We extend Ziv and Lempel's model of finite-state encoders to the realm of lossy compression of individual sequences. In particular, the model of the encoder includes a finite-state reconstruction codebook followed by an information lossless finite-state encoder that compresses the reconstruction codeword with no additional distortion. We first derive two different lower bounds to the compression ratio that depend on the number of states of the lossless encoder. Both bounds are asymptotically achievable by conceptually simple coding schemes. We then show that when the number of states of the lossless encoder is large enough in terms of the reconstruction block-length, the performance can be improved, sometimes significantly so. In particular, the improved performance is achievable using a random-coding ensemble that is universal, not only in terms of the source sequence, but also in terms of the distortion measure.

Most popular statistical models in epidemic evolution focus on the dynamics of average relevant quantities and overlooks the role of small fluctuations on the model parameters. Models for Covid-19 are no exception. In this paper we show that the role of time-correlated fluctuations, far from being negligible, can in fact determine the spreading of an epidemic and, most importantly, the resurgence of the exponential diffusion in the presence of time-limited episodes in promiscuity behaviours.

We show that the van der Waals gas does not exhibit just the celebrated liquid-gas 1 transition but also a quantum-classical one. We study the issue with reference to the LMC statistical 2 complexity and in relation to the order-disorder contrast.

Bovine mastitis (BM) has been causing great economic and financial losses in the dairy industry worldwide and one of its major pathogenic agents is S. aureus. BM treatment still relies on antibiotics. The extensive use of antimicrobials gives rise to bacterial strains such as methicillin-resistant S. aureus (MRSA) and mupirocin-resistant S. aureus (MuRSA). This study aimed to investigate and compare the prevalence of MRSA and MuRSA and antimicrobial susceptibility in S. aureus isolates from bovine mastitis milk in conventional and organic dairy farms. Milk samples were taken from mastitis-infected cattle in 6 conventional and 7 organic dairy farms from South Korea. According to the Food Codex, 163 suspected S. aureus colonies were isolated from the pooled milk samples from each farm. Further rapid coagulase test confirmed 11 out of 74 isolates from 4 conventional farms (CF1, CF2, CF3, CF4) while 17 out of 89 isolates from 3 organic farms (OF1, OF2, OF3) exhibited coagulase activity. Multiplex PCR amplification showed that the nuc gene marker for S. aureus was found in all coagulase-positive isolates from OF 1 and at least one isolate from CF1, CF2, CF3, and CF4. Conversely, only 2 isolates from CF2 contained mecA gene for MRSA while none had the mupA gene for MuRSA. Antimicrobial susceptibility testing revealed that conventional farm isolates were more resistant to antibiotics particularly, against ampicillin and tetracycline, and, in turn, could imply a potential to develop multidrug resistance if stringent measures to control antimicrobial use in dairy farms is not implemented properly.

Background/Objectives Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infections and persistent gas-trointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from Silybum marianum seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis; Methods NMR spectroscopy (¹H, ¹³C, and DEPT) identi-fied silydianin as the primary compound, with minor flavonolignans and trace amounts of an oxidation product. The study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included Coxsackievirus B2, Coxsackievirus A10, Poliovirus SL-1, and Enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model of gastroparesis using doses of 100 and 200 mg/kg compared to a control; Results: The silydianin-rich extract exhibited con-sistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC50 values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with Coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%; Conclusions These results suggest that silydianin may be effective in treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

Volatile organic compounds (VOCs) are among the most abundant air pollutants. Their high concentrations can adversely affect the human body and therefore, early detection of VOCs is of outmost importance. Among the different VOCs, in this review paper, we have focused our attention on the monitoring of acetaldehyde by chemiresistive gas sensors using nanostructured semiconducting metal oxides. These sensors not only can provide a high sensing signal for detection of acetaldehyde, but also high thermal and mechanical stability and low price. This review paper is divided into three major sections. First, we will introduce acetaldehyde as the target gas and the importance of its detection. Then, the fundamentals of chemiresistive gas sensors will be briefly presented and, in the last section, a survey of literature on acetaldehyde gas sensors will be discussed. Acetaldehyde sensors working mechanism, their structures and configurations are reviewed. Finally, the future development outlook and potential applications are discussed, giving a complete panoramic view for researcher working and interested in acetaldehyde detection for different purposes in many fundamentals and applicative fields.

In this paper we establish information theoretical bridges between 1) Thermal Heisenberg uncertainties $\Delta x \Delta p$ (at temperature $T$), and 2) LMC structural quantifiers. After having achieved such purpose, we determine to what an extent our bridges can be extended to both the semi classical and classical realms. Also, we find a strict bound relating a special LMC structural quantifier to quantum uncertainties.

Fire is a common disturbance in the Brazilian savanna (Cerrado), wherein high-frequency fires drive the vegetation structure, composition, function, and dynamics of savanna ecosystems. Under climate change pressure, further understanding of fire-vegetation relationships and interactions can provide new approaches for establishing strategies for integrated fire management and promote savanna vegetation recovery post-fire. To understand how 15 years of yearly manipulated burning affects the vertical and horizontal structure of the vegetation, the species composition and diversity metrics (species richness, Shannon's diversity, and Pielou's evenness), and the aboveground carbon stocks, we surveyed all woody plant species with a diameter greater than three centimeters in 15 plots of a typical Brazilian savanna (cerrado stricto sensu) at an experimental research station in central Brazil (Cerrado biome). Fifteen plots (five per treatment) were differently affected by fire events over a decade, comprising three treatments: (i) annual fire, (ii) legacy fire (> 11 years since the last fire event), and control (not burned in the past 30 years). Non-metric multidimensional scaling (NMDS) analysis indicated a significant effect of fire on the species composition among treatments and that some species benefited from fire, such as Erythroxylum suberosum, whereas others propagated better without fire, such as Camisala montana and Dalbergia miscolobium. Over a decade of annual fire events led to decreases in Shannon's diversity, species richness, and stem density, which were significantly lower in the annual fire treatment than in the control and legacy fire treatments. Stem density by diameter and height size class (except for the 1-2 m class and above 8 m) was higher in the control than in the annual fire treatment, but the number of dead trees did not differ between the control and annual fire treatments. Our results also showed that fire was a factor in changes in the evaluated parameters, such as annual fire treatment, which reduced the amount of biomass and, therefore, the carbon stock. This study suggests that, if burned yearly, typical Brazilian savannas can become less biodiverse in terms of woody plant species and negatively affect their fire resilience. Therefore, fire management practices should focus on determining the frequency with which these ecosystems may benefit the most from fire disturbances.

In this paper, we use a machine learning method, known as Nonnegative Matrix Factorization, to extract from a given image some new information obtained from a number of color space representations. Such kind of information, termed ``metacolor'', can be considered as a particular color space representation of the image, which can be used to obtain a binary segmentation of the investigated image by distinguishing foreground and background pixels. Some numerical experiments prove that the proposed method shows improved results when compared with common simpler thresholding algorithms.

We investigate the physics of a medium-size quantum particle' gases, of the order of hundreds or thousands of fermions/bosons (far below the thermodynamic limit $N \, \rightarrow \, 10^{24}$). Appeal to microcanonical ensemble becomes then unavoidable. The so-called statistical complexity is our protagonist. Interesting facts are uncovered, both for fermions and bosons, yielded by statistical quantifiers.

School-aged children may benefit from education interventions focused on healthy eating and physical activity to improve their quality of life. This article aims to review scientific evidence on food and nutrition education (FNE) in Spanish-speaking countries for the prevention of overweight and obesity in school-aged children (6-12 y). Articles were searched between April and August 2021. The searches were conducted using MEDLINE, Google Scholar, and SciELO. The primary search for articles focused on the experience of FNE interventions in Spanish-speaking countries. Overall, 518 articles were found and 33 studies were eligible for data extraction. Forty-two percent of the studies had a focus on FNE and 64% were focused on describing the eating habits of schoolchildren. Nutritional assessments (anthropometric) were found frequently with 91% and 30% of the studies focused on physical activity. All interventions focused on preventing or reducing overweight and obesity in school-age children. Educational, cognitive, dietary, and physical activity practices were described, whit being educational the most frequent intervention. Interventions reported positive effects of FNE interventions to improve knowledge and practices of healthy lifestyles in school-age children.

Water resources management is one of the most important challenges worldwide because water represents a vital resource for sustaining life and environment. In the aim of sustainable groundwater management, the identification of aquifer recharge areas is a useful tool for water resources protection. In a well-developed karst aquifer, environmental isotopes provide support for identifying aquifer recharge areas, residence time and interconnections between aquifer systems. This study deals the use of environmental isotopes to identify the main recharge area of a karst aquifer in the Upper Valley of Aniene River (Central Italy). The analysis of 18O/16O and 2H/H values and their spatial distribution in the aquifer, make it possible to trace back groundwater recharge areas based on average isotope elevations. The Inverse Hydrogeological Balance Method was used to validate spring recharge elevations obtained by the use of stable isotopes. Areas impacted by direct and rapid rainfall recharge into the study area were delineated, showing groundwater flowpaths from the boundaries to the core of the aquifer. The results of this study demonstrate the contribution that spatial and temporal isotope changes can provide to the identification of groundwater flowpaths in a karst basin, taking into account the hydrogeological setting

An increasing amount of electric energy is consumed by computers as they progress in function and capabilities. All of it is dissipated in heat during the computing and communicating operations and we reached the point that further developments are hindered by the unbearable amount of heat produced. In this paper we briefly review the fundamental limits in energy dissipation, as imposed by the laws of physics, with specific reference to computing and memory storage activities.

COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.

Microalgae biomass is considered a promising alternative feedstock for biodiesel production due to its high productivity of neutral lipids, specially under abiotic stress conditions. Among the unicellular microalgae that show this characteristic, Chlamydomonas reinhardtii appears as one of the most important model species that have increased lipids production under abiotic stress conditions. In this study, we show that cells cultivated under mixotrophic condition supplemented with 0.1 M of NaCl rapidly raises their amount of neutral lipids in C. reinhardtii without reduction of their cellular growth rate, being therefore a promising condition for biomass towards bioenergy production. The nuclear proteome of these cells was investigated where we identified 323 proteins with an enrichment of almost 60% of nuclear proteins in the total dataset. We found 61 proteins differentially regulated upon salt treatment, including proteins annotated in functional categories related to translation and nucleosome assembly functions, among others. Additionally, we identified Transcription factor proteins (TFs) and analyzed their likely Transcription factors-binding regulatory elements identifying target genes related to lipids metabolism and kinase functions, indicating possible regulatory pathways of lipids biosynthesis. Together these data can help understand regulatory nuclear mechanisms leading to an increase of lipids in the first 24h of salt stress 0.1M NaCl.

The metastatic disease is a complex and sequential process that involves the migration of tumor cells from the primary site to distant areas. This metastatic pathway is not always predictable. Therefore, this paper presents three rare cases of unusual metastases, due to their primary site: two metastases of a clear cell renal cell carcinoma, one gingival and one nasal, as well as a mandibular metastasis of a hepatocellular carcinoma. In all cases, an incisional biopsy was performed in order to sign out the diagnosis. After microscopical examination of morphological Hematoxylin and Eosin stained slides, for all cases, immunohistochemical reactions were performed to support the primary tumor site. Two cases had a previous histopathological diagnosis of a primary tumor, while for the third case, the metastatic lesion represented the first manifestation of the neoplastic disease, with an unfavorable prognosis.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These pa-tients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmaco-logic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infec-tious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and modalities of vaccination in SOT adult candidates and recipients.

Adiposity is associated with adverse health conditions such as obesity, cardiovascular disease and type 2 diabetes. The combination of resistance exercise and creatine supplementation has been shown to decrease body fat % in adults ≥ 50 years of age. However, the effects in adults < 50 years of age is unknown. To address this limitation, we systematically reviewed the literature and performed several meta-analyses comparing studies that included resistance exercise and creatine supplementation to resistance exercise and placebo. Twelve studies were included involving 266 participants. Adults (< 50 years of age) that supplemented with creatine and performed resistance exercise experienced a significant reduction in body fat % (-1.19%, p=0.006) and a non-significant reduction in absolute fat mass (-0.09 kg, p=0.88). Collectively, the combination of resistance exercise and creatine supplementation produces a very small reduction in body fat % in adults < 50 years of age.

Large volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics including immune responses follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to 3 years we have established a well characterized large segmental tibial bone defect ovine model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups in which all ovine segmental defects were treated with a bone grafting technique combined with a three-dimensionally printed medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold. The qualitative data set is based on osteoimmunological findings gained from IHC analyses of over &gt;350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research.

Radiomics represents the science of extraction and analysis of a multitude of quantitative features from medical imaging, unrevealing quantitative potentiality of Radiologic images. This scientific review aims to provide radiologists a comprehensive understanding of radiomics, emphasizing its principles, applications, challenges, limits, and future prospects. Limits of standardization of actual scientific production are analyzed with the possible solutions proposed by some papers reported and commented. As the continuous evolution of medical images is ongoing, radiologists must be aware of new perspective to perform a central role in patients management.

Fabry disease (FD) is a X-linked inheritable storage disease caused by deficiency of al-pha-galactosidase causing lysosomal overload of sphingolipids. FD cardiomyopathy is character-ized by left ventricular (LV) hypertrophy and should be considered in differential diagnosis with all the other causes of LV hypertrophy. An early diagnosis of FD is very important because the enzyme replacement therapy (ERT) may change the fate of patients by blocking both cardiac and systemic involvement and improving prognosis. Diagnosis may be relatively easy in young patients with the typical signs ans symptoms of FD, but in male patients with late onset of disease and in females, diagnosis may be very challenging. Morphological and functional aspects are not specific for FD, which cannot be diagnosed or excluded by echocardiography. Cardiac magnetic resonance (CMR) with tissue characterization capability, is the preferred technique for the differential diagnosis of LV hypertrophy. The finding of decreased myocardial T1 value in LV hypertrophy is very specific for FD. Late gadolinium enhancement (LGE) is found in late stage of disease but it is useful to predict the cardiac response to ERT and to stratify the prognosis.

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of the ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analysis of randomized controlled trials (RCTs), assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identify, analyzed in terms of safety/efficacy ratio and of risk of bias, and graded using Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In IVF population not at high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of GnRH antagonist may reduce the OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have shown to be promising.

In the last years, advances in materials engineering based on adaptive electronics have found a new paradigm to optimize drawbacks in signal processing. A two-layer MnO/ZnO:Zn heterostructure envisioned for frequency adaptive electronic signal processing is synthesized by sputtering where the use of internal states allows reconfigurability to obtain new operating modes at different frequency input signals. An X-Ray Diffraction (XRD) is performed on each layer, MnO:Mn had a cubic and ZnO:Zn a hexagonal structure with preferential growth in [111] and [002] directions respectively. It is determined that the coupling in this heterojunction is compatible with a mismatch less 1 % due texture in each layer which implies a low number of defects. An electrical characterisation with an oscilloscope and signal generator was carried out to obtain the time-response signals and current-voltage (I-V) curves where no degradation is detected when changing from a range of frequencies (100 Hz – 1 MHz). An equivalent circuit is proposed to explain the effects in the interface. Finally, the MnO/ZnO:Zn heterojunction delivers states that are stable, repeatable, and reproducible and it demonstrates how the interaction of the materials can be used in adaptive device applications applying frequencies and internal states as to create new and innovative design schematics, reducing the numbers of components/connections in a system for future sustainable electronics.

The current paper presents a case of a 33-year-old female with an uncommon localization of a leiomyoma in the oral cavity - the anterior palatal fibromucosa and the incisive papilla. The patient referred to the Oro-Maxillo-Facial Surgery Clinic of the Emergency City Hospital Timisoara, Romania accusing a slight discomfort in the act of mastication and the occurrence and persistence of a diastema between the upper central incisors, due to the presence of a tumoral mass located in the anterior palatal mucosa, between the upper central incisors, without any changes of the subjacent bone structure in the anterior hard palate visible on the cone beam computed tomography image (CBCT). The tumor was removed by a surgical excisional biopsy and a histopathological examination was performed using morphological Hematoxylin–Eosin (HE) staining and additional immunohistochemical (IHC) reactions, in order to confirm the diagnosis. On microscopic examination, there were found bundles of spindle cells with eosinophilic cytoplasm and vesicular nuclei, with finely granular chromatin. The immunohistochemically staining found positive results for smooth muscle actin (SMA) and desmin and negative result for vimentin. The treatment of choice for leiomyoma of the oral cavity is surgical excision with clear margins, followed by periodical clinical monitoring.

Kinetic estimation of glomerular filtration rate (KeGFR) proved its utility in predicting acute kidney injury (AKI) in both adults and children. Our objective is to assess the clinical utility of KeGFR in predicting AKI severity and progression to acute kidney disease (AKD) in patients already diagnosed with AKI and to examine major adverse kidney events at 30 days (MAKE30). We retrospectively calculated the KeGFR in the first 24 hours of identified AKI (KeGFR1) and in the 24 hours prior to AKD (KeGFR2) in all admitted children under 18 years old. The cohort consisted of 803 patients with AKI. We proposed a new classification of KeGFR stages, from 1 to 5, and assessed the predictive value of KeGFR stages for AKD development and MAKE30. AKI severity was associated with lower KeGFRs. KeGFR1 and KeGFR2 predicted AKD with AUC values between 0.777 and 0.841 respectively, p<0.001. KeGFR2 had the best performance in predicting MAKE30 (AUC of 0.819) with a sensitivity of 66.67% and specificity 87.7%. KeGFR1 stage 3, 4 and 5 increased the risk of AKD by 3.07, 6.56 and 28.07 times respectively while KeGFR2 stage 2, 3, 4 and 5 increased the risk of AKD 2.79, 3.58, 32.75 and 80.14 times fold. Stage 5 KeGFR1 and KeGFR2 stages 3, 4 and 5 increased the risk of MAKE30 by 7.77, 4.23. 5.89 and 69.42 times in the adjusted models. KeGFR proved to be a useful tool in AKI settings. KeGFR dynamics can predict AKI severity, duration and outcomes.

Breast cancer remains a significant health concern worldwide, necessitating early detection and treatment. The rapid appearance or a change in the shape of skin lesion on the breast or just of the nipple-areola complex(NAC), especially if it is unilateral needs to be evaluated. Several primary or secondary tumours such as inflammatory skin lesions can affect this body area. Ultrasound, mammography, or magnetic resonance imaging (MRI) are the most used non-invasive diagnostic techniques for breast cancer, but in recent years reflectance confocal microscopy (RCM) and optical coherence tomography have emerged as additional tools to diagnose cases characterized by cutaneous changes.The introduction of new techniques such as reflectance confocal microscopy (RCM), may open new perspectives in the non-invasive diagnosis of mammary paget disease (MPD). RCM is a non-invasive diagnostic technique that allows high-resolution images of the skin at microscopic level in real time. It is non-invasive, painless and repeatable, making it a valuable tool in the early diagnosis and monitoring of skin diseases. We describe an atypical clinical presentation of mammary paget disease early diagnosed by reflectance confocal microscopy evaluation.

Several methods can be used to evaluate antibody avidity, one of which is the modified ELISA, in which a chaotropic agent is added to disrupt the binding between the antigen and the antibody. Although the avidity index provides relevant information about the functionality of antibodies, it does not allow us to characterize which antigens the antibodies are strongly bound to. To this end, we adapted the Immunoblot and Dot-Blot techniques by adding potassium thiocyanate (KSCN) after incubating nitrocellulose membranes with serum from mice immunized with Neisseria meningitidis outer membrane vesicles (OMVs) or serum from mice immunized with recombinant receptor-binding domain (RBD) of SARS-CoV-2, with different adjuvants for each antigen. In terms of results, when standardizing the incubation time of sera with KSCN, we observed that 5 minutes was the ideal time for both assays, however, when using different dilutions of serum from mice immunized with RBD, there was an influence on the strength of antigen-antibody binding. For the N. meningitidis assay, the antibodies maintained high avidity for the antigens present in the OMVs, PorA, NadA, and Opa, especially in the presence of the aluminum hydroxide adjuvant. The research showed that standardizing the Immunoblot and Dot-Blot in the same assay optimizes time and resources, allowing qualitative analysis for two different antigens, and resulting in more robust information for immunization studies against these pathogens.

Fatal hemoptysis secondary to severe pulmonary veins stenosis is an exceptional late complication of radiofrequency ablation for atrial fibrillation. We report the case of a 53-year-old male with a history of atrial fibrillation treated by radiofrequency ablation and admitted in our center 6 months after the initial procedure because of aggravating dyspnea and fatigability. Transthoracic echocardiography showed moderate dilation of right heart cavities, severe pulmonary hypertension, and a turbulent flow in superior pulmonary veins. The cardiologist suspected pulmonary vein(s) stenosis and cardiac computed tomography (CT) angiography was performed with findings of severe stenosis of the right superior, right inferior and left inferior pulmonary veins, near-occlusion of the left superior pulmonary vein and the vein draining the apical segment of the right lower lobe. The CT scan also revealed soft tissue attenuation of the mediastinum posterior to the left atrium suggesting fibrosing mediastinitis together with parenchymal findings consistent with pulmonary venooclusive disease and an area of hemorrhagic infarction. Fatal hemoptysis occurred 3 days after the evaluation before any treatment was attempted. In conclusion, severe pulmonary stenosis remains a rare but severe complication of radiofrequency ablation. Prevention is the key element together with an early diagnosis as the entity is potentially life-threatening.

Plant loss in experimental plots occurs occasionally in field experiments with coffee crops. In breeding programmes, such loss can be extremely harmful, especially when the statistical analysis methods used are not consistent with the data generated in the experiments. In this study, we analysed a set of productivity data to determine whether the compensatory effect occurs in coffee crops, analyse the need for correcting the number of failures in experiments, and identify the best stand correction method to use. Productivity data from six harvests of 11 experiments with Coffea arabica plants were used. The experiments were implemented in a randomised block design, with four replications and six plants per plot. The following stand correction methods were evaluated: rule of three, Zuber [1], Vencovsky and Cruz [2]covariance of the average or ideal stands, and Cruz [3] and compared to data without correction adjustments. The most adequate correction methods were chosen based on the existence of genetic variance, selective accuracy, and progeny ordering. The compensatory effect was evident from the analysed data, with stand correction shown to be beneficial in progeny competition experiments. The covariance methods using average or ideal stands presented the best results, followed by the method proposed by Cruz [3]. The rule of three and Zuber [1] methods showed unsatisfactory results and are not recommended for stand correction in progeny competition experiments with coffee crops

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) versus Deauville score (DS) in assessing chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (age 8-16 years) were enrolled at baseline, interim (after the 2nd or 3rd chemotherapy round), and post-therapy (upon completion of first-line chemotherapy) 18F-FDG PET-CT. Interim and post-therapy DS and ΔSUVmax% were compared as response predictors. Patients were classified as responders and non-responders based on 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively in predicting response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, with a 76.8% cutoff. Sensitivity, specificity (p<0.05) and NPV (p<0.01) were significantly higher using DS than ΔSUVmax%. In conclusion, DS can predict chemotherapy response better than ΔSUVmax% in pediatric HL patients.

Despite the productivity, achieving long-term sustainability and maintaining plant biodiversity become the pivotal goals in orchard floor management, especially along tree rows. Thus, the paradigm of eradicating weeds in the tree row using chemical herbicide or repeated soil tillage needs to be substituted with more sustainable alternatives. This study was conducted in two commercial apple and peach orchards in Marche region (Italy). Two integrated mechanical approaches, integrated mowing (mower + brush or disc) and integrated tillage (blade weeder + integrated mowing), were compared with standard herbicide system in a 2-years trial. Weed species abundance, soil coverage rate, and weed biomass productions, including gas exchange parameters, tree growth, fruit yield and quality were measured. Both integrated practices had significant effects on the number of weed species, total vegetation coverage, and dry weed biomass production. No significant differences were found in terms of tree gas exchange parameters, growth and fruit yield. However, a few fruit quality parameters such as fruit firmness, solid soluble content and dry matter content responded positively to the integrated practices. These results suggest that the integrated mechanical approaches of weed management increased orchard biodiversity, and they had no adverse effects on tree growth, fruit yield, and quality.

The response of a single tin oxide nanowire was collected at different temperatures to create a virtual array of sensors working as a nano-electronic nose. The single nanowire, acting as a chemiresistor, was first tested with pure ammonia and then used to determine the freshness status of trout fish (Oncorhynchus mykiss) in a rapid and non-invasive way. The gas sensor reacts to total volatile basic nitrogen, detecting the freshness status of the fish samples in less than 30 seconds. The sensor response at different temperatures correlates well with the total viable count (TVC), demonstrating that it is a good (albeit indirect) way of measuring the bacterial population in the sample. The nano-electronic nose is able to classify the samples according to their degree of freshness, but also to quantitatively estimate the concentration of microorganisms present. The system was tested with samples stored at different temperatures, managing to classify them perfectly (100%) and estimating their log(TVC) with an error lower than 5%.

The concept of artisanal products has been largely discussed mainly due to concerns about the inappropriate use of the term that may cause confusion for the consumers. Cheeses are important food models to evaluate consumers’ and producers’ perception about artisanal foods worldwide. Thus, the objective of the present study was to evaluate the perception of consumers and cheesemakers towards artisan foods, focusing on artisanal cheeses. For this purpose, two focus group were performed either with cheese producers and with consumers to discuss the topic. Colonial and Serrano cheeses, traditional and cultural dairy products in Brazil, were used as food model for the discussion. Producers and consumers related artisan foods to small scale of production, handicraft and freshness. Affective memories were also an important issue related to artisanal cheeses. For cheesemakers, artisan cheeses must be produced with unpasteurized milk, which was not cited by consumers. Consumers disclosed the intention of pay a premium price for food products that present artisan seals on front-package-label, mainly due to the guarantee of acquiring a quality product. The confusion about artisanal and traditional food concepts were observed, which is a subject to be deeply evaluated further. The findings provide useful implications to policy makers and institutions that can influence citizens’ attitudes and consumption patterns of artisanal products.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

: Consumption of plant-based milk replacers has increased in recent years due to health benefits, benefits attributed mainly to the content of phenolic compounds, fatty acids, or bioactive compounds with antioxidant activity. In this context, we proposed to obtain two types of less studied plant-based beverages, namely lupine and chickpea beverages, as well as the possibility of getting these beverages using germinated seeds and even obtaining probiotic drinks through fermentation with Lactobacillus plantarum 299v. To evaluate the quality of the obtained products, we determined their content of proteins, fatty acids, organic acids, volatile compounds, and phenolic compounds. We evaluated the antioxidant activity of the obtained herbal drinks, and a load of probiotic microorganisms present after the fermentation process. Both lupine and chickpea drinks have the desired properties, high content of fatty acids and phenolic compounds, that bring probiotic benefits.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

NK population is characterized by distinct NK cell subsets which respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e. resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Immersive experiences in green areas and particularly in forests have long been known to produce beneficial effects for human health. However, the exact determinants and mechanisms leading to healthy outcomes remain to be elucidated. The purpose of this study was to investigate whether inhaling plant-emitted biogenic volatile compounds, namely monoterpenes (MTs), can produce specific effects on anxiety. Data from 505 subjects participating in 39 structured forest therapy sessions in different Italian sites, were collected. Monoterpenes air concentration was measured at each site. STAI State questionnaires were administered before and after the sessions as a measure of anxiety. A propensity score matching analysis was then performed, considering an above-average exposure to inhalable air MTs as the treatment: the estimated effect was -1.28 STAI-S points (95% C.I. -2.51 to -0.06, p = 0.04), indicating that the average effect of exposure to high MT air concentrations during forest therapy sessions is to decrease anxiety.

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

Sorghum plants naturally produce dhurrin, a cyanogenic glycoside which may be hydrolysed to cyanide resulting in often lethal toxicoses. Ruminants are particularly sensitive to cyanogenic glycosides due to the active role of rumen microbiota in dhurrin hydrolysis. This work provides an overview of a poisoning outbreak occurred in 5 farms from North-West Italy in August 2022; a total of 66 cows died, and many others developed an acute toxicosis after being fed on either cultivated- (Sorghum bicolor) or wild Sorghum (Sorghum halepense). Clinical signs were recorded, and all cows received an antidotal/supportive therapy. Dead animals were subjected to necropsy and dhurrin content was determined in Sorghum specimens by a LC-MS/MS method. Rapid onset, severe respiratory distress, recumbency and convulsions were the main clinical features; bright red blood, bitter almond smell and lung emphysema were consistently observed at necropsy. The combined i.v. and oral administration of sodium thiosulphate resulted in a rapid improvement of clinical signs. Dhurrin concentrations corresponding to cyanide levels higher than the tolerated threshold of 200 mg/kg were detected in sorghum specimens from 4 out 5 involved farms; thereafter, such levels declined reaching tolerable concentrations in September-October. Feeding cattle with wild or cultivated Sorghum green fodder is a common practice in Northern Italy, especially in summer. However, care should be taken in case of adverse climatic conditions, such as severe drought and tropical temperatures (characterising summer 2022), which are reported to increase dhurrin synthesis and storage.

The agricultural sector is currently confronting multifaceted challenges such as an increased food demand, a slow adoption of sustainable farming, a need for climate-resilient food systems, resource inequity, and protection of the small-scale farmers’ practices, all issues integral to food security and environmental health. Remote sensing technologies can assist precision agriculture to effectively address these complex problems, by providing farmers with a high-resolution lens. The use of vegetation indices (VIs) is an essential component of remote sensing, which combine the variability of spectral reflectance value (derived from remote sensing data) with the growth stage of crops. Currently a wide array of VIs is available that could be used to provide a classification and an evaluation of the state and health of crops. However precisely this high number leads to difficulties in selecting the best VI and combination of VIs for a specific objective. Without a thorough documentation and analysis of appropriate VIs, users might be confronted with difficulties in using remote sensing data or even with a very low accuracy of the results. Thus, the objective of this review is to conduct a critical analysis of the existing state of the art on the most important features related to the effective use of VIs for the discrimination and monitoring of the most important agricultural crops (wheat, corn, sunflower, soybean, rape, potatoes, and forage crops), grasslands and meadows. This data could be highly useful for all the stakeholders involved in agricultural activities (from farmers, researchers up to institutions dealing with the centralization and monitoring of agricultural crops).

Currently, ovarian cancer (OC) is a target of intense biomarkers research because of its frequent late diagnosis and poor prognosis. Serum determination of Human epididymis protein 4 (HE4) is a very important early detection test. Most interestingly, HE4 plays a unique role in OC as it has been implicated not only in OC diagnosis but also in the prognosis and recurrence of this lethal neoplasm, actually acting as a clinical biomarker. There are several evidence about the predictive power of HE4 clinically, conversely less has been described concerning its role in OC oncogenesis. Based on these considerations, the main goal of this review is to clarify the role of HE4 in OC proliferation, angiogenesis, metastatization, immune response and also in the development of targeted therapy. Through a deeper understanding of its functions as a key molecule in the oncogenetic processes underlying OC, HE4 could be possibly considered as an essential resource not only for diagnosis but also for prognosis and therapy choice.

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. The aim of the present study was to investigate the protective effects on dysmetabolism and neurodegeneration of a natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin, on the brains of high fat diet (HFD)-fed mice. A decreased expression of FACL-4, CerS-1 and CerS-4, reduced cholesterol concentration, increased IR expression and insulin signaling activation, were found in brains of NDS-treated HFD mice, suggesting that NDS is able to prevent brain lipid accumulation and central insulin resistance. In the brains of NDS-treated HFD mice, the levels of RNS, ROS and lipid peroxidation, the expression of p-ERK, H-Oxy, i-NOS, HSP60, NF-kB, GFAP, IL-1β, IL-6, and CD4 positive cell infiltration were lower than in untreated HFD mice, suggesting antioxidant and anti-inflammatory effects of NDS. The decreased expression of p-ERK and GFAP in NDS-treated HFD mice was confirmed by immunofluorescence. Lastly, a lower number of apoptotic nuclei was found in cortical sections of NDS-treated HFD. All these data indicate that NDS exerts neuroprotective effects in HFD mice by reducing brain fat accumulation, oxidative stress and inflammation and improving brain insulin resistance.

Oxidative stress (OS) is reported in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyzes the dismutation of superoxide anion with a protective role on endothelial cells. In chronic kidney diseases (CKD), OS and thyroid dysfunction (low T3 syndrome) are fre-quently present, but their relationship has not been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into: “acute hemodialytic pa-tients” (AH, 1-3 months of treatment) and “chronic hemodialytic patients” (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and the relation-ships with thyroid hormones. Two basal samples (“basal 1”, 3 days after the last dialysis and “basal 2”, 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs AH in all determinations. Moreover, they pre-sented lower TAC values. Dividing CH patients into two subgroups according to fT3 levels (nor-mal or low) we found significantly lower ec-SOD values in the group with low fT3 at basal, 5 and 10 min samples. Finally, a significant correlation was observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low T3 syndrome in CKD, suggest that low fT3 concentrations can influence ec-SOD activity and therefore contribute to possible endothelial oxi-dative damage in such a situation.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis

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.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with an atypical phenotype, due to the presence of a progressive ocular ptosis. Genetic analyses revealed two variants in SOD1 and TBK1 genes respectively and the LHON-associated m.14484T>C variant in the mitochondrial DNA (mtDNA). We discuss how all these variants may synergically impinge on mitochondrial function, contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, possibly influencing the clinical ALS phenotype.

Targeted radionuclide therapy (TRT) has recently seen a surge in popularity, with the use of radionuclides conjugated to small molecules and antibodies. Similarly, immunotherapy also has shown promising results – an example being chimeric antigen receptor (CAR) T-cells therapy in hematologic malignancies. Moreover, TRT and CAR T therapies possess unique features that require special consideration when determining how to dose, time, and sequence combination treatments, including the distribution of TRT dose in the body, the decay rate of the radionuclide, and the proliferation and persistence of the CAR-T cells. These characteristics complicate additive or synergistic effects of combination therapies and warrant a mathematical treatment which includes these dynamics in relation to the proliferation and clearance rates of the target tumor cells. Here we combine two previously published mathematical models in a multiple myeloma setting to explore the effects of dose, timing, and sequencing of TRT and CAR-T cell based therapies. We find that for a fixed TRT and CAR-T cell dose, the tumor proliferation rate is the most important parameter in determining the best timing of TRT and CAR T therapies.

Increasing evidence supports the direct healing effects of forests, partly attributed to the exposure to plant-emitted monoterpenes available in the forest atmosphere. The potential benefits on respiratory functions from inhaling monoterpenes have gained attention, especially due to the global rise in respiratory diseases. This study involved 42 asthmatic adolescents attending a summer rehabilitation camp at an Altitude Pediatric Asthma Center within a densely forested area in the Eastern Italian Alps. Volatile organic compound measurements indicated a pristine atmosphere, enabling modeling of continuous hourly monoterpenes concentration. Monoterpene concentration exposure and total inhaled dose were assessed over a 14-day stay, during which spirometry, lung oscillometry, and fractional exhaled nitric oxide were measured. Statistically significant correlations were observed between modifications in lung function parameters among asthmatic adolescents and monoterpenes exposure. These findings suggest a potential localized airway effect specific to monoterpenes. This pilot cohort study might pave the way for further investigations into the therapeutic effects of forest monoterpenes on lung function tests, asthma, and the broader healing potential of forest environments.

We sought to compare native T1 mapping to conventional Late gadolinium enhancement (LGE) and T2-STIR techniques in a cohort of consecutive patients undergoing cardiac MRI (CMR).. CMR was performed in 323 patients, 206 males (64%), mean age 54±8 years and in 27 age- and sex- matched healthy controls. At T2-STIR images myocardial hyperintensity suggesting edema was found in 41 patients (27%). LGE images were positive in 206 patients (64%). T1 mapping was abnormal in 171 (49%). In 206 patients (64%) a matching between LGE and native T1 was found. T1 was abnormal in 32 out of 41 (78%) with edema at T2-STIR. Overall, LGE and/or T2-STIR were abnormal in 209 patients, whereas native T1 in 154(52%). Conventional techniques and T1 mapping were concordant in 208 patients (64%). In 39 patients T1 mapping was positive despite negative conventional techniques (12%). T1 mapping was able in conditions with diffuse myocardial damage as cardiac amyloidosis, scleroderma and Fabry disease (additive role in 42%). On contrast, T1 mapping was less effective in cardiac disease with regional distribution of myocardial damage as myocardial infarction, HCM, myocarditis. In conclusion, conventional LGE/T2-STIR and T1 mapping are complementary techniques and should be used together in every CMR examination.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

This study focused on the characterization of lactic acid bacteria (LAB) in a renowned traditional Italian cheese, Pecorino di Farindola, to select an autochthonous culture and investigate its po-tential for the improvement of safety and functional properties. Two hundred and six LAB isolated throughout production and maturation from nine cheese lots of three farms were identified by 16S rRNA gene sequencing and tested for the presence of genes encoding virulence factors, vancomycin resistance (for enterococci), biogenic amines (BAs) and bacteriocin production, for antimicrobial activity, and for the capacity to survive in the gastro-intestinal tract (GIT) based on tolerance to low pH and bile salts and adhesion to CaCo-2 cells. A Lacticaseibacillus paracasei isolate was used in cheese making and determined a decline of spiked Listeria monocytogenes and Escherichia coli O157 faster than in control cheese. The autochthonous bacterial groups were numerically unaffected, apart from lactobacilli that were recovered in higher numbers in the cheese with added L. paracasei. Based on Repetitive Extragenic Palyndrome (Rep) PCR profiles, the added strain possibly dominated until day 88 in cheese. Results encourage further trials with autochthonous cultures to efficiently inhibit hazardous bacteria and enrich a functional microbiota in Pecorino di Farindola and similar cheeses.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rate and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. Test-retest reliability was evaluated using Pearson correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p=0.284). In conclusion, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

Porcine Circovirus 2 (PCV2) vaccines are based on either inactivated whole virion, or recombinant ORF2 capsid protein assembled into Virus-like Particles (VLPs). No data are available instead about the immunizing properties of free, non-assembled capsid protein. To investigate this issue, ORF2 of a reference PCV2b strain was expressed in a Baculovirus-based expression system without assembly into VLPs. The free purified protein was formulated into an oil vaccine at three distinct Ag payloads: 10.8 / 3.6 / 1.2 micrograms /dose. Each dose was injected intramuscularly into five, 37-day old piglets, carefully matched for maternally-derived antibody. Five control piglets were injected with sterile PBS in oil adjuvant. Twenty-eight days later, all the pigs were challenged intranasally with 200,000 TCID50 of PCV2b strain DV6503. After challenge infection, all the pigs remained in good clinical conditions. The recombinant vaccine did not induce significant antibody and PCV2-specific IFN-gamma responses. ELISPOT and lymphocyte proliferation data confirmed poor induction of cell-mediated immunity. In terms of PCV2 viremia, there was no significant difference between vaccinated and control animals. The histological data indicated the absence of a detectable viral load and of PCVAD lesions in both vaccinated and control animals, as well as of histiocytes and multi-nucleated giant cells. We conclude that free, non-assembled ORF2 capsid protein does not induce protective immunity.

Objective: To investigate the association between deprivation and COVID-19 outcomes in Italy during pre-lockdown, lockdown and post-lockdown periods.Design: Retrospective cohort study.Setting: All municipalities in Italy with less than 50,000 population.Participants: 38,534,169 citizens and 222,875 COVID-19 cases reported to the Italian epidemiological surveillance were assigned to quintiles based on the deprivation index of their municipality of residence.Interventions: The COVID-19 pandemic during pre-lockdown, lockdown and post-lockdown from the 20th of February to the 15th of October of 2020.Main outcome measures: Multilevel negative binomial regression models, adjusting for age, sex, population-density and region of residence were conducted to evaluate the association between deprivation and COVID-19 incidence, case-hospitalisation rate and case-fatality. The association measure was the rate ratio.Results: During pre-lockdown, lockdown and post-lockdown, the incidence rate ratios (IRR) with 95% confidence interval (CI) in the most deprived quintile with respect to the least deprived quintile were 1.17 (95% CI 0.98 to 1.41), 1.14 (1.03 to 1.27) and 1.47 (1.32 to 1.63), respectively. In those three periods, the case-hospitalization IRR were 0.68 (0.51 to 0.92), 0.89 (0.72 to 1.11) and 0.99 (0.81 to 1.22) and the case-fatality IRR were 0.92 (0.75 to 1.13), 0.95 (0.85 to 1.07) and 1.02 (0.73 to 1.41), respectively.Conclusions: During lockdown and post-lockdown, but not during pre-lockdown, a higher incidence of cases was observed in the most deprived municipalities compared with the least deprived ones. No differences in case-hospitalisation and case-fatality according to deprivation were observed in any period under study.

Ruderal plants designate native or exotic plant species that grow spontaneously in anthropized environments, being important from the ecological succession perspective. The present study aimed to identify ruderal plants that occur in an anthropized area of the Campus Floresta of the Federal University of Acre (UFAC), in the municipality of Cruzeiro do Sul, in the Southwest Amazon. Toward this end, botanical material was collected and herborized, and identified based on consultation of the specialized literature, virtual herbariums, and by comparison with the Campus Floresta Herbarium (CFCZS) collection. Finally, these data were incorporated to the referred collection, according to the usual plant systematics procedures. The results revealed 28 species and 28 genera, distributed in 14 families. The most representative families were Fabaceae, Malvaceae and Poaceae, with four species each; followed by Asteraceae with three; Cyperaceae, Rubiaceae and Amaranthaceae with two each; and the others, Plantaginaceae, Ochnaceae, Urticaceae, Verbenaceae, Iridaceae, Lamiaceae and Dennstaedtiaceae with one species each. The occurrence of predominant species in planted pastures, agricultural use, and mining area ecosystems is highlighted, such as Pteridium aquilinum (L.) Kuhn., Andropogon bicornis L., and Crotalaria micans Link.

Obesity represents a worldwide epidemic disorder, increasing the overall morbidity and mortality rate. In this study we investigated the impact of obesity on peri-operative and long-term functional outcomes of Robotic assisted simple prostatectomy (RASP). Baseline flowmetry parameters and validated questionnaires’ scores were prospectively recorded. Follow-up assessments included Flowmetry and validated questionnaires. Composite outcomes (Trifecta) was defined as combination of: post-operative Q-max>15 ml/sec, IPSS score<8 and absence of complications. Pentafecta included also post-operative ejaculation persistence (MSHQ score>0) and the Erectile function maintenance (∆IEEF<6). Data were stratified by BMI (<30 or ≥30). 81 patients underwent RASP in our Institution. Baseline demographics and clinical features, questionnaires score and baseline flowmetry results were comparable between obese and non-obese cohorts. At follow-up, obese patients reported lower subjective improvement in IPSS (p=0.02) and OABQ scores (p<0.001) and higher incidence of stress incontinence requiring Duloxetin (p<0.001). Flowmetry outcomes, were also worse in this cohort (p=0.02 and p=0.03, respectively). At comprehensive outcomes assessment, obese patients had comparable Trifecta (67% vs 54%, p=0.39) and pentafecta achievement rate (p=0.76). Our prelimirary results proved that obesity is associated with worse functional outcomes (storage LUTS and incontinence rate) after RASP, but doesn’t affect trifecta and pentafecta achievement rate.

The TREX1 exonuclease degrades DNA to prevent aberrant nucleic acid sensing through the cGAS-STING pathway, and dominant Aicardi-Goutières Syndrome type 1 (AGS1) represents one of numerous TREX1-related autoimmune diseases. Monoallelic TREX1 mutations were identified in patients showing early-onset cerebrovascular disease, ascribable to small vessel disease, and CADASIL-like neuroimaging. We report the clinical-neuroradiological features of two patients with AGS-like (Patient A) and CADASIL-like (Patient B) phenotypes carrying the heterozygous p.A136V and p.R174G TREX1 variants, respectively. Genetic findings, obtained by a customized panel including 183 genes associated with monogenic stroke, were combined with interferon signature testing and biochemical assays to determine the mutations’ effects in vitro. Comprehensive studies revealed no pathological impact on TREX1 enzymatic function for the p.A136V variant. The p.R174G variant modestly altered exonuclease activity consistently with perturbation of substrate interaction rather than catalysis, which represents the first robust enzymological data for a TREX1 variant identified in a CADASIL-like patient. In conclusion, functional analysis allowed us to interpret the impact of TREX1 variants on patients’ phenotypes. Whilst Patient A’s manifestations are not related to p.A136V variant, Patient B’s phenotype is likely related to the p.R174G variant. Further functional investigations of TREX1 variants found in CADASIL-like patients are warranted to establish a causal link and interrogate the molecular disease mechanism.

Self-regulatory Self-efficacy belief (i.e., SRSE) represents a fundamental factor for adjustment in adolescence, as a vehicle to promote positive behaviors and protect youths from transgressions and maladjustment Bandura et al., 2003; LaRose et al., 2010). Research attested that, during adolescence, boys are more vulnerable to externalizing behaviors than girls, especially when they perceive themselves as scarcely capable of managing and orienting their behaviors, and when they possess impairments in impulsivity (Bandura et al., 2001; Muris, 2006). Previous studies firmly supported the key role of SRSE especially in the offline context in adolescence, but very few studies investigated its impact in the online context, although nowadays Internet represents one of the most significant environments for youths’ daily lives (LaRose et al., 2010; Favini et al., 2023). Thus, we aimed to examine the protective moderating role of SRSE in online and offline aggressive behaviors, beyond youths’ temperamental vulnerabilities, such as high levels of impulsivity. A sample of 318 Italian adolescents (Mage=15.21; SD=.51; 57% boys; 40% girls; 3% third gender) were asked to complete the Impulsivity Scale at Wave1, online and offline aggressive behaviors scales at Wave 2, and SRSE at Wave 2. Multiple-group-by-gender moderation model evidenced that, for what concerns online aggression, beyond the direct effects of impulsivity in boys and girls, SRSE directly affected online aggression and mediated the effect of impulsivity in girls. In contrast, impulsivity significantly affected offline aggressive behaviors only indirectly through the effects of SRSE, and SRSE directly influenced these behaviors in both genders. These results hold for the effects of youth’s age, sexual orientation, socioeconomic status, and years of education completed. This work preliminary evidenced that, contrary to previous studies which focused especially on the vulnerability of boys to aggressive conduct, impulsivity had direct effects on online aggressive behaviors in girls, and SRSE can protect adolescents of both genders in the online context, by predicting low online aggression, and represent a protective factor from the indirect effects that im-pulsivity impairments can have also in the offline context.

Athlete’s heart is characterised by structural, functional, and electrical remodelling. During an exercise session, the heart increases the use of oxygen, which is associated with decreased vascular resistance in the lungs’ circulation. Left ventricular hypertrophy is an echocardiographic modification especially met in endurance athlete’s heart. Moreover, left atrial dilatation represents another important characteristic of endurance athletes. Electrical modulation in the athletic heart induces neurological modifications leading to sinus arrhythmia, bradycardia, early repolarisation, and first-grade atrioventricular (AV) blocks. Athletes' nutritional status involves the assimilation of macronutrients such as proteins, carbohydrates, and fats. Depending on the duration of physical exercise, ATP can be obtained in aerobic or anaerobic conditions. This systematic review aims to find correlations between different evaluative methods of cardiac adaptation and present the metabolism in performance athletes.

Background: COVID-19 infection has received the attention of the scientific community due its respiratory manifestations and association with evolution to severe acute respiratory syndrome (SARS-CoV-2). There are few studies characterizing SARS-CoV-2 in pediatric immunocompromised patients, such as liver transplanted (LT) patients.The aim of this study was to analyze the outcomes of the larger cohort of pediatric liver transplant recipients (PLTR) from a single center in Brazil who where contaminated with COVID-19 during the pandemic. Methods: Cross-sectional study. Primary outcomes: COVID-19 severity. The Cox regression method was used to determine independent predictors associated with the outcomes. Results: 74 PLTR were included. Patients were divided into two groups according to the severity of COVID-19 disease: moderate-severe COVID and asymptomatic-mild COVID. Patients categorized as moderate-severe COVID were younger (12.6 months vs. 82.1 months, p 0.03), higher prevalence of transplantation with deceased donor (50% vs. 4.3%, p 0.02) and with a higher prevalence of COVID-infected patients before 6 months after LT (75% vs. 5.7%, p 0.002). The independent predictor of COVID-19 severity identified in the multivariate analysis was COVID-19 infection < 6 months after LT (HR=0.001, 95% CI=0.001-0.67, p 0.03). Conclusion: The time interval of less than 6 months between COVID-19 infection and LT was the only predictor of disease severity in pediatric patients.

Background: Dimethylfumarate (DMF) is an orally administered fumaric acid esters (FAE) approved for plaque psoriasis. The most represented adverse event for incidence reported in all studies regarding multiple sclerosis and psoriasis treatment was flushing followed by gastrointestinal and lymphopenia (AEs). We report our experience on effective management strategies in patients with dimethylfumarate fushing induced. Methods: The purpose of our study is addressed to propose feasibles strategies able to mitigate adverse events developing in order to improve therapy compliance. We report our real life experience of 20 patients affected by mild to moderate plaque psoriasis in treatement with DMF 10 male and 10 female, with 45,4 years old mean age underwent to a reducing a daily dosage regimen with DMF from 120 mg to 30 mg tablets. Patients experience flushing around 30-45 minutes after assuming the medication.per day. Results: Patients achieving a good adherence and efficacious results in terms of PASI 75 reduction after 16 weeks of treatment. Conclusion: DMF is efficacious and has a favorable benefit–risk profile, thanks to the possibility of implementing posology strategies in order to optimize adherence to the therapy.

LncRNA are involved in multiple regulatory pathways, its versatile mode of action has disclosed a new layer in gene regulation. They are reportedly modulated during plant development, with specific tissue functions and in response to stresses. In this study, we analyzed LncRNA from leave samples collected from the legume Copaifera langsdorffii (copaiba) from two divergent ecosystems: Cerrado (CER) and Atlantic Rain Forest (ARF). We identified 8020 novel lncRNAs, from which 2893 transcripts were regulated above 2-fold and 566 above 5-folds in either condition. This putative lncRNA set was compared with seven Fabaceae genomes, of which 1747 and 1879 transcripts (from ARF and CER, respectively) aligned to at least two genomes. Further, 2194 copaiba lncRNAs were successfully mapped to at least one of six Fabaceae transcriptomes. The secondary structures of the lncRNAs that were conserved and differentially expressed between the populations were predicted using in silico methods. Our results indicate the potential involvement of lncRNAs in the adaptation of C. langsdorffii to two different biomes.

Aging is the results of several complex and multifactorial processes, where several agents contribute to increase intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms, finely regulated and strictly interconnected, initiating or contributing to biological changes anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic affects. Vitamin D (VitD) is known to have positive impact not only on muscle and bone health, but also on several extra-skeletal districts, due to the widespread presence of VDRs (VDR). VitD and VDR could be molecules potentially targeting the hallmark of aging network. To date, evidence about the potential effect of VitD on the hallmark of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seems to confirm the modulatory effect of VitD on some hallmarks aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

It is known that exposure to heavy metals such as lead (Pb) and cadmium (Cd) has several adverse effects, particularly on the human reproductive system. Pb and Cd have been associated with infertility in both men and women. In pregnant women, they have been associated with spontaneous abortion, preterm birth, and impairment of the development of the fetus. Since these heavy metals come from both natural and anthropogenic activities and their harmful effects have been observed even at levels of exposure, their exposure remains a public health issue, especially for the reproductive system. Given this, the present study aimed to investigate the potential reproductive effects of Pb and Cd levels in the follicular fluid (FF) of infertile women and no-smokers exposed to heavy metals for professional reasons or living in rural areas near landfills and waste disposal areas, to correlate the intrafollicular presence of these metals with possible alterations in the ultrastructure of human cumulus-oocyte complexes (COCs), probably responsible of infertility. Blood and FF metals were measured using atomic absorption spectrometry. COCs corresponding to each FF analyzed were subjected to ultrastructural analyses by transmission electron microscopy. We demonstrated for the first time that intrafollicular levels of Pb (0.66 µg/dL to 0.85 µg/dL) and Cd (0.26 µg/L - 0.41 µg/L) could be associated with morphological alterations of both the oocyte and CCs ultrastructure. Since blood Cd levels (0.54 µg/L - 1.87 µg/L) were above the current reference values established by the guidelines of the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA), whereas blood Pb levels (1.28 µg/dL - 3.98 µg/dL) were below the ATSDR reference values we believe that these alterations could be due especially to Cd, even if we cannot exclude a possible additional effect of Pb. Our results highlighted that oocytes were affected in maturation and quality, whereas CCs showed scarcely active steroidogenic elements. Regressing CCs, with cytoplasmic alterations, were also numerous. According to Cd's endocrine-disrupting activity, the poor steroidogenic activity of CCs might correlate with delayed oocyte cytoplasmic maturation. So, we conclude that levels of heavy metals in the blood and the FF might negatively affect fertilization, embryo development, and pregnancy, compromising oocyte competence to fertilization both directly and indirectly, impairing CC steroidogenic activity, and inducing CC apoptosis.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Immersion in forest environments was shown to produce beneficial effects to human health, in particular psychophysical relaxation, so much that this practice is increasingly recognized as a form of integrative medicine. Limited evidence exists about both statistical significance and size of the effects conditioned on personal characteristics, as well as on the main external variables. The primary purpose of this study was to substantiate the very concept of forest therapy by means of the quantification and significance of the psychological effects, stratified by gender, age groups and place of residence. A preliminary qualitative analysis of the main determinants, in particular the method of conducting, the meteorological comfort and the concentration of volatile organic compounds in the forest atmosphere, was afforded. Seven forest therapy sessions were performed in late summer though early fall, resulting in 150 psychological self-assessment questionnaires administered before and after each session. The results were comparable or even better than others reported in the international literature. Moreover, preliminary evidence arose about different functionality towards specific psychological indexes conditioned at least on gender and age groups, as well as meteorological comfort, structured programs and, possibly, volatile organic compounds showed an impact on the outcomes.

Recent discoveries have shown that enteric glial cells play an important role in different neurodegenerative disorders such as Parkinson's disease (PD), which is characterized by motor dysfunctions caused by progressive loss of dopaminergic neurons in the substance nigra pars compacta and non-motor symptoms including gastrointestinal dysfunction. In this study we observed the modulatory effects of the flavonoid rutin on enteric glia in a PD animal model. Adult male Wistar rats were submitted to stereotaxic injection with 6-hydroxydopamine or saline, treated or not with rutin (10 mg/Kg) for 14 days. Intestinal segments (ileum and colon) were collected to analyze tissue reactivity and immunohistochemistry for neurons (HUc/d) and enteric glial cells (S100b) in the myoenteric plexuses. Behavioral tests demonstrated that treatment with rutin im-proved the motor capacity of parkinsonian animals, and also improved intestinal transit without interfering with the cell population; rutin treatment modulated reactivity of the ileal musculature by muscarinic activation, reducing relaxation through the signaling pathway of nitric oxide donors, and increasing the longitudinal contractility of the colon musculature in parkinsonian animals. Rutin demonstrated modulatory activities on the enteric nervous system, bringing relevant answers about the effect of the flavonoid in this system and po-tential application for PD adjuvant treatment.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 enters the host by infecting nasal ciliated cells. Then, the virus can spread towards the oropharyngeal cavity and the pulmonary tissues. The antiviral adaptive immunity is promptly induced in response to virus detection, with virus-specific T lymphocytes appearing before antiviral antibodies. Both breadth and potency of the antiviral CD8+ T cell immunity have a key role in containing viral spread and disease severity. Current anti-SARS-CoV-2 vaccines do not impede the virus replication in the upper respiratory tract, and there is consensus on the fact that the best potency of the antiviral immune response in both blood and upper respiratory tract can be reached upon infection in vaccinees (i.e., breakthrough infection). However, whether the antiviral CD8+ T cells developing in response to the breakthrough infection in the upper respiratory tract diffuse to the lungs also is still largely unknown. To fill the gap, we checked the CD8+ T cell immunity elicited after infection of K18-hACE2 transgenic mice both 3 weeks and 3 months after anti-Spike vaccination. The virus-specific CD8+ T cell immunity was monitored in both blood and the lungs before and after infection. By investigating the de novo generation of CD8+ T cells specific for SARS-CoV-2 viral proteins, we found that both membrane (M) and/or nucleocapsid (N)-specific CD8+ T cells were induced at comparable levels in blood of both unvaccinated and vaccinated mice. Conversely, N-specific CD8+ T cells were readily found in the lungs of control mice, but were either rare or absent in those of vaccinated mice. These results support the idea that the hybrid cell immunity developing after asymptomatic/mild breakthrough infection strengthens the antiviral cell immunity at lungs only marginally, implying that the direct exposition of the viral antigens is required for the induction of an efficient antiviral cell immunity in the lungs.

Brain imaging studies have recently provided some evidence in favour of covert cognitive processes ongoing in patients with disorders of consciousness (DoC) (e.g., minimally consciousness states, vegetative state/unresponsive wakefulness syndrome) engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, provided that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. Results indicate that some form of motor resonance is spared in a subset of patients with DoC with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials following the stimulation of the median nerve at the wrist (i.e., the temporal marker signalling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.

The social recognition of cultural landscapes has increased in recent years. Culture must be accessible to all citizens, helping them to interpret the cultural landscape in the most respectful and autonomous way possible. Nevertheless, the link between accessibility and heritage requires a sensitive perception of the environment and individuals in their different situations. Usually, however, only partial solutions are offered, whereas a global, truly sustainable and inclusive approach should be adopted. In this sense, information design can play an essential role in the enjoyment and knowledge of Heritage Landscapes. The aim of this article is to present some reflections on this topic, which have led a group of teachers and students from the Laboratory of Architectural, Cultural and Heritage Landscape of the University of Valladolid (LAB/PAP) to develop experimental design proposals for the archaeological site of Tiermes, in Soria, Spain. The method applied is based on field research, case studies, project proposals, workshops and user testing. The resulting proposals emerge from the previous research developed by the LAB/PAP. They will focus on information design to present this extraordinary site in an inclusive way. The final discussion will decide which of these proposals will be easier and more useful to implement.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

Abstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.

Methylmercury (MeHg) intoxication is a global health concern. Although MeHg neurotoxicity is well-recognized, less is known about MeHg's effects on metabolism. In this study, we evaluated MeHg intoxication (20mg/L in drinking water for 20 days) effects on liver and epididymal white fat (EWF) in young ApoE knockout (ko) and wild-type mice. The former is well-known to show spontaneous dyslipidemia. Hg levels in hair, liver, and EWF were measured to assess the degree of MeHg exposure. We also evaluated body weight gain, plasma triglycerides, total cholesterol levels, and liver injury by assessing steatosis score, AST, ALT, SOD, and TBAR levels. To evaluate EWF, we analyzed mean wet weight and adipocyte diameter, plasma leptin levels and metabolomics. Hg levels were markedly higher among intoxicated mice. ApoE ko mice showed higher Hg in the hair but lower levels in the liver and EWF than wild-type controls. Among wild-type mice, MeHg compromised weight gain and increased liver TBAR levels compared to non-challenged controls. Among non-intoxicated mice, ApoE deficiency significantly increased triglyceride, total cholesterol, and liver transaminases with reduced EWF wet weight, hepatic SOD, and plasma leptin levels. MeHg accumulation together with ApoE deficiency elevated total cholesterol, triglycerides, hepatic transaminases, and TBARS. We found distinct EWF metabolite activity in different scenarios of ApoE deficiency and MeHg intoxication, highlighting increased cardiovascular risk especially when both challenges occur. Further studies are required to elucidate the underlying mechanisms involved in these effects and the target nutritional interventions in most need to ameliorate them.

Despite the wide variety of variables commonly applied to measure different aspects of rehabilitation, the assessment and subsequent definition of indicators of environmental rehabilitation status are not simple tasks. The main challenges are comparing rehabilitated sites with target ecosystems as well as integrating individual environmental and eventually collinear variables into a single tractable measure of the state of a system before effective indicators that track rehabilitation may be modeled. For that, a consensus is lacking regarding which and how many variables need to be surveyed. Our approach considered ecological processes, vegetation structure, and community diversity from nonrehabilitated, rehabilitating and reference sites. We applied this approach to a curated set of 32 environmental variables retrieved from nonrevegetated, rehabilitating and reference sites associated with iron ore mines from the Urucum Massif, Mato Grosso do Sul, Brazil. By integrating variables from a single attribute or the entire set of variables into a single estimation of rehabilitation status, the proposed multivariate approach is straightforward and able to adequately address collinearity among variables. The proposed approach allows for the identification of biases towards single variables, surveys or analyses, which is necessary to rank environmental variables regarding their importance to the assessment. Furthermore, we show that bootstrapping permitted the detection of the minimum number of environmental variables necessary to achieve reliable estimations of the rehabilitation status. Finally, we show that the proposed variable integration enables the definition of environmental indicators for more comprehensive monitoring of mineland rehabilitation. Thus, the proposed multivariate ordination represents a powerful tool to outline the benefits of rehabilitating sites for the maintenance of biodiversity and ecosystem functions and services provided that sufficient environmental variables related to ecological processes, diversity and vegetation structure are gathered from nonrehabilitated, rehabilitating and reference study sites. By identifying deviations from predicted rehabilitation trajectories and providing assessments for environmental agencies, this proposed multivariate ordination increases the effectiveness of (mineland) rehabilitation.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Background: Introduction of new technologies in the management of oral disease has revolutionized treatment approaches, offering less invasive options and improved patient outcomes. Among oral cavity diseases, sialolithiasis is the most common disorder of the salivary glands. It involves the formation of calculi or stones within the salivary ducts, primarily affecting the submandibular gland due to its tortuous duct and the alkaline nature of its saliva. In particular, Laser-assisted techniques have shown significant promise in enhancing the precision and safety in the management of sialolith removal. This article aims to present a case report and also explores the scientific evidence supporting these innovative methods, highlighting their benefits and limitations in clinical practice.; Methods: The research was conducted using PubMed and Scopus search engines with a combination of relevant keywords, including laser, laser-assisted, laser treatment in combination with sialolith, sialolith removal, and sialoadenectomy. Selected articles were carefully reviewed to identify studies reporting data on the effectiveness of laser-assisted sialolith removal; Results: The results of the literature review indicate a growing interest in the application of Diode Laser and CO2, with evidence suggesting improved clinical outcomes and reduced postoperative pain compared to traditional methods; Conclusions: Although lasers offer enhanced safety and reduced morbidity and bleeding, which ensures optimal visibility, their high cost and the need for specialized training are limitations. Further randomized clinical trials and longer follow-up studies are needed to better evaluate their use in sialolith removal.

Plants exhibit the capacity for adaptation through their metabolic processes to various changes in environmental conditions. Investigating these adaptations in current and future climatic scenarios is of great importance for ensuring productive agricultural crops. This adaptative potential is commonly employed as an indicator of genotypes with higher potential in breeding programs. However, the complexity and interaction of plant metabolic parameters pose a challenge to selection strategies. In this context, the aim of this study was to explore phenotypic plasticity within the germplasm of Hybrid Timor coffee. Additionally, we assessed the utility of the Phenotypic Plasticity Index (MVPi) as a promising tool to predict genotype performance across diverse climatic conditions. To achieve this, we evaluated the performance of seven accessions from the Hybrid Timor germplasm in comparison to the Rubi and IPR 100 cultivars, known for their susceptibility and resistance to drought, respectively. The experiment was conducted at greenhouse conditions, with two treatments: a control scenario, maintaining soil moisture near its maximum water-holding capacity, and a water deficit scenario involving irrigation cessation followed by rehydration. Data encompassing physiological, biochemical, and growth aspects were collected during three distinct stages: pre-application of water deficit, its imposition, and subsequent rehydration. Furthermore, field evaluations of the productivity of the same genotypes were carried out over two consecutive seasons. Based on physiological and biochemical assessments, the MVPi was computed, employing Euclidean distance between principal component multivariate analysis scores. Subsequently, this index was correlated with growth and productivity data through linear regressions. Our findings reveal that the more plastic genotypes, capable of significantly altering physiological and biochemical parameters in response to environmental stimuli, exhibited reduced biomass loss in both aerial and root parts, consequently positively influencing their productivity. Enhanced plasticity was particularly prominent in accessions from the MG Germplasm Collection: MG 311 - Hybrid Timor UFV 428-02, MG 270 - Hybrid Timor UFV 377-21, and MG 279 - Hybrid Timor UFV 376-31, alongside the Rubi MG 1192 cultivar. The MVPi emerged as a valuable instrument to assess genotype adaptability and predict their performance under varying climatic scenarios.

Regulatory T cell master transcription factor, Forkhead box P3 (Foxp3) has been detected in cancer cells, but its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumor administration of Ad.P60 in breast tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells, and that gene therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

Introduction. The management of anemia in chronic kidney disease (CKD-An) presents significant challenges for nephrologists due to variable responsiveness to erythropoietin-stimulating agents (ESA), hemoglobin (Hb) cycling, and multiple clinical factors affecting erythropoiesis. The Anemia Control Model (ACM) is a decision support system designed to personalize anemia treatment, which has shown improvements in achieving Hb targets, reducing ESA doses, and maintaining Hb stability. This study aimed at evaluating the association between ACM-guided anemia management with hospitalizations and survival in a large cohort of hemodialysis patients. Methods. This mul-ti-center, retrospective cohort study evaluated adult hemodialysis patients within the European Fresenius Medical Care NephroCare network from 2014 to 2019. Patients treated according to ACM recommendations were compared to those from centers without ACM. Data on demographics, comorbidities, and dialysis treatment were used to compute a propensity score estimating the like-lihood of receiving ACM-guided care. The primary endpoint was hospitalizations during follow-up; the secondary endpoint was survival. A 1:1 propensity score-matched design was used to minimize confounding bias. Results. A total of 20,209 eligible patients were considered (reference group: 17,101; ACM adherent group: 3,108). Before matching, the mean age was 65.3±14.5 years, with 59.2% men. Propensity score matching resulted in two groups of 1,950 patients each. Matched ACM adherent and non-ACM patients showed negligible differences in baseline characteristics. Hospi-talization rates were lower in the ACM group both before matching (71.3 vs. 82.6 per 100 per-son-years, p<0.001) and after matching (74.3 vs. 86.7 per 100 person-years, p<0.001). During fol-low-up, 385 patients died, showing no significant survival benefit for ACM-guided care (hazard ratio = 0.93; p=0.51). Conclusions: ACM-guided anemia management was associated with a sig-nificant reduction in hospitalization risk among hemodialysis patients. These results further support the utility of ACM as a decision support tool enhancing anemia management in clinical practice.

Sewage surveillance can be used as an effective complementary tool for detecting pathogens in local communities, providing insights into emerging threats and aiding in the monitoring of outbreaks. In this study using qPCR and whole genomic sewage surveillance, we detected Mpox virus along with other viruses, in municipal and hospital wastewaters in Belo Horizonte, Brazil over a 9 months period (from July 2022 till March 2023). MPXV DNA detection rates varied in our study, with 19.6% (11 out of 56 samples) detected through the hybrid capture method of whole genome sequencing and 20% (12 out of 60 samples) through qPCR. In hospital wastewaters, the detection rate was higher at 40% (12 out of 30 samples), compared to 13.3%(4 out of 30 samples) in municipal wastewaters. This variation could be attributed to the relatively low number of MPXV cases reported in the city, which ranged from 106 to 341 cases during the study period, and to dilution effects, given that each of the two wastewater treatment plants (WWTP) investigated serves approximately 1.1 million inhabitants. Additionally, nine other virus families were identified in both hospitals and municipal wastewaters including Adenoviridade, Astroviridae, Caliciviridae, Picornaviridade, Polyomaviridae, Coronaviridae (which includes SARS-CoV-2), Herspesviridae, Papillomaviridae and Flaviviridae (notably including Dengue). These findings underscore the potential of genomic sewage surveillance as a robust public health tool for monitoring a wide range of viruses circulating in both community and hospitals environments including MPXV.

The aim of this study was synthesize and evaluate the effects of Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of metformin (PLGA+ Met) on inflammation, and bone loss in a ligature-induced periodontitis rat model. The prepared NPs were characterized by mean diameter, size particle, polydispensity index and encapsulation efficiency by Atomic force microscopy (AFM). Male albino Wistar rats were randomly divided into four groups of 20 rats in each group, and given the following treatments for 10 days to evaluate in vivo activity: (1) Sham: no ligature + water; (2) Positive control: ligature + water (with Periodontal disease and Diabetes); (3) ligature + PLGA+ 10 mg/kg Met (With Periodontal disease and Diabetes); and (4) ligature + PLGA+ 100 mg/kg Met (with Periodontal disease and Diabetes). Water or PLGA + Met was administered orally by gavage. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantify linear of bone loss. Histopathological characteristics were assessed through immunohistochemical staining for Osteocalcin, Cathepsyn K, RANKL/RANK/OPG pathway. IL-1β and TNF-α from gingival tissues were analysed by Elisa immunoassay. Quantitative RT-PCR reaction was used to evaluate gene expression of AMPK, NF-κB p-65, Hmgb1 and TAK-1 from gingival tissues. Statistical analysis was performed using one-way ANOVA at 5% significance. The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm with a polydispersity index of 0.285, zeta potential: 8.16 ± 1.1 mV and entrapment efficiency (EE) was 70%. The results suggest that the addition of MET in the core slightly affected the particle sizes. Treatment with PLGA+ 10 mg/kg Met showed low inflammatory cells, decreased bone loss and integrity cement and levels of IL-1β, and TNF-α (p < 0.05) were significantly reduced. Additionally, weak staining was shown by RANKL, Cathepsyn K, OPG, and osteocalcin. Radiographically, linear measurements showed a statistically significant reduction in bone loss after treatment with PLGA+ 10 mg/kg Met compared to the positive control (p < 0.05). RT-PCR showed increased AMPK expression (p < 0.05) and decreased expression of NF-κB P65, HMGB1 and TAK-1 after PLGA+ 10 mg/kg Met (p < 0.05). The PLGA nanoparticle + 10 mg/kg Met decreased glucose levels and also decreased the inflammatory response, and bone loss in ligature-induced periodontitis in rats.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might have reduced the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patient with diabetes and those with obesity, as well as considering sex-based differences. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to develop a personalized approach.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.