Search

Nowadays, the diagnosis of Parkinson's disease (PD) remains essentially clinical, based on the subjective observations of clinicians. In addition, misdiagnosis with other neuro disorders, such as Alzheimer's (AD), can occur. Herein, an untargeted lipidomic analysis of 75 plasma samples was performed to identify lipid species capable of discriminating between these two neuro groups. Therefore, PLS-DA and OPLS-DA analysis revealed significant differences in patient profiles in the sphingolipid and glycerophospholipid categories. As a result, a putative lipid biomarker panel was developed, which included HexCer (40:1; O2) and PC (O-32:0), with an area under the receiver operating characteristic curve (AUC) > 80, respectively. This panel was effective in discriminating between diseased and healthy subjects, but most importantly, it could discriminate between two neurodegenerative disorders that can present similar symptoms, namely PD and AD. Together, these findings suggest that the dysregulated metabolism of lipids plays a critical role in AD and PD pathology and may represent a valuable clinical tool for their diagnosis. Thus, further targeted studies are encouraged to better understand the underlying mechanisms of PD and confirm the diagnostic potency of the identified lipid metabolites.

Background and Objectives : Retinal detachment is a severe ophthalmological condition requiring urgent surgical intervention and comprehensive postoperative management. This study aimed to evaluate the impact of perceived social support (PSS) on postoperative adherence, pain management, and reintervention rates in patients undergoing retinal detachment surgery. It was hypothesized that higher levels of PSS would be associated with better postoperative outcomes, particularly in adherence and anxiety management. Materials and Methods : A prospective observational study was conducted with 166 patients at a tertiary hospital between 2022 and 2024. Sociodemographic and clinical data were collected, and PSS was assessed using the Medical Outcomes Study (MOS) questionnaire (Cronbach's alpha = 0.96). The primary outcomes included adherence to postoperative recommendations, reintervention rates, additional analgesic use, and local complications. Given the non-normal distribution of key variables, non-parametric statistical analyses were performed, with significance set at p < 0.05. Results : PSS scores were consistently high (median: 5; IQR: 4.7-5.0). Adherence rates were excellent (100% at 7 and 15 days; 99.04% at 30 days). Reintervention rates remained low (0.5%, 1.0%, and 1.5% at 7, 15, and 30 days, respectively). The need for additional analgesia decreased significantly over time (46.43% at 7 days vs. 13.33% at 30 days; p = 0.041). Preoperative anxiety was significantly associated with higher postoperative analgesic consumption (median STAI score: 38 [IQR: 34-42], p = 0.041). A significant relationship was found between higher preoperative anxiety levels and greater postoperative analgesic use ( p = 0.041). However, no significant associations were found between PSS and major clinical outcomes such as reintervention or complications. Conclusions : These findings suggest that PSS may influence adherence to postoperative recommendations, although its direct impact on clinical outcomes remains uncertain. The significant association between higher preoperative anxiety and increased postoperative analgesic consumption highlights the need for psychosocial and educational interventions in RD surgical care. These results support a multidisciplinary approach incorporating psychosocial support alongside surgical treatment to optimize patient outcomes.

The objective of this study was to assess the effect of sustained reading on the temporal changes in the wavefront error in the presbyopic eye. The wavefront aberration of the eyes was measured using an IRX3 Shack-Hartmann aberrometer before and after (immediately, 5 min, and 10 min after) a reading task. Temporal changes in C20, C40, and C3-1 coefficient values of the eyes were plotted, showing a predominant number of V-shaped patterns (for C40 and C3-1) and inverse V-shaped patterns (for C20) among the study group, and the percentages (between 27 and 73%) were reported. The median of the total RMS of aberrations and the RMS of HOA (higher-order aberrations), which included comatic (3rd order) and spherical-like aberrations (4th and 6th order), increased immediately after finishing the near-vision reading task and then decreased. The median of RMS of comatic aberrations had a similar pattern of variations, while the median of RMS of spherical-like aberrations displayed an opposite pattern. Simulating the aberration changes due to lens decentration caused by relaxed zonules during 4 D accommodation in an eye model demonstrated that the expected range of changes for the vertical coma and spherical aberrations are in the order of 0.001 and 0.01 μm, respectively, which could justify why the observed changes were not statistically significant. The observed dynamic changes in HOA might be linked to the biomechanical characteristics and alterations in the displacement of the crystalline lens following prolonged near-vision tasks in presbyopic people. Although some predominant patterns under some conditions were shown, they exhibit considerable inter-subject and inter-ocular variability. This might be due to slight misalignments while fixating on the internal extended object in the aberrometer.

Nanocellulose, a nanoscale derivative from renewable biomass sources, possesses remarkable colloidal properties in water, mechanical strength, and biocompatibility. It emerges as a promising bio-based dispersing agent for various nanomaterials in water. This mini-review explores the interaction between cellulose nanomaterials (nanocrystals or nanofibers) and water, elucidating how this may enable their potential as an eco-friendly dispersing agent. We explore the potential of nanocellulose derived from top-down processes, nanocrystals, and nanofibers for dispersing carbon nanomaterials, semiconducting oxide nanoparticles, and other nanomaterials in water. We also highlight its advantages over traditional methods by not only effectively dispersing those nanomaterials but also potentially eliminating the need for further chemical treatments or supporting stabilizers. This not only preserves the exceptional properties of nanomaterials in aqueous dispersion, but may even lead to the emergence of novel hybrid functionalities. Overall, this mini-review underscores the remarkable versatility of nanocellulose as a green dispersing agent for a variety of nanomaterials, inspiring further research to expand its potential to other nanomaterials and applications.

Wine aroma is one of the most frequently used and explored quality indicators. Typically, its assessment involves estimating the volatile composition of wine or highly trained assessors conducting sensory analysis. However, current methodologies rely on slow, expensive and complicated analytical procedures. Additionally, sensory evaluation is inherently subjective in nature. Therefore, the aim of this work is to verify the feasibility of using FTIR spectroscopy as a fast and easy methodology for the early detection of some of the most common off-odors in wines. FTIR spectroscopy was combined with partial least squares (PLS) regression for the simultaneous measurement of isoamyl alcohol, isobutanol, 1-hexanol, butyric acid, isobutyric acid, decanoic acid, ethyl acetate, furfural and acetoin. The precision and accuracy of developed calibration models (R 2 P > 0.90, range error ratio > 12.1 and RPD > 3.1) proved the ability of the proposed methodology to quantify the aforementioned compounds.

Insulin is a powerful pleiotropic hormone that affects processes such as cell growth, energy expenditure, and carbohydrate, lipid, and protein metabolism. The molecular mechanisms by which insulin regulates muscle metabolism and the underlying defects that cause insulin resistance have not been fully elucidated. This study aimed to perform a microarray data analysis to find differentially expressed genes. The analysis has been based on the data of a study deposited in Gene Expression Omnibus (GEO) with the identifier "GSE22309". The selected data contain samples from three types of patients after taking insulin treatment: patients with diabetes (DB), patients with insulin sensitivity (IS), and patients with insulin resistance (IR). Through an analysis of omics data, 20 genes were found to be differentially expressed (DEG) between the three possible comparisons obtained (DB vs. IS, DB vs. IR, and IS vs. IR); these data sets have been used to develop predictive models through machine learning (ML) techniques to classify patients with respect to the three categories mentioned previously. All the ML techniques present an accuracy superior to 80%, reaching almost 90% when unifying IR and DB categories.

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.

Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic., Methods: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old., Results: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%)., Conclusions: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.

Pickering emulsions (PEs) differ from conventional emulsions in the use of solid colloidal particles as stabilizing agents instead of traditional amphiphilic molecules. Nanostructured biopolymers (NBs) emerge as a promising alternative for PE stabilization owing to their remarkable biocompatibility, abundant availability, and low cost. To explore this potential, a study is herein presented, in which cellulose nanocrystals (CNCs), both type I and type II allomorphs, and chitin nanocrystals (ChNCs) were used for stabilizing oil-in-water PEs prepared by the use of ultrasound. Sunflower oil was selected as the oil phase as it offers the advantages of being edible, renewable, and inexpensive. By utilizing ζ-potential, static light diffraction, and visual observations, we determined the optimal oil/water ratio for each type of NB to obtain stable emulsions after 14 days. The optimized PEs were used to form bacterial nanocellulose composites through emulsion templating. To our knowledge, this study represents a pioneering work in exploiting oil-in-water PEs for this approach. Additionally, it entails the first utilization of nonmercerized type II CNCs as stabilizers for PEs, while also establishing a direct comparison among the most relevant NBs. The resulting composites exhibited a unique morphology, composed of larger pores compared to standard bacterial nanocellulose aerogels. These findings highlight the notable potential of NBs as stabilizers for PEs and their ability to generate green nanocomposites with tailored properties.

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm 3 ; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir <200/mm 3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

The transport properties of commercial carbon nanofibers (CNFs) produced by chemical vapor deposition (CVD) depend on the various conditions used during their growth and post-growth synthesis, which also affect their derivate CNF-based textile fabrics. Here, the production and thermoelectric (TE) properties of cotton woven fabrics (CWFs) functionalized with aqueous inks made from different amounts of pyrolytically stripped (PS) Pyrograf ® III PR 25 PS XT CNFs via dip-coating method are presented. At 30 °C and depending on the CNF content used in the dispersions, the modified textiles show electrical conductivities (σ) varying between ~5 and 23 S m -1 with a constant negative Seebeck coefficient (S) of -1.1 μVK -1 . Moreover, unlike the as-received CNFs, the functionalized textiles present an increase in their σ from 30 °C to 100 °C (dσ/dT > 0), explained by the 3D variable range hopping (VRH) model as the charge carriers going beyond an aleatory network of potential wells by thermally activated hopping. However, as it happens with the CNFs, the dip-coated textiles show an increment in their S with temperature (dS/dT > 0) successfully fitted with the model proposed for some doped multiwall carbon nanotube (MWCNT) mats. All these results are presented with the aim of discerning the authentic function of this type of pyrolytically stripped Pyrograf ® III CNFs on the thermoelectric properties of their derived textiles.

The historical stone heritage that we inherit must be passed on to future generations, not only in the same conditions that we found it but, if possible, in better ones. Construction also demands better and more durable materials, often stone. The protection of these materials requires knowledge of the types of rocks and their physical properties. The characterization of these properties is often standardized to ensure the quality and reproducibility of the protocols. These must be approved by entities whose purpose is to improve the quality and competitiveness of companies and to protect the environment. Standardized water absorption tests could be envisaged to test the effectiveness of certain coatings in protecting natural stone against water penetration, but we found that some steps of these protocols neglect any surface modification of the stones, and hence may not be completely effective when a hydrophilic protective coating (i.e., graphene oxide) is present. In this work, we analyze the UNE 13755/2008 standard for water absorption and propose alternative steps to adapt the norm for use with coated stones. The properties of coated stones may invalidate the interpretation of the results if the standard protocol is applied as is, so here we pay special attention to the characteristics of the coating applied, the type of water used for the test, the materials used, and the intrinsic heterogeneity of the specimens.

Drug-drug salts are a kind of pharmaceutical multicomponent solid in which the two co-existing components are active pharmaceutical ingredients (APIs) in their ionized forms. This novel approach has attracted great interest in the pharmaceutical industry since it not only allows concomitant formulations but also has proved potential to improve the pharmacokinetics of the involved APIs. This is especially interesting for those APIs that have relevant dose-dependent secondary effects, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this work, six multidrug salts involving six different NSAIDs and the antibiotic ciprofloxacin are reported. The novel solids were synthesized using mechanochemical methods and comprehensively characterized in the solid state. Moreover, solubility and stability studies, as well as bacterial inhibition assays, were performed. Our results suggest that our drug-drug formulations enhanced the solubility of NSAIDs without affecting the antibiotic efficacy., Competing Interests: The authors declare no conflict of interest.

Introduction: The implementation of optimal sprint training volume is a relevant component of team sport performance. This study aimed to compare the efficiency and effectiveness of two different configurations of within-season training load distribution on sprint performance over 6 weeks. Methods: Twenty male professional FH players participated in the study. Players were conveniently assigned to two groups: the experimental group (MG; n = 11; applying the microdosing training methodology) and the control group (TG; n = 9; traditional training, with players being selected by the national team). Sprint performance was evaluated through 20 m sprint time (T20) m and horizontal force−velocity profile (HFVP) tests before (Pre) and after (Post) intervention. Both measurements were separated by a period of 6 weeks. The specific sprint training program was performed for each group (for vs. two weekly sessions for MG and TG, respectively) attempting to influence the full spectrum of the F-V relationship. Results: Conditional demands analysis (matches and training sessions) showed no significant differences between the groups during the intervention period (p > 0.05). No significant between-group differences were found at Pre or Post for any sprint-related performance (p > 0.05). Nevertheless, intra-group analysis revealed significant differences in F0, Pmax, RFmean at 10 m and every achieved time for distances ranging from 5 to 25 m for MG (p < 0.05). Such changes in mechanical capabilities and sprint performance were characterized by an increase in stride length and a decrease in stride frequency during the maximal velocity phase (p < 0.05). Conclusion: Implementing strategies such as microdosed training load distribution appears to be an effective and efficient alternative for sprint training in team sports such as hockey.

The purpose of this review is to aggregate technical information on existent optomechanical eye models (OME) described in the literature, for image quality assessment in different applications. Several physical eye models have been reviewed from peer-reviewed papers and patent applications. A typical eye model includes an artificial cornea, an intraocular lens or other lens to simulate the crystalline lens, an aperture as the pupil, and a posterior retinal surface, which may be connected to a light sensor. The interior of the eye model may be filled with a fluid to better emulate physiological conditions. The main focus of this review is the materials and physical characteristics used and the dimensional aspects of the main components including lenses, apertures, chambers, imaging sensors and filling medium. Various devices are described with their applications and technical details, which are systematically tabulated highlighting their main characteristics and applications. The models presented are detailed and discussed individually, and the features of different models are compared when applicable, highlighting strengths and limitations. In the end there is a brief discussion about the potential use of artificial eye models for industrial applications.

Verbenone and carvone are allylic monoterpenoid ketones with many applications in the fine chemicals industry that can be obtained, respectively, from the allylic oxidation of α -pinene and limonene over a silica-supported iron hexadecachlorinated phthalocyanine (FePcCl 16 -NH 2 -SiO 2 ) catalyst and with t -butyl hydroperoxide (TBHP) as oxidant. As there are no reported analyses of the environmental impacts associated with catalytic transformation of terpenes into value-added products that include the steps associated with synthesis of the catalyst and several options of raw materials in the process, this contribution reports the evaluation of the environmental impacts in the conceptual process to produce verbenone and carvone considering two scenarios (SI-raw-oils and SII-purified-oils). The impact categories were evaluated using ReCiPe and IPCC methods implemented in SimaPro 9.3 software. The environmental impacts in the synthesis of the heterogeneous catalyst FePcCl 16 -NH 2 -SiO 2 showed that the highest burdens in terms of environmental impact come from the use of fossil fuel energy sources and solvents, which primarily affect human health. The most significant environmental impacts associated with carvone and verbenone production are global warming and fine particulate matter formation, with fewer environmental impacts associated with the process that starts directly from turpentine and orange oils (SI-raw-oils) instead of the previously extracted α-pinene and limonene (SII-purified-oils). As TBHP was identified as a hotspot in the production process of verbenone and carvone, it is necessary to choose a more environmentally friendly and energy-efficient oxidizing agent for the oxidation of turpentine and orange oils.

Background: Multiparametric Flow Cytometry (MFC) is an essential tool to study the involved cell lineages, the aberrant differentiation/maturation patterns and the expression of aberrant antigens in acute myeloid leukemia (AML). The characterization of leukemia-associated immunophenotypes (LAIPs) at the moment of diagnosis is critical to establish reproducible strategies for the study of measurable residual disease using MFC (MFC-MRD). Methods: In this study, we identify and characterize LAIPs by comparing the leukemic populations of 145 AML patients, using the EuroFlow AML/ MDS MFC panel, with six databases of normal myeloid progenitors (MPCs). Principal component analysis was used to identify and characterize the LAIPs, which were then used to generate individual profiles for MFC-MRD monitoring. Furthermore, we investigated the relationship between the expression patterns of LAIPs and the different subtypes of AML. The MFC-MRD study was performed by identifying residual AML populations that matched with the LAIPs at diagnosis. To further validate this approach, the presence of MRD was also assessed by qPCR (qPCR-MRD). Finally, we studied the association between MFC-MRD and progression-free survival (PFS). Results: The strategy used in this study allowed us to describe more than 300 different LAIPs and facilitated the association of specific phenotypes with certain subtypes of AML. The MFC-MRD monitoring based on LAIPs with good/strong specificity was applicable to virtually all patients and showed a good correlation with qPCR-MRD and PFS. Conclusions: The described methodology provides an objective method to identify and characterize LAIPs. Furthermore, it provides a theoretical basis to develop highly sensitive MFC-MRD strategies.

Y55W mutants of non-selective NaK and partly K + -selective NaK2K channels have been used to explore the conformational dynamics at the pore region of these channels as they interact with either Na + or K + . A major conclusion is that these channels exhibit a remarkable pore conformational flexibility. Homo-FRET measurements reveal a large change in W55-W55 intersubunit distances, enabling the selectivity filter (SF) to admit different species, thus, favoring poor or no selectivity. Depending on the cation, these channels exhibit wide-open conformations of the SF in Na + , or tight induced-fit conformations in K + , most favored in the four binding sites containing NaK2K channels. Such conformational flexibility seems to arise from an altered pattern of restricting interactions between the SF and the protein scaffold behind it. Additionally, binding experiments provide clues to explain such poor selectivity. Compared to the K + -selective KcsA channel, these channels lack a high affinity K + binding component and do not collapse in Na + . Thus, they cannot properly select K + over competing cations, nor reject Na + by collapsing, as K + -selective channels do. Finally, these channels do not show C-type inactivation, likely because their submillimolar K + binding affinities prevent an efficient K + loss from their SF, thus favoring permanently open channel states.

The aim of this research was to analyze how the need for psychological support of health workers (HCWs) influenced the beliefs, perceptions and attitudes towards their work during the COVID-19 pandemic and to predict the need of psychological assistance. A descriptive transversal study was conducted based on a self-administered questionnaire distributed to health professionals working in the Canary Islands, Spain. The data were analyzed using Pearson's chi-squared test and the linear trend test. The correlation test between ordinal and frequency variables was applied using Kendall's Tau B. Multiple logistic regression was used to predict dichotomous variables. The sample included 783 health professionals: 17.8% ( n = 139) of them needed psychological or psychiatric support. Being redeployed to other services influenced the predisposition to request psychological help, and HCWs who required psychological support had more negative attitudes and perceptions towards their work. After five waves of COVID-19, these HCWs reported to be physically, psychologically and emotionally exhausted or even "burned out"; they did not feel supported by their institutions. The commitment of health personnel to fight against the COVID-19 pandemic decreased after the five waves, especially among professionals who required psychological support.

(1) Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to cause profound health, economic, and social problems worldwide. The management and disinfection of materials used daily in health centers and common working environments have prompted concerns about the control of coronavirus disease 2019 (COVID-19) infection risk. Ozone is a powerful oxidizing agent that has been widely used in disinfection processes for decades. The aim of this study was to assess the optimal conditions of ozone treatment for the elimination of heat-inactivated SARS-CoV-2 from office supplies (personal computer monitors, keyboards, and computer mice) and clinical equipment (continuous positive airway pressure tubes and personal protective equipment) that are difficult to clean. (2) Methods: The office supplies and clinical equipment were contaminated in an area of 1 cm 2 with 1 × 10 4 viral units of a heat-inactivated SARS-CoV-2 strain, then treated with ozone using two different ozone devices: a specifically designed ozonation chamber (for low-medium ozone concentrations over large volumes) and a clinical ozone generator (for high ozone concentrations over small volumes). SARS-CoV-2 gene detection was carried out using quantitative real-time polymerase chain reaction (RT-qPCR). (3) Results: At high ozone concentrations over small surfaces, the ozone eliminated SARS-CoV-2 RNA in short time periods-i.e., 10 min (at 4000 ppm) or less. The optimum ozone concentration over large volumes was 90 ppm for 120 min in ambient conditions (24 °C and 60-75% relative humidity). (4) Conclusions: This study showed that the appropriate ozone concentration and exposure time eliminated heat-inactivated SARS-CoV-2 RNA from the surfaces of different widely used clinical and office supplies, decreasing their risk of transmission, and improving their reutilization. Ozone may provide an additional tool to control the spread of the COVID-19 pandemic.

Investigating vaccine effectiveness (VE) in real-world conditions is crucial, especially its variation across different settings and populations. We undertook a test-negative control study in Galicia (Northwest Spain) to assess BNT162b2 effectiveness against acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as well as COVID-19 associated hospitalization, intensive care unit (ICU) admission and mortality. A total of 44,401 positive and 817,025 negative SARS-CoV-2 test results belonging to adults were included. Adjusted odds ratios of vaccination and their 95% confidence interval (CI) were estimated using multivariate logistic-regression models. BNT162b2 showed high effectiveness in reducing SARS-CoV-2 infections in all age categories, reaching maximum VE ≥ 14 days after administering the second dose [18-64 years: VE = 92.9% (95%CI: 90.2-95.1); 65-79 years: VE = 85.8% (95%CI: 77.3-91.9), and ≥80 years: VE = 91.4% (95%CI: 87.9-94.1)]. BNT162b2 also demonstrated effectiveness in preventing COVID-19 hospitalization for all age categories, with VE more pronounced for those aged ≥80 years [VE = 60.0% (95%CI: 49.4-68.3)]. Moreover, there was a considerable reduction in ICU admission [VE = 88.0% (95%CI: 74.6-95.8)] and mortality [VE = 38.0% (95%CI: 15.9-55.4)] in the overall population. BNT162b2 showed substantial protection against SARS-CoV-2 infections and COVID-19 severity. Our findings would prove useful for systematic reviews and meta-analysis on COVID-19 VE.

Absent in melanoma 2 (AIM2) is a cytosolic dsDNA sensor that has been broadly studied for its role in inflammasome assembly. However, little is known about the function of AIM2 in adaptive immune cells. The purpose of this study was to investigate whether AIM2 has a cell-intrinsic role in CD4 + T cell differentiation or function. We found that AIM2 is expressed in both human and mouse CD4 + T cells and that its expression is affected by T cell receptor (TCR) activation. Naïve CD4 + T cells from AIM2-deficient ( Aim2 -/- ) mice showed higher ability to maintain forkhead box P3 (FOXP3) expression in vitro, while their capacity to differentiate into T helper (Th)1, Th2 or Th17 cells remained unaltered. Transcriptional profiling by RNA sequencing showed that AIM2 might affect regulatory T cell (Treg) stability not by controlling the expression of Treg signature genes, but through the regulation of the cell's metabolism. In addition, in a T cell transfer model of colitis, Aim2 -/- -naïve T cells induced less severe body weight loss and displayed a higher ability to differentiate into FOXP3 + cells in vivo. In conclusion, we show that AIM2 function is not confined to innate immune cells but is also important in CD4 + T cells. Our data identify AIM2 as a regulator of FOXP3 + Treg cell differentiation and as a potential intervention target for restoring T cell homeostasis.

Swimmers take great advantage by reducing the drag forces either in passive or active conditions. The purpose of this work is to determine the frontal area of swimmers by means of an automated vision system. The proposed algorithm is automated and also allows to determine lateral pose of the swimmer for training purposes. In this way, a step towards the determination of the instantaneous active drag is reached that could be obtained by correlating the effective frontal area of the swimmer to the velocity. This article shows a novel algorithm for estimating the frontal and lateral area in comparison with other models. The computing time allows to obtain a reasonable online representation of the results. The development of an automated method to obtain the frontal surface area during swimming increases the knowledge of the temporal fluctuation of the frontal surface area in swimming. It would allow the best monitoring of a swimmer in their swimming training sessions. Further works will present the complete device, which allows to track the swimmer while acquiring the images and a more realistic model of conventional active drag ones.

For the last 20 years, silica-based mesoporous materials have provided a sound platform for the development of biomedical technology applied to tissue engineering and drug delivery. Their unique structural and textural characteristics, chiefly, the ordered distribution of homogeneous and tunable pores with high surface areas and large pore volume, and their excellent biocompatibility provide an excellent starting point for bone tissue regeneration on the mesoporous surface, and also to load species of interest inside the pores. Adequate control of the synthesis conditions and functionalization of the mesoporous surface are critical factors in the design of new systems that are suitable for use in specific medical applications. Simultaneously, the use of appropriate characterization techniques in the several stages of design and manufacture of mesoporous particles allows us to ascertain the textural, structural and compositional modifications induced during the synthesis, functionalization and post-in vitro assays processes. In this scenario, the present paper shows, through several examples, the role of transmission electron microscopy and associated spectroscopic techniques in the search for useful information in the early design stages of mesoporous systems, with application in the fields of tissue regeneration and drug delivery systems.

The aims of the current study were to compare the pacing patterns of all-time 800 m, 1500 m and mile running world records (WRs) and to determine whether differences exist between sexes, and if 800 m and 1500 m WRs were broken during championship or meet races. Overall and lap times for men and women's 800 m, 1500 m, and mile WRs from World Athletics were collected when available and subsequently compared. A fast initial 200 m segment and a decrease in speed throughout was found during 800 m WRs. Accordingly, the first 200 m and 400 m were faster than the last 200 m and 400 m, respectively ( p < 0.001, 0.77 ≤ ES ≤ 1.86). The first 400 m and 409 m for 1500 m and mile WRs, respectively, were faster than the second lap ( p < 0.001, 0.74 ≤ ES ≤ 1.46). The third 400 m lap was slower than the last 300 m lap and 400 m lap for 1500 m and mile WRs, respectively ( p < 0.001, 0.48 ≤ ES ≤ 1.09). No relevant sex-based differences in pacing strategy were found in any event. However, the first 409 m lap was faster than the last 400 m lap for men but not for women during mile WRs. Women achieved a greater % of WRs than men during championships (80% vs. 45.83% in the 800 m, and 63.63% vs. 31.58% in the 1500 m, respectively). In conclusion, positive, reverse J-shaped and U-shaped pacing profiles were used to break 800 m, men's mile and 1500 m, and women's mile WRs, respectively. WRs are more prone to be broken during championships by women than men.

Heusler Ni-Mn-Sn-based alloys are good candidates for magnetic refrigeration. This application is based on cycling processes. In this work, thermal cycles (100) have been performed in three ribbons produced by melt-spinning to check the thermal stability and the magnetic response. After cycling, the temperatures were slowly shifted and the thermodynamic properties were reduced, the entropy changed at about 3-5%. Likewise, the thermomagnetic response remains similar. Thus, these candidates maintain enough thermal stability and magnetic response after cycling. Likewise, Cu addition shifts the structural transformation to higher temperatures, whereas the Curie temperature is always near 310 K. Regarding magnetic shape memory applications, the best candidate is the Ni 49 Mn 36 Sn 14 Cu 1 alloy.

The allosteric coupling between activation and inactivation processes is a common feature observed in K + channels. Particularly, in the prokaryotic KcsA channel the K + conduction process is controlled by the inner gate, which is activated by acidic pH, and by the selectivity filter (SF) or outer gate, which can adopt non-conductive or conductive states. In a previous study, a single tryptophan mutant channel (W67 KcsA) enabled us to investigate the SF dynamics using time-resolved homo-Förster Resonance Energy Transfer (homo-FRET) measurements. Here, the conformational changes of both gates were simultaneously monitored after labelling the G116C position with tetramethylrhodamine (TMR) within a W67 KcsA background. At a high degree of protein labeling, fluorescence anisotropy measurements showed that the pH-induced KcsA gating elicited a variation in the homo-FRET efficiency among the conjugated TMR dyes (TMR homo-FRET), while the conformation of the SF was simultaneously tracked (W67 homo-FRET). The dependence of the activation p K a of the inner gate with the ion occupancy of the SF unequivocally confirmed the allosteric communication between the two gates of KcsA. This simple TMR homo-FRET based ratiometric assay can be easily extended to study the conformational dynamics associated with the gating of other ion channels and their modulation.

Background: The major limitation of piecemeal endoscopic mucosal resection (EMR) is the inaccurate histological assessment of the resected specimen, especially in cases of submucosal invasion., Objective: To classify non-pedunculated lesions ≥20 mm based on endoscopic morphological features, in order to identify those that present intramucosal neoplasia (includes low-grade neoplasia and high-grade neoplasia) and are suitable for piecemeal EMR., Design: A post-hoc analysis from an observational prospective multicentre study conducted by 58 endoscopists at 17 academic and community hospitals was performed. Unbiased conditional inference trees (CTREE) were fitted to analyse the association between intramucosal neoplasia and the lesions' endoscopic characteristics., Result: 542 lesions from 517 patients were included in the analysis. Intramucosal neoplasia was present in 484 of 542 (89.3%) lesions. A conditional inference tree including all lesions' characteristics assessed with white light imaging and narrow-band imaging (NBI) found that ulceration, pseudodepressed type and sessile morphology changed the accuracy for predicting intramucosal neoplasia. In ulcerated lesions, the probability of intramucosal neoplasia was 25% (95%CI: 8.3-52.6%; p < 0.001). In non-ulcerated lesions, its probability in lateral spreading lesions (LST) non-granular (NG) pseudodepressed-type lesions rose to 64.0% (95%CI: 42.6-81.3%; p < 0.001). Sessile morphology also raised the probability of intramucosal neoplasia to 86.3% (95%CI: 80.2-90.7%; p < 0.001). In the remaining 319 (58.9%) non-ulcerated lesions that were of the LST-granular (G) homogeneous type, LST-G nodular-mixed type, and LST-NG flat elevated morphology, the probability of intramucosal neoplasia was 96.2% (95%CI: 93.5-97.8%; p < 0.001)., Conclusion: Non-ulcerated LST-G type and LST-NG flat elevated lesions are the most common non-pedunculated lesions ≥20 mm and are associated with a high probability of intramucosal neoplasia. This means that they are good candidates for piecemeal EMR. In the remaining lesions, further diagnostic techniques like magnification or diagnostic +/- therapeutic endoscopic submucosal dissection should be considered.

Fritillaria bulbs are used in Traditional Chinese Medicine to treat several illnesses. Peimine (Pm), an anti-inflammatory compound from Fritillaria , is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored. We have studied if Pm affects nicotinic acetylcholine receptors (nAChRs), since they play broad functional roles, both in the nervous system and non-neuronal tissues. Muscle-type nAChRs were incorporated to Xenopus oocytes and the action of Pm on the membrane currents elicited by ACh ( I ACh s) was assessed. Functional studies were combined with virtual docking and molecular dynamics assays. Co-application of ACh and Pm reversibly blocked I ACh , with an IC 50 in the low micromolar range. Pm inhibited nAChR by: (i) open-channel blockade, evidenced by the voltage-dependent inhibition of I Ach , (ii) enhancement of nAChR desensitization, revealed by both an accelerated I ACh decay and a decelerated I ACh deactivation, and (iii) resting-nAChR blockade, deduced from the I ACh inhibition elicited by Pm when applied before ACh superfusion. In good concordance, virtual docking and molecular dynamics assays demonstrated that Pm binds to different sites at the nAChR, mostly at the transmembrane domain. Thus, Pm from Fritillaria bulbs, considered therapeutic herbs, targets nAChRs with high affinity, which might account for its anti-inflammatory actions.

Swimming coaches have prescribed dry-land training programs over the years to improve the overall swimming performance (starts, clean swimming, turns and finish). The main aim of the present systematic review was to examine the effects of dry-land strength and conditioning programs on swimming turns. Four online databases were scrutinised, data were extracted using the Preferred PRISMA guidelines and the PEDro scale was applied. A total of 1259 articles were retrieved from database searches. From the 19 studies which were full-text evaluated, six studies were included in the review process. The review indicated that plyometric, strength, ballistic and core training programs were implemented for improving swimming turn performance. Strength, ballistic and plyometric training focusing on neural enhancement seem to be effective for improving swimming turn performance. The data related to training of the core were not conclusive. Coaches should consider incorporating exercises focusing on improving the neuromuscular factor of the leg-extensor muscles into their daily dry-land training programs. More researches are needed to provide a better understanding of the training methods effects and training organisations for improving swimming turn performance.

The aim of the present research was to examine the stroking rate (SR) values of successful and non-successful swimmers in the 10 km and 25 km races of the FINA 2019 World Swimming Championships. Data from 175 participants (95 men and 80 female) were classified according to their finishing positions. There were no meaningful differences in the overall SR values displayed by successful or non-successful participants during the 10 km and 25 km open water races of the FINA 2019 World Swimming Championships. However, there were changes in the SR throughout the races that depended on the swimmer's performance group and gender. Successful swimmers in the 10 km event typically displayed even SR in the first 5 km but, unlike the remaining performance groups, increased their SR at some point in the second 5 km of the race. In the 25 km race, successful female swimmers presented an even SR profile for most of the race, whereas successful males presented a more variable profile. Nevertheless, no relationships between partial or average SR and finishing positions occurred, either in the 10 km or in the 25 km race. Changes in the SR values should be included in the race plan of open water swimmers according to tactical and pacing strategies.

Knowledge in the scientific domain of individual medley (IM) swimming training over a competitive season is limited. The purpose of this study was to propose a detailed coaching framework incorporating the key elements of a periodized training regimen for a 400 m IM swimmer. This framework was based on the available coaching and scientific literature and the practical experience and expertise of the collaborating authors. The season has been divided in two or three macrocycles, further divided in three mesocycles each (six or nine mesocycles in total), in alignment with the two or three main competitions in each macrocycle. The principal training contents to develop during the season expressed in blood lactate zones are: aerobic training (~2 mmol·L -1 ), lactate threshold pace (~4 mmol·L -1 ) and VO 2 max (maximum oxygen uptake) (~6 mmol·L -1 ). Strength training should focus on maximum strength, power and speed endurance during the season. Altitude training camps can be placed strategically within the training season to promote physiological adaptation and improvements in performance. A well-constructed technical framework will permit development of training strategies for the 400 m IM swimmer to improve both training and competitive performance.

Despite the crucial advances in understanding the biology of cholangiocarcinoma (CCA) achieved during the last decade, very little of this knowledge has been translated into clinical practice. Thus, CCA prognosis is among the most dismal of solid tumors. The reason is the frequent late diagnosis of this form of cancer, which makes surgical removal of the tumor impossible, together with the poor response to standard chemotherapy and targeted therapy with inhibitors of tyrosine kinase receptors. The discovery of genetic alterations with an impact on the malignant characteristics of CCA, such as proliferation, invasiveness, and the ability to generate metastases, has led to envisage to treat these patients with selective inhibitors of mutated proteins. Moreover, the hope of developing new tools to improve the dismal outcome of patients with advanced CCA also includes the use of small molecules and antibodies able to interact with proteins involved in the crosstalk between cancer and immune cells with the aim of enhancing the immune system's attack against the tumor. The lack of effect of these new therapies in some patients with CCA is associated with the ability of tumor cells to continuously adapt to the pharmacological pressure by developing different mechanisms of resistance. However, the available information about these mechanisms for the new drugs and how they evolve is still limited.

The synthetic nucleoside acyclovir is considered an outstanding model of the natural nucleoside guanosine. With the purpose of deepening on the influence and nature of non-covalent interactions regarding molecular recognition patterns, three novel Cu(II) complexes, involving acyclovir (acv) and the ligand receptor N-(2-hydroxyethyl)ethylenediamine (hen), have been synthesized and thoroughly characterized. The three novel compounds introduce none, one or two acyclovir molecules, respectively. Molecular recognition has been evaluated using single crystal X-ray diffraction. Furthermore, theoretical calculations and other physical methods such as thermogravimetric analysis, infrared and UV-Vis spectroscopy, electron paramagnetic resonance and magnetic measurements have been used. Theoretical calculations are in line with experimental results, supporting the relevance of the [metal-N7(acv) + H-bond] molecular recognition pattern. It was also shown that (hen)O-H group is used as preferred H-donor when it is found within the basal coordination plane, since the higher polarity of the terminal (hen)O-H versus the N-H group favours its implication. Otherwise, when (hen)O-H occupies the distal coordination site, (hen)N-H groups can take over.

The present study examines the association between the success at junior and senior level for British swimmers in World Championships (WCs). It also explores the relationships between swimming performance and the swimmers' gender, swim stroke, distance, status (finalist, semifinalist and heats) and swimming category. Data were collected for swimmers participating in junior and/or senior World Championships (29,000 entries: 5585 swimmers) from 2006-2017. The final filtered database included only swimmers from the United Kingdom (836 entries: 141 swimmers). A descriptive analysis was made to characterize the swimmers who reached elite status in the senior category. A lineal regression model was run by gender to predict the influence of category, swim stroke, and distance in the results reached in the senior category. The results showed that the ratio of conversion from junior to senior was quite low. Females who participated in both junior and senior WCs were likely to reach top positions in the senior category. Overall, few British swimmers participated in a junior category before the senior level, but female swimmers participating in both junior and senior WCs were likely to reach top positions in the senior category.

Alkylammonium salts have been used extensively to study the structure and function of potassium channels. Here, we use the hydrophobic tetraoctylammonium (TOA + ) to shed light on the structure of the inactivated state of KcsA, a tetrameric prokaryotic potassium channel that serves as a model to its homologous eukaryotic counterparts. By the combined use of a thermal denaturation assay and the analysis of homo-Förster resonance energy transfer in a mutant channel containing a single tryptophan (W67) per subunit, we found that TOA + binds the channel cavity with high affinity, either with the inner gate open or closed. Moreover, TOA + bound at the cavity allosterically shifts the equilibrium of the channel's selectivity filter conformation from conductive to an inactivated-like form. The inactivated TOA + -KcsA complex exhibits a loss in the affinity towards permeant K + at pH 7.0, when the channel is in its closed state, but maintains the two sets of K + binding sites and the W67-W67 intersubunit distances characteristic of the selectivity filter in the channel resting state. Thus, the TOA + -bound state differs clearly from the collapsed channel state described by X-ray crystallography and claimed to represent the inactivated form of KcsA.

The propulsive forces and instantaneous power that are generated by a swimmer have a great influence on the swimming performance. This works presents a new device, called SwimOne, for measuring propulsive force and estimating the instantaneous power of the swimmer. In addition, the detailed prototype is able to exert a customizable opposition force to the swimmer for training purpose. The conceptual idea is presented by describing the differential equation of the swimmer and the protocol for a factible estimation of the instantaneous power. The variables that are to be measured and estimated are identified and, consequently, the sensor and actuator systems can be selected. The high-level and detailed designs of the prototype are presented together with the protocol that is carried out in order to validate the sensor and actuation systems. The device is able to monitor the variables of interest of the swimmer together with the propulsive force and instant power. Finally, some experiments are carried out providing the results of several participants swimming in crawl, backstroke, butterfly, and breaststroke styles in the presence of different opposition force. The preliminary results show that SwimOne is valid for measuring instantaneous force and power with different loads in swimming.

Swimming training programs may help to limit declines in cardiovascular conditioning, muscle strength, mobility and social functioning in individuals with Down's Syndrome (DS): (1) Background: This study aims to analyze the effects of a periodized swimming training program on swimming speed, lower body force and power and body composition in a group of swimmers with DS; (2) Methods: Nine swimmers with DS (2 men and 7 women; aged 21-30 years-old) completed an 18-week periodized swimming program. The swimmers were assessed, pre and post-training, for 25 m, 50 m and 100 m freestyle swim performance, countermovement jump performance and body composition; (3) Results: Significant and large improvements in 25 m (mean -6.39%, p < 0.05, d = 1.51), 50 m (mean -4.95%, p < 0.01, d = 2.08) and 100 m (mean -3.08%, p < 0.05, d = 1.44) freestyle performance were observed following training, with no significant changes in body composition or consistent changes in jump performance (although a large mean 14.6% decrease in relative peak force, p < 0.05, d = 1.23) (4) Conclusions: A periodized 18-week training intervention may improve swimming performance in a small group of trained swimmers with DS, with less clear changes in jump performance or body composition. This program provides a training profile for coaches working with swimmers with DS and a platform for further research into the benefits of swimming training with this under-represented population.

Abnormal activation of the Wnt/β-catenin pathway is common in many types of solid cancers. Likewise, a large proportion of cancer patients have vitamin D deficiency. In line with these observations, Wnt/β-catenin signaling and 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), the active vitamin D metabolite, usually have opposite effects on cancer cell proliferation and phenotype. In recent years, an increasing number of studies performed in a variety of cancer types have revealed a complex crosstalk between Wnt/β-catenin signaling and 1,25(OH) 2 D 3 . Here we review the mechanisms by which 1,25(OH) 2 D 3 inhibits Wnt/β-catenin signaling and, conversely, how the activated Wnt/β-catenin pathway may abrogate vitamin D action. The available data suggest that interaction between Wnt/β-catenin signaling and the vitamin D system is at the crossroads in solid cancers and may have therapeutic applications.

This work proposes a real-time electricity bill for quantifying the energy used in domestic facilities in Mexico. This bill is a low-cost tool that takes advantage of the IoT technology for generating an easy reading real-time bill allowing the customers to constantly review and administrate their energy consumption. Using low-cost sensors and the electronic board Particle ® Photon, an energy meter is proposed. The presented prototype is extremely compact and satisfies safety measures to be used by anyone in a domestic installation. The measurement data is displayed and processed in real-time, and an appropriate algorithm determines the accumulated kWh. The energy consumed is displayed using an Html interface of easy interpretation for the customers, given recommendations about their consumption habits and some alarms in case of abnormal or high consumption. As a reinforcement measure for avoiding large consumption bills, the system is programmed to send messages to the user, remembering if the estimated consumption is large.

Absent in melanoma 2 (AIM2) is a cytosolic receptor that recognizes double-stranded DNA (dsDNA) and triggers the activation of the inflammasome cascade. Activation of the inflammasome results in the maturation of inflammatory cytokines, such as interleukin (IL)-1 β and IL-18, and a form of cell death known as pyroptosis. Owing to the conserved nature of its ligand, AIM2 is important during immune recognition of multiple pathogens. Additionally, AIM2 is also capable of recognizing host DNA during cellular damage or stress, thereby contributing to sterile inflammatory diseases. Inflammation, either in response to pathogens or due to sterile cellular damage, is at the center of the most prevalent and life-threatening liver diseases. Therefore, during the last 15 years, the study of inflammasome activation in the liver has emerged as a new research area in hepatology. Here, we discuss the known functions of AIM2 in the pathogenesis of different hepatic diseases, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and hepatocellular carcinoma (HCC).

Hepatic immune function is compromised during cirrhosis. This study investigated the immune features of liver sinusoidal endothelial cells (LSECs) in two experimental models of cirrhosis. Dendritic cells, hepatic macrophages, and LSECs were isolated from carbon tetrachloride and bile duct-ligated rats. Gene expression of innate receptors, bacterial internalization, co-stimulatory molecules induction, and CD4+ T cell activation and differentiation were evaluated. Induced bacterial peritonitis and norfloxacin protocols on cirrhotic rats were also carried out. LSECs demonstrated an active immunosurveillance profile, as shown by transcriptional modulation of different scavenger and cell-adhesion genes, and their contribution to bacterial internalization. LSECs significantly increased their expression of CD40 and CD80 and stimulated CD4+ T cell activation marker CD71 in both models. The pro-inflammatory Th17 subset was expanded in CCl 4 -derived LSECs co-cultures. In the bile duct ligation (BDL) model, CD4+ T cell differentiation only occurred under induced bacterial peritonitis conditions. Differentiated pro-inflammatory Th cells by LSECs in both experimental models were significantly reduced with norfloxacin treatment, whereas Foxp3 tolerogenic Th CD4+ cells were expanded. Conclusion: LSECs' participation in the innate-adaptive immune progression, their ability to stimulate pro-inflammatory CD4+ T cells expansion during liver damage, and their target role in norfloxacin-induced immunomodulation granted a specific competence to this cell population in cirrhosis.

The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in DNMT3A, TET2, and ASXL1 (DTA genes) was positively associated with age for the whole cohort ( p = 0.025, OR: 1.047, 95% CI: 1.006-1.090). Also, while not related with events in the whole cohort, DTA mutations were strongly associated with the development of vascular events in PV patients ( p = 0.028). To confirm the possible association between the presence of DTA mutation and thrombotic events, we performed a case-control study on 55 age-matched patients with PV (including 12 PV patients from the initial cohort, 25 with event vs. 30 no event). In the age-matched case-control PV cohort, the presence of ≥1 DTA mutation significantly increased the risk of a thrombotic event (OR: 6.333, p = 0.0024). Specifically, mutations in TET2 were associated with thrombotic events in the PV case-control cohort (OR: 3.56, 95% CI: 1.15-11.83, p = 0.031). Our results suggest that pathogenic DTA mutations, and particularly TET2 mutations, may be an independent risk factor for thrombosis in patients with PV. However, the predictive value of TET2 and DTA mutations in ET and PMF was inconclusive and should be determined in a larger cohort.

KcsA, a prokaryote tetrameric potassium channel, was the first ion channel ever to be structurally solved at high resolution. This, along with the ease of its expression and purification, made KcsA an experimental system of choice to study structure-function relationships in ion channels. In fact, much of our current understanding on how the different channel families operate arises from earlier KcsA information. Being an integral membrane protein, KcsA is also an excellent model to study how lipid-protein and protein-protein interactions within membranes, modulate its activity and structure. In regard to the later, a variety of equilibrium and non-equilibrium methods have been used in a truly multidisciplinary effort to study the effects of lipids on the KcsA channel. Remarkably, both experimental and "in silico" data point to the relevance of specific lipid binding to two key arginine residues. These residues are at non-annular lipid binding sites on the protein and act as a common element to trigger many of the lipid effects on this channel. Thus, processes as different as the inactivation of channel currents or the assembly of clusters from individual KcsA channels, depend upon such lipid binding.

This paper presents a methodology for manufacturing nanocomposites from an epoxy resin reinforced with graphene oxide (GO) nanoparticles. A scalable and sustainable fabrication process, based on a solvent-free method, is proposed with the objective of achieving a high level of GO dispersion, while maintaining matrix performance. The results of three-point bending tests are examined by means of an analytical technique which allows determining the mechanical response of the material under tension and compression from flexural data. As result, an increase of 39% in the compressive elastic modulus of the nanocomposite is found with the addition of 0.3 wt % GO. In parallel, we described how the strain distribution and the failure modes vary with the amount of reinforcement based on digital image correlation (DIC) techniques and scanning electron microscopy (SEM). A novel analytical model, capable of predicting the influence of GO content on the elastic properties of the material, is obtained. Numerical simulations considering the experimental conditions are carried out. the full strain field given by the DIC system is successfully reproduced by means of the finite element method (FEM). While, the experimental failure is explained by the crack growth simulations using the eXtended finite element method (XFEM).

This work presents the development and construction of an adaptive street lighting system that improves safety at intersections, which is the result of applying low-power Internet of Things (IoT) techniques to intelligent transportation systems. A set of wireless sensor nodes using the Institute of Electrical and Electronics Engineers (IEEE) 802.15.4 standard with additional internet protocol (IP) connectivity measures both ambient conditions and vehicle transit. These measurements are sent to a coordinator node that collects and passes them to a local controller, which then makes decisions leading to the streetlight being turned on and its illumination level controlled. Streetlights are autonomous, powered by photovoltaic energy, and wirelessly connected, achieving a high degree of energy efficiency. Relevant data are also sent to the highway conservation center, allowing it to maintain up-to-date information for the system, enabling preventive maintenance., Competing Interests: The authors declare no conflict of interest.

In this investigation, the reaction of 2-dithiomethylcarboimidatebenzothiazole with a series of six chiral amino-acids was studied. The reaction proceeds through the isolable sodium salt of SMe-isothiourea carboxylates as intermediates, whose reaction with methyl iodide in stirring DMF as solvent affords SMe-isothiourea methyl esters. The presence of water in the reaction leads to the corresponding urea carboxylates as isolable intermediates, whose methyl esters were obtained. Finally, the urea N -methyl amide derivatives were isolated when SMe-isothiourea or urea methyl esters were reacted with methylamine in the presence of water. The structures of synthesized compounds were established by 1 H and 13 C nuclear magnetic resonance and the structures of SMe-isothiourea methyl esters derived from ( l )-glycine, ( l )-alanine, ( l )-phenylglycine, and ( l )-leucine, by X-ray diffraction analysis. This methodology allows to functionalize 2-aminobenzothiazole with SMe-isothiourea, urea, and methylamide groups derived from chiral amino acids to get benzothiazole derivatives containing coordination sites and hydrogen bonding groups. Further research on the biological activities of some of these derivatives is ongoing.

Random mutations and selective pressure drive protein adaptation to the changing demands of the environment. As a consequence, nature favors the evolution of protein diversity. A group of proteins subject to exceptional environmental stress and known for their widespread diversity are the pore-forming hemolytic proteins from sea anemones, known as actinoporins. In this study, we identified and isolated new isoforms of actinoporins from the sea anemone Actinia fragacea (fragaceatoxins). We characterized their hemolytic activity, examined their stability and structure, and performed a comparative analysis of their primary sequence. Sequence alignment reveals that most of the variability among actinoporins is associated with non-functional residues. The differences in the thermal behavior among fragaceatoxins suggest that these variability sites contribute to changes in protein stability. In addition, the protein-protein interaction region showed a very high degree of identity (92%) within fragaceatoxins, but only 25% among all actinoporins examined, suggesting some degree of specificity at the species level. Our findings support the mechanism of evolutionary adaptation in actinoporins and reflect common pathways conducive to protein variability.

Cation binding under equilibrium conditions has been used as a tool to explore the accessibility of permeant and nonpermeant cations to the selectivity filter in three different inactivated models of the potassium channel KcsA. The results show that the stack of ion binding sites (S1 to S4) in the inactivated filter models remain accessible to cations as they are in the resting channel state. The inactivated state of the selectivity filter is therefore "resting-like" under such equilibrium conditions. Nonetheless, quantitative differences in the apparent K D 's of the binding processes reveal that the affinity for the binding of permeant cations to the inactivated channel models, mainly K⁺, decreases considerably with respect to the resting channel. This is likely to cause a loss of K⁺ from the inactivated filter and consequently, to promote nonconductive conformations. The most affected site by the affinity loss seems to be S4, which is interesting because S4 is the first site to accommodate K⁺ coming from the channel vestibule when K⁺ exits the cell. Moreover, binding of the nonpermeant species, Na⁺, is not substantially affected by inactivation, meaning that the inactivated channels are also less selective for permeant versus nonpermeant cations under equilibrium conditions.

The objectives of this longitudinal study were to compare salivary cortisol release patterns in medical residents and their self-perceived anxiety levels between a regular working day and a day when on call in the emergency department (ED-duty day) and to determine any differences in cortisol release pattern as a function of years of residency or sex. The study included 35 residents (physicians-in-training) of the Granada University Hospital, Granada, Spain. Acute stress was measured on a regular working day and an ED-duty day, evaluating anxiety-state with the Spanish version of the State-Trait Anxiety Inventory. Physiological stress assessment was based on salivary cortisol levels. Cortisol release concentrations were higher on an ED-duty day than on a regular working day, with a significantly increased area under the curve (AUC) ( p < 0.006). This difference slightly attenuated with longer residency experience. No gender difference in anxiety levels was observed ( p < 0.001). According to these findings, the hypothalamic-pituitary-adrenal axis activity and anxiety levels of medical residents are higher on an ED-duty day than on a regular working day., Competing Interests: The authors report no conflicts of interest.