions, immaterial welfare (i.e., the capabilities activated by the schools), and initial monetary and non-monetary motivations to become a music teacher, then we run two ordered logit regressions to test whether a set of variables of interest and the estimated constructs contribute to explaining junior teachers’ satisfaction. Our findings highlight that junior teachers are satisfied if they can preserve the desired proportion of artistic activity and can teach a consistent number of hours so as to leave the desired space and time for making music independently of school activities. They consider teaching to be one of the components of their professional activities and can be expected to try to maintain sufficient space to be able to also develop the independent artistic sphere of their career as musicians.

BackgroundCardiovascular diseases contribute to premature mortality globally, resulting in substantial social and economic burdens. The Global Burden of Disease (GBD) Study reported that in 2019 alone, heart attack and strokes accounted for the deaths of 18.6 million individuals. Ischemic heart diseases, including acute myocardial infarction (AMI), accounted for 182 million disability-adjusted life years (DALYs) and it is leading cause of death worldwide.AimThe aim of this study is to present the burden of AMI in Kazakhstan and describe the outcome of hospitalized patients.MethodsThe data of 79,172 people admitted to hospital with ICD-10 diagnosis I21 between 2014 and 2019 was derived from the Unified National Electronic Health System and retrospectively analyzed.ResultsThe majority of the cohort (53,285, 67%) were men, with an average age of 63 (±12) years, predominantly of Kazakh (38,057, 48%) and Russian (24,583, 31%) ethnicities. Hypertension was the most common comorbidity (61,972, 78%). In males, a sharp increase in incidence is present after 40 years, while for females, the morbidity increases gradually after 55. Throughout the observation period, all-cause mortality rose from 101 to 210 people per million population (PMP). In 2019, AMI account for 169,862 DALYs in Kazakhstan, with a significant proportion (79%) attributed to years of life lost due to premature death (YLDs). Approximately half of disease burden due to AMI (80,794 DALYs) was in age group 55–69 years. Although incidence is higher for men, they have better survival rates than women. In terms of revascularization procedures, coronary artery bypass grafting yielded higher survival rates compared to percutaneous coronary intervention (86.3% and 80.9% respectively) during the 5-year follow-up.ConclusionThis research evaluated the burden and disability-adjusted life years of AMI in Kazakhstan, the largest Central Asian country. The results show that more effective disease management systems and preventive measures at earlier ages are needed.

The Province of Rieti (Italy) hosts well-preserved historical villages rich in natural and cultural resources, as well as attractive food traditions. Consequently, being close to the Metropolitan City of Rome, many urban residents may consider it an ideal place for out-of-town trips integrating a mix of nature, taste, and culture. Based on these premises, the research answers the following questions: what are the most attractive destinations for out-of-town trips in the Province of Rieti? What territorial factors may negatively affect local tourism attractiveness? To answer these questions, a multidimensional quantitative analysis is developed at the municipal scale through the design and implementation of a composite index based on two dimensions (tourism attractiveness and territorial development). The results of the quantitative analysis suggest how the small municipalities located in the Province of Rieti are characterized by a heterogeneous mix of tourism attractiveness and territorial development, and most of them may be ideal destinations for out-of-town trips. However, supra-local development strategies (such as the Reatini Mountains strategy) are needed to narrow the territorial and socioeconomic distances from the poles of services and to elaborate a culturally sustainable local tourism offer that may foster entrepreneurship, increase welfare, and trigger rural development in the localities.

AimsThe current study aimed to validate the Italian version of the Staff Attitude to Coercion Scale (SACS), which assesses mental health care staff’s attitudes to the use of coercion in treatment.MethodsThe original English version of the SACS was translated into Italian, according to the back-translation procedure. Subsequently, it was empirically validated by performing an exploratory factor analysis on a sample of 217 mental health professionals (Mean = 43.40 years, SD = 11.06) recruited form Italian general hospital (acute) psychiatric wards (GHPWs), with at least 1 year of work experience (i.e., inclusion criteria).ResultsResults confirmed the three-factor solution of the original version for the Italian version of the SACS, though three items loaded on different factors, compared to the original. The three extracted factors, explained 41% of total variance, and were labeled similarly to the original scale and according to their respective item content, i.e., Factor 1 “Coercion as offending” (items: 3, 13, 14, and 15), Factor 2 “Coercion as care and security” (items: 1, 2, 4, 5, 7, 8, and 9), and Factor 3 “Coercion as treatment” (items: 6, 10, 11, and 12). The internal consistency of the three-factor model of the Italian version of the SACS was assessed through Cronbach’s α and yielded acceptable indexes, ranging from 0.64 to 0.77.ConclusionThe present findings suggest that the Italian version of the SACS is a valid and reliable tool that can be used to assess healthcare professionals’ attitudes toward coercion.

Respiratory tract infections represent the main cause of death from infectious diseases worldwide. SARS-CoV-2 infection (i.e. COVID-19) added to the existing global burden of respiratory tract infections, including tuberculosis. Among nanomaterials for fabric functionalization, graphene, in combination with hydrophobic molecules such as phytochemicals, represents a promising low-cost alternative to antibiotics. In this work, we used graphene and curcumin to create fabric coatings on cotton and polyester for the production of personal protective equipment resistant to infective agents. These coatings ensure the trapping of microorganisms via interaction with SARS-CoV-2 or mycobacteria surface and inhibit microbial infections.

Background: Hemodynamic forces (HDF) analysis has been proposed as a method to quantify intraventricular pressure gradients, however data on its reliability are still scanty. Thus, the aim of this study is to assess the reliability of HDF parameters derived from cardiac magnetic resonance (CMR). Methods: CMR studies of 25 athletes were analysed by two independent observers and then re-analysed by the same observer one week apart. Intraclass Correlation Coefficient (ICC [95% CI]) and Bland-Altman plots were used to assess association, agreement, and bias of the longitudinal (A-B) HDF, transverse (L-S) HDF, and Impulse Angle. The sample size required to detect a relative change in the HDF parameters was also calculated. Results: In terms of inter-observer variability, there was a good correlation for the A-B and L-S (ICC 0.85 [0.67–0.93] and 0.86 [0.69–0.94]; p<0.001 for both, respectively) and a moderate correlation for the Impulse Angle (ICC 0.73 [0.39–0.87]; p = 0.001). For intra-observer variability, A-B and L-S showed excellent correlation (ICC 0.91 [0.78–0.93] and 0.93 [0.83–0.97]; p<0.001 for both, respectively). Impulse Angle presented good correlation (ICC 0.80 [0.56–0.90]; p<0.001). Frame selection and aortic valve area measurements were the most vulnerable step in terms of reliability of the method. Sample size calculation to detect relative changes ranged from n = 1 to detect a 15% relative change in Impulse Angle to n = 171 for the detection of 10% relative change in A-B HDF. Conclusions: The results of this study showed a low inter- and intra-observer variability of HDF parameters derived from feature-tracking CMR. This provides the fundamental basis for their use both in research and clinical practice, which could eventually lead to the detection of significant changes at follow-up studies. [ABSTRACT FROM AUTHOR]

PE_PGRS proteins of Mycobacterium tuberculosis (Mtb) constitute a large family of complex modular proteins whose role is still unclear. Among those, we have previously shown, using the heterologous expression in Mycobacterium smegmatis, that PE_PGRS3 containing a unique arginine-rich C-terminal domain, promotes adhesion to host cells. In this study, we investigate the role of PE_PGRS3 and its C-terminal domain directly in Mtb using functional deletion mutants. The results obtained here show that PE_PGRS3 is localized on the mycobacterial cell wall and its arginine-rich C-terminal region protrudes from the mycobacterial membrane and mediates Mtb entry into epithelial cells. Most importantly, this positively charged helical domain specifically binds phosphorylated phosphatidylinositols and cardiolipin, whereas it is unable to bind other phospholipids. Interestingly, administration of cardiolipin and phosphatidylinositol but no other phospholipids was able to turn-off expression of pe_pgrs3 activated by phosphate starvation conditions. These findings suggest that PE_PGRS3 has the key role to serve as a bridge between mycobacteria and host cells by interacting with specific host phospholipids and extracting them from host cells, for their direct integration or as a source of phosphate, during phases of TB pathogenesis when Mtb is short of phosphate supply.

Abstract Background In many high-income countries, life expectancy (LE) has increased, with women outliving men. This gender gap in LE (GGLE) has been explained with biological factors, healthy behaviours, health status, and sociodemographic characteristics, but little attention has been paid to the role of public health policies that include/affect these factors. This study aimed to assess the contributions of avoidable causes of death, as a measure of public health policies and healthcare quality impacts, to the GGLE and its temporal changes in the UK. We also estimated the contributions of avoidable causes of death into the gap in LE between countries in the UK. Methods We obtained annual data on underlying causes of death by age and sex from the World Health Organization mortality database for the periods 2001–2003 and 2014–2016. We calculated LE at birth using abridged life tables. We applied Arriaga’s decomposition method to compute the age- and cause-specific contributions into the GGLE in each period and its changes between two periods as well as the cross-country gap in LE in the 2014–2016 period. Results Avoidable causes had greater contributions than non-avoidable causes to the GGLE in both periods (62% in 2001–2003 and 54% in 2014–2016) in the UK. Among avoidable causes, ischaemic heart disease (IHD) followed by injuries had the greatest contributions to the GGLE in both periods. On average, the GGLE across the UK narrowed by about 1.0 year between 2001–2003 and 2014–2016 and three avoidable causes of IHD, lung cancer, and injuries accounted for about 0.8 years of this reduction. England & Wales had the greatest LE for both sexes in 2014–2016. Among avoidable causes, injuries in men and lung cancer in women had the largest contributions to the LE advantage in England & Wales compared to Northern Ireland, while drug-related deaths compared to Scotland in both sexes. Conclusion With avoidable causes, particularly preventable deaths, substantially contributing to the gender and cross-country gaps in LE, our results suggest the need for behavioural changes by implementing targeted public health programmes, particularly targeting younger men from Scotland and Northern Ireland.

Abstract Background Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, hence their impact on occupational and public health has become a concern. In recent years, interest on the effect that exposure to NPs may exert on human reproduction has grown, however data are still scant. In the present work, we investigated whether different metal oxide NPs interfere with mouse cumulus cell-oocyte complex (COC) expansion. Methods Mouse COCs from pre-ovulatory follicles were cultured in vitro in the presence of various concentrations of two types of TiO2 NPs (JRC NM-103 and NM-104) and four types of ZnO NPs (JRC NM-110, NM-111, and in-house prepared uncoated and SiO2-coated NPs) and the organization of a muco-elastic extracellular matrix by cumulus cells during the process named cumulus expansion was investigated. Results We show that COC expansion was not affected by the presence of both types of TiO2 NPs at all tested doses, while ZnO NM-110 and NM-111 induced strong toxicity and inhibited COCs expansion at relatively low concentration. Medium conditioned by these NPs showed lower toxicity, suggesting that, beside ion release, inhibition of COC expansion also depends on NPs per se. To further elucidate this, we compared COC expansion in the presence of uncoated or SiO2-coated NPs. Differently from the uncoated NPs, SiO2-coated NPs underwent slower dissolution, were not internalized by the cells, and showed an overall lower toxicity. Gene expression analysis demonstrated that ZnO NPs, but not SiO2-coated ZnO NPs, affected the expression of genes fundamental for COC expansion. Dosimetry analysis revealed that the delivered-to-cell mass fractions for both NPs was very low. Conclusions Altogether, these results suggest that chemical composition, dissolution, and cell internalization are all responsible for the adverse effects of the tested NPs and support the importance of a tailored, safer-by-design production of NPs to reduce toxicity.

Lipids are central at various stages of host–pathogen interactions in determining virulence and modulating plant defense. Free fatty acids may act as substrates for oxidizing enzymes [e.g., lipoxygenases (LOXs) and dioxygenases (DOXs)] that synthesize oxylipins. Fatty acids and oxylipins function as modulators of several pathways in cell-to-cell communication; their structural similarity among plant, fungal, and bacterial taxa suggests potential in cross-kingdom communication. We provide a prospect of the known role of fatty acids and oxylipins in fungi and bacteria during plant–pathogen interactions. In the pathogens, oxylipin-mediated signaling pathways are crucial both in development and host infection. Here, we report on case studies suggesting that oxylipins derived from oleic, linoleic, and linolenic acids are crucial in modulating the pathogenic lifestyle in the host plant. Intriguingly, overlapping (fungi-plant/bacteria-plant) results suggest that different inter-kingdom pathosystems use similar lipid signals to reshape the lifestyle of the contenders and occasionally determine the outcome of the challenge.

In 2013, Xylella fastidiosa (Xf) was detected for the first time in Apulia and, subsequently, recognized as the causal agent of the olive quick decline syndrome (OQDS). To contain the disease, the olive germplasm was evaluated for resistance to Xf, identifying cultivars with different susceptibility to the pathogen. Regarding this, the resistant cultivar Leccino has generally a lower bacterial titer compared with the susceptible cultivar Ogliarola salentina. Among biomolecules, lipids could have a pivotal role in the interaction of Xf with its host. In the grapevine Pierce’s disease, fatty acid molecules, the diffusible signaling factors (DSFs), act as regulators of Xf lifestyle and are crucial for its virulence. Other lipid compounds derived from fatty acid oxidation, namely, oxylipins, can affect, in vitro, biofilm formation in Xf subsp. pauca (Xfp) strain De Donno, that is, the strain causing OQDS. In this study, we combined high-performance liquid chromatography-mass spectrometry-MS-based targeted lipidomics with supervised learning algorithms (random forest, support vector machine, and neural networks) to classify olive tree samples from Salento. The dataset included samples from either OQDS-positive or OQDS-negative olive trees belonging either to cultivar Ogliarola salentina or Leccino treated or not with the zinc-copper-citric acid biocomplex Dentamet®. We built classifiers using the relative differences in lipid species able to discriminate olive tree samples, namely, (1) infected and non-infected, (2) belonging to different cultivars, and (3) treated or untreated with Dentamet®. Lipid entities emerging as predictors of the thesis are free fatty acids (C16:1, C18:1, C18:2, C18:3); the LOX-derived oxylipins 9- and 13-HPOD/TrE; the DOX-derived oxylipin 10-HPOME; and diacylglyceride DAG36:4(18:1/18:3).

Graphene Oxide has been proposed as a potential adjuvant to develop improved anti-TB treatment, thanks to its activity in entrapping mycobacteria in the extracellular compartment limiting their entry in macrophages. Indeed, when administered together with linezolid, Graphene Oxide significantly enhanced bacterial killing due to the increased production of Reactive Oxygen Species. In this work, we evaluated Graphene Oxide toxicity and its anti-mycobacterial activity on human peripheral blood mononuclear cells. Our data show that Graphene Oxide, different to what is observed in macrophages, does not support the clearance of Mycobacterium tuberculosis in human immune primary cells, probably due to the toxic effects of the nano-material on monocytes and CD4+ lymphocytes, which we measured by cytometry. These findings highlight the need to test GO and other carbon-based nanomaterials in relevant in vitro models to assess the cytotoxic activity while measuring antimicrobial potential.

Even though Everolimus has been investigated in a phase II randomized trial as a host-directed therapy (HDT) to treat tuberculosis (TB), an oncological patient treated with Everolimus for a neuroendocrine pancreatic neoplasia developed active TB twice and a non-tuberculous mycobacterial (NTM) infection in a year and a half time span. To investigate this interesting case, we isolated and genotypically characterized the Mycobacterium tuberculosis (Mtb) clinical strain from the patient and tested the effect of Everolimus on its viability in an axenic culture and in a peripheral blood mononuclear cell (PBMCs) infection model. To exclude strain-specific resistance, we tested the activity of Everolimus against Mtb strains of ancient and modern lineages. Furthermore, we investigated the Everolimus effect on ROS production and autophagy modulation during Mtb infection. Everolimus did not have a direct effect on mycobacteria viability and a negligible effect during Mtb infection in host cells, although it stimulated autophagy and ROS production. Despite being a biologically plausible HDT against TB, Everolimus does not exert a direct or indirect activity on Mtb. This case underlines the need for a careful approach to drug repurposing and implementation and the importance of pre-clinical experimental studies.