Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widespread in European pig production, and although it is not an important food-borne pathogen, it constitutes a potential occupational hazard to farm workers and possibly to their household members. Farm workers can be exposed to LA-MRSA via direct contact with pigs and via airborne transmission. Bacteria can then be carried home in the nose or on the skin, potentially exposing household members. Therefore, it is important to consider LA-MRSA in a one-health context, studying human exposure by investigating LA-MRSA levels in pigs and in the farm environment, air, and dust. In the present investigation, we quantified LA-MRSA levels in nasal swab samples, air samples, and dust, collected at three different time points in a farm rearing pigs from appr. 30 kg until slaughter. Sampling was repeated across seven batches of pigs, resulting in the analysis of 504 nasal swab samples, together with air and dust samples. LA-MRSA was cultured and quantified on MRSA2 agar plates. Our findings revealed a significant batch-to-batch variation and a significant decrease of 94.1 % in LA-MRSA levels during the rearing period. Despite this decrease, all nasal swab samples tested positive, with the highest level reaching 353,000 cfu in a sample. In the 42 air samples collected, we found low to moderate LA-MRSA levels, with a maximum of 568 and an average of 63 cfu/m3. In the 28 dust samples collected during the second and third sampling periods, LA-MRSA counts were high, reaching up to 37,272 cfu/g, with an average of 17,185 cfu/g. The results indicate that while LA-MRSA levels in pigs gradually decrease with age and reach low levels before slaughter, the bacterium remains highly abundant in dust, which may pose an occupational hazard to farm workers.

The presence of Staphylococcus aureus in six dry-cured meat-processing facilities was investigated. S. aureus was detected in 3.8% of surfaces from five facilities. Prevalence was clearly higher during processing (4.8%) than after cleaning and disinfection (1.4%). Thirty eight isolates were typified by PFGE and MLST. Eleven sequence types (STs) were defined by MLST. ST30 (32%) and ST12 (24%), were the most abundant. Enterotoxin genes were detected in 53% of isolates. The enterotoxin A gene (sea) was present in all ST30 isolates, seb in one ST1 isolate and sec in two ST45 isolates. Sixteen isolates harbored the enterotoxin gene cluster (egc) with four variations in the sequence. The toxic shock syndrome toxin gene (tst) was detected in 82% of isolates. Regarding the antimicrobial resistance, twelve strains were susceptible to all the antibiotics tested (31.6%). However, 15.8% were resistant to three or more antimicrobials, and therefore multidrug-resistant. Our results showed that, in general, efficient cleaning and disinfection procedures were applied. Nonetheless, the presence of S. aureus with virulence determinants and resistance to antimicrobials, and particularly multidrug resistant MRSA ST398 strains might represent a potential health hazard for consumers, even though the pathogen was not isolated from final products.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.

In the provinces of the region, empirical constructions reached maximum points with these practices. The effects and pathologies appear as physical, chemical and mechanical failures in pillars, walls and roofs, generating uncertainty for the user. The current powerful design can detect the interior deterioration of coatings in adobe, brick and concrete constructions, and prevent collapses, material and economic losses. Experimental methods performed affirm the serious validity. The accuracy of the simulation and design provide a pre-test reliability of 95%. Five piles constructed of various materials participate in the prototype performance test, there is a correlation (R=0.9997) between the magnetic field range "B" (cm) and density "ρ" (g/cm³), also by increasing the current (i) in transit Q1 and coil L1, the induction of the "B" increases proportionally until penetrating the density of the wall of the building, having 5% reading error.

The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

Background: Staphylococcus aureus (S. aureus) is an opportunistic pathogen and a predominant cause of life-threatening nosocomial infections. Drug resistance in S. aureus is attributed to production of biofilm, which is controlled largely by bacterial quorum sensing (QS) systems. Methodology: In vitro analysis of biofilm inhibition assay was performed using crystal violet staining assay, swarming motility, light microscopy and growth curve analyses. Identification of the major constituents of I. verum fruit extract was performed by GC-MS. Ligand-protein interaction was analyzed by molecular docking investigations. Results: The methanol extract of I. verum inhibited the growth of MRSA at the concentration of 4.8 mg/ml. At the sub-inhibitory concentration (2.4mg/ml), the extract showed significant reduction in biofilmogenesis. Light microscopy analysis confirmed the antibiofilm activity as well as the efficacy in disturbing biofilm architecture. A reduced swarming motility was observed at the lowest concentration of 2.4mg/ml. GC-MS analysis revealed anethol (AL) as the major constituent. The molecular docking analysis attributes the antibiofilm activity to an active ligand AL, which strongly interacted with the active site residues of AgrA and SarA proteins of S. aureus. Conclusion: We report the activities of I. verum to be immensely interfering with QS system and biofilm formation in MRSA.

On 19 September 2021, La Palma volcano (Canarias Archipelagos) started an eruption that persisted until 13 December 2021. Despite the Volcano Explosive Index (VEI) being estimated equal to 3, corresponding to not so powerful eruption, the long eruption activity posed much scientific in-terest in this natural hazard event. In this paper, we searched for possible effects of this eruption on the atmosphere and ionosphere, investigating the climatological archive and Swarm magnetic satellite data. In particular, we explored Aerosol, Sulphur Dioxide and Carbon Monoxide con-centrations in the atmosphere identifying both the direct emissions from the volcano as well as the plume that drifted toward West-South-West and was reinforced during the eruption period. The vertical profile of temperature from the Saber satellite was analysed to search for the possible presence of acoustic gravity waves induced by volcanic activity. Compared with the year before without eruption in the areas, a lot of Saber profiles present an Energy Potential very much higher than the previous year, proposing the presence of Acoustic Gravity Waves (AGW) induced by volcano eruption activity. We also identified Swarm magnetic disturbances on the day of the eruption and in November. The mechanism of coupling could be different for the latter one, as there is no evidence for AGW. They may be due to a more complex of physical and chemical al-terations that propagate from the lower atmosphere to the upper one into the ionosphere.

This study was conducted to investigate the impact of El Niño Southern Oscillation on rainfall distribution and productivity of major Agricultural crops in the Kembta Tembaro Zone of Southern Ethiopia over the past 30 years. Precipitation and temperature data were obtained from the National Meteorology Agency, crop data from the Central Statistical Agency of Ethiopia, and the Sea Surface Temperature data from the NOAA website. The rainfall trend had shown decreasing trend with high variability at all the stations (p<0.05). Over the same period, El Niño and La Niña event were observed and highly affected rainfall distribution. It was found that Coefficient Variation was greater than 30%, which indicates the area was prone to drought episodes. The impacts of the ENSO events on the yield of Maize, Wheat, Barely, Sorghum and Enset were assessed. Wheat and Maize were highly affected by the ENSO events. Enset was found to be more resistant crop to the influence of ENSO. Barely and Sorghum were affected at varying magnitude. Among the five chosen crop for this investigation two of the crops were seriously affected during the two extremes, i.e. El Niño and La Niña. From this investigation it is conclude that the overall cereal crop productivity was decreased and precipitation variability was noticed. So, having the information about ENSO phase in advance can be used to forecast ENSO and select crop types and varieties to maximize agricultural rain fed cereal crop productivity while minimizing the crop risk associated with seasonal rainfall and ENSO phases.

Abstract. The increasing frequency of isolation of methicillin-resistant Staphylococcus aureus (MRSA) limits the chances of effective antibacterial therapy of staphylococcal diseases and results in development of persistent infection such as bacteremia and osteomyelitis. The aim of this study was to identify features of the MRSAST239 0943-1505-2016 (SA943) genome, that contribute to the formation of both acute and chronic musculoskeletal infections. The analysis was performed using comparative genomics data of the dominant epidemic S. aureus lineages namely ST1, ST8, ST30, ST36, ST239. SA943 genome encodes proteins that provide resistance to the host immune system, suppress immunological memory and form biofilms. The molecular mechanisms of adaptation responsible for development of persistent infection were as follows: amino acid substitution in PBP2 and PBP2a, providing resistance to ceftaroline; loss of a large part of prophage DNA and restoration of nucleotide sequence of beta-hemolysin, that greatly facilitates escape of phagocytosed bacteria from phagosome and formation of biofilms; dysfunction of the AgrA system due to the presence of psm-mec and several amino acid substitutions in the AgrC; partial deletion of nucleotide sequence in genomic island vSAβ resulting in the loss of two proteases of Spl - operon; deletion of SD repeats in SdrE amino acid sequence.

From the hospital wastewater, a novel bacteriophage was isolated and characterized. According to characterization properties, this bacteriophage belongs to the Siphoviridae family, the maximum bacteriophage titer was recorded at 37°C and a pH of 7.2, had a 44,789 bp linear double-strand DNA genome, and within the genome sequence, there are 61 genes, all of which are encoded into proteins. Although this bacteriophage does not have any virulence factors or antimicrobial resistance genes and had specific lytic activity against some antimicrobial resistance S. aureus clinical isolates.

In the Yucatán Peninsula, anthropogenic activities such as urbanization and final dispose of solid and wastewaters critically impact aquatic systems. Here, we evaluated the anthropogenic-related environmental alteration of Lake La Sabana, located in the northern limit of one of the main cities of the Mexican Caribbean. We evaluate lake water quality using physical, chemical, and microbiological indicators, and heavy metals in surficial sediments and fish tissue to evaluate the potential environmental risk. Multivariate analyses reveal that environmental conditions in La Sabana are spatial and temporal heterogeneous. Medium to bad water quality was determined within basins by the NSFWQI, related with the degree of anthropogenic influence. The center-south zones display critical microbiological values largely exceeding national standards. Heavy metals in sediments (Zn&gt;Hg) and fish tissue (Hg) were relatively low, but Hg concentration threat the ecological environment. Incipient wastewater treatment and final dispose in La Sabana is the main responsible of changes in the trophic status and nutrients availability, which in turn may have promoted changes in the biological structure and aquatic plant invasions. Lake La Sabana can be considered a model of the potential sequential effects of the anthropogenic alterations in oligotrophic karts tropical aquatic systems in Yucatán Peninsula.

We present a cost- and time-efficient method for the controlled preparation of single phase La(IO3)3 nanoparticles via a simple soft-chemical route which takes a matter of hours, thereby providing an alternative to the common hydrothermal method which takes days. Nanoparticles of pure α-La(IO3)3 and pure δ-La(IO3)3 were synthesised via the new method depending on the source of iodate ions, thereby demonstrating the versatility of the synthesis route. The crystal structure, nanoparticle size-dispersal and chemical composition were characterised via angle- and energy-dispersive powder X-ray diffraction, scanning electron microscopy and Fourier-transform infrared spectroscopy.

El Niño is warming of the sea surface temperature of the Pacific Ocean. Extreme flooding, drought, lack of potable water for livestock and domestic use, food insecurity and market imbalance are associated with El Niño and La Niña in Ethiopia. Drought following El Niño caused 50 to 90% crop failure, in the eastern parts of Ethiopia. El Niño episodes are detected using different statistical indices such as Oceanic Nino Index (ONI), Agricultural Stress Index System (ASIS) and the Southern Oscillation Index (SOI), with magnitude ranging from weak to strong. Identifying the El Niño and La Niña seasons it is very important to adopt suitable adaptation strategies, which can resolve and/or reduce the negative impacts. Early warning and immediate support to the impacted areas have been carried out to minimize risks from El Niño animal feed for livestock from other areas has been transported to the vulnerable areas. Planting early maturing and drought resistant crops, supplementary irrigation, early waning information on weather and climate have been exercised as climate change adaptation strategies, early warning mechanisms by the government of Ethiopia. El Niño and La Niña are natural phenomena; however, it is necessary to study the occurrence and distribution of El Niño and La Niña episodes to enable early warning and identify suitable adaptation strategies and policy implications in the country.

It is important for researchers in material domain to reconstruct and visualize the microstructure of alloy, which helps discover morphologies and properties that can only be found in three dimensional and microscopic space. However, because of the limitation of state-of-the-art sensors, the internal microstructure of the material is not easy to obtain. In this paper, a novel automatic 3D reconstruction method is proposed using diffraction contrast tomography technology to capture the 3D microstructure of Al-La alloy. The pipeline of the proposed method starts from the imaging of Al-La alloy with the LabDCT technique from Carl Zeiss AG, which produces a sequence of 2D microstructure sections. Then, a segmentation algorithm based on superpixel and lifted multicut is proposed to extract the 2D microstructure in an image section. Finally, 2D segmentations are joined together to reconstruct and visulize the 3D microstructure. As a result, a novel morphology of Al-La alloy is recovered with both dendrite and lamellar morphologies. The proposed method has the advantage of the ability to losslessly recover the internal microstructure.

The purpose of the present study was to investigate anti-staphylococcal activity of liposomal daptomycin, against four biofilm-producing S. aureus and S. epidermidis clinical strains, three of which are methicillin resistant. Neutral and negatively charged Daptomycin-loaded liposomes were prepared by three methods thin film hydration (TFH), DRV and microfluidic mixing (MM), and characterized for drug encapsulation (EE%), size distribution, zeta-potential, vesicle stability, drug release and drug integrity. Interestingly, whilst drug loading in THF and DRV nanosized (by extrusion) vesicles was around 30-35, very low loading (~4%) was possible in MM vesicles, requiring further explanatory investigations. Liposomal encapsulation protected daptomycin from degradation and preserve its bioactivity. Quantitative microtiter plate (crystal violet, CV), methylthiazoltetrazolium (MTT), and growth curve (GC) assays evaluated antimicrobial activity of neutral and negative charge daptomycin-liposomes towards planktonic bacteria and biofilms. Neutral liposomes exhibited dramatically enhanced inhibition of bacteria growth (compared to free drug) for all species studied, while negative charged liposomes were totally inactive. Biofilm prevention and treatment studies revealed high antibiofilm activity of liposomal daptomycin. Neutral liposomes were more active for prevention and negative charge ones for treating established biofilms. Planktonic bacteria as well as matured biofilms of low daptomycin susceptible MRSE and MRSA strains were almost completely eradicated by liposomal-daptomycin indicating the need for their further exploration as antimicrobial therapeutics.

Antimicrobial resistance is a major public health concern. Rodents and shrews live in closer proximity to humans and animals and serve as reservoirs for the transmission of several diseases, including AMR pathogens. There is no data available from India on surveillance of AMR bacteria in rodents and shrews. In this study, bacterial pathogens viz, Staphylococcus sp, Escherichia coli and Salmonella sp were isolated from rodents and shrews and genetic elements conferring antimicrobial resistance in the pathogens were screened by PCR. Bacterial pathogens in the oropharyngeal and anal swabs collected from the rodents and shrews trapped (n=100) were cultured on selective media such as Mannitol salt, Mac Conkey and Xylose lysine deoxycholate media to isolate Staphylococcus sp., E. coli and Salmonella sp. respectively. A total of 76 (80%) S. aureus and 19 (20%) Staphylococcus non aureus were isolated. E. coli was isolated in 89 samples and among the Salmonella sp (n=59), 16 (27%) were S. enteritidis and 29 (49.1%) were S. typhimurium. In S. aureus isolates, mec A and mec C (MRSA) were detected in 40 (52.6%) and 6 (7.9%) isolates respectively. Also, 7 (36.84%) and 1 (5.3%) Staphylococcus non aureus isolates were tested to harbour mec A and mec C genes. A total of 77 (86.5%) E. coli isolates had genes encoding ESBL [TEM in 21 (23.59%), SHV in 45 (50.6%) and CTXM in 11 (12.4%)]. Among the 45 pathogenic Salmonella sp, 44 (97.78%) harboured AMR genes [tet in 13 (28.9%), sul3 & sul4 in 20 (44.4%) and qnrA in 11 (24.4%)]. Thirty-eight animals harboured more than one zoonotic pathogen and 21 with multi-drug resistant genes. Our findings signify that these rodents and shrews may serve as sentinels to screen environment spillover of AMR pathogens and also act as reservoir to transmit MRSA, ESBL, Salmonella sp. human/animals. Also these animals aid in the transfer of antimicrobial resistance genetic elements to non-pathogenic organisms.

Staphylococcus aureus (S. aureus), particularly Methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen that causes a variety of infections in hospital and community settings. It poses a significant risk and challenge for global health that hinders our ability to control and treat bacterial infections. Recently, the emergence and spread of variant strains of bacteria, misuse of the limited available options of effective antibiotics, spread of fake drugs, and climate change that increased the contact between humans and animals’ populations carrying different bacterial has significantly increased the incidence of Multi-Drug Resistance strains (MDR). This in turn, has created a severe problem in the infection control treatment of S. aureus infected patients. Treatment options for MRSA infection are increasingly limited and complicated. Unfortunately, different strains of MRSA are showing tolerance and resistance toward vancomycin, which is the standard of care for complicated MRSA. Therefore, it is crucial now to invest developing new effective anti-biotics and synergies, develop and implement national action plans for the management of an-tibiotic resistance, as well as improving our understanding of the antimicrobial resistance mechanisms. Here, in this review we explain the main mechanisms of antibiotic resistance in MRSA and describes different approaches to manipulate it in MRSA, providing a basis for de-signing effective drugs, and shedding some light on the evolution of S. aureus.

On the afternoon of January 31, 2022, the northwest and central part of the city of Quito (Ecuador) was hit by a mud-flow that originated in one of the ravines of the Pichincha volcanic complex. According to the official reports, there were 28 fatalities, one missing person, 52 injured, and 53 families affected. The mudflow was triggered by unusual and heavy rainfall in the upper part of the drainage. However, the analysis of the deposits allowed us to establish the existence of anthropogenic elements as crucial components of a local disaster that affected daily life in the city for more than a week. Based on the preliminary data, we were able to determine that the mud and water flowed through different streets of the city, reaching a maximum distance of 3.2 km from the overflow point (collector, construction works to dam the drainage under the city). The analysis of the multimedia material published on social networks and in the press also made it possible to detect the change in the behavior of the flow during its evolution, which went from a hyper-concentrated flow to muddy water. A similar event occurred in 1975, and although it was a larger event (52000 m3, seven times larger than in 2022), it caused two deaths and little damage in the same area. The main causes of the disaster included urban development that did not meet the needs of the area and a lack of awareness or ignorance about the management and intervention of drainage in Quito City.

The La Oroya metallurgical complex reveals a process of structural or power pathology, where economic and environmental social policies lead to a citizenry without systemic freedom, characterized by environmental contamination (PAMA executed on average 67%, some processes with 0%) and sanitary (plumbosis 8.39 to 10.28 μg / dL), the economic dependence of this industry is also observed, which caused the weakening of the communities to maintain autonomy over their own destinies.The Doe Run Peru, operated the metallurgical complex, creating added value to the extractive-export chain of mineral concentrate, but also took advantage of the legal loopholes, the little coordination between the State institutions and the little authority of the supervisory institutions to get the most out of it, complying with the law in some cases, but without moral quality in some others, such as health in the oroinos.Government institutions must have strong links that provide a normative framework with prospects with sustainable development, where the beneficiary is society and not only certain interest groups. The economic benefits of the metallurgical complex operation are multiple, which begin with labor, the purchase and sale of materials and services, the collection of taxes and energy.

Corundum-rich (up to 55 vol.%) felsic dykes formed by albite, ±K-feldspar, ±hercynite and ±biotite-siderophyllite cut the lower crustal rocks exposed in the Ivrea-Verbano Zone (NW Italy). Zircon is an abundant accessory mineral and its investigation through LA-ICP-(MC)MS has allowed to directly constrain the timing of emplacement, as well as petrology and geochemistry of parental melts. Zircons are characterised by very large concentration in REE, Th, U, Nb and Ta, and negative Eu anomaly. U–Pb analysis points to Norian emplacement ages (223±7 Ma and 224±6 Ma), whereas large positive εHf(t) values (+13 on average) indicate a derivation from depleted to mildly enriched mantle source. The mantle signature and the corundum oversaturation were preserved thanks to limited crustal contamination of the host, HT refractory granulites and mafic intrusives. According to the geochemical data and to the evidence of the development of violent explosions into the conduits, it is proposed that dykes segregated from peraluminous melts produced by exsolution processes affecting volatile-rich differentiates during alkaline magmatism. This work provides robust evidence about the transition of the geochemical affinity of Southern Alps magmatism from orogenic-like to anorogenic during Norian, linked to a regional uprising of the asthenosphere and change of tectonic regime.

Abnormal Tau phosphorylation and aggregation into neuronal paired helical filaments and neurofibrillary tangles cause tauopathies, a class of neurodegenerative diseases, that include Alzheimer’s disease, frontotemporal dementia and parkinsonism linked to chromosome 17, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration. Glycogen synthase kinase-3β (GSK-3β) is the most critical kinase to phosphorylate Tau. We have developed the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), with cyclopropane rings instead of cis-double bonds, as an anti-dementia drug. DCP-LA serves as a selective activator of PKCε and a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B). DCP-LA prevents Tau phosphorylation due to PKCε-mediated direct inactivation of GSK-3β, to PKCε/Akt-mediated inactivation of GSK-3β, and to receptor tyrosine kinase-mediated inactivation of GSK-3β in association with PTP1B inhibition. DCP-LA targeting GSK-3β, thus, could become a valid drug for treatment of tauopathies.

The wound management sector has attracted considerable attention due to the increasing challenge posed by antimicrobial resistance (AMR) and the specialized care required for chronic wounds. Effective wound care involves selecting appropriate dressings tailored with antimicrobial agents to prevent bacterial infection. Among various types of wound dressings, fibers and electrospun fibers, with their unique characteristics, have emerged as innovative new materials. However, the rise of AMR necessitates the exploration of new antimicrobial agents for wound dressings, particularly for addressing bacterial pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Endophytic fungi, known for producing diverse bioactive compounds, including novel antibacterial agents, represent a promising source of such new agents. This study tested thirty-two endophytic fungi from thirteen distinct Australian native plants for their antibacterial activity against S. aureus, the most common wound-associated bacteria. Ethyl acetate (EtOAc) extracts from fungal culture filtrates exhibited inhibitory effects against both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. DNA sequence analysis was employed for fungal identification, with EtOAc extracts from the most active sample, EL 19 (Chaetomium globosum), selected for further bactericidal and antibiofilm testing against the chosen bacteria. Biofilm of S. aureus ATCC 25923 was reduced by 55% by EtOAc extracts of EL 19 at 1/2 × MIC. To demonstrate the potential application in wound dressing materials, three different concentrations of the extract were incorporated into Polycaprolactone fiber mats through electrospinning, with resultant inhibition of S. aureus ATCC 25923 being observed. This research underscores the potential of endophytic fungi from Australian plants as sources of substances effective against common wound pathogens. Further exploration of the responsible compounds and their mechanisms could facilitate the development of wound dressings effective against MRSA and innovative biofilm-resistant electrospun fibers, contributing to the global efforts to combat AMR.

Of late, the focus has been shifted towards quorum sensing inhibitors which reduce bacterial virulence and lower the probability of resistance and refining infections. In this work, meta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor against Staphylococcus aureus and MRSA phenotypes, was formulated in chitosan nanoparticles (ChNPs) using ionic gelation method. mBTL-loaded-ChNPs were characterized for particle size, polydispersity index, zeta potential. Morphology was visualized by Transmission Electron Microscopy (TEM), drug release profile and antibiofilm analysis using Confocal Laser Scanning Microscope (CLSM) and Scanning Electron Microscopy (SEM) were performed. Synthesized mBTL-loaded-CNPs showed homogenized nano-size particles ranging from 158+1.3 to 284+5.6 nm with spherical particles that exhibited sustainable release profile over 48 hr at 37 °C. These findings revealed successful preparation of mBTL-loaded-ChNPs, that further showed effective antibiofilm activity at MIC50 (0.5 mg/mL) where all strains displayed reduced biofilm formation compared to untreated strains. CLSM results showed a significant reduction in the number of viable cells, indicating the effectiveness of m-BTL as an antibacterial agent. SEM analysis permitted visualization of biofilm structure in relation to the spatial localization of important biofilm matrix components, the formed biofilms were clearly distinguished in the SEM images. Bacterial cells in the control group were enclosed in thick biofilms. In contrast, there was a considerable reduction in biofilm production when mBTL was present, where bacterial cells seemed less ordered and more scattered with no detectable biofilms. In conclusion, mBTL-loaded-ChNPs is a potential alternative treatment to overcome antimicrobial resistance and condensed MRSA infections.

In the former mining district of La Carolina (southern Spain), waste materials were accumulated without first waterproofing the substrate. Additionally, these mining dams were abandoned without any type of restoration, conditions that present a significant risk of contaminating the surrounding soils and waters. Prior to carry out the necessary works for isolating these residues, morphological characterization of the contact with the base substrate is needed. For that purpose, in recent years, different indirect study techniques have been used, among which electrical to-mography stands out. In this work, a less common geophysical technique, magnetometry, both in its magnetic and gra-diometric modalities, is used as an alternative method to analyse the geometry and structure of a mining dam. The results obtained with this methodology are compared with the results provided by electrical techniques, as well as with direct data from mechanical surveys and aerial photo-graphs prior to waste deposition. The magnetic anomaly curves obtained with geometric models generated with the Mag2dc program were also analysed. This comparative study shows the use-fulness of magnetic prospecting in characterizing the base geometry of these mining structures and therefore the interest in its application to environmental characterization studies.

In this study, the hot deformation of Cu-0.55Sn-0.08La (wt%) alloy was studied by gleeble-3180 testing machine at deformation temperatures of 400-700oC and various strain rates. The stress-strain curve showed that the hot deformation behavior of Cu-0.55Sn-0.08La (wt%) alloy was greatly affected by work hardening, dynamic recovery, and dynamic recrystallization. The activation energy Q was calculated as 287.141 kJ/mol , and hot compression constitutive equation was determined as ε ̇=[sinh(0.006388σ)]^12.123∙exp⁡(37.7505-287.141/RT). The microstructural evolution of the alloy during deformation at 400oC revealed the presence of both slip and shear bands in the grains. At 700oC, dynamic recrystallization grains were observed but recrystallization was incomplete. In sum, these results provided the theoretical basis for continuous extrusion process of alloys with promising future use.

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against Methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.

Necrotizing pneumonia due to Methicillin-Resistant Staphylococcus Aureus (MRSA) is devastating and difficult to treat in preterm infants. We report a case of severe MRSA necrotizing pneumonia in a preterm infant. As an add-on rescue therapy to vancomycin, linezolid rapidly cured this case after the failure of vancomycin plus rifampicin. This rapid cure suggests that adjunctive rather than rescue linezolid may be considered in such cases.

Average of 41,900 patients are diagnosed annually with staphylococcus bacterial infection in California, 24,089 patients have Methicillin-resistant Staphylococcus Aureus (MRSA) and 17,810 patients have Methicillin-Sensitive Staphylococcus (MSSA). This paper demonstrates that there is a difference in mortality rate due to staphylococcus infection between males and females (P-value<0.05, CI 95%). Male patient diagnosed with S. aureus has 1.3 chance of mortality incidence than female patient. In addition, MRSA infection rate is 1.4 times MSSA infection (P-value<0.05, CI 95%), but the gap of infection is decreasing; however, mortality of both infections combined are more than threefold greater compared to three decades ago.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing some antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrating remarkable efficacy against planktonic cells and biofilms of MRSA, outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, was showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wound in mice. Together the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

Wound infections evidently appeared in times of World War I that accounted a significant mortality and morbidity rate among injured soldiers. Currently, around 11 million people worldwide require medical treatment for wound infections and 300,000 die every year due to untreated wound infection. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high priority area of research. During the past few decades, nanotechnology has arisen with new promising technology for synthesis of nanobiomaterials. Metallic nanoparticles (NPs) are considered as new alternative treatment with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC ® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.

To investigate proposed ferromagnetic fluctuations in the single-layer Bi-2201 and La-214 high-Tc cuprates, we performed magnetization and electrical-resistivity measurements using single-layer Tl-2201 cuprates Tl2Ba2CuO6+d as well as La-214 La2-xSrxCuO4 in the heavily overdoped regime. Magnetization of Tl-2201 exhibited the tendency to be saturated in high magnetic fields at low temperatures, suggesting the precursor behavior toward the formation of a ferromagnetic order. It was found that the power of temperature n obtained from the temperature dependence of the electrical resistivity is ~ 4/3 and ~5/3 for Bi-2201 and La-214, respectively, and is ~ 4/3 at high temperatures and ~5/3 at low temperatures in Tl-2201. These results suggest that two-dimensional ferromagnetic fluctuations exist in Tl-2201 at high temperatures and Bi-2201 and that three-dimensional ferromagnetic fluctuations exist in Tl-2201 at low temperatures and La-214. The dimensionality of ferromagnetic fluctuations is understood in terms of the dimensionality of the crystal structure and the bonding of atoms in the blocking layer.

In the paper, the results of an investigation into trace elements found in slag sulphides from 14 archaeological Bronze Age settlements of the Cis-Urals, Trans-Urals and North and Central Kazakhstan are presented. The study used Cu-(Fe)-sulphides as indicator minerals. Cu-(Fe)-S minerals in slags are primarily represented by covellite and chalcocite, as well as by rarer bornite and single chalcopyrite grains. Slag sulphides formed relic clasts and neogenic droplets of different shapes and sizes. Supergenic ores in the Bronze Age in Urals and Kazakhstan played a significant role in the mineralogical raw material base. In sulphides, the main indicator elements Fe, Co, Ni, As, Se, Te, Sb, Ag, Pb, and Bi are important markers of copper deposit types. Sulphides from olivine Cr-rich spinel containing slags of Ustye, Turganik, and Kuzminkovskoe 2 are characterised by As-Co-Ni assemblages and confined to copper deposits in ultramafic rocks. Olivine sulphide-containing slags from Kamenny Ambar, Konoplyanka and Sarlybay 3 are characterised by Co-Se-Te assemblage and confined to mafic rocks. Glassy sulphide-containing slags from Katzbakh 6, Turganik, Ordynsky Ovrag, Ivanovskoe, Tokskoe, Bulanovskoe 2, Pokrovskoe, Rodnikovoe, and Taldysay are characterised by Ag-Pb-(Ba)-(Bi) assemblage and confined to cupriferous sandstone deposits. High As, Sb, Sn and Ba contents found in slags can be seen as indicators of alloying or flux components in primary copper smelting. These include samples from Ustye, Katzbakh 6, Rodnikovoe, and Taldysay sites, where high Ba and As slag contents are identified. The compilation of a database with a broad sample of sulphide compositions from Bronze Age slags and mines in the Urals and Kazakhstan will permit the further identification of ore types and raw materials associated with a particular deposit.

In the quest for robust and efficient digital communication, this paper introduces cutting-edge key exchange protocols leveraging tropical semirings’ computational prowess and block matrices’ structural resilience. Moving away from the conventional use of finite fields, these protocols deliver markedly faster processing speeds and heightened security. We present two implementations of our concept, each utilizing a different platform for the set of commuting matrices: one employing tropical polynomials of matrices and the other employing Linde-de la Puente matrices. The inherent simplicity of tropical semirings leads to a decrease in operational complexity, and using block matrices enhances our protocols’ security profile. The security of these protocols relies on the Matrix Decomposition Problem. We also provide a comparative analysis of our protocols against existing matrix block-based protocols in finite fields. This research marks a significant shift in cryptographic protocol design, specifically tailored for demanding engineering applications, and sets a new standard in secure and efficient digital communication.

In Spain, the National Health System, of a public nature, provides care to Spaniards and other residents in Spain. It is a system adapted to the State of Autonomies, decentralized. Each Auton-omous Community has legislative capacity in its organization and management. We studied the agreement of private hospitals by the public system in La Rioja, an Autonomous Community of Spain located in the North of the Iberian Peninsula. Documentary sources from the General archives of La Rioja, the Institute of Riojan Studies, municipal funds (Logroño, Haro, Calahorra), and in-formation from catalogs and censuses of hospitals from the Ministry of Health, National Institute of Statistics, and Institute of Statistics of La Rioja have been reviewed. The hospital model of La Rioja is characterized by a predominance of public beds over private ones, although there is a growing trend in the number of private beds from 2013 onwards, due to the incorporation of two conva-lescent socio-health hospitals. A characteristic element of La Rioja has been the promotion of pub-lic-private collaboration, conceived as a strategic alliance. Regarding agreements, in La Rioja there has been a specialization in the socio-health space, whose formulas have been the management service contract and the concession of work. The development of the Health System in La Rioja, 1986-2019, has been determined by the presence of a mixed public-private hospital system and a progressively lower dependence on specialized hospitals from other Autonomous Communities.

In this paper, 6063 aluminum alloy for common building profiles is used as the research object. By adding a new Al-Ti-C-La composite alloy, the effect of 6063 aluminum alloy on the microstructure and properties of 6063 aluminum alloy is studied. The results show that Al-Ti-C-La composite alloy has obvious effect on grain refinement of 6063 aluminum alloy. With the addition of Al-Ti-C-La composite alloy, the grain size decreased significantly. When the addition amount of Al-Ti-C-La composite alloy is 1%, the grain size is reduced from 482 μm to 121 μm. Rare earth La is mainly distributed near the Mg2Si phase and β-AlFeSi, and complex compounds such as AlFeSiMgLa are formed. After aging for 270 days on the basis of T6 heat treatment, the tensile strength and elongation of 6063 aluminum alloy augmented with the addition of Al-Ti-C-La composite alloy, and the Vickers hardness gradually diminished. When the addition amount of Al-Ti-C-La composite alloy is 1%, the tensile strength, elongation and Vickers hardness of 6063 aluminum alloy reach 177.2 MPa, 17.8% and 60.9 HV, respectively, and the tensile strength is increased by 16.3%. The elongation is increased by 50.8%, the Vickers hardness is reduced by 15.4%, and the fracture of the alloy is mainly ductile fracture.

Metal hydrides are one of the types of functional materials that allow safe and compact storage of a large amount of hydrogen, which is increasingly used today as an alternate fuel or energy source. The possibility of obtaining the initial energy necessary for the production of hydrogen by electrolysis process from renewable energy sources, such as solar panels and wind generators, makes hydrogen energetic quite attractive and rapidly developing industry sector. Solid form of hydrogen storage with the possibility of reversible sorption, gives opportunity for creation autonomous energy storage systems. La-Ni based alloys allow hydrogen storing at ambient temperatures and pressure not higher than 15 bar, which makes the application of these alloys quite practical, interesting and prospects for analysis and modifications on the ways of stored hydrogen capacity increasing, alloys price reducing and application for renewable energy storage.

In this study, global response analysis was performed to explore the mechanism of action of Usnic acid and its synergy with Norfloxacin, a well-known quinolone antibiotic to which MRSA clinical isolates showed resistance (MIC, 500 µg/mL). Microdilution assay, growth kinetics, microscopic analysis, and cell-based assays consistently showed that Usnic acid possess strong anti-staphylococcal activity (MIC, 7.8 µg/ml), causes cell leakage, modulates efflux pump activity, and synergizes with Norfloxacin against multi-drug resistant clinical isolate MRSA 2071. Whole cell proteome profiling using gel-free based nano-LC-ESI-QTOF-MS/MS revealed several proteins whose expression was significantly modulated by Usnic acid and Norfloxacin alone or in combination. Usnic acid downregulated the abundance of RNA polymerase subunits (RpoB, RpoC), carbamoyl phosphate synthase large subunit (PyrAB), chaperone (GroEL), and adenylosuccinate synthetase (PurA). Interestingly, proteins found to be upregulated in the presence of Usnic acid and Norfloxacin included oxidative stress-related proteins such as peroxidase (Tpx), alkyl hydroperoxide reductase (AphC), and general stress protein (UspA). This study clearly showed that Usnic acid affects numerous cellular targets and can potentiate the action of Norfloxacin. Furthermore, an in-vivo study emphasized the use of Usnic acid to develop as a safe phytopharmaceutical to repurpose old antibiotics through combination therapy against MRSA infections.

Discovery and development of effective strategies to treat emerging and often drug resistant strains of viral and microbial pathogens presents one of the greatest challenges of the 21st century. Despite nearly a century of progress in developments in antimicrobial and antiviral therapies, infectious diseases still account for a substantial proportion of deaths worldwide, including over 100 million globally in the recent pandemic to date. In recent decades, the plague of antimicrobial resistance also represents an additional and alarming signal for both human and animal healthcare and signals a renewed sense of urgency in addressing this issue. This has made the search for novel classes of antibiotics, antivirals and therapeutics found to be capable of bypassing the microbial and viral resistance mechanisms necessary to in order to replenish our current arsenal of antimicrobial and antiviral drugs and update our therapeutic regimens. In addition, the tremendous impact exerted by viral infections and related pathologies on our lives during the recent decade has forced scientists to acknowledge the opportunities and challenges associated with tackling infectious diseases by developing effective antiviral agents endowed with novel mechanisms of action. The discovery of new antimicrobial/antiviral agents, as well as the repurposing of existing drugs and therapeutic options will be crucial to fight the ever-increasing resistance of “superbugs”, pathogenic fungi, viruses, and parasites. Proponents of modern biophoton therapy proposed in this paper can trace its origins to the Russian scientist Alexander Gurwitsch, who a century ago observed ultra-weak emissions of light emerging from an onion root and soon found additional living tissues to be emanating similar energetic phenomena, thus energizing research which continues to the present day and projected toward the development of useful applications of the new-found biological photonic phenomena. The purpose of the present paper is to introduce the past experiences, potential applications and highly successful outcomes of biophotonic therapy as an option to treat infectious diseases including HIV, Hepatitis C, MRSA, and others, with emphasis on efficacy of using biophotonic therapies to treat and ameliorate the drug resistant variants of the above infectious agents, including potential applications for the current COVID-19 pandemic and in preparation for the emergence of the next epidemic or pandemic.

International basins are divided into sub-basins that are managed at the national and local levels, within the territory of each country, before reaching the level of international concern. The management of international basins could be developed using an integrated water management, based on multi-level governance model in which many actors are involved, from local to international scale. However, in the La Plata River Basin this model is not working, even with international agreements such as the La Plata Basin Treaty, which was signed in 1969. The understanding of political interests behind the law helps to explain its inefficiency. Therefore, considering the lack of a systemic view in an international watershed, it could be possible to have accumulating effects caused by the transformations of watercourses in the sub-basins. Then, the 2014 water crisis in the State of São Paulo, Brazil, is an example of the possible consequences arising from the lack of an integrated water management in the La Plata River Basin. Finally, this article demonstrates that the only way to have water resources utilization efficiency in an international basin is considering it as an integrated ecosystem, in order that any local problem may affect the whole basin.

It is an utmost importance to characterize drug candidates as early in the development pipeline as possible. Appropriate application of the emerging high throughput analytical techniques unlocks the opportunities to obtain experimental data for in vitro absorption, distribution, metabolism and elimination (ADME) profiling of large compound libraries which is crucial for selection of lead compounds. In an usual scenario, only one drug candidate will be selected from thousands of early compounds based on several stability and screening results. A high to medium throughput screening approaches could significantly accelerates the subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high throughput LC-MS/MS techniques to meet with the lead profiling demands. In this study presented an innovative experimental approach that can offer a refreshing alternative. Laser Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS) is a quick and efficient method for characterizing complex biological samples without laborious sample preparation and chemical separation. Therefore, using an automated LA-REIMS well plate reader as fast as 8 seconds per sample, we assessed the oxidative metabolic stability of active agents using biomimetic metalloporphyrin-based oxidative model reactions at various pH for commercially available drug substances and compared stability measurements with traditional HPLC-DAD-MS results.

Fetuses of pregnant women affected by anti-Ro/anti La antibodies are at risk to develop complete atrioventricular heart block (CAVB) and other potentially life-threatening cardiac affections. CAVB can develop in less than 24 hours. Treatment with anti-inflammatory drugs and immuno-globulins (IVIG) can restore normal rhythm if applied in the transition period. Routine weekly echocardiography as often recommended will seldomly detect emergent AVB. Surveillance of these pregnancies is controversial. To obtain an overview of the current practice in Germany we have developed a web-based survey sent by the DEGUM (German Society of Ultrasound in Med-icine) to ultrasound specialists. Home-monitoring by hand-held Doppler is a promising new approach. With the intention to evaluate practicability, we instructed pregnant women at risk to use hand-held Doppler in the vulnerable period between 18-26 weeks at our university center.

Natural time is a new time domain introduced in 2001. The analysis of time series associated with a complex system in natural time may provide useful information and may reveal properties that are usually hidden when studying the system in conventional time. In this new time domain, an entropy has been defined and complexity measures based on this entropy as well as its value under time-reversal have been introduced and found applications in various complex systems. Here, we review these applications in the electric signals that precede rupture, e.g., earthquakes, in the analysis of electrocardiograms, as well as in global atmospheric phenomena like the El Nino/La Nina Southern Oscillation.

This article aims to present the outcomes of a study focused on collaboratively developing an Innovation Management Model (IMG) tailored for Colombia's leather agro-industrial chain. The study integrates stakeholder participation, prioritization of variables, literature review, and model validation, emphasizing sustainability considerations throughout the process. Methodologically, it involved a literature review using Scopus, focusing on innovation management models, open innovation, and sustainability, particularly within the leather sector. The search identified 43 documents in Scopus, of which 15 were directly relevant; this analysis was complemented by 18 articles from Google Scholar. Three surveys were conducted to prioritize variables, utilizing Lik-ert-scale questions to assess relevance and congruence. Conceptual innovation models were validated graphically. Initial variables were identified, with 53 selected for the entry stage, 36 for the transformation stage, and 31 for the exit stage. These variables were classified for each stage, resulting in three innovation management models for validation. Key findings included 26 critical variables covering aspects such as agricultural and technological innovation in platforms and projects, capacity development, R&D activities, supply chain dynamics, innovation management processes, knowledge and technology integration, business model adaptation for sustainable development, and environmental impact assessment. The prioritized innovation model is in-tended to assist stakeholders in the leather sector's innovation system by promoting open inno-vation strategies, sustainable and regenerative innovation generation, and enhancing strategic and technological capacities. The prioritized innovation model aims to assist stakeholders in the leather sector's innovation system by promoting open innovation strategies, sustainable and re-generative innovation generation, and enhancing strategic and technological capacities.

: Low-temperature growth of diamond films by chemical vapor deposition (CVD) method is not so widely reported and especially its initial periods of nucleation and growth phenomenon are of particular interest to the researchers. Four sets of substrates were selected for growing diamond films by linear antenna microwave plasma enhanced CVD (LA-MPCVD). Among them, silicon and sapphire substrates were pre-treated with detonation nanodiamond (DND) seeds before diamond growth for enhancement of its nucleation. On the other hand, carbon nanotube (CNT) films on Si substrates were also used as another template for LA-MPCVD diamond growth. In order to enhance the diamond nucleation during CVD growth, some of the CNT films were again pre-treated by electrophoretic deposition (EPD) of diamond nanoparticles. All these substrates were then put inside the LA-MPCVD chamber for growing diamond films under variable processing conditions. Microwave input powers (1100 – 2800 W), input power modes (pulse or continuous), antenna to stage distances (5 - 6.5 cm), process gas recipes (with or without CO2), methane gas percentages (3 - 5%), deposition times (11 – 120 minutes) were altered to investigate their effect on the growth of diamond film on the pre-treated substrates. The substrate temperatures were found to vary from as low as 170oC to a maximum of 307oC during the alteration of the different processing parameters. Contrary to the conventional MPCVD, it was observed that during the first hour of LA-MPCVD diamond growth, DND seeds or the nucleating structures, do not coalesce together to make a continuous film. Deposition time was the most critical factor in fully covering the substrate surfaces with diamond film, since the substrate temperature could not become stable during the first hour of LA-MPCVD. CNT was found to be oxidised rapidly under LA-MPCVD plasma conditions; therefore, a CO2-free process gas recipe was used to reduce CNT burning. Moreover, EPD-coated CNT was found to be less oxidised by the LACVD plasma during diamond growth.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Background: Chronic exposure to severe hypoxia causes an increase in hematocrit (Hct) and hemoglobin concentration ([Hb]), which can lead to Excessive Erythrocytosis (EE), which could impact physical performance. This work aims to determine the differences in the six-minute walking test (6MWT) outputs between EE and healthy subjects residing at more than 5000 meters. Methods: A prospective, cross-sectional study was performed on 71 men (36 healthy and 25 suffering EE) living in La Rinconada, Peru (5100 m). Basal levels of [Hb] and Hct were obtained. All the subjects per-formed the 6MWT, and distance reached, vital signs, dyspnea, and fatigue (Borg scale) at the end of the test were recorded. Results: The average [Hb] and Hct levels in the control group were 18.7 ± 1.2 g/dL and 60.4 ± 7.1%, respectively, contrasting with EE subjects who showed 23.4 ± 1.6 g/dL and 73.6 ± 5.9% (p < 0.001). However, no statistically significant differences were observed in BMI or other anthropometric parameters. At the end of the 6MWT, the distance traveled, and vital constants were similar between both groups, except for arterial oxygen saturation which was consistently lower in subjects with EE along the test. Conclusion: EE does not significantly affect 6MWT performance at high altitudes nor the hemodynamic control during moderate aerobic exercise of subjects who live permanently in a severe hypoxic environment.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

Empirical Orthogonal Functions (EOF) analysis between the anomalies of Lake Titicaca water levels (WLs) and the Pacific Interdecadal Oscillation (IPO) reveals a correlation coefficient of 0.71 between the WLs and the principal component (PC1). These findings demonstrate the high accuracy of the IPO in representing the positive and negative phases of the water levels. By utilizing wavelet functions, we identified multi-decadal variability with periods ranging between 20 and 30 years. The statistical techniques employed indicate a relationship between IPO and ENSO; however, they operate on different timescales of climate variability. The IPO exhibits longer-term variability, typically spanning 20-30 years, while ENSO events occur on average every 2-7 years. Nevertheless, the IPO has the ability to modulate the strength and frequency of El Niño and La Niña events, and vice versa. During the positive phase of the IPO, there is a tendency for more frequent and intense El Niño events, accompanied by fewer La Niña events. This can be attributed to warmer sea surface temperatures in the central and eastern Pacific, which create favorable conditions for El Niño development. Conversely, during the negative phase of the IPO, there is a tendency for more frequent and intense La Niña events, with fewer occurrences of El Niño events, due to cooler sea surface temperatures in the central and eastern Pacific.

Post-COVID-19 bacterial infections are a significant threat to global health, mainly due to the overuse and misuse of antibiotics. The review highlights the importance of using antibiotics judiciously and following appropriate guidelines and recommendations. The article also examines the potential indirect contribution of steroids to antibiotic resistance through immune suppression in severe cases of COVID-19. Anti-microbial resistance (AMR) is one of the leading causes of death worldwide that continues as a silent pandemic caused by the major AMR superbug includes Carbapenem-resistant Acinetobacter baumannii (CRAB), Methicillin-resistant Staphylococcus aureus (MRSA), Carbapenem-resistant Enterobacterales (CRE), Extended-spectrum Beta Lactamase producing Enterobacterales (ESBL) which is resistant to cephalosporin and Multidrug-resistant (MDR) Pseudomonas aeruginosa. Ongoing surveillance and monitoring of antibiotic use and resistance helped to minimize the risk of antibiotic resistance and shrink it from pandemic to endemic.

“White matter disease” identifies series of different conditions and pathological mechanisms: autoimmune, infectious, toxic-metabolic and vascular. Each of these leads to a global impairment of the neural myelination process through the secondary destruction of previously myelinated structures. To date, the imaging spectrum represents an irreplaceable tool to detect these lesions, describe their distribution patterns and stage them over time. This study aims presents a pictorial review of white matter disease, from pathology to imaging spectrum, reporting current main staging systems with greater emphasis to relationship between cerebrovascular disease and white matter hyper-intensity appearance, and the newest advances in this field.

The presence of potentially pathogenic bacteria on veterinary clinic surfaces may be problematic. In this study we collected swab samples (Fisherbrand, double transport swabs with Stuart’s liquid medium) and water samples from five veterinary rehabilitation clinics. Swabs and water samples were transported to a microbiology lab for processing. At the lab swabs were used to inoculated Hardy’s Cdiff Banana broth (for Clostridium difficile [Cdiff]), and five different types of bacterial growth media, including: Hardy CHROM MRSA agar (methicillin resistant Staphylococcus aureus [MRSA], and S. pseudintermedius [SIM]), Mannitol Salt Agar (S. aureus), Eosin Methylene Blue agar (enterics [ENT]), Pseudomonas Isolation agar (Pseudomonas sp.), and Tryptic Soy Agar [TSA] (non-specific). The most prominent species cultured was Cdiff (on nearly 55% of swabs). Bacillus sp. and Enterics were encountered on nearly 35% of swabs, with MRSA and SIM on just over 10% of swabs. The most contaminated sample site was harnesses/life jackets used with the underwater treadmill (33% of swabs). Underwater treadmill water had total bacterial counts from 1.6 to 2.7 e3 cfu/ml. Of all bacterial species detected SIM tends to be more pathogenic for dogs. Targeted cleaning/disinfecting in these clinics could help reduce risks for both animals and caregivers utilizing these clinics.

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

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.