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: The incidence of traumatic acute subdural hematomas (ASDH) in elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays a no clear role as predictor. We investigated if the timing of surgery has a major role in influencing outcome in these patients.Methods: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 years period in 5 Italian Hospitals. Patients were divided in 3 surgical timing groups from hospital arrival: ultra-early (within 6h); early (6-24h); delayed (after 24h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed.Results: We included 136 patients. About 33% died for consequences of ASDH and among the survivors only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting GCS, which was on average lower in ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared associated neither with survival nor with functional outcome also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. Conclusions: An earlier surgery was offered to patients with worse clinical-radiological findings. Also after stratification for GCS it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.

Introduction: Data on peri-operative management of direct-acting oral anticoagulants (DOACs) during transcatheter pacing leadless system (TPS) implantation remain limited. This study aimed to evaluate a standardized DOAC management regime consisting in interruption of a single dose prior to implantation and reinitiation within 6-24 hours; also, patient clinical characteristics associated with this approach were identified. Method Consecutive patients undergoing standard TPS implantation procedure from two Swiss tertiary centers were included. DOAC peri-operative management included the standardized approach (Group 1A) or other different approaches (Group 1B). Results Three hundred and ninety two pts (mean age 81.4±7.3 years, 66.3% male, left ventricular ejection fraction 55.5±9.6%) underwent TPS implantation. Two hundred and eighty two pts (71.9%) were under anticoagulation therapy: 192 pts were treated with DOAC; 90 pts were under vitamin-K antagonist. Patients treated with DOAC less often had structural heart disease, diabetes mellitus, and advanced renal failure. The rate of major peri-procedural complications did not differ between Groups 1A (n=115) and 1B (n=77) (2.6% and 3.8%, p=0.685). Compared to 1B, 1A patients were implanted with TPS for slow ventricular rate atrial fibrillation (AF)(p=0.002), were in better overall clinical status, and were implanted electively (<0.001). Conclusions Standardized peri-procedural DOAC management was more often implemented for elective TPS procedure and did not seem to increase bleeding or thromboembolic adverse events.

Based on the elasticity theory, this paper deals with the static analysis of a cracked double beam system in presence of a Winkler medium. The double-beam system is also supposed to be constrained at both ends by elastically flexible springs, with transverse and rotational stiffness. Using a variational formulation, the static governing equations are derived and solved by using analytical and numerical approaches. In the first approach, the closed-form solutions for the displacements functions are obtained based on the Euler-Bernoulli beam theory. In the second approach, the Cell-Discretization Method (CDM) is performed, according to which the two beams are reduced to a set of rigid bars linked together by means of elastic constraints, where the bending stiffness of the bars is concentrated. The resulting stiffness matrix is easily deduced, and the governing equations of the static problem can be immediately solved. A comparative analysis is performed in order to verify the accuracy and validity of the proposed method. This study focuses on the effect of various parameters including the crack depth and position, boundary conditions, elastic medium and slenderness. The validity of the proposed analysis is confirmed by comparing the present results with those obtained from the other approach. In particular, the results obtained by closed-form solution and Cell-discretization method (CDM) are compared by Finite element method (FEM). Accuracy of the results has been evaluated by making comparisons with the results in literature and reported in bibliography. It is demonstrated that the proposed algorithm provides a simple and powerful tool in dealing with the static analysis of a double-beam system. Finally, some concluding remarks are made.

This article responds to an identified and significant gap in the existing scholarly canon to consider the extent to which cinematic representations construct heroin users—the ‘junkie’—as a criminalised ‘Other’ which confer legitimacy on the notion that such are criminogenic and deviant. Positioned within the disciplinary bounds of cultural criminology, this article focuses on five films - Sid and Nancy (1986); The Basketball Diaries (1995); Trainspotting (1996); Requiem for a Dream (2000); and, T2 Trainspotting (2017). Drawing together Hall’s (1997) theories of representation and Hjelm’s (2014) theories of social constructionism, the findings from a narrative analysis of each of the films—individually and comparatively—explores the following themes, junkies: as criminogenic; as dangerous underclass; as embodying decay and depravity; and in relation to female junkies, as junkie whores. In doing so, this article elucidates new thinking and ideas about cinematic representations of junkies and how this shapes and influences social norms and mores.

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.

The genus Allium L. attracts the attention of researchers due to the presence of valuable medicinal, nutritional and decorative properties, adaptive capabilities, resistance to pests and diseases, ecological plasticity in its representatives, which contributes to the competitiveness of species and the manifestation of a high degree of adaptation outside natural areas and wide geographical distribution. Allium resources in Russia are a potential source of genes for expanding the genetic base of agricultural crops. The leaves of Allium crops have a short freshness period and quickly deteriorate due to spoilage and loss of water. Spoilage and loss of water affect their freshness and properties. The aim of the work was to establish the yield and change in the quality of green leaves of Allium species introduced into the Moscow region during short-term storage, depending on the type of packaging, storage period and temperature. 4-5-year-old plants of 4 species (A. altyncolicum, A. chyatophorum, A. nutans and A. turkestanicum) were grown on the collection plot of perennial onions of VNIIO, a branch of the FGBNU FNTSO. In the conditions of the Moscow region, the yield per leaf generation varied from 2.7 kg/m2 (A. altyncolicum) to 4.9 kg/m2 (A. cyathophorum). The maximum yield of marketable products was noted in hermetically sealed plastic bags when stored for 10 days at a temperature of +6 ... + 80С in a refrigerator with controlled conditions: A. turke-stanicum - 70.0%, A. cyathophorum - 75.5%, A. altyncolicum - 84.9%, A. nutans - 92.9%. However, an increase in the dry matter content (10.1-15.5%) was found during storage in an open polymer box in all tested species. The maximum content of vitamin C during storage in hermetically sealed bags with a density of 100 μm was found in A. altyncolicum (37.1 mg%) and A. nutans (42 mg%). In other species, the maximum value of this indicator was noted before storage. A slight increase in the amount of sugars after storage for 10 days was noted in species with a linear leaf shape when stored in a polymer box. Temperature control is the most effective approach to extend the shelf life of fresh green leaves by measuring its weight loss and vitamin C. Packaging cannot prevent spoilage of vegetables but can protect it against contamination, damage and excessive moisture loss.

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by food selectivity in a significant portion of the population. The nature of this selectivity remains unclear, with hypotheses suggesting associations with sensory disorders or stereotypical and repetitive patterns of activity and interests. This study aimed to determine the prevalence and nature of food selectivity traits in individuals with ASD compared to the neurotypical population. The study involved 219 participants, with 115 diagnosed with autism and 92 without. 12 children undergoing diagnosis were excluded from the analyses. Findings revealed that food selectivity traits are more common in individuals with ASD, with differences in preferences mainly involving structure, color, taste, and serving method. Children with ASD had more food selectivity traits than those without, and certain food characteristics could alter intake as they grow. Selectivity occurred for both sensory and stereotypical reasons, but stereotypical features significantly differentiated neurotypical individuals from those with ASD.

Menin inhibitors are new and promising agents currently in clinical development that target the HOXA/MEIS1 transcriptional program which is critical for leukemogenesis in histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) and in NPM1-mutated (NPM1mut) acute leukemia. The mechanism of action of this new class of agents is based on the disruption of menin-KMT2A complex (constitute of chromatin remodelling proteins), leading to the differentiation and apoptosis of AML cells expressing KMT2A or mutated NPM1. This new class of drugs has been tested alone, or in combination with synergistic drugs, in phase I and II clinical trials (AUGMENT-01 and 02, KOMET-01 and 07, SAVE, COVALENT trial and others), showing promising results in terms of response rates and safety in heavily pre-treated acute leukemia patients. In this review, we summarise the key findings on menin inhibitors, focusing on the mechanism of action and preliminary clinical data of this emerging and promising class of agents, in particular revumenib and ziftomenib.

Evidence points to a link between gluten-free diet or celiac disease and eating disorders, but not with orthorexia. This study is the first to examine adults with celiac disease in terms of the prevalence of risk of orthorexia. The study included 130 adults diagnosed with celiac disease. The standardized ORTHO-15 questionnaire was used to assess the risk of orthorexia. Cronbach's alpha test was used to determine the reliability of the ORTHO-15 questionnaire. Eating habits of the subjects were assessed using a questionnaire. The effect of celiac disease on diet was assessed on a 5-point scale. A risk of orthorexia was found in 69% of subjects with celiac disease. A statistically significant (p&lt;0.005) positive correlation was observed between age and ORTHO-15 test scores (rho=0.37). In the group with orthorexia risk, meals were more often self-prepared (93.3%) compared to those without orthorexia (80%) (p=0.023). For 80% of those at risk for orthorexia versus 20% without risk, mood was a factor influencing dietary choices (p=0.001). The study observed a strong association between celiac disease and the presence of orthorexia risk. The numerous risk factors for orthorexia suggest the need for holistic care, including nutritional and psychological support among individuals with celiac disease.

Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated timely. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in two decades. We evaluated visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. Data included parameters for age, sex, age at the diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average 36±25 months follow-up. Bevacitzumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), > 5 ETDRS letters in 309 (28%) and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5-<15 ETDRS letters in 44 (4%) and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the criteria of visual impairment, whereas 179 patients (22%) were visually impaired after the follow-up. Improvement or stabilization in vision was noted in 90% of the anti-VEGF-treated eyes with nAMD. In addition, anti-VEGF agents are crucial in diminishing nAMD-related visual impairment.

Carbon nanotubes have sparked a substantial amount of scientific and technological research due to their exceptional mechanical, physical and electrical characteristics compared to conventional materials. As a result, detailed studies on their mechanical properties have been conducted, and static and dynamic behavior of single-walled and multi-walled carbon nanotubes have been proposed using Euler-Bernoulli and Timoshenko beam models. The main objective of this paper is to study the free vibration of a Timoshenko-Ehrenfest single-walled carbon nanotube based on the nonlocal theory and taking surface effects into account. To model these effects on frequency response of nanotubes, we use Eringen’s nonlocal elastic theory and surface elastic theory proposed by Gurtin and Murdoch to modify the governing equation. A modified version of Timoshenko nonlocal elasticity theory - known as the nonlocal truncated Timoshenko beam theory - is put forth to investigate the free vibration behavior of single-walled carbon nanotubes (SWCNT). Using the Hamilton’s principle, the governing equations and the corresponding boundary conditions are derived. Finally, to check the accuracy and validity of the proposed method, some numerical examples are carried out. The impacts of the nonlocal coefficient, surface effects and nanotube length on the free vibration of single-walled carbon nanotube (SWCNT) are evaluated and the results are compared with those found in the literature. The findings indicate that the length of the nanotube, the nonlocal parameter and the surface effect all play important roles and should not be disregarded in the vibrational analysis of nanotubes. Finally, the results show how effective and successful the current formulation is at explaining the behavior of nanobeams.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

The positive impact of nature on human health has been explored by researchers. Although studies have indicated that olfaction and odors have an impact on both memory and health, re-search on the odor perception in relation to perceived health is scarce. A recent study found that the naturenatural scent from stem cuttings and potted plants of a specific rose-scented geranium Pelargonium graveolens, ‘Dr. Westerlund,’Westerlund’ had positive effects on stress-related mental disorders. reduction. Essential oils from many Pelargonium species, in particular ‘Dr. Westerlund’, are known to have phytochemical properties and pharmacological activities. No study has, so far, explored and identified the chemical com-pounds and the sensory perception of these compounds in stem cuttings and the potted ´Dr. Westerlund´ plantplants. Such knowledge would be an important contribution forto an increased understanding of the effects of plants’ chemical odor properties on human well-being and link this to the expressed perceived scents. Resulting sensory profiles of P.This study aimed to identify the sensory profile and suggest responsible chemical compounds of Pelargonium graveolens ´Dr. Westerlund´ as a potted plant and as stem cuttings were reported, as well as´. The sensory and chemical analysis results revealed sensory profiles of Pelargonium graveolens ´Dr. Westerlund´s, and suggestions for the chemical compounds that are attributed to the sensory profiles. Further studies are recommended to investigate the odor experience of scented pelargonium species in relation to various levels ofcorrelation between volatile com-pounds and possible stress hormones. reduction in humans.

Medicinal plants have antibacterial, antifungal and antiviral activities. More or less all plants have medicinal properties. In this research article, we have selected four economically important plants (three fruit plants and an economically important plant), Malus domestica Borkh., Prunus persica L., Ricinus communis L., and Carica papaya L. found in several areas of Indian state Uttarakhand. Using the methanolic extract of leaves, we have screened those four plants against four human pathogenic bacteria, Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus and Micrococcus luteus. For our experiment we have screened the methanolic leaf extracts of four plants against the above-mentioned bacteria. Statistical analysis was also performed for validation. Result revealed the said bacteria have potential antibacterial activities. So, these leaves can be used for clinical trial. These plants can also be used for making herbal medicines.

Plant sterols are compounds with multiple biological functions, mainly cholesterol-reducing. There are no comprehensive databases on plant sterols, which makes it difficult to estimate their intake in the Polish population. In this study we used international food databases, supplemented by scientific data from the literature, to create a database on plant sterols in the food consumed in Poland to assess the size and sources of dietary plant sterols in the adult population of Poland. The literature search was conducted using PubMed, Web of Science, Scopus, and Google Scholar to identify possible sources of published food composition data for plant sterols. The study group consisted of 5690 participants of the WOBASZ II survey. We identified 361 dietary sources of plant sterols based on the consumption of foods and dishes reported by participants. Cereals and fats provided 61% of the total plant sterols, and together with vegetables and fruits, this totaled 80%. Total plant sterol intake for the Polish population was 282.97 mg/day, and divided by men and women was 320.77 and 252.19 mg/day, respectively. Canola oil provided the most plant sterols at 16.92%, followed by white bread at 16.65% and soft margarine at 8.33%. This study found that the database of plant sterols facilitates the calculation of plant sterols in the typical Polish diet, and the results are comparable to those of other studies, despite different methodologies of nutritional assessment and slightly different databases. The main sources of dietary plant sterols did not differ from the data for other populations. This study confirmed the observations of other research that women's diets may have a higher plant sterol density compared to men.

Understanding the structure and properties of MgCl2/TiCl4/ID nanoclusters is a key to uncover the origin of Ziegler-Natta catalysis. In this work MgCl2/TiCl4 nanoplatelets derived by machine learning and DFT calculations have been used to model the interaction with ethyl-benzoate EB (as internal donor) with available exposed sites of binary TixCly/MgCl2 systems. The influence of vicinal Ti2Cl8 and coadsorbed TiCl4 on energetic, structural and spectroscopic behaviour of EB has been considered. The adsorption of homogeneous-like TiCl4EB and TiCl4(EB)2 at the various surface sites have been also simulated. Calculations have been carried out by employing B3LYP-D2 and M06 functionals. The adducts have been characterized by computing IR and Raman spectra that have been found to provide specific fingerprints useful to identify surface species; IR spectra have been successfully compared to available experimental data.

The study investigated the chemical and functional characterization of propolis collected in southern Italy, in particular in Basilicata, a region rich in ecological and vegetative biodiversity. Sixteen samples of propolis, collected within a radius of 40 km from each other in the Basilicata region, showed significant differences between the chemical and functional parameters investigated: color index (L*, a*, b*; P<0.05), variation in chemical composition and antioxidant activities, by ABTS and FRAP assays. In general, Lucanian propolis had a low content of waxes (P<0.05) and a high content of resin (P<0.05) and balsams (P<0.05). The content of total phenolic compounds and flavonoids were highly variable, as was the biological capacity. In conclusion, Lucanian propolis showed a remarkable variability, highlighting a significant diversification according to the geographical position and the diversity of the flora surrounding the apiary of which the bees use as a source of resin. This study therefore contributes to the enhancement of the quality of propolis, laying the foundations for the production and marketing of propolis not only in the food industry, but also in the pharmaceutical and cosmetic industries.

The increase in arrivals of new forest pests highlights the need for effective phytosanitary legislation and measures. This paper introduces legislation targeted at prevention and management of potential introductions of forest pests and pathogens. A summary is given on plant health regulations on a global and regional level with detailed information on the situation in the European Union (EU). The current and new European legislation is discussed and a particular focus is given on eradication and contingency plans for Fusarium circinatum.

We investigate the shear quasinormal modes (QNMs) in the context of electron stars, focusing on the Lifshitz geometry and exploring the behavior in the small star limit. The study begins by analyzing the shear sector modes in the infrared (IR) Lifshitz limit, where the geometry approaches that of a pure Lifshitz space. We derive and solve the differential equations governing the shear modes, revealing the asymptotic behavior in terms of the Lifshitz exponent. In the special case of integer values of the exponent, we obtain analytic corrections to the solutions to extract hydrodynamical QNMs. We then explore the cases with a Lifshitz exponent equal to or greater than three, providing analytical corrections to the Lifshitz IR solutions. A special case with an exponent of two is also considered, leading to modified solutions. The study extends to finding hydrodynamical QNMs, emphasizing the role of the Lifshitz geometry. Further investigations involve the flux with real and complex frequencies, considering the off-shell Lagrangian and deriving conserved flux expressions. Our analysis focuses on the exterior of the star, modeled by the Reissner-Nordström-AdS geometry. The small star limit is examined, revealing interesting features in the behavior of fermionic excitations. In summary, we provide a detailed exploration of shear quasinormal modes in electron stars, shedding light on their behavior in Lifshitz geometry, small star limits, and the interplay between real and complex frequencies. Our findings contribute to our understanding of the dynamics of electron stars and their gravitational properties.

We explore the relationship between the exact renormalization group (RG) equation and quantum mechanics. The central idea is to rewrite the exact Wilsonian RG equation as a Schrödinger-type equation, opening avenues for analysis. By introducing a functional transformation, the RG equation takes on a form analogous to a quantum mechanical Schrödinger equation. The study investigates solutions to this equation and draws parallels with quantum mechanics, paving the way for understanding the infrared behavior of quantum field theories. Furthermore, we extends its insights to a one-dimensional toy model, providing illustrative examples. The discussion encompasses the implications of these findings in multiple dimensions and quantum field theory, with a brief exploration of their relevance in the context of inflationary cosmology.

Marine Protected Areas (MPAs) are vital for biodiversity conservation, yet their effectiveness in preserving foundation seaweeds remains understudied. This study investigates the diversity and distribution of Cystoseira sensu lato (including Cystoseira, Ericaria and Gongolaria) populations in the an MPA located in the central Mediterranean Sea, comparing them with those in two unprotected control sites. We hypothesize that MPA Cystoseira s.l. populations will display higher diversity and structure compared to outside control sites. Results reveal a total of 19 Cystoseira s.l. species at depths of 0-20 m, with the MPA exhibiting a higher diversity than control sites. Thus, MPAs can play a crucial role in fostering the diversity of Cystoseira s.l. populations. However, no significant differences were observed among the MPA's protection zones, raising questions about the zoning effectiveness. Additionally, our survey uncovered a substantial presence of non-indigenous seaweeds within the MPA. In conclusion, while MPAs improve Cystoseira s.l. diversity compared to unprotected sites, the varying efficacy of protection within MPA zones suggests a necessity for site-specific conservation strategies. The presence of non-indigenous seaweeds emphasizes ongoing challenges. This study provides a baseline for understanding Cystoseira s.l. population dynamics, crucial for future monitoring and conservation efforts in the face of climate change.

Due to the rapid emergence of multi drug resistant (MDR) pathogens against which current an-tibiotics are no longer functioning, severe infections are becoming practically untreatable. Con-sequently, the discovering of new classes of effective antimicrobial agents with novel modes of action is becoming increasingly urgent. The bioactivity of Cannabis sativa, an herbaceous plant used for millennia for medicinal and recreational purposes, is mainly due to its content in phytocan-nabinoids (PCs). Among the 180 PCs detected, cannabidiol (CBD), Δ8 and Δ9-tetrahydrocannabinols (Δ8-THC and Δ9-THC), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and some their acidic precursors have demonstrated from moderate to potent antibacterial effects against Gram-positive bacteria (MICs 0.5–8 µg/mL), including methicillin-resistant Staphylococcus aureus (MRSA), epidemic MRSA (EMRSA), as well as fluoroquinolones and tetracycline-resistant strains. Particularly, the not psychotropic CBG was also capable to inhibit MRSA biofilm formation, to eradicate that mature, and to rapidly exterminate MRSA persiters cells. On this scenario, CBG, as well as other minor not psychotropic PCs, such as CBD, and CBC could represent promising compounds for developing novel antibiotics with high therapeutic potential. Anyway, further studies are necessary, needing abundant quantities of such PCs, scarcely provided naturally by Cannabis plants. Here, after an extensive overture on cannabinoids including their reported an-timicrobial effects, aiming at easing the synthetic production of the necessary amounts of CBG, CBC and CBD for further studies, we have, for the first time, systematically reviewed the synthetic pathways utilized for their synthesis, reporting both reaction schemes and experimental details.

Aging involves several changes depending on genetic and behavioural factors, such as lifestyle and number and quality of social relationships, which in turn can be influenced by empathy. Here, the change in the perceived social support across the life span as a function of empathy was investigated, considering the mediating role of the empathy, after controlling for gender and education. 441 people (18-91 years old) filled in the Italian short version of the Interpersonal Support Evaluation List (ISEL-12) and the Social Support Questionnaire (SSQ6) as well as the Empathy Questionnaire (EQ) and the Reading the Mind in the Eyes test (RMET). The mediation analyses with ISEL-12 showed that age and the EQ fully mediated the relationship between age and Appraisal, Belonging and Tangible scores. Further, the EQ fully mediated only the relationship between age and SSQ6-People. These results showed that empathic skills play a key role in the relationships between age and social support. This suggests: empathy can trigger social support and ultimately well-being if stimulated across the lifespan, especially since young age; this would help to form the socio-emotional competence across the years, as a sort of cushion that can be useful in the elderly to fulfil active aging.

The described data set contains features from the machine control of a five-axis milling machine. The features were recorded during thirteen series productions. Each series production includes a changeover process in which the machine was set up for the production of a different product. In addition to the timestamps and the twenty recorded features derived from Numerical Control (NC) control variables, the data set also contains labels for the different production phases. For this purpose, up to 23 phases were assigned, which are based on a generalized milling process. The data set consists of thirteen .csv files, each representing a series production. The data set was recorded in a production company in the contract manufacturing sector for components with real series orders in ongoing industrial production.

Pure silver as well as silver compounds have been used as antiseptics for centuries. Nowadays, the most frequently applied form of silver is a nanoparticle form. Several studies demonstrate the ability of silver nanoparticles and silver salts to accumulate in the brain of laboratory ani-mals as well as the ability of silver nanoparticles to influence behavioral and cognitive functions of laboratory mammals. For the first time, the influence of a silver salt, in particular, silver citrate on the change dynamics of behavioral and cognitive functions of laboratory mice at the daily oral exposure during 30, 60, 120 and 180 days is investigated in the present research. We observed the anxiety increase after 30 days of the exposure as well as the ability of mice to adapt to the prolonged oral exposure of silver citrate manifested in the anxiety decrease, increase of locomotor activity and the tendency of long-term contextual memory improvement. Increase of locomotor activity and memory improvement might be associated with the sensitivity increase and regarded as compensatory mechanism to anxiety increase. The observed phenomenon is classified as a hormetic effect. A comparison with the analogous study implemented polyvi-nylpyrrolidone coated silver nanoparticles is carried out. It was concluded that the nanoform is more neurotoxic.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

Sulfenic acids as small molecules are too unstable to be isolated and their transient nature offers the possibility to involve them in concerted processes that lead to the obtainment of functional groups such as sulfoxides, sulfones and disulfides. All these functions are present in a number of natural and synthetic drugs and can represent structural motives inducing biological relevant properties. In this small review the generation and reactions of sulfenic acid bearing naturally occurring residues are described. Carbohydrate and aminoacid-derived sulfenic acids have been used in concerted addition to triple bonds to obtain alliin derivatives and thiosugars in enantiomerically pure form. Glycoconjugates with sulfinyl, sulfonyl and disulfane functional groups and pyridine-derived disulfides have been obtained from bis and tris-sulfinyl precursors of sulfenic acids. Small families of such compounds have been subjected to preliminary biological tests. Starting from the evidence that the control of molecular architecture and the presence of suitable functional groups can play a significant role on the exhibition of biological properties, apoptotic effects on malignant cells by glycoconjugates and inhibitory activity against the important human pathogen S. aureus by pyrimidine-derived disulfides have been found.

The present study is aimed to determine the predicting role of objective (lifestyle) and subjective factors of middle-aged women’s psycho-emotional health such as their attitude towards parents, attachment and separation types. Women who are overloaded with professional and family roles have high stress level, their indicators of psychological well-being and emotional level decrease when they have to give everyday care to their elderly parents. (2) Methods: Sample consists of 146 women aged 38 to 56 ( =41.1, ó=3.5), married (70.5%) and divorced (29.5%), having children of 14-28 years old; giving everyday care to elderly parents for more than 1.5 yrs. Some live separately (62.3 %), or have to cohabitate with parents (37.7%). All women evaluate their life situation as difficult and manifest signs of high psycho-emotional stress. We used methods adapted for the Russian-speaking sample: getting socio-demographic information, an interview; Attachment style and Interpersonal Guilt Questionnaires (study 1); Psychological Separation Inventory, Purpose-in-Life Test, projective methods of incomplete sentences and metaphors` analysis (study 2), mathematical statistics. (3) Results: A number of factors and indicators of women`s psycho-emotional health decrease in the situation of role overload have been identified. Among the factors there are four main types of women’s attitudes towards parents: strong (anxious), distancing, ambivalent, normative closeness, predicting low indicators of psycho-emotional health: dependence on the others` opinions and feedbacks in making decisions, a lack of meaningfulness of life; reduced sense of control over life are showing the decrease. Anxiety about future and neurotic symptoms (increased demands on oneself, irritability, reduced emotional background) distinguish these respondents. (4) Conclusions: The study confirms that middle-aged Russian women`s psycho-emotional health depends on contextual factors (difficult role-overloaded lifestyle) and factors integrating women`s attitudes towards parents, attachment and separation types. Among the most important risk factors there are a difficult life situation, conflict separation type and gilt.

Many neuropsychological theories agree that the brain maintains a relatively persistent representation of one’s own body, as indicated by vivid “phantom” experiences. It remains unclear how the loss of sensory and motor information contributes to the presence of this representation. Here, we focus on new empirical and theoretical evidence of phantom sensations following damage to or an anesthetic block of the brachial plexus. We suggest a crucial role of this structure in understanding the interaction between peripheral and central mechanisms in health and in pathology. Studies of brachial plexus function have shed new light on how neuroplasticity enables “somatotopic interferences,” including pain and body awareness. Understanding the relations among clinical disorders, their neural substrate, and behavioral outcomes may enhance methods of sensory rehabilitation for phantom limbs.

In this report, we describe the course and successful treatment of complicated infective endocarditis (IE). A patient presented with a high-grade irregular fever with chills lasting at least 2 months, dyspnoea, chest pain, fatigue, weight loss, and night sweats during the previous 3 months. Above cardiac congenital disorders, he was found to have Granulicatella adiacens infective aortic valve endocarditis, presumably transmitted from the oral cavity niche. Validated metagenomic 16S rDNA next generation sequencing was used to perform taxonomic identification, allowing for specific adequate antibiotic therapy instead of empiric therapy. This paper highlights the critical role of rapid taxonomic identification of nutritionally variant streptococci crucial and the benefit of proper IE treatment to avoid relapses or fatal complications.

Human oncoviruses are able to subvert telomerase function in cancer cells through multiple strategies. The activity of the catalytic subunit of telomerase (TERT) is commonly enhanced in virus-related cancers. Viral oncoproteins, such as high-risk human papillomavirus (HPV) E6, Epstein-Barr virus (EBV) LMP1, Kaposi sarcoma-associated herpesvirus (HHV-8) LANA, hepatitis B virus (HBV) HBVx, hepatitis C virus (HCV) core protein and human T-cell leukemia virus-1 (HTLV-1) tax protein, interact with regulatory elements in the infected cells and contribute to the transcriptional activation of TERT gene. Specifically, viral oncoproteins have been shown to bind TERT promoter, to induce post-transcriptional alterations of TERT mRNA and to cause epigenetic modifications, which have important effects on the regulation of telomeric and extra-telomeric functions of the telomerase. Other viruses, such as herpesviruses, operate by integrating their genomes within the telomeres or by inducing alternative lengthening of telomeres (ALT) in non-ALT cells. In this review, we recapitulate recent findings on virus-telomerase/telomeres interplay and the importance of TERT-related oncogenic pathways activated by cancer causing viruses.

Falls at height are among the major causes of fatal accidents at work, especially in the construction sector. Maintaining balance while performing a tool with both hands generates physical efforts and mental loading that needs to be managed for workers’ safety and health. The purpose of the study is to compare perceived (dis)comfort (overall and localized), the ergonomic risk and the perceived effort through the acquired postures that subjects assumed during the execution of simple and common tasks both on a ladder and on the ground. 26 subjects were asked to perform four tasks in both conditions: top screwing, frontal screwing, object picking from the bottom forward, and object picking from the bottom sideways. Subjective and objective data were gathered for assessing subjective experience (discomfort and effort, perceived) and ergonomic risk. Results highlighted few ergonomic risk differences among “on ladder” and “on ground” tasks, while subjective data reveal significant differences in different scenarios. Main results regard knees and neck areas as the most critical ones.

The drug discovery process is a rigorous and time-consuming endeavor, typically requiring several years of extensive research and development. Although classical machine learning (ML) has proven successful in this field, its computational demands in terms of speed and resources are significant. In recent years, researchers have sought to explore the potential benefits of quantum computing (QC) in the context of ML, leading to the emergence of Quantum Machine Learning (QML) as a distinct research field. The objective of the current study is twofold: first, to present a review of the proposed QML algorithms for application in the drug discovery pipeline, and second, to compare QML algorithms with their classical and hybrid counterparts in terms of their efficiency. A query-based search of various databases took place, and five different categories of algorithms were identified in which QML was implemented. The majority of QML applications in drug discovery are primarily focused on the initial stages of the drug discovery pipeline, particularly with regard to the identification of novel drug-like molecules. Comparison results revealed that QML algorithms are strong rivals against the classical ones and a hybrid solution is the recommended approach at present.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

Vector-borne disease (VBD) accounts for more than 17% of the global infectious disease burden, disproportionately affecting developing nations within tropical and subtropical areas. As Aedes aegypti mosquitoes are the principal vector for the transmission of many Public Health pathogens, our study examined their population dynamics within the seasonal context of tropical dry biomes in El Salvador as incidence of VBD in this region has increased in recent years. Species that rely on sexual reproduction must maintain a balanced sex ratio (1:1) to support their population dynamics, however, our phenological analysis of field-collected A. aegypti specimens revealed significant sex ratio variations during dry and wet seasons. Interestingly, we detected a seasonal shift that favored female mosquitoes during the dry season, highlighting the dynamic nature of mosquito populations in highly urbanized environments like El Salvador. By linking sex ratio distortions to anthropogenic factors, our study underscores the importance of comprehensively characterizing the urban ecology of vectors for the development of effective biocontrol strategies. As such, we advocate for more nuanced vector control approaches that consider ecological factors as well as the human behaviors that influence mosquito breeding habitats to effectively combat the rise of VBDs amid global climate changes.

In the last decades, climate and environmental changes have highlighted the fragility and vulnerability of the landscape, especially in mountain areas where the effects are most severe. The strategy for hazard mitigation must deploy synergistic actions based on a thorough knowledge of the territory and its phenomena to enable integrated and effective land planning and management through suitable communication tools. This study promotes the methodological setup of a Landscape Digital Twin to establish a multi-disciplinary and multi-scalar hazards overview according to a matrix framework implementable over time and space. The original contribution to the research addresses a holistic vision that combines meaningfully qualitative with quantitative approaches to generate risk maps by integrating various indicators within a multi-hazard framework from the socio-economic perspective. This contribution presents road network risk analysis by exploiting flooding and landslide scenarios. The critical road segments or nodes most vulnerable or impacted by network performance and accessibility can be identified with minimal preprocessing from credible open-source sources. The method's applicability is tested in a Piedmont Region, northern Italy case study. The integration proposed will help generate comprehensive risk analysis maps that effectively portray the interconnectedness among natural hazards, infrastructure, and socio-economic factors fostering more resilient decision-making processes.

Increasingly, conservation genetics pinpoint the use of biological matrices collected without stressing wildlife. Cervid’s antlers seem to fit with this need. We verified the amplification success rate from DNA obtained from red deer antlers collected in the State Nature Reserve of Bosco della Mesola, Northern Italy and its use for conservation purposes. Here occurs the only native red deer population of peninsular Italy, recently recognized as a distinct subspecies (Cervus elaphus italicus). Four antlers stored at room temperature for four years and four samples highly degraded by environmental conditions were analyzed using a multimarker approach. We utilized a simple, inexpensive method to extract DNA from drilled antlers powder. This study confirms that weathered antlers can be a suitable source of DNA also in Mediterranean climate characterized by strong seasonal fluctuations, and not only in dry climates. Our results pointed out that only burr drilling yielded good quality amplifiable DNA. Antlers can be used in particular for molecular genetic studies on rare or threatened species of cervids as providing an efficient and cost-effective non-invasive sampling.

Background and Objectives: Acute compartment syndrome (ACS) is an emergency condition of the lower limb in which prophylactic fasciotomy is required to prevent complications. A negative pressure wound therapy (NPWT) used to the treatment of fasciotomy wounds provide beneficial clinical results. This study aimed to exchange the authors’ experience of using the NPWT installation system on the lower limb wounds after fasciotomy in ACS. Materials and Methods: This is a retrospective study enrolled consecutive patients with ACS, who underwent fasciotomy and was treated with the NPWT installation system at Department of Vascular Surgery, Provincial Hospital in Kielce from April 2016 to July 2017. Results: The study enrolled 15 patients with a diagnosis of ACS (87% men, mean age 65 years old). An open four-compartment fasciotomy (87%) or two-compartment fasciotomy (13%) was performed. The NPWT was applied on the first day after fasciotomy in 87% of patients. Therapy was initiated by the negative pressure of 125 mm Hg, which maintained at this level until the therapy was finalized. In 80% of patients, the vacuum-assisted wound closure (VAC) dressing changes were performed every 3 days. The first approximation of fasciotomy wounds margins occurred on the 4th day after surgery among 67% of individuals. The average time of using VAC on fasciotomy wounds was 9 days. The average time to definitive closure edges of fasciotomy wounds was 12 days. The average time of hospital stay was 17 days. Conclusions: Our experience indicates the legitimacy of using NPWT in wound treatment after fasciotomy in ACS. The NPWT enables faster primary closure of wounds, reduces edema, as well as decreases hospitalization time.

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. Also, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We have detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (Liver, Lung, Kidney, Small intestine terminal ileum, Skin not sun-exposed, and Whole Blood). Among them, as expected, we observed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response related genes, reinforce the need to overcome the sex bias of clinical trials.

The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, n = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay. For RT-PCR, NA were investigated. For LAMP, NA from 26 NPS in viral transport medium (VTM) were tested. The other 194 NPS were analyzed directly without prior NA extraction [140 samples in VTM; 54 dry swab samples stirred in phosphate buffered saline]. Ten NPS were tested directly by LAMP using a sous-vide cooking unit. The isothermal assay demonstrated excellent specificity (100%) but moderate sensitivity (68.8%), with a positive predictive value of 1 and a negative predictive value of 0.65 for direct testing of NPS in VTM. The use of dry swabs, even without NA extraction, improved the analytical sensitivity; up to 6% of samples showed signs of inhibition. The LAMP could be performed successfully with a sous-vide cooking unit. This technique is very fast, requires little laboratory resources and can replace rapid antigen tests or verify reactive rapid tests on site.

This research concerns in to understand the link between urban heat and cool island, the Local Climatic Zones (LCZ) and atmospheric systems during the winter season in the city of Balneário Camboriú, Southern Brazil. To collect meteorological data on urban environmental, 11 permanent points in the Balneário Camboriú metropolitan region were installed. To understand the atmos-pheric systems operating in the region, a synoptic analysis of the dates was performed, and then, the LCZs map created for the city in World Urban Database and Acess Portal Tools was used to cor-relate the magnitudes of the heat and cool islands found in Balneário Camboriú in the winter period. The results indicate that the increasing verticalization with the construction of skyscrapers in Balneário Camboriú has a significant influence on local conditions for the occurrence of heat and cold islands. The findings indicate that LCZs with sparsely distributed buildings (LCZs 6, 8 and 9) and LCZs with dense vegetation (LCZ A) have lower intensity magnitudes of heat and cool con-ditions. The biggest magnitudes of heat and cool islands were reported in LCZs 1 and 3 during the timeframe. The synoptic analysis supports earlier researches that points to atmospheric stability (Anticyclonic domain) as a favorable atmospheric setting for the emergence of urban hear and coolness islands.

Training has a significative effect on physiology of blood coagulation both in humans and in horses. Several hemostatic changes have been reported after exercise in the horse but data available are inconclusive. The aim of this study was to investigate the platelet activation and primary platelet-related hemostasis modifications in young untrained Thoroughbred racehorses in the first 4-month timeframe incremental training period in order to improve knowledge on this topic. Twenty-nine clinically healthy, untrained, 2-year-old Thoroughbred racehorses. Never trained Thoroughbreds were followed during their incremental 4-month sprint exercise schedule. Blood collection was performed once a month (T-30, T0, T30, T60, and T90). Platelet aggregation was measured by light transmission aggregometer in response to various agonists: adenosine diphosphate (ADP), collagen and calcium ionophore A23187. Platelet function was evaluated using the Platelet Function Analyzer (PFA-100®) using collagen/ADP and collagen/adrenaline cartridges. Nitrite-nitrate (NOx) plasma concentrations were measured by a colorimetric assay to assess in vivo nitric oxide bioavailability. Platelet activation was investigated also through gene expression analyses (selectin P-SELP, ectonucleotidase CD39-ENTPD1, prostaglandin I2 synthase-PTGIS, endothelial nitric oxide synthase 3-NOS3). Differences among the time points were analyzed and mean±SEM were calculated. Significant modifications were identified compared with T-30 with increase of platelet aggregation (collagen:32.6±4.8 vs 21.6±4.9%; ADP: 35.5±2.0 vs 24.5±3.1%; A23187: 30±4.7 vs 23.8±4%) and a shorter closure time of C-ADP cartridges (75.6±4.4 vs 87.7±3.4 sec) that tended to return to baseline value at T90. NOx concentrations in plasma significantly increased after 30 days of training program compared with baseline. The first long-term training period induce platelet hyperactivity already after 30 days in untrained Thoroughbreds. Regular physical training blunts the negative effects of acute efforts on platelets activation.

This article presents a quantitative assessment of pedagogical support aimed at improving collaborative education at a modern technical university. The article analyzes the structural composition of the universal communicative competence in a foreign language to identify the advantages of the proposed content detailization. An algorithm for constructing educational and speech actions of students with the use of collaborative digital technology, regarding the monitoring and control of tools, is developed and theoretically justified. Microsoft Teams is offered as a platform for implementing digital collaborative learning technology. The didactic possibilities and methodological functions of Microsoft Teams in foreign language teaching are revealed. The digital technology of the collaborative learning algorithm is relevant for building collaborative actions is relevant, since it contributes to the development of the ability to solve common professional tasks. The algorithm of the dialogic communication, including problem, contradiction, conflict, intellectual difficulty, having general professional context as a stimulus to enhance the interaction in pair work is proposed as pedagogical support. The analysis and quantitative assessment of students' oral responses showed that the dialogue in a foreign language, based on the algorithmic component, is more structured and stimulates students' communication on relevant professional-oriented topics.

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.

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 affected upper limb in children with Unilateral Spastic Cerebral Palsy (US CP) has motor and somatosensory impairments, that contribute negatively to children’s bimanual performance and quality of life. Mirror Therapy (MT) is being studied to become an approachable intensive and home-based therapy, suitable for children with US CP. The aim of this study is to examine the feasibility of a 5-week home-based program of MT for children with US CP. Six children aged 8-12 years old performed the therapy, five days per week, 30 minutes per day. A minimum of an 80% of compliance was required. The evaluations included the feasibility of the therapy (compliance, total dosage, perceived difficulty of the exercises, and losses of follow-ups and evaluations), the bimanual performance, the somatosensory function and the quality of life at baseline, at the end of the intervention, and at 1-month follow-up. All children completed the therapy and were included in the analysis. The total accomplishment was 86.47 ± 7.67. The perceived difficulty of the exercises ranged from 2,37 to 4,51. As a conclusion, a home-based program of Mirror Therapy is suitable and feasible for children with US CP.

Introduction: This study aims to investigate the activity of the remdesivir-nirmatrelvir combination against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and to report a case of Coronavirus Disease 2019 (COVID-19) cured with this combination. Methods: A Vero E6 cell-based infection assay was used to investigate the in vitro activity of the remdesivir-nirmatrelvir combination. The SARS-CoV-2 strains tested were 20A.EU1, BA.1 and BA.5. After incubation, a viability assay was performed. The supernatants were collected and used for viral titration. The Highest Single Agent (HSA) reference model was calculated. An HSA score >10 is considered synergic. Results: Remdesivir and nirmatrelvir showed synergistic activity at 48 and 72 h with an HSA score of 52.8 and 28.6, respectively (p<0.0001). This data has been confirmed performing supernatant titration and against the omicron variants: the combination reduced the viral titer better than the more active compound alone. An immunocompromised patient with prolonged and critical COVID-19 was successfully treated with remdesivir, nirmatrelvir/ritonavir, tixagevimab/cilgavimab, and dexamethasone, with an excellent clinical-radiological response. However, she required further off-label prolonged therapy with nirmatrelvir/ritonavir up to the negativization. Conclusion: Remdesivir-nirmatrelvir combination has synergic activity in vitro. This combination may have a role in immunosuppressed patients with severe COVID-19 and prolonged viral shedding.

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.

Parents play an important role in shaping the eating habits of their children through: appropriate selection of food products, snacking between meals and appropriate exposure to information from television advertisements, the press or the Internet. The level of parents' knowledge about proper nutrition and substances added to food is therefore crucial in promoting appropriate dietary choices in children and adolescents in order to prevent diet-related diseases. Objectives: Assessment of the consumption of snack foods by children and adolescents according to the surveyed parents and analysis of parents' knowledge about additional substances in food. Methods: The study was conducted among 129 parents of students from selected primary schools. The research tool was an original survey questionnaire consisting of 24 questions. Survey interviews were conducted with parents during meetings at schools. Statistical analysis was performed using the Pearson ch2 test, the significance level was set to p&lt;0.05. Results: Parents most often indicated sweets, confectionery products and sweetened drinks (25%) and vegetables or fruit (21%) as the form of snack for their children. 46% of children and adolescents drank sweetened drinks at least once a day. Parents had an average level of knowledge about food additives. Significant correlations were found between the level of knowledge of parents of school-age children about food additives and their level of education. Parents' knowledge and education did not significantly influence the level of snack consumption by their children. Children's eating behavior should be considered unsatisfactory. Conclusions: Research has shown the need for parents to be educated about food additives and to pay more attention to reading food labels so that they can reliably prepare their children to make the right food choices. Measures should be implemented to improve the eating habits of children and adolescents.

In recent years cultivated soils have been increasingly supplemented with nutrients that at low doses are necessary for proper plant functioning but become toxic at high doses. New methods are needed to prevent these destructive actions, and for this reason we studied the effects of two elements – Mn treated as a stressor and Se treated as a potential defense in two wheat cultivars. The intensity of stress was manifested in tissue browning and weight reduction and was determined by an increase in lipid peroxidation and quantitative analysis of hydrogen peroxide levels. It was found that the excess of Mn in the substrate caused more intense changes in these indicators in the root system than in the leaves, and that Se presence partly eliminated the stress evoked effects. Moreover, Mn-treatment was accompanied by a greater absorption of this element by the roots, and a reduced uptake of other elements (K, Fe, S, P), with the exception of Ca, an increase in which was observed especially in the additional presence of Se. It was suggested that the rise in Ca level can lead to modification of cell differentiations and may be one of the steps in defense mechanisms. The change in the direction of cell differentiation in the apical part of the root was observed microscopically under Mn stress and was accompanied by a quantitative increase in 5-met C. Based on DNA methylation profiles detected by MSAP we concluded that various types of methylation sites may be activated under Mn treatment in roots.

Tomato pomace (TP), an agricultural industrial waste product from the tomato processing industry, was valorized by being used as a rearing substrates for Tenebrio molitor (L.). This study evaluated bran-based diets with increasing tomato pomace (0%, 27%, 41% and 100%). Protein sources, as brewer’s spent grain and yeast, are used in TP27 and TP41 diets, respectively, to ensure equal protein content to control diet (TP0). Results showed larval survival, larval and pupal weight no different between diets; however, growth time significantly increases in TP100 compared at all diets. The feed conversion rate progressively increases from 2.7 to 4.3, respectively from TP0 to TP100. Conversely, Lycopene and β-Carotene increases in the larvae. Fatty acid composition improves by increasing polyunsaturated fatty acids (mainly -Linoleic acid). Although the best nutritional quality was obtained in T100, the TP41 is the optimal diet for balance between larval performance and qualitative improvement of larvae. Therefore, tomato pomace is suitable for the formulation of mealworm diets, even in high dosages when supplemented with sustainable protein sources.

Background Binge eating disorder (BED) is the most common eating disorder, categorized in DSM-V, but many patients are not diagnosed, because of the difficulty to consider BED distinct condition from obesity. Its identification is important for targeting individuals at high risk of obesity, adverse metabolic pattern, and cardiovascular disease. In this review we have highlighted the main aspects of screening, diagnosis and treatment of patients with BED and Obesity.

The use of natural stone has a historical and environmental value that makes it strategically valuable for landscape conservation in Europe. Marble, among others, is widely spread on Earth, and it offers high-performance features in architectural applications. However, the complexity of these formations and the rock variability in different ore bodies require detailed studies of the natural and induced stress state, the fracturing degree, and the influence of external factor (such as temperature and/or chemical agents) on the mechanical properties in order to optimize the exploitation processes by reducing extractive waste. This article shows a series of studies conducted by the authors over the last 20 years aimed at making the exploitation of marble blocks in the Carrara basin safer, more efficient, and, therefore, more sustainable. In particular, studies for increasing the knowledge on the natural and the induced stress state through on-site measurements and numerical modeling, studies to improve the quality of the exploited material through improvements of cutting technologies, studies to improve the knowledge of the mechanical behavior of the material under varying loads and temperature conditions and studies to improve the reuse of water materials and their reduction are reported.

Introduction: Emotional intelligence plays a critical role in nursing leadership, influencing organizational dynamics and patient care. However, there is limited understanding of the impact of Emotional Intelligence on leadership in Primary Health Care in the Greek context. Methods: A longitudinal experimental design assessed the effects of an educational intervention on EI and leadership among Greek Primary Health Care nurses. Questionnaires, including the Wong and Law Emotional Intelligence Scale (WLEIS) and Multifactor Leadership Questionnaire - form 5x (MLQ), were administered pre- and post-intervention. Results: The intervention group exhibited significant improvements in Emotional Intelligence and adoption of transformational leadership styles compared to the control group. Tables highlighted nuanced changes in leadership dynamics post-intervention. Conclusions: Educational interventions effectively enhance nurses' Emotional Intelligence and influence leadership styles, emphasizing the need for tailored professional development programs in nursing education.

Pediatric obesity management strategies suffer from a high rate of dropout and persistence of weight excess, despite the use of new tools, such as the automated mobile technology (MT). We aimed to compare the efficacy of two personalized MT protocols with/without monthly in-presence recalls in terms of better adherence to follow-up, and improved anthropometric and lifestyle parameters. MT contacts consisted in three not automated messages per week, inserted between three-monthly in-presence regular visits with (PediaFit 1.2) or without (PediaFit 1.1) monthly in-presence recalls. The sample included 103 children (mean age 10 years, range 6-14) recruited in the Pediatric Obesity Clinic between January 2017 and February 2019, randomized in Intervention group (IG) (n=24 PediaFit 1.1; n=30 PediaFit 1.2) and Control group (CG) (total n=49). Both IGs achieved significantly better results than the CGs for all considered parameters. Comparison of the two IGs at the 6th month showed that IG 1.2 had a statistically significant lower drop-out rate (10% vs. 62%), along with improved body mass index z-score, systolic blood pressure, sleep duration and physical activity. The study suggests that the hybrid association of messaging through personalized/not automated MT plus monthly in-presence recalls may be considered for a favorable outcome of pediatric obesity programs.

Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive, cognitive and neurotrophin alterations and their correlation, demonstrating the AD-like symptoms presented in older males SAMP8. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in two of the most important neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin modifications, cognitive impairment and neuropsychiatric disorders (ND).

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet and now widely dis-tributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anti-cancer, insecticidal, antifeedant, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Research on potential uses, under-standing of the nutritional and functional composition, and applications of C. parqui extracts is important and very promising for its commercial use. To date, there are some reports on the potential applications of C. parqui extracts as selective natural pesticides and for their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui as a biopesticide.

Background: In the last years, many new treatment options have widened the therapeutic scenario of genitourinary malignancies. Immunotherapy has shown efficacy, especially in the urothelial and renal cell carcinomas, with no particular relevance in prostate cancer. However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neo-plasms. Cancer vaccines represent another way to activate the immune system. We sought to summarize the most recent advances in vaccine therapy for genitourinary malignancies with this review. Methods: We searched Pubmed, Embase and Cochrane Database for clinical trials conducted in the last ten years, focusing on cancer vaccines in the prostate, urothelial and renal cancer. Results: Various therapeutic vaccines, including DNA-based, RNA-based, peptide-based, dendritic cells, viral vectors, and modified tumor cells, have been demonstrated to induce specific immune responses in a variable percentage of patients. However, these responses rarely corresponded to significant survival improvements. Conclusions: Further pre-clinical and clinical studies will improve the knowledge about cancer vaccines in genitourinary malignancies to optimize dosage, select targets with a driver role for tumor development and growth, and finally overcome resistance mechanisms. Combination strategies represent possibly more effective and long-lasting treatments.

Researchers are exploring solutions to meet the growing demand for protein due to the expected increase in global population by 2050. Interest in alternative protein sources like insects has risen, driven by concerns about environmental impact and the need for sustainable food production. This study aimed to develop and evaluate the physicochemical properties of soy protein-based burger enriched with insect protein from Alphitobius diaperinus. Three formulations were developed: a control (B0), and burgers with 5% (B5) and 10% (B10) insect protein - Whole Buffalo Powder (WBP). Results showed that adding insect protein decreased the burger analogue's pH. There was observed a clear trend of increasing total lipids and SFA, and decreasing MUFA and PUFA, as the WBP concentration increases from 0% to 10%. No significant differences with increasing WBP concentration in the protein content of the burger analogue, as well as the cooking yield, were noted. The WBP addition had a notable effect on the color change, especially decrease in brightness (L*). It was shown that as the WBP concentration increased, there were no significant differences in the texture profile of the burger analogues. The formulation with 5% WBP concentration was the most acceptable in sensory analysis.

The aim of this pilot study was to investigate whether single nucleotide polymorphisms (SNP) in the gene encoding the catalytic subunit of glutamate cysteine ligase (GCLC) are associated with the risk and clinical features of psoriasis. A total of 944 unrelated individuals, including 474 patients with a diagnosis of psoriasis and 470 healthy controls, were recruited for the study. Six common SNPs in the GCLC gene were genotyped using the MassArray-4 system. Polymorphisms rs648595 (OR=0.56 95%CI 0.35-0.90, Pperm=0.017) and rs2397147 (OR=0.54 95%CI 0.30-0.98, Pperm=0.05) were associated with susceptibility to psoriasis in males. In the male group, diplotype rs2397147-C/C×rs17883901-G/G was associated with decreased risk of psoriasis (FDR-adjusted P=0.014), whereas diplotype rs6933870-G/G×rs17883901-G/G (FDR-adjusted P=0.045) showed association with increased disease risk in females. Joint effects of SNPs with tobacco smoking (rs648595 and rs17883901) and alcohol abuse (rs648595 and rs542914) on the risk of psoriasis were observed (Pperm≤0.05). Furthermore, we found multiple sex-independent associations between GCLC gene polymorphisms and various clinical features such as earlier disease onset, the psoriatic triad, and specific localizations of skin lesions. The present study is the first to show that polymorphisms of the GCLC gene are significantly associated with the risk of psoriasis and related to its clinical features.

Polyalcohol liquefaction can be done by acid or basic catalysis producing polyols with different properties. This study compared the mechanical properties of foams produced using polyols from liquefied Cytisus scoparius obtained by acid and basic catalysis and using two different foam catalysts. The differences were monitored using FTIR analysis. Acid-catalyzed liquefaction yielded 95.1 %, with the resultant polyol having an OH index of 1081 mg KOH/g while basic catalysis yielded 82.5 %, with a similar OH index of 1070 mg KOH/g. Generally, compressive strength with dibutyltin dilaurate (DBTDL) ranged from 16 - 31 kPa (acid-liquefied polyol) and 12 -21 kPa (base-liquefied polyol), while with stannous octoate (TIN), it ranged from 17 - 42 kPa (acid) and 29 - 68 kPa (base). Increasing water content generally decreased the compressive modulus and strength of foams. Higher water content led to a higher absorption at 1670 cm-1 in the FTIR spectrum due to the formation of urea. Higher isocyanate indices generally improved compressive strength, but high amounts led to unreacted isocyanate that could be seen by a higher absorption at 2265 cm-1 and 3290 cm-1. DBTL was shown to be the best foam catalyst due to higher trimer conversion seen in the spectra by a higher absorption at 1410 cm-1. Acid and base-derived polyols lead to different polyurethane foams with different FTIR spectra, particularly with a higher absorption at 1670 cm-1 for foams from acid-derived liquefaction.

Existing methods for simulating missile dynamics and training often rely on three degrees of freedom (3DOF) motions, limiting their ability to represent the complex maneuvers and targeting strategies of modern missiles. This paper proposes integrating virtual reality (VR) technology with six degrees of freedom (6DOF) dynamics to enhance the accuracy and efficiency of missile simulation and training. By incorporating 6DOF dynamics, simulations can capture the full range of missile motion, providing a comprehensive understanding of their capabilities and limitations. Through VR, users can immerse themselves in realistic missile scenarios, interact with dynamic behaviors in real-time, and refine their targeting and interception skills. The integration of VR with 6DOF dynamics also facilitates real-time feedback and evaluation, enhancing training efficiency and proficiency in missile operations. This approach aims to revolutionize missile training by bridging the gap between traditional simulation methods and real-world dynamics.

Gentiopicroside (GPS) is a leading component of several plant species from Gentianaceae botanical family. As a compound with plenty biological activities and a component that is often consumed in dietary supplements and herbal drugs, GPS has an important role in the regulation of physiological processes in humans. Recent studies on the type 2 receptors shed new light on GPS applications showing its agonistic properties that could be meaningful in the future therapeutic strategies of Parkinson’s disease, thyroid disorders or cancer states. This review aims to collect previously published reports on the biological properties of GPS as a single compound that were confirmed by in vitro and in vivo studies, and to draw attention at the newly discovered role of this bitter-tasting secoiridoid as a type 2 receptor agonist. Thanks to these properties, the research on this substance could be revisited.

In order to achieve global climate goals, it is necessary to estimate greenhouse gases (GHG) fluxes from ecosystems. To obtain a comprehensive assessment of CO2, СН4, N2O natural fluxes for the Russian Federation we used the "bottom-up" method according to [1]. We updated estimates for forest ecosystems based on State Forest Inventory data and satellite monitoring of forest disturbances. For grassland ecosystems, it was based on the correct distribution of areas between steppe and non-steppe zones. The estimated net uptake of natural ecosystems of Russia was 1.1 ± 1.8 billion tons of CO2-eq./year. The study shows that if only CO2 is taken into account, the net absorption of terrestrial ecosystems in Russia corresponds to more than -2.5 billion tons of CO2 (35% of forests’ contribution). However, given the emissions of non-CO2 GHGs, total net absorption in Russia’s natural ecosystems is reduced to about -1 billion tons of CO2-eq (with the forests’ contribution increasing to 80%). With regard to anthropogenic fluxes, the overall balance of GHGs in Russia corresponds to net-emissions of 1 billion tons of CO2-eq/year into the atmosphere. To improve reporting under the Paris Agreement, countries should aim to include only anthropogenic ("manageable") GHG fluxes on managed land.

Uveal melanoma represents the most prevalent form of primary malignant intraocular tumor in adults. Historically, enucleation was considered the gold-standard approach in the treatment of uveal melanoma. Nowadays, radiotherapy is the most commonly used therapy, aiming at a better quality of life. However, radiotherapy can result in several ocular complications, some of which may be vision-threatening. Radiation-induced dry eye, scleral necrosis, cataract, rubeosis iridis, neovascular glaucoma, radiation retinopathy and maculopathy and optic neuropathy are the most common. This article aims to summarize the current literature on the ocular complications after radiotherapy, their clinical features, risk factors and management strategies. A thorough understanding is crucial for ophthalmologists and oncologists to provide optimal patient care, improve visual outcomes, and minimize long-term complications.

This paper considered the issue of agricultural fields boundary recognition in satellite images. A novel algorithm based on the aggregated history of vegetation index data obtained via open satellite data, Sentinel-2, was proposed. The proposed algorithm included several basic steps, namely the detection of parcel regions on aggregated index data; the calculation of aggregated edge maps; the segmentation of parcel regions using the edges obtained; the computation of connected components and their contour extraction. In this paper, we showed that the use of aggregated vegetation index data and boundary maps allow for much more accurate agricultural field segmentation compared to the instant vegetation index approach. The quality of segmentation within regions of Russia and the Ukraine was estimated. The dataset that was used and Python implementation of the proposed algorithm were provided.

Hotel water systems colonized with Legionella spp. have been the source of travel-associated Legionnaires’ disease and cases, clusters or outbreaks continue to be reported worldwide each year. A total of 132 hotels linked with travel-associated Legionnaires’ disease, as reported through the European Legionnaires’ Disease Surveillance Network, were inspected and tested for Legionella spp. during 2000–2019 by the public health authorities of the island of Crete (Greece). A total of 3,311 samples were collected: 1,885 (56.93%) from cold water supply systems, 1,387 (41.89%) from hot water supply systems, 37 (1.12%) were swab samples and two (0.06%) were soil. Of those, 685 (20.69%), were collected from 83 (62.89%) hotels, testing positive (≥ 50CFU/L) for Legionella pneumophila) serogroups 1-10, 12-14 and non-pneumophila species (L. anisa, L. erythra, L. tusconensis, L. taurinensis, L. birminghamensis, L. rubrilucens, L. londiniesis, L. oakridgensis, L. santicrusis, L. brunensis, L. maceacherii). The most frequently isolated L. pneumophila serogroups were 1 (27.92%) and 3 (17.08%). Significantly higher isolation rates were obtained from hot water supply systems (25.96%) versus cold water systems (16.98%) and swab samples (13.51%). A Relative Risk (R.R.) > 1 (p < 0.0001) was calculated for hot water temperature <55 °C (R.R.: 4.43), chlorine concentrations <0.2 mg/L (R.R.: 2.69), star rating <4 (R.R.: 1.73) and absence of Water Safety Plan implementation (R.R.: 1.57).

The main objective of this paper was description of seasonal and interannual trends in secondary production and mortality rates of the three most important Copepoda taxa in the Gulf of Gdańsk (southern Baltic Sea). Samples were collected monthly from 6 stations located in the western part of the Gulf of Gdańsk during three research periods: 1998-2000, 2006-2007 and 2010-2012. Production was computed basing on copepod biomass and mortality rates estimated according to vertical life table approach. Redundancy analysis was used to investigate relationship between secondary production and environmental conditions. Considering the entire research period there was significant interannual and seasonal variability of secondary production, mortality rate as well as abundance and biomass anomalies. Conducted analysis revealed correlation between increasing temperature and production of Acartia spp. and T.longicornis developmental stages, while older copepodites of P.acuspes showed almost negative correlation with temperature. The mortality rate estimations obtained for Acartia spp. Were highest in summer, while for T.longicornis peak was usually noted in spring-summer period. Lowest mortality rate estimations were noted in autumn and winter for almost all stages of investigated taxa.

Despite Low Power Wide Area Networks’ ability to offer an extended range, it might still encounter challenges with coverage blind spots in the network. This article proposes an innovative energy-efficient nature-inspired relay selection algorithm for LoRa-based LPWAN networks, serving as a solution for challenges related to poor signal range in areas with limited coverage. A behavior swarm-inspired approach has been utilized to select the relays’ localization in the network, providing network energy efficiency and radio signal extension. These relays help bridge communication gaps, significantly reducing the impact of coverage blind spots by forwarding signals from devices with poor direct connectivity with the gateway. The proposed algorithm considers critical factors for the LoRa standard, such as the Spreading Factor or device energy budget analysis. The simulation experiments validate the proposed scheme’s effectiveness in terms of energy efficiency under diverse multi-gateway topology scenarios involving thousands of devices. Specifically, it has been verified that the proposed approach outperforms the reference method in preventing the battery depletion of relays, which is vital for battery-powered IoT devices. Furthermore, for some large-scale problems, the proposed heuristic method achieves over twice the speed of the exact method with a negligible accuracy loss of less than 2%.

Pancreatic ductal adenocarcinoma (PDAC) is a ravaging disease whose poor prognosis requires a more detailed understanding of its biology to foster the development of effective therapies. The unsatisfactory results of treatments targeting cell proliferation and its related mechanisms suggested to rather focus on the inflammatory tumor microenvironment (TME). Here, we discuss the role of cancer secreted proteins in the complex TME tumor-stroma crosstalk, to sched lights on druggable molecular targets for the development of innovative, safer and more efficient therapeutic strategies.

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive and cognitive states as well as molecular alterations and their relationship, demonstrating the AD-like symptoms presented in older SAMP8 males. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in three of the most important neurotrophins, such as NT3, BDNF, and NGF as well as their receptors TrkA and TrkB, were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin alterations, cognitive impairment and neuropsychiatric disorders (ND).

The interactive approach implies that a heterogeneous group of actors cooperates to identify, develop, and introduce innovative solutions into the ground. 20-year studies showed this approach as the most suitable to support innovation and knowledge sharing in the agri-food system. With the introduction of the EIP initiative in the EU policy, this approach has become a privileged tool to support innovation within the CAP, via the implementation of Operational Groups. The present study aims to analyse how the interaction process works in the implementation of the OGs in Italy, and its effectiveness. An online survey submitted to 270 OGs and 10 in-depth case studies were used to analyse interaction process and its effectiveness in the Italian OGs. The results show that the EIP AGRI in Italy helped to capture the real issues of farmers and other actors in the rural territories. Furthermore, participation in the OGs supported the creation and strengthening of relationships between partners. The major difficulties were identified in maintaining active interaction in all phases of the projects and with all partners involved and in the traditional approach used for dissemination of results, both within and outside the partnership. The study showed how complex is to describe the processes triggered by the interactive approach, being it influenced by the type of relationships existing between partners and by other external factors.

The development of virtual models has recently been generalized in the field of complex mechatronic product design. Virtual models have various advantages such as: the systemic design approach, most often parametric, the implementation of extreme, expensive, and perhaps risky scenarios for the operation of the designed product, the testing of a large number of variants, etc. The main contribution of the paper consists of the development of an interface family called DeSeRoI (Dedicated Serial Robot Interface). Each member of the interface family integrates Simulink libraries and is created by the programmer in accordance with user requests. It follows that the interfaces composing the DeSeRoI family can have different levels of complexity depending on user needs and constraints. We are implementing a MATLAB-based application with user-provided configuration for serial robots in order to automatically visualize the kinematics data and simulation. Within MATLAB, two scripts are created responsible for generating Simulink models that compute the kinematics problem. One of the scripts (Main) saves information about the configuration of the robot and the other one (Generates_Simulink_Models) computes the kinematics problem. Different types of functions (software module) have been developed. Using these functions, the Simulink models result as modular entities. The automated approach eases user’s interaction and understanding of serial robots’ kinematics by performing the simulation procedure in a shorter amount of time and with higher efficiency, assuring a precise outcome despite the chosen parameters.

The increasing emergence of multidrug resistant (MDR) pathogens causes difficult-to-treat infections, with long-term hospitalizations and high incidence of death, thus representing a global public health problem. To manage MDR bacteria bugs, new antimicrobial strategies are necessary, and their introduction in practice is a daily challenge for scientists in the field. An extensively studied approach to treat MDR infections consists in inducing high levels of reactive oxygen species (ROS) by several methods. Although further clinical investigations are mandatory on the possible toxic effects of ROS to mammalian cells, clinical evaluations are extremely promising, and their topical use to treat infected wounds and ulcers, also in presence of biofilm, is already clinically approved. Biochar (BC) is a carbonaceous material obtained by pyrolysis of different vegetable and animal biomass feedstocks, at 200−1000 °C in limited presence of O2. Recently, it has been demonstrated that BC capability of removing organic and inorganic xenobiotics is mainly due to the presence of persistent free radicals (PFRs), which can activate oxygen, H2O2 or persulfate in the presence or not of transition metals by electron transfer thus generating ROS, which in turn degrade pollutants by advanced oxidation processes (AOPs). In this context, the antibacterial effects of BC containing PFRs have been demonstrated by some authors against Escherichia coli and Staphylococcus aureus, thus giving birth to our idea of the possible use of BC-derived PFRs as a novel method capable of inducing ROS generation for antimicrobial oxidative therapy. Here, the general aspects concerning ROS physiological and pathological production and regulation, and the mechanism by which they could exert antimicrobial effects have been reviewed. The methods currently adopted to induce ROS production for antimicrobial oxidative therapy have been discussed. Finally, for the first time, BC-related PFRs have been proposed as a new source of ROS for antimicrobial therapy via AOPs.

Mathematical models of cognition measure individual differences in cognitive processes, such as processing speed, working memory capacity, and executive functions, that may underlie general intelligence. As such, cognitive models allow identifying associations between specific cognitive processes and tracking the effect of experimental interventions aimed at the enhancement of intelligence on mediating process parameters. Moreover, cognitive models provide an explicit theoretical formalization of theories regarding specific cognitive process that may help overcoming ambiguities in the interpretation of fuzzy verbal theories. In this paper, we give an overview of the advantages of cognitive modeling in intelligence research and present models in the domains of processing speed, working memory, and selective attention that may be of particular interest for intelligence research. Moreover, we provide guidelines for the application of cognitive models in intelligence research, including data collection, the evaluation of model fit, and statistical analyses.

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.

Coronaviruses are highly transmissible and pathogenic viruses for humans and animals. The vast quantity of information collected about SARS-CoV-2 during the pandemic helped to unveil details on the mechanisms behind the infection, which are still largely elusive. Recent research demonstrated that different class I/II human leukocyte antigen (HLA) alleles might define an individual susceptibility to SARS-CoV-2 spreading, contributing to the differences in the distribution of the infection through different populations; additional studies suggested that the homolog of the HLA in cats, the Feline Leukocyte Antigen (FLA), plays a pivotal role in the transmission of viruses. With these premises, this study aimed to exploit a bioinformatic approach for the prediction of the transmissibility potential of two distinct Feline Coronaviruses (FCoVs) in domestic cats (Feline enteric Coronavirus, FeCV and Feline Infectious Peritonitis Virus, FIPV) using SARS-CoV-2 as the reference model. We performed an epitope mapping of nonapeptides deriving from SARS-CoV-2, FeCV and FIPV glycoproteins and predicted their affinities for different alleles included in the three main loci in class I FLAs (E, H and K). The predicted complexes with the most promising affinities were then subjected to molecular docking and molecular dynamics simulations to provide insights into the stability and binding energies in the cleft. Results showed the FLA proteins encoded by alleles in FLA-I H (H*00501 and H*00401) and E (E*01001 and E*07001) loci are largely responsive to several epitopes deriving from replicase and spike proteins of the analyzed coronaviruses. The analysis of the most affine epitope sequences resulting from the prediction can stimulate the development of anti-FCoV immunomodulatory strategies based on peptide drugs.

Mothers’ own milk (MOM) for premature babies is considered a life-saving drug for its proven protective action against the complications of prematurity and for the effects on the outcome in the short and long term, especially the neurological one. We studied the use of the MOM for WLBWs over a 5-year period. Statistical comparisons concerned data on feeding with the MOM during stay in NICU and at discharge with respect to maternal and neonatal variables (gestational age, birth weight, type of pregnancy if single or twin, maternal age) and to feeding data (timing of the start of the Minimal Enteral Feeding and the availability of the MOM, the achievement of the Full Enteral Feeding, the type of nutrition at discharge). We observed an increase, between 2017 and 2021, of MOM use (p=0.003). The availability of the MOM occurred on average on the fourth day of life and improved over the years. Start of MEF with human milk averaged 1.78 days and 54.3% of VLBWs received MEF with donor milk on the first day of life (50% within the first 6 hours). The average MOM at discharge was 47.6% with 36.1% exclusive MOM (EMOM) and an increase from 45.8% in 2017 (EMOM 33.3%) to 58.82% (EMOM 41.18%) in 2021. The mean average daily growth of the weight improved (p<0.001) during this period. There is no statistical difference between infants fed with MOM and those fed with bank milk. The maternal age, the start day of the MOM feeding and gestational age have a significant impact on the type of feeding at discharge.

Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments of the nephron, consistent studies demonstrated that well-characterized, distinct populations of progenitor cells, localized in the parietal epithelium of Bowman capsule and scattered in the proximal and distal tubules, could generate segment-specific cells in physiological conditions and following tissue injury. However, defective or abnormal regenerative responses of these progenitors can contribute to pathologic conditions. The molecular characteristics of renal progenitors have been extensively studied, revealing that numerous classical and evolutionarily conserved pathways, such as Notch or Wnt/β-catenin, play a major role in cell regulation. Others, such as retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-Like Receptor 2) and leptin, are also important in this process. In this review, we summarize the plethora of molecular mechanisms directing renal progenitor responses during homeostasis and following kidney injury. Finally, we will explore how single cell RNA sequencing could bring the characterization of renal progenitors to the next level, while knowing their molecular signature is gaining relevance in the clinic.

The import and export of tree seed carries with it risks of inadvertent introduction of pests and pathogens to hitherto unaffected regions. Although trade in seed of specified trees is regulated, phytosanitary requirements for most tree species are minimal, even those related to the most important forest tree species in a given region. A better understanding of the microbiome associated with seed intended for commercial production or ornamental use, and their potential risk with the transport from the source origin of distributors, will help regulatory agencies implement measures to prevent new and emerging risks. In this study we used high throughput sequencing to show that highly diverse fungal communities were associated with seed of 14 different Pinus species obtained from seed banks (seed orchards) and retail sources (online distributors) in North America and Europe. Fungal diversity differed among the 23 seedlots tested. Community composition did not relate to the species of Pinus nor the country of origin. Assigned potential functions based on sequence identity using FUNGuild provided an overall understanding of the likely life strategies associated fungal OTUs. Of those sequences classified to a trophic level, 453 were plant pathogens, with the Dothideomycetes having the highest prevalence. The most common plant pathogens detected included Sydowia polyspora, Lasiodiplodia theobromae, Diplodia intermedia and Diplodia sapinea. The evidence presented here illustrates an urgent need for plant protection authorities, practitioners and the general public to recognize the potential risk of introducing harmful pathogens through innocent transport of seed.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

Background: Our study investigates the prevalence and causes of injuries among undergraduate dental students during clinical sessions. Methods: The study was conducted at the Department of Dentistry, National and Kapodistrian University of Athens, focusing on injuries reported from 2021 to 2024. Data were collected through self-reported questionnaires and clinical records. The primary variables assessed included the type of injury, the instrument involved, the clinical procedure being performed, and the immediate actions taken post-injury. Serological testing was conducted on both students and patients to assess the risk of bloodborne pathogen transmission. Results: The findings revealed a high prevalence of injuries, with needles being the most common cause, followed by burs and dental probes. The most frequent injury type was piercing, primarily affecting the fingers. Periodontal treatments, restorative procedures, and endodontic treatments were the main activities leading to injuries. Despite normal medical records for most patients treated by injured students, serological testing showed significant positivity rates for HCV and HBV. It is noteworthy that most injured students demonstrated their commitment to safety by adhering to recommended post-exposure protocols, including wound cleaning, disinfecting, and serological testing. Our study highlights the critical need for enhanced biosafety awareness and training among dental students to reduce injury risks. Conclusions: These findings underline the necessity for integrated safety protocols and continuous education to improve clinical practices and ensure student safety.

Telemonitoring and telerehabilitation have shown promise in delivering individualized healthcare remotely. We introduce STASISM, a Sensor-Based Telerehabilitation and Telemonitoring System, in this work. This platform has been created to facilitate individualized telerehabilitation and telemonitoring for those who need rehabilitation or ongoing monitoring. To gather and analyze pertinent and validated physiological, kinematic, and environmental data, the system combines a variety of sensors and data analytic methodologies. The platform facilitates customized rehabilitation activities based on individual needs, allows for remote monitoring of patients' progress, and offers real-time feedback. To protect the security of patient data and to safeguard patient privacy, STASISM also provides secure data transmission and storage. The platform has the potential to significantly improve the accessibility and efficacy of telerehabilitation and telemonitoring programs, enhancing patients' quality of life and allowing healthcare professionals to provide individualized care outside of traditional clinical settings/

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked with age-related epigenetic changes in fathers sperm. Understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here we characterize changes in sperm sncRNA between young pubertal and mature rats. We also analyze modification of these changes by exposure to environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). SncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. Distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (2-fold change, FDR p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, piRNA were enriched for LTR targets. BDE-47 accelerated age dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposures.

Tomato (Solanum lycopersicum L.) has almost 190 million tonnes produced in 2023. Tomato fruit suffer losses of up to 50% during harvest and transport, which causes financial hardship, reduces the amount of food available and causes environmental harm. Calcium plays an important role in cell wall strength. This work assessed the use of a calcium transport stimulants (MCAS) to increase the firmness of tomato fruit in the laboratory and the foliar application to tomato plants. Then handling damage was simulated. In the laboratory, the calcium with MCAS significantly increased the fruit firmness compared to the untreated and calcium without MCAS, which were not significantly different. When calcium with MCAS was applied to tomato plants foliarly before harvest, the calcium with MCAS treated fruit were significantly firmer than the untreated or calcium without MCAS treated fruit for up to 10 weeks after harvest, and this was achieved by applying only 0.91 kg ha-1 calcium. Finally, when fruit were exposed to a simulated drop, the calcium with MCAS treated fruit remained firmer than the undamaged fruit or dropped fruit with calcium without MCAS. Calcium with MCAS could significantly increase the fruit firmness and increase the shelf-life of tomatoes while applying less calcium.

Throughout the Covid19 period, families were forced to stay indoors, adapting to online school-ing, remote work, and virtual social engagements, inevitably altering the dynamics within households. There is a notable increase in mental health challenges in terms of anxiety and de-pression in children and adolescents. This study intends to explore the psychosocial effects of the Covid-19 pandemic in Italian families adopting self- and proxy-report questionnaires on anxiety, anger, and health-related quality of life. The results showed that approximately 20% obtained a clinical anxiety score and only 10% obtained a clinical anger score. There was found a difference in the perception of the quality of life reported by the child and that perceived by the parent. The stepwise regression model showed that total anxiety scores were predicted by sex, quality of life scores from the parents' self-report version and total anger score. Another stepwise regression model identified physiological and social anxiety as the best predictors that impact the quality of life. Parental well-being actively influences the well-being of children, so it is fundamental to implement preventive programmes and promote child well-being providing parents the most adequate support possible.

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilizing the membrane protein arrangement in the virion. The residues responsible for the M protein inter-actions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein, which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.

A variety of environmental factors contribute significantly to age-related cognitive decline and Alzheimer’s Disease (AD). Nutrition can alter epigenetics, improving health outcomes, which transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in offspring. We feed females SAMP8 with resveratrol-enriched diet during two months prior to mating. Direct exposed F1 generation and the transgenerational F2 generation were investigated. Object novel recognition and Morris water maze demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring resulted from resveratrol fed mother showed increase AMPKα activation, mTOR inhibition and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.

Talking about sustainable development refers mainly to the environmental sphere, but the concept is much broader and also takes into account the social and economic conditions. The concept of sustainability, in this sense, is linked to the compatibility between the development of economic activities, the related social phenomena, and the protection of the environment. Therefore, the ability to balance social, economic and environmental sustainability is the very meaning of the concept of sustainable development. Firms that choose to develop policies and strategies to enhance and pursue sustainable development in the medium to long term have the burden of having to quantitatively document the improvements in production processes with the aim of sustainable development. As a result, one of the biggest challenges for European industry is to introduce sustainability principles into business models leading to competitive advantage. This is particularly important in raw material and energy intensive manufacturing sectors such as the ceramic industry. The present state of knowledge lacks a comprehensive operational tool for industry to support decision-making processes geared towards sustainability. In the ceramic sector, the economic and social dimensions of the product and processes have not yet been given sufficient importance. Moreover, the traditional research on industrial districts lacks an analysis of the relations between firms and the territory with a view to sustainability. Finally, the attention of scholars in the field of economic and social sustainability, has not yet turned to the analysis of the Sassuolo district. Therefore, in this paper we introduce the Life Cycle Sustainability Assessment (LCSA), as a method that can be a suitable tool to fill this gap, because through a mathematical model it is possible to obtain the information useful for decision makers to integrate the principles of sustainability both at the microeconomic level in enterprises, and at the meso-economic level for the definition of economic policies and territorial governance. Environmental and socio-economic analysis was performed from the extraction of raw materials to the packaging of the product on different product categories manufactured by the Italian ceramic industries of the Sassuolo district (northern Italy). For the first time the LCSA model, usually applied to unitary processes, is extended to the economic and industrial activities of the entire district, extending the prospect of investigation from the enterprise and its value chain to the integrated network of district enterprises.

IBD, encompassing CD and UC, are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The bidirectional communication between the gut and the brain, known as the GBA, is disrupted in IBD, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBD affects the brain's inflammatory response system, hormonal axis, and BBB integrity, influencing gut microbiota and clinical responses to probiotics. This review aims to explore the links between dysregulations in the GBA, serum biomarkers, and the development of MCI and NDDs. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on NDDs. Studies suggest a potential link between IBD and extraintestinal complications such as MCI and NDDs. Mechanisms include systemic inflammation, BBB dysfunction, autoimmune responses, GBA dysfunction, medication effects, and comorbidities. Serum biomarkers, including vitamin D3, C-reactive protein, high-sensitivity C-reactive protein, vitamin B12, homocysteine, serum amyloid, neuron-specific enolase, neurofilament light chain, S100 proteins, brain-derived neurotrophic factor, IL-6, LP-2 associated phospholipase, prostaglandin E2, IL-1β, and TNF-α, have been investigated for their potential to predict MCI but current results are lacking clarity.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

Cognitive function, arthrogryposis, obstetrics palsy, children, motor disorder

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.

Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care. Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis. Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions. Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.

The structure and physicochemical properties of polyvinyl alcohol (PVA) and PVA/glycerol films have been investigated by Fourier-transform infrared spectroscopy (FT-IR), X-ray Diffraction (XRD), thermogravimetry/differential thermal analysis (TG/DTA), and advanced scanning probe microscopy (SPM). In the pure PVA films, SPM allowed us to observe ribbon-shaped domains with a different frictional and elastic contrast, which apparently originated from a correlated growth or assembly of PVA crystalline nuclei located within individual PVA clusters. The incorporation of 1.0 wt.% glycerol led to modification in shape of those domains from ribbon-like in pure PVA to rounded in PVA/glycerol 1.0 wt.% films; changes in the relative intensities of the XRD peaks and a decrease of the amorphous halo in the XRD pattern were also detected, while the DTA peak corresponding to the melting point remained at almost the same temperature. For higher glycerol content, FT-IR revealed additional glycerol-characteristic peaks presumably related to the formation of glycerol aggregates, and XRD, FT-IR, and DTA all indicated a reduction in crystallinity. For more than 2.0 wt.% glycerol, the plasticization of the films complicated the acquisition of SPM images without tip-induced surface modification. Our study contributes to the understanding of crystallinity in PVA and how it is altered by a plasticizer such as glycerol.

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% ee with use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. Deprotonation of the starting phenol building block was base catalyzed. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles compared to previously reported protocols.

Background: Children with anorectal malformation (ARM) require long-term follow-up, especially for fecal continence and main predictors of longer-term success are the type of ARM, associated anomalies and sacral integrity. Three-Dimensional High Resolution Anorectal Manometry (3D-HRAM) provides an image of the pressure profile of anal sphincter complex. Aim of study was to evaluate the anal sphincter function in ARM patients with 3D HRAM correlating this analysis to clinical outcome and to associated malformations. Methods: Forty ARM patients, were submitted to 3D HRAM: manometric, anatomical and clinical score were correlated to response to bowel management (BM). Results: A positive correlation between all scores and type of ARM was found: in high ARM and in patients with spinal anomalies (regardless to ARM type) lower scores were reported and even after BM they do not achieve good continence. Conclusions: 3D-HRAM provides information on the functional anatomy of the sphincter complex. Our study shows good correlation between the manometric results and clinical outcome, confirming spinal malformations and ARM type as most important prognostic risk factors for poor outcome. Specific sphincteric defects can be explored with manometry, allowing for tailored bowel management strategies.

Academics in healthcare grapple with the challenge of efficiently managing time while addressing diverse roles and responsibilities, leading to heightened levels of anxiety and stress within the academic community. The primary objective of this study is to offer a sustainable and systemic solution to the prevalent time-management challenges in healthcare academia, through the development of a predictive model. Employing systemic analysis software and adopting a systemic management approach, we crafted a model to address academic time-management concerns. The dynamics of time allocation for academicians are governed by three fundamental pillars: teaching, research, and administrative tasks. Significantly prioritizing administrative tasks depletes valuable academic time, making time management within academia excessively costly. This occurs as highly skilled individuals find themselves diverted towards administrative duties at the expense of their academic roles diminishing resilience levels. The proposed Timebooster Academic Systemic Model (TASM) advocates for the cultivation of soft skills in academia, en-compassing prioritization, seeking assistance, and addressing tendencies of perfectionism and procrastination. Additionally, TASM recommends the implementation of full automation, delegation of administrative responsibilities, and the mitigation of both overt and covert time-consuming elements. Furthermore, TASM reports on the pivotal role of the academic resilient manager-leaders, who actively contribute to their own satisfaction and academic growth by enhancing collaboration and teamwork. Time-management challenges emerge as a critical determinant of academic well-being and resilience. Systemic models, exemplified by TASM, offer a valuable framework for investigating prioritization concerns, identifying administrative impediments in academic processes, and managing low-value time-consuming elements. The TASM model, along with the systemic philosophy underpinning its design, presents an avenue for advancing the exploration of time-management phenomena within the context of healthcare academia.