Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the EU for pwCF with non-phe508del mutations is lacking, with limited data on treatment response in this subgroup. Methods: This retrospective study analyzed data from six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy. Evaluations were conducted at 0, 3, 6, 9, and 12 months, assessing lung function (FEV1), sweat chloride levels, BMI, quality of life (CFQ-R), medication satisfaction (TSQM), ENT symptoms (SNOT-22), and physical performance. A control group of four pwCF with classic symptoms and no ETI treatment was included. Results: FEV1 improved significantly after 3 and 6 months (p<0.05) and stabilized by 12 months. Sweat chloride levels decreased significantly, with four pwCF achieving levels below 60 mmol/l. Improvements in ENT and respiratory symptoms, medication satisfaction, and increased BMI were noted. Conclusion: ETI demonstrates high efficacy in selected non-phe508del mutations, offering an effective treatment option that warrants further monitoring and evaluation.

This paper presents a novel approach to decoding the Indus script, which was used by the Indus Valley Civilization (IVC) from approximately 3300 to 1900 BCE. The main focus of this research is the structural analysis of the signs within the Indus script. The central objective of the paper is to determine whether the Indus script can be classified as an alphabet, and it aims to provide compelling evidence regarding the number of primary signs. This includes establishing the actual count of Indus signs through the decomposition of compound signs, identifying diacritics and analyzing their consistent usage, as well as exploring the underlying concepts and implications associated with sign extraction. To comprehensively examine the Indus script, the paper analyzes over 400 signs, encompassing the entire script rather than a select subset of signs or texts. The visual decomposition of the signs employs a simple grid methodology. By summarizing the logical findings, the paper successfully identifies the primary signs and develops an understanding of their phonetic representation within the alphabet. The study recognizes the diverse writing styles used to combine the basic signs, The writing style of the Indus script incorporates variations in formation, composition, and combination, resulting in a significant number of signs. The research findings indicate that the Indus Script primarily consists of only 40 core signs.

This study evaluates the effectiveness of Darknet53 and VGG16 pretrained models to develop a hybrid ensemble model named HybridPlantNet23 deep learning model for effective plant disease classification, using the publicly available dataset ‘A Dataset of Leaf Images’ from Mendeley webpage. The preprocessing of the dataset involved resizing the images to the respective requirements of the pretrained models to develop a combined datastore which served as the input. All experiments were conducted using MATLAB R2023b deep network designer interface. Model performances were evaluated based on the conventional accuracy, precision, recall, and F1-score. VGG16 achieved the highest accuracy (97.25%), precision (96.30%), recall (96.96%), and F1-score (96.55%), outperforming both Darknet53 and the ensemble HybridPlantNet23 model. Despite the advanced architecture of the ensemble model, its performance (accuracy: 95.37%, precision: 93.56%, recall: 94.20%, F1-score: 93.74%) was not significantly superior, thus highlighting scientific reasons behind this development. Recommendations for future works were provided accordingly.

Objective: To evaluate audiological outcomes, quality of life, and complications in patients implanted with Active middle ear implants (AMEI). The secondary objective is to investigate the required duration after implantation to reach satisfactory outcomes. Methods: This retrospective study included 31 patients implanted with Active middle ear implants (AMEI) with different methods of floating mass transducer attachment. Patients with incomplete medical records and those who did not respond to postoperative follow-up were excluded. Patients were assessed preoperatively, and at one, three, and six months postoperatively. The assessment included Pure Tone Average (PTA4), Speech Reception Threshold (SRT) and Speech Discrimination Score (SDS). The Speech Spatial and Qualities of Hearing scale (SSQ12) was also used to evaluate levels of satisfaction. Result: There are no significant differences found in PTA and SRT between the 3-, 6-, and 12-month visits. The speech reception threshold (SRT) showed a statistically significant improvement at 3, 6, and 12 months post-operative measures compared to pre-operative. Additionally, the SDS exhibited a significant increase only after 12 months, compared to the 3-month time point. However, satisfaction levels did not significantly differ between the 6-month and 12-month measurements following surgery. Conclusion: Vibrant Sound bridge improves subjective satisfaction scores and audiological test scores in patients with different types of hearing loss. AMEI has a low risk of medical or surgical complications, the ease of using a hearing implant, and the social benefits of good hearing and communication.

During the COVID-19 pandemic, individuals with symptoms other than cough or fever have refrained from seeking medical advice. However, a delay in treatment might lead to serious consequences. At the same time, digital health initiatives have emerged to overcome this bottleneck of healthcare. Herein, we report the results of a multi-center initiative using a combination of patient history and artificial intelligence (AI) to identify individuals with rare neuromuscular diseases. First, a questionnaire with 46 items was developed by interviewing patients with muscular dystrophies, amyotrophic lateral sclerosis, Morbus Pompe, neuropathies, and myasthenia gravis. Second, patients with proven neurological diseases answered the questionnaire. Third, a combination of classifiers (artificial neural network, support vector, and random forest) was trained and, finally, the system was challenged with new questionnaires. Users with an abnormal questionnaire pattern received a unique code for data privacy and contact details for a neurologist for further advice. The neurologists confirmed or refuted the AI-based diagnosis. The questionnaire was accessed 3122 times, leading to 853 unique codes. Only for a few patients the computer-based diagnoses and the confirmed final diagnoses were reported to us. However, for these few patients, the genetic testing and high CK levels finally ended their long-lasting diagnostic odyssey.

The specifics of a shock wave propagation down a positive column of a dc discharge in molecular chemically inert gases has been investigated. It was shown that axial gradients caused by the imbalance in the charged particle momentum transfer to the gas molecules can be a reason for the shock velocity dependence on the electric field direction. In the pure nitrogen gas, the calculated shock velocity difference up to 13.5% is in good agreement with 12% value obtained in the experiment. A returning gas flow organizing in the discharge as a possible mechanism for an extended shock structure, and a number of kinetical factors capable of affecting the shock motion are discussed.

Some time ago, Kobayashi et al. experimentally studied the so-called Lee-Naughton-Lebed's (LNL) angular effect in strong electric fields [K. Kobayashi, M. Saito, E. Omichi, and T. Osada, Phys. Rev. Lett. \textbf{96}, 126601 (2006)]. They found that strong electric fields split the LNL conductivity maxima in $\alpha$-(ET)$_2$-based organic conductor and hypothetically introduced the corresponding equation for conductivity. In this Letter, for the first time we suggest quantum mechanical theory of the LNL angular oscillations in moderately strong electric fields. In particular, we demonstrate that the obtained by us approximate theoretical formula coincides with the hypothetical one and well describes the above mentioned experiments.

Weight thresholding (WT) is a method intended to decrease the number of links within weighted networks that may otherwise be excessively dense for network science applications. WT aims to remove links to simplify the networks by holding most of the features of the original network. Here, we test the robustness and the efficacy of the node attack strategies on real-world networks subjected to WT that remove links of higher weight (strong links). We measure the network robustness along node removal with the largest connected component (LCC). We find that the real-world networks under study are generally stable in terms of robustness when subjected to WT. Nonetheless, WT by strong link removal changes the efficacy of the attack strategies and the rank of node centralities. Also, WT by strong link removal may trigger a greater change in node centrality rank than WT by removing weak links. Network science research finding important/influential nodes in the network has to consider that simplifying the network with WT methodologies may change the node centrality.

We show that the compound samarium hexaboride is a strong topological insulator using the eigenvalues of the space inversion operator in the low-energy limit of the periodic Anderson model. Additionally, we assume the presence of the ferromagnetic exchange interaction (M). A Dirac cone like feature in the surface state energy spectra is observed for M equals zero in a certain parameter range. For M not equal to zero, there is no Kramers degeneracy. We have been able to show that this phase corresponds to the quantum anomalous Hall state by calculating Berry curvature and the Chern number. Using Floquet theory, we further show that the access to a novel state with broken time reversal symmetry is possible due to the normal incidence of circularly polarized optical field on the surface of the compound despite M being absent.

Chan and colleagues in their paper titled “Human origins in a southern African palaeo-wetland and first migrations” (https://www.nature.com/articles/s41586-019-1714-1) report 198 novel whole mitochondrial DNA (mtDNA) sequences and infer that ‘anatomically modern humans’ originated in the Makgadikgadi–Okavango palaeo-wetland of southern Africa around 200 thousand years ago. This claim relies on weakly informative data. In addition to flawed logic and questionable assumptions, the authors surprisingly disregard recent evidence and debate on human origins in Africa. As a result, the emphatic and high profile conclusions of the paper are unjustified.

Current study aims to evaluate the possibilities to increase part strength by optimizing the FFF process parameters. Five different CAD models of parts with same coupling dimensions but different shape inherited from a recent study were converted into test samples with Ultimaker 2 3D printer. The main measure of success was the sample strength, defined as the load at which the first crack in the stressed area of the part appeared. Three different modifications to the FFF process with verified positive effect on interlayer bonding were applied. First modification included raising the extrusion temperature and disabling printed part cooling. Second modification consisted in reduction of the layer thickness. Third modification combined the effects of the first and the second ones. For four out of five shapes tested applied process modifications resulted in significant strengthening of the part. The shape that exhibited the best results was subject to further research by creating special printing mode. The mode included fine-tuning of three technological parameters on different stages of the part fabrication. As result it was possible to increase the part strength by 108% only by tuning printing parameters of the best shape designed with increasing its weight by 8%.

Abstract The emergence of mRNA vaccines represents a significant advancement in public health by conferring protection against a variety of infectious diseases. However, concerns regarding the potential risk of inducing or exacerbating autoimmune disorders, particularly connective tissue diseases (CTDs), have arisen. This paper explores the mechanisms by which mRNA vaccines may lead to the onset or worsening of CTDs, focusing on the immune responses induced by Pathogen-Associated Molecular Patterns (PAMPs), the interactions between Toll-like receptors 7/8 and 9 (TLR7/8 and TLR9), and the activation of self-reactive B cells. Furthermore, guidelines are suggested for administering vaccines to individuals at elevated risk, such as those with a positive antinuclear antibody (ANA) test or specific rheumatic disease genes. Our findings underscore the necessity for targeted vaccination strategies that mitigate risks while maintaining public health efficacy.

With the term neuroinflammation has defined the typical inflammatory response of the brain closely related to the onset of many neurological diseases. Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Currently, some progress has been achieved through many efforts and research. Consequently, new cellular and molecular mecha-nisms, diverse from conventional ones, are emerging. In listing some of those that will be the sub-ject of our description and discussion, essential are the important role of peripheral and infiltrated monocytes and clonotypic cells, alterations in gut/brain axis, dysregulation of the apelinergic sys-tem, as well as changes in the endothelial glycocalyx of blood-brain barrier, variation in expres-sion of some genes and levels of the encoding molecules by microRNAs (miRNAs), or other epige-netic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences and modifications in the circadian cycle. Such mentioned mechanisms can add significant pieces in understanding the complex etiological puzzle of neuroinflammation. In addi-tion, they could represent biomarkers and targets of neurodegenerative diseases, in increase in our old populations.

The stability of the gut barrier is very important for keeping the gut healthy and stopping dangerous substances from getting into the bloodstream. Several diseases, including cancer, have been linked to the gut barrier being broken. Live bacteria called probiotics that are good for the host have been shown to have the ability to improve the gut barrier and lower the risk of cancer in the gastrointestinal system. This review looks at how probiotics affect the health of the gut barrier and what that might mean for preventing cancer. Researchers have found that probiotics strengthen the connections between intestine cells, encourage the production of protective mucins, and change the make-up and balance of the gut bacteria. These processes help keep the gut barrier strong and stop harmful chemicals from getting into the bloodstream. Probiotics may help lower the chance of cancer by reducing inflammation throughout the body and protecting the GI tract from harmful substances. But more study is needed to fully understand the benefits of different probiotic strains, the best amounts to take, and how they affect the health of the gut barrier. Understanding how probiotics, the health of the gut barrier, and the risk of cancer all work together can help us come up with new ways to avoid and treat cancer.

General derivation of the well-known Ren-Otsuka relation, 1/α (dTo)/dx=-α/β (where To, x, α and β(>0) are the transformation temperature, the composition, as well as the composition and temperature coefficient of the critical shear constant, c’, respectively) for shape memory alloys, SMAs, is provided based on the similarity of interatomic potentials in the framework of dimensional analysis. A new dimensionless variable, to(x)=(To (x))/(Tm (x) ), describing the phonon softening (where Tm is the melting point) is introduced. The dimensionless values of the heat of transformation, H, and entropy, S as well as the elastic constants c’, c44, A=c44/c' are universal functions of to(x) and have the same constant values at to(0) within sub-classes of host SMAs having the same type of crystal symmetry change during martensitic transformation. The ratio of (dto)/dx and α has the same constant value for all members of a given sub-class and relative increase of c’ with increasing composition should be compensated by the same decrease of to. In the generalized Ren-Otsuka relation the anisotropy factor, A appears instead of c’ and α as well as β are the differences of the corresponding coefficients for the c44 and c’ elastic constants. The obtained linear relation between h and to rationalizes the observed empirical linear relations between the heat of transformation measured by DSC (QAM) and the martensite start temperature, Ms.

The geometry of mesoscopic inhomogeneities plays an important role in determining the macroscopic propagation behaviors of elastic waves in a heterogeneous medium. Non-equiaxed inhomogeneities can lead to anisotropic wave velocity and attenuation. Developing an accurate scattering theory to describe the quantitative relation between the microstructure features and wave propagation parameters is of fundamental importance for seismology and ultrasonic nondestructive characterization. This work presents a multiple scattering theory for strongly scattering elastic media with general tri-axial heterogeneities. A closed analytical expression of the shape-dependent singularity of the anisotropic Green’s tensor for the homogeneous reference medium is derived by introducing a proper non-orthogonal ellipsoidal coordinate. Renormalized Dyson’s equation for the coherent wave field is then derived with the help of Feynman’s diagram technique and the first-order-smoothing approximation. The exact dispersion curves and the inverse Q-factors of coherent waves in several representative medium models for the heterogeneous lithosphere are calculated numerically. Numerical results for small-scale heterogeneities with the aspect ratio varying from 1 to 7 show satisfactory agreement with those obtained from real earthquakes. The results for velocity dispersion give rise to a novel explanation to the formation mechanism of different seismic phases. The new model has potential applications in seismology and ultrasonic microstructure characterization.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally, posing significant challenges to public health. The rapid development of artificial intelligence, particularly Large Language Models like ChatGPT, has revolutionized various fields, including cardiovascular medicine. ChatGPT, recognized for its broad applicability, efficiency, and public acceptance, has been integrated into multiple facets of CVD management. This comprehensive review examines the current applications of ChatGPT in cardiovascular medicine, emphasizing its innovative and significant role in enhancing diagnosis and clinical decision-making, improving medical education, and facilitating research and academic communication. Furthermore, the review article addresses the significant challenges associated with ChatGPT and proposes directions for future development to overcome these obstacles and boost its effectiveness. By exploring the vast potential of ChatGPT to meet the needs of the large CVD patient population and the extensive community of cardiovascular professionals, this review aims to provide valuable insights for optimizing its use in cardiovascular medicine, ultimately improving patient outcomes and advancing the field.

In the fields of partnership research and social innovation, there have been an increasing number of calls for evidence regarding the kind of collaborative multi-level governance structures that might support large scale transformation processes, specially towards climate-neutral cities. This paper conceptualizes a new type of intermediary actor; the Systemic Collaborative Platform (SCP). Using the example of a multi-stakeholder arrangement set up to design and implement Madrid’s Climate Neutrality Roadmap, the key features of an SCP include a focus on multi-stakeholder and cross-sectoral collaboration for public policy development, in this case operating at both a systemic level and a city scale, and a strong link to a key actor within this regime (a city council). Our study reveals how a SCP can contribute to articulation of a shared mandate among city actors and enhance the efficiency and effectiveness of a targeted transition by attracting, aligning and managing a wide and diverse organizational ecosystem through distributed facilitation, collaborative leadership and continuous learning.

This review delves into using natural antimicrobials in the dairy industry and examines various sources of these compounds, including microbial, plant, and animal sources. It highlights dairy products' most commonly used natural antimicrobials, such as nisin, lysozyme, lactoferrin, chitosan, and essential oils. It discusses the mechanisms by which they inhibit microbial growth and improve the shelf life of dairy products. Moreover, the review explores encapsulation technology as a promising approach for increasing the viability of natural antimicrobials. It discusses how encapsulation technology can protect these compounds from environmental factors that can reduce their effectiveness, such as pH, temperature, and oxygen exposure. The review also highlights the different materials that can be used for encapsulation, such as alginate, chitosan, and starch, and discusses their properties and suitability for encapsulating different natural antimicrobials. Finally, the review examines the benefits and challenges of using natural antimicrobials in dairy products. While natural antimicrobials offer several advantages, including improved safety, quality, and sensory properties of dairy products, it's crucial to be aware of the challenges associated with their use, such as potential allergenicity, regulatory requirements, and consumer perception. The review concludes by emphasizing the need for further research to identify and develop effective and safe natural antimicrobials for the dairy industry to ensure the quality and safety of dairy products for consumers.

Alginate-silver nanocomposites in the form of spherical beads and films were prepared using a green approach by using the aqueous extract of Ajwa dates seeds. The nanocomposites were fabricated by in situ reduction and gelation method by ionotropic crosslinking using calcium ions in solution. The rich phytochemicals of the dates seeds extract played a dual role as reducing and stabilizing agent in the synthesis of silver nanoparticles. The formation of silver nanoparticles was studied using UV-Vis absorption spectroscopy and a distinct surface plasmon resonance (SPR) peak at 421 nm characteristic of silver nanoparticles confirmed the green synthesis of silver nanoparticles. The morphology of the nanocomposite beads and film was compact with even distribution of silver nanoclusters. The catalytic property of the nanocomposite beads was evaluated for the degradation of 2-nitrophenol in the presence of sodium borohydride. The degradation followed pseudo-first order kinetics with a rate constant of 1.40 ´ 10^-3 s^-1 at 23 °C with an activation energy of 18.45 kJ mol^-1. The thermodynamic parameters such as changes in enthalpy and entropy were evaluated to be 15.22 kJ mol^-1 and -197.50 J mol^-1 K^-1, respectively. The nanocomposite exhibited properties against three clinically important pathogens (Gram-positive and Gram-negative bacteria)

This mini-review examines the complex relationship between the gut microbiota and human health, with a special focus on its role in conditions such as inflammatory bowel disease (IBD) and cardiovascular disease (CVD). It explores how dietary patterns can affect the composition of the gut microbiota, thus contributing to the development of various diseases. The gut microbiota is crucial in the production of metabolites such as trimethylamine N-oxide (TMAO), which play a significant role in the development of both IBD and CVD. High levels of TMAO and other metabolites, such as phenylacetylglutamine, have been linked to an increased risk of CVD. The review highlights the potential of dietary interventions and therapies designed to modulate the gut microbiota in reducing these risks. Following a Mediterranean diet may offer cardiovascular protection, emphasizing the need for further research into the molecular mechanisms of diet-related changes in the microbiota.

Complex diseases are prevalent medical conditions which are characterized by strong inter-patient differences in symptom profiles, disease trajectory and treatment response. The challenges in understanding and managing these diseases are due to their complex pathophysiology, comprising of a combination of genetic and environmental factors. The traditional model of disease assumes a clear distinction between health and disease, as well as between different diagnoses, but recent findings with regards to diseasomes and network pleiotrophy suggest that this dogma is not useful in understanding complex diseases. This paper presents a novel model, in which the individual disease burden is determined as a function of molecular, physiological and pathological factors simultaneously: disease(symptoms(traits(genes AND environment))). From this a high-dimensional space is defined which includes all individual disease burdens, ranging from healthy (i.e. low disease burden) to multi-morbidity (i.e. high disease burden), termed the disease landscape. This model provides a novel way to conceptualize human physiology and pathophysiology in the context of complex diseases and may present a useful concept to simultaneously address the strong interindividual heterogeneity of diagnose cohorts as well as the lack of clear distinction between diagnoses and health and disease, thus facilitating the progression towards personalized medicine.

Abstract: Wildfires in forest ecosystems exert substantial ecological, economic, and social impacts. The effectiveness of fire management hinges on precise pre‐fire risk assessments to inform mitigation efforts. This study aims to investigate the relationship between predictions from pre‐fire risk assessments and outcomes observed through post‐fire burn severity analyses. In this study, forest fire risk was assessed with the Fuzzy Analytical Hierarchy Process, in which fire behavior factors were used as input. The degree of burn was determined using the Random Forest method using 11519 training points and 400 test points on Sentinel‐2 satellite images in three different classes. According to the results obtained from 266 selected test points located within the forest boundaries, all primary factors showed an increased effect in areas with high burn severity. Climate, in particular, emerged as the most influential factor, accounting for 52% of the overall impact. However, in cases of high fire severity, climate proved to be the most effective risk factor, ac‐counting for 67%. It followed by topography with 50% accuracy at high fire intensity. In the risk assessment is based on the FAHP method, climate was assigned the highest weight value among other factors with 32.2%. Topography emerged as the second most effective risk factor with 27 %. To evaluate the results more comprehensively both visually and statistically, two regions with different stand canopy characteristics were selected within the study area. While high burn severity had the highest accuracy in Case 1 area, moderate burn severity had the highest in Case 2 area. During the days when the fire continued, the direction of spread was obtained from MODIS images. In this way, the fire severity depending on the direction of fire progression was also interpreted. Through an analysis of various case studies and existing literature, the research underscores both the strengths and limitations inherent in predicting forest fire behavior‐based pre‐fire risk assessments. Furthermore, it emphasizes the necessity of continuous improvement to increase the success of forest fire management.

World Health Organization recommends adjusting the salt intake as a part of the nine global targets to reduce premature mortality from non-communicable chronic diseases as priority and most cost-effective intervention. In 2006. the main aim of the Croatian Action on Salt and Health was to decrease salt intake for 16% because of its critical intake and consequences on human health. We have organized educative activities for increasing awareness on salt harmfulness, defined food categories of prime interest, collaborate with industries and determine salt intake (24h urine-sodium excretion). It was determined that the proportion of salt in ready-to-eat baked bread should not exceed 1.4%. In the period 2014 –2022, salt in the semi-white bread was reduced 14%, in bakery 22% and in largest meat industry in Croatia 25%. Awareness of the harmfulness of salt on health increased from 65.3% in 2008 to 96.9% in 2023 and salt intake was reduced 15.9%-1.8 grams/day (22.8% men, 11.7% women). In last 18 years a significant decrease in salt intake was achieved in Croatia, awareness of its harmfulness increased, collaboration with food industry established and regulatory documents launched. However, salt intake is still very high underlying the need for continuation of efforts and even stronger activities.

Cholesterol homeostasis is pivotal for cellular function. Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), also abbreviated as SOAT1, is an enzyme catalyzing the storage of excess cholesterol to cholesteryl esters. ACAT1 is an emerging target to treat diverse diseases including atherosclerosis, cancer, and neurodegenerative diseases. F12511 is a high affinity ACAT1 inhibitor. Previously, we developed a stealth liposome-based nanoparticle to encapsulate F12511 to enhance its delivery to the brain and showed its efficacy in treating a mouse model for Alzheimer’s disease (AD). In this study, we introduce F26, a close derivative of F12511 metabolite in rats. F26 was encapsulated in the same DSPE-PEG2000/phosphatidylcholine (PC) liposome-based nanoparticle system. We employed various in vitro and in vivo methodologies to assess F26's efficacy and toxicity compared to F12511. Results demonstrate that F26 is more effective and durable than F12511 in inhibiting ACAT1, in both mouse embryonic fibroblasts (MEFs) and in multiple mouse tissues including the brain tissues, without exhibiting any overt systemic or neurotoxic effects. This study demonstrates the superior pharmacokinetic and safety profile of F26 in wild-type mice, and suggests its therapeutic potential against various neurodegenerative diseases including AD.

Here we report a new synthetic protocol based on Microwave- Assisted Synthesis (MAS) for the preparation in higher yields of zinc and copper MOFs based on different bis(pyrazolyl)-tagged ligands ([M(BPZ)]n where M = Zn(II), Cu(II), H2BPZ = 4,4′-bipyrazole, [M(BPZ-NH2)]n where M = Zn(II), Cu(II); H2BPZ-NH2 = 3-amino-4,4’-bipyrazole, and [Mx(Me4BPZPh)] where M = Zn(II), x = 1; Cu(II), x = 2; H2Me4BPZPh = bis-4′-(3′,5′-dimethyl)- pyrazolylbenzene) and a detailed study of their antibacterial activity, tested against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, as representative agents of infections. The results show that all MOFs exert a broad-spectrum activity and strong efficiency in bacterial growth inhibition, with a mechanism of action based on surface contact of MOFs particles with bacterial cells through the so-called “chelation effect” and reactive oxygen species (ROS) generation, without a significant release of Zn(II) and Cu(II) ions. In addition, morphological changes were elucidated by using scanning electron microscope (SEM) and bacterial cell damage was further confirmed by confocal laser scanning microscopy (CLSM) test.

This article is devoted to the problem of genetically coding of inherited cyclic structures in biological bodies, whose life activity is based on a great inherited set of mutually coordinated cyclic processes. The author puts forward and arguments the idea that the genetic coding system is capable of encoding inherited cyclic processes because it itself is a system of cyclic codes connected with Boolean algebra of logic. In other words, the physiological processes in question are cyclical because they are genetically encoded by cyclic codes. In support of this idea, the author presents a set of his results on the connection of the genetic coding system with cyclic Gray codes, which are one of many known types of cyclic codes. This opens up the possibility of using for modeling inherited cyclic biostructures those algebraic and logical theories and constructions that are associated with Gray codes and have long been used in engineering technologies: Karnaugh maps, Hilbert curve, Hadamard matrices, Walsh functions, dyadic analysis, etc. Additionally, the connections of these constructions with statistical rules of genomic DNAs and binary-genomic numbers are considered.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

The viscoelastic properties and structure parameters have been investigated for aqueous solutions of wormlike micelles of cationic surfactant erucyl bis(hydroxyethyl) methylammonium chloride with long C22 tail in the presence inorganic salt KCl. The salt content has been varied to estimate linear to branched transition conditions due to screening of the electrostatic interaction in the networks. The local cylindrical structure and low electrostatic repulsion was obtained by SANS data. The drastic power law dependencies of rheological properties on surfactant concentrations were obtained at intermediate salt content. Two power law regions were detected in semi-dilute solutions related to “unbreakable” and “living” micellar chains. The fast contour length growth with surfactant concentration was demonstrated that is in good agreement with theoretical predictions.

Nanobubbles, gas-filled entities that possess a size of less than , have notably emerged as critical components within various domains such as environmental science and medicine, primarily due to their remarkable stability and distinctive diffusion characteristics that differentiate them from larger bubbles. This comprehensive study meticulously explores the diffusion rates and stability of hydrogen and oxygen when encapsulated in oxyhydrogen nanobubbles, specifically within aqueous environments, utilizing the Chapman-Enskog theory, which is a well-established framework for understanding gas diffusion processes, alongside a modified Arrhenius equation to effectively evaluate activation volume and stability parameters. The findings from this investigation reveal that the diffusion processes of both gasses experience a significant reduction in rate due to the influence of high internal pressure, as well as the molecular interactions occurring with water, whereby hydrogen is observed to exhibit a marginally accelerated diffusion rate in comparison to oxygen. It is crucial to understand that elements like surface charges, zeta potential, and the idea of activation volume significantly influence the enduring stability of nanobubbles, particularly in specific environmental scenarios that could boost their longevity. These significant findings pose a challenge to classical diffusion models, thereby suggesting a promising potential for the sustained application of nanobubbles in various fields such as water treatment processes and therapeutic medical interventions. Future research endeavors should prioritize the refinement of theoretical models while also aiming to experimentally validate the mechanisms of stability that have been observed across a range of diverse applications to further substantiate these findings.

Vaccination is an important method of immunological preventive care required for health management of all animal including fish. More particularly, immunization is important in in-land fisheries for the management of diseases in fish brood stocks and healthy seed production. According to the latest statistics in 2020, 90.3 million tonnes of captured fish production was achieved from the aquaculture sector. Out of the above, 78.8 million tonnes from marine and 11.5 million tonnes from inland waters aquaculture sectors. About 4% decline in fish production was achieved in 2020 than 2018 from inland fisheries sectors. On the other hand, the digestive protein content, healthy fats and nutritional values of fish products are comparitively more affordable as compared to other meat sources. In 2014, about 10% aquatic cultured animals were lost (costing &gt; 10 billion $ global annual loss) due to infectious diseases. Therefore, vaccination in fish especially in brood stocks is one of the most important approaches to stop such losses in the fisheries sector. Fish vaccines consist of either whole killed pathogens, subunit of a protein, a recombinant protein, DNA vaccines or live attenuated vaccines. Challenges existing are adaption of vaccination in fisheries sector, route of administration, use of effective adjuvants and most importantly lack of effective results. Use of autogenous vaccines, vaccination via intramuscular, intraperitoneal or oral routes, and most importantly adding vaccines in feed using top dressing methods or as a constituent in fish feed are now in emerging. These method shall lower the risk of using antibiotics in cultured water which in turn will reduce the environmental contamination.

The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.

Anderson-Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient or absent activity of the enzyme alfa-galactosidase A. This defect enzyme leads to accumulation of glycolipids, primarily globotriaosylceramide (Gb3), in the vascular endothelium of several organs, including the skin, kidneys, nervous system, and heart. The characteristic early clinical features of Fabry disease include acroparaesthesia, angiokeratoma, heat intolerance, hypohidrosis, cornea verticillata and gastrointestinal symptoms. Later complications occur with the disease progression and include progressive renal failure, hypertrofic cardiomyopathy, cerebrovascular disease and reduced life expectancy. Anderson Fabry disease is therefore a disabling and systemic disease which requires a timely diagnosis. The purpose of our study is to define sweat glands morphological abnormalities in children and adolescents with Fabry disease with minimal symptoms and in patients affected by variants of Fabry disease in which biopsy is essential, to establish a baseline morphological diagnosis of the disease before to undergo to kidney or endomyocardial biopsy or when the classical approach is not possible because of some complications, with minimal discomfort for patients.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent and irreversible neurological disorders that primarily affect the aged population. These conditions lead to disability and mortality as there is currently no medication for a complete cure. Existing drugs only provide symptomatic relief of the disease. Inhibition of Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) will reduce the hydroxylation of Acetylcholine, a molecule possessing a significant role in the neurotransmission pathways and is accounted as a remedial objective for the treatment of AD and PD. This study aimed to identify potent lead molecules from plants that could inhibit AChE and BuChE. We employed molecular docking, molecular dynamic simulation, and MMPBSA approaches to screen and evaluate potential compounds. The docking results were analysed based on binding affinity and hydrogen bond interactions at the active-site residues of the targets. From the analysis, four phytocompounds - Tricetin, Luteolin, Withasomniferol C, and Withanolide were identified as potential hits. These compounds demonstrated strong binding affinities of -8.49, -9.85, -25.26, and -24.1 kcal/mol, respectively. The significant binding affinity suggests that these compounds may effectively inhibit the activity of AChE and BuChE, potentially leading to therapeutic benefits for AD and PD. However, further in-vitro analysis is recommended to validate the activity of these compounds. In-vitro experiments will provide a better understanding of their efficacy, safety, and potential as drug candidates for treating AD and PD.

We will apply Pascal’s hydrostatic pressure law to black holes and also to the Hubble sphere. Haug has recently demonstrated how hydrostatic pressure in water can be utilized to determine the Planck length. One can conceptualize the energy in the Hubble sphere as a type of superfluid, and if this is correct, then Blaise Pascal’s hydrostatic pressure formula may also be applicable to such a superfluid, even within the Hubble sphere. By employing the same method on the Hubble sphere and considering it as a Schwarzschild black hole with the critical Friedmann mass, we can estimate the Planck length based on its hypothetical hydrostatic pressure.

This study investigates the effectiveness of a range of timber-based solutions for seismic and energy retrofitting of existing masonry buildings. These solutions are designed not only to prevent structural collapse during earthquakes but also to create integrated interventions that enhance thermo-physical performance and reduce emissions in existing buildings. Various case scenarios were considered and both mechanical and energetic behavior post-intervention were evaluated. Timber-engineered products serve as foundational components for the retrofit approach, encompassing one-dimensional vertical elements (strong-backs) and various types of panels (cross-laminated timber panels, laminated veneer lumber panels, and oriented strand board panels). The analyzed retrofit techniques share a common principle, involving the attachment of these timber-based elements to the building's wall surfaces through mechanical point-to-point connections. The proposed solutions integrate strong-backs and timber panels with membranes and insulation layers, yielding cohesive and highly effective interventions. Finite element modeling was employed to analyze the mechanical and thermal responses of the retrofitted walls. A comprehensive comparative analysis of various techniques was conducted to determine the most effective solution for each specific scenario.

Harnessing the Remarkable Bio-Remediation Potential of Vernonia spp. for the Sustainable Restoration of Hydrocarbon-Polluted Clay Soil in Ogoni Land, Nigeria This study explores the potential of utilizing Vernonia spp. for eco-friendly bio-remediation of hydrocarbon-polluted clay soil in Ogoni Land, Nigeria. The aim is to find a sustainable and effective solution that promotes the restoration of the polluted soil while minimizing the use of external additives. The process of bio-remediation can occur naturally, through natural attenuation or intrinsic bio-remediation. However, it has been observed that in certain cases, the addition of fertilizers, oxygen, or organic matter is required to enhance the effectiveness of bio-remediation. In this research, we focus on the bio-remediation potential of Vernonia spp., a native plant species known for its strong phytoremediation abilities. By harnessing the remarkable bio-remediation properties of Vernonia spp., we seek to restore the hydrocarbon-polluted clay soil in Ogoni Land in an environmentally friendly and sustainable manner. Our methodology involves conducting greenhouse experiments to assess the bio-remediation efficiency of Vernonia spp. in different soil conditions. We will analyze the soil's physical and chemical properties, as well as the degradation of hydrocarbons over time. The experimental results will provide valuable insights into the effectiveness of Vernonia spp. in removing hydrocarbon pollutants from clay soil. Through this study, we aim to develop a cost-effective and sustainable approach to restore hydrocarbon-polluted clay soil in Ogoni Land. By leveraging the natural bio-remediation potential of Vernonia spp., we can potentially reduce the reliance on external additives, thus minimizing the environmental impact associated with traditional remediation methods. The research article explores methods to promote the growth of pollution-eating microbes in order to enhance bio-remediation. Bio-remediation refers to the use of naturally occurring organisms to break down harmful substances into less toxic or non-toxic forms. In situ bio-remediation involves treating the contaminated material directly at the site, while ex-situ bio-remediation involves removing the contaminated material for treatment elsewhere. This study specifically investigates ex-situ bio-remediation techniques for hydrocarbon-contaminated clay soil. The researchers found that the application of room dry and wet blended bitter leaf showed promising results in the bio-remediation of hydrocarbons in the clay soil. Using Vernonia galamensis, a concentration as high as 0.55 ug/ml was achieved, while Vernonia amygdalina yielded a concentration as high as 0.67 ug/ml when applied at 35g and 40g respectively, based on the wet blended approach. These findings highlight the effectiveness of wet blended Vernonia species in the bio-remediation process.During the remediation process of the clay soil, the pH levels showed a trend of increasing from acidic to normal to alkaline. This can be attributed to the remediation of excessive metals present in the soil. After 40 days, the pH of the clay soil reached 6.97 when treated with 40 grams of Vernonia galamensis, and 7.00 when treated with 40 grams of Vernonia amygdalina. Interestingly, while the remediation efficiency of HC (hydrocarbon) decreased with increasing mass of Vernonia galamensis, the remediation efficiency of HC increased when using Vernonia amygdalina. These observations highlight the varying effects of different Vernonia species on hydrocarbon remediation.The highest remediation values were observed when using Vernonia galamensis at 35g and Vernonia amygdalina at 40g. These particular amounts of these Vernonia species demonstrated effective remediation of the targeted pollutants. However, in comparison to other metals, the remediation effects were relatively lower for zinc (Zn), with only approximately 0.25 ug/ml being remediated. This suggests that the remediation potential of the Vernonia species may vary depending on the specific contaminant.The higher remediation effects observed for Zn metal in the soil can be attributed to the wet blended preparation method of the Vernonia species. In contrast, the room dried Vernonia species exhibited the lowest performance in remediating the soil, with approximately 0.17 ug/ml and 0.10 ug/ml remediation for galamensis and amygdalina, respectively. Both Vernonia leaf extracts achieved a remediation of 0.5 ug/ml for chromium. The sun dried and room dried methods also showed considerable remediation potential, with values above 0.4 ug/ml. The level of significance for the model was attained at 0.05, and the r2 value was appreciable. These findings indicate the effectiveness of different preparation methods and Vernonia species in soil remediation

The aim of this expository article is to present recent developments in the centuries-old discussion on the interrelations between several types of domination in graphs. However, the novelty even more prominent in the newly discovered simplified presentations of several older results. Domination can be seen as arising from real-world application and extracting classical results as first described by this article.The main part of this article, concerning a new domination and older one, is presented in a narrative that answers two classical questions: (i) To what extend must closing set be dominating? (ii) How strong is the assumption of domination of a closing set? In a addition, we give an overview of the results concerning domination. The problem asks how small can a subset of vertices be and contain no edges or, more generally how can small a subset of vertices be and contain other ones. Our work was as elegant as it was unexpected being a departure from the tried and true methods of this theory that had dominated the field for one fifth a century. This expository article covers all previous definitions. The inability of previous definitions in solving even one case of real-world problems due to the lack of simultaneous attentions to the worthy both of vertices and edges causing us to make the new one. The concept of domination in a variety of graphs models such as crisp, weighted and fuzzy, has been in a spotlight. We turn our attention to sets of vertices in a fuzzy graph that are so close to all vertices, in a variety of ways, and study minimum such sets and their cardinality. A natural way to introduce and motivate our subject is to view it as a real-world problem. In its most elementary form, we consider the problem of reducing waste of time in transport planning. Our goal here is to first describe the previous definitions and the results, and then to provide an overview of the flows ideas in their articles. The final outcome of this article is twofold: (i) Solving the problem of reducing waste of time in transport planning at static state; (ii) Solving and having a gentle discussions on problem of reducing waste of time in transport planning at dynamic state. Finally, we discuss the results concerning holding domination that are independent of fuzzy graphs. We close with a list of currently open problems related to this subject. Most of our exposition assumes only familiarity with basic linear algebra, polynomials, fuzzy graph theory and graph theory.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

The use of smartphones, coupled with different sensors, makes it an attractive solution for measuring different physical and physiological features, allowing for the monitoring of various parameters and even identifying some diseases. The BITalino device allows the use of different sensors, including Electroencephalography (EEG) and Electrocardiography (ECG) sensors, to study different health parameters. With these devices, the acquisition of signals is straightforward, and it is possible to connect them using a Bluetooth connection. With the acquired data, it is possible to measure parameters such as calculating the QRS complex and its variation with ECG data to control the individual's heartbeat. Similarly, by using the EEG sensor one could analyze the individual's brain activity and frequency. The purpose of this paper is to present a method for recognition of the diseases related to ECG and EEG data, with sensors available in off-the-shelf mobile devices and sensors connected to a BITalino device. The data were collected during the elderly's experiences, performing the Timed-Up and Go test, and the different diseases found in the sample in the study. The data were analyzed, and the following features were extracted from the ECG, including heart rate, heart rate variability, the average QRS interval, the average R-R interval, and the average R-S interval, and the EEG, including frequency and variability. Finally, the diseases are correlated with different parameters, proving that there are relations between the individuals and the different health conditions.

Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated to IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and of weak evidence. This review summarizes the current knowledge on the complex interactions among diet, microbiome and epigenetics in IBD. Whereas over-abundance of calories and some macronutrients increases gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, D, folic acid and beta-carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, anti-inflammatory dietary patterns as a complex intervention approach have become popular over the recent years. Hence, exclusive enteral nutrition in pediatric Crohn’s disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet, the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet and most recently the Mediterranean diet have shown strong anti-inflammatory properties and provide a promise for improving disease symptoms. Definitely, more work is required to evaluate the role of individual food compounds and complex nutritional interventions with potential to decrease inflammation as means for prevention and management of IBD.

Gc protein-derived Macrophage Activating Factor (GcMAF), a powerful immunostimulant endowed with anti-cancer and anti-angiogenetic activities, offers significant advantages when combined with radiation therapy. A stronger immune response improves the effectiveness of radiation therapy by allowing the body to better eliminate residual cancer cells after treatment. In addition, by boosting the immune system, GcMAF mitigates some of the immunosuppressive side effects of radiation therapy, leading to faster recovery. In order to fully exploit the potential of GcMAF in cancer therapy, knowledge of the molecular interactions with its receptor is essential. This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the GcMAF receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

Knowledge on the health of banana trees is critical for farmers to profit from banana cultivation. Fusarium wilt and banana blood diseases (BDB), two significant diseases infecting banana trees, are caused by Fusarium oxysporum and Ralstonia syzygii, respectively. They have successfully caused a decline in crop yield as they destroy the trees, starting sequentially from the pseudostem to the fruits. The entire distribution of BDB and Fusarium on a plantation can be understood using advanced geospatial information obtained from multispectral aerial photographs taken using an unmanned aerial vehicle (UAV), combined with the reliable data field of infected trees. Vegetation and soil indices derived from a multispectral aerial photograph, such as normalized difference vegetation index, modified chlorophyll absorption ratio index, normalized difference water index (NDWI) and soil pH, may have to be relied on to explain the precise location of these two diseases. In this study, a random forest algorithm was used to handle a large dataset consisting of two models: the banana diseases multispectral model and the banana diseases spectral model. The results show that the soil indices, soil pH and NDWI are the most important variables for predicting the spatial distribution of these two diseases. Simultaneously, the plantation area affected by BDB is more extensive than that affected by Fusarium, if the variation of planted banana cultivars is not considered.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

In the field of delta-sigma modulators, reducing system power consumption without sacrificing accuracy has become a challenge. The summing circuit, as the main part of the cascade-of-integrator-in-feedforward delta-sigma modulator, consumes a significant amount of power in active summing. On the other hand, passive summing circuits have low power consumption but can cause attenuation in the summing results. This article proposes a low-power multi-bit delta-sigma modulator based on passive and attenuationless summation scheme. The summation circuit achieves multiplication of the voltage signal carried on the summation capacitor through bidirectional sampling technique, compensating for the inherent attenuation caused by passive summation, thus eliminating the need for active OTA to achieve perfect summation. A 2-order delta-sigma modulator based on 4-bit 1-order passive noise-shaping (NS) SAR quantizer is designed to verify the scheme. By combining a passive NS SAR as the 4-bit quantizer and the third-stage integrator of the system, and incorporating an energy-efficient cascode floating inverter amplifier (FIA) structure as the core active OTA, these elements have significantly enhanced the energy-efficiency of the modulator. Simulation results show that at a supply voltage of 1.2 V and a bandwidth of 20 kHz, the SNDR reaches 102.62 dB, power consumption is only 148.32 μW, and Schreier figure-of-merit (FoM) of SNDR is 183.92 dB.

This study examined how Information Use Environments (IUEs) influence the information behavior of people living with neglected tropical diseases (PLWNTDs) and how this affects their participation in diagnosis and treatment programs. The author demonstrated that local information use environments (IUEs) significantly impacted the information behavior of people living with neglected tropical diseases (PLWNTDs'), which can be harnessed to improve their involvement in diagnosis and treatment programs. The author compared user-centered and program-centered approaches within common IUEs in remote and impoverished areas, finding that NTDs persist due to a disconnect between program organizers and the affected individuals’ information use environments (IUEs). Data was sourced from published papers, and OpenAI (ChatGPT) was used to generate list of local sources (IUEs) in affected remote communities. The findings indicated that understanding local IUEs can help program organizers enhance participation rates of individuals with NTDs in diagnosis and treatment initiatives.

Autoimmune Glomerulonephritis represents a homogeneous area of renal pathology with clinical relevance for either the numerical impact or difficulties in treatment. SLE and Lupus nephritis are the most frequent occurrences. They are characterized by glomerular deposition of circulating autoantibodies that recognize glomerular antigens Technologies for studying tissue and circulating antibodies have evolved over the years and culminated with the direct analysis of the antigen-antibody complex in renal bioptic fragments. Mass-spectrometry of immunoprecipitates from the renal tissue is, in fact, the most recent evolution that eliminates the need for tissue microdissection. The results obtained with this technique have led to the discovery of several new glomerular antigens in Membranous Nephropathy and in Lupus Nephritis, two conditions whose pathogenesis remained unknown for decades, Peptide and protein arrays (Immunopeptidomics and immunoproteomics, respectively) for the characterization of circulating autoantibodies represent the new frontier for identifying autoantibodies. Immunopeptidomics consists in 7.5 million aligned peptides of 16 amino acids each which cover the whole human proteome; immunoproteomics utilizes a chip containing structured proteins, 26.000 overall. Both are very sensitive techniques that allow the characterization of hundreds of new antibodies in circulation. The contribution of arrays to amplify the panel of potential autoantibodies involved in glomerulonephritis is expected to be relevant for improving our knowledge of the pathogenesis of several autoimmune conditions.

This cross-sectional, analytical, and observational study aimed to investigate the relationship between Visceral Adiposity Index (VAI) and anthropometric, biochemical, and insulin resistance (IR) parameters in Brazilians at risk of CVD. Biochemical parameters and anthropometric measurements were evaluated. The Pearson test was used to assess the correlation between VAI and anthropometric, biochemical, and IR parameters, with a predefined significance level of 5%. The analyzed sample consisted of 88 men and 72 women, with an average age of 58.78±13.48. VAI revealed noteworthy and positive correlations with all anthropometric parameters assessed (p&lt;0.0001). Furthermore, significant positive associations were noted between VAI and total cholesterol in women (p=0.0064), glycemia in men (p=0.0105), and LDL-c (p&lt;0.01) and triglycerides in both genders (p˂0.0001). A significant negative association was observed between VAI and HDL-c in both genders (p&lt;0.0001). Notably, the correlation between VAI and total cholesterol in men, glycemia in women, and CRP in both genders was not found to be significant. However, a significant relationship between VAI and IR parameters was observed in both sexes (p&lt;0.05). The results obtained from our study suggest that VAI functions as a simple and non-intrusive instrument, demonstrating significant effectiveness in identifying metabolic changes primarily associated with adipose tissue dysfunction, particularly dyslipidemia.

Asthma is the most prevalent cause of chronic respiratory diseases. Herein, we evaluate asthma burden in Mexico based on results from the Global Burden of Disease (GBD 2019) study 2019. Using data from the GBD 2019, we estimated asthma prevalence, incidence, mortality, and disability-adjusted lived years (DALYs) counts and crude and age-standardized rates per 100,000 people with a 95% uncertainty interval (UI) by sex and age at the national and subnational levels in Mexico from 1990 to 2019. At the national level, asthma affected 3.35 million (95% UI, 2.59-4.37) people, with 606.0 thousand (433.0-811.1) new incident cases and 1,655 (3-1,931) deaths during 2019. Asthma caused a slightly higher burden in females and affected mainly age groups between 1 and 14 years of age. The burden of asthma gradually decreased from 1990 to 2010. However, during the last decade (2010-2019), prevalence increased by 8.2%, as did incidence by 11.3%, whereas mortality and DALYs decreased by 23.3 and 1.6%, respectively. Finally, the burden of asthma displayed a heterogeneous pattern of disease at the subnational level. In conclusion, asthma causes a significant health loss in Mexico that differentially affects the population distributed among the states of the country, thus causing health disparities that should be addressed to provide sustainable asthma diagnosis and control to reduce its burden, especially at early stages of life.

Various measures have been attempted to prevent infectious diseases in calves, such as envi-ronmental improvement and vaccine administration. Probiotics are commonly used to im-prove the body condition of newborn calves and prevent disease. In our previous research, Lactiplantibacillus plantarum RGU-LP1 (LP1) inhibited the expression of inflammatory cyto-kines in PBMC from cows fed LP1. In this study, we evaluated the effect of LP1 on calf growth and disease control. Methods: Twenty-six one-week-old Holstein bull calves were divided into two groups (13 each), LP1 group (LP1 treated) and CN group (no LP1 fed), and tested as follows. The LP1 group was fed lyophilised LP1 (10⁹ CFU/head/day) in milk replacer for 40 days. The CN group was fed the same diet only. Calves were followed for 63 days. During this period, the weight and treatment times of the calves were recorded. Faeces and blood were collected from each calf during this period. Faeces were examined for gut microbiota, and blood for immune assay and cytokine gene expression. The LP1-treated group showed a de-crease in disease incidence and an increase in body mass compared to controls. Results: The average treatment cost during the observation period was significantly reduced compared to the CN group. The expression of TGFβ and IL10, inhibitory cytokines of inflammation, was sig-nificantly increased. The simultaneous expression of this set of inhibitory molecules resulted in low serum IL1β levels during the growth period. Conclusions: The Th1-type cytokine IFNγ was also significantly increased in LP1-treated calves. By reducing the number of disease treatment times and increasing body weight, LP1 is effective in preventing infectious diseases in calves. In addition, the increase in IFNγ by LP1 indicates improved Th1-type immunity in calves. These results show that LP1 has effects on the regulated inflammatory response and growth of calves.

Dirac's Large Number Hypothesis (LNH), proposed in 1937, has captivated the scientific community with its exploration of profound correlations between cosmic and atomic scales. This hypothesis delves into the intricate interplay between the infinitesimally small and the vastly large, offering potential insights into the fundamental nature of the universe. As we continue to uncover the mysteries of the cosmos, the LNH oscillates on the precipice of scientific acceptance—neither fully validated nor entirely dismissed. In this review paper, we embark on a comprehensive journey through Dirac's LNH, shedding light on its theoretical underpinnings, its implications for universe models, and its resonance with the Anthropic Principle. We delve into the possibilities of variable gravitational constants and continuous mass creation, inviting further exploration into the intricacies of our cosmic symphony. By embracing the ongoing quest for understanding, we endeavor to unravel the profound harmonies that connect the infinitesimal with the infinite, contributing to the symphony of knowledge in theoretical physics and cosmology.

High-quality optical Fano resonances, which exist in a spherical dielectric microparticle in the spatial configurations of the "whispering-gallery modes" (WGMs) and recently are referred to as the “super-resonances”, possess extremal sensitivity not only to the micro-cavity size and shape but also to the optical properties of the particulate material. The increase in the power of light radiation coupling into a super-resonance can lead to the manifestation of strong optical nonlinearity of the resonator material due to the cubic nonlinearity (optical Kerr effect) and generation of free electron plasma in certain regions of the spherical microcavity. In fact, an optically linear medium of the resonance cavity transforms into a Drude-Kerr-type medium with a strong dependence on input laser intensity. With the help of the finite-elements numerical simulations, we theoretically analyze the transformations of the resonant contour for a number of high-quality WGMs excited in a lanthanum-glass microsphere exposed to an optical radiation of different intensity. We show that in a certain input intensity range, the competition of Kerr and plasma optical nonlinearities can stop and even reverse the Stokes shift of the super-resonance observed in a pure Kerr medium. Additionally, optical ionization and plasma generation within the mode volume significantly reduce the strength of the magnetic super-resonance and lead to its spoiling and frequency splitting.

Current artificial intelligence (AI) technology is still considered weak AI. However, the progression towards strong AI unavoidably involves grappling with concerns surrounding consciousness, the mind, and creativity. This paper focuses on analyzing consciousness, creativity, and the generation of emotions to explore the possibility of machine-based consciousness, creativity, and emotion. We believe that the emergence of consciousness relies on the complex interplay at different layers within a complex system, rather than wholly relying on the underlying substrates of the system. Thus, it is plausible to consider the existence of machine-based consciousness, creativity, and emotion. Furthermore, swarm intelligence should be recognized as a distinct form of intelligence. Human individuals serve as the foundational substrate enabling the realization of swarm intelligence, with individual intelligence reflecting the projection of swarm intelligence at the individual level. The advanced state of human civilization is primarily attributable to the effect of swarm intelligence. Building upon basic emotions to adapt to environmental conditions, advanced human emotions are a product of the evolutionary process by swarm intelligence. Emotions serve as a pivotal impetus for the formation and development of societies grounded in swarm intelligence. In pursuit of super-AI that surpasses human civilization in the future, nurturing swarm intelligence represents an inevitable trajectory.

The overcrowding of high-rise buildings in the city adversely affects the wind environment by changing the air currents in the surrounding areas. In particular, extreme climate phenomena caused by climate change are stronger and more frequent, causing social damages in cities. To comprehensively better understand the wind properties around high-rise buildings, actual filed measurement is necessary to determine the environment assessment of wind effect. We performed the on-site measurement on LCT residential complex regions (411.6m tall) with highly concentrated high-rise buildings in coastal city Busan, South Korea under extreme weather conditions such as typhoon invasions to determine wind fluid characteristics. In the field monitoring, five anemometers were installed to analyze the wind environment around high-rise buildings when typhoon 'Hinnamnor' invaded. Compared to the nearby weather station operated by KMA(Korea Meteorological Administration), the gust was 3.7 times stronger and the max 1 min-mean wind speed was 3.1 times stronger, and the characteristics of the downward wind and the canyon wind were shown depending on the location characteristics of the point. Turbulence intensity decreased as the wind speed increased and converged to a certain value. Likewise, the gust factor also decreased as the wind speed increased and converged to 2.0, which is considered to be the parameter that best represents the intensity of the instantaneous gust caused by the skyscraper wind effect.

Neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson’s, and Amyotrophic Lateral Sclerosis, involve neuron degeneration linked to the misfolding of amyloidogenic proteins, resulting in β-sheet-enriched aggregates. This phenomenon disrupts the normal folding of proteins critical for cellular function. Genetic mutations, proteolytic cleavage, oxidative stress, and aging contribute to misfolding. Parkinson's disease (PD) is closely tied to alpha-synuclein (αS) misfolding, with A53T mutation and Lewy bodies (LB) in PD brains pivotal to understanding the disease mechanism. Other synuclein homologues (βS, γS) further contribute to synucleinopathies. Mutants (A30P, A53T, E46K, H50Q, and G51D) underscore αS&#39;s role in PD development. This concise review focuses on molecular and pathological aspects of neurodegenerative diseases, emphasizing αS in PD. The integration of genetic, structural, and mechanistic insights highlights the disorders. complexity, paving the way for future therapeutic strategies targeting protein misfolding and aggregation.

Epidemiological studies indicate that skipping breakfast as a universal behavior, may have adverse effects on cardiovascular diseases [CVDs}and metabolic diseases. However, eating breakfast regularly, may increase satiety, thereby reducing overeating later in the day which prevents weight gain. Recent studies indicate that skipping breakfast increases the risk of obesity, metabolic syndrome, hypertension, hypercholesterolemia, type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and cardiovascular mortality as well as all-cause mortality. However, many studies also reported that regular taking of breakfast decreases the risk of CVDs and T2DM and all-cause mortality. Previous studies reported that heavy breakfast, in particular eating western diet may increase circadian rhythm of CVDs and sudden cardiac death. It seems that those who do not eat breakfast, they tend to eat refined and sweetened products, possibly, more in the night resulting in to greater risk of CVDs and T2DM. Breakfast skipping and eating in the night, may be associated with circadian misalignment in the central and peripheral clocks, leading to oxidative stress and inflammation. Increased systemic inflammation damages the adipocytes, beta cells of pancreas, endothelial cells and smooth muscle cells as well as neurons, which may produce dysfunction in these cells resulting in to related diseases. The beneficial effects of breakfast, may also be, at least in part, due to nutrient dense foods rather than time of eating. Eating regular breakfast, in particular rich in Indo-Mediterranean foods; vegetables, whole grains, fruits, spices and nuts may be protective against circadian increase in oxidative stress in the morning, resulting in to significant decline in the risk of CVDs and T2DM.

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

Cold atmospheric plasma (CAP) has emerged as a promising therapeutic technology, distinguished by its safety, efficiency, and minimal side effects. With increasing applications in dermatology, CAP demonstrates antimicrobial efficacy against bacteria, viruses, and fungi, supports tissue proliferation and wound healing, and hinders the growth and migration of tumor cells. This review encompasses the concept, physical characteristics, and current research applications of CAP in dermatology. CAP, a gas cloud produced by ionizing gases, operates at room temperature, ensuring safety and efficacy in dermatological use. Its effects are mediated through active components like reactive oxygen and nitrogen species (RONS) and ultraviolet radiation. The extensive research covered in this paper explores CAP's applications in skin infections, immune-related diseases, and tumor diseases. As a biologically suitable technology, cold atmospheric pressure plasma finds widespread use in medicine, including medical device sterilization, dentistry, oncology, and dermatology. The direct and indirect forms of CAP applications, including plasma-activated liquids, complement each other. CAP holds promise as a dermatological treatment technique, but further exploration and research are needed. This article briefly explores CAP's diverse applications and potential utility within dermatology. The objective is to enhance the progress of plasma medicine by furnishing a concise overview of the applications of this groundbreaking technology in dermatological contexts.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) linked with coronavirus disease 2019 (COVID-19) poses a serious threat to public health worldwide. Firstly, the SARS-CoV-2 was reported in Wuhan, Hubei Province, China in December 2019. Initially, the major proportion of virus-infected cases (i.e. about 99%) was reported in China and now it is being reported in other counties as well. Humans begin to be infected within their communities and transmittance of the viral epidemic increased rapidly due to lack of understanding of its transmission routes and precautionary measures. The existence of SARS-CoV-2 in China threatened the population greatly due to the high incidence of fatal respiratory infections. Current investigations speculated that this virus transferred into a human from viral-infected bats. However, the process of interspecies viral transmission is an important scientific question to be addressed. Due to the continuous increase in the patients infected with COVID-19 associated pneumonia, the World Health Organization (WHO) has included this viral epidemic to the priority list of diseases. Therefore, accelerated research developments are required to control the spread of this outbreak, as it is declared as a public health emergency by WHO especially in the absence of efficacious drugs and vaccines. Our review encompasses the recent status of disease severity in China, a particular replication mechanism of SARS-CoV-2 and potential risks and precautionary measures required to avoid contact with this fatal viral infection.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

Plant-based alternative medicine is normally grounded on empiric cultural perception, as the main objective, these practices intent to either maintain good health or to provide a route to turn-the-tide on a specific disease or ailment. Amongst the thousands of plants that have been used and studied, Neem (Azadirachta indica) seems to have a very interesting tale to tell, since its properties to ward-off certain diseases have overtime, and in a rigorous way, been proven. The preceding concise review is a collection of some of the most relevant studies today, not only focusing on the health benefits obtained by its use, but digging into the molecular mechanisms of how the properties come about. In particular, we take a look over antioxidant properties and how these mediate and mitigate important molecules such as IL-6 and TNF-, leading the way in reducing systematic damage by oxidative stress. Further, we relate this oxidative reduction to other systemic diseases such as cancer and diabetes, as these are currently becoming the most rampant killers. As of yet not all is known about the different ways of extracting or the total composition of an extract, as these may be from different parts of the plant. Therefore, we also allude to an important cautionary view where toxicological effects and conflicting outcomes arise. Overall, presented results show a great potential for the different extracts of Neem as their antioxidant activity can be taken advantage off, and potentially used in modern medicine.

Abstract: Autoimmune diseases (AIDs) are a group of disorders, in which the immune system attacks the body own tissues leading to chronic inflammation and organ damage. These diseases are difficult to treat due to variability in drug PK among individuals, patient responses to treatment, and the side effects of long-term immunosuppressive therapies. In recent years, pharmacometrics has emerged as a critical tool in Drug Discovery and Development (DDD) and precision medicine. The aim of this review is to explore the diverse roles that pharmacometrics has played in addressing the challenges associated with DDD and personalized therapies in the treatment of AIDs. Methods: The review synthesizes research from past two decades on pharmacometric methodologies, including Physiologically Based Pharmacokinetic (PBPK) modeling, Pharmaco-kinetic/Pharmacodynamic (PK/PD) modeling, Disease Progression (DisP) modeling, population modeling, and Quantitative Systems Pharmacology (QSP). The incorporation of Artificial Intelli-gence (AI) and Machine Learning (ML) into pharmacometrics is also discussed. Results: Pharmacometrics has demonstrated significant potential in optimizing dosing regimens, improving drug safety, and predicting patient-specific responses in AIDs. PBPK and PK/PD models have been instrumental in personalizing treatments, while DisP and QSP models provide insights into disease evolution and pathophysiological mechanisms in AIDs. AI/ML implementation has further enhanced precision of these models. Conclusions: Pharmacometrics plays a crucial role in bridging preclinical findings and clinical applications, driving more personalized and effective treatments for AIDs. Its integration into DDD and translational science in combination with AI and ML algorithms holds promise for advancing therapeutic strategies and improving autoimmune patient outcomes.

The upper ocean heat content in the equatorial Pacific usually serves as a primary precursor for an upcoming El Niño, while the strong atmospheric perturbations such as westerly wind burst and easterly wind surge sometimes play a decisive role in determining the final intensity of the event. The tropical Pacific Ocean has just experienced a rare 3-year La Niña, which accumulated a huge amount of warm water in the western basin by the winter of 2022. Using a state-of-the-art climate prediction system, here we show that the restored warm water is sufficient to boost a strong El Niño toward the end of 2023, and that an extreme event could take place if a few sizable westerly wind bursts would occur in spring and early summer. This prediction is not sensitive to initial errors within the tropical Pacific, but may be subject to some uncertainties brought about by influences from elsewhere.

Patriarchy culture is formed indirectly through a concept of a man as a head of family or the holder of the highest position. It leads to viewpoint that catcalling is assumed normally. Although catcalling seems like a compliment, but it is quite different with the exact compliment. The basic difference from them both is a compliment comes to sincerely from its giver, meanwhile catcalling is aimed to harass indirectly to women. This study aims to give an information and solution about the catcalling expansion in public areas especially by women community. The use of method to finish this study is qualitative design from literature sources for the last four years about problems of catcalling. The result of this study is giving information about catcalling by providing data and looking for solution related to catcalling phenomenon.

Over the last few decades, advancements in astrophysics have been closely linked to the development of powerful machine-learning models that can accurately classify celestial bodies. At the same time, however, many astronomical datasets are filled with new features collected by increasingly powerful telescopes. These features can cause overfitting, clouding predictive abilities, and dampening the ability of many models to classify images. Therefore, motivation to design more efficient models has skyrocketed—aiming to optimize for lower run times and high accuracies, even with fewer provided features. In our project, we seek to optimize a convolutional neural network model using a technique known as wavelet analysis. This technique allows us to pick the key features of an astronomical image and accentuate niche details, saving time and boosting accuracy. We applied it to the MiraBest Dataset, a dataset compiled from the FIRST sky survey using a virtual telescope. In the end, after training our neural network on the original images and the five filters (approximation, horizontal, vertical, diagonal, and combined), we found that with fewer features and less overfitting, the vertical Daubechies-family wavelet filter outperformed the original runs with the unaltered images by over 10%. Our findings suggest that wavelet analysis can help harvest the most valuable features in images of celestial bodies–leading to enhanced predictions in astronomical applications and perhaps bolstering modern astrophysical theory.

Prostate cancer is the second most frequent malignancy (after lung cancer) in men worldwide. Prostate tissue biopsies are usually graded using scores according to the Gleason grading system. This Gleason score is the most popular prognostic marker that reveals the potential aggressiveness of the disease. However, inter-observer variability in rating by human assessors is a major limiting factor. Such variability could lead to missing a severe case or suggesting unnecessary treatments. This study explores the discriminative ability of artificial intelligence (deep learning models) for Gleason score assessment. The study was designed to use whole-slide images of digitized H&E-stained biopsies of prostate tissues to automate the grading process and provide a remotely accessible clinical decision support system. Custom convolutional neural network architectures were trained on 10,616 images of prostate tissues. Gaussian filters were applied to pre-process the images and improve model performance. Transfer learning was applied to train eight machine learning architectures namely: Xception, VGG16 & 19, ResNet101, MobileNet, DenseNet121, EfficientNetB5 & B7. Efficient NetB7 had the best performance 85.2% compared with ground-truth classification by experts. Performance improves as more data is available. The model was deployed and hosted as a web application API on Google cloud service to ensure remote access. Tissue biopsy images can be uploaded and the corresponding Gleason score recovered immediately. This system reduces diagnostics turnaround time, increase throughput, and compensate for limited skills, especially in low resource settings.

To accurately identify high-quality functional wood with superior mechanical properties and enhance its durability, it is imperative to understand the relationships between the physical and mechanical attributes of diverse wood types. Presently, there exist issues related to accuracy, efficiency, and differentiation in studying these performance correlations. The Liang Kleeman (L-K) information flow theory, a causative analytical approach rooted in fundamental physics principles, offers swift computational capabilities. Furthermore, the coefficient of variation in L-K information flow quantitatively gauges the intensity of causal effects. Therefore, this article adopts a causal artificial intelligence perspective and introduces a wood performance analysis method based on L-K information flow.This study focuses on four Chinese fir varieties, including fast-growing Chinese fir (YKS), red heart Chinese fir (CSH, XXH), and iron heart Chinese fir (XXT). By computing and comparing variation coefficients of L-K information flow for various physical properties and their impact on mechanical properties, causal relationships between these properties are elucidated. These findings are then applied to predict wood mechanical properties, achieving a remarkable maximum accuracy of 90%.In the future, these findings will prove invaluable for the selection of high-quality wood and for improving the manufacturing process to prolong the service life of functionalized wood.

With a mild Mediterranean-type climate, Corsica is endemic for canine vector-borne diseases (CVBDs) such as dirofilariosis (a mosquitoes borne-diseases: MBDs), leishmaniosis and ehrlichiosis. The aim of this present study was to evaluate a monthly multi-modal prophylactic strategy (MMP) against CVBDs occurring in Corsica. The study was conducted as a comparative field trial in which eighty dogs allocated into two groups were included: (i) Group 1 consisted of 25 dogs under the MMP [per-os administration of 1.5 tablet of milbemycine oxime-praziquantel and a topical line-on application of a 3.6 mL solution of dinotefuran-permethrin-pyriproxyfen] and (ii) Group 2 under various real-life prophylactic treatment (RLP) based on the use of ectoparasiticide products [different formulations: deltamethrin, fluralaner, fipronil] and/or macrocyclic lactones based-products [milbemycin oxime/praziquantel, milbemycin oxime, moxidectin] during the period ranging from June to October 2017. All animals were followed for one year and had blood drawn at day 0, followed by follow-up at 6 and 12 months. Samples were screened for filariosis using molecular tools as well as for leishmaniosis and ehrlichiosis using indirect immunofluorescence assay (IFA). At the end of the study, no new cases of CVBDs were recorded within Group 1. In Group 2, the cumulative incidence of CVBDs was 20.0% (n= 11; p= 0.015) including dirofilarioses due to Dirofilaria immitis and/or D. repens, with 16.4% (n= 9; p=0.027). Ehrlichiosis was 5.5% (n= 3; p=0.241). No new cases of leishmaniosis were detected in Group 2. The data illustrated that, unlike the RLP treatment which failed to protect at least 20% of dogs, the MMP based on the concurrent administration of milbemycine oxime-praziquantel and dinotefuran-permethrin-pyriproxyfen is efficient to protect dogs against CVBDs in a high-risk area.

Maternal obesity and gestational diabetes predispose to metabolic disturbances in the next generation. Moreover, the lactation phase also stands as critical for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here we investigate the consequences of maternal diet lipid-rich diet during gestation and lactation, and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that fed a standard diet during gestation and lactation periods and an overnutrition group that fed a high-fat diet (HF, 60% lipid-rich) during the same phases. Offspring were analyzed at postnatal days 21, 28, and 2 months-old (PD21, PD28, PD60) for metabolic profile (weight, fasting glycemia insulin sensitivity, glucose tolerance) and euthanized for brain collection to evaluate by western blot markers of synaptic dynamics, metabolism and inflammation in the hypothalamus, hippocampus and prefrontal cortex. At 2 months-old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observe that female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuates with age. In offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. Offspring of HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to HF diet during pregnancy and lactation induces dysmetabolism in the offspring accompanied by heightened stress and anxiety. There was sexual dimorphism in metabolic traits but not behavioral phenotypes.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders.MELAS syndrome is a multi-organ disease that presents with a wide range of symptoms, such as dementia, epilepsy, lactic acidemia, myopathy, hearing loss, stroke-like episodes, diabetes, short stature, and myopathy. MELAS primarily affects tissue with high energy demands such as the brain, muscles, and heart. With 65–76% of affected people presenting at or before the age of 20, childhood is the typical age of onset. Genetic testing, imaging tests such as magnetic resonance imaging (MRI) scans, and other techniques, tests of blood, urine, and cerebrospinal fluid in addition to muscle biopsy (if necessary) may be used to diagnose MELAS syndrome. Management of MELAS remains largely supportive, focusing on symptom alleviation and metabolic stabilization. The long-term prognosis of MELAS is variable, influenced by factors such as age of onset, severity of symptoms, and presence of comorbidities. While some patients experience a relatively stable course with intermittent exacerbations, others may exhibit progressive neurological deterioration and multiorgan involvement. Early recognition, prompt intervention, and close monitoring are essential for optimizing outcomes and mitigating complications.Presenting here a case report of an occurrence of MELAS in a 31-year old male patient with chief complaints of perspiration, uneasiness and weight loss with increase in appetite and past history of bilateral hearing loss and vision loss in left eye.

We hypothesized that reticuloruminal temperature and pH, as well as cow activity, can be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows. Therefore, we aimed to detect the relationship between reticuloruminal temperature and pH, cow activity, and clinical mastitis in dairy cows. We randomly selected cows with clinical mastitis and clinical healthy cows (HG) out of 600 milking cows. We recorded the following parameters during the experiment: reticulorumen tem-perature (RR temp.), reticulorumen pH (RR pH), and cow activity. We used smaXtec boluses (smaXtec animal care technology®, Graz, Austria). In this investigation, reticulorumen data ob-tained seven days before diagnosis were compared to HG data from the same time period. CM cows were observed on the same days as the healthy cows. The healthy group’s RR pH was 7.32% higher than that of cows with CM. Reticulorumen temperature was also 1.25% higher in the CM group than in the control group. The healthy group had a higher average value for walking activity and was 17.37% higher than the CM group. The data of reticulorumen pH changes during 24 h showed that during the day, the pH changed from 5.53 to 5.83 in the CM group. By contrast, pH changed from 6.05 to 6.31 in the control group. The lowest reticulorumen pH in the CM group was detected on the third day before diagnosis. It was 15.76% lower than the highest reticulorumen pH detected on the sixth day before diagnosis. The lowest reticulorumen pH in CM cows was detected at 0 and 1 days before diagnosis. It was 1.45% lower than the highest reticulorumen pH detected on the second day before diagnosis. The lowest walking activity in the CM group was detected 0 days before diagnosis, 50.60% lower than on the fifth day before diagnosis. The lowest walking activity was detected 0 days before diagnosis, 39.57% lower than on the seventh day before diagnosis. In this study, we found that reticuloruminal temperature, reticuloruminal pH, and cow ac-tivity could be used as biomarkers for the early diagnosis of clinical mastitis in dairy cows.

The plague caused by the Yersinia pestis bacterium is primarily a flea-transmitted zoonosis of rodents that can also be conveyed to humans and other mammals. In this work, we analyzed the spatial and temporal distribution of rodents’ populations during active and quiescent periods of the plague in the municipality of Exu, northeastern Brazil. The geospatial analyses had shown that all rodent species occurred through the whole territory of the municipality with different hotspots for the risk of occurrence of the different species. Important fluctuation in the rodent populations was observed with a reduction in the wild rodent fauna following the end of a plague epidemic period, mostly represented by Necromys lasiurus and increase of the commensally species Rattus rattus. A higher abundance of rats might lead to an increased exposure of humans populations, favoring spillovers of plague and other rodent-borne diseases. Our analysis contributed to further highlight the role of the wild rodent species as the amplifier hosts and of the commensally rats (Rattus rattus) as the preserver hosts on the quiescent period on that transmission infection area.

Pomegranate juice possesses therapeutic properties against metabolic syndrome. Microencapsulation of pomegranate juice (MPJ) may extend its shelf life; however, further research is necessary to ascertain its comparative efficacy with fresh juice. This work evaluated the effect of (MPJ) in an animal model with induced metabolic syndrome (MetS). Male Wistar rats were induced-MetS by administering 30% sucrose orally for 22 weeks. Once MetS was verified in the animals, 7 groups were formed as follows: control (Ctrl); MetS, MetS+Placebo; Ctrl+MPJ; MetS+MPJ1 600, MetS+MPJ2 1800, and MetS+MPJ3 2900 mg/kg. Systolic and diastolic blood pressure, glucose, triglycerides, and total HDL-c levels in the MetS+MPJ groups improved significantly (p &lt; 0.05) vs. the MetS group at the end of the study. Microencapsulation maintained the anti-metabolic syndrome properties of pomegranate juice and could be used to control metabolic syndrome.

Over the last 20 years, begomoviruses have emerged as devastating pathogens, limiting the production of different crops worldwide. Weather conditions increase vector populations, with negative effects on crop production. In this work we evaluated the relationship between the in-cidence of begomovirus and climatic conditions before and during the crop cycle. Soybean and bean fields from the northwest (NW) of Argentina were monitored for 14 years and classified as moderate (≤50%) and severe (> 50%) according to the relative incidence. Two hundred bio-meteorological variables were constructed, summarizing meteorological data in 10-day peri-ods from June to March of each crop year. The studied variables included temperature, precipi-tation, relative humidity, wind (speed and direction), pressure, cloudiness and visibility. For bean, high maximum winter temperatures, low spring humidity and precipitation 10 days before planting correlated with severe incidence. In soybeans, high late winter and pre-planting tem-peratures, and low spring precipitations were found to be good predictors of high incidence of begomovirus presence. The results suggest that temperature and pre-sowing precipitations can be used to predict incidence status [predictive accuracy: 82% (bean) and 75% (soybean)]. Thus, these variables can be incorporated in early warning systems for crop management deci-sion-making to reduce the virus impact on bean and soybean crops.

Autoimmune bullous diseases (AIBDs) are a group of conditions marked by the formation of blisters and erosions on the skin and mucous membranes. Knowing that, most of the AIBDs are severe and resistant to treatment, we decided to look upon the nutritional aspect as a light for the future for both - patients and clinicians. In this review, we would like to summarize the evidence of the role of nutrition in pathogenesis and treatment of the following AIBDs: i) pemphigus, ii) bullous pemphigoid and mucous membrane pemphigoid, iii) dermatitis herpetiformis, and iv) epidermolysis bullosa aqusita.

Cafestol, a bioactive compound found in coffee, has attracted considerable attention due to its potential impact on cardiovascular health. This review aims to comprehensively explore the association between cafestol and cardiovascular diseases. We delve into the mechanisms through which cafestol influences lipid metabolism, inflammation, and endothelial function, all of which are pivotal in cardiovascular pathophysiology. Moreover, we meticulously analyze epidemiological studies and clinical trials to elucidate the relationship between cafestol and cardiovascular outcomes. Through a critical examination of existing literature, we aim to provide insights into the potential benefits and risks associated with cafestol concerning cardiovascular health.

Clopidogrel; a prescription drug to reduce ischemic events in cardiovascular patients; has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases; divided into poor and normal responders) were enrolled along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet function (PRU); PON1 abundance by western blotting and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p> 0.05). However; a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Stem cells can be used in cellular therapy. This happended in order to replace damaged cells or having aim to regenerate organs. The definition of stem cells can be extended. From this point of view, we can mention taking in consideration the idea in which it is known that these cells form the base of the building body. More than, we can mention that stem cells are characterized by two knowing properties namely differentiation and self renewal. Based on the observation that differentiation of adult stem cells into specific derivative scan be controlled by laboratory techniques, it is anticipated that adult stem cells may become the basis of therapies for many, and various types of medical conditions. Taking on stem cells, regenerative medicine (RM) it is known as being one of the hottest topics in biotechnology nowadays. From this purpose, stem cells can be used in regenerative medicine (RM). The principles of regeneration are found in different types of cultures, from long time ago. As an interdisciplinary field of research, regenerative medicine, play a great role in tissues and organs damaged reparation with a higher potential in transplantation if necessary.

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

It seems that natural compounds with bioactivity are the food constituents, present in the diets, that may provide protective effects on health due to their biochemical effects. The main benefits appear to be decline in oxidative stress and inflammation that are crucial in the pathogenesis of obesity, diabetes and metabolic syndrome. Apart from anti-inflammatory activity, these molecules also possess antifungal, and anti-infective preventative effects. Further evidence indicate that these bioactive molecules are the constituents, which are known to increase function of the foods. This review aims to emphasize that plant based diet is rich in phytochemicals such as antioxidants, vitamins, minerals, polyphenolics and flavonoids, amino acids and fatty acids, that are able to cause benefits via these compounds. These bioactive molecules can target mechanisms of oxidative stress and inflammation that are crucial in the management of metabolic syndrome. These antioxidant compounds appear to be essential component of plant based diets and are crucial for healthiness. Most investigators have proposed that bioactive compounds act as nutraceuticals which are able to regulate certain patho-physiological mechanisms responsible for metabolic diseases. The bioactive compoundspresent in the plant based diets are primary and secondary metabolites of nutritive and non-nutritive natural components generating health benefits by preventing or managing chronic disease or its symptoms. The bioactive compounds are known for their beneficial effects to health. Despite their small quantity in the diets, these bioactive compounds may trigger certain mechanisms that may cause alteration with improvement in health. It seems that most of the bioactive compounds co-existing in the plant-based diets, may be extremely healthful. However, if they are taken in excess, they can cause toxic effects. There is an urgent need to evaluate each bioactive compound to establish a beneficial quantity and a threshold of toxicity, while treating metabolic syndrome.

Aim: the main aim of this study is to compare the onset of effectiveness of mental nerve block with lingual infiltration and inferior alveolar nerve block on patients visiting dental hospital for extraction of mandibular anterior teeth. Materials and methods: The study was set in a clinical setting. This was a randomized controlled double-blind cross study, where 25 subjects received two treatments at an interval of at least 1 week in a within a dental hospital.Inferior alveolar nerve block and lingual nerve block injection is given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered for the right side. Mental nerve block along with lingual infiltration of the corresponding tooth was given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered on the left side.Visual analogue scale (VAS) was used in this study, which consists of a scale with range of 0-10 pain severity on which 0 indicated absence of pain and 10 the worst pain possible. The patients were asked to give scores corresponding to his/her pain, after IANB, mental nerve block and lingual infiltration and these scores were recorde.Results: From the results we can see that patients gave scores between 3-4, stating that they had moderate pain during extraction after administration of IANB (54%) (graph 2) and VAS scores of 0-1 were given by patients, which is suggestive of no pain during extraction after administration of Mental nerve block and lingual nerve infiltration (62%)Conclusion: Within the limits of the study we can conclude that mental nerve block along with lingual infiltration is an effective way to completely and quickly anaesthetise the central incisor to the 1st premolar region.

The COVID-19 pandemic has highlighted the vitalness of telehealth in our medical world, where considering a restructuring of healthcare services has become paramount. In fact, telemedicine has recently earned a valuable place in many specialties; and its implications in cardiology and cardiovascular medicine were among the leading interests. In this letter, we gathered previous evidence supporting the merit of telemedicine in the fields of cardiology and cardiovascular medicine—medical branches in which patients require meticulous care and continuous monitoring—as well as protrusions of concerns about the uncertainty regarding the efficacy of telemedicine’s future implications and technologies. In sum, in the context of this still on-going pandemic, medical institutions must strive to improve telehealth technologies and implement solid future research directions in this growing field—to be able to persevere in meeting the needs of the patients. As long as no conclusive evidence exists regarding the fields where telemedicine is most worthwhile, healthcare systems will always keep the dread of wasting resources on developing ineffective programs. We conclude that telemedicine has been attributed a considerable attention in managing cardiac and cardiovascular conditions; nevertheless, further studies with solid designs are still needed to confirm its validity and utility in those specialties.

There is a lack of knowledge concerning the effects of ambient heat exposure on morbidity in Northern Europe. Therefore, this study aimed to evaluate the relationships of daily summer-time temperature and heatwaves with cardiorespiratory hospital admissions in the Helsinki metropolitan area, Finland. Methods: Time-series models adjusted for potential confounders such as air pollution were used to investigate the associations of daily temperature and heatwaves with cause-specific cardiorespiratory hospital admissions, during summer months of 2001-2017. Daily number of hospitalizations was obtained from the national hospital discharge register, weather information from the Finnish Meteorological Institute. Results: Increased daily temperature was associated with decreased risk of total respiratory hospital admissions and asthma. Heatwave days were associated with 20.5% (95% CI: 6.9, 35.9) increased risk of pneumonia admissions and during long or intense heatwaves also with total respiratory admissions in the oldest age group (≥ 75 years). There were also suggestive positive associations between heatwave days and admissions due to myocardial infarction and cerebrovascular diseases. In contrast, risk of arrhythmia admissions was decreased 20.8% (95% CI: 8.0, 31.8) during heatwaves. Conclusions: Heatwaves, rather than single hot days, are a health threat affecting the morbidity even in a Northern climate.

Similar to humans, the renin-angiotensin-aldosterone system (RAAS) plays a key role in regulating blood pressure and body fluid homeostasis in dogs and cats. The classical RAAS pathway, which involves the conversion of angiotensin I to angiotensin II by the angiotensin converting enzyme (ACE), leads to aldosterone production and associated maladaptive effects in cardiovascular and renal diseases. Recent studies have highlighted the alternative RAAS pathway, which counteracts these effects through angiotensin 1-7, promoting vasodilation and reducing inflammation. Beyond RAAS modulation, RAAS inhibitors have been shown to exert significant anti-inflammatory properties. This is particularly relevant given the American Heart Association's recent focus on Cardiovascular-Kidney-Metabolic (CKM) health, which emphasizes the interconnected risks of cardiovascular disease, chronic kidney disease (CKD), type 2 diabetes, and obesity. These conditions share common pathophysiological pathways, including chronic inflammation, oxidative stress, and metabolic dysregulation. Advances in biomedical research, including the development of adult stem cell-derived canine organoids, provide impetus to study the effects of RAAS modulators and new CVD drugs on CKM health, with a focus on epithelial inflammation within the context of One Health.

Ticks drive a wide diversity of pathogens to a great variety of hosts, including humans. We conducted a tick surveillance study in northwestern Spain between 2014 and 2019. Ticks were removed from people and were identified. Tick numbers, species, development stages, evolution over time, seasonal and geographical distribution, and epidemiological characteristics of people bitten by ticks were studied. We collected ticks from 8143 people. Nymphs of Ixodes ricinus were the most frequently collected. Rhipicephalus bursa, Rhipicephalus sanguineus sensu lato (s.l), Hyalomma marginatum, Hyalomma lusitanicum, Dermacentor marginatus, Dermacentor reticulatus and Haemaphysalis punctata were also found, with adults as the main stage. Hyalomma spp. and R. bursa have been progressively increasing over time. Although bites occurred throughout the year, the highest number of incidents were reported from April to July. The distribution patterns of the tick species were different between the north and the south of the region, which was related to cases detected in humans of the pathogens they carried. Adult men were more likely to be bitten by ticks than women. Ticks were most frequently removed from adults from the lower limbs, while for children they were mainly attached to the head. Epidemiological surveillance is essential given the increase in tick populations in recent years, mainly of species potentially carrying pathogens causing emerging diseases in Spain, such as the Crimean Congo Hemorraghic Fever (CCFH).

Antibiotics are commonly used to treat infectious diseases. However, massive and inappropriate antibiotics usage cause many problems including the emergence and spread of antibiotic-resistant bacteria. To avoid this issue, in modern countries the interest of using probiotics in feed supplementation to promote health and prevent or treat intestinal infectious diseases in companion animals like dogs has been increasing. We evaluate the probiotic potential of Lactobacilli isolated from healthy dogs faeces. The isolated Lactobacilli were first confirmed by 16SrRNA sequencing, then in vitro tests were conducted to assess survival potential of Lactobacilli under simulated gastrointestinal conditions and adhesion ability to gut epithelia, effects on epithelial barrier function, anti-inflammatory activities, effects on defensin peptides (beta-defensin 3) and inhibitory effects on common pathogens. Lactobacilli showed considerable potential to survive in simulated gastrointestinal environmental conditions, low pH, high bile salt concentrations along with good adhesion properties with MODE-K cells. Pathogenic bacterial growth and their adhesion to MODE-K cells was significantly inhibited by Lactobacilli. Real-time PCR analyses further demonstrated that L. acidophilus strain AR1 and AR3 inhibit Salmonella-induced proinflammatory cytokines (IL-6, IL-8, 1ꞵ) production and reinforce expression of tight junction protein (occludin). None of the strain induce mRNA expression of beta-defensin 3 in MODE-K cells. Based on in vitro results the L. acidophilus strain AR1 has potential to be supplemented in canine feed. However, further in vivo studies investigating health-promoting effects are awaited.

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease that infects both human and animals. This is a descriptive study summarizes investigation and response to RVF outbreak, using surveillance data. A RVF outbreak occurred in Berber locality in northern Sudan. We identified 246 cases of RVF including seven deaths among humans, 119 deaths and 82 abortions among Livestock. Our entomological surveillance confirmed the presence of Anopheles arabiensis, An. stephensi, Aedes aegypti, Ae. vexans, Culex pipiens, Cx. Quinquefasciatus, and Cx. theileri in the area during the outbreak. In a comparison with another outbreak of Rift Valley fever in nearby area while ago, a multisectoral One Health response strategy has resulted in strengthening the health system through re-innovating health facilities and centres and training about 200 healthcare and emergency responders. Additionally, it reduced cases and fatalities among humans by 78% and 63%, respectively, and loss in livestock due to deaths and/or abortions by 82%. The added-value of implementing One Health strategy was saving more lives and resources, while strengthening the health system. We recommend the systematic institutionalization of One Health strategy in the country as a core part of the national prevention and control strategy for zoonotic diseases epidemics and pandemics.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

Periodontal diseases and Thalassemia Major (TM), which are two chronic inflammatory diseases, are associated with increased levels of proinflammatory cytokines in bio-fluids. Interleukin (IL)-6 and IL-8 have been identified as potent proinflammatory biomarkers in periodontal diseases as well as in patients with β-thalassemia (TM-β). This suggests that patients with TM-β and gingival inflammation have two chronic inflammatory conditions, each of which may affect the other. The objective of this pioneer research was to evaluate the effect of oral hygiene maintenance and care on serum levels of IL-6 and IL-8. 31 participants selected after screening and were given Non-surgical periodontal therapy(NSPT). IL-6 and IL-8 were evaluated by enzyme linked immunohistochemistry assay (ELISA) at baseline and compared at 6 weeks after NSPT. Statistical analysis was done with SPSS v23. The comparison from the baseline to 6-weeks follow-up for both IL-6 and IL-8 was done using Wilcoxon Signed rank test. The descriptive statistics are represented as median and inter quartile range (IQR). Highly significant improvement (p-&lt;0.000) was found for IL-6 and IL-8 when compared at 6 weeks from baseline. Results provide a gateway to new modality in lowering systemic burden of the disease, thereby reducing morbidity, via local measures or oral care.

Lycopene is a compound of colored origin that shows strong antioxidant activity. The ability to neutralize free radicals by lycopene is the basis of its pro-health effect, including the ability to inhibit the development of many civilization diseases. Therefore, this study focuses on the importance of the antioxidant effect of lycopene in inhibiting the development of such diseases as cardiovascular diseases, diseases of the etiology of etiology, diseases within the nervous system.

Objective: The purpose of the present study was to analyze the management of dental extractions in patients affected by coagulation disorders in order to prevent bleeding intraoperative and postoperative complications. Subjects and Methods: This study included 17 patients with a diagnosis of a coagulation disorder, who had been subjected to a single or multiple dental extraction. Recombinant activated Factor VII was administered in those patients who were affected by a deficit of factor VII ranged between 10,5% and 21%. The other patients were treated locally with tranexamic acid. Results: A total of 50 teeth were extracted, 7 by surgical extraction and 43 by simple extraction. Of the 17 patients included 9 of them suffering from factor VII deficiency, 5 from factor V deficiency, 1 from Glanzmann's thrombasthenia and 2 from Haemophilia A. Pretreatment with recombinant activated factor VII was performed on a total of 8 patients with factor VII deficiency; the remaining 9 patients underwent tranexamic acid treatment. 1 hemorragic postoperative complication was observed. Conclusions: Surgical and no surgical extractions appear to be a safe procedure for patients affected by coagulation disorders when appropriate prophylaxis is adopted.

Although genome-wide association studies (GWAS) have identified several hundred loci associated with autoimmune diseases, their mechanistic insights are still poorly understood. The human genome is more complex than common single nucleotide polymorphisms (SNPs) that are interrogated by GWAS arrays. Some structural variants such as insertions-deletions, copy number variations, and minisatellites that are not very well tagged by SNPs cannot be fully explored by GWAS. Therefore, it is possible that some of these loci may have large effects on autoimmune disease risk. In addition, other layers of regulations such as gene-gene interactions, epigenetic-determinants, gene and environmental interactions also contribute to the heritability of autoimmune diseases. This review focuses on discussing why studying these elements may allow us to gain a more comprehensive understanding of the aetiology of complex autoimmune traits.

In this work, the properties of a composition based on synthetic rubber ethylene-propylene ter-polymer and polymers with functional groups of the mixture are studied. Low efficiency of some compositions based on ethylene and propylene copolymer limits their use in the production of tires and rubber products. Therefore, we conducted a study to improve the disadvantages of SREPT-60 using butyl rubber + choro polyisoprene + butadiene-nitrile + butadiene styrene rubber and adding a plasticizer to the composition = α, methacrylate-(bis-diethylene glycol phthalate) -(btegf-9) The data obtained showed that a number of its indicators of rubber based on them were improved. Tear resistance, resistance to repeated stretching increased, adhesion of the composition to metal, chemical resistance increased, the degree of swelling in benzene and gasoline-benzene mixture decreased. Compositions based on the mixture SREPT-60 using butyl rubber + choro polyisoprene + butadiene-nitrile + butadiene styrene rubber and adding a plasticizer to the composition = α, methacrylate-(bis-diethylene glycol phthalate) -(btegf-9) +Dioctyl phthalate: (70:20:10) have high resistance to swelling in an aggressive environment (Benzene, gasoline, alcohol, acid, oil, etc.) mixture.

This work explores the significance of toothbrushing in maintaining optimal oral health, delving into its benefits, proper techniques, and types of toothbrushes. The primary cause of caries, periodontal diseases, and halitosis is oral biofilm development. One of the most fundamental practices in maintaining oral health is toothbrushing. Studies have confirmed that mechanical procedures for controlling plaque and toothbrushing, in particular, significantly decrease plaque accumulation. The significance of teeth brushing in preventing dental caries has been well-acknowledged for a considerable period. Dentists recommend brushing twice daily for at least two min to ensure thorough cleaning. Unfortunately, precise guidelines from dental associations are often missing. Authors mention that two min of brushing are insufficient for significant plaque removal; plaque removal increases with augmented brushing time, with maximum removal at 180 s. Multiple studies have documented that engaging in the practice of brushing one’s teeth twice a day has a preventive impact. Various toothbrush designs, including both manual and electric options, have been created to improve the elimination of dental biofilm and reduce the accumulation and persistence of bacteria. In conclusion, toothbrushing is a simple yet incredibly important practice for maintaining oral health. The benefits extend beyond just a bright smile, encompassing caries, gum disease, halitosis prevention, and the preservation of tooth enamel. Adhering to proper toothbrushing techniques, selecting the right toothbrush, and understanding the connection between oral health and overall well-being can lead to a healthier life. To foster favorable toothbrushing behaviors among the population, dental practitioners and public health experts must know the factors that influence toothbrushing habits.

Introduction: In Traditional Chinese Medicine (TCM), tongue diagnosis plays an important role. Besides shape, colour and textural attributes of tongue regions have significance due to their association with different organs (viz. heart, lung, kidney-bladder, liver-gallbladder and stomach-spleen) in health and disease. Although numerous quantitative methods have been proposed to reduce inter and intra observer variability in tongue diagnosis, almost all of them considered only global colour/ textural features i.e. from entire body of tongue. In this work, regional colour and texture information of tongue have been analysed for healthy subjects (NOM) and patients suffering from chronic acidity-indigestion (ACD). Methods: Tongue boundaries are marked manually in each image and then tongue bodies are automatically partitioned into five regions linked with said internal organs. Rough assessments of regions’ boundaries are obtained from literature and then they are fine-tuned according to experts’ advice. As boundaries are not well defined, regions near the common boundary of two or more organs, are not assigned to any organ. Several first and second order statistical features based on grey scale intensities and a* values of LAB colour space (indicative of redness) have been extracted from five different regions of tongue images. Intragroup analysis using Wilcoxon signed rank test compared different regions within individual study group. Additionally, intergroup analysis using Wilcoxon rank sum test compared tongues of NOM with ACD for each region separately. Results: Intragroup analysis reveals a* values are statistically different (p&lt;0.01) between stomach-spleen and liver-gallbladder regions for ACD while no significant change of a* are noted between these regions of normal tongue. It was found from intergroup analysis that correlation (one of the second order texture features extracted from grey scale images) of heart region has significantly decreased while correlation of kidney, liver-gallbladder and stomach-spleen regions significantly increased from NOM to ACD. Conclusion: This study sheds light on importance of inclusion of regional textural analysis of tongue in quantitative studies and can be applied to automated tongue diagnosis for other diseases.

Thalassemia is one of the most prevalent genetic disorders worldwide which has been previously found to have an association with several physiological and organ complications. Several studies found both its positive and inverse correlation with glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of thalassemia with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles we finally could include 15 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was -6.45, 95%CI: -18.50, 5.60 (P<0.00001), which indicated a negative correlation of GFR with thalassemia. The sensitivity analyses found one study as a slight outlier and reanalyzing the data excluding that study MD was achieved as -13.90, 95%CI: -24.22, -3.59 (P<0.00001) which even strongly supports our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to thalassemia patients.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.