The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. Telomere length homeostasis is critical for cancer development then telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere’s dysfunction impinges on intracellular signalling pathways, in particular DNA damage signalling and repair affecting cancer cell survival and proliferation. This review summarizes and discusses about the recent findings in anti-cancer drug development targeting different “telosome” components.

We have studied the very large amount of literary works written by the Italian mystic Maria Valtorta to assess similarities and differences in her writings because she claims that most of them are due to mystical visions. We have used mathematical and statistical tools developed for specifically studying deep linguistic aspects of texts. The general trend indicates that the literary works explicitly attributable to Maria Valtorta differ significantly from her other literary works, that she claims are attributable to the alleged characters Jesus and Mary. Mathematically, they seem to have been written by different authors. The comparison with the Italian literature is very striking. A single author, namely Maria Valtorta, seems to be able to write texts so diverse to cover the entire mathematical range (suitable defined) of the Italian literature of seven centuries.

Background: Patients with allergic rhinitis (AR) have bothersome symptoms that may assess using the visual analog scale (VAS). Asthma frequently is associated with AR. The present study investigated the role of VAS in children with newly-diagnosed AR. Methods: Parameters were VAS for nasal and asthma symptoms, and doctor’s perception of these diseases, medication use, and asthma comorbidity. Results: 67% of AR children had asthma. Severity of perceived nasal symptoms was associated with more intense asthma symptoms and doctor’s perception of disease severity (p<0.001 and p=0.02, re-spectively. Conclusions: Allergic rhinitis frequently is associated with asthma in child-hood. Symptom perception assessment using VAS is a simple tool for assessing their intensity. Moreover, the severity of nasal symptoms is associated with asthma symptom severity. Therefore, asthma should be carefully considered in AR children and require appropriate symptom perception assessment.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

1) Background: Parents are increasingly fascinated by alternative weaning methods, such as ba-by-led or vegetarian weaning. However, international pediatric societies are still cautious to-wards alternative weaning methods, due to their significant risk of nutritional deficiencies. The aim of this study is to describe the attitude of Italian pediatricians towards unconventional weaning, with particular regard to vegetarian and baby-led. (2) Methods: A 20-question ques-tionnaire was sent to Italian pediatricians, from January to December 2019; (3) Results: Responses were received from 73/1000 (7.3%) pediatricians. The vast majority of surveyed pediatricians (78.1%) is familiar with baby-led and vegetarian weaning, but only 24.7% is in favor of their practice. A significant number of pediatricians (63.0%) received request from parents for an al-ternative weaning regimen. (4) Conclusions: The survey revealed a significant gap between pedi-atricians’ attitude and parental demand concerning unconventional weaning. This could signifi-cantly impair the alliance between parents and pediatricians with the risk to expose infants and children to severe nutritional deficiencies due to self-management by parents with poor surveil-lance from health professionals.

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined T cell subsets both before and after ex vivo anti CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 euthymic BD patients and 21 healthy controls as well as human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of baseline (unstimulated) CD3+CD8+CD71+ and CD4+CD25+FOXP3 and increased CD4+CD25+FOXP3+CD152+ frequencies and with lowered stimulated frequencies of CD3+CD8+CD71+, CD4+CD25+FOXP3+CD152+ and CD4+CD25+FOXP3+GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3+CD4+CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4+CD25+FOXP+GARP T phenotypes. In conclusion, BD is characterized by deficits in immune-regulatory functions while the staging of illness is characterized by additional impairments is Teff and Treg activation. HCMV seropositivity may contribute to an immune-risk phenotype associated with BD.

In multi-objective optimization problems, the optimization target is to obtain a set of non-dominated solutions. Comparing solution sets is crucial in evaluating the performances of different optimization algorithms. The use of performance indicators is common in comparing those sets and, subsequently, optimization algorithms. A good solution set must be close to the Pareto-optimal front, well-distributed, maximally extended and fully filled. Therefore, an effective performance indicator must encompass these features as a whole and must be Pareto dominance compliant. Unfortunately, some of the known indicators often fail to properly reflect the quality of a solution set or cost a lot to compute. This paper demonstrates that the Degree of Approximation (DOA) quality indicator, is a weakly Pareto compliant unary indicator that gives a good estimation of the match between the approximated front and the Pareto-optimal front. Moreover, DOA computation is easy and fast.

Vitamin D and ω-3 fatty acids (ω-3) co-supplementation potentially improve type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation.This cohort study preliminary to a randomized control trial (RCT) is aimed to evaluate, in a series of T1D children assuming Mediterranean diet and taking cholecalciferol 1000U/day fromT1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS).Therefore, 22 new onsets of 2017 received ω-3 [eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60mg/kg/day], and were compared retrospectively vs. 37 previous onsets without ω-3 supplementation. HbA1c%, daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/dayx4 + HbA1c%) as surrogate of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As outcome, decreased insulin demand (p<0.01), particularly pre-meal boluses (p<0.01), and IDAA1c (p<0.05), were found in the ω-3 group while HbA1c% were not different in the two groups. Diet analysis, at T12 vs. T0, showed that the intake of arachidonic acid (AA) was decreased (p<0.01) in the ω-3 supplemented group while other nutrients were unchanged; at T0, the AA intake was inversely correlated with HbA1c% (p<0.05; r;.0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation and AA reduction in Mediterranean diet display benefits for T1D children and deserve further investigation.

We studied the link between carbon and water fluxes to understand the response of net ecosystem carbon exchange (NEE) to water availability conditions of three different potato water regimes cropping systems [full irrigation (FI), deficit irrigation (DI) and rainfed (RF)]. Through the eddy covariance technique, we measured CO₂ and water vapor exchanges and determined surface resistances, omega factor, and inherent water use efficiency (IWUE). Additionally, continuous plant growth determinations of leaf area index (LAI) and specific leaf area (SLA) were made over the three cropping systems. The RF potato was a net carbon source (NEE = 187.21 ± 3.84 g C m⁻²), while both, FI (NEE= −311.96 ± 12.82 g C m⁻²) and DI (−17.3 ± 4.6 g C m⁻²) were a net carbon sink. Greater sink activity is due to high fluxes of gross primary productivity (GPP) [where the GPP > ecosystem respiration (R_eco)] and evapotranspiration (ET), and the high efficiency in the exchange of carbon and water. Without water limitations, the larger canopy, with greater photosynthetic activity (GPP/R_eco > 2) as well as with low internal resistance offers a greater area for water and carbon exchange, and the highly coupled and synchronized ET – GPP fluxes are primarily controlled by the radiative environment. The lower sink capacity of the DI potato crop and the carbon source activity from the RF, are consequences of a smaller area for water and carbon exchange due to the smaller canopy, and a low IWUE from decoupled and desynchronized carbon and water exchange caused by unbalanced restrictions on ET and GPP fluxes. Specifically, at DI potato, ET remained at a high rate, while GPP was reduced by means of non-stomatal limitations. In the rainfed potato, vapor pressure deficit (VPD) played a significant role increasing midday canopy resistance (Rc) up to 13 times compared to irrigated sites, when VPD was around 0.8 kPa. In consequence, ET and GPP fluxes decreased together, but GPP decreased more than ET because of stomatal and non-stomatal limitations.

The growing interest in the use of energy storage systems to improve the performance of tramways has prompted the development of control techniques and optimal storage devices, displacement, and sizing to obtain the maximum profit and reduce the total installation cost. Recently, the rapid diffusion of renewable energy generation from photovoltaic panels has also created a large interest in coupling renewable energy and storage units. This study analyzed the integration of a photovoltaic power plant, supercapacitor energy storage system, and railway power system. Random optimization was used to verify the feasibility of this integration in a real tramway electric system operating in the city of Naples, and the benefits and total cost of this integration were evaluated.

Background: Many clinical conditions are affected by meteorological factors and climate changes. Psychiatric disorders are large contributors to the global disease burden, but the literature on the impact of climate changes on mental health is limited. The aim of this study is to investigate the correlation between rising temperatures and admissions for acute exacerbations of psychiatric disorders. Methods: Data were collected for summer months of years 2013 to 2022. Mean monthly tempera-tures were obtained from the meteorological station of the Department of Physics of the Universi-ty of Turin. Data on patients admitted to the acute psychiatric unit of San Luigi Gonzaga Univer-sity Hospital (Turin, Italy) were extracted from the hospital registry. Linear regression analyses were used to investigate the correlation between temperature and number of admissions. Results: A total of 1600 admissions to our psychiatric ward were recorded. Mean monthly temper-ature and monthly number of admissions were directly correlated (P = 0.0020). The correlation between temperature and admissions was significant for the subgroup of admissions due to Bipo-lar Disorders (BD) (P=0.0011), but not for Schizophrenia (P=0.6070) (SCZ) or Major Depressive Disorder (MDD) (P=0.0588). Conclusions: These results confirm the impact of meteorological factors on mental disorders, and in particular on the course of BD. This provides new insights into etiopathological mechanisms and can contribute to improved follow up and relapse prevention.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

The current emergency due to the worldwide spread of the COVID-19 caused by the new SARS-CoV-2 is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness was not yet assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Background: Adiposity rebound (AR) refers to the second rise of the BMI curve that usually occurs physiologically between 5 and 7 years of age. AR timing has a great impact on children´s health, being the early adiposity rebound (EAR) associated with the development of metabolic disease later in life. Aim: We aimed to investigate the prevalence of EAR in a cohort of preterm newborns. Secondary outcomes evaluated if some determinants such as (1) gender (male/female), (2) type of delivery (caesarean/vaginal), (3) birth weight (SGA/NGA/LGA), (4) type of feeding (5) duration of breastfeeding, (6) timing of introduction of solid food, (7) parental education and (8) parental pre-pregnancy BMI can influence EAR in this cohort. Tertiary aim was to evaluate the prevalence of obesity or overweight at 7 years of age in children according to early versus timely AR. Methods: This is a perspective, population-based longitudinal study, where infants born preterm were evaluated at birth and at 1, 3, 6, 9, 12, 15, 18, 24 months and 3, 4, 5, 6, 7 years of gestational-corrected age. Weight and height data were analyzed, and BMI was calculated. AR was assessed in the growth trajectory in a body mass index (BMI) plot. Results: Of the 250 preterm newborns included, 100 completed the 7 years follow-up and entered in the final analysis. The prevalence of EAR in our cohort of preterm newborns was 54%. EAR was associated with being LGA at birth. No other factors were associated to EAR. Early adiposity rebounders have a significant higher BMI at 7 years compared to children with timely AR (17.2 ±2.7 vs 15.6 ± 2.05, p=0.021). No significant differences were found in the prevalence of obesity or overweight at 7 years of age in children with early or timely AR (29% vs 14% p=0.202). Conclusions: Clinical management of preterm infants should focus on reducing excess weight gain to prevent long-term metabolic risk. Others neonatal factors are not associated to an higher risk of EAR.

Background: Recent years have seen chaos in the neonatology use of antibiotics with diverse opinions and recommendations in international guidelines and societies. This has created great uncertainty in which cases to use, for how long, and which tests apply to make these decisions. We conducted a retrospective cohort study about the use of antibiotics in the EpicLatino neonatal units and a Latin American network database, after noting these variations in the 2019 report. Methods: For the year 2019 using the EpicLatino database, we included cases (only first admission) ≤32 weeks gestational age at birth, excluding one unit that did not accept to participate. The number of cases and days receiving antibiotics were recorded as well as the progression for each unit. Inappropriate use of antibiotics was defined as greater than 3 days in patients with negative cultures (blood/CSF cultures) excluding: major malformations, urinary tract infections, necrotizing enterocolitis (NEC) and cases with suspected chorioamnionitis in the mother (the latter two only during the course of diagnosis of NEC or chorioamnionitis). This study was approved by the EpicLatino board of directors and by the participating units. Results: A total of 6,543 days of antibiotics were observed, 49.5% of cases had at least one positive blood/CSF culture. A total of595 days of antibiotics without justification were found in 72 courses in 61 cases; 14/72(19.4%) had no diagnosis of infection in the database, 7/72(9.7%) did not document any culture throughout their stay, and 37/72(51,4%) obtained only one blood/CSF culture during their entire stay. Most diagnosis were clinical sepsis and in 24/58(41%) curses, a diagnosis of pneumonia with a poor positive culture correlation was found. Furthermore, 74% of the units didn´t use pneumonia as a justification to use antibiotics. Other diagnosis found: Conjunctivitis, NEC 1A and rotavirus NEC. Conclusions: Although the method of reviewing the use of antibiotics in a database has a number of limitations, especially the cause that motivated the use of antibiotics and other tools used for diagnosis of infections, the notable differences between units is striking. Although it is difficult to make recommendations to all units, it is important to control infections in some units and in others to reduce the excessive use of antibiotics, especially with diagnosis of pneumonia in neonates and negative blood/CSF cultures.

Xylella fastidiosa (Xf) is classified as a quarantine pest due to its consequences on economically significant crops. Its main form of transmission in Europe is through the insect Philaenus spumarius. Due to climate change, populations of insect vectors became more extensive, resulting in the dissemination of the bacteria through longer periods, but destruction of these insects raises issues, due to their role in nature. Upon infection, Xf causes the occlusion of xylem vessels by bacterial aggregates, and tylosis production by the plant as a response to infection. Although symptomatic manifestations of Xf are often linked to water stress, a variety of plant species have been found to carry the pathogen without symptoms, making it all too easy to evade detection when relying on visual inspections. Beyond water stress, other conditions (individual plant resistance/tolerance, bacterial concentrations, transpiration rates, and interactions between subspecies) may be implicated in symptom development. A thorough understanding of how this disease develops, especially its capacity to spread from the initial focus and establish a systemic infection, is imperative. This review focuses on the Xf infection process, the development of symptoms, its spread within Portugal, and the actions that have been taken to counter it.

Introduction The climate crisis is essentially a public health crisis. Response is imperative to prevent economic and social crises associated with the growing burden of climate impacts on human health and the health care sector. Green Podiatry Pillars By adopting the three pillars of Exercise, Evidence, and Everyday changes, podiatrists can contribute to more sustainable health and health care. Discussion Educating our patients to use their feet for low carbon active transport, eliminating interventions not supported by evidence, and reducing fossil fuel driven supply chains and energy use, are three impactful measures that all podiatrists, and indeed, all health and medical personnel, need to adopt. The avoidable suffering, enormous and costly use of resources for diabetic foot disease, is a scourge that must realise its preventable potential. It is too late, too costly, too polluting, and too sad, to continue to direct health care and research efforts and budgets, to an expensive modifiable diabetes disease process, potentiated by poor food and physical inactivity. Affected patients require skilled support, to avert such chronic disease processes, often not of their making. Conclusions Healthcare contributes 5 to 8% of green house gases (GHG), and non-communicable diseases (NCD) are increasing, so healthcare must lead on primary health. As citizens and health professionals, we must advocate for better community health, and educate our patients. Future Directions All health and medical personnel need to consider planetary health and sustainable healthcare within their daily work. Healthcare must act to address climate change, and realise benefits for people and planet.

Cancer immunotherapies are gaining a large popularity and many of them have been approved as standard second-line or in some cases even as first-line treatment for a wide range of cancers. However, immunotherapy has not shown a clinically relevant success in glioblastoma (GBM), principally due to the brain’s “immune-privileged” status and the peculiar tumor microenvironment (TME) of GBM featured by lack of presence of tumor-infiltrating lymphocytes and the establishment of immunosuppressive mechanisms. Emerging evidence has highlighted the key role played by innate immune cells in immunosurveillance and in initiating and driving immune responses against GBM. Immunogenic cell death (ICD) is a promising approach to elicit direct activation of the innate immune system by inducing in target cancer cells the expression of molecular signatures recognized through a repertoire of innate immune cell pattern recognition receptors (PRRs) by effector innate immune cells. Herein, we explored local mild thermal treatment, generated by using ultrasmall (size ~ 17 nm) cubic-shaped iron oxide nanoparticles exposed to an external alternating magnetic field (AMF), to induce ICD in U87 glioblastoma cells. In accordance with what has been previously observed with other types of tumors, we found that mild hyperthermia modulates the immunological profile of U87 glioblastoma cells by inducing stress-associated signals leading to enhanced phagocytosis and killing of U87 cells by macrophages. Finally, we demonstrated that mild magnetic hyperthermia has a modulatory effect on the expression of inhibitory and activating NK cell ligands on target cells. Interestingly, alteration in the expression of NK ligands, caused by mild hyperthermia treatment, in U87 glioblastoma cells, increased their susceptibility to NK cell killing and NK cell functionality. The overall findings demonstrate that mild magnetic hyperthermia stimulates ICD and sensitizes GBM cells to NK-mediated killing by inducing the upregulation of specific stress ligands, providing a novel immunotherapeutic approach for GBM treatment, with potential to synergize with existing NK cell-based therapies thus improving their therapeutic outcomes.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of is-chemic stroke secondary to large-artery atherosclerosis. At the macroscopic evaluation, vulnera-ble plaques are characterized by one or more of the following features: microcalcification, neo-vascularization, lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), thin fibrous caps, plaque surface ulceration, huge dimension determining stenosis, and plaque rupture. Recognizing these macroscopic characteristics is crucial to estimating the risk of cerebrovascular events, also in case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that will be scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talking govern-ing plaque inflammation, rupture potential, and thrombogenicity. Current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with as many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehen-sive analysis of current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional at-tributes that characterize vulnerable plaques

Background: Online teaching has resulted in university students adopting a sedentary lifestyle. Prolonged sitting and reduced physical activity due to pandemic restrictions have led to musculoskeletal pain in various body areas, significantly impacting the students’ quality of life. This study aims to investigate the effects of remote learning on Sicilian physiotherapy students during the COVID-19 pandemic, specifically focusing on the occurrence of musculoskeletal pain. Methods: An observational study was conducted using an online survey administered through Google Forms. The survey consisted of 26 multiple-choice questions and was distributed to students enrolled in Physiotherapy programs at the Universities of Catania, Messina, and Palermo. Participants were contacted via social channels or email, and data collection spanned 5 weeks. The collected data were analyzed using R software. Results: A total of 128 questionnaires were collected. More than half of the students (51.6%) reported dedicating 15–22 h per week to distance learning for a duration of 6–12 months (50%). Regarding study location, most students preferred studying at a desk (82.8%), with slightly over half (57.8%) adopting a backrest while studying remotely. Analysis of the students’ posture during study hours revealed common positions, including tilting the head forward by more than 20 degrees (47.8%), leaning the trunk forward by more than 20 degrees (71.9%), both shoulders being hunched forward (57.0%), wrists positioned above the level of the elbows (46.1%), thighs pointing upwards (41.4%), and one or both feet in a downward or dorsiflexed position (69.5%). Conclusion: The questionnaire responses indicate that the lifestyle of university students, influenced by online teaching, has deteriorated, leading to musculoskeletal pain, including myofascial pain. These results are primarily influenced by the adopted posture and the duration of time spent in these positions.

Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections with the pathophysiology of each disease. Untargeted urine metabolomic profiles of 21 patients (7 MMA, 7 PA, 7 cblC) were identified through statistical analysis (p&lt;0.05; log2FC &gt;|1|) and then used for the annotation. Annotated features were associated with different metabolic pathways potentially involved in the diseases development. Comparative statistic showed markedly different metabolomic profiles between MMA, PA and cblC, highlighting characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (MMA, PA, cblC), amino acids (MMA, PA, cblC), glycine and its conjugates (PA), transsulfuration pathway (cblC), oxidative processes (cblC) and neurosteroid hormones (cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast of cblC profile compared to MMA and PA. Some new biomarkers are proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.

Background: This article evaluates the perception of drug use control and strategies in Valencia City (Spain) in a general and clinical population, in two independent studies. Material and Methods: 1071 people participated. In the Study 1 (n= 924) the entire sample came from general population (GP), and in the Study 2 (n=147), 68 were drug users being treated in an Addictive Behaviors Unit (ABU), and 79 people of the GP. The drug use control perception and strategies in both subgroups were compared. The participants filled in the Drug Use Strategies Scale and a Drug Use Survey. Results: A high level of perception of drug control in GP was obtained (72,7% in the Study 1 and 67,5% in the Study 2), and 32.5% in ABU subgroup. People in the PG and drug users in treatment differ in some control strategies. A predictive profile of the perception of control was obtained for the Study 2. Conclusion: The high degree of perception of controlling drug use in the GP, and partially in drug users being treated, and the specific control strategies reported suggests that moderate use and drug control strategies are a great value alternative to bear in mind compared to abstinence.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

The paper first compares the turn-off performance of two package solutions (3-lead vs 4-lead) in Super-Junction MOSFETs. It is commonly assumed that the better performance (lower switching losses) of the 4-lead is obtained thanks to the decoupling of the power and driving loop. On the contrary, in this work, the experimental results, circuit models, and Kirchhoff laws have shown that the turn-off improvement (lower turn-off losses) obtained by adopting the Kelvin source is due to the lower inductance of the driver loop in comparison with the power loop inductance, instead of the decoupling between these loops.

Long Covid is a debilitating condition that has been well-documented over the past 4 years and shares many similarities with other post-viral chronic illnesses. Despite this, clinicians are not confident in recognising the signs of Long Covid, or effectively managing the symptoms of their patients. This paper presents a single patient case report from a biomedical researcher who has had Long Covid for 2 years; it is written in relatively plain language to be accessible to both patients and clinicians across multiple specialities. The author has had the ability and expertise to keep up with the Long Covid research literature, and from that has cobbled together a management strategy that has alleviated her own symptoms, and those of other people with whom she has shared her protocol. The author’s experience of developing and managing her Long Covid is presented here, in the hopes that it may be of assistance to clinicians in identifying and managing Long Covid in their own patients.

Introduction: In general, everyone believes that the smallest preterm infants should achieve normal intrauterine growth rates, but many thinks that this is not possible with current nutrition guidelines. There is resistance to giving enough nutrition for fear of "toxicity". The difference in weight Z-score between birth and a corrected gestational age (CGA) at discharge is assess in postnatal growth in our unit. Material and methods: An observational study was done between January 2018 and December 2020 where all cases that had ≤ 29 weeks of GA at birth and survived to 36 weeks corrected GA or that were discharged home. An aggressive nutrition protocol including parenteral as well as enteral nutrition was followed. Patients and their weight trajectory was plotted on the Fenton 2013 growth curve. The patients who had had a smaller WZP difference were also plotted. Results: A total of 32 cases were found. The median change in Z-score between birth and discharge of the whole group was -0.52 (IQR 0.53). Six of 32 (19%) had a more than one WZP, all of whom had severe pathologies. The median decline in Z score for this group with poor growth was 1.24 (IQR 0.22). There were 26 cases with a < 1 WZP (81%) and a median Z score fall of 0.39 (IQR 0.55). No important complications secondary to the ingested volumes or parenteral nutrition were reported. Conclusion: The group of cases with a > 1 WZP drop had severe pathologies. All the other cases had adequate growth parallel to normal weight growth charts and a few cases had some catch-up growth. The study showed that it is possible for many preterm infants to achieve normal intrauterine growth rates if they are given enough nutrition, but bigger multicenter studies are needed to confirm these findings.

Cratylia argentea is a leguminous shrub with a great potential for livestock feeding in tropical areas. However, time consuming and labor-intensive methods of chemical analysis limits the understanding of its nutritive value. Near infrared spectroscopy (NIRS) is a low-cost technology that has been widely used in forage crops to fasten the assessment of its chemical composition. The objective of this study was to develop prediction models to assess crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and dry matter (DM) of Cratylia based on NIRS and partial least square analysis. A total of 155 samples were harvested at different maturity levels and used for model development, whereas 107 were used for calibration and 48 for external validation. The cross-validation presented Root Mean Square Error of Prediction of 0.77, 2.56, 3.43, and 0.42; a Ratio of Performance to Deviation of 4.8, 4.0, 3.8, and 3.4; an R2 of 0.92, 0.92, 0.87, and 0.84 for CP, NDF, ADF, and DM, respectively. Based on the obtained results, we conclude the ability to predict chemical parameters of Cratylia with the current model was accurate. This way, livestock producers and researchers may use it to fasten the assessment of Cratylia’s nutritive value.

The period of study in the online environment can be a very demanding trial for students and masters, especially for those who are not familiar with computer technology. This is largely due to a complex of factors that come from the changes to which they are subjected, such as: leaving the parental home and settling into another living environment (living in dormitories or other forms of accommodation) but also settling with an unfamiliar and very different educational environment from what they were familiar with. Along with all the changes occurring in the family and social plan, the students had to adapt to the educational system made exclusively online. Higher educa-tion institutions in Romania use, as a method of knowledge transmission, traditional learning methods, namely they use face-to-face lecture-type courses in a lecture hall or practical and ex-planatory activities in a seminar/laboratory room. The emergence of this pandemic forced higher education institutions to switch to an online teaching mode for all types of activities included in the educational process.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect in stabilizing symptoms. In silico and preclinical studies identified ONC201, as a cytotoxic agent against some human cancer cell lines, including DIPG ones. Single crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed to identify hClpP as its main target. Hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients, receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of β -carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based Virtual Screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline.

Objective: to evaluate the effects of excitatory repetitive transcranial magnetic stimulation (rTMS) of the international 10-20 system P3 point (intraparietal sulcus region) in chronic patients with a frontal lesion and parietal sparing due to stroke on the impaired upper (UL) and lower limb (LL) as measured by Fugl-Meyer Assessment (FMA). Methods: three patients (C1: 49.83/2.75, C2: 53.17/3.83, C3: 63.33/3.08 years-old at stroke/ years post-stroke, respectively) received two weeks (five days/ week) of rTMS at 10 Hz of P3. A patient was treated in similar conditions with a sham coil (S1: 56.58/4.33). No complimentary therapy was delivered during the study. Patients were evaluated before, after- and two months post-treatment (A1, A2 and A3, respectively). Results: we found increased scores for LL in motor function subsection for C1 and C3 and in sensory function for C2 by A2 that remained at A3. We also found an increased score for UL motor function for C2 and C3, but the score decreased by A3 for C2. C3 score for UL range of motion increased by A3 compared to A1 and A2. Conclusion: In a variable way, P3 excitatory rTMS increased FMA scores in different upper and lower limb subsections of our three treated patients.

Alphaherpesviruses cause genital lesions and reproductive failure in both humans and animals. Their control is mainly based on prevention by hygienic prophylactic measures, due to the ab-sence of vaccines and limitations of antiviral drug therapy. Ozone is an oxidating gas showing a strong microbicidal activity on bacteria, fungi, viruses, and protozoa. The present study assessed the in vitro virucidal and antiviral activity of ozone against Caprine herpesvirus type 1. Virucidal activity of a gaseous mixture containing O3 at 20 and 50 μg /mL was assessed against the virus for different contact times (30 s, 60s, 90s, 120s, 180s and 300s). Antiviral activity of a gaseous mix-ture containing O3 at 20 and 50 μg /mL was evaluated against the virus to for 30s and 60s. Ozone displayed significant virucidal activity when used at all the tested concentrations whilst signifi-cant antiviral activity was observed using ozone at 50 μg/ml. The gaseous mixture, tested in the present study, showed virucidal and antiviral activity against CpHV-1 with a dose- and a time-contact -dependent fashion. Ozone therapy could be evaluated in vivo for the treatment of CpHV-1-induced genital lesions in goats, through topical applications.

Urban planning is recognized as an interaction between the state and society, which aims to articulate public policies in the territory, facilitating their administration in favor of greater development and well-being of society. However, this interaction becomes complex because consumption demands increase, and the needs of the community exceed the capacity of the urban ecosystem to supply them, hindering its sustainable functionality. With this panorama, it becomes relevant to study urban planning from a sustainable environmental planning perspective, based on four topics: urban planning, sustainability, resilience and smart cities. The methodology used is based on a bibliometric study through a PRISMA adjustment to 87 articles, supported by VOSviewer® to construct and visualize the co-occurrence networks of important terms extracted from a body of scientific literature. The main result is to consider cities with a complex systems approach that works like a gear, that is, there is a connective element between inter- and intra-urban processes. This relationship is the key factor that allows understanding their synchronization, stating that the deepening of each of these topics is crucial to the ideal of a territorial administration through time scales, by means of adaptive cycles, allowing to provide new tools to concepts such as carrying capacity and the measurement of the environmental footprint.

The meridian line is a basic instrument for positional astronomy, it was used to study the motion of Sun, Moon, planets and the position of stars by measuring position and time of their passage through the meridian plane. The accuracy of such positions was dependent on precise theories of the atmospheric refraction (Cassini, 1655 and Laplace, 1825) and by the use of reference marks present originally on the meridian line, and now cancelled by the centuries. From October 27, 2018 the new pinhole of the meridian line in the Basilica of S. Maria degli Angeli in Rome (1702) is a circle 25 mm wide and 6.11 mm thick and its position is fixed, in order to perform a series of observations of astrometric quality, the IGEA campaign. The comparison of the observed positions of the meridian passages of the Sun, Southern and Northern limbs, with the ephemerides of Calsky.org and Stellarium 0.20.2 for the Sun are examined for the dates of the ingresses into the zodiacal signs, when the ecliptic longitude is exactly 0°/180° (Aries and Libra, spring and fall equinox), 30°/150° (Taurus, Virgo), 60°/120° (Gemini, Leo), 90° (Cancer), 330°/210° (Pisces, Scorpio), 300°/240° (Aquarius/Sagittarius), 270° (Capricorn). The former geometrical calibration of the marks present on the line, with a total station, is compared with another calibration done with a metal and laser meter. The first star on the floor of the Basilica representing the position of the Sun on August 20, 1702 when the pope Clement XI visited the meridian line, financed by him, has been calibrated with the solar image. The present pinhole is 4.4±0.1 mm South with respect to the original one of 1702.

We present a numerical calculation of the heat transport in a Bragg mirror configuration made of materials that do not obey Fourier's law of heat conduction. The Bragg mirror is made of materials that are described by the Cattaneo-Vernotte equation. By analyzing the Cattaneo-Vernotte equation's solutions, we define the thermal wave surface impedance to design highly reflective thermal Bragg mirrors. Even for mirrors with a few layers, very high reflectance is achieved ($>90\%$). The Bragg mirror configuration is also a system that makes evident the wave-like nature of the solution of the Cattaneo-Vernotte equation by showing frequency pass-bands that are absent if the materials obey the usual Fourier's law.

Stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V exhibit properties for bio-medical applications; however their tribocorrosion associated with metallosis is still a major concern. Therefore smoothing DLC coatings aiming for the improvement of tri-bocorrosion and cell viability of stainless steel 316L (SS316L) and titanium-alloy Ti6AL4V with and without DLC coatings were compared. The motivation was due to many papers detailing metallosis caused by metal debris in the body's soft tissues. Nowadays, metallosis is responsible for almost of prosthesis replacement surgeries. DLC coatings were produced using the Plasma Enhanced Chemical Vapor Deposition (PECVD) technique; acetylene gas was used as a carbon precursor, and silane gas produced an amorphous silicon interface between the DLC coating and metal substrate. A combined setup of techniques thoroughly evaluated the coatings considering chemical composition, coatings adhesion at a metallic substrate, scratch resistance, and tribocorrosion susceptibility. The cytotoxicity and genotoxicity of metallic samples with and without DLC coatings were analyzed, considering cell viability and its correlation with coatings’ chemical composition

In the modern era of genomic research, the scientific community is witnessing an explosive growth in the volume of published findings. While this abundance of data offers invaluable insights, it also places a pressing responsibility on genetic professionals and researchers to stay informed about the latest findings and their clinical significance. Genomic variant interpretation is currently facing a challenge in identifying the most up-to-date and relevant scientific papers, while also extracting meaningful information to accelerate the process from clinical assessment to reporting. Computer-aided literature search and summarization can play a pivotal role in this context. By synthesizing complex genomic findings into concise, interpretable summaries, this approach facilitates the translation of extensive genomic datasets into clinically relevant insights. To bridge this gap, we present VarChat (varchat.engenome.com), an innovative tool based on generative AI, developed to find and summarize the fragmented scientific literature associated with genomic variants into brief yet informative texts.VarChat provides users with a concise description of specific genetic variants, detailing their impact on related proteins and possible effects on human health. Additionally, VarChat offers direct links to related scientific trustable sources, and encourages deeper research. Availability: VarChat is freely available at varchat.engenome.com

Objective. It is unknown whether the public accurately estimate socioeconomic health inequality and whether they wish to see it reduced or eliminated. Methods. Representative samples of the UK and US indicated the perceived and ideal lifespan of people working in “higher managerial/professional” and “routine” occupations. We present perceived and desired lifespan ratios for each sample and for key socio-demographic variables. Results. The UK public estimated the lifespan of professionals to be 5.9% longer than routine workers (true value of 5.8%), and 67.8% (UK) and 53.7% (US) participants correctly identified that professionals live longer than routine workers. In both populations, the median respondent expressed equal ideal lifespans for routine workers and professional workers. Conclusion. The UK public appear well-appraised on the average lifespan for professionals and routine workers. Across nationalities and most socio-demographic groups, the median respondent was aware of social class inequalities in lifespan and preferred that they be eliminated.

Rabies, caused by the rabies virus (RABV), remains a significant public health issue in the Philippines despite efforts to control it. To eliminate rabies by 2030, effective surveillance strategies are crucial. In this study, we examined RABV evolution and phylodynamics in the Davao Region using genome sequences from Davao City and nearby provinces. We adapted the RABV ARTIC Protocol for Oxford Nanopore High-Throughput Sequencing to optimize workflow efficiency under limited resources. Comparing new virus samples collected from June 2019 to June 2021 (n=38) with baseline samples from June 2018 to May 2019 (n=49), new sub-clades were observed in the phylogenetic tree, suggesting divergence from older variants that were previously undetected. Most of the new viruses belonged to the Asian SEA4_A1.1.1 lineage, but new (SEA4_B1 and SEA4_B1.1) and emerging (SEA4_B1.1_E1) lineages that have never been reported in the Philippines were also identified. The baseline study reported phylogeographic clustering of RABV isolates from the same areas. However, this pattern was disrupted in the current biosurveillance, with variants detected in areas outside the original cluster. Furthermore, our findings revealed significant transmission routes between Davao City and neighboring provinces, contrasting with the predominantly intra-city transmission observed in the baseline study. These results underscore the need for ongoing and timely genomic surveillance to monitor genetic diversity changes and the emergence of novel strains, as well as to track alterations in transmission pathways. Implementing cost-effective next generation sequencing workflows will facilitate the integration of genomic surveillance into rabies control programs, particularly in resource-limited settings. Collaborations between different sectors can empower local laboratories and experts in genomic technologies and analysis.

The purpose of this study was to evaluate the morpho-functional change of the patellar ligament in dogs affected by cranial cruciate ligament rupture. The hypothesis is that it may show increased thickening and stiffness with increasing days from trauma to diagnosis. Understanding this aspect have implications on the choice of timing to treat patients suffering from cranial cruciate ligament rupture, and also in the contextualization of patellar ligament desmitis pictures after surgical treatment with tibial plateau levelling osteotomy or tibial tuberosity advanced. Thirty-three dogs were affected affected by unilateral cranial cruciate rupture were examined and divided into three groups based on the time elapsed from the onset of lameness to diagnosis: Group 1 (from 1 to 15 days), Group 2 (from 16 to 60 days), Group 3 (over 60 days). Conventional B-mode ultrasonographic and elastosonographic examinations of patellar ligament were performed without sedation for each dog. At the ultrasonographic examination, all dogs showed alterations in the echostructure of the patellar ligament. In addition, the patellar ligament tended to become harder and less soft with increasing days after rupture, although there were not significant differences between groups. Our results showed that as time increases between the onset of cranial cruciate ligament rupture and diagnosis and treatment, the patellar ligament progressively thickens and loses its elasticity.

The search for molecular biosignatures at the surface of Mars is complicated by an intense irradiation in the mid- and near- ultraviolet (UV) spectral range for several reasons: (i) many astrobiologically relevant molecules are electronically excited by efficient absorption of UV radiation and rapidly undergo photochemical reactions; (ii) even though the penetration depth of UV radiation is limited, aeolian erosion continually exposes fresh material to radiation; and (iii) UV irradiation generates strong oxidants such as perchlorates that can penetrate deep into soils and cause subsurface oxidative degradation of organics.As a consequence, it is crucial to investigate the effects of UV radiation on organic molecules embedded in mineral matrices mimicking the martian soil, in order to validate hypotheses about the nature of the organic compounds detected so far at the surface of Mars by the Curiosity rover, as well as organics that will be possibly found by the next rover missions Mars 2020 and ExoMars 2020. In addition, studying the alteration of possible molecular biosignatures in the martian environment will help to redefine the molecular targets for life detection missions and devise suitable detection methods.Here we report the results of mid-UV irradiation experiments of Mars soil analog samples obtained adsorbing relevant organic molecules on a clay mineral that is quite common on Mars, i.e. montmorillonite, doped with 1 wt% of magnesium perchlorate. Specifically, we chose to investigate the photostability of a plausible precursor of the chlorohydrocarbons detected on Mars by the Curiosity rover, namely phthalic acid, along with the biomarkers of extant life L-phenylalanine and L-glutamic acid, which are proteomic amino acids, and adenosine 5’-monophosphate, which is a nucleic acid component.We monitored the degradation of these molecules adsorbed on montmorillonite through in situ spectroscopic analysis, investigating the reflectance properties of the samples in the Near InfraRed (NIR) spectral region. Such spectroscopic characterization of molecular alteration products provides support for two upcoming robotic missions to Mars that will employ NIR spectroscopy to look for molecular biosignatures, through the instruments SuperCam on board Mars 2020, ISEM, Ma_Miss and MicrOmega on board ExoMars 2020.

During summer 2016 in the District of Palermo, Italy, the rapid succession of four cases of invasive meningococcal disease among young adults, with one death, have had an extraordinary emphasis by Local and National mass media. The resultant “epidemic of panic” among general population overloaded vaccination Units of the Palermo District during following months. Strategies implemented by Sicilian and Local Public Health Authorities to counteract “meningitis fear” were: a) extension of active and free of charge anti-meningococcal tetravalent vaccination from age class 12–18 to 12–30 years old; b) implementation of vaccination units usual opening hours and rooms tailored for vaccine administration; c) development of informative institutional tools and timely communications throughout local mass media to reassure general population. In 2016, was observed an increase of anti-meningococcal coverage in Palermo District (+18% for 16th y.o. and + 14% for 18th y.o. cohorts) and at Regional Level (+11.2% and +13.5% respectively). Concurrent catch-up of other recommended vaccination for age (diphtheria-tetanus-pertussis-poliomyelitis and papillomavirus), resulted in further increase of doses administered. The fear for meningitis, managed by Sicilian Public Health Authorities, had positive reverberations in terms of prevention. In particular, informative strategies adopted sensibly contributed to get Sicilian young adults closer to vaccination issues.

The use of antibiotics in neonatal units worldwide varies significantly. We included data from 2015-2022 from the EpicLatino database, which comprises a network of 32 units in Latin America and the Caribbean with gestational age at birth (GA) of ≤ 32 weeks. A questionnaire was sent to the EpicLatino units, to correlate practice with outcomes. Negative binomial regression with standard errors and confidence intervals computed for incidence-rate ratios (IRRs) was used for comparative statistics on antibiotic days per 1000 patient-days between units. All units that responded had 1-6 differences with the reference unit (Unit 2) with the best results, but there was no clear association with the IRR. Each EpicLatino unit should review its statistics to explore possibilities for reducing antibiotic usage.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature data concerning the immunogenicity of breast cancer have been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune re-sponse in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ sub-types where increased TIL levels have been linked to better response to neoadjuvant chemotherapy and with improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10–30% of cases and is extremely variable based on tumor stage and molecular subtypes . In detail, TNBC shows the highest percentages of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points and scoring systems have been utilized across published studies. In the present paper an extensive review on the current knowledge of immune landscape of BC is provided. In detail TILS and PD-L1 expression across different BC subtypes is discussed also providing a guide for their pathological assessment and reporting.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

: In our previous work we had developed an hxt-null Saccharomyces cerevisiae strain displaying high xylose reductase, xylitol dehydrogenase and xylulokinase activities that proved to be useful as a chassis strain to study new xylose transporters, as SsXUT1 from Scheffersomyces stipitis. Spathaspora passalidarum and Spathaspora arborariae have in their genomes genes with high sequence similarity (78-80%) to SsXUT1. To characterize these putative transporter genes (SpXUT1 and SaXUT1, respectively) they were expressed in the same chassis strain as SsXUT1. Surprisingly, the cloned genes could not restore the ability to grow in several monosaccharides tested, although the strains expressing the SsXUT1 and SpXUT1 permeases, after growth on maltose, showed the presence of 14C-glucose and 14C-xylose transport activity. An important feature of these permeases is that SsXUT1 lacks lysine residues in its N-terminal domain with high-confidence ubiquitinylation potential, and has only one at the C-terminal domain, while the SpXUT1 transporter had several of such residues at its C-terminal domain. When the SpXUT1 gene was cloned in a truncated version lacking such lysine residues, the permease allowed grow on glucose or xylose, and even promoted xylose fermentation by the hxt-null strain. In another approach, we deleted two arrestins known to be involved in sugar transporter ubiquitinylation and endocytosis (ROD1 and ROG3), but only the rog3Δ strain allowed modest growth on these sugars. Taken together, these results suggest that to allow efficient sugar transporter expression in S. cerevisiae the lysines involved in transporter endocytosis should be removed from the sequence of the permease.

Biogenic-Silver nanoparticles emerge as new nanosilver platfmorm that allow to obtain silver nanoparticles via “green chemistry”. In our study we obtained biogenic-Silver nanoparticles from Iris tuberosa leaves extract. Nanoparticles were characterized by UV-vis spectroscopy, dinnamical light scattering technique and Transmission electron microscope, showing spheric and irregular nanoparticles with 5 to 50 nm in diameter. Antioxidant and antimicrobial properties were evaluated against typical microbial contaminants found in cosmetic products, showing high antioxidant and antimicrobial properties. We formulated a natural moisturizing cream with biogenic-silver nanoparticles to evaluate the preservative efficiency trought challenge test, confirming that our nanoparticles are a promising alternative to use as cosmetic preservative.

Background There is increasing awareness of problems associated with global warming but a lack of a systematic approach on how to deliver more environmentally sustainable dental care. A sustainable world aims to ensure that basic needs and quality of life of everyone are met, now and for future generations. The carbon footprint is an indicator of environmental sustainability. Aim The aim is to suggest an environmental management change for the dental practice focusing on the objective of carbon footprint reduction. Environmental management change design The management change is based on the concept of “Plan-Do-Check-Act”, as recommended by the International Organisation for Standardisation (ISO) and described through the environmental aspects of the dental practice. The approach focuses on establishing and implementing environmental objectives, followed by monitoring results and taking actions to improve continually. The environmental aspects considered for the dental practice are activities causing an impact on the carbon footprint: energy use, travel, product purchasing, waste production, emission to air, water use, and contamination of land. Conclusions The “Plan-Do-Check-Act” ISO 14100-2015 model can be effectively integrated into the dental practice setting for its environmental management. A reduction of the carbon footprint of the dental practice is achieved by applying the environmental management change described for each activity.

Significant efforts in the past decades to teach evidence-based practice (EBP) implementation has emphasized increasing knowledge of EBP and developing interventions to support adoption to practice. These efforts have resulted in only limited sustained improvements in the daily use of evidence-based interventions in clinical practice in most health professions. Many new interven-tions with limited evidence of effectiveness are readily adopted each year - indicating openness to change is not the problem. The selection of an intervention is the outcome of an elaborate and complex cognitive process which is shaped by how they represent the problem in their mind and is mostly invisible processes to others. Therefore, the complex thinking process which support appropriate adoption of interventions should be taught more explicitly. Making the process visible to clinicians increases the acquisition of the skills required to judiciously select one in-tervention over others. The purpose of this paper is to provide a review of the selection process and the critical analysis that is required to appropriately decide to trial or not trial new intervention strategies with patients.

Semi-arid Namibia is marginal for agricultural production. Low soil fertility combined with low and variable rainfall restrict the livelihoods of smallholder farmers who often struggle to produce enough food. Although historically communities have adopted a number of coping mechanisms, climate change threatens to further reduce agricultural production. There are many additional options available to smallholder farmers to adapt to climate change, but they are not necessarily adopting these measures despite having noticed increasing temperatures and declining rainfall. Semi-structured interviews were conducted in three villages in Onesi constituency to examine what agricultural practices smallholder crop farmers use, perception of changes in their yields, their perspective on future yields and whether they are planning on changing their agricultural practices. The results suggest that to sustain the livelihoods of rural communities in north-central Namibia support is needed from local and regional authorities, as well as traditional and religious leaders to assist with enhancing access to information, enabling information sharing on adaptation options, and increasing awareness on climate change, it’s impacts and what can be done about it. In addition to this the implementation of adaptation action also requires demonstration sites and building capacity to enable the development of self-help groups.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Exploring the contribution of proximal family risk factors on SLC6A4 DNA methylation in children with a history of maltreatment

In the area of dental healthcare services, where patients and professionals deal with multiple auditory stimuli, this cross-sectional study reports on the intricate dynamics of sound preferences, noise obstacles, and the profound impact of music on anxiety reduction within dental office set-tings. The sample comprises of 134 dental patients, primarily females (56.7%), with varying age groups, education levels, and therapy durations in the university clinics of the department of Dentistry, National and Kapodistrian University of Athens and four private dental offices at the metropolitan area of Athens, Greece. Notably, 92.5% of the participants report no hearing loss, and 56.7% exhibit some level of noise sensitivity. The study reveals a moderate to good perceived health status (M=3.84, SD=0.95) among participants, with low perceived noise disturbance in university dental clinics. Preferences for instrumental music, foreign pop, and classical music are prominent during waiting times. Potential irritations include impersonal treatment (44%) and staff behavior (41.8%). Music player usage within the settings of the dental clinic involves radios (49.3%) and headphones (41.0%). Correlations and predictors indicate associations between health status, music preferences, and noise disturbances. More specifically, visiting the university dental clinics (β = .300, p = .005) as well as younger age (β = .300, p = .034) were significant predictors of better perceived health status. Clearer perception of external sounds while using the music player (β = .190, p = .039) was a significant predictor of better perceived health status, while poorer health was predicted by the preference of Greek folk songs (β = -.200, p = .030). Also, the use of smartphones for playing music was related to poorer health (β = -.370, p < .001). Following, younger age (β = -.270, p = .015), lower education (β = -.210, p = .035), higher noise sensitivity (β = .190, p = .027), as well as feelings of anxiety and nervousness due to ambient noise from people and machines (β = .510, p = .027) were significant predictors of noise disturbance from machines. Also, visiting private clinics (β = .240, p = .018), preferences of specific playlist (β = .310, p = .012), no music (β = .280, p = .016) and use of smartphones to play music (β = .230, p = .029) were significant predictors of noise disturbance from patients or staff. Finally, the preference of listening to a specific playlist was related to better health status (r = .190, p < .05). Findings aim to optimize eco-soundscapes in dental offices, con-tributing to enhanced patient well-being. The research underscores the potential of music inter-ventions to alleviate dental anxiety and improve the overall dental experience and quality care.

A newly synthesized upper rim azocalix[4]arene, namely, 5,11,17,23-tetra[(4-ethylacetoxyphenyl) (azo)]calix[4]arene, CA-AZ was fully characterized and its chromogenic and selective properties for anions are reported. The receptor is selective for the fluoride anion and its mode of interaction in solution is discussed. The kinetics of the complexation process was found to be very fast as reflected in the immediate color change observed with a naked eye resulting from the receptor-anion interaction. Emphasis is made about the relevance in selecting a solvent in which the formulation of the process is representative of the events taking place in the solution. The composition of the fluoride complex investigated by UV/VIS spectrophotometry, conductance measurements and titration calorimetry was 1:1 and the thermodynamics of complexation was determined. The fluoride complex salt was isolated, and a detailed investigation was carried out to assess its ability to remove CO₂ from the air. Recycling of the complex was easily achieved. Final conclusions are given.

Several lime mortars for the repair of painted plasters of the rock cut church of Ss. Pietro and Paolo in Matera were studied. They were designed taking into account both aesthetic criteria that need to be fulfilled in the field of paintings restoration, and physical-mechanical compatibility with the original materials on site, i.e. the pre-existing plasters and the supporting rock. Mixes with calcareous and silica aggregates, based on different grain size proportions, were prepared for filling missing portions of the original painted plaster. The effects of the mineralogical nature and size of the aggregates on the characteristics and properties of the mixes were investigated in relation to the microstructure, physical-mechanical features and resistance to salt ageing. At the end of the experimental campaign, the overall performances were evaluated.

The molecular mechanisms underlying heat stress tolerance in animals to high temperatures remain unclear. This experiment was performed with Sprague-Dawley rats housed at 22 ℃ (control group; CT), and 42 ℃ for 30 min (H30), 60 min (H60), and 120 min (H120). Transcriptomic analysis using RNA-Sequencing (RNA-Seq) from blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120) was performed. The differentially expressed mRNA isoforms (DEIs) were identified and annotated by the CLC Genomics Workbench. Biological process and metabolic pathway analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A total of 225, 5,764, and 4,988 DEIs in the blood, liver, and adrenal glands were observed. Furthermore, the number of novel differentially expressed transcript lengths with annotated genes and the novel differentially expressed transcript with non-annotated genes were 136 and 8 in blood, 3,549 and 120 in the liver, as well as 3,078 and 220 in adrenal glands, respectively. A total of 35 genes were involved in the heat stress response, out of which Dnaja1, LOC680121, Chordc1, AABR07011951.1, Hsp90aa1, Hspa1b, Cdkn1a, Hmox1, Bag3 and Dnaja4 were commonly identified in the liver and adrenal glands, suggesting that these genes may regulate heat stress response through interactions between liver and adrenal glands. The results suggest that the identified mRNA isoforms could be considered as potential candidates for selecting mammals to improve thermotolerance.

The exploration and identification of targets and pathways for Atopic dermatitis (AD) treatment and diagnosis are critical for AD control. The conventional target exploration approach such as the literature review is not satisfying in terms of efficiency and accuracy. Recently, the bioinformatic approach is drawing attention for its unique advantage of high-volume data analysis for target and pathway exploration; Open Targets Platform is the targets source for this study to extract top 200 high-rank proteins from 3122 AD associated proteins. STRING, Cytoscape, CytoHubba, ClueGo, and CluePedia function had been applied for data analysis. The KEGG Mapper search & colour pathway was the pathway map resource for identified pathways; 23 key hub genes (VDR, KIT, BCL2L11, NFKBIA, KRAS, IL13, JAK2, STAT3, IL21, IL4R, REL, PDGFRB, FOXP3, RARA, RELB, EGFR, IL21R, MYC, CREBBP, NR3C1, IL2, JAK1, and KITLG). Additionally, 8 correlated pathways and the biological process had been identified; Through this study, a viable approach for target and pathway exploration had been presented. The identified AD targets and pathways will be tested for upcoming research for traditional Chinese medicinal herb interactions

The issue of environmental sustainability is increasingly topical and one of the most impactful sectors is that of the construction industry. As stated in the reports of the GlobalABC, the building sector is the main responsible for GHG emissions, generating about 37% of global CO2e emissions. Already during the phases of production and construction of buildings about 10% of global emissions are produced, while the remaining part comes from their use, from the energy for air conditioning and lighting. Reducing emissions in the pre-use phase of buildings is therefore a crucial issue for combating climate change. The research investigates the potential of timber construction systems, thanks to the carbon storage property of the material. The proposed calculation methodology is structured according to the LCA-Life Cycle Assessment approach, referring to the C2H phase (from Cradle-To-Handover), and evaluates emissions related to the production and construction of buildings. To identify the timber construction system that minimizes CO2e emissions, within the limits of the investigation (A1-A5 phases), the method was applied to two buildings built with different technologies: one with X-Lam panels and one with a framed structure. The results were analyzed, compared, and discussed to demonstrate that the timber buildings are the most virtuous solution in the Net Zero Carbon perspective by 2050.

Introduction: Intraventricular Hemorrhage (IVH) is a devastating condition mostly in preterm infants at < 30 weeks GA with large morbidities and mortality usually in the first 72 hours after birth. Prevention seems to be the only way to completely deal with this problem. The IVH prevention in this age group has been studied and includes some strategies such as prenatal corticosteroids, cesarean delivery, careful extraction among others, but still, it has an unacceptably high incidence in this population. A protocol with the name Drive to Zero IVH Prevention Project that was presented in one of EpicLatino conferences some years ago. As with any quality improvement in practices, we adapted this project to our unit. Objective: To compare the IVH incidence in our unit after the protocol implementation with and historic cohort from the same unit and with all other units un the epilactino network. Material and method: In October 2017 we begun to implement a neuro protection protocol. For this analysis we include every patient born <30 weeks of GA, inborn or outborn but less than 2 days old, that survived at least three days and had a neuroimaging preformed. We include cases until July 2022, and we use the EpicLatino, a Latin-American database, from 2018 to 2020 excluding our own unit for comparison as well as an historical cohort from our unit from 2010-2017. The protocol consists of: Minimal manipulation, low volume ventilation, one routine fiscal exam a day, neutral head position, one blood pressure measured per shift, no keel stick measurements, continuous dim light and low noise level, minimal touch, no vasoactive therapy except in extreme cases, temperature and humidity at 80%, catheters, when possible, fluid restriction followed with diuresis, no PDA therapy or Echo if possible and routine therapy with hydrocortisone, erythropoietin, caffeine, parenteral nutrition, and trophic feeding. e performed a univariate analysis for IVH and groups and a logistic regression model with variables that had statistical significance in the univariate analysis. Results: The study group included 64 cases, the historic cohort 123 and the EpicLatino 1029. Demographic characteristics were similar with few statistically significant differences. We found four grade 1-2 and six grade 3-4 IVH in the study group (some caused by very traumatic delivery with multiples hematomas in head, body, and extremities), all significantly lower that the other two groups. The logistic regression model confirmed the independent statistically significant result in the study group. Conclusion: The hemorrhage during delivery must be prevented by the obstetric team. Afterwards, a set of interventions like very gentle handling with minimal manipulation and unnecessary strict lab managing seams to decrease the incidence of IVH.

Introduction: Some of the practices in medicine are carried out of habit without proven benefits. This is the case of premature babies from 30 to 34 weeks of gestation who are always given parenteral fluids, even though this practice has been associated with an increase incidence of infection. At the end of 2017, we started a protocol of rationalization in the use of parenteral fluid. To administer nutrition/fluids, we used oral fluids by suction if this was possible or otherwise by oral/nasogastric tube at volumes of 70-80 mL/Kg/day divided every 3 hours, with 5 mL increments every 12-24 hours until 200 mL/K/day was achieved, always using breast milk when possible. Material and methods: The present study sought to compare results before and after this new policy. For this work, we review all premature babies between 30-34 weeks of gestation in two time periods, the first from 01/01/2010 to 12/31/2017 and the second from 01/01/2018 to 08/15/2022. The number of cases with and without parenteral fluids (PF), the incidence of infection, the weight at admission and discharge, and the change in the weight Z score between birth and discharge were compared. Both the anthropometric and outcome variables were compared using the different statistical methods according to each variable. Results: were found 920 cases with the described characteristics. The groups before and after the intervention did not show significant differences in their general demographic characteristics. We observed a decrease use of PF in the second period, from 425 cases (82.0%) before to 297 (26.2%) after implementation, p <0.0001 and fewer days of use (4.1 days/average before vs 1.3 after, p <0.0001) of PF. The weight at discharge and the change in weight Z-score were the same in both groups. Infections went from nine cases before to two cases after but it was not statistically significant. There were no complications due to less use of PF. Discussion: This study showed that the use of PF is not associated with significant changes in outcomes of interest, which reinforces that its use does not generate any benefit for the patient. Larger number of cases is required to detect differences in low incidence events such as infections.

In recent years, soil addition with organic amendments, such as biochar and compost, has gained attention as an effective agronomic practice to sustain soil fertility, enhance plant growth and crop yield. Well known are the positive effects of compost on yield of a wide crop varieties, while both positive and negative responses are reported for biochar Therefore, the aim of the study was to verify the effect of biochar mixed with three types of compost on quanti-qualitative response of Swiss chard (Beta vulgaris L. cycla), a leafy green vegetable rich in dietary antioxidants, largely consumed worldwide. A factorial experiment in pots with two factors, including biochar (without biochar and with biochar from vine pruning residues) and compost (without compost, with compost from olive pomace, with vermicompost from cattle manure and with compost from cattle anaerobic digestate), was setup. Two growth cycles were considered and a set of quantitative (height of plants, number, area and fresh weight of leaves) and qualitative parameters (carotenoid, chlorophyll, total N and NO3-content of leaves) were analyzed. Biochar decreased plant growth and NO3- leaf content; on the contrary, it increased total N leaf content, while compost improved all the considered parameters. The interactive effect of biochar and compost was evident only on total N and NO3- leaf content. In our experimental conditions, the compost showed to be the best option to improve Swiss chard growth and increase the phytopigments content, while the biochar-compost mixtures didn’t produce the expected effect.

This paper aims to review the challenges, toxicity, and routes of synthesis and usage of silver nanoparticles in different applications but also highlighting their sustainability from both medical and environmental issues. Regarding their toxicity, it is known that silver nanoparticles can destroy over 650 microorganisms comparing with antibiotics. Supplementary, will be presented in a comparative manner some conventional synthesis routes (physical and chemical methods) and green synthesis routes using plant extracts. The approach using plant extracts have various advantages comparing with physical, chemical and microbial synthesis methods because there is no need to use chemicals, wasteful purifications and high energy requirements. The paper presents an overview on “green nanotechnology” focused on using either biological micro-organisms or plant extracts as an alternative to the classical chemical and physical methods. An important issue discussed in the paper is an overview of the synthesis routes of silver nanoparticles, some expected applications of silver based active agents and their toxicity and challenges that must be overcome. Also, it needs to focus our attention on the dismissal of silver nanoparticles into the environment and especially in water systems, fact which suggests that this issue must be fully understood and applied the law.

Our work is regarding the analysis of land use changes, in the light of “saving soil” against the expansion due to unearned plus value of land: The loss of natural and agricultural surface in front of the expanding urban environment is a critical aspect of unsustainability of urban development, especially in the way it was carried out in the past decades. The measure of the physical transition of land use and characters from a more natural condition of land surface to a new artificial one, joint with a parallel analysis of the increase of land value due to such change is nowadays a major land-policy tool. The interplay of urban economics regulation with planning, reveals new key issues in urban governance and environmental preservation. In this paper it will be shown some experiment about the impact assessment of soil take, related with the seek of valorization of property inside the planning process. Our paper reports as well about the experimental activity carried out inside the MITO Lab of the Polytechnic of Bari, where reports about property values and environmental values have been produced, specially looking at the reality of the Apulia, a southern Italian Region, that is rich of farmlands and coastlines, often invaded by constructions with a severe loss of nature, landscape and ecosystems services.

Hybrid lead halide perovskites have been revolutionary in the photovoltaic research field, reaching efficiencies comparable with the most established photovoltaic technologies, although they do not yet reach their competitor stability. The search for a stable configuration required the engineering of the charge extraction layers; in this work, molecular doping is used as an efficient method for small molecule and polymer, employed as hole transport materials in planar heterojunction configuration on compact-TiO2. We proved the viability of this approach, obtaining significantly increased performances and reduced hysteresis on compact titania-based devices. We investigated the photovoltaic performance, correlating to the hole transport material structure. We have demonstrated that the molecular doping mechanism is more reliable than the oxidative doping, and verified that molecular doping in polymeric hole transport materials leads to highly efficient perovskite solar cell, with long-term stability.

Little is known about fertility preservation within the TGD community. Few receive adequate counseling placing them at risk for decision regret. The goal of this project was to develop, and pilot test the Transgender Fertility Preservation Knowledge Scale (TFPKS) to support the development and evaluation of health education resources. A community engaged; cross sectional retrospective design was used. Participants (n=189) provided information describing demographics, healthcare decision-making preferences, experiences/knowledge of fertility preservation, and treatment decision regret. The sample included 189 TGD adults. Most were white and aged 26-35 (33.3%) and not offered a consultation (73.0%). Many (41.2%) report they would have participated if offered. Knowledge regarding fertility preservation to support this desire was low. Most participants identified a patient-centered (69.4%) decision making preference. Much remains to address the healthcare inequities within the TGD population regarding fertility preservation. Overall participants had low levels of knowledge to support decision making. Further, healthcare system and individual barriers to fertility preservation remain prevalent. A foundational step towards addressing these disparities, is the identification of a valid and reliable instrument to measure TGD knowledge of fertility preservation.

Here we first report, how cholera toxin (CT) A subunit (CTA), the bacterial enzyme moiety responsible of cell signaling alteration, can take over the exosomal pathway, spread extracellularly and be transmitted in a cell population. A first evidence for long-term transmission of CT toxic effect via extracellular vesicles was obtained in CHO cells. To follow CT intracellular route towards exosome secretion we adopted a strategy apt to convert multivesicular body (MVB) derived exosomes in traceable fluorescent vectors. CT treated Me665 cells, a human melanoma cell line highly expressing caveolin-1 (Cav-1) and GM1, were used to purify and characterize fluorescent exosomes. Our results clearly show association of CT with exosomes together with typical exosomal markers and the HSP90 and PDI molecules, the required membrane translocation elements of CTA to the cytoplasm. Confocal microscopy proved direct CT containing fluorescent exo transfer into CHO cells coupled with the morphological cell change characteristic of CT action. Moreover, direct assessment of cAMP levels in Me665 cells treated with CT containing exo showed an efficient induction of cAMP increase comparable with CT alone. From our results, we can infer that CT can exploit exosome-mediated cell communication to target and extend its pathophysiological action throughout cell tissues.

Vaccination, particularly against pneumoccus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients, never practiced before, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023-2024 influenza season at the outpatient clinics of the Geriatrics section, University Hospital of Palermo (Italy). A total of 101 vaccinations were carried out. Half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among participants, 46.3% received only vaccination against Pneumococcus and 26.8% only anti-influenza or the combination of anti-pneumococcus and anti-influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2 % of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejections, namely 74.8% for influenza and 29.5% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings is possible. Proposing influenza and pneumococcal vaccination for outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

Reducing GHG emissions is a crucial challenge in urban areas, characterized by high energy consumption and reduced exposure to nature. In this context, the urban green system could play a pivotal role. In the literature, scholars analyzed both the ability of species-specific and layout-specific green infrastructures to increase carbon sequestration and the best location sites of new green infrastructures, to increase the provision of overall ecosystem services. There is a lack of studies helping green urban planners and designers choose where and which green infrastructure to implement, based on vegetation species-specific performance and local carbon emissions of city components. This paper uses tree inventory data from a medium-sized city in central Italy (Perugia) to develop a spatial analysis of the urban parks' performance in carbon sequestration. Then, the method evaluates the carbon emission of a public city building to generate a spatialized balance between buildings’ demand and trees’ supply, to support local decisions about the best locations for new green infrastructures and the choice between species. The paper contributes to GIS-based tools that vary the recommended location sites and species for new green infrastructures based on the demanded ecosystem service.

Cutaneous Melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors (PD-1 and CTLA4) constituted a main breakthrough in the treatment of metastatic CM, particularly in the long-term benefit. However, several molecular pathways are responsible for the failure of this strategy in about 50-70% of CM patients. Some Long Non-coding RNAs (lncRNAs), and circular RNAs (circRNA) are implicated in triggering pro- and antitumorigenic responses to various cancer treatments. The relationship between lncRNA, circRNA and Immune Checkpoint Blockade (ICB) immunotherapy is not extensively explored in cutaneous metastatic melanoma (CMM). The aim of this study is to evaluate the potential role of both circRNA and lncRNA as a predictive immunotherapy biomarker in CMM. RNA-seq from 12 FFPE samples from the metastatic biopsy of metastatic melanoma patients treated with Nivolumab were analyzed. Our findings indicate that specific lncRNA and circRNA are involved in regulatory networks of the immune response against metastatic melanoma under treatment with nivolumab. Moreover, we have established a risk score that allows the prediction of Overall survival (OS) and Progression-free survival (PFS) of CMM patients with high accuracy. This proof of principle work provides a possible insight on the function of ceRNA, contributing to decipher the complex molecular mechanism of ICB cancer treatment response.

Nicaragua is preparing the construction of an interoceanic canal that will be the longest and largest canal on earth. An environmental and social impact assessment has been published in 2014 supporting a general viability of the canal. Nonetheless, several scientist and societal actors raised serious concerns regarding the social, economic and ecological sustainability. Despite an open dispute within the Nicaraguan society, no independent, transparent and scientifically sound assessment has been carried out. Only the environmental and social impact assessment, charged by the canal constructor, has so far been realized. The aim of this study is to contribute to an open scientific debate through an objective and independent quantification of land use and hydrological impacts. This article presents a transparently documented and comprehensible impact assessment investigation of the West Canal Segment of the Nicaragua Canal. Based on publically available data and scientifically sound and recognized methods land use, hydrological (water availability) and socio-economic impacts (streets, population) are described, quantified and compared with official declarations in the impact assessment. While some results support official declarations other do not. The number of affected population and the water use of the Brito Lock resulted much higher in this study, for instance. Hence, society and water availability could be affected much higher than estimated in the impact assessment.

Smart health applications have received significant attention in recent years. Novel applications hold significant promise to overcome many of the inconveniences faced by persons with disabilities throughout daily living. For people with blindness and low vision (BLV), environmental perception is compromised, creating myriad difficulties. Precise localization is still a gap in the field and is critical to safe navigation. Conventional GNSS positioning cannot provide satisfactory performance in urban canyons. 3D mapping-aided (3DMA) GNSS may serve as an urban GNSS solution, since the availability of 3D city models has widely increased. As a result, this study developed a real-time 3DMA GNSS-positioning system based on state-of-the-art 3DMA GNSS algorithms. Shadow matching was integrated with likelihood-based ranging 3DMA GNSS, generating positioning hypothesis candidates. To increase robustness, the 3DMA GNSS solution was then optimized with Doppler measurements using factor graph optimization (FGO) in a loosely-coupled fashion. This study also evaluated positioning performance using an advanced wearable system’s recorded data in New York City. The real-time forward processed FGO can provide a root-mean-square error (RMSE) with about 21 m. The RMSE drops to 16 m when the data is post-processed with FGO in a combined direction. Overall results show that the proposed loosely-coupled 3DMA FGO algorithm can provide a better and more robust positioning performance for the multi-sensor integration approach used by this wearable for persons with BLV.

Food production is a complex matter, affecting people’s lives, organizations’ profits, and the well-being of the whole planet and has multifaceted ethical considerations surrounding its production, distribution, and consumption. This paper addresses the pressing need to confront ethical challenges within the food system, encompassing issues such as environmental sustainability, food security, and individual food choices for better oral and systemic health of all individuals around the globe. From agricultural practices to global trade and food waste, ethical implications are addressed across various domains, highlighting the interconnectedness of ethical decision-making in the food industry. Central themes explored include the ethical dimensions of food production methods, the impact of global trade on food ethics, and the role of individuals in making ethically informed food choices. Additionally, the paper dives into the spiritual and physical significance of food, particularly through the lens of oral health as a gateway to holistic well-being. Recognizing the complexity of the food ecosystem, the paper calls for serious interventions in legislation and economics to promote ethical protocols and techniques for sustainability reasons. It emphasizes the importance of ethical considerations in food safety management systems, regulatory frameworks, and quality standards. Moreover, the paper underscores the need for a comprehensive approach to address ethical dilemmas and moral values inherent in the food industry and oral health policies, advocating for the adoption of the precautionary principle and ethical decision-making frameworks. The article aims to serve as a call to action for stakeholders across the food industry and the healthcare sector, to prioritize ethical practices, promote transparency, rearrange economic parameters and work towards a more sustainable and equitable food system for inner and outer oral and systemic health and human sustainability for all.

This work seeks to approach the comparative analysis of the distribution of POFs (polymeric optical fibers) arranged in a random and sorted manner in the manufacture of translucent concretes. The following characteristics were analyzed: compressive strength, flexural tensile strength, capillary water absorption and light transmittance. Portland cement, water, fine aggregate (sand), silica fume, polycarboxylate ether-based superplasticizer and polymeric optical fiber were used in the production of the composites. Except the fiber content, the mixture of all other inputs was kept as a fixed parameter. Groups with the following levels of POFs were produced: 0%, 2%, 3.5% and 5%. The POF content is the sum of the areas of the fiber sections in the composite with the total area of the translucent surface. The results showed that for the analysis of mechanical behavior (flexural tensile and compressive strength) and durability (capillary water absorption), composites with random and sorted fibers within the 2% POF presented to belong to statistically distinct groups. For the other fiber contents, there was no pattern of behavior, that is, it cannot be said that there is a difference within 3.5% or 5% POF between sorted and random fibers in relation to the mechanical and durability characteristics analyzed. As for the light transmittance, it was attributed that the statistical difference between the fiber arrangements only within the 5% POF content can be a consequence of their accumulation in certain points of the material, thus influencing this characteristic measured by a light meter.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Metastatic pancreatic ductal adenocarcinoma pancreatic (PDAC) is characterized by poor prognosis and short survival. Today, the use of new polytherapeutic regimens increases clinical outcome of these patients opening new clinical scenario. A crucial issue related to the actual improvement achieved with these new regimens is represented by the occasional possibility to observe a radiological complete response of metastatic lesions in patients with synchronous primary tumor. What could be the best therapeutic management of these patients? Could surgery represent an indication? Herein we reported a case of a patient with a PDAC of the head with multiple liver metastasis, who underwent first line chemotherapy with mFOLFIRINOX. After 10 cycles, he achieved a complete radiological response of liver metastases and a partial response of pancreatic lesion. A, duodenocephalopancreasectomy was performed. Due to liver a lung metastases after 8 months from surgery, a second line therapy was started with a disease free survival and overall survival of 8 months and 45 months, respectively. Improvement in the molecular characterization of PDAC could help in the selection of patients suitable for multimodal treatments.

In this paper, we compare the performance between systems of ordinary and (Caputo) fractional differential equations depicting the susceptible-exposed-infectious-recovered (SEIR) models of diseases. In order to understand the origins of both approaches as mean-field approximations of integer and fractional stochastic processes, we introduce the fractional differential equations as approximations of some type of fractional nonlinear birth--death processes. Then, we examine validity of the two approaches against empirical courses of epidemics; we fit both of them to case counts of three measles epidemics that occurred during the pre-vaccination era in three different locations. While FDEs appear more flexible in fitting empirical data, our ODEs offered better fits to two out of three data sets. Important differences in transient dynamics between these modeling approaches are discussed.

Ribotoxin-like proteins (RL-Ps) are specific ribonucleases found in mushrooms that are able to cleave a single phosphodiester bond located in the Sarcin-Ricin Loop (SRL) of the large rRNA. The cleaved SRL interacts differently with some ribosomal proteins (P-stalk). This action blocks protein synthesis because the damaged ribosomes are unable to interact with elongation factors. Here, the amino acid sequence of eryngitin 3 and 4, RL-Ps isolated from Pleurotus eryngii fruiting bodies, was determined to: i) obtain structural information on this specific ribonuclease family from edible mushrooms; and ii) explore the structural determinants which justify their different biological and antipathogenic activities. Indeed, eryngitin 3 (exhibited higher toxicity with respect to eryngitin 4 against tumoral cell lines and model fungi. Structurally, eryngitin 3 and 4 consist of 132 amino acids, most of them identical and exhibit a single free cysteinyl residue. The amino acidic differences between the two toxins are: i) an additional phenylalanyl residue at the N-terminus of eryngitin 3, not retrieved in eryngitin 4; and ii) an additional arginyl residue at C-terminus of eryngitin 4, not retrieved in eryngitin 3. The 3D-models of eryngitins show slight differences at the N- and C-terminal regions. In particular, the positive electrostatic surface at C-terminal of eryngitin 4 is due to the additional arginyl residue not retrieved in eryngitin 3. This additional positive charge could interfere with the binding to the SRL (substrate) or with some ribosomal proteins (P-stalk structure), during substrate recognition.

Mitochondrial dysfunction is relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the heart of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n=8) or placebo (n=8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and abundance of mtDNA4834 deletion), and mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. TFAM binding to mtDNA regions involved in replication and deletion generation was increased following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling was found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

Despite the popularity of Zumba in several countries, research is scarce about its impact on older adults. Meanwhile, the integration of cognitive tasks with physical exercises, known as dual-tasking, is an evolving strategy to facilitate activities for older people. This study investigated the perceptions of older adults regarding Zumba and the potential of implementing it in a dual-task program. We conducted a qualitative-descriptive research involving 44 Filipino older adults from August to November 2020. Content analysis was employed to analyze the data. Four themes were identified: moving towards match or mismatch; balancing benefits with burdens; dual-tasking as innovative yet potentially challenging; and overcoming barriers with enablers. While Zumba is an inclusive and beneficial activity, individual and contextual limitations could hinder its suitability for older people. Dual-tasking in Zumba was also recognized as an innovative approach, although challenges should be addressed to promote its utility. Several strategies could support the design of these programs in communities. This is the first study to explore older adults’ perceptions towards Zumba and its potential utilization as a dual-tasking program. Findings could guide the implementation of appropriate Zumba and dual-tasking activities that seek to integrate cognitive and physical training for older adults.

Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of non-invasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% reduction of lung cancer mortality. However, it is not particularly suitable for clinical practice because of the costs, radiation, and the false positive rate. Several studies have therefore focused on research into biomarkers in body fluids. Despite the power of certain molecules to distinguish lung cancer patients from healthy subjects, no biomarker has yet been shown to significantly and reliably influence clinical decisions or to be translated from the laboratory to clinical practice. We performed an overview of the peer-reviewed biomedical literature published in the last 10 years on the research regarding biomarkers for the early diagnosis of lung cancer via a comprehensive analysis of the reviews published this past year. Our main aim was to bring to light the limitations and strengths of the research already conducted. Furthermore, future prospectives have been explored, bearing in mind the management of clinical trials and their integration into clinical practice.

Climate change affects water resources through the decrease of rainfall and the increase in temperatures and evapotranspiration. An indirect impact of climate change is also the increase of water uses by human activities. In this review, 320 papers were retrieved, of which 134 spanning five continents impacts and solutions to be used to better understand the effects of climate change on water resources, ecosystems, human health, security and socio-economic aspects were selected. Here, suggestions and proposals by scientists from around the world towards solutions, tips and ideas to deal with climate change and the best solutions for future water management were presented. The main solutions highlighted concern integrated water resources management, political direction, policies, increase in knowledge and new technologies. Furthermore, most of the papers analyzed underline that water resources management needs to incorporate protection and restoration of ecosystems and their services. Nature-based solutions need to be the starting point of new scientific and innovative ways to deal with climate change and towards future climate adaptation. In this complex evolution of the water resource, where is the management of the water resource in Italy going?

Chironomids are the species richest family among macroinvertebrates and are often used as indicators of ecological condition in inland waters. High taxonomic expertise is needed for identification and new species are still described even in the well-known West Palaearctic region. Data were filed in a Microsoft Access relational database and analysed using the R environment. Our database comprises data on Chironomid species collected in rivers and lakes in Italy and some other European countries over a period of about 50 years, often associated with physical-chemical data, but in some cases only benthic macroinvertebrates are available with no associated environmental data. In this case, the possibility of estimating water quality with only species composition available is discussed. Traits summarizing the species response to environmental variables were evaluated, with emphasis on natural and man influenced factors: current velocity, water temperature, conductivity, dissolved oxygen, nutrients. Traits calculations was possible using the subset of database including both environmental data and Chironomid abundances. The relations between sites, species and traits were evaluated using correspondence analysis and other multivariate methods. The response of species showed an interaction among different factors, with the possibility to order species along a single environmental gradient, extending from cold running waters to warm standing waters, with few exceptions. The utility and limits of the use of ecological traits are discussed.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Pufferfish (Tetraodontidae) inhabiting the Mediterranean Sea can represent an emerging public health risk due to the possible accumulation of marine neurotoxins (TTXs and STXs) in their tissues. In this study, the presence of pufferfish species in the Strait of the Sicily (Lampedusa Island, Italy) was investigated using a Citizen Science (CS) approach involving local fishermen. A sub-group of specimens collected were sent to the National reference Laboratory on Marine Biotoxins for de-termining the presence of TTXs using a validated HILIC-MS/MS method on fish tissue. The STXs presence was also screened in some specimens. Overall, 56 specimens, identified as Sphoeroides pachygaster (Müller &Troschel, 1848) were collected. Data on specimen total length, body weight, fishing method, catch area (with relative depth temperature and salinity) were analyzed and compared with the S. pachygaster records reported in Guardone et al. (2018), which were appro-priately updated until 2022. All the analysed tissues were found to be negative for both TTXs and STXs. The key role of the CS in monitoring potentially toxic marine species was proved. Outcomes from this study, the first investigating the toxicity of S. pachygaster in Italian waters, may provide useful data for the proper assessment of this emerging risk

Human induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them human attractive disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as source cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs. We also cover the phenotypic characteristics of the hiPSCs derived CMs, their ability to rescue injured CMs through paracrine effects, the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their potential use in biomedical applications.

The physical environment is of critical importance to child development. Understanding how exposure to domains of the physical environment such as greenspace, urbanicity, air pollution or noise affects externalising problems in typical and neurodiverse children is of particular importance given the significant long-term impact of those problems. In this narrative review we investigated the evidence for domains of the physical environment that may ameliorate or contribute to the display of externalising behaviours. We have considered a broad range of study designs that include typically developing and neurodiverse children and young people aged 0-18 years. We used the GRADE system to appraise the evidence. Searches were performed in 8 databases in July 2020 and updated in June 2022. Additional articles were further identified by hand-searching reference lists of included papers. The protocol for the review was preregistered with PROSPERO. Results: We retrieved 7174 studies of which 67 are included in this review. The studies reported on green space, environmental noise and music, air pollution, meteorological effects, spatial density, urban or rural setting, and home elements (e.g., damp/sensory aspects/colour). They all used well validated parent and child reported measures of externalising problems. Most of the studies were rated as having high or probably high risk of bias. Greenspace rurality and interior design had most evidence, although the certainty of the association was low. As expected, noise, air pollution, urbanicity, spatial density, colour and humidity appeared to increase the display of externalising behaviours. There was a dearth of studies on the role of the physical environment in neurodiverse children. The studies were heterogeneous and measured a range of externalising behaviours from symptoms to full syndromes. Greenspace exposure was the most common domain studied but certainty of evidence for the association between environmental exposures and externalising problems in the child or young person was low across all domains. We found a large knowledge gap in the literature concerning neurodiverse children, which suggests that future studies should focus on these children, who are also more likely to experience adverse early life experiences including living in more deprived environments as well as being highly vulnerable to the onset of mental ill health. Such research should also aim to dis-aggregate the mechanisms of action for both environmental influences on the externalising problems the results of which may point to pathways for public health interventions and policy development to address inequities that can be relevant to ill health in neurodiverse young people.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Background: Although autophagy is a pro-survival process of tumor cells, in particular conditions and when differently regulated by specific signals it can stimulate cell death. We previously demonstrated that the selective stimulation of the M2 muscarinic receptor subtype (M2 mAChR) negatively controls cell proliferation and survival and causes oxidative stress and cytotoxic and genotoxic effects in both GBM cell lines and GBM stem cells (GSCs). In this work, we have evaluated whether autophagy was induced as a downstream mechanism of the observed cytotoxic processes induced by M2 mAChR activation by the orthosteric agonist APE or the dualsteric agonist N-8-Iper. Methods: To assess the activation of autophagy, we analyzed the expression of LC3B by Western blot analysis and in LC3B-EGFP transfected cell lines. Apoptosis was assessed by Caspases 3 and 9 protein expression. Results: Our data indicate that activation of M2 mAChR by N-8-Iper promotes autophagy in both U251 and GB7 cells lines as suggested by the LC3B-II expression level and analysis of the transfected cells by fluorescence microscopy. Autophagy induction by M2 mAChRs is regulated by the decreased activity of the PI3K/AKT/mTORC1 pathway and upregulated by the pAMPK expression. Downstream autophagy activation, the increase of apoptosis was also observed in both cell lines after treatment with the two M2 agonists. Conclusions: N-8-Iper treatment causes autophagy via pAMPK upregulation, followed by apoptosis in both investigated cell lines. In contrast, the absence of autophagy in APE-treated GSC cells seems to indicate that cell death could be triggered by mechanisms alternative to those observed for N-8-Iper.

Many cognitive functions face a decline in the healthy elderly. Within the cognitive domains, both attentional processes and executive functions are impaired with aging. Attention includes three attentional networks, i.e., alerting, orienting, and executive control that showed a hemispheric lateralized pattern in adults. This lateralized pattern could have a role in modulating the efficiency of attentional networks. For these reasons could be relevant to analyze the age-related change of hemispheric specialization of attentional networks. This study aims to clarify this aspect with a lateralized version of the ANTI-Fruit. One hundred sixty-seven participants took part in this study. They are divided in three age groups: early adulthood (N=57; Range: 20-30); late adulthood (N=57; Range 31-64) and elderly/older people (N=57; Range: 65-87). Results confirm the previous outcomes on the efficiency and interactions among attentional networks. Moreover, an age-related generalized slowness was evidenced. These findings also support the hypothesis of a hemispheric asymmetry reduction in elderly/older adults. This pattern could partially explain the decrease in attentional functioning in elderly/older age.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p&lt;0.001) and age at maternity discharge (p&lt;0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

This literature review offers a comprehensive analysis of antenna designs tailored for 6G applications and THz communications. Various antenna types, including elliptical lens, WHEMS, grid array, CP horn, Quasi Yagi-Uda, patch, transmit array, Vivaldi patch, SRR slotted waveguide array, RCA, and Cassegrain antennas, are scrutinized in terms of their dimensions, characteristics, frequency ranges, and materials. The study highlights existing works on antenna design for 6G applications, exploring different fabrication techniques like PCB technology, LCP technology, Topas fabrication, Wire-cutting EDM, 3D Printing, Laser-drilling processes, and CNC machining. Notably, PCB technology exhibited promise with antennas such as WHEMS, patch, and Vivaldi patch, achieving significant bandwidth and gain. However, gaps remain in research, urging further exploration into additional fabrication methods and antenna designs to meet the demands of 6G networks. The study underlines the need for advanced, intelligent antennas capable of higher bandwidth and better performance in view of future wireless communications technologies such as 6G.

Mediterranean climate is marked by arid climate conditions in summer, therefore, crop irrigation is crucial to sustain plant growth and productivity in this season. If groundwater is utilized for irrigation, an impressive water pumping is needed to satisfy crop water requirements at catchment scale. Consequently, irrigation water quality gets worse, specifically considering groundwater salinization near the coastal areas due to seawater intrusion, also triggering soil salinization. With reference to an agricultural coastal area in the Mediterranean basin (Southern Italy), close to the Adriatic sea, an assessment of soil salinization risk due to processing tomato cultivation was carried out. A simulation model was arranged to perform, on daily basis, a water and salt balance along the soil profile. Long-term weather data and soil physical parameters representative of the considered area were utilized in applying the model, also considering three salinity levels of irrigation water. Based on the climatic analysis performed and the model outputs, the probability of soil salinity came out very high, such as to seriously threaten tomato yield. Autumn-winter rainfall resulted frequently insufficient to leach excess salts away from the soil profile and reach sustainable conditions of tomato cultivation. Therefore, alternative cropping strategies were prospected.

The consequences of a fall on an elderly person can be reduced if the accident is attended by medical personnel within the first hour. Independent elderly people use to stay alone for long periods of time, being in more risk if they suffer a fall. The literature offers several approaches for detecting falls with embedded devices or smartphones using a triaxial accelerometer. Most of these approaches were not tested with the target population, or are not feasible to be implemented in real-life conditions. In this work, we propose a fall detection methodology based on a non-linear classification feature and a Kalman filter with a periodicity detector to reduce the false positive rate. This methodology requires a sampling rate of only 25 Hz; it does not require large computations or memory and it is robust among devices. We test our approach with the SisFall dataset achieving 99.4% of accuracy. Then, we validate it with a new round of simulated activities with young adults and an elderly person. Finally, we give the devices to three elderly persons for full-day validations. They continued with their normal life and the devices behaved as expected.

Coronavirus Disease 2019 (Covid-19) was first described in December 2019 in Wuhan, Hubei Province, China; and produced by a novel coronavirus designed as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 has become a pandemic reaching over 1.3 million confirmed cases and 73,000 deaths. Several efforts have been done to identify pharmacological agents that can be used to treat patients and protect healthcare professionals. The sequencing of the virus genome not only has offered the possibility to develop a vaccine, but also to identified and characterize the virus proteins. Among these proteins, main protease (M^pro) has been identified as a potential therapeutic target, since it is essential for the processing other viral proteins. Crystal structures of SARS-CoV-2 M^pro and inhibitors has been described during the last months. To describe additional compounds that can inhibit SARS-CoV-2 M^pro, in this study we performed a molecular docking-based virtual screening against a library of experimental and approved drugs. Top 10 hits included Pictilisib, Nimorazole, Ergoloid mesylates, Lumacaftor, Cefuroxime, Cepharanhine, and Nilotinib. These compounds were predicted to have higher binding affinity for SARS-CoV-2 M^pro than previously reported inhibitors for this protein, suggesting a higher potential to inhibit virus replication. Since the identified drugs have both pre-clinical and clinical information, we consider that these results may contribute to the identification of treatment alternative for Covid-19. Nevertheless, in vitro and in vivo confirmation should be performed before these compounds could be translated to the clinic.

This study aimed to conduct a cross-cultural adaptation of the development of the cat-owner/dog-owner relationship scales. The method encompassed several stages: conceptual, item, semantic, operational, measurement, and functional equivalence. Processes included translations, synthesis of translations, back-translations, consensus on the English versions, external evaluation by the original authors, expert committee evaluation, and pre-tests. The study involved surveying 342 pet owners throughout Brazil using a 20-item questionnaire. Data analyses utilized confirmatory factor analysis, covariance-based modeling, and multigroup analysis. The techniques confirmed that the scale preserved its psychometric properties and showed no variance between dog and cat owners, indicating that the measured constructs are universal and unaffected by specific cultural nuances. Hence, the cross-cultural adaptation and validation of the scale facilitate applying and testing concepts and measures in diverse contexts, enriching our understanding of the dynamics between owners and their pets (dogs and cats) in different living situations. In addition, this research holds particular significance in Brazil, given the country’s vast cultural diversity.