Single-Anastomosis Duodeno-Ileal bypass with Sleeve Gastrectomy (SADI-S) is a modification of the duodenal switch in which only one anastomosis is performed, with a longer common limb and an expected less malabsorptive effect. The present study analyzes presentation and treatment of malnutrition after SADI-S. 258 consecutive patients undergoing SADI-S between May 2007 and September 2017 were included. The common limb length was 200 cm in 50 cases, 250 cm in 156 and 300 in 52. 30 patients were admitted for severe hypoalbuminemia and 16 patients were submitted to revisional surgery and constitute the series of our study. Mean weight before reoperation was 57 kg and mean body mass index (BMI) was 21 kg/m2. Mean number of daily bowel movements was 5,6. Mean time to reoperation was 56 months. Revisional surgery consisted mainly in elongation of the common limb. Mean weight regain was 14 kg and mean final BMI was 26 kg/m2. Daily bowel movements were decreased to 1,3. Factors related to hypoalbuminemia were hypertension, poor controlled diabetes, age over 55 years and a shorter common limb. Although SADI-S is expected to be less malabsorptive than previous biliopancreatic diversions, caution has to be taken with selected patients to avoid postoperative malnutrition.

Brain capillary endothelial cell(s) (BECs) have numerous functions including their semipermeable interface-barrier (transfer and diffusion of solutes), trophic (metabolic homeostasis), tonic (vascular hemodynamics), and trafficking (vascular permeability, coagulation, and leukocyte extravasation) functions to provide brain homeostasis. BECs also serve as the brain’s sentinel cell of the innate immune system and are capable of antigen presentation. In metabolic syndrome (MetS) there are two regions resulting in proinflammatory signaling of BECs. Namely, visceral adipose tissue depots supplying excessive peripheral cytokines/chemokines (pCC) and gut microbiota dysbiotic regions supplying excessive soluble lipopolysaccharide (sLPS), small LPS-enriched extracellular vesicle exosomes (lpsEVexos), and pCC. This dual signaling of BECs at their receptor sites results in BEC activation and dysfunction (BECact/dys) and neuroinflammation. sLPS and lpsEVexos signal BECs toll-like receptor four, which then signals translocated nuclear factor kappa B (NFkB). Translocated NFkB promotes the synthesis and secretion of BEC proinflammatory cytokines and chemokines. Specifically, the chemokine CCL5 (RANTES) is capable of attracting microglia cells to BECs. BEC neuroinflammation activates perivascular space(s) (PVS) resident macrophages. Excessive phagocytosis by reactive resident PVS macrophages results in a stagnation-like obstruction, which along with increased capillary permeability due to BECact/dys could expand the fluid volume within the PVS to result in enlarged PVS (EPVS). Importantly, this remodeling may result in pre- and post-capillary EPVS that would contribute to their identification on T2-weighted MRI, which are considered to be biomarkers for cerebral small vessel disease.

This text deals with exploring random solutions for generalized nonlinear variational inequality problems. Using the Fan-KKM theorem and Aumann's measurable selection theorem, we are able to prove the existence and uniqueness of random solution sets under the conditions of monotonicity and convexity. Additionally, we use Minty's lemma to demonstrate the compactness and convexity of the random solution sets.

Hydrogen is the lightest atom and composes roughly half of the atomic content in macromolecules, yet their location can only be inferred or predicted in most macromolecular structures. This is because hydrogen can rarely be directly observed by the most common structure determination techniques (such as X-ray crystallography and electron cryo-microscopy). However, knowledge of hydrogen atom positions, especially for enzymes, can reveal protonation states of titratable active site residues, hydrogen bonding patterns, and the orientation of water molecules. Though we know they are present, this vital layer of information, which can inform a myriad of biological processes, is frustratingly invisible to us. The good news is that, even at modest resolution, neutron crystallography (NC) can reveal this layer and has emerged this century as a powerful tool for elucidating enzyme catalytic mechanisms. Due to its strong and coherent scattering of neutrons, incorporation of deuterium into the protein crystal amplifies the power of NC. This is especially true when solvation and the specific participation of key water molecules are crucial for catalysis. Neutron data allow the modeling of all three atoms in water molecules and have even revealed previously unobserved and unique species such as hydronium (D3O+) and deuteroxide (OD-) ions as well as lone deuterons (D+). Herein, we briefly review why neutrons are ideal probes for identifying catalytically important water molecules and these unique water-like species, limitations in interpretation, and four vignettes of enzyme success stories from disparate research groups. One of these groups was that of Dr. Chris G. Dealwis, who died unexpectedly in 2022. As a memorial appreciation of his scientific career, we will also highlight his interest and contributions to the neutron crystallography field. As both the authors were mentored by Chris, we feel we have a unique perspective on his love of molecular structure and admiration for neutrons as a tool to query those structures.

: We report the synthesis and characterization of Mn(III) chloride (MnIIICl3) complexes coordinated with N-oxide ylide ligands, namely trimethyl-N-oxide (Me3NO) and pyridine-N-oxide (PyNO). The compounds are reactive and, while isolable in the solid-state at room temperature, readily decompose into Mn(II). For example, “[MnIIICl3(ONMe3)n]” decomposes into the 2D polymeric network compound complex salt [MnII(µ-Cl)3MnII(µ-ONMe3)]n[MnII(µ-Cl)3]n•(Me3NO•HCl)n (4). The reaction of MnIIICl3 with PyNO forms varied Mn(III) compounds with PyNO coordination and these react with hexamethylbenzene (HMB) to form the chlorinated organic product 1-cloromethyl-2,3,4,5,6-pentamethylbenzene (8). In contrast to N-oxide coordination to Mn(III), the reaction between [MnIIICl3(OPPh3)2] and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) resulted in electron transfer forming d5 manganate of the [TEMPO] cation instead of TEMPO–Mn(III) adducts. The reactivity affected by N-oxide coordination is discussed through comparisons with other L–MnIIICl3 complexes within the context of reduction potential.

Background: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neuro-degeneration and disease progression. Methods: We evaluated the concentrations of the param-eters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) and the se-lected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. Results: The levels of GFAP, S100B and UCHL were higher in the PMS group compared to RRMS as opposed to the levels of NF-H. We observed a positive correlation be-tween the selected pro-inflammatory cytokines and the parameters of brain injury. The Ex-panded Disability Status Scale score (EDSS) increased with GFA and NF-H levels and correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. Conclusions: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Glycosylation is a complex post-translational modification that conveys functional diversity to glycoconjugates. Cell surface glycosylation mediates several biological activities such as induction of intracellular signaling pathway and pathogen recognition. Red blood cell (RBC) membrane N-glycans determine blood type and influence cell lifespan. Although several proteomic studies were carried out, glycosylation of RBC membrane proteins has not been systematically investigated. This work aims at exploring the human RBC N-glycome by high-sensitivity MALDI-MS techniques to outline a fingerprint of RBC N-glycans. To this purpose, MALDI-TOF spectra of healthy subjects harboring different blood groups were acquired. Results showed the predominant occurrence of neutral and sialylated complex N-glycans with bisected N-acetylglucosamine, core- and/or an-tennary fucosylation. In the higher mass region these species presented with multiple N-acetyllactosamine repeating units. Amongst the detected glycoforms, the presence of glycans bearing ABO(H) antigens allowed us to define a distinctive spectrum for each blood group. For the first time, advanced glycomic techniques have been applied to a comprehensive exploration of human RBC N-glycosylation, providing a new tool for the early detection of distinct glycome changes associated with disease conditions as well as to understand pathogens molecular recognition.

Protein oligomerzation is key to countless physiological processes, but also to abnormal amyloid conformations implicated in over 25 mortal human diseases. Angiogenin (h-ANG), a ribonuclease A family member, produces RNA fragments that regulate ribosome formation, the creation of new blood vessels and stress granule function. Too little h-ANG activity leads abnormal protein oligomerization resulting in Amyotrophic Lateral Sclerosis (ALS) or Parkinson’s disease. While a score of disease linked h-ANG mutants has been studied by X-ray diffraction, some elude crystallization. There is also debate regarding the structure that RNA fragments adopt after cleavage by h-ANG. Here, to better understand the beginning of the process that leads to aberrant protein oligomerization, the solution secondary structure and residue-level dynamics of WT h-ANG and two mutants: H13A and R121C, are characterized by multidimensional heteronuclear NMR spectroscopy under near physiological conditions. All three variants are found to adopt well folded and highly rigid structures in solution, although the elements of secondary structure are somewhat shorter than those observed in cystallography studies. R121C alters the environment of nearby residues only. By constrast, the mutation H13A affects local residues as well as nearby active site residues residues K41 and H119. The conformation characterization by CD and 1D 1H NMR spectroscopies of tRNAAla before and after h-ANG cleavage reveals a retention of most duplex structure and little or no G-quadruplex formation.

The research paper presents a new approach towards constructing motion equations for structures with attached MTMDs (multiple tuned mass dampers). A primary system, with MDOF (multiple dynamic degrees of freedom) was reduced to an equivalent system with a SDOF (single degree of freedom) through the modal approach, and equations from additional MTMDs were added to a thus-created system. Optimization based on H2 and H∞ for the transfer function associated with the generalized displacement of an SDOF system. The research work utilized GA (genetic algorithms) and SA (simulated annealing method) optimization algorithms to determine the stiffness and damping parameters for individual TMDs. The effect of damping and stiffness (MTMD tuning) distribution depending on the number of TMDs was also analyzed. The paper also reviews the impact of primary system mass change on the efficiency of optimized MTMDs, as well as confirms the results of other authors involving greater MTMD effectiveness relative to a single TMD.

The sound field properties for non-cavitating marine propellers are studied using FW-H (Ffowcs William-Hawkings) acoustic analogy and BEM (Boundary Element Method) approach. For the first time, the FW-H formula to calculate acoustic pressure generated by the propeller wake sheet is proposed. The corresponding sound signal can be dominant up to several kilometres. Secondly, non-physical fictitious volume flux is observed when the permeable FW-H approach is used together with BEM. The reason is explained and a virtual source correction method is proposed to solve this problem. Furthermore, analytical analyse show that the second thickness term and the first two loading terms in Farassat 1A formula are important, and the others are negligible. The numerical studies show that the permeable FW-H approach produces underestimation when compared to the direct FW-H method, and the underestimation is severer for larger permeable surface and higher frequency. It is also found that the first loading term in Farassat 1A formula is the dominant source term in the direct FW-H method, while the first thickness term is dominant when the permeable FW-H approach is used.

The Koka gold deposit is located in the Elababu shear zone between the Nakfa terrane and the Adobha Abiy terrane, NW Eritrea. Based on the paragenetic study two main stages of gold mineralization were identified in the Koka gold deposit: 1) an early stage of pyrite-chalcopyrite-sphalerite-galena-gold-quartz vein; and 2) a second stage of pyrite-quartz veins. NaCl-aqueous inclusions, CO2-rich inclusions, and three-phase CO₂-H₂O inclusions occur in the quartz veins at Koka. The ore-bearing quartz veins formed at 268℃, from NaCl-CO₂-H₂O(-CH₄) fluids averaging 5 wt% NaCl eq. The ore-forming mechanisms include fluid immiscibility during stage I, and mixing with meteoric water during stage II. Oxygen, hydrogen and carbon isotopes suggest that the ore-forming fluids originated as mixtures of metamorphic water, meteoric water and magmatic water, whereas sulfur isotope suggest an igneous origin. Features of geology and ore-forming fluid at Koka deposit are similar to those of orogenic gold deposits, suggesting the Koka deposit might be an orogenic gold deposit related to granite.

A series of penta-1,4-dien-3-one containing a H-phosphonate scaffold were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and HRMS. Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compounds 3c and 3o exhibited substantial antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In addition, compounds 3c, 3f, and 3r showed remarkable curative activities against tobacco mosaic virus (TMV), with 50% effective concentration (EC50) values of 290.0, 234.0, and 373.6 μg/mL, respectively. These were superior to that of ningnanmycin (386.2 μg/mL). Compound 3r exhibited comparative protective activity against TMV, with an EC50 value of 291.1 μg/mL, which was better than that of ningnanmycin (297.1 μg/mL). Notably, the solubility of all title compounds improved relative to the lead compound curcumin. These results suggest that penta-1,4-dien-3-one containing a H-phosphonate scaffold may be considered as an activator for antibacterial and antiviral agents.

The number of citations that a paper has received is the most commonly used indicator to measure the quality of research. Researchers, journals, and universities want to receive more citations for their scholarly publications to increase their h-index, impact factor, and ranking respectively. In this paper, we tried to analyses the effect of the number of available Google Scholar versions of a paper on citations count. We analyzed 10,162 papers which are published in Scopus database in year 2010 by Malaysian top five universities. Then we developed a software to collect the number of citations and versions of each paper from Google Scholar automatically. The result of spearman correlation coefficient revealed that there is positive significant association between the number of Google Scholar versions of a paper and the number of times a paper has been cited.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases including PD and type 2 diabetes mellitus (T2DM) suggesting a crucial interplay between the gut–brain axis. GLP-1R agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between February 2023 and February 2024. We used the terms “GLP-1”, “GLP-1 receptor”, “GLP-1R agonists”, “PD”, “T2DM”, “insulin”, “neurodegenerative disease”, “glucose”, “animal models”, “clinical trials” in different combinations. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies are also very promising enhancing the possibility of adding GLP1-R agonists in the current armamentarium of drugs available for PD treatment.

We report an unusual case of Terson's syndrome that resulted in the di-agnosis of a right posterior communicating artery aneurysm. Interest-ingly Terson's syndrome presented with Roth spot resembling features accompanied by third nerve palsy in a patient without any disturbance of consciousness. To our knowledge, the association of Terson's syndrome with third nerve palsy has not been described before in the absence of radiologically diagnosed subarachnoid haemorrhage. We present the case of a 48-year old woman who presented in the De-partment of Emergencies of the University Hospital of Patras with right-sided complete pupil-involving third nerve palsy combined with bilateral Terson's syndrome. More precisely, fundoscopy revealed multi-ple scattered intra- and pre-retinal haemorrhages in both eyes while some retinal haemorrhages had a white-centered pattern resembling Roth spots. Neurological examination revealed no nuchal rigidity or any other neurological signs. The Glasgow coma scale was 15/15. A cerebral computed tomography angiography revealed a 5mm aneurysm of the right posterior communicating artery and the patient underwent a mi-crovascular clipping operation after craniotomy. The significant contribution of the ophthalmological consultation to the appropriate and timely diagnosis and management of a life-threatening condition is highlighted.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

Cytokinesis, the process by which the cytoplasm divides to generate two daughter cells after mitosis, is a crucial stage of the cell cycle. Successful cytokinesis must be coordinated with chromosome segregation and requires the fine orchestration of several processes, such as constriction of the actomyosin ring, membrane reorganisation, and, in fungi, cell wall deposition. In Saccharomyces cerevisiae, commonly known as budding yeast, septins play a pivotal role in the control of cytokinesis by assisting the assembly of the cytokinetic machinery at the division site and controlling its activity. Yeast septins form a collar at the division site that undergoes major dynamic transitions during the cell cycle. This review will discuss the functions of septins in yeast cytokinesis, their regulation and the implications of their dynamic remodelling for cell division.

Background and objective: Symptoms of most neurodegenerative diseases, including Parkinson’s disease (PD), usually do not occur until substantial neuronal loss occurs. This makes the process of early diagnosis very challenging. Hence, this research used variant call format (VCF) analysis to detect variants and novel genes that could be used as prognostic indicators in the early diagnosis of prodromal PD. Materials and Methods: Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI), and we analyzed prodromal patients with gVCF data collected in the 2021 cohort. A total of 304 participants were included, including 100 healthy controls, 146 prodromal genetic individuals, 21 prodromal hyposmia individuals, and 37 prodromal RBDs. A pipeline was developed to process the samples from gVCF to reach variant annotation and pathway and disease association analysis. Results: Novel variant percentages were detected in the analyzed prodromal subgroups. The prodromal subgroup analysis revealed novel variations of 1.0%, 1.2%, 0.6%, 0.3%, 0.5%, and 0.4% for the genetic male, genetic female, hyposmia male, hyposmia female, RBD male, and RBD female, respectively. Interestingly, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) that were recently detected in PD patients were detected in the prodromal stage of PD. Conclusion: Genetic biomarkers are crucial for the early detection of Parkinson’s disease and its prodromal stage. The novel PD genes detected in prodromal patients could aid in the use of gene biomarkers for early diagnosis of the prodromal stage without relying only on phenotypic traits.

Dynamic virtual testing by Hardware in the Loop (HIL) real time simulation systems is common to minimize physical tests to validate and verify control algorithms, logics and software, under normal and emergency conditions. The accurate but costly HIL models setup activities could have an extended use to simulate faulty conditions that are seldom observable in the real system, yet they must be detected in advance and recognized. Data driven diagnostic methods have reached a mature development, in various sectors, proving effective in early detecting slowly varying deviations from nominal patterns of signals, even without a priori knowledge of their nature and behavior. These methods rely on vast amount of data logged from real systems that are ever and ever richer of monitoring telemetries that are worth being exploited. However, due to the usually reliable and safe systems being managed, it is often difficult to collect enough data on anomalous situations to validate fault detection and isolation and limit false positives. HIL model-based simulations allow generating and observing operational domains or transients rarely observed in real operations. This allows identifying the signals that are most correlated to faults and that could be selected to setup data-based diagnostic models of parts or subsystems, which are more suitable than the whole HIL model for online diagnostics, as well as to identify the features and trends that are most symptomatic of anomalous conditions.

The article proposes asymptotic methods for calculating Sommerfeld integrals, which enable us to calculate the integral using the expansion of a function into an infinite power series at the saddle point, where the role of a rapidly oscillating function under the integral can be fulfilled either by an exponential or by its product by the Hankel function. The proposed types of Sommerfeld integrals are generalized on the basis of integral representations of the Hertz radiator fields in the form of the inverse Hankel transform with the subsequent replacement of the Bessel function by the Hankel function. It is shown that the numerical values of the saddle point are complex. During integration, auxiliary or so-called standard integrals, which contain the main features of the integrand function, were used. As a demonstration of the accuracy of the technique, a previously known asymptotic formula for the Hankel functions was obtained in the form of an infinite series. The proposed method for calculating Sommerfeld integrals can be useful in solving the half-space Sommerfeld problem. An example is the expression in the form of an infinite series for the magnetic field of reflected waves, obtained directly through the Sommerfeld integral (SI).

The variation of the cationic composition in I2-II-IV-VI4 semiconductor compounds is an effective tool for altering their properties in a controlled manner. In particular, a partial substitution of Cu for Ag in kesterite Cu2ZnSnS4 was proposed to suppress Cu-Zn antisite defects and the improve photovoltaic performance. However, the efficiency of this approach may substantially depend on the fabrication route. Here, we report on the synthesis of (Cu,Ag)-Zn-Sn-S (CAZTS) and Ag-Zn-Sn-S (AZTS) nanocrystals (NCs) by means of "green" chemistry in aqueous solution and their detailed characterization by Raman spectroscopy and by several complementary techniques. Through a systematic variation of the nominal composition and quantification of the constituent elements in CAZTS and AZTS NCs by XPS, we identified the vibrational Raman and IR fingerprints of both the main AZTS phase and secondary phases of Ag-Zn-S and Ag-Sn-S compounds (for the first time). The formation of the secondary phases of Ag-S and Ag-Zn-S cannot be avoided entirely for this type of synthesis. The Ag-Zn-S phase, having its bandgap in near infrared range, is the reason of the non-monotonous dependence of the absorption edge of CAZTS NCs on the Ag content, with a trend to redshift even below the bandgaps of bulk AZTS and CZTS.

Recently, the conformable derivative and its properties have been introduced. In this paper, we propose and prove some new results on conformable Boundary Value Problems. First, we introduce a conformable version of classical Sturm´s separation, and comparison theorems. For a conformable Sturm-Liouville problem, Green's function is constructed, and its properties are also studied. In addition, we propose the applicability of the Green´s Function in solving conformable inhomogeneous linear differential equations with homogeneous boundary conditions, whose associated homogeneous boundary value problem has only trivial solution. Finally, we prove the generalized Hyers-Ulam stability of the conformable inhomogeneous boundary value problem.

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

After three years of the onset of the pandemic, there is scarce evidence about how COVID-19 disease affect the female reproductive system, and consequently, the menstrual cycle. Since the common causes of secondary amenorrhea are considered as exclusion criteria in the studies about menstrual changes following SARS-CoV-2 infection, the prevalence of this event and the influencing factors in formerly menstruating women remains unknown. A retrospective observational cross-sectional study was conducted on Spanish adult women (N= 17,512), using an online survey; a subpopulation of SARS-CoV-2-infected-formerly menstruating women was included in the present analysis (n= 72). Collected data included general characteristics, medical history, and specific information about COVID-19 disease. 38.9% of the respondents experienced menstrual-related disturbances after suffering from the COVID-19 disease, unexpected vaginal bleeding being the most common (20.8%). Other alterations related with the length – “shorter” by 12.5% − and the flow − “heavier than usual” 30.3% − of the menstrual bleeding were reported. The binary logistic regression showed that being a perimenopausal woman (AOR 4.608, CI 95%, 1.018 – 20.856, p = 0.047) and having heavy menstrual bleeding (AOR 4.857, CI 95%, 1.239 – 19.031, p=0.023) are influential factors. This evidence could help health professionals to provide scientifically up-to-date information to their patients, empowering them to actively manage their reproductive health, especially in those societies where menstrual health is still a taboo.

Nitrogen oxides (NOx), pivotal atmospheric pollutants, significantly imperil the environment and human health. The CH4-SCR process, leveraging the abundant and accessible methane (CH4), emerges as a promising avenue for NOx abatement. Previous studies have demonstrated that zeolite support with twelve-membered ring (12-MR) and five-membered ring (5-MR) structures are susceptible to framework collapse in the presence of water, leading to catalyst deactivation. Consequently, there is a necessity to explore novel zeolites with enhanced hydrothermal stability for application in CH4-SCR processes. This research introduced for the first time an investigation into a novel In-H-SSZ-39 catalyst, synthesized via ion exchange and meticulously optimized for preparation conditions, including calcination temperature, In ions concentraiton, and reaction conditions, including CH4/NO ratio, O2 concentration, water vapor content, and Gas hourly space velocity (GHSV). Notably, the In/H-SSZ-39 catalyst achieved superior performance of 42.1% at 605 °C, with a calcination temperature of 500 °C and an In ion concentration of 0.066 M, under CH4/NO ratio of 1.5:1, 10% O2, and GHSV of 21000 h-1. In addition, the catalytic performance was influenced by the concentration of water vapor and the GHSV value.

On the H-type group G⊂Rm×Rn, we study the existence of solutions for the Brezis-Nirenberg problem

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

Edible oils have commercial and nutritional value due to the presence of essential fatty acids. They can be consumed fresh in the form of capsules known as nutraceuticals. The quality of such products is of interest to the consumer. In this context, this study describes a method based on high resolution nuclear magnetic resonance (NMR) and Fourier transform mid-infrared spectroscopic analysis (FTIR), combined with statistical analyzes to differentiate different edible oils used as nutraceuticals in Brazil by fatty acid content. Through the analysis of 1H NMR spectra, the levels of saturated and unsaturated fatty acids in edible oils were characterized and quantified. Statistical analysis of the data confirmed the real distinction between nutraceutical raw materials, with emphasis on ω-9, ω-6 and ω-3 fatty acids. The analytical approach presented also demonstrated potential to identify the origin (animal or vegetable) of edible oils used as nutraceuticals.

Cutaneous T cell lymphoma (CTCL) is a devastating, potentially fatal T lymphocyte malignancy affecting the skin. Despite all efforts, the etiology of the disease remains unknown. Infectious agents have long been suspected as factors or co-factors in CTCL pathogenesis. This review deals with the panel of bacterial and viral pathogens that have been investigated so far in an attempt to establish a potential link between infection/carriage and CTCL development. A special focus is given to a recently discovered human protoparvovirus, namely the cutavirus (CutaV), which has emerged as a plausible CTCL etiological agent. Available evidence in support of this hypothesis as well as alternative interpretations and uncertainties raised by some conflicting data are discussed. The complexity and the multifacetedness of the Parvoviridae family of viruses are illustrated by presenting another protoparvovirus, the rat H-1 parvovirus (H-1PV). H-1PV belongs to the same genus as the CutaV but carries a considerable potential for therapeutic applications in cutaneous lymphoma.

Nanoindentation load-depth (P-h) plots is the basis for determination of mechanical properties of the samples and is especially vital for thin coatings deposited on substrates of various mechanical makeup from amorphous-brittle (borosilicate glass) to Silicon (having different crystallographic texture) to ductile substrates like stainless steel as well other aspects like indenter tip shape. The elastic-plastic response by simulated P-h plots as per modified empirical relations have been presented. The outcomes of this computational studies enlighten the database on the P-h plots for various coating/substrate systems and shall aid in the analysis of experimental P-h plots obtained,

Sumatriptan is a serotonin receptor agonist approved by FDA in 1992 to treat migraines. Its’ solid form used in commercially available drugs Imitrex, Treximet, Onzetra Xsail and Zembrace symtouch is sumatriptan succinate. Herein we report on crystal structure of sumatriptane succinate hemi(ethanol solvate), HSum+·HSucc–·0.5EtOH, its comparison with previously reported solids containing derivatives of sumatriptan.

This paper addresses a mode-dependent state-feedback H∞ control for descriptor hybrid systems, considering both the absence and presence of actuator saturation. Firstly, the necessary and sufficient conditions for the stochastic admissibility criterion with H∞ performance ? of the closed-loop system is proposed. Given the proposed non-convex condition, the author reformulates it into linear matrix inequalities (LMIs). Then, to extend the result to the systems with actuator saturation, the actuator saturated control input is expressed as a linear combination of given state-feedback control input and a virtual control input that remains under the saturation level. To verify this expression, the set invariant condition is also suggested by using the singular mode-dependent Lyapunov function candidate. Therefore, the LMI conditions for the existence of the mode-dependent state-feedback H∞ control and the ellipsoidal shape of invariant set are successfully derived. Two numerical examples demonstrate the effectiveness of the proposed approach in optimizing H∞ performance $\gamma$ and identifying the largest invariant set.

This paper presents various procedures for determining the optimal control law for a wing section in compressible flow. The flow regime includes subsonic as well as supersonic flows. For the evolution of the system in the Laplace plane the present method makes use of the exact unsteady aerodynamic forces in the Laplace plane once the control law is established. This is a great advantage against other results previously published, where the unsteady aerodynamics in the Laplace plane are just approximations of the curve-fitted values in the frequency domain (imaginary axis). Different control techniques are investigated like pole-placement, LQR and H-infinity norm. Among these, the H-infinity norm emerges as the optimal choice, exhibiting a norm magnitude approximately two orders of magnitude lower than the LQR case. Furthermore, the H-infinity controller demonstrates lower pole values that those of the pole placement and LQR compensator, showing the advantage of the H-infinity controller in terms of economic efficiency.

Using the colloidal method, Au NP’s were deposited onto 6 different supports (TiO2,  and -Al2O3, HFeO2, CeO2, and C), and their catalytic activity and selectivity were compared in the alkylation of aniline by benzyl alcohol. Correlations were made between the nature of the support, the Au NP size and H-binding energy.

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

The closed forms of the non-resonant thermonuclear function in the Maxwell-Boltzmann and Tsallis case with depleted tail are obtained in generalized special functions. The results are written in terms of H-function of two variables. The importance of the results in this paper lies in the fact that the reaction rate probability integrals in Maxwell-Boltzmann and Tsallis cases are not obtained by the conventional method of approximation or by means of a single variable transform technique but by means of a two variable transform method. The Behaviour of the depleted non-resonant thermonuclear functions are examined using graphs. The results in the paper are of much interest to astrophysicists and statisticians in their further work in this area.

This paper proposes a multifractal model, with the aim of providing a possible explanation for the locality phenomenon that appears in the estimation of the Hurst exponent in stationary second order temporal series representing self-similar traffic flows in current high-speed computer networks. It is shown analytically that this phenomenon occurs if the network flow consists of several components with different Hurst exponents.

In this paper, I introduce a new concept of representing numbers in base ; in other words, I have found new series for any number similar to series that could be written according to the collatz sequence which is called zi(n) in this article. These series need to end with 1. Then, we use two sets of rules to make a diagram which then proves the existence of such series for any number.In this diagram, by branching numbers into different branches in accordance to the modularity of 4 and continuing branching to the point that their numbers have enough common terms in their collatz series, we could reduce zi(n) to zi(k) so that k<n in any branch by Rule Number One. This diagram shows that zi(n) exists for every number, in other words, this proves the theorem (A) or zi-existence theorem. The proof of zi-existence theorem leads to a proof of the collatz conjecture because the collatz series could be written as a linear combination of such series that all of them end with 1, so the collatz series for any number ends with 1.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Using the h-index to assess individual researchers is not only unethical and unfair but also inaccurate and misleading. This index fails to offer a reliable measure of a researcher's impact based on their citation scores. Beyond statistical and conceptual considerations, authorship practices, especially in the case of multi-authored publications, give rise to significant problems that often go unnoticed. While some modifications of the h-index have been proposed to mitigate these weaknesses, the fundamental deficiencies persist. Most of these flaws have been effectively addressed by the c-score, a composite citation index. The c-score excludes self-citations, normalizes the number of citations by considering the number of authors in each paper, and takes into account first, single, and last authorship. This approach provides a more realistic measure of the impact of each individual researcher based on raw citations.

Individuals with Parkinson’s disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MRL) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in freezers. Thirty-four freezers were assessed in the ON-medication state. During a functional magnetic resonance imaging protocol of simulated APA task, we assessed beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR), in addition to PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APAs amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2=0.32, P=0.0006) and APA amplitude (R2=0.13, P=0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Helicobacter pylori, a gram-negative bacteria usually found in stomach and first part of small intestine, is known to cause infections and ulcers and may have association with cancer. Normally, the treatment options include combinations of antibiotics with proton pump inhibitors and antiinflammatory drugs. However, all of them have high systemic exposure, and hence, unfavourable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is very limited. We have attempted to develop a predominantly gut-restricted formulations of antibiotic + adjuvant combinations as a basis for potentially more safe and efficacious treatment of gastrointestinal tract infections. We have considered E. coli (as a model of H. pylori) and Lactobacilli to study the antibacterial activity of nanogel with combined drugs (classical antibiotics and individual components of essential oils). It has been shown that levofloxacin (LF) in combination with zephirol demonstrates synergy effect against E. coli (cell viability has decreased by about 50%) and weakens the effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant is also shown to be effective. Using FTIR and UV spectroscopy, it has been proved that chitosan nanogels with the drug are well adsorbed on the mucosal model, thereby increasing the bioavailability of drugs. Using ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which is potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. Thus, chitosan nanogels loaded with a combination of drugs can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract, and applicable to difficult-to-treat bacteria.

The increased emergence of multidrug-resistant Helicobacter pylori influences the prevention of stomach cancer. Zingiber officinale is a plant usually used in folk medicine to treat a variety of diseases involving infections, nausea, vomiting, peptic ulcer, dyspepsia, and inflammation. This study was conducted to evaluate the ability of Z. officinale extract to combat resistant H. pylori. The disc diffusion, microdilution, and microplate assays were performed to evaluate the susceptibility to antibiotics, and the antibacterial and antibiofilm activities of the Z. officinale extracts. Using the checkerboard method, the combined effects of the gentamicin and Z. officinale extract were investigated. In addition, anti-inflammatory activity and GC-MS analysis were determined by the modified protocol. According to the findings, H. pylori isolates exhibited resistance rates of 56.33, 50.0, and 45.85 for metronidazole, gentamicin, and tetracycline, respectively. The methanolic extract of Z. officinale had the strongest effectiveness against resistant H. pylori isolates with MIC of 20.0 to 50.0 µg/ml against both H. pylori isolates and the stranded strain NCTC 11637. Z. officinale extract suppress the biofilm formed by H. pylori isolates with a percentage of 92.96% at 50.0µg/ml, compared with 97.19% for gentamicin at the same concentration. According to FICI values, combination of methanolic Z. officinale extract to gentamicin increases bacterial sensitivity to such drugs. Moreover, the Z. officinale extract exhibits strong anti-inflammatory activity. The GC-MS analysis of Z. officinale extract exhibits 17 different chemical compounds. Conclusions: The Z. officinale extract contain the anti-inflammatory compound gingerol as the main constituent which inhibits the growth of H. pylori and its biofilm, are a promising natural therapeutic alternative or enhance antibiotics activity

Lead, known as a metal with high neurotoxicity to children, cadmium, which is a carcinogenic and bioaccumulative contaminant, and arsenic, a class 1 carcinogenic according to the International Agency for Research on Cancer, are toxic elements (TEs) whose relevant route of exposure may be diet. We determined the bio-accessible fraction of lead, cadmium, and arsenic from the diet of preschool children from two day care centers (DCC). A cross-sectional study was conducted with 64 one–four-year-old children from two DCCs where the 24-h duplicate diet samples were collected. The diet samples were analyzed by ICP-MS for lead, cadmium, and arsenic total concentrations (n = 64) and their bio-accessibility were analyzed for a subsample (n = 10). The dietary intake (DI) mean for lead, cadmium, and arsenic were 0.18 ± 0.11 µg kg⁻¹ bw, 0.08 ± 0.04 µg kg⁻¹ bw, and 0.61 ± 0.41 µg kg⁻¹ bw, respectively. All DI calculated for TEs, considering total intake, were found lower than the tolerable limits (TL) (European Union, or World Health Organization, WHO, when applicable) except for one child’s Pb intake. Bio-accessibilities ranged between 0% to 93%, 0% to 103%, and 0% to 69%, for lead, cadmium, and arsenic, respectively. Although DI for TEs has been found lower than TL, these reference values have been recently decreased or withdrawn since it was for lead and arsenic whose TL were withdrawn by WHO.

It is argued that if the non-unitary measurement transition, as codified by Von Neumann, is a real physical process, then the ‘probability assumption’ needed to derive the Second Law of Thermodynamics naturally enters at that point. The existence of a real, indeterministic physical process underlying the measurement transition would therefore provide an ontological basis for Boltzmann’s Stosszahlansatz and thereby explain the unidirectional increase of entropy against a backdrop of otherwise time-reversible laws. It is noted that the Transactional Interpretation (TI) of quantum mechanics provides such a physical account of the non-unitary measurement transition, and TI is brought to bear in finding a physically complete, non-ad hoc grounding for the Second Law.

This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis entourage effects was conducted using the PRISMA model. Two research questions conducted the review: (1) What are the Physiological Effects of Terpenes and Terpenoids found in Cannabis? (2) What are the proven Entourage Effects of Terpenes in Cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed/MEDLINE, Web of Science, and EBSCO databases, using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity, however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa-prevalent monoterpenes and their triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically, however, in combination with CBD did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxing; linalool as sleep aid, exhaustion relief and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection, borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm these constituents' individual and combined effects.

Background/Objectives: The primary life-threatening complication in Spinal-bulbar muscular atrophy (SBMA) is ventilatory failure, which results from the weakening of the bulbar and respiratory muscles. However, systematic studies assessing respiratory function over the long-term have not been performed. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years, aiming to identify any potential, sustained decline during this time. Furthermore, we explored possible correlations between respiratory function tests and clinical and biochemical serum indices. Methods: We collected data from 9 genetically confirmed SBMA patients and conducted spirometric measurements twice a year for eleven years. The spirometric data included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)]. Additionally, we measured serum biochemical indices and SBMA functional rating scale (SBMAFRS) for clinical analysis. Results: All three respiratory function tests showed a descending trend. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with the three pulmonary function tests. MIP and MEP correlated with creatine phosphokinase and creatinine levels, and FVC correlated with serum level of transaminases. Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in patients with SBMA. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

Dogs and cats have become the most influential and successful pets through long-term domestication. People keep them for various reasons, such as their functional roles or for physical or psychological support. However, why humans are so attached to dogs and cats remains unclear. A comprehensive understanding of the current state of human preferences for dogs and cats and the potential influential factors behind it is required. Here, we investigate this question using two independent online datasets and anonymous questionnaires. We find that current human preferences for dogs and cats are relatively higher than for most other interests, such as games and music. Genetic variations, gender, age, and economic development levels notably influence these preferences for dogs and cats. Specifically, dog and cat ownership is significantly heritable (h2 = 0.43, 95%CI: 0.35 -0.51) and further analysis found that women, young people, and those with higher incomes are more likely to keep dogs and cats, and the primary reason is to gain emotional support. Our study provides insights into why humans get so attached to dogs and cats and establishes a foundation for developing co-evolutionary models.

We have shown that Newton’s third law does not strictly hold in a system with remote elements, due the finite speed of signal propagation and thus force imbalance occurs at the system’s center of mass. As the said system is affected by a total force for a finite duration, mechanical energy and momentums are gained by the system. In early works we assumed that the bodies were macroscopically charge neutral. Later we removed this restriction, thus analyzing the consequences on a possible electric charged relativistic motor. On the first published paper on this subject we studied this phenomena in general but gave only an example of a system reaching a stationary state, in this paper we shall analyze a charged retarded electromagnetic motor in a more general time dependent setting giving specific examples in which the system never reaches a stationary state yet produces steady linear momentum non the less.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Malocclusions have a continuously increasing prevalence from a generation to another as a result of climate changes, soil, atmosphere and water pollution. All of these aspects have unfavorable consequences on the nutritional scheme. Thus, nutrition together with other etiopathogenic factors contribute to complex alterations in the somatic development of the entire organism and, implicitly, of the cephalic extremity. The study group included 4147 children from randomly selected schools from Vâlcea County, Romania. The aim of this study is to determine the prevalence of malocclusions in schoolchildren from Vâlcea County, Romania, according to the three main classes of malocclusions (according to Angle’s classification), age groups (from 6 to 10 years old and from 11 to 14 years old), gender (male and female) and place of origin (rural and urban). For Angle class I malocclusions we recorded the highest prevalence (48,78% from the total number of schoolchildren with malocclusions), followed by Angle class II malocclusions (45,85% from the total number of schoolchildren with malocclusions) and for Angle class III malocclusions we found the lowest prevalence (5,37% from the total number of schoolchildren with malocclusions).According to gender, we found the highest prevalence in female gender (29,90% from the total number of female subjects), while in male gender we recorded a prevalence of 27,70% from the total number of male subjects. Regarding the place of origin, there is a higher prevalence of malocclusions in the urban areas (29,16%). The study subgroup included 140 children randomly selected from the total number of subjects from the study group. They were included in a more advanced study. The aim is to find potential associations between the presence of malocclusions and various oral variables. Categorical variables were expressed as numerical values and percentages, and their association was evaluated with either the Chi-square test of association or homogeneity, or the Fisher Exact test. The acquired data were incorporated into a binomial logistic regression model to assess the likelihood of developing malocclusions in relation to the following variables: defective phonation, bruxism, frequency of teeth brushing, onychophagia, oral respiration, infantile deglutition, placing objects between the maxillaries, thumb sucking and salivary aspects. It is also aimed to compare the results obtained with similar ones from the specialized literature.

Histone post-translational modification is one of the main mechanisms of epigenetic regulation, which plays a crucial role in the control of gene expression and various biological processes. However, whether or not it affects fungal virulence is not clear in Sclerotinia sclerotiorum. In this study, we identified and cloned the histone methyltransferase Defective in methylation 5 (Dim5) in S. sclerotiorum, which encodes a protein containing a typical SET domain. SsDim5 was found to be dynamically expressed during infection. Knockout experiment demonstrated that deletion of SsDim5 reduced the virulence in Ssdim5-1/Ssdim5-2 mutant strains, accompanied by a significant decrease in H3K9 trimethylation levels. Transcriptomic analysis further revealed the downregulation of genes associated with mycotoxins biosynthesis in SsDim5 deletion mutants. Additionally, the absence of SsDim5 affected the fungus's response to oxidative and osmotic, as well as cellular integrity. Together, our results indicate that the H3K9 methyltransferase SsDim5 is essential for H3K9 trimethylation, which regulating fungal virulence to host plants through impacting on mycotoxins biosynthesis, and the response to environmental stresses in S. sclerotiorum.

Coagulase negative Staphylococci (CoNS) are reported to be responsible for 50-60% of bloodstream infections in very preterm (&lt;1500 g) infants in Neonatal Intensive Care Units (NICU). Staphylococcus capitis is an increasingly prevalent pathogen in neonatal setting, frequently causing central-line associated bloodstream infections (CLABSI) that can be difficult to eradicate. CVC removal versus in situ treatment of CoNS CLABSIs is a matter of debate, with no clear consensus emerging in the existing literature. We revised all S. capitis CLABSIs in our NICU between 2019 and 2022, focusing on the role of catheter removal for eradication. Among 25 cases, 17 CVCs were removed after diagnosis, leading to a 76.5% eradication rate in this group. 3 infants had a persistently positive blood culture after CVC substitution. A new catheter was than inserted after a 48-hours washout period, resulting in resolution of the infection. Only 2 of 8 patients (25%) who retained the catheter after diagnosis, underwent infection eradication with antibiotic therapy alone. Catheter removal, when feasible, seems to be the most effective strategy to eradicate S. capitis CLABSIs, sometimes even requiring a 48-hours washout period before reinsertion. Further studies on this subject are needed to better standardize the management of this kind of infections.

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate expression of differentiated phenotype of chondrocytes. We also found that cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2 and chondroitin sulfate biosynthetic enzymes. Blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

Cognitive impairment in patients with Parkinson’s disease (PD), which may occur in various severities, represents one of the commonest and most disabling non-motor manifestations during the course of the disease, causing a negative impact on patients’ quality of life. Eventually, it becomes a burden for the family members and/or the caregivers of patients, as it progresses to PD dementia. Current pharmacological treatments for cognitive impairment in PD exhibit partial efficacy, while novel effective therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline, and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, improvement of mitochondrial function, regulation of synaptic plasticity, impact on gut-brain axis, modulation of neuroinflammation, upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this overview, we aim to cover the clinical aspects of PD associated cognitive impairment, highlighting recent evidence on emerging treatment approaches that are currently under investigation at a preclinical and clinical level.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here we analysed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a posthoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, taper/stop) as the predictor. 282 patients were analysed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that functional decline after tapering or stopping DMARDs in RA patients with stable remission is small and related to relapses but to on overall functional decline.

Chloride (Cl-) is applied in coffee in rates as a “macronutrient” due that potassium (K+) is one of the most demanded nutrients by the coffee plant, and the potassium muriate (KCl) bases fertilizer is one the most used by the coffee growers. Does not exist scientific evidence that addresses the question regarding with which is the influences of the Cl- applied in the K fertilization base on MOP on coffee growth, nutrient uptake, and nitrogen use efficiency (NUE). Over four years, two trials were conducted on greenhouse and field conditions to address these questions. The trials set up were designed to test the influence of increased Cl- and reduced S rates on biomass accumulation, nutrient uptake, and NUE. A significant effect of the Cl- rates on growth was observed under greenhouse conditions but a non-significant effect on yield under field conditions. Cl- and S significantly influence the NUE in coffee. The result allows us to conclude that Cl- rates need to be balanced with S rates and that Cl- applied as a macronutrient can improve the NUE in coffee when those rates do not exceed 180 mg. L-1 Cl- and 80 mg.L-1 S in the greenhouse and 150 kg.ha-1.year-1 Cl- and 50 kg. ha-1.year-1 S in field conditions. In practical terms, coffee farmers need to balance the K base fertilizers sources to improve the nutrient use efficiency, especially the NUE.

INTRODUCTION: Superficial cutaneous bacterial infections have a high incidence in geriatric patients. The most implicated pathogens are gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes) while gram-negative germs are also implicated. Resistances to common topical antibiotics (mupirocin, fusidic acid) require alternatives to gram-positive and gram-negative microorganisms.Ozenoxacin cream for topical use (non-fluorinated bactericidal quinolone), in other countries and with other galenics, is indicated in children older than 6 months and in adults as a treatment of superficial bacterial infections, such as acne. In Spain, ozenoxacin cream is indicated only for non-bullous impetigo; scientific evidence show effectiveness also in other superficial skin bacterial infections.A cases series of clinical use of ozenoxacin in bacterial superficial skin infections in geriatric patients (institutionalized or community dwelling) is presented.METHODS: Multicenter case series (March-August 2022) of bacterial superficial skin infections treated with ozenoxacin cream (10mg/g every 12h, 5days); data from medical records (controls: 1-3-5 days), after obtaining informed consent (use of data and images).RESULTS: Series of 28 patients (mean age: 84,79) from nine nursing homes and one outpatient geriatric service, including acute and subacute/chronic cases.In all cases treatment was ozenoxacin 10mg/g topical cream applied every 12 hours for 5 days according to medical prescription (except for one case in which 3 days were enough for complete healing and another case treated for 10 days).Results showed complete healing in all 20 acute cases and significant clinical improvement in all subacute/chronic cases (with complete healing in one of them). Professionals scored the effectiveness in acute cases as a mean 4.5 points (maximum score: 5, p<.0001) and in subacute/chronic cases as 3.8 points (p=.010).There was no skin irritation or other adverse effects in anyone of the patients, and clinical improvement of pain, itching and other symptoms was observed, suggesting an anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: Our results seem to demonstrate the effectiveness and tolerability of ozenozacin cream in bacterial infections other than non-bullous impetigo. Ozenoxacin cream is indicated only for the treatment of non-bullous impetigo; however, it is also shown to be effective, both in the scientific evidence and in our case series, for other superficial bacterial skin infections, both acute and subacute/chronic, suggesting the opportunity for clinical studies with an experimental design to evaluate the findings of clinical practice and to be able to have a therapeutic alternative to compensate for the complications of the appearance of resistance.

This study was designed to assess the reliability of geographic information using satellite image information in ungauged basins. For this, this study constructed geographic information using actual gauged data and satellite information data and conducted runoff analysis through S-RAT, a rainfall–runoff model, and performed the comparison and analysis of geographic information and runoff data. For actual gauged data, the gauged geographic information of the Water Resources Management Information System (WAMIS) was collected, and for satellite information, the image information of moderate-resolution imaging spectroradiometer (MODIS) observation sensor loaded on Terra Satellite was collected. As analysis areas, three basins where mountains occupy more than 80% and another three basins where urban areas occupy more than 7% in the Han River basin were selected. According to the analysis result, the gauged information and satellite image information showed great difference in runoff, maximum 50% in peak flood and maximum 17% in total flood, in the rivers with many urban areas, while the runoff difference in the rivers with many mountains showed maximum 13% in peak flood and 4% in total flood. What showed the greatest difference in image information was land use, and it turned out that the MODIS satellite recognized the urban rivers as cities for more than maximum 60% compared to WAMIS-gauged data. Meanwhile, in the forest area, the MODIS satellite image showed error of less than 5% of the WAMIS-gauged data, which indicates that it has higher applicability in Mountain Rivers.

Family Fabaceae traditionally serves as food and herbal remedies source. Several plants are already used for menopausal symptoms treatment based on a presence of typical secondary metabolites, isoflavones. Beside soybean and clovers, isoflavones could be produced by other plants or in vitro cultures. This type of production can be further enhanced by elicitation that stimulates metabolites biosynthesis via stress reaction. Vanadium compounds have been already described as potential elicitors and the aim of this study was to determine an impact of NH₄VO₃ and VOSO₄ solutions on isoflavones production in Genista tinctoria L. cell cultures. The significant increase of isoflavones content such as genistin, genistein or formononetin was measured in a nutrient medium or dry mass after NH₄VO₃ treatment for 24 or 48 hours. The possible transport mechanism of isoflavones was also evaluated. An incubation with different transport inhibitors prior elicitation took effect on isoflavones content in the medium. However, there was non-ended result for particular metabolites such as genistein and daidzein, where ABC or alternatively MATE proteins can participate. Possible elicitation by some inhibitors was also discussed as result of their pleiotropic effect. Despite this outcome, the determining of transport mechanism is important step for identification of specific transporter.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

In this paper, we propose an extension of the Planck distribution function derived from the Boltzmann principle. That is, we consider extending Planck's law with new distribution functions. In addition, using ideas applied to the expansion of the Planck distribution function, Von Koch's inequality is derived without using the Riemann hypothesis, showing that the abc conjecture is negated. We also describe some challenges for the future. Namely, we will discuss that Entropy is related to dynamical systems described by logistic function models, such as the bacterial and the population growth.

This study explores the intricate relationship between the angle of vehicle-to-vehicle (V2V) conflicts and the severity of conflicts at signalized intersections during traffic signal failures, leveraging the advanced capabilities of LiDAR sensor technology. The research delves into the impact of conflict angles on collision outcomes and introduces LiDAR as a novel and precise tool for capturing spatial dynamics during unregulated traffic movements. Findings reveal that as the angle of V2V conflicts increases, indicating a wider approach between vehicles, the severity of conflicts tends to decrease. This reduction in severity is attributed to the detailed spatial data provided by LiDAR, enabling the identification of glancing impacts rather than direct head-on collisions. The mitigation of forces involved in collisions at increased angles contributes to a decreased likelihood of severe consequences, such as extensive vehicle damage and serious injuries to occupants.Conversely, as the angle of V2V conflicts decreases, signifying a narrower approach between vehicles, the potential for severe collisions tends to increase. LiDAR technology facilitates precise measurements of spatial coordinates and temporal dynamics, revealing that collisions occurring at smaller angles involve more direct and concentrated impact forces. This heightened risk of extensive damage to vehicles and increased injury severity is crucially captured by LiDAR, providing valuable insights into the relationship between conflict angles and collision outcomes during traffic signal failures. This study underscores the efficacy of LiDAR sensor technology in understanding the nuanced dynamics of V2V conflicts and highlights its role in developing targeted safety interventions. The integration of LiDAR data into traffic safety analyses offers a sophisticated approach to mitigating the impact of conflicts and enhancing overall safety at signalized intersections during signal failures. The research also highlighted that as the angle of V2P conflicts widens, PET experiences a proportional increase. A larger conflict angle signifies a more complex interaction between vehicles and pedestrians, leading to prolonged PET values. Conversely, a decrease in the angle of V2P conflicts is associated with a reduction in PET during traffic signal failures.The study commences with an examination of traffic characteristics at the E Cold Spring Ln – Hillen Rd intersection in Baltimore City, MD, utilizing a deployed LiDAR sensor. When the signal at this intersection experienced a temporary malfunction on a regular working day in September 2023, the LiDAR captured data related to vehicle and pedestrian volumes, as well as V2V and V2P conflicts. The primary objective of the research is to evaluate the repercussions of traffic signal failures on both traffic flow and safety, specifically V2V and V2P conflicts, occurring during periods of improper signal functionality. Additionally, this investigation delves into various factors that impact traffic signal performance, encompassing traffic demand, geometric layout, pedestrian interactions, and the incorporation of emerging technologies.

In this present paper, we deal with the generalized (k, s)-fractional integral and differential operators recently defined by Nisar et al. and obtain some generalized (k, s)-fractional integral and differential formulas involving the class of a function as its kernels. Also, we investigate a certain number of their consequences containing the said function in their kernels.

This prospective study provides data on long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison to two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. Concentration of antibodies against SARS-CoV-2 spike protein in plasma 5-7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after first vaccine dose was 86% after ChAd compared to 35% and 39% after BNT and m1273, respectively (p &lt; 0.0001), and after second vaccine dose highest (89%) in the m1273/m1273 group (p &lt; 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

Alzheimer's Disease (AD) and Parkinson's Disease (PD) are two neurodegenerative diseases posing a significant disease burden due to their increasing prevalence and socio-economic cost. Traditional therapeutic approaches for these diseases exist but provide limited symptomatic relief without addressing the underlying pathologies. This review examines the potential of immunotherapy, specifically monoclonal antibodies (mAbs), as disease-modifying treatments for AD and PD. We analyze the pathological mechanisms of AD and PD, focusing on the roles of amyloid-beta (Aβ), tau (τ), and alpha-synuclein (α-syn) proteins. We discuss the latest advancements in mAbs therapies targeting these proteins, evaluating their efficacy in clinical trials and preclinical studies. We also explore the challenges faced in translating these therapies from bench to bedside, including issues related to safety, specificity, and clinical trial design. Additionally, we highlight future directions for research, emphasizing the need for combination therapies, improved biomarkers, and personalized treatment strategies. This review aims to provide insights into the current state and future potential of antibody-based immunotherapy in modifying the course of AD and PD, ultimately improving patient outcomes and quality of life.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

This paper investigates the leader-following H∞ consensus of fractional-order multi-agent systems (FOMASs) under input saturation via the output feedback. Based on the bounded real lemma for FOSs, the sufficient conditions of H∞ consensus for FOMASs are provided in α∈0,1 and 1,2, respectively. Furthermore, the iterative linear matrix inequalities (ILMIs) approaches are applied for solving quadratic matrix inequalities (QMIs). The ILMI algorithms show a method to derive initial values and transform QMIs into LMIs. Mathematical tools are employed to transform the input saturation issue into optimal solution of LMIs for estimating stable regions. The ILMI algorithms avoid the conditional constraints on matrix variables during the LMIs construction and reduce conservatism. The approach does not disassemble the entire MASs by transformations to the Laplacian matrix, instead adopting a holistic analytical perspective to obtain gain matrices. In the end, numerical examples are conducted to validate the efficiency of the approach.

Six solvent fractions isolated from flower bud and leaf ethanolic extracts of Cleistocalyx operculatus were analyzed for their phytochemical contents including phenolics, flavonoids, saponins, tannins, and alkaloids. Antioxidant activities were measured using the ABTS, DPPH, and FRAP assays. The results showed that flower bud aqueous fraction (BAF) and leaf aqueous fraction (LAF) rich in phenolic content (768.18 and 490.74 mg GAE/g dry extract, respectively) exhibited significantly higher antioxidant activities than other fractions. Flower bud hexane fraction (BHF) had remarkably high flavonoid and saponin contents (134.77 mg QE/g and 153.33 mg OA/g dry extract, respectively), followed by that of leaf hexane fraction (LHF) (76.54 mg QE/g and 88.25 mg OA/g dry extract, respectively). BHF and LHF were found to have extremely high antibacterial activity against two H. pylori strains ATCC 51932 and 43504 (MICs of 125 µg/ml). Interestingly, DMC (2’,4’-Dihydroxy-6’-methoxy-3’,5’-dimethylchalcone) isolated from BHF displayed greater antibacterial activity against the bacterial strains (MICs of 25–50 µg/ml) than those of the fractions. In addition, DMC presented potent inhibitory effects on H. pylori-urease (IC50 of 3.2 µg/ml) and α-amylase (IC50 of 83.80 µg/ml), but no inhibition against α-glucosidase. It was also demonstrated that DMC showed its pronounced inhibitory effects on urease activity and biofilm formation of H. pylori, and could increase the membrane permeability of the bacterial cells. Scanning electron micrographs depict that BHF and DMC had strong effects on the cell shape and significantly induced distortion and damage of the cell membrane. The fractions and DMC showed no significant toxicity to four tested human cell lines. Efforts to reduce antibiotic use indicate the need for further researches of the flower buds and DMC as potential products to prevent or treat gastric H. pylori infections.

This research aims to deepen the understanding of the relationship between conductivity and morphology in polypyrrole (PPy) via a comparison of the bipolaron to polaron ratios with a focus on the C-H deformation area. PPy samples were synthesized with different surfactants: sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and tween 80 (TW). The study revealed that SDS significantly altered the bipolaron and polaron in C-H deformation region and showed higher conductivity than other surfactants. Notably, the morphological shifts to a sheet-like structure when using ammonium sulfate (APS) contrasted with the particle-like form observed with ferric chloride (FeCl3). These results showed that if the oxidant changed, the bi-polaron and polaron ratios in C-H deformation were unrelated to PPy morphology. However, this work showed a consistent relationship between SDS use, the bipolaron and polaron ratios in the C-H deformation, and the conductivity properties. Moreover, the natural positive charge of PPy and negatively charged SDS molecules may lead to an electrostatic interaction between PPy and SDS. This work assumes that this interaction might cause the transformation of polaron to bipolaron in the C-H deformation region, resulting in improved conductivity of PPy. This work offers more support for the future investigation of PPy characteristics.

Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Fractal behavior and long-range dependence are widely observed in measurements and characterization of traffic flow in high-speed computer networks of different technologies and coverage levels. This paper presents the results obtained when applying fractal analysis techniques on a time series obtained from traffic captures coming from an application server connected to the Internet through a high-speed link. The results obtained show that traffic flow in the dedicated high-speed network link have fractal behavior when the Hurst exponent is in the range of 0.5, 1, the fractal dimension between 1, 1.5, and the correlation coefficient between –0.5, 0. Based on these results, it is ideal to characterize both the singularities of the traffic and its impulsiveness during a fractal analysis of temporal scales. Finally, based on the results of the time series analyses, the fact that the traffic flows of current computer networks exhibit fractal behavior with a long-range dependency is reaffirmed.

Specifically this work is based on the concept of ‘dark energy’ as a phenomenal effect of expansion through which a theoretical value of Hubble’s constant has been introduced. It is a constant that is based on a postulate that the square root of ratio of the Siva’s constant ‘K’ and Hubble’s constant ‘H’ is exactly equal to the diameter of the neutral hydrogen atom. That is the, exact theoretical value of Hubble’s constant. This is always constant .However, space-time conversions and the changes in the velocity of light will affect the distance and velocity in Hubble’s equation. Deviation factors in velocity, distance and the Hubble’s constant have been calculated separately which are affected by change of velocity of light with expansion of space time. The observations are related to red shift. So the change factor in terms of Hubble’s constant has been calculated with respect to red shift. Thus a factor which affects the theoretical Hubble’s constant has been calculated to find the exact value of Hubble’s constant that satisfies the experimental results. The present theoretical value of Hubble’s constant has been calculated. The experimental results by plank, ACT (Atacama Cosmology Telescope), WMAP (Wilkinson Microwave Anisotropy Probe) etc. experiments are at par with the theoretical result. Thus the ontology of space time introduced in this theoretical work supposed to be correct and leads to a new theory of origin of universe for which a brief description has been provided.

In the article, by applied the concept of strongly convex function and one known identity, we establish several Ostrowski type inequalities involving conformable fractional integrals. As applications, some new error estimations for the midpoint formula are provided as well.

The current work addresses the control of two-input two-output (TITO) Wood and Berry model of a binary distillation column. The controller design problem is formulated in terms of multivariable H_∞ control synthesis. The controller structure takes the form of simplest static output feedback (SOF) control. The controller synthesis is performed using a hybrid approach of blending linear matrix inequalities (LMI) and genetic algorithm (GA). The performance of the static output feedback controller is compared with three other controllers designed for Wood and Berry model available in the literature. The first simulation study is performed for the case of tracking a unit step command in the presence of a step change in output disturbance. A second simulation study is performed for rejecting a change in sinusoidal output disturbance.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

The rapidly evolving field of artificial intelligence (AI) continues to witness the introduction of innovative open-source pre-trained models, fostering advancements in various applications. One such model is Llama 2, an open-source pre-trained model released by Meta, which has garnered significant attention among early adopters. In addition to exploring the foundational elements of the Llama v2 model, this paper investigates how these early adopters leverage the capabilities of Llama 2 in their AI projects. Through a qualitative study, we delve into the perspectives, experiences, and strategies employed by early adopters to leverage Llama 2's capabilities. For the purpose of data analysis, the capabilities inherent in the Llama 2 model were employed to conduct keyword extraction from the context of the early adopters' case studies. The findings shed light on the model's strengths, weaknesses, and areas of improvement, offering valuable insights for the AI community and Meta to enhance future model iterations. Additionally, we discuss the implications of Llama 2's adoption on the broader open-source AI landscape, addressing challenges and opportunities for developers and researchers in the pursuit of cutting-edge AI solutions. The present study constitutes an early exploration of the Llama 2 pre-trained model, holding promise as a foundational basis for forthcoming research investigations.

Staphylococcus aureus is the primary cause of mastitis in dairy cattle globally and frequently exhibits multidrug resistance due to excessive antibiotic use on farms. This study aimed to isolate S. aureus from mastitis affected cows and evaluate its antimicrobial susceptibility. A total of 172 milk samples from confirmed mastitic cows were cultured using standard bacteriological methods. Forty-four S. aureus isolates were tested against 11 common antimicrobials using the Kirby–Bauer disk diffusion method. S. aureus was isolated from 51.2% of samples, with significant resistance observed against ampicillin (84.1%), penicillin (81.8%), tetracycline (36.4%), and amoxicillin-clavulanic acid (34.1%). MDR was noted in 43.2% of isolates. In contrast, S. aureus demonstrated complete susceptibility to ceftriaxone and gentamicin (100%), and high susceptibility to streptomycin (88.6%), erythromycin (88.6%), nitrofurantoin (72.7%), and cefotaxime (72.7%). The significant isolation rate of S. aureus and its MDR underscore the urgent need for enhanced veterinary practices and public health strategies. A comprehensive approach that includes improved management, ongoing education for veterinarians and dairy farmers, responsible antimicrobial usage, and regular monitoring of resistance is essential to tackle the escalating threat of antimicrobial resistance in bovine mastitis.

This paper focuses on the long-standing issue of galactic rotation, i.e. the discrepancy between observed rotation rates and predictions based on Newtonian gravity. While Newton's law holds within the solar system, it fails to explain the higher-than-expected rotation speeds of galaxies, particularly at greater distances from their centers. This study finds that Newton's gravitational formula applies only when gravitational lensing has a negligible impact. We examine the gravitational force on objects farther from the galactic center, where the lensing effect of a supermassive black hole becomes significant. This lensing causes the actual gravitational force to exceed Newtonian predictions, with the discrepancy increasing with distance. This effect offers an alternative explanation for the galactic rotation curve without the need for dark matter. Our findings suggest that Newton's formula requires revision to account for gravitational lensing, a key factor in understanding galactic dynamics and its broader cosmic implications.

This study aims to explore methods for automating the replication of correlated portfolios across shares using various algorithms. The goal is to select one algorithm for implementation in a visualization tool that will facilitate portfolio building. The dynamics of the stock market provide a comprehensive view of the global economy, acting as a catalyst for stakeholders to participate and benefit various sectors financially, primarily through investments in companies that yield returns and contribute to the economy. The evaluation and comparison of these algorithms are crucial for making well-informed decisions regarding the core objectives of the study. Ultimately, a determination will be made as to whether the program can effectively analyse data from Yahoo finance to provide a quick overview of the financial market state of companies in the S&P 500 US stock prices.

A 64-year-old woman with primary Sjogren’s syndrome which was not treated, was admitted to our hospital for nasal bleeding, oral bleeding, and purpura on her entire body. On this admission, laboratory findings were as follows: WBC counts, 8,910 /μL; hemoglobin, 9.9 g/dL; and platelet counts, 0.1×10⁴/μL. Although the anti-PLT antibody was positive, other autoimmune antibodies such as anti-DNA were negative. Moreover, cytomegalovirus IgM, Parbovirus B19 IgM, and Helicobacter pyroli IgG antibodies were not detected. No abnormal findings suggestive of infection were identified in the systemic examination. A bone marrow aspiration smear revealed normal bone marrow. Based on these findings, the patient was diagnosed with primary Sjogren’s syndrome-related immune thrombocytopenia. The patient initially received intravenous immunoglobulin, methyl prednisolone pulse therapy, and subsequent high dose prednisolone without significant improvement. Therefore, eltrombopag, a thrombopoietin-receptor agonist, was added. Subsequently, erythromycin was also added, considering its immunomodulatory effects. After initiating the erythromycin treatment, the platelet counts increased. Therefore, add-on eltrombopag and erythromycin treatment was effective; however, the platelet counts gradually decreased with reducing the prednisolone dosage. Instead of increasing the prednisolone dosage again, tacrolimus, a calcineurin inhibitor, was successfully added. Consequently, the prednisolone dosage could be reduced. This case shows that treatment with erythromycin and tacrolimus may be efficacious when conventional immunosuppressants show limited effectiveness in primary Sjogren’s syndrome-related immune thrombocytopenia.

Phosphorus (P) is an important and irreplaceable macronutrient. It is central to energy and information storage and exchange in living cell. P is an element with “broken geochemical cycle” since it lacks abundant volatile compounds capable of closing the P cycle. P fertilizers are critical for global food security, but the reserves of minable P are scarce and non-evenly distributed between countries of the world. Accordingly, the risks of global crisis due to limited access to P reserves is expected to be graver than those entailed by competition for fossil hydrocarbons. Paradoxically, despite the scarcity and value of P reserves, its usage is extremely inefficient: current waste rate reaches 80% giving rise to a plethora of unwanted consequences such as eutrophication leading to harmful algal blooms. Microalgal biotechnology comprise a promising solution to tackle this challenge. The proposed review briefly presents the relevant aspects of microalgal P metabolism such as cell P reserve composition and turnover, and the regulation of P uptake kinetics for maximization of P uptake efficiency with the focus on novel knowledge. Multifaceted role of polyPhosphates, the largest cell depot for P, is discussed with emphasis on the P toxicity mediated by short-chain polyPhosphates. Opportunities and hurdles of P bioremoval via P uptake from waste streams with microalgal cultures, either suspended or immobilized, is discussed along with the role of bacterial components of microalgal-bacterial consortia in these processes. Possible avenues of P-rich microalgal biomass such as biofertilizer production or extraction of valuable polyPhosphates and other bioproducts are considered. The review concludes with a comprehensive assessment of the current potential of microalgal biotechnology for ensuring the sustainable usage of phosphorus.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium’s dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. Aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, being the effect pronounced also when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin treated cells, which were unable to form colonies, were actually ROS+/PI–. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.

Introduction and Purpose: Nurses are expected to be competent in practice based on the domain of standards and interpersonal soft skills (ISS). Nurses are faced with inadequate physical assessment 28%, formulating diagnoses 56%, plans 34%, implementation 31%, evaluation 37,5%, and communication skills 41%. Aims to develop an ISS learning model based on transformative learning theory and digitalization (TLTD) to improve nurses’ competencies. Method: Used Explanatory cross-sectional involved 190 practitioner nurses. Variables of individual characters (X1), facilities (X2), Social environment support/SES (X3), TLTD (X4), ISS (X5), and nursing competencies (Y) were measured. Data was collected using a checklist questionnaire, conducted on 6 June to 10 August 2022 at Dili, Baucau, and Maliana hospitals. Used descriptive and inferential analysis with SEM-PLS. Result: Five of the 11 hypotheses of statistical p-value < 0,05 and T-Test > 1,96, including X2>X4, X3>X5, X4>X5, and X5>y, to form ISS learning model. The characteristic of respondents were 81,8% young adults, 67,9% women, 57,8% undergraduates, judging the previous training 35% was unsuccessful, and 45,8% did not meet expectations. Learning facilities that are still lacking include policies 23,7%, curriculum 23,4%, guideline 22,7%, modules 27,9%, infrastructure 20,3%, social environment support 24,2% low, organizational support, 30,0% low peer support and 26,3% low family support. The average TLTD is 25,3% to 34,2%, ISS 22,1% to 30,5%, and nurse competence 25,3% to 30,5%.Suggestion: Result of the study become base to improve nurse’s competencies. Conclusion: Learning model was formed by facilities, SES, TLTD, ISS, and nurses’ competencies.

Background: Takayasu’s arteritis is a rare type of vasculitis, with severe complications like stroke, ischemic heart disease, pulmonary hypertension, secondary hypertension, aneurysms. Diagnosis is conducted by clinical and angiographic criteria. Treatment is medical and surgical, but unfortunately, the outcome is reserved. Case presentation: A 34- year- old Caucasian women had an ischemic stroke (2009). She was diagnosed with Takayasu’s arteritis and she received treatment with methotrexate, prednisolone, antiplatelet agents, with a mild improvement of clinical state. After 5 years (2014) she associated ascending aorta aneurysm, pulmonary hypertension, mild aortic regurgitation. The surgical treatment solved both ascending aorta aneurysm and left carotid artery stenosis (ultrasound in 2009 and computed tomography angiogram in 2014). Morphopathology revealed typical appearance for Takayasu’s arteritis. Tumor necrosis factor inhibitors (TNF-inhibitors) were associated to methotrexate. At 48 years (2023) she developed coronary heart disease (angina, electrocardiogram); echocardiography revealed severe pulmonary hypertension; angiography described normal coronary arteries, abdominal aorta pseudoaneurysm and arterial-venous fistula, with origin in right coronary artery and drainage on medium pulmonary artery. The patient refused surgical/ interventional treatment; she received again TNF- inhibitors, methotrexate, antiplatelet agents, statins. Conclusions: This case report presents us a severe form of Takayasu’s arteritis. We consider that morphopathology had a great importance in revealing to clinicians the typical appearance and the stadialization of inflammatory arterial process: acute or chronic. The verdict of morphopathologist was chronic phase, with acute relapses, so we decided that immunosuppressive treatment was still necessary.

Machine learning approaches are currently used to understand or model complex physical systems. In general, a substantial number of samples must be collected to create a model with reliable results. However, collecting numerous data is often relatively time-consuming or expensive. Moreover, the problems of industrial interest tend to be more and more complex and depending on a high number of parameters. High dimensional problems intrinsically involve the need of large data amount through the curse of dimensionality. That is why, new approaches based on smart sampling techniques are investigated to minimize the number of samples to be given to train the model, such as Active Learning methods. Here, we propose a technique based on a combination of Fisher information matrix and of Sparse Proper Generalized Decomposition that enables the definition of a new Active Learning informativeness criterion in high dimensions. We provide examples proving the performances of this technique on a theoretical 5D polynomial function and on an industrial crash simulation application. The results prove that the proposed strategy over-perform the usual ones.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin

Based on the high-precision quantitative measurement ability, the S-band subsystem of China's high- resolution aviation system carried out the agricultural application test for the first time in Jilin elm, China. The experiment is mainly carried out in combination with vegetation growth, soil moisture content inversion, wheat straw returning and ground feature classification. Through the design of quantitative measurement scheme, the results of different straw coverage and observation at different times are compared, which shows the prospect of S-band full polarization synthetic aperture radar system in the field of agricultural application.

Autophagy is a highly conserved catabolic process in eukaryotic cells. Reactive nitrogen species play roles as inductors and signaling molecules of autophagy. A key mechanism of NO-mediated signaling is S-nitrosylation, a posttranslational modification (PTM) of proteins at cysteine resi-dues. In the present work we analyzed the patterns of protein S-nitrosylation during the induc-tion of autophagy in Triticum aestivum roots. The accumulation of S-nitrosylated proteins in the cells during autophagy induced by KNO2 and antimycin A was visualized using monoclonal an-tibodies by Western blot analysis, and proteins were identified using a standard bottom-up pro-teomics approach. Protein S-nitrosylation is a labile and reversible PTM, and therefore SNO group can be lost during experimental procedures. Subsequent bioinformatic analysis using predictive algorithms and protein-ligand docking showed that identified proteins possess hypothetical S-nitrosylation sites. Analyzing protein-protein interaction networks enabled us to discover the targets that can directly interact with autophagic proteins, and those that can interact with them indirectly via key multifunctional regulatory proteins. In this study, we show that S-nitrosylation is a key mechanism of NO-mediated regulation of autophagy in wheat roots. A combination of in silico predictive algorithms with a mass spectrometry analysis provides a targeted approach for the identification of S-nitrosylated proteins.

Atherosclerosis (AS) is a chronic progressive disease caused by various factors, and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) -protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.

Sepsis is a serious and life-threatening medical emergency associated with dysregulated host immune responses to infection. Like cerebral vascular or acute cardiovascular incidents, sepsis is considered a time-dependent condition having severe and long-term consequences on human health. Apart from organ support, prompt administration of appropriate antimicrobial therapy is crucial to limit the burden of complications related to sepsis in ICU patients. The management of septic patients requires comprehensive and multi-disciplinary strategies for an adequate diagnosis. Most of the ICU population receives empirical antibiotic therapy without having a confirmed diagnosis. The misuse of antibiotics in intensive care units may increase the possibility of developing multidrug resistance along with considerable ecological side effects. The first doses of empirical anti-microbial therapy are slightly higher, regardless of the presence or absence of organ dysfunction, which may upregulate the production of circulating pro-and-anti-inflammatory mediators, having negative effects on the general well-being of the patients. This notion supports the introduction of individualized antimicrobial approaches based on local patterns of resistance to ensure the appropriate dosage of empirical therapy, as well as to limit the emergence of multidrug resistance in advanced-care patients. The adequacy and treatment duration must be viewed at regular intervals for effective de-escalation, and novel diagnostic approaches must be introduced to improve the quality of care in the ICU population.

Till date there are three full length COVID 19 virus genome sequences available from India. The earlier two were reported from Kerala, Southern India and the more recent one has been reported from Gujarat, western part of India. In this paper we report two novel mutations in the Spike protein sequence of Gujarat’s isolate. These mutations are based on comparison with the original Wuhan sequence. The two mutations have been found to be located just upstream and downstream of the receptor binding domain (RBD). Out of these two one has also been found to affect the secondary structure of the S1 domain. Since both of these mutations lie near the receptor binding domain, they might influence the spike receptor interactions by changing the conformation of the spike protein S1 domain. These mutations are uniquely placed and might be important in the context of vaccine engineering and therapeutic interventions.

Staphylococcus aureus (S. aureus) is recognized worldwide as one of the major agents of dairy cow intra-mammary infections. This microorganism can express a wide spectrum of pathogenic factors used to attach, colonize, invade and infect the host. The present study evaluated 120 isolates from eight different countries that were genotyped by RS-PCR and investigated for 26 different virulence factors to increase the knowledge on the circulating genetic lineages among the cow population with mastitis. New genotypes were observed for South African strains while for all the other countries new variants of existing genotypes were detected. For each country, a specific genotypic pattern was found. Among the virulence factors, fmtB, cna, clfA and leucocidins genes were the most frequent. The sea and sei genes were present in seven out of eight countries; seh showed high frequency in South American countries (Brazil, Colombia, Argentina), while sel was harboured especially in one Mediterranean country (Tunisia). The etb, seb and see genes were not detected in any of the isolates, while only two isolates were MRSA (Germany and Italy) confirming the low diffusion of methicillin resistance microorganism among bovine mastitis isolates. This work demonstrated the wide variety of S. aureus genotypes found in dairy cattle worldwide. This condition suggests that considering the region of interest might help to formulate strategies for reducing the infection spreading.

Variable-Angle Tow (VAT) laminates can improve straight fiber composites mechanical properties thanks to the application of curvilinear fibers. This characteristic allows to achieve ambitious objectives for design and performance purposes. Nevertheless, the wider design space and the higher number of parameters result in a more complex structural problem. Among the various approaches that have been used for VATs study, Carrera’s Unified Formulation (CUF) allows to obtain multiple theories within the same framework, guaranteeing a good compromise between the results accuracy and the computational cost. In this article, the linear buckling behavior of VAT laminates is analyzed through the extension of CUF 2D plate models within the Reissner’s Mixed Variational Theorem (RMVT). Results show that RMVT can better approximate the prebuckling non-uniform stress field of the plate when compared to standard approaches, thus improving the prediction of the linear buckling loads of VAT composites.

With the aim to develop novel scaffolds for sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably S-4-methoxytrityl (Mmt) protected mercapto acids, followed by removal of the acid labile S-Mmt group. This method allowed the efficient synthesis of the title compounds in high yield and purity, which were further used in the development a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with preformed nano-sized liposomes bearing maleimide groups on their surface. The reaction process was followed by 1H-NMR, using a Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment (1H-NMR CPMG), which allowed real-time monitoring and optimization of the reaction process. The thioether cross-linked liposomal scaffold that was synthesized was proven to preserve the nanosized characteristics of the initial liposomes and allowed sustained release of calcein (which was used as a chromophore), providing evidence for the efficient synthesis of a novel drug release scaffold consisted of nanoliposome building blocks.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori (H. pylori) infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To meet the need to develop test systems for personalized drug selection, we conducted a study of H. pylori molecular resistance in Moscow using a self-developed Sanger sequencing test platform. We validated our test system on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100%, and to levofloxacin - 93% and 92%, respectively. Then we tested our platform on 112 H. pylori -positive patients who had not previously received proton pump inhibitors (PPI) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples, and to levofloxacin in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G, to levofloxacin resistance – 261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.