Let R be a commutative graded ring with unity, S be a multiplicative subset of homogeneous elements of R and P be a graded ideal of R such that P\bigcap S=\emptyset In this article, we introduce several results concerning graded S-prime ideals. Then we introduce the concept of graded weakly S-prime ideals which is a generalization of graded weakly prime ideals. We say that P is a graded weakly S-prime ideal of R if there exists s\in S such that for all x, y\in h(R), if 0\neq xy\in P, then sx\in P or sy\in P. We show that graded weakly S-prime ideals have many acquaintance properties to these of graded weakly prime ideals.

Let $G$ be a group with identity $e$ and $R$ be a commutative $G$-graded ring with nonzero unity $1$. Graded semi-primary and graded $1$-absorbing primary ideals have been investigated and examined by several authors as generalizations of graded primary ideals. However, these three concepts are different. In this article, we characterize graded rings over which every graded semi-primary ideal is graded $1$-absorbing primary and graded rings over which every graded $1$-absorbing primary ideal is graded primary.

Let R be a commutative ring with identity and S be a multiplicatively closed subset of R. The purpose of this paper is to introduce the concept of weakly S-primary ideals as a new generalization of weakly primary ideals. An ideal I of R disjoint with S is called a weakly S-primary ideal if there exists s∈S such that whenever 0≠ab∈I for a,b∈R, then sa∈√I or sb∈I. The relationships among S-prime, S-primary, weakly S-primary and S-n-ideals are investigated. For an element r in any general ZPI-ring, the (weakly) S_{r}-primary ideals are charctarized where S={1,r,r²,⋯}. Several properties, characterizations and examples concerning weakly S-primary ideals are presented. The stability of this new concept with respect to various ring-theoretic constructions such as the trivial ring extension and the amalgamation of rings along an ideal are studied. Furthermore, weakly S-decomposable ideals and S-weakly Laskerian rings which are generalizations of S-decomposable ideals and S-Laskerian rings are introduced.

The Cohen-Macaulay vertex splittable ideals are characterized. As a consequence, we recover several Cohen-Macaulay classifications of families of monomial ideals known in the literature by new simpler combinatorial proofs.

In this paper we present two ways to solve the Jacobian conjecture. The first way is an equivalent statement to the Jacobian conjecture using idempotent ideals. The second way is to use an equivalent thesis to the thesis of the Jacobian conjecture. In both cases we will show that the Jacobian conjecture is true.

This manuscript employs a surface stress-driven nonlocal model to explore the combined effects of long-range interaction and surface energy on higher vibration modes of functionally graded nanobeams. The nanobeam theory, based on Bernoulli-Euler kinematics, incorporates surface effects such as surface elasticity, surface residual stresses, surface density, and rotary inertia. Hamilton's principle is applied to derive the governing equation with size-dependent considerations. The main outcomes of a parametric investigation, considering four different kinematic boundary conditions (Cantilever, Simply-Supported, Clamped-Pinned, and Doubly-Clamped) while varying the nonlocal parameter and material gradient index, are presented and discussed. Additionally, the normalized natural frequencies for the second, third, fourth and fifth modes of vibrations are provided and analyzed for each case under study. The results underscore the model's effectiveness in capturing surface energy effects on the overall dynamic behavior of functionally graded Bernoulli-Euler nanobeams, offering a cost-effective approach for designing and optimizing nano-scaled structures.

Let R be a commutative ring with identity and m, n be positive integers. In this paper, we introduce the class of (m,n)-prime ideals which lies properly between the classes of prime and (m,n)-closed ideals. A proper ideal I of R is called (m,n)-prime if for a,b∈R, a^{m}b∈I implies either aⁿ∈I or b∈I. Several characterizations of this new class with many examples are given. Analougus to primary decomposition, we define the (m,n)-decomposition of ideals and show that every ideal in an n-Noetherian ring has an (m,n)-decomposition. Furthermore, the (m,n)-prime avoidance theorem is proved.

A well-known result of Posner’s second theorem states that if the commutator of each element in a prime ring and its image under a nonzero derivation is central, then the ring is commutative. In the present paper, we extend this bluestocking theorem to an arbitrary ring with involution involving prime ideals. Further, apart from proving several other interesting and exciting results, we establish *-version of Vukman’s theorem [48, Theorem 1]. Precisely, we describe the structure of quotient ring A/L, where A is an arbitrary ring and L is a prime ideal of A. Further, by taking advantage of the *-version of Vukman’s theorem, we show that if a 2-trosion free semiprime ring A with involution admits a nonzero *-centralizing derivation, then A contains a nonzero central ideal. This result is in a spirit of the classical result due to Bell and Martindale [19, Theorem 3]. As the applications, we extends and unify several classical theorems proved in [6],[25,[42], and [48] . Finally, we conclude our paper with a direction for further research.

Throughout this paper, we will establish a comprehensive theoretical foundation and rigorously develop the methodology to investigate the structure of quotient ring S/P under the influence of symmetric generalized n-derivations, where S represents an arbitrary ring, and P signifies a prime ideal of S satisfying certain algebraic identities acting on prime ideal P without relying on the assumption of primeness or semi-primeness of the ring.

In this paper we define families of open sets as sums of idempotent ideals and sums of square-free ideals in a ring. We investigate some topological properties of such topologies. We define the square-free spectrum of a ring as the set of all square-free ideals and examine what topological properties it has for a given monoid.

We propose a thermodynamic model describing the thermoelastic behavior of composition graded materials. The compatibility of the model with second law of thermodynamics is explored by applying a generalized Coleman-Noll procedure. We calculate the speeds of coupled first- and second-sound pulses, propagating either trough nonequilibrium or trough equilibrium states. We characterize several different types of perturbations, depending on the value of the material coefficients. Under the assumption that the deformation of the body can produce changes in its stoichiometry, altering locally the material composition, the possibility of propagation of pure stoichiometric waves is pointed out. Thermoelastic perturbations generated by the coupling of stoichiometric and thermal effects are analyzed as well.

We propose a notion of $(q,\sigma,\tau)$-differential graded algebra, which generalizes the notions of $(\sigma,\tau)$-differential graded algebra and $q$-differential graded algebra. We construct two examples of $(q,\sigma,\tau)$-differential graded algebra, where the first one is constructed by means of generalized Clifford algebra with two generators (reduced quantum plane), where we use a $(\sigma,\tau)$-twisted graded $q$-commutator. In order to construct the second example, we introduce a notion of $(\sigma,\tau)$-pre-cosimplicial algebra.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p>0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

The acoustic environment in learning spaces significantly influences learning effectiveness and occupant well-being. Recent studies have shown that a series of architectural factors within physical learning environments can impact students' educational experiences. This research delves into the relationship between architectural characteristics and the perceived acoustic environment among 467 primary students in 19 learning spaces across 9 schools in Chile. The survey comprises a student questionnaire, a checklist evaluating space characteristics, and acoustic measurements of indoor noise levels during occupied conditions. Examined topics include Indoor Environmental Quality (IEQ) comfort perception, noise annoyance, hearing ability, and acoustic preference. Architectural characteristics considered encompass flexible and acoustic space design parameters. The results indicated that noise discomfort was a common issue, especially in traditional learning spaces without acoustic treatment. The type of learning space (traditional or flexible settings) has a greater impact on acoustic perception particularly concerning noise discomfort and acoustic preference. However, poorly acoustic spaces lacking absorbing materials or exhibiting lower spatial density (m2 per student) contribute to increased indoor noise levels affecting noise annoyance caused by children's talking inside. The study emphasizes the importance of considering both architectural design and acoustic conditioning for optimizing the acoustic experience in educational spaces.

Let $a, b$ and $n > 1$ be three positive integers such that $a$ and $\sum_{j=0}^{n-1} b^j$ are relatively prime. In this paper, we prove that the toric ideal $I$ associated to the submonoid of $\mathbb{N}$ generated by $\{\sum_{j=0}^{n-1} b^j\} \cup \{\sum_{j=0}^{n-1} b^j + a\, \sum_{j=0}^{i-2} b^j \mid i = 2, \ldots, n\}$ is determinantal. Moreover, we prove that for $n > 3$, the ideal $I$ has a unique minimal system of generators if and only if $a < b-1$.

Resection of malignant lesions in the oral and maxillofacial area causes functional and morphological defects. To recover from these defects, reconstruction surgery is needed such as a primary closure or a flap. There are advantages and disadvantages to the method of using the primary closure and the flap, and the choice of procedure is entirely up to a surgeon. The purpose of this study is to evaluate availability of primary closure in patients. For 10 years from January 2010 to May 2020, patients who recovered using flaps after removing malignant lesions from the oral cavity and those who closed the lesion using primary closure were investigated. The investigation was conducted by searching the database of the hospital. There were 85 patients who removed malignant lesions in the oral and maxillofacial area, and among them 16 patients closed the soft tissue defects using primary closure. Operation time, histologic types, stages, wound status, and period of hospitalization according to the patients' medical records were investigated retrospectively. Between the staging and the primary closure, statistically significant differences were observed between stage I and stage II patients in 13 patients using the primary closure. (P=0.046). Statistically significant differences were identified between operation time and primary closure, with an average of 4.02 hours (P=0.015). The average period of hospitality for patients who underwent primary closure was 13.4 days, compared to 26.7 days for those who underwent flap surgery. This difference was statistically significant (P=0.0003). This study evaluated the use of primary closure in patients who underwent resection of malignant lesions in the oral and maxillofacial area. Although the majority of patients underwent reconstruction with flaps, our results showed that primary closure can be a viable option for certain patients with early-stage lesions. Therefore, oral and maxillofacial surgeons should carefully consider various evaluation criteria and select appropriate reconstruction methods to optimize functional and aesthetic outcomes for each patient.

The paper describes the Field Boundary Element Method applied to the fracture analysis of a 2D rectangular plate made of Functionally Graded Material to calculate Mode I Stress Intensity Factor. The object of the Field Boundary Element Method is the transversely isotropic plane plate. Its material presents an exponential variation of the elasticity tensor depending on a scalar function of position, i.e., the elastic tensor results from multiplying a scalar function by a constant taken as a reference. Several examples using a parametric representation of the structural response show the suitability of the method that constitutes a sight of Stress Intensity Factor evaluation of Functionally Graded Materials plane plates even in the case of more complex geometries.

Let N = N₀+ N₁+ N₂ be a Z₃-graded Novikov algebra. The main goal of the paper is to prove that over a field of characteristic not equal to 3 the algebra N is solvable if N₀ is solvable. We also show that a $Z_2$-graded Novikov algebra N=N₀+ N₂ over a field of characteristic not equal to 2 is solvable if N₀ is solvable. This implies that for every n of the form n=2^k3^l, any Z_n-graded Novikov algebra N over a field of characteristic not equal to 2,3 is solvable if N₀ is solvable.

We present a case report of a young patient with pectus carinatum who experienced a small right apex pneumothorax and exhibited Brugada patterns on electrocardiogram tracing. This is the first clinical case reporting Brugada pattern presentation in both a patient with pectus carinatum and a small pneumothorax. We conducted a clinical, anatomical, and electrocardiographic analysis to explore a physiopathological explanation for these findings, considering our patient had no history or clinical signs of Brugada Syndrome. We conclude that: 1. Pectus carinatum may create a window that facilitates the less resistive measurement of cardiac action potentials; 2. Small pneumothoraces can induce modifications in the cardiac electrical signal detected by surface electrodes, and pectus carinatum could unmask these modifications; and 3. Surface electrodes may measure subepicardial potentials that include and are modified by adjacent pericardial tissues, potentially resulting in alterations in transmural potential differences, thus producing fictitious Brugada patterns. Similarly, there is a possibility that the right ventricular outflow tract may be included within the subendocardial potentials.

Porous structured metallic implants are preferable as bone graft substitutes due to their faster tissue integration mediated by bone in-growth and vascularization. The porous scaffolds/ implants should also mimic the graded structure of natural bone to ensure a match of mechanical properties. This article presents a method to design graded porous structured acetabular implant and identifies the suitable parameters for manufacturing the model through additive manufacturing. The design method is based on slice-wise modification to ensure continuity of gradation. Modification of the slices was achieved through the binary image processing route. A geodesic dome type design was adopted for developing the acetabular cup model from the graded porous structure. The model had a solid shell with the target porosity and pore size gradually changing from 65% and 950 µm, respectively, in the inner side to 75% and 650 µm, respectively, towards the periphery. The required dimensions of the unit structures, and the combinations of pore structure and strut diameter to obtain the target porosity and pore size were determined analytically. Suitable process parameters were identified to manufacture the model by Direct Metal Laser Sintering (DMLS) using Ti6Al4V powder after carrying out a detailed experimental study to minimize the variation of surface roughness and warping over different build angles of the strut structures. A dual contour scanning was implemented to simplify the scan strategy. The minimum diameter of struts that could be manufactured using the selected scanning strategy and scanning parameters was found to be 375 µm. Finally, the model was built and from the micro-CT data, the porosities and pore sizes were found to be closely conforming to the designed values. The stiffness of the structures, as found from compression testing, was also found to be well matching with that of human trabecular bone. Further, the structure exhibited compliant bending-dominated behavior under compressive loading.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in 70% of Puerto Rican patients, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the framework for PCD evaluation and diagnosis, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

Noninvasive brain stimulation technique can be used for modulation of motor behaviors such as reaction time (RT). The main aim of this study was to investigate whether RT during a sequential visual isometric pinch task (SVIPT) can be affected by anodal transcranial direct current stimulation (a-tDCS) over three different stimulation sites such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1) or posterior parietal cortex (PPC). We also aimed to assess if stimulation of these cortical sites affect the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: 1) left M1, 2) left DLPFC, 3) left PPC and 4) sham. A-tDCS was applied concurrent with SVIPT in which the participants were precisely controlled their forces to reach seven different target forces from 10 to 40% of maximum voluntary contraction (MVC) presenting on a computer screen with right dominant hand. Four test blocks were randomly performed at baseline and 15 min after the intervention including sequence and random blocks with either hand. Our results showed significant differences between a-tDCS groups on ratio RT in the sequence blocks of both the right trained (P = .041) and left untrained hands (P = .023) for target forces of 15% and 30 % of MVC, respectively. In sequence blocks, M1 showed significant elongation in ratio RT for the target force of 15% and 30 % MVC compared to PPC and Sham groups in the right hand. In sequence blocks with left hand, this negative effect were found between M1-DLPFC and M1-Sham groups. In random blocks, no significant differences were found among four groups at each target forces for the left hand while there were significant differences for 15% (P =. 04) and 40% MVC (P =. 035) in the right hand. Our findings suggest that three different stimulation sites (DLPFC, M1 or PPC) were differentially affected by a single session of a-tDCS at some target forces during SVIPT. The effects of a-tDCS on ratio RT were transferred in the left untrained hand for sequence blocks but not random blocks. Further research is needed to understand fundamental aspects of these main areas of the brain on temporal processing in a precision control task such as SVIPT.

The presented research article shows a functionally graded lattice as an infill structure in designing a 3D printed mechanical element—a bicycle crank arm. The authors want to answer the fundamental question: whether the functionally graded lattice structures can efficiently improve structural performance and how they can be implemented in real complex components. Intuitively, everyone senses that using such elements must bring profit. A good example might be nature, which commonly reaches for such a solution in the skeletons of animals and humans. Two aspects determine their realisations: the lack of adequate construction and analysis methods and the limitations of existing manufacturing methods. Thus, the authors used relatively simple crank arm design and design exploration methods for structural analysis. The design exploration method enabled us to find the optimum solution efficiently. A developed prototype was created utilising additive manufacturing. One of the 3D printing methods - fused filament fabrication technology for metals, allowed the prototype of a crank arm with the optimised infill to be made. As a result, the authors developed a lightweight and manufacturable crank arm showing the new construction and analysis method implementable in similar 3D printed elements.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Transmission of values and religious concepts to children is one of the most important issues in the third millennium and it has drawn varied and different views among experts and scholars in the world. Research specialized in religious literature for children and adolescents create new capacities in the presentation of religious concepts to the group. Plans have been considered to transfer values and religious concepts in the curricula of primary school children in the group in Iran. It is one of the topics that the authors note to the introduction of the minutiae of religion in the first three elementary grades. In this study, the collection and analysis methods providing content related to the minutiae of religion in reading books the first till third sections of the years 2013-2015. In addition, the plan includes aspects of other branches of religion in these books on information collected from text books that collected and classified. The result is that "definitely good and forbidding the evil" and "prayer" have the highest frequency of applications in the selected books. Further branches made of branches of religion in these books, represents the values of religious, moral and social as well.

Model-based approaches form the basis of the majority of damage detection and localization studies; however, built-in online detection technique can offer an alternative for future structural health monitoring technologies. Thus, in this paper, we present a dynamic localization algorithm for damage localization in functionally graded plates. The method depends on the creation of a grid matrix that contains the dynamic response of the structure over time. Subsequently, an optimization process is carried out via a linear equation representing the information contained within the grid to achieve accurate localization of damage. Due to the inherent sparsity of the localization nature, the FISTA algorithm has been employed as a problem solver. The approach is tested in the case of the functionally graded plate under clamped free boundary conditions. Several, damage scenarios were investigated for the case of damage signals on and off the grid. The results show that the proposed approach is capable of accurately predicting damage position and can be suitable for use in low size data systems.

Single nanowires (NWs) are of great importance for optoelectronic applications, especially solar cells serving as powering nanoscale devices. However, weak off-resonant absorption can limit its light-harvesting capability. Here, we propose a single NW coated with the graded-index dual shells (DSNW). We demonstrate that with appropriate thickness and refractive index of the inner shell, the DSNW exhibits significantly enhanced light trapping compared with the bare NW (BNW), and the NW only coated with the outer shell (OSNW) and the inner shell (ISNW), which can be attributed to the optimal off-resonant absorption mode profiles due to the improved coupling between the reemitted light of the transition modes of the leak mode resonances of the Si core and the nanofocusing light from the dual shells with the graded refractive index. We found that the light absorption can be engineered via tuning the thickness and the refractive index of the inner shell, the photocurrent density is significantly enhanced by 134% (56%, 12%) in comparison with that of the BNW (OSNW, ISNW). This work advances our understanding of how to improve off-resonant absorption by applying graded dual-shell design and provides a new choice for designing high-efficiency single NW photovoltaic devices.

Spin-orbit coupling and nonparaxiality effects during propagation of vortex vector light beams in a cylindrical graded-index waveguide are investigated by solving the full three-component field Maxwell’s equations. Symmetry breaking effects for left- and right-handed circularly polarized vortex light beams propagating in a rotationally symmetric graded-index optical fiber are considered. The mode-group delay in a graded-index fiber due to spin-orbit interaction is demonstrated. It is shown that the relative delay times between vortex pulses of opposite circular polarizations of the order of 10 ps/km can be observed in graded-index fibers for high-order topological charges.

Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investigated differences in the biomechanical responses among human cartilage of ICRS grades I, II and III using polymer dynamics theory. We collected 24 explants of human articular cartilage (eight each of ICRS grade I, II and III) and acquired stress-relaxation data applying a continuous load on the articular surface of each cartilage explant for 1180 s. We observed a significant decrease in Young’s modulus, stress-relaxation time, and stretching exponent in advanced stages of OA (ICRS grade III). The stretch exponential model indicated that significant loss in hyaluronic acid polymer might be the reason for the loss of proteoglycan in advanced OA. This work encourages further biomechanical modelling of osteoarthritic cartilage utilizing these data as input parameters to enhance the fidelity of computational models aimed at revealing how mechanical behaviors play a role in pathogenesis of OA.

Background: We compared corneal visualization Scheimpflug technology (CST) parameters between eyes with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: A retrospective analysis was done on data from 89 eyes with POAG and 83 eyes with PACG that had CST examinations. CST parameters were compared between eyes with POAG and those with PACG using a linear mixed model (LMM). Results: No differences were observed in age, central corneal thickness, intraocular pressure, or use of antiglaucoma eye drops between the two groups. Patients with PACG had a significantly shorter axial length (AL), a higher proportion of females, CST parameters, longer applanation 2 (A2) time, deeper A2 deformation amplitude, shorter peak distance (PD), longer whole eye movement, and longer whole eye movement time than patients with POAG. Highest concavity (HC) length and PD showed a significant positive correlation with AL. However, A1 length, A1 deformation amplitude, A2 time, A2 velocity, A2 length, A2 deformation amplitude, HC time, whole eye movement, and whole eye movement time were negatively correlated with AL. Conclusions: Biomechanical properties of the cornea differed between PACG and POAG. In some parts, AL differences between the POAG and PACG groups might contribute to the variation in CST parameters.

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematous, celiac disease and Sjögren syndrome, and lymphoma has been widely demonstrated by several epidemiologic studies. By a not yet entirely elucidated mechanism, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to persistent stimulation of both of B- and T-cells, and to the onset of different types of lymphoma in such patients. Specifically, patients affected by may develop lymphomas may years after the original diagnosis. Several epidemiologic, hematologic and histological factors may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly diffuse large B-cell and extranodal marginal zone lymphomas is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma and predictive factors still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57 y.o. patient. The diagnostic work-up, including radiograms, core needle biopsy and histological examination are discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

The global issues of overweight and sedentary lifestyles demand comprehensive responses from health systems, yet health education still needs to be more cohesive and less sporadic. This study focuses on primary school children as a specific target for instilling healthy habits, employing ac-tive learning strategies to address healthy diet and physical activity. Through Problem-Based Learning projects, the study engaged fourth-grade primary students in acquiring healthy habits. The study was carried out over four consecutive years at a school with two lines, allowing the employment of an opportunity sample and evaluating intervention and control groups by com-paring their corresponding scores. Control groups integrated a total of 54 students, while the in-tervention group included a total of 159 students. A pre-test and post-test questionnaire were used for data collection. Evaluation differential scores revealed statistically significant higher scores in the intervention groups: 3.62 points in control groups and 6,94 in intervention groups, particu-larly in attitudinal competences. These strategies not only facilitated the development of crucial skills such as information search, synthesis, representation, analysis, decision-making, teamwork, and intrapersonal awareness but also significantly broadened the knowledge acquired in aspects related to healthy habits. This approach proved effective in helping children comprehend the im-portance of healthy choices and encouraged integrating such habits into their daily lives.

The influence of applied loads on free vibrations analysis of plates and shells panels made of functionally graded materials is analyzed in the present work. Formulations for the static analysis considering geometrically nonlinear behavior, as well as linear buckling and free vibrations analyses are considered. The calculation of the through-thickness stress distribution is also performed. A finite element model based on a higher order shear deformation theory and using a non-conforming triangular flat plate/shell element with 3 nodes, and 8 degrees of freedom per node is used in the numerical implementation. The results obtained with this numerical model are presented, discussed, and compared with alternative solutions published by other authors in some benchmark applications.

This study investigates the elastic buckling behaviour of skew Functionally Graded Material (FGM) thin plates featuring a circular opening. FGM materials, known for their unique property gradients, have gained prominence in structural engineering due to their mechanical performance and durability. Including a circular opening introduces a critical geometric consideration, influencing the structural stability and load-carrying capacity of FGM plates. The study examines the effects of the skew angle, plate’s aspect ratio, opening position, and size on the critical buckling load, normalized buckling load, and various buckling failure modes through computer modelling and finite element analysis. The results offer valuable insights into the interplay between material heterogeneity, geometric configuration, and structural stability. For instance, the critical buckling load increases by 29%, 82%, and 194% with the increment of skew angle from 0° to 30°, 45°, and 60°, respectively. Moreover, as the opening shifts from the plate’s edge closer to the center, the critical buckling load decreases by 26%. This research contributes to the advancement of understanding FGM thin plates’ behaviour under skew loading conditions, with implications for the design and optimization of innovative structures. The findings presented provide a foundation for further exploration of advanced composite materials and their applications in structural engineering.

Background. Primary Stabbing Headache (PSH) is characterized by brief, focal and paroxysmal pain (“stab”), occurring sporadically or in clusters. Data on pediatric cases are poor. Methods. We performed a comprehensive literature review searching Pubmed, Cochrane and Embase in order to collect pediatric case reports and case series of PSH. Results. Twelve out of 162 articles assessed for eligibility were finally included. Prevalence of PSH and probable PSH varies from 2.5 to 10% among children with primary headaches and it is higher among children aged less than 6 years old. The mean age of onset is between 7 and 11 years of age. Attack duration greatly varies, ranging from a few seconds to several minutes. Intensity of pain is usually from moderate to severe. Associated symptoms are infrequent but may be observed (mainly photophobia, vertigo, nausea and vomiting). Neuroradiological findings are usually unremarkable; EEG may show sporadic epileptiform abnormalities (up to 30% of cases). Preventive therapy is anecdotal, including treatment with indomethacin, trazodone, valproate and amitriptyline. Conclusion: PSH is a common but still underdiagnosed entity among children with primary headache; further and larger cohort studies are needed to better assess, in particular, prognosis and response to therapy.

This paper presents an approach to the vibration analysis of axially functionally graded non-prismatic Timoshenko beams (AFGNPTB) using the finite difference method (FDM). The characteristics (cross-sectional area, moment of inertia, elastic moduli, shear moduli, and mass density) of axially functionally graded beams vary along the longitudinal axis. The Timoshenko beam theory covers cases associated with small deflections based on shear deformation and rotary inertia considerations. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, differential equations were formulated with finite differences, and additional points were introduced at the beam’s ends and at positions of discontinuity (supports, hinges, springs, concentrated mass, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. Vibration analysis of AFGNPTB was conducted with this model, and natural frequencies were determined. Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of AFGNPTB, considering the damping. The results obtained in this study showed good agreement with those of other studies, and the accuracy was always increased through a grid refinement.

In this research, a design method for the graded triply periodic minimal surface (TPMS) structures with lightweight, high-strength, and high sound absorption properties is proposed. The graded TPMS structures are controlled by linear, quadratic, and sine functions. Uniform TPMS and graded TPMS were manufactured by laser powder bed fusion (LPBF) with AlSi7Mg powder, and an acoustic impedance tube test, compression test, and digital image correlation (DIC) test were ap-plied to obtain the sound absorption and compression properties. The sound absorption coefficient of a uniform Gyroid increases as the number of layers and surface thickness increase, and it in-creases as element size decreases. The sound absorption peak shifts to low frequencies as the number of layers increases. The sound absorption property of Type-Ⅰ graded TPMS is superior to the Type-Ⅱ, and the G-LinearⅠ has the highest sound absorption properties among the three functions. It reveals that the graded TPMS has superior sound absorption performance at low and medium frequencies. The compression and DIC results of graded TPMS also show excellent mechanical properties and energy absorption characteristics.

In an attempt to improve free-range beef cattle herds and explore the economic viability of utilizing Opuntia ficus-indica (spineless cactus) cladodes as supplementary feed, we investigated the impact of cactus diets on animal growth performance and carcass characteristics of Nguni cattle heifers. Four dietary treatments were randomly assigned to 32 heifers aged 24-months, weighing on average 172.2±27.1 kg, with each dietary treatment replicated to 8 individually penned heifers for 90 days. The dietary treatments were control diet (pasture-based energy + protein sources), 10% cactus diet, 20% cactus diet and commercial diet (crop-based energy and commercial protein source). The heifers fed commercial and control diets attained significantly (P < 0.05) higher dry matter intake, average daily gains, fat thickness, carcass conformation scores and lower feed conversion ratio than those fed cactus diets. However, the final body weight gains, slaughter and carcass weights, rib-eye muscle area and meat pH45 min and 24h were comparable (P > 0.05) between heifers fed cactus diets and those fed commercial and control diets. The 10 and 20% cactus diets had greater gross margins (P < 0.05) of R278.6 and R296.9, respectively than the other diets, due largely to reduced total variable costs. The comparability of carcass traits of heifers fed cactus diets and those fed non-cactus diets as well as higher economic returns from cactus inclusion warrants the use of cactus diets, particularly during drought when commercial feed prices rise.

Free vibration analysis of the porous functionally graded circular plates has been presented on the basis of classical plate theory. The three defined coupled equations of motion of the porous functionally graded circular/annular plate were decoupled to one differential equation of free transverse vibrations of plate. The one universal general solution was obtained as linear combination of the multiparametric special functions for the functionally graded circular and annular plates with even and uneven porosity distributions. The multiparametric frequency equations of functionally graded porous circular plate with diverse boundary conditions were obtained in the exact closed-form. The influences of the even and uneven distributions of porosity, power-law index, diverse boundary conditions and the negligibled effect of the coupling in-plane and transverse displacements on the dimensionless frequencies of the circular plate were comprehensively studied for the first time. The formulated boundary value problem, the exact method of solution and the numerical results for the perfect and imperfect functionally graded circular plates have not yet been reported.

The objective of this study is to analyze the assessment practices in primary education and how they relate to the valuation of the learning process. It seeks to understand the perceptions of teachers and students regarding assessment and to observe classroom activities, as well as to analyze the assessment instruments used. The method used is a mixed approach that combines qualitative interpretations of the participants’ realities with a phenomenological analysis to reflect on the evaluative practices. The results indicate a contradiction between what is said and what is done in terms of evaluation, with a tendency to use written tests and traditional exams instead of a combination of techniques that allow for a significant evaluation of student learning. In addition, significant differences are observed among teachers regarding the importance they give to evaluation within their practices and evaluative models.

Background: Primary lymphedema is a chronic condition caused by a developmental abnormality of the lymphatic system and its malfunction. Different surgical options such as physiologic and excisional procedures have been proposed. The aim of this study was to present a complete algorithm for the treatment of primary lower extremity lymphedema: Primary LYmphedema Multidisciplinary Approach (P-LYMA). Methods: Nineteen patients were treated according to the P-LYMA. Patients underwent pre- and post-operative complex decongestive therapy (CDT). Different physiologic and excisional procedures were performed independently or in combination. The primary outcome was the circumferential reduction rate (CRR). The Lymphedema Quality of Life Score (LeQOLiS), reduction in the number of episodes of cellulitis, length of stay, and complications were recorded. Results: The mean CRR calculated was 72.8±19.6% after twelve months. The episodes of cellulitis per year decreased from a mean of 1.9±0.8 preoperative to 0.4± 0.6 throughtout follow-up. Two patients experienced minor complications. Mean hospitalization time was 5 days. Patients’ quality of life (LeQOLi score) drastically improved from 70.4±11.6 to 24.2 ±13.9 at twelve months post-op. Conclusion: The P-LYMA algorithm allows to maximize surgical results and improve the quality-of life in patients who suffer from primary lymphedema. CDT is mandatory to optimize results.

This paper presents an approach to the vibration analysis of axially functionally graded (AFG) non-prismatic Euler-Bernoulli beams using the finite difference method (FDM). The characteristics (cross-sectional area, moment of inertia, elastic moduli, and mass density) of AFG beams vary along the longitudinal axis. The FDM is an approximate method for solving problems described with differential equations. It does not involve solving differential equations; equations are formulated with values at selected points of the structure. In addition, the boundary conditions and not the governing equations are applied at the beam’s ends. In this paper, differential equations were formulated with finite differences, and additional points were introduced at the beam’s ends and at positions of discontinuity (supports, hinges, springs, concentrated mass, spring-mass system, etc.). The introduction of additional points allowed us to apply the governing equations at the beam’s ends and to satisfy the boundary and continuity conditions. Moreover, grid points with variable spacing were also considered, the grid being uniform within beam segments. Vibration analysis of AFG non-prismatic Euler-Bernoulli beams was conducted with this model, and natural frequencies were determined. Finally, a direct time integration method (DTIM) was presented. The FDM-based DTIM enabled the analysis of forced vibration of AFG non-prismatic Euler-Bernoulli beams, considering the damping. The results obtained in this paper showed good agreement with those of other studies, and the accuracy was always increased through a grid refinement.

Improving the quality and access to healthcare services in rural areas is fundamental to develop sustainable healthcare systems. This research aims to explore the motivations of healthcare professionals to work and settle in rural island areas of Greece with limited access to secondary and tertiary care. The study suggests practical ways to encourage self-motivation and attract more health workers in rural areas. An exploratory qualitative research approach was employed, involving semi-structured interviews with 16 healthcare professionals working in primary care units that lack direct hospital or hospital-health center access. The research was conducted specifically in the rural islands of Cyclades. Thematic analysis was conducted to identify common themes and unique insights from the participants. The analysis revealed three thematic categories. Τhe «attraction» thematic was influenced by personal factors, random selection, origin, accommodation factors, professional factors and obligatoriness. The «recruitment» thematic was associated with understaffing, special care issues, unstable working environment, educational and organizational aspects, and insular lifestyle. The thematic of «retention» highlighted personal issues, accommodation difficulties, economic and work-related issues, and unique challenges posed by an insular lifestyle. This research provides valuable insights into the motivations that drive healthcare professionals to settle, work, and remain in remote island units, as well as the challenges they encounter in making this decision. The study proposes strategies to motivate and attract more healthcare professionals to rural areas. These findings should be considered when formulating or reviewing primary healthcare empowerment policies to ensure equitable healthcare access for all individuals.

If we assume that: a. The four fundamental forces of nature are independent waves without rest masses, and their speeds are constant in a vacuum, just like light. b. Light or electromagnetic waves and gravity are comparable in structures. Weak and strong interactions are similar in structures. c. Light and weak interaction have the same speed c_L with spin number +1 or –1. d. Gravity and strong interaction have the same speed c_G without spin. e. The primary particles, namely electrons, electron neutrinos, and dark neutrinos in this paper, are made by the above four waves. We can find and describe some fundamental characteristics of the primary particles (e.g., their sizes, energies, and interactions) and introduce new attractive results from them (e.g., the source of the Pauli exclusion principle, the solution to the Einstein-Podolsky-Rosen paradox, and c_G slightly faster than c_L).

In zebrafish inner ear, hair cell orientation in anterior and posterior maculae of the embryonic otic vesicle is different (about 30–40 degrees): this is rather unusual in planar polarity mechanism of action, instead suggests that kinocilia may be rotationally polarized. In mice node, the innermost monociliated cells generate a left-ward fluid flow sensed by the immotile primary cilia of Left peri-nodal cells: the Nodal signaling pathway is then expressed asymmetrically, in the Left lateral plate mesoderm, breaking symmetry in visceral organs (situs solitus); however, Right peri-nodal cells also, if artificially excited by a right-ward flow, break symmetry and activate the Nodal cascade, though inverting visceral organ asymmetry (situs inversus); surprisingly, peri-nodal cells prove to be adept at distinguishing flow directionality. Recently, in the Kupffer vesicle (the zebrafish laterality organ), chiral primary cilia orientation has been described: primary cilia, in the left and right side, are symmetrically oriented, showing a mirror average divergence of about 15–20 degrees from the midline. This finding, taken together with the mirror behavior of mouse perinodal cells and zebrafish hair cells, champions the idea of primary cilia enantiomerism.

Headache is considered to be one of the most common causes of medical treatment and evaluation worldwide in both acute and outpatient settings. It is the most common neurological symptom seen worldwide affecting all genders, ages, ethnicities, and socioeconomic levels. It’s impact is noted in educational decline in school-aged children and decreased productivity through sick leave in adults. Its overall burden is well documented in well-resourced countries but limited data is seen low resourced countries. While many underlying causes bring about secondary headaches, primary headaches and more specifically migraines have been more widely explored. Migraines have a distinct criterion that is inclusive of one day duration (4 hours to 7 days, unilateral distribution, nausea and vomiting and disability as a few examples. However, migraines can vary and proper documentation through a migraine diary can help to guide treatment. Management of migraines can vary. Lifestyle modification is a key factor in the overall prevention and reduction of triggers in migraines. In addition to this, pharmacotherapy can be given in a tier-based approach based on overall severity and frequency of the migraine. Interventions have progressed from botox injection and have seen the advent of new medications such as nasal sprays to novel formulations of pre-existing drug formulations. Nonetheless, there is great room for further studies of headaches and migraines. Research specifically in low-resource countries can prove to beneficial.

The present article investigates the threshold analysis of yielding in a variable thickness rotating disk based on the Tresca criterion. The analysis is conducted on a Functionally Graded Material (FGM) constructed from tailored materials, following the theory of small deformations and for the case of plane stress. The elasticity modulus, density, and yield stress are assumed to be power functions of the radial coordinate. Poisson’s ratio is considered constant due to small variations in different materials. Additionally, the governing equation for the rotating disk is solved analytically. Besides the material type, another factor affecting the distribution of effective stress magnitudes is the cross-sectional shape (profile) of the disk. The thickness of the cross-sectional disk varies radially as a power function. In the current analysis, different conditions for the onset of yielding and the evolution of plastic flow are considered. For evaluation and validation, the obtained results are compared and validated against similar results for specific cases (homogeneous disk and constant thickness graded disk) available in previous references. The results indicate that considering variable thickness for the disk section significantly affects the stresses and the location of the initiation of yielding

Functionally graded materials (FGM) have attracted considerable attention in the field of composite materials and rekindled interest in research on composite materials, due to their unique mechanical response achieved through material design and optimization. Compared to conventional composites, FGMs offer several advantages and exceptional properties, including improved deformation resistance, improved toughness, lightness properties, and excellent recoverability. This study focused on the production of functionally graded (FG) polymer materials by additive manufacturing (AM) method. FG structures were produced by the Fused Deposition Modeling (FDM) method using Acrylonitrile benzidine styrene (ABS) and Polylactic acid (PLA) materials and tensile tests were performed according to ASTM D638. The effects of different layer thicknesses, volume ratios, and total thicknesses on mechanical behavior were investigated. In addition, tensile tests were carried out by producing single-layer samples at certain volume ratios to create a numerical model with the Finite element method to verify the experimental data. As a result of this study, it is presented that the FG structure produced with FDM improves mechanical behavior.

Directed energy deposition (DED) is an efficient method to fabricate functionally graded materials (FGMs) with gradient composition and complex structures, allowing for local tailoring of properties instead of the costly need for extraneous welds and joints. In this study, a FGM from stainless steel to Inconel alloy was successfully fabricated using the powder-based laser DED. A very refined grain structure has been observed in at the composition with 75 wt.% Inconel alloy content, which also exhibits the highest (entropy). For the first time, the post heat treatments, microstructure and aging precipitation behaviors of FGMs were systematically studied via experimental characterization and computation, to elucidate their effects on the gradient smoothing and mechanical properties. The diffusion and segregation of Ni, Nb and Ti elements underly the transformation mechanism between Laves, δ, γ’ and γ’’ phases during precipitation. Homogenization on FGMs not only eliminates the heterogeneity inherited from the AM process, but also provides a practical way to smoothen the gradient on composition and microstructure for the eventual good gradient properties. It has a direct influence on the following precipitation behaviors in the FGM, which highly relies on the diffusion degree of the elements in the matrix and grain boundaries. The high-throughput thermodynamic modeling and kinetic modeling were exploited to evaluate the experimental microstructure and address computational uncertainty using different thermodynamic conditions and databases, which enables an accelerated design through local tailoring of process-structure-property relationships to develop new functional materials.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Primary Biliary Cholangitis (PBC) is a chronic, cholestatic liver disease with a heterogeneous presentation, symptomatology, disease progression, and response to therapy. The current risk stratification assessment, aimed at identifying patients with a higher risk of disease progression, encompasses an in-depth analysis of demographic data, clinical and laboratory findings, antibody profiles, and the evaluation of liver fibrosis using both invasive and non-invasive techniques. Treatment response scores after one year of therapy remain to date a major factor influencing the prognosis of PBC patients. While the initial therapeutic approach with ursodeoxycholic acid (UDCA) is universally applied, new second-line treatment options have recently emerged, with many others under investigation. Consequently, the prevailing one-size-fits-all approach is poised to be supplanted by tailored strategies, ensuring high-risk patients receive the most appropriate treatment regimen from diagnosis. This will require the development of a risk prediction model to assess, at the time of diagnosis, the course, outcome, and response to first and additional treatments of PBC patients. This manuscript provides a comprehensive overview of the current and emerging tools used for risk stratification in PBC and speculates on how these developments might shape the disease landscape in the near future.

Abstract Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant, plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Because of the multiplicity of roles in cell function, it is not surprising that deficiency of CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation.

Restrictive cardiomyopathy is a rare cardiac disease causing severe diastolic dysfunction, ventricular stiffness and dilated atria. In consequence, it induces heart failure often with preserved ejection fraction and is associated with a high mortality. Since a poor clinical prognosis, patients with restrictive cardiomyopathy require frequently heart transplantation. Genetic as well as non-genetic factors contribute to restrictive cardiomyopathy and a significant portion of cases remains of unknown etiology. However, the genetic forms of restrictive cardiomyopathy and the involved molecular pathomechanisms are only partially understood. In this review, we summarize the current knowledge about primary genetic restrictive cardiomyopathy and describe its genetic landscape, which might be of interest for geneticists as well as for cardiologists.

Schiff bases attract research interest due to their applications in chemical synthesis and medicinal chemistry. In recent years, benitrobenrazide and benserazide containing imine moiety, have been synthesized and characterized as promising inhibitors of hexokinase 2 (HK2) an enzyme overexpressed in most cancer cells. Both compounds possess a common structural fragment, a 2,3,4-trihydroxybenzaldehyde moiety connected through hydrazone or hydrazine linker with acylated on N’-nitrogen atom by serine or 4-nitrobenzoic acid fragment. To avoid presence of toxicophoric nitro group in benitrobenrazide molecule we introduced common pharmacophores 4-fluorophenyl or 4-aminophenyl substituents. Modification of benserazide regards an introduction of other endogenous amino acids instead of serine. Herein we report the synthesis of benitrobenrazide and benserazide analogues and preliminary results of inhibitory activity against HK2 evoked by these structural changes. The derivatives contain a fluorine atom or amino group instead of a nitro group in BNB, exhibited the most potent inhibitory effects against HK2 at a concentration of 1 µM, with HK2 inhibition rates of 60% and 54%, respectively.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Primary urethral malignancies are rare in clinical practice and elderly female are prone to suffer. The cause of PUC is unknown and may be related to long-term chronic inflammation, infection, sexual intercourse, pregnancy and irritation of the urethra. Incipient symptom of PUC is not distinctness and can easily lead to misdiagnosis. The final diagnosis relied on transvaginal ultrasound-guided mass biopsy and urethral biopsy. Early tumor treatment is mainly based on surgical resection. For advanced tumors, it is recommended to adopt a comprehensive treatment plan combining surgery, radiotherapy and chemotherapy We report this case with the aim of bringing attention to that primary urethral cancer progresses rapidly and has a poor prognosis, it is urged to call for a need of diagnostic and treatment specification.

Introduction: The coronary flow reserve (CFR) is a sign of early-stage coronary artery disease (CAD). Plasma atherogenic index (PAI) is related to atherosclerosis and cardiovascular mortality. Therefore, our aim was to determine CFR and PAI in patients with primary hyperparathyroidism (PHPT) and investigate whether PAI can be used in the detection of early-stage CAD. Material and Methods: The sample was comprised of 44 patients with PTHT and 33 healthy volunteers. We defined CFR as the ratio of the hyperemic diastolic peak velocity to the baseline diastolic peak velocity. PAI values were calculated with the formula of log 10 triglyceride (TRG) / high-density lipoprotein (HDL). Result: The comparison of the groups for PAI and CFR demonstrated that PAI levels were significantly higher while CFR levels were significantly lower in the PTHT patients (p<0.01, p=0.01, respectively). The correlation analysis revealed that CFR was negatively correlated with PAI and TRG (PAI- p<0.0001 r=-0.537).The multivariate logistic regression analysis showed that only a high PAI level (OR: 151.6, 95% confidence interval (CI): 4.1-5480, p=0.006) was an independent predictor of reduction in CFR in PHPT patients. Conclusion: Overall, we found an independent correlation between PAI and CFR values. Hence, PAI may be useful in identifying PHPT patients facing a high risk of adverse cardiovascular events and may also allow early diagnosis of subclinical atherosclerosis.

In our study we investigated the additive manufacturing (AM) of ceramic-based Functionally Graded Materials (FGM) by the direct AM technology Thermoplastic 3D-Printing (T3DP). Zirconia components with a varying microstructure were additively manufactured by using thermoplastic suspensions with different contents of pore forming agents (PFA) and were co-sintered defect-free. Different materials were investigated concerning their suitability as PFA for the T3DP process. Different zirconia-based suspensions were prepared and used for AM of single- and multi-material test components. All samples were sintered defect-free and in the end we could realize a brick wall-like component consisting of dense (<1% porosity) and porous (approx. 5% porosity) zirconia areas to combine different properties in one component. The T3DP opens the door to AM of further ceramic-based 4D-components like multi-color or multi-material, especially multi-functional components.

Aim: The purpose of this study was to collect prevalence data of Hypomineralized Second Primary Molars (HSPM) and Molar Incisor Hypomineralization (MIH) among pediatric patients treated by dental practitioners in Northern Italy and assess the practitioners’ awareness of these conditions. Methods: A cross-sectional pilot study was conducted using a structured online questionnaire administered through Google Forms. The survey comprised 10 single-choice questions addressing the prevalence of opacities affecting molars and an index of HSPM and MIH in caries-free children aged 6-9 years, categorized by percentage. Results: A total of 315 dentists participated in the survey, yielding a response rate of 31.5%. The majority of respondents (59%) reported HSPM prevalence in 1-25% of their patients, while 18% observed no opacity in any of their patients. MIH was observed in HSPM patients in 1-25% and 25-50% of cases, as reported by 44% and 31% of respondents, respectively. Among non-HSPM patients, MIH was observed in 1-25% of children (reported by 74% of respondents). Conclusion: The findings from this pilot survey show substantial agreement with existing prevalence data on HSPM and MIH reported in the literature. The co-occurrence rate of HSPM and MIH defects supports the hypothesis of HSPM potentially serving as a predictor of MIH. The study underscores a significant need to enhance awareness of these defects for early diagnosis and effective management. Additionally, there is a call for the promotion of standardized diagnostic protocols to obtain more accurate epidemiological data.

(1) Background Diabetic Retinopathy (DR) is the primary cause of poor vision in young adults. Screening for DR is important but many patients do not attend; (2) Methods: We validated an algorithm for predicting DR and its progression by conducting a retrospective study of 11 children in a population of 120,389 T2DM (3) Results: By applying the algorithm to the population showed an AUC of 0.93 (95% CI, 0.92–0.94) for any-DR and 0.90 (95% CI, 0.89–0.91) for referable-DR(4) Conclusions: The algorithm is useful for predicting patients who could develop referable forms of DR and also for any-DR. This would allow a personalized screening plan to be drawn up for each patient.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

This study investigates effective strategies for second language education in primary schools, analyzing the efficacy of immersive and interactive methods, digital literacy tools, and mixed-method approaches. The findings reveal significant improvements in language proficiency and student engagement through these methodologies, with immersive and interactive strategies showing substantial benefits in oral proficiency and engagement, digital tools enhancing accessibility and engagement, and mixed-method approaches yielding the highest overall effectiveness. The study underscores the importance of a balanced, flexible approach to language education, integrating traditional and modern methods to cater to diverse learner needs. These strategies not only advance linguistic skills but also contribute to the broader cognitive and emotional development of young learners, emphasizing the critical role of effective language education in preparing students for a globalized world.

Background: Disorders of immunity are poorly recognised in some rare multisystem genetic con-ditions. We aim to describe syndromic features and immunological defects in children with syn-dromic primary immunodeficiencies (sPIDs). Methods: This is a retrospective descriptive study of children aged 0-18 years with sPIDs under the care of the paediatric immunology service at the Bristol Royal Hospital for Children, United Kingdom from January 2006 to September 2021. Results: sPIDs were identified in 36 patients. Genetic diagnoses which are not commonly associ-ated with PIDs and not included in the International Union of Immunological Societies classifica-tion were present in 7/36 (19%): Trisomy 22, Arboleda-Tham syndrome, 2p16.3 deletion syn-drome, supernumerary ring chromosome 20 syndrome, Myhre syndrome, Noonan syndrome, trichothiodystrophy/Cockayne syndrome complex. Recurrent and/or severe infections were the commonest clinical features (n=33, 92%). Approximately half had combined immunodeficiency or antibody deficiency. Commonest extra-immunological manifestations include dysmorphism (72%), disorders of nervous (78%), musculoskeletal (69%), haematology/lymphatic (58%), and gastrointestinal, hepatic/pancreatic (58%) systems. Conclusions: Patients with sPIDs often have multiorgan involvement and some are non-immunologically mediated. There should be low threshold to clinically assess and investi-gate for disorders of immunity in any patients with syndromic features especially when they pre-sent with recurrent/severe/opportunistic infections, features of immune dysregulation, autoin-flammation or lymphoproliferation.

Background: The main of this study was to realize a systematic review of clinical features and prognosis factors associated to diagnosis and prognosis of primary hyperaldosteronism in cats. Methods: Clinical cases with hyperaldosteronism confirmed with histopathological analysis have been included. Studies without information about clinical confirmation, type of carcinoma or affected system were excluded. A total of nine studies with seventeen patients with primary hyperaldosteronisms were used for this systematic review. Results: All cats included presented hypertension, renal failure (34.48%), ocular problems (27,59%), cardiovascular alterations (24.14%) and nervous system defects (13.79%). High levels of blood pressure and serum levels of aldosterone are related to adenocarcinoma, whereas the potassium levels were lower than cats with adenoma or bilateral hyperplasia. Conclusions: In primary feline hyperaldosteronism, patients with adenocarcinoma show higher levels of aldosterone, higher blood pressure and lower potassium levels than patients with adenoma or nodular hyperplasia. Adrenocortical adenocarcinomas are more frequent in older cats than young, and these patients present several clinical signs, mainly renal failure, and ocular complications. Regardless of aldosterone levels, a favorable prognosis is associated with adrenalectomy.

Monitoring photosynthesis is a great challenge to improve our knowledge of plant productivity at the ecosystem level, which may be achieved using remote-sensing techniques with synoptic abilities. The main objective of the current study is to take up this challenge for microphytobenthos (MPB) primary production in intertidal mudflats. This was achieved by coupling hyperspectral radiometry (reflectance, ρ and second derivative, δδ) and PAM-fluorometry (non-sequential light curve, NSLC) measurements. The later allowed the estimation of the primary production via the light use efficiency (LUE) and the electron transport rate (ETR) whereas ρ allowed to estimate pigment composition and optical absorption cross-section (a*). Five MPB species representative of the main growth forms: epipelic (benthic motile), epipsammic (benthic motile and non motile) and thycoplanktonic (temporarily resuspended in the water column) were lighted at increasing light intensity from dark to 1950 µmol photons.m^-2.s^-1. After spectral measurements, a* was retrieved using a radiative transfer model and several radiometric indices were tested for their capacity to predict LUE and ETR. The spectral estimation of these two photosynthetic variables was subsequently compared to the values estimated by PAM-fluorometry. Results showed that different responses related to the xanthophyll cycle (de-epoxydation state) were observed for the three growth-forms with increasing light levels. However, a single relationship with radiometric index was not affected by species/growth-forms, i.e. δδ_496/508, called the MPB_LUE index to predict LUE and ETR. This index has the potential to be applied to air borne hyperspectral imagery for large-scale assessment of MPB production.

Background: Mosaic cancers are composed of two or several genetically different cell populations. Mosaicism has been considered to be rare among malignancies, with the exception of the germ cell tumours. Although it has been described that neuroendocrine foci might be present within adenocarcinomas of the prostate, this was meant for advanced stage diseases and the clinical relevance of the histological finding has not been clarified. Patients and methods: We recall a single centre cohort of patients with neuroendocrine cancer of the prostate. We show for the first time histological images of a primary mosaic neuroendocrine/adenocarcinoma of the prostate. Results: Contrarily to the general assumption of a rare disease with poor prognosis, the clinical incidence was found to be 2%, being 50 fold higher than the earlier data. During the follow-up the overall survival of some metastatic patients reached several years. The particularity of patients with favourable outcome was the parallel elevation of PSA and NSE. They received anticancer treatments in an alternating way directed according to the tumour marker that was actually in rise. Histological images of primary mosaic prostate cancers are shown. A model explaining the development of mosaic cancers is presented. Conclusion: Mosaic neuroendocrine-/adenocarcinoma of the prostate is underdiagnosed and its prognosis is underestimated.

Today, concepts such as Emotional Education and Emotional Intelligence are recognized by many authors and researchers, emphasizing the importance of their development in all people, but especially in schools, specifically in teachers or educators and children. However, we still find many shortcomings within the schools that are needed to continue working. The aim of this study is to investigate the presence of emotional intelligence and empathy in teachers, through a sample of 42 participants. The research was conducted based on two validated and highly reliable assessment tools, called TMMS-24 and TECA. The results of the TMMS-24 indicate that a large percentage of participants have an adequate score of emotional intelligence. The results of the TECA indicate that most of the participants are in the middle, high or extremely high scores in relation to the level of empathy.

Olfactory ensheathing cells (OECs) are the glial cells that accompany axons from the olfactory epithelium to their targets in the olfactory bulb. They possess unique features that have made them the subject of much study as being potentially useful in cell-based therapeutic approaches to CNS repair. Investigation of OECs has demonstrated antigenic and morphological heterogeneity in their population. No marker specific to and selective for OECs have yet been identified, and many of the markers used are variably expressed by other glial cells. Even among OECs, these markers appear to vary in vivo (depending on their anatomical location, contact with other cells, and developmental timing) and in vitro. The variation across the population of OECs has compromised their isolation and characterization. It has also made the task of identifying meaningful subpopulations - with greater or lesser therapeutic utility - dependent on identifying the source of their variability. Such information would aid in both the harvest and experimental manipulation of OECs to optimize their therapeutic effect. One way to understand the nature of this variability is to seek its potential causes in vivo. This must begin with an examination of the structure of the olfactory nerve. Here, the structure and development of the primary olfactory projection are thoroughly reviewed with an emphasis on OECs and the cells with which they make contact. The relevant experimental results are also discussed. The weight of anatomical evidence indicates that the structural variations described in different locations and across species are mostly the result of spatiotemporal developmental factors. As such, the formation of the olfactory projection is mediated primarily by the source tissue, the olfactory epithelium. Cell-autonomous development is common elsewhere, and suits the evolutionary age and importance of olfaction, as well as its continued regenerative capacity. Our findings provide a more systematic anatomical understanding of this nerve. That understanding indicates that variation in axon ensheathment by OECs is an inherent feature arising from the flexibility of the ensheathing program. This perspective, along with the anatomical data reviewed here, can inform more carefully controlled laboratory investigations designed to uncover the detailed mechanisms governing OEC biology.

The process of international migration causes a situation of vulnerability in people's health and greater difficulty in coping with disease. Furthermore, the adversities suffered during migration can trigger reactive signs of stress and cause anxious, depressive, confusional and somatic symptoms. This article studies the relationships between psychosocial risk, psychological distress and somatization in immigrants from 4 communities: Maghrebis, Sub-Saharans, South Americans and South Asian. A cross-sectional study was carried out with questionnaires on 602 immigrants who were surveyed in the Primary Care Centres of an urban area of Catalonia. The instruments used were the Demographic Psychosocial Inventory (DPSI), the Brief Symptom Inventory (BSI) and the Somatic Symptom Inventory (SSI). The average psychosocial risk obtained was 0.35, with the highest values in the sub-Saharan community. Psychological distress showed a mean value of 0.66, with the sub-Saharan community scoring the lowest in all dimensions except depression. The average somatization values were 1.65, with the sub-Saharan community scoring the least. The female gender is a risk factor for somatization and psychological distress. Perceived psychosocial risk is a predictor of psychological distress, but not somatization, suggesting that the use of more adaptive coping strategies could minimize the effect of the migration process on somatizations.

Due to the difficult metallurgical conditions during production, advanced processing techniques are required to produce functionally graded metal matrix composites. In this study, we explored a novel approach by using a combination of two different methods to produce Functionally Graded 7075 Al / SiCp composites. First process was direct semi-solid stirring that was used to prevent particle agglomeration, brittle reaction products, floating or settling of the reinforcements and poor wettability for the production of SiCp (wt. 5-20%) reinforced aluminum matrix composites. In the direct semi-solid mixing process, the matrix material remains in a semi-solid state until the reinforcement addition process is completed. The second novel process was sequential squeeze casting to provide liquid diffusion between two composite layers that were used to produce functionally graded aluminum matrix composite. The microstructure and interlayer zones were characterized by using optical microscopy and scanning electron microscopy. The resulting functionally graded material was subjected to spectrometer analyses, density measurements, and metallographic examinations in order to determine the characteristics of its layers and interfacial zones, as well as to assess the formation of the graded structure. The results obtained from this research provide the potential to use this new combined manufacturing method, which is relatively inexpensive, efficient and easily applicable, in order to produce functionally graded SiCp reinforced aluminum composites.

Construction and demolition waste (CDW) represents 1/3 of the weight of all-waste produced. Increasing their recycling and reutilization with recycled aggregates (RA) means closing the life cycle of construction materials. Research has been carried out on artificial aggregates from the exclusive crushing of structural concrete waste in selective demolitions (CDWRConc). This study analyses the use of recycled concrete as graded aggregate (GARConc) and in cement soil (CSRConc). The material complies with the requirements as a road base, although due to the low values of resistance to fragmentation these materials are adequate for use in sensitive road systems and other places such as urban roads and car parks. The sensitive road systems are infrastructures in places of great natural wealth and low traffic intensity, with an annual average of heavy vehicle traffic (AADTh) below 50 vhp/d. As soluble salt contents have been detected, additional waterproofing or drainage measures must be adopted to prevent water infiltration into the layers made up of CDWRHorm. Finally, the high initial values of UCS allow the temporary passage of light vehicles over CSRConc after 3 days.

Research is scarce regarding antimicrobial use and antimicrobial resistance (AMR) for specific localities in Northern Ireland (NI). Additionally, the effects of COVID-19 on antimicrobial pre-scribing patterns and AMR are unknown. Between the European Union (EU) and United States (US), AMR causes approximately 68,000 deaths annually. This study will provide a better understanding of antimicrobial use and prescribing patterns in Belfast and link with AMR. An electronic survey was developed and distributed to eighty-five community pharmacists in Belfast. Yearly and monthly prescription data was gathered from the Business Services Organisation and COVID-19 statistics from Gov.uk. All data was analysed on Microsoft Office Excel® and IBM® SPSS® Statistics 25. Overall response rate was 46%. Most pharmacists (82%) failed to address prescriber non-compliance with guidelines and antimicrobial dosing errors (59%). The most common in-dication for antibiotics was upper respiratory tract infections (URTIs). Overprescribing of anti-biotics was perceived as the leading cause of AMR, therefore 69% of pharmacists indicated in-creased General Practitioner (GP) compliance with guidelines would reduce AMR. Pharmacists’ are in an ideal position to reduce AMR through patient education however, it is demonstrated that pharmacists failed to adequately counsel patients on antibiotic use. All GP practices demonstrated inappropriate antibiotic use, especially for URTIs which suggests antibiotic appropriateness should be reviewed. Many patients avoided contact with GP’s during COVID-19 which may have resulted in reduced antibiotic use. This research established amoxicillin as the most commonly prescribed antibiotic, which is contributing to increased AMR with its broad-spectrum activity and has recognised a decrease in antibiotic prescribing during COVID-19. Based on the results found and a critical review of the literature it is recommended antimicrobial guidelines should be re-viewed and improved, enhanced training should be provided to pharmacists and the antibiotic guardian (AG) campaign should be reenergised.

Although there is a common physiological notion that the origin of the membrane potential is attributed to transmembrane ion transport, it is theoretically possible to explain its generation by the mechanism of ion adsorption. It was previously suggested that the ion adsorption mechanism led even to the potential formulas which are even identical to either the famous Nernst equation or Goldman-Hodgkin-Katz equation. Our further analysis shown in this paper indicates that the potential formula based on the ion adsorption mechanism leads to one equation which is the function of material surface charge density and the material surface potential. Furthermore, we confirmed that the equation holds in all the different experimental systems we studied. Although we have not succeeded in elucidating why such an equation is established, the equation appears to be the key equation governing the characteristics of the membrane potential regardless of the systems in question.

The primary cilium plays a pivotal role during embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as sonic hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to severe developmental disorders called ciliopathies. Beyond its obvious role in early morphogenesis, growing evidence points towards an essential function of the primary cilium in neural circuit formation in the central nervous system. However, very little is known about a potential role in the formation of the peripheral nervous system. Here, we investigated the presence of the primary cilium in neural crest cells and their derivatives in the trunk of the developing chicken embryo in vivo. We found that neural crest cells, sensory neurons, and boundary cap cells all bear a primary cilium during key stages of early peripheral nervous system formation. Moreover, we described differences in the ciliation of neuronal cultures of different populations from the peripheral and central nervous system. Our results offer a framework for further in vivo and in vitro investigations on specific roles that the primary cilium might play during peripheral nervous system formation.

Background: New controversies have raised on brain death (BD) diagnosis when lesions are localized in the posterior fossa. Objective: To discuss the particularities of diagnosis BD in patients with posterior fossa lesions. Material and Methods. The author made a systematic review of literature on this topic. Results and Conclusions: A supratentorial brain lesion usually produces a rostrocaudal transtentorial brain herniation, resulting in forebrain and brainstem loss of function. In secondary brain lesions [i.e., cerebral hypoxia], the brainstem is also affected like the forebrain. Nevertheless, some cases complaining posterior fossa lesions [i.e., basilar artery thrombotic infarcts, or hemorrhages of the brainstem and/or cerebellum] may retain intracranial blood flow and EEG activity. In this article I discuss that if a posterior fossa lesion does not produce an enormous increment of intracranial pressure, a complete intracranial circulatory arrest does not occur, explaining the preservation of EEG activity, evoked potentials, and autonomic function. I also address Jahi McMath, who was declared braindead, but ancillary tests, performed 9 months after initial brain insult, showed conservation of intracranial structures, EEG activity, and autonomic reactivity to “Mother Talks” stimulus, rejecting the diagnosis of BD. Jahi McMath’s MRI study demonstrated a huge lesion in the pons. Some authors have argued that in patients with primary brainstem lesions it might be possible to find a in some cases partial recover of consciousness, even fulfilling clinical BD criteria. This was the case in Jahi McMath.

The approach to the personal experience and previous ideas about Physical Education of future Primary Education teachers is a starting point of great interest for the teaching of the subject of Didactics of Physical Education. The study aims to investigate these prior beliefs and to verify to what extent this initial perception changes after taking the course on “Didactics of Physical Education”. A concurrent mixed-methods study was conducted, which included two data collection procedures: (1) a pre-experimental design with a single group featuring pre-test and post-test; (2) the analysis of students' autobiographical accounts of their school experience with physical education. The participants were students enrolled in the Bachelor’s degree program in Primary Education at the University of Santiago de Compostela (USC) who undertook the course last year. The results obtained reveal that after taking the subject of Didactics of Physical Education, students give greater value to more positive concepts of learning, socializing, participating, and playing, among others. Similarly, in the post-test, the assessment of concepts such as competitiveness and physical fatigue diminished. In their autobiographical memories, students associate good memories with relationships with classmates and the playful and socializing nature of the subject; and among the bad memories, they highlight the content related to physical performance, competitiveness, and lack of attention to the diversity of students and their individual characteristics.

Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, recur-rence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with ominous prognosis and chemotherapy resistance, but the role of DNMTs in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and DNMT2 lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage II to Stage IV carcinomas. Proteomic data also suggested that DNMT1 and DNMT3A levels were increased in tumors. Similarly, DNMT1, DNMT3A and DNMT3L protein levels were overex-pressed and DNMT2 expression was reduced in high grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. DNMT3A, DNMT1 and DNMT3B mRNA lev-els were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights a presumptive tumor-suppressor activity of this gene in ovarian car-cinoma.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

Microbial-based biostimulants containing arbuscular mycorrhizal fungi (AMF), Trichoderma fungi and plant growth-promoting rhizobacteria (PGPR) have been applied in an open-field tomato cultivation. A two-years field experiment (2020-2021) was performed in Southern Italy on “Heinz 1534” processing tomato hybrid, using three commercial formulations characterized by different microbial consortia (MIC: Glomus spp., Rhizophagus spp., Bacillus spp., Streptomyces spp., Pichia spp., Trichoderma spp.; EKO: Glomus spp., Bacillus spp., Streptomyces spp., Pseudomonas spp., Arthrobotrys spp., Monacrosporium spp., Paecilomyces spp., Myrothecium spp., Trichoderma spp.; FID: Glomus spp., Bacillus spp., Trichoderma spp.) and comparing them to untreated control (CTRL). The effect of growing season and microorganism-based treatments on yield, technological traits and functional quality of tomato fruits was assessed. The year of cultivation (Y) affected yield (with lower fruit weight, higher marketable to total yield ratio and higher % of total defected fruits in 2020), and technological components (higher dry matter, total acidity, total soluble solids in 2020). During the first year of the trial, all evaluated treatments (MIC, EKO and FID) enhanced soluble solids content by 10%, on average, compared to CTRL. Sucrose and lycopene contents were influenced both by the microbial-based treatments and the growing season (greater values found in 2021 with respect to the first year). Y factor also significantly affected all evaluated metabolites contents, except for tyrosine, essential (EAA) and branched-chain (BCAAs) amino acids. Over two years of field trial, FID biostimulant enhanced the contents of proteins (+53.71%), alanine (+16.55%), aspartic acid (+31.13%), γ-aminobutyric acid (+76.51%), glutamine (+55.17%), glycine (+28.13%), monoethano-lamine (+19.57%), total amino acids (+33.55), essential amino acids (+32.56%) and branched-chain amino acids (+45.10%) compared to the untreated control. Our findings highlighted the valuable effect of FID microbial inoculant in boosting several primary metabolites (proteins and amino acids) in the fruits of processing tomato crop grown under Southern Italy environmental condi-tions, although no effect on yield and its components was appreciated.

The RHAPS project was launched in 2019 with the major objective to identify specific properties of the fine atmospheric aerosol from combustion sources that are responsible for toxicological effects and can be used as new metrics for health-related outdoor pollution studies. In this paper, we present the overall methodology of RHAPS, and introduce the phenomenology and the first data observed. A comprehensive physico-chemical aerosol characterization has been achieved by means of high-time resolution measurements (e.g. number size distributions, refractory chemical components, elemental composition,) and low-time resolution analyses (e.g. oxidative potential, toxicological assays, chemical composition,…). Preliminary results show a high complexity in the relations observed, the link between air quality and toxicological endpoints being not obvious. We explore data from different points of view: source apportionment of PM1 and the role of source emissions on aerosol toxicity, the oxidative potential as a predictive variable for PM1 toxicity with focus on the secondary organic aerosol possessing redox-active capacity, exposure-response relationships for PM1, and air quality models to forecast PM1 toxicity. We provide a synthesis of results with the outlook to companion papers where data are analyzed in more detail.

Primary energy consumption is one of the key drivers of global CO₂ emissions that, in turn, heavily depend on the efficiency of involved technologies. Either the improvement in technology efficiency or the expansion of non-fossil fuel consumption require large investments. The planning and financing of such investments, by policy makers or global energy firms, require, in turn, reliable measures of associated global spreads and their evolution in time. In this paper, our main contribution is the introduction of index measures for accessing global spreads (that is, measures of inequality or inhomogeneity in the statistical distribution of a related quantity of interest) of technology efficiency and CO₂ emission in primary energy consumption. These indexes are based on the Gini index, as used in economical sciences, and generalised entropy measures. Regarding primary energy sources, we consider petroleum, coal, natural gas and non-fossil fuels. Between our findings, we attest some stable relations in the evolution of global spreads of technology efficiency and CO₂ emission, and a positive relation between changes in global spreads of technology efficiency and use of non-fossil fuel.

The species and bio-availability of phosphorus (P) in primary, secondary and digested sludge were fractionated and further analyzed in this study. Results showed that inorganic P (IP) was the primary P fraction in the secondary sludge and digested sludge, in which non-apatite IP (NAIP) amounted to 91.6% and 69.3% of IP, respectively. Organic P (OP), accounting for about 71.7% of total P (TP), was the dominant P composition in primary sludge. The content of bio-available P was about 9.7, 43.4, 29.8 mg-P/g-TS in primary sludge, secondary sludge and digested sludge, respectively, suggesting secondary sludge is the optimal choice when land application of sewage sludge is taken into consideration, followed by digested sludge and primary sludge. Polyphosphate and orthophosphate, comprising approximately 54.3% and 89.2% of TP, was the dominant P species in the secondary sludge and digested sludge, respectively. Monoester-P (54.6% of TP in extract) and diester- P (24.1%) were identified as OP species in primary sludge by Phosphorus-31 nuclear magnetic resonance (31PNMR). The present results would be helpful for P recovery and recycle from sewage sludge in wastewater treatment plant.

Cerebral cavernous malformations (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene (CCM1/Krit1, CCM2, CCM3) and its origin (spontaneous or familial), different types of this dis-ease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression pro-file of these cells were analyzed and compared to primary ECs from a healthy donor. The muta-tion of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased ex-pression of genes involved in intercellular junction formation, angiogenesis, and vascular ho-meostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and someway predisposed to vascular damage.

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

Introduction: A dual malignancy with both Ewing Sarcoma and Prostate Adenocarcinoma has not been reported in the English literature. We report a case of simultaneous diagnosis of Ewing sarcoma and prostate adenocarcinoma with profound clinical manifestation. Case presentation: A 53-year-old male with advanced metastatic prostate cancer (Gleason-9) admitted with classical presentation of cauda equina syndrome including incontinence, back pain, and paresis following bilateral nephrostomy insertion for the treatment of bilateral renal hy-dronephrosis. The patient was diagnosed with an epidural abscess at the level of L5-S1 and an emergency surgical spine decompression was performed. No abscess was found, and pathology results showed a concomitant primary Ewing sarcoma in the spine. Conclusions: Very rare occurrences of a dual primary malignancy, in this case, Ewing sarcoma and prostate adenocarcinoma, should be kept in mind in patients suffering from complex clinical course of malignancies.

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.

The aim of the present work was to map Estonian primary school students' ratings of symptoms of digital addiction and to identify both class and gender differences. The sample consisted of 5493 primary school pupils from 46 schools in Estonia participating in the 2022 Student Survey conducted by the Tallinn University Centre for Educational Innovation (CIE). The results showed that the digital addiction symptoms scores were highest in 8th and 9th grades. Girls and those who did not disclose their gender, scored higher than boys on digital addiction symptom statements. Symptoms of digital addiction were moderately positively related to screen time during school days and weekends and to school burnout and weakly negatively related to feeling refreshed in the morning.

Ovarian cancer affects thousands of women every year and represents the female cancer with the highest mortality rate. Surgery is currently the cornerstone of the treatment of this disease and several methods have been analyzed and developed to predict the possibility of obtaining a residual tumor of 0 (RT=0). The aim of this review is to analyze the data available in the literature about minimally invasive surgical methods to predict the optimal cytoreduction of patients with advanced epithelial ovarian cancer undergoing primary debulking surgery (PDS). A review of the literature has been performed on the available data about the criteria of cytoreducibility during PDS for the surgical treatment of advanced epithelial ovarian cancer. The assessment of the extent of intra and extrabdominal pathology is essential to guide the surgeon in the most appropriate therapeutic choice for patients with ovarian cancer, so radiological methods (MRI, PET-scan and CT), surgical (mini-laparotomy, laparoscopy) and serological (CA-125, HE4) can provide a huge help for tailoring the therapeutic approach of these patients.

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to an increased destruction and a reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document which had been launched in 2011. The updated guidelines have been the reference for diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have properly updated the main recommendations. Our aim is to provide a practical tool to enable the integral management of all the aspects concerning primary ITP management.

Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in Primary Sjogren’s syndrome (pSS). The aim of this research was to assess the imbalance of subsets within CD8+ cells in peripheral blood. We examined blood samples from 34 patients with pSS and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA, and CD45. For immunophenotyping of ‘polarized’ CD8+ T cell subsets we used the following monoclonal antibodies:CXCR5, CCR6,CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, Rheumatoid factor, the Schirmer test, and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.

It is proposed that the primary living cells (“probionts”) cannot emerge of organic substance simply by continuous chemical complication of prebiotic macromolecules and microsystems. The complication must be accompanied by the radical thermodynamic transformation (“jump”) of prebiotic microsystems that resulted in the acquired ability to extract free energy from the environment and export entropy. This transformation is called “the thermodynamic inversion” The inversion may occur by means of the efficient (intensified) response of the microsystems on the oscillations of physic-chemical parameters in hydrothermal environment. In this case the surplus available free energy within a microsystem, when combined with the informational modality, facilitates its conversion into a new microsystem—a living probiont. It is shown the schematic representation of an oscillating prebiotic microsystem that is transforming into a living probiont. A new kind of laboratory and computational experiments on prebiotic chemistry under oscillating conditions is offered to verify the inversion concept.

The current clinical model for genetic-testing is based on clinical-criteria/family-history(FH) and a pre-defined mutation probability threshold. It requires people to develop cancer before identifying unaffected individuals in the family to target prevention. This process is inefficient, resource intense and misses >50% of individuals/mutation carriers at risk. Population genetic-testing can overcome these limitations. It is technically feasible to test populations on a large scale; genetic-testing costs are falling and the acceptability/awareness is rising. MEDLINE/EMBASE/Pubmed/CINAHL/PsychINFO databases were searched using a free-text and MeSH terms; reference lists of publications retrieved screened; additionally web-based platforms, Google, and clinical-trial registries were searched. Quality of studies were evaluated using appropriate check-lists. A number of studies have evaluated population-based BRCA-testing in the Jewish-population. This has been found to be acceptable, feasible, clinically-effective, safe, associated with high satisfaction rates and extremely cost-effective. Data support change in guidelines to population-based BRCA-testing in the Jewish-population. Population panel-testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 gene mutations is the most cost-effective genetic-testing strategy in general-population women and can prevent thousands more breast/ovarian cancers than current clinical-criteria based approaches. A few ongoing studies are evaluating population-based genetic-testing for multiple cancer susceptibility genes in the general-population but more implementation studies are needed. A future population-testing programme could also target other chronic diseases.

In order to meet the Millennium Development Goals set forth by the United Nations’ Millennium Summit that took place in 2000, in New York, particularly in the area of education, the Mozambican Government decided that, from 2003 onwards, during their primary school formation, students should be passed automatically even if they do not have enough intellectual capacities that justify their progress. In fact, this decision was made during a period when there were many pupils being failed, due to various reasons. After more than 15 years of its implementation, this paper aims to analyzing the results acquired from this decision, from the point of view of the quality of education. This will be done taking into account the prevailing situation of education in Mozambique. Having considered these aspects, the paper will move on to presenting some of the challenges and opportunities that the country should consider in the area of education, as a way to bring about better outcomes and promote development, in the country.

The Lagrangian and Eulerian structure and dynamics of a strong wind event in the Tokar Gap region are described using a WRF model hindcast for 2008. Winds in the Tokar Gap reach 25 m s-1 and remain coherent as a jet far out over the Red Sea, whereas equally strong wind jets occurring in neighboring gaps are attenuated abruptly by a jump-like hydraulic transition that occur just offshore of the Sudan coast. The transition is made possible by the supercritical nature of the jets, which are fed by air that spills down from passes at relatively high elevation. By contrast, the spilling flow in the ravine-like Tokar Gap does not become substantially supercritical and therefore does not undergo a jump, and also carries more total horizontal momentum. The Tokar Wind Jet carries some air parcels across the Red Sea and into Saudi Arabia, whereas air parcel trajectories in the neighboring jets ascend as they cross through the jumps, then veer sharply to the southeast and do not cross the Red Sea. The mountain parameter Nh/U is estimated to lie in the rage 1.0-4.0 for the general region, a result roughly consistent with a primary gap jet having a long extension, and supercritical jets spilling down from higher elevation passes. The strong event is marked by the formation of a cyclonic cell near the upstream entrance to the Tokar Gap, a feature absent from the more moderate events that occur throughout the summer. The cell contains descending air parcels that are fed into the primary and secondary jets. An analysis of the Bernoulli function along air parcel trajectories reveals an approximate balance between the loss of potential energy and gain of internal energy and pressure, with surprisingly little contribution from kinetic energy, along the path of the descending flow. All jets attain the critical wind speed nominally required to loft dust into the atmosphere, though only the Tokar Gap has a broad, delta region with plentiful deposits of silt.

Neutrophil elastase (NE) is taken up by macrophages, retains intracellular protease activity and induces a pro-inflammatory phenotype. However, the mechanism of NE-induced pro-inflammatory polarization of macrophages is not well understood. We hypothesized that intracellular NE degrades histone deacetylases (HDAC) and Sirtuins, disrupting the balance of lysine acetylation and deacetylation, and resulting in nuclear to cytoplasmic translocation of a major alarmin, High Mobility Group Box 1 (HMGB1), a pro-inflammatory response in macrophages. Human blood monocytes were obtained from healthy donors, or from subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Monocytes were differentiated into blood monocyte derived macrophages (BMDM) in vitro. Human BMDM were exposed to NE or control vehicle and the abundance of HDACs and Sirtuins was determined by western blotting of total cell lysates or nuclear extracts, or determined by ELISA. HDAC, Sirtuin, and Histone acetyltransferase (HAT) activities were measured. NE degraded most HDACs and Sirtuin (Sirt)1, resulting in decreased HDAC and sirtuin activities, with minimal change in HAT activity. We then evaluated whether the NE-induced loss of Sirt activity or loss of HDAC activities would alter the cellular localization of HMGB1. NE-treatment or treatment with Trichostatin A (TSA), a global HDAC inhibitor, both increased HMGB1 translocation from the nucleus to the cytoplasm, consistent with HMGB1 activation. NE significantly degraded Class I and II HDAC family members and Sirt 1 which shifted BMDM to a pro-inflammatory phenotype.

The aim of this study was to assess the differences in motor coordination (MC) of primary school students based on sex, age, and physical activity participation (PAP), as well as investigation the binary and triple interactions of these variables on MC. In addition, ıt is aim to determine the validation and reliability of the KTK3+ test for Turkish schoolchildren aged 6-9. The sample consisted of 848 students from public primary schools, aged between 6-9 years, including 412 boys and 436 girls. Anthropometric characteristics such as height and body weight were meas-ured, and Body Mass Index (BMI) was calculated. The Körperkoordinationstest für Kinder (KTK3+) test battery was utilized to evaluate the levels of MC of the students. One-way multi-variate analysis of variance (MANOVA) was used to determine the binary and triple interactions of sex, age and PAP variables on the MC parameters of the participants. The study revealed that boys had higher scores than girls on eye-hand coordination (EHC) (p < 0.05). No significant dif-ference was found balancing backwards (BB), jumping sideways (JS) and moving sideways (MS) (p > 0.05). When the subtests of the KTK3+ were compared by age levels, a significant difference was determined between the groups in all subtests (p < 0.05). With respect to PAP, students who PAP had a significant advantage in all subtests of the KTK3+ (p < 0.05). It was determined that none of the interaction terms between sex, age, and PAP created a significant difference in any KTK (p= 0.294; 0.680; 0.471; 0.970, p > 0.05, respectively). The results that the boys aged 6-9 per-formed better than girls in EHC, but girls Furthermore, an increase in age level and PAP result-ed in higher scores in all subtests. This study presents evidence supporting sex differences in the motor skills of children within this age range and highlights the potential impact of age and physical activity on motor development.