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Dynamic development of various technologies replacing existing, difficult or in various ways arduous, is the reason for replacing equipment with modern ones. New equipment may be associated with a different power supply, a different way that the construction materials are processed or the tools used, than the previous one. Then arises a need to re-examine whether the working conditions at a workplace are safe, what onerous and hazardous factors are associated with the work. An example of such a technological change could be a laser processing, when equipment using a concentrated energy stream, properly controlled, produces a specific effect on materials. However, along with the benefits of the new technology, come also many risks, such as the effects of radiation on matter and the human body, electricity, fire hazards, the problem of toxic emissions and others. This paper presents the problem of ensuring work safety at a newly commissioned CO2 laser station. Technique of brainstorming was used to identify and analyze the working conditions and types of hazards. These may be different from what was previously known, partially known, or even unconscious. Ishikawa diagram was developed and shown to be an effective tool for detailing and structuring problems in relation to safety. In the case of a technical problem, a poka-yoke solution to eliminate the hazard was proposed. Problems occurring at the workstation during machining and related to its operation were assigned, using the affinity diagram, to specific departments of the company, according to its work organization, which can significantly facilitate the management of the work and employees of the different departments in the future, in order to ensure safe and hygienic working conditions.

Ever since cartoons were created as a medium of political and social commentary, they have been used to both criticize and uplift religious communities. The anti-Catholic cartoons of Thomas Nast and Jack Chick are easily recognizable, but interestingly, among twenty-first-century Catholic communities in Europe and the United States, Catholics themselves have been creating caricatures of Pope Francis, a more left-leaning pope in favor of reinforcing post-Second Vatican Council modernizations. These digital cartoons are tangible examples of a radically traditional antagonistic Catholic counter-public. This study delves into how radical traditional Catholic communities, who argue that pre-Vatican II traditions are a more authentic form of Catholicism than that encouraged by the current Pope Francis, are using cartoons to voice their agenda. By drawing from discourse theoretical analysis and hermeneutics, we identify four themes of criticism and discontent surrounding the pope: exposing his “bad agency,” ridiculing papal values, unveiling Francis’ “polarized and unbalanced” behavior, and expressing his predatory attitude toward representatives of Catholic traditionalism. Ultimately, we see these cartoons as the product of an antagonistic and anti-Pope Francis force internal to the Church, hypermediation without sources to public actions, and the digital milieu based on modernity in technology.

Abstract Population irruptions of crown-of-thorns starfish (COTS; Acanthaster spp.) remain a major cause of coral reef degradation throughout the Pacific and Indian Oceans and are inherently modulated by larval settlement and recruitment success. Gregarious larval settlement, as exhibited by many other ecologically important marine invertebrates, can catalyse population growth and replenishment. However, whether conspecific cues induce or influence the settlement of COTS larvae remains a critical information gap. This experimental study examined the induction of COTS settlement in response to a range of conspecific cues associated with early- and late-stage herbivorous juveniles, corallivorous juveniles and adults. Competent COTS larvae were generally not induced to settle by the presence of conspecifics or cues associated with conspecifics, while the settlement success of COTS in the presence of coralline algae was not inhibited or enhanced by adding conspecific conditioned seawater. Rather than being reinforced by gregarious settlement, the recruitment of COTS populations appears dependent on associative settlement cues (i.e., coralline algae and/or associated microbial communities) signalling suitable benthic habitat.

Anna Felis-Giemza,1 Magdalena Massalska,2 Leszek Roszkowski,3 Katarzyna Romanowska-Próchnicka,4 Marzena Ciechomska2 1Biologic Therapy Center, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, Poland; 2Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, Poland; 3Department of Outpatient Clinics, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, Poland; 4Department of Biophysics, Physiology and Pathophysiology, Faculty of Health Sciences, Warsaw Medical University, Warsaw, PolandCorrespondence: Magdalena Massalska, Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Spartanska 1, Warsaw, 02-637, Poland, Tel +48226709564, Email magdalena.massalska@spartanska.plAbstract: It is well known that fatigue is a highly disabling symptom commonly observed in inflammatory rheumatic diseases (IRDs). Fatigue is strongly associated with a poor quality of life and seems to be an independent predictor of job loss and disability in patients with different rheumatic diseases. Although the pathogenesis of fatigue remains unclear, indirect data suggest the cooperation of the immune system, the central and autonomic nervous system, and the neuroendocrine system in the induction and sustainment of fatigue in chronic diseases. Fatigue does not correspond with disease activity and its mechanism in IRDs. It is suggested that it may change over time and vary between individuals. Abnormal production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interferons (IFNs), granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF, IL-15, IL-17 play a role in both IRDs and subsequent fatigue development. Some of these cytokines such as IL-6, IFNs, GM-CSF, and common gamma-chain cytokines (IL-15, IL-2, and IL-7) activate the Janus Kinases (JAKs) family of intracellular tyrosine kinases. Therapy blocking JAKs (JAK inhibitors – JAKi) has been recently proven to be an effective approach for IRDs treatment, more efficient in pain reduction than anti-TNF. Therefore, the administration of JAKi to IRDs patients experiencing fatigue may find rational implications as a therapeutic modulator not only of disease inflammatory symptoms but also fatigue with its components like pain and neuropsychiatric features as well. In this review, we demonstrate the latest information on the mechanisms of fatigue in rheumatic diseases and the potential effect of JAKi on fatigue reduction.Plain Language Summary: JAKi block pro-inflammatory cytokines, decrease activation of IDO, diminish the effects of genetic polymorphism (particularly mediated by IL-6 and IL-1β) as well as sickness behavior also connected with IL-1β expression, which result in fatigue and pain inhibition.In patients treated with JAKi, it was observed that there was significantly greater improvement compared to placebo and MTX in fatigue and pain reduction measured using PROs.Administration of JAKi (BARI+UPA) benefits over TNFi treatment in pain and fatigue reduction assessed by PtGA in RA patients.The effectiveness of fatigue reduction in PROs under recently approved JAKi still needs to be proven in clinical practice, especially in selective and nonselective groups of JAKi.Keywords: fatigue, JAK inhibitors, patient-reported outcomes, tofacitinib, baricitinib, upadacitinib

The study evaluated the effect of 1-methylcyclopropene (1-MCP) treatment on broccoli quality and storage ability. Broccoli ‘Parthenon’ was treated the day after harvest with 1.0 or 3.0 cm3·m−3 1-MCP. The treatment was performed at 5 °C for 20 h, and then the plant material was stored at 0–1 °C for 30 or 60 d. After 30 d of refrigerated storage, broccoli was transferred to conditions simulating retail (15 °C) for 6 d. During 30 d of storage, the broccoli crowns maintained excellent quality. The fleshy stalks were slightly inferior due to the darkening of the leaf scar areas. After 60 d, there was a marked reduction in broccoli quality. Still, the positive effect of 1-MCP treatment on broccoli was observed as inhibiting the senescence of the remaining petiole fragments. During shelf life after 30 days of cold storage, broccoli treated with 1-MCP retained better quality of the crowns and fleshy stems, evident after six days of shelf life evaluation. The study did not find that 1-MCP treatment inhibited the respiration rate of broccoli, or ethylene production.

Paweł Płatek,1 Natalia Daniel,1 Kamil Cieplak,1 Marcin Sarzyński,1 Przemysław Siemiński,2 Bartosz Sadownik,3,4 Paweł Andruszkiewicz,3 Łukasz Wróblewski3 1Faculty of Mechatronics, Armament and Aviation, Military University of Technology, Warsaw, Poland; 2Faculty of Automotive and Construction Machinery Engineering, Warsaw University of Technology, Warsaw, Poland; 3 2nd Department of Anaesthesiology and Intensive Care, Medical University of Warsaw, Central Teaching Hospital, Central Teaching Hospital, Warsaw, Poland; 4Department of Descriptive and Clinical Anatomy, Medical University of Warsaw, Warsaw, PolandCorrespondence: Paweł Płatek, Military University of Technology, gen. Sylwestra Kaliskiego 2, Warsaw, 00-908, Poland, Tel/Fax +48 261839657, Email pawel.platek@wat.edu.plPurpose: The paper describes the design concept and findings from technological and initial clinical trials conducted to develop a helmet for non-invasive oxygen therapy using positive pressure, known as hCPAP (Helmet Continuous Positive Airway Pressure).Methods: The study utilized PET-G filament, a recommended material for medical applications, along with the FFF 3D printing technique. Additional technological investigations were performed for the production of fitting components. The authors proposed a parameter identification method for 3D printing, which reduced the time and cost of the study while ensuring high mechanical strength and quality of the manufactured elements.Results: The proposed 3D printing technique facilitated the rapid development of an ad hoc hCPAP device, which was utilized in preclinical testing and treatment of Covid-19 patients, and yielded positive results. Based on the promising outcomes of the preliminary tests, further development of the hCPAP device’s current version was pursued.Conclusion: The proposed approach offered a crucial benefit by significantly reducing the time and costs involved in developing customized solutions to aid in the fight against the Covid-19 pandemic.Graphical Abstract: Keywords: 3D printing, fused filament fabrication, Covid-19, SARS-CoV-2, respiratory failure, hCPAP

Mobile phone data were used to examine the differences in the number and structure of visitors to the Forest Promotion Complex Sudety Zachodnie in 2019 (pre-pandemic year) and 2020 (pandemic year). The studies not only compared the total number of visitors in each year, but also distinguished four pandemic and restriction periods. This allowed us to capture the dynamics of the impact of the pandemic on visits to forest areas. The results show that although the total number of visitors increased in 2020 compared to 2019, different trends were observed in each pandemic period. In general, the number of visitors to forest areas decreased during the first lockdown, as well as during the ban on entering green areas and forests. However, during the easing of restrictions and the second lockdown in the fall of 2020, there was an increase in visitor numbers. The article also shows the evolution of visitor numbers at a very detailed level of a grid of 750 × 750 m. During the pandemic, the structure of visitors also changed taking into account the place of residence. Local tourism was more important than national tourism. A significant decrease in the number of visitors from abroad was also observed, which is a consequence of the introduced restrictions on travel between countries.

Barbara Pospieszna,1 Krzysztof Kusy,1 Ewa Maria Slominska,2 Monika Ciekot-Sołtysiak,1 Jacek Zieliński1 1Department of Athletics, Strength and Conditioning, Poznan University of Physical Education, Poznan, Poland; 2Department of Biochemistry, Medical University of Gdansk, Gdansk, PolandCorrespondence: Barbara Pospieszna, Department of Athletics, Strength and Conditioning, Poznan University of Physical Education, Królowej Jadwigi 27/39, Poznan, 61-871, Poland, Tel +48-618-355-270, Email bpospieszna@awf.poznan.plIntroduction: The guanine nucleotide pool (GTP, guanosine-5’-triphosphate; GDP, guanosine-5’-diphosphate, and GMP, guanosine-5’-monophosphate) is an essential energy donor in various biological processes (eg protein synthesis and gluconeogenesis) and secures several vital regulatory functions in the human body. The study aimed to predict the trends of age-related changes in erythrocyte guanine nucleotides and examine whether competitive sport and related physical training promote beneficial adaptations in erythrocyte guanylate concentrations.Methods: The study included 86 elite endurance runners (EN) aged 20– 81 years, 58 sprint-trained athletes (SP) aged 21– 90 years, and 62 untrained individuals (CO) aged 20– 68 years.Results: The concentration of erythrocyte GTP and total guanine nucleotides (TGN) were highest in the SP group, lower in the EN group, and lowest in the CO group. Both athletic groups had higher guanylate energy charge (GEC) values than the CO group (p = 0.012). Concentrations of GTP, TGN, and GEC value significantly decreased, while GDP and GMP concentrations progressively increased with age.Conclusion: Such a profile of change suggests a deterioration of the GTP-related regulatory function in older individuals. Our study explicitly shows that lifelong sports participation, especially of sprint-oriented nature, allows for maintaining a higher erythrocyte guanylate pool concentration, supporting cells’ energy metabolism, regulatory and transcription properties, and thus more efficient overall body functioning.Keywords: guanosine triphosphate, GTP, guanylate energy charge, GEC, purine metabolites, endurance, sprint, master athletes

Abstract Spinal cord injury (SCI) is a devastating and disabling medical condition generally caused by a traumatic event (primary injury). This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage (secondary injury). The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI, explaining the progression and detrimental consequences related to this condition. Psychoneuroimmunoendocrinology (PNIE) is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism, considering the mind and the body as a whole. The initial traumatic event and the consequent neurological disruption trigger immune, endocrine, and multisystem dysfunction, which in turn affect the patient’s psyche and well-being. In the present review, we will explore the most important local and systemic consequences of SCI from a PNIE perspective, defining the changes occurring in each system and how all these mechanisms are interconnected. Finally, potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

Objective: This study examines the knowledge and confidence of college healthcare providers in discussing vaping with their college student populations. Methods: This is a mixed-methods descriptive study using a sequential-explanatory approach, consisting of a cross-sectional, online survey followed by qualitative interviews. Survey data was collected from 50 college health providers located at 26 colleges in the 64-campus State University of New York system. Targeted semi-structured interviews (N = 11) were conducted by telephone with providers who completed the survey. Results: Despite high reported levels of knowledge and confidence, few providers had participated in educational activities relative to vaping. There was evidence of misinformation about e-cigarettes, and they did not know what product (nicotine/cannabis) students typically vape. Conclusions: Findings indicate a potential disconnect between providers’ perceived and actual knowledge of college student vaping and demonstrate areas of opportunity to assist college health providers in comprehensively addressing vaping with their college student populations. Innovation: College health providers played a key role in lowering rates of combustible cigarette smoking, but little is known about how they are now are communicating with college students about e-cigarette and cannabis vaping. This paper examines college health providers’ knowledge, confidence, and training needs relative to vaping communications.

Since the 2010s cryptocurrencies have started to acquire a popularity never seen before, influencing the way the general population, investors, and governments treat investments. It is no surprise that central banks are pursuing their own digital currency in order to boost the security of transactions and reduce counterfeiting. Throughout this paper, we are going to analyze and compare the market valuation of the ten most valuable cryptocurrencies and explain if it is possible that one of them could become a viable and widely used currency in the future. Additionally, we are going to examine the central banks that will pursue their own digital currency and the reasons as of why they chose to venture into this new uncharted technology.

In this work, the results of investigations of polyurethane materials were presented. Innovative materials based on polyurethane-polyisocyanurate (PUR/PIR) foam were obtained. Different types of additives (flame retardants, aerogels – additives that decrease thermal conductivity) are used in the composition of PUR/PIR foam. Foams are a type of composite composed of two phases: continuous (polyurethane polymers) and dispersed (composed of gases). All samples have been tested for thermal parameters: thermal conductivity, specific heat, and thermal diffusivity. Then they have been compared with each other and with a reference sample (RS) without additives. Based on the research, it was shown that innovative insulation materials were characterized by thermal conductivity λ in the range of 0.0254–0.0294 W/(m · K). The thermal properties of foams depending on the type and chemical composition of the material. Depending on the used substrates, their molar ratio, type, synthesis conditions, modifying agents and catalysts, a different polyurethane material is obtained.

Abstract The pancreatic islet β-cell’s preference for release of newly synthesized insulin requires careful coordination of insulin exocytosis with sufficient insulin granule production to ensure that insulin stores exceed peripheral demands for glucose homeostasis. Thus, the cellular mechanisms regulating insulin granule production are critical to maintaining β-cell function. In this report, we utilized the synchronous protein trafficking system, RUSH, in primary β-cells to evaluate proinsulin transit through the secretory pathway leading to insulin granule formation. We demonstrate that the trafficking, processing, and secretion of the proinsulin RUSH reporter, proCpepRUSH, are consistent with current models of insulin maturation and release. Using both a rodent dietary and genetic model of hyperglycemia and β-cell dysfunction, we show that proinsulin trafficking is impeded at the Golgi and coincides with the decreased appearance of nascent insulin granules at the plasma membrane. Ultrastructural analysis of β-cells from diabetic leptin receptor deficient mice revealed gross morphological changes in Golgi structure, including shortened and swollen cisternae, and partial Golgi vesiculation, which are consistent with defects in secretory protein export. Collectively, this work highlights the utility of the proCpepRUSH reporter in studying proinsulin trafficking dynamics and suggests that altered Golgi export function contributes to β-cell secretory defects in the pathogenesis of Type 2 diabetes.

Abstract Background The importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings. Methods MEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE’s risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol. Discussion Our systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews. Systematic review registration PROSPERO CRD42022367726.

The paper presents the results of improving the production process using the SMED method. The process improvement was carried out in a company in the construction industry, using a machine park consisting of CNC machines. The study evaluated the current state of changeover times for selected CNC machines and proposed a reduction in changeover times for the machine park analysed. By introducing changes to the changeover process on selected CNC machines, it was possible to minimise the changeover time by more than 20% on all the machines analysed. The proposed reorganisation of the CNC operators’ workstations resulted in a time reduction of approximately 61% for machine 1, 52% for machine 2 and 12% for machine 3. The installation of barcode readers on the profiles, on the other hand, made it possible to load the machining programmes into the CNC machines more quickly and resulted in a reduction in loading time of approximately 88% on average for each of the machines analysed.

BackgroundParacetamol, codeine, and tramadol are commonly used to manage mild pain, and their availability without prescription or medical consultation raises concerns about potential opioid addiction. ObjectiveThis study aims to explore the perceptions and experiences of Twitter users concerning these drugs. MethodsWe analyzed the tweets in English or Spanish mentioning paracetamol, tramadol, or codeine posted between January 2019 and December 2020. Out of 152,056 tweets collected, 49,462 were excluded. The content was categorized using a codebook, distinguishing user types (patients, health care professionals, and institutions), and classifying medical content based on efficacy and adverse effects. Scientific accuracy and nonmedical content themes (commercial, economic, solidarity, and trivialization) were also assessed. A total of 1000 tweets for each drug were manually classified to train, test, and validate machine learning classifiers. ResultsOf classifiable tweets, 42,840 mentioned paracetamol and 42,131 mentioned weak opioids (tramadol or codeine). Patients accounted for 73.10% (60,771/83,129) of the tweets, while health care professionals and institutions received the highest like-tweet and tweet-retweet ratios. Medical content distribution significantly differed for each drug (P

BackgroundOpioids are used for the treatment of refractory pain, but their inappropriate use has detrimental consequences for health. Understanding the current experiences and perceptions of patients in a spontaneous and colloquial environment regarding the key drugs involved in the opioid crisis is of utmost significance. ObjectiveThe study aims to analyze Twitter content related to opioids, with objectives including characterizing users participating in these conversations, identifying prevalent topics and gauging public perception, assessing opinions on drug efficacy and tolerability, and detecting discussions related to drug dispensing, prescription, or acquisition. MethodsIn this cross-sectional study, we gathered public tweets concerning major opioids posted in English or Spanish between January 1, 2019, and December 31, 2020. A total of 256,218 tweets were collected. Approximately 27% (69,222/256,218) were excluded. Subsequently, 7000 tweets were subjected to manual analysis based on a codebook developed by the researchers. The remaining databases underwent analysis using machine learning classifiers. In the codebook, the type of user was the initial classification domain. We differentiated between patients, family members and friends, health care professionals, and institutions. Next, a distinction was made between medical and nonmedical content. If it was medical in nature, we classified it according to whether it referred to the drug’s efficacy or adverse effects. In nonmedical content tweets, we analyzed whether the content referred to management issues (eg, pharmacy dispensation, medical appointment prescriptions, commercial advertisements, or legal aspects) or the trivialization of the drug. ResultsAmong the entire array of scrutinized pharmaceuticals, fentanyl emerged as the predominant subject, featuring in 27% (39,997/148,335 posts) of the tweets. Concerning user categorization, roughly 70% (101,259/148,335) were classified as patients. Nevertheless, tweets posted by health care professionals obtained the highest number of retweets (37/16,956, 0.2% of their posts received over 100 retweets). We found statistically significant differences in the distribution concerning efficacy and side effects among distinct drug categories (P

BackgroundChagas disease (ChD) is the most important endemy in Latin America. Some patients, develop chronic Chagasic cardiopathy (CCC) years after the acute phase. It is unknown if patients infected by the oral route have higher risk of developing early CCC.Methods and findingsA prospective cohort study was conducted to assess morbidity and mortality during 10 years observation in 106 people simultaneously infected and treated in the largest known orally transmitted ChD outbreak in 2007. A preschooler died during the acute phase, but thereafter was no mortality associated to ChD. All acute phase findings improved in the first-year post-treatment. Each person was evaluated 8.7 times clinically, 6.4 by electrocardiogram (ECG)/Holter, and 1.7 by echocardiogram. Based on prevalence, the number of people who had any abnormalities (excluding repolarization abnormalities and atrial tachycardia which decreased) was higher than 2007, since they were found at least once between 2008-2017. However, when we evaluated incidence, except for clinical bradycardia and dizziness, it was observed that the number of new cases of all clinical and ECG findings decreased at the end of the follow-up. Between 2008-2017 there was not incidence of low voltage complex, 2nd degree AV block, long QT interval, left bundle branch block or left ventricular dysfunction that allowed the diagnosis of CCC. Total improvement prevailed over the persistence of all clinical and ECG/Holter findings, except for sinus bradycardia. Incomplete right bundle branch block, sinus bradycardia and/or T-wave inversion were diagnosed persistently in 9 children. The second treatment did not have significant influence on the incidence of clinical or ECG/Holter findings.ConclusionsAt the end of the 10-year follow-up, there were not clinical or ECG/Holter criteria for classifying patients with CCC. The incidence of arrhythmias and repolarization abnormalities decreased. However, special attention should be paid on findings that not revert as sinus bradycardia, or those diagnosed persistently in all ECG as sinus bradycardia, incomplete right bundle branch block or T-wave inversion. Early diagnosis and treatment may have contributed to the rapid improvement of these patients. In ChD follow-up studies prevalence overestimates the real dimension of abnormalities, the incidence looks as a better indicator.

IntroductionCandida albicans is an opportunistic human pathogen that typically resides as part of the microbiome in the gastrointestinal and genitourinary tracts of a large portion of the human population. This fungus lacks a true sexual cycle and evolves in a largely clonal pattern. The ability to cause disease is consistent across the species as strains causing systemic infections appear across the known C. albicans intra-species clades.MethodsIn this work, strains collected from patients with systemic C. albicans infections isolated at the Nebraska Medicine clinical laboratory were typed by MLST analysis. Since the ability to form filaments has been linked to pathogenesis in C. albicans, these clinical strains, as well as a previously genotyped set of clinical strains, were tested for their ability to filament across a variety of inducing conditions.ResultsGenotyping of the clinical strains demonstrated that the strains isolated at one of the major medical centers in our region were as diverse as strains collected across the United States. We demonstrated that clinical strains exhibit a variety of filamentation patterns across differing inducing conditions. The only consistent pattern observed in the entire set of clinical strains tested was an almost universal inability to filament in standard solid inducing conditions used throughout the C. albicans field. A different solid filamentation assay that produces more robust filamentation profiles from clinical strains is proposed in this study, although not all strains expected to filament in vivo were filamentous in this assay.DiscussionOur data supports growing evidence that broad phenotypic diversity exists between the C. albicans type strain and clinical strains, suggesting that the type strain poorly represents filamentation patterns observed in most clinical isolates. These data further highlight the need to use diverse clinical strains in pathogenesis assays.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The “response-to-injury” model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay.

IntroductionIt is unclear whether admission-blood-glucose-to-albumin ratio (AAR) predicts adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with percutaneous coronary intervention (PCI). Here, we performed a observational study to explore the predictive value of AAR on clinical outcomes.MethodsPatients diagnosed with STEMI who underwent PCI between January 2010 and February 2020 were enrolled in the study. The patients were classified into three groups according to AAR tertile. The primary outcome was in-hospital all-cause mortality, and the secondary outcomes were in-hospital major adverse cardiac events (MACEs), as well as all-cause mortality and MACEs during follow-up. Logistic regression, Kaplan–Meier analysis, and Cox proportional hazard regression were the primary analyses used to estimate outcomes.ResultsAmong the 3,224 enrolled patients, there were 130 cases of in-hospital all-cause mortality (3.9%) and 181 patients (5.4%) experienced MACEs. After adjustment for covariates, multivariate analysis demonstrated that an increase in AAR was associated with an increased risk of in-hospital all-cause mortality [adjusted odds ratio (OR): 2.72, 95% CI: 1.47–5.03, P = 0.001] and MACEs (adjusted OR: 1.91, 95% CI: 1.18–3.10, P = 0.009), as well as long-term all-cause mortality [adjusted hazard ratio (HR): 1.64, 95% CI: 1.19–2.28, P = 0.003] and MACEs (adjusted HR: 1.58, 95% CI: 1.16–2.14, P = 0.003). Receiver operating characteristic (ROC) curve analysis indicated that AAR was an accurate predictor of in-hospital all-cause mortality (AUC = 0.718, 95% CI: 0.675–0.761) and MACEs (AUC = 0.672, 95% CI: 0.631–0.712).DiscussionAAR is a novel and convenient independent predictor of all-cause mortality and MACEs, both in-hospital and long-term, for STEMI patients receiving PCI.

Composite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits. In this study, we aimed to replicate and extend the biomarker, composite study relationships using expanded surface-based morphometry and single measures of cognition in a memory clinic population. We examined 271 clinically diagnosed symptomatic individuals with mild cognitive impairment (N = 93) and Alzheimer's disease dementia (N = 178), as well as healthy controls (N = 29). Surface-based morphometry measures included cortical thickness, sulcal depth, and gyrification index within the “signature areas” of Alzheimer's disease. The cognitive variables pertained to hallmark features of Alzheimer's disease including verbal learning, verbal memory retention, and language, as well as executive function. The results demonstrated that verbal learning, language, and executive function correlated with the cortical thickness of the temporal, frontal, and parietal areas. Verbal memory retention was correlated to the thickness of temporal regions and gyrification of the inferior temporal gyrus. Language was related to the temporal regions and the supramarginal gyrus' sulcal depth and gyrification index. Executive function was correlated with the medial temporal gyrus and supramarginal gyrus sulcal depth, and the gyrification index of temporal regions and supramarginal gyrus, but not with the frontal areas. Predictions of each of these cognitive measures were dependent on a combination of structures and each of the morphometry measurements, and often included medial temporal gyrus thickness and sulcal depth. Overall, the results demonstrated that the relationships between cortical thinning and cognition are widespread and can be observed using single measures of cognition in a clinically diagnosed AD population. The utility of sulcal depth and gyrification index measures may be more focal to certain brain areas and cognitive measures. The relative importance of temporal, frontal, and parietal regions in verbal learning, language, and executive function, but not verbal memory retention, was replicated in this clinic cohort.

Once established within a water resource, harmful algal blooms (HABs) can occur seasonally with an intense and rapid onset, giving water resource managers limited time to respond to lessen risks. An attractive strategy to decrease human, ecological, and economic risks from HABs is to implement proactive algaecide treatments applied to overwintering cyanobacteria (i.e., akinetes and quiescent vegetative cells) in sediments prior to the formation of a HAB; however, this approach is novel and very limited efficacy data exist. Therefore, the specific objectives of this research were to 1) evaluate copper- and peroxide-based algaecides, applied as single and repeat treatments at the bench scale, to identify effective proactive treatments, and 2) compare correlations between cell density and other response measurements (i.e., in vivo chlorophyll a and phycocyanin concentrations and percent benthic coverage), to identify informative metrics to assess overwintering cyanobacteria responses. Twelve treatment scenarios using copper- and peroxide-based algaecides were applied to sediments containing overwintering cyanobacteria prior to a 14 d incubation under favorable growth conditions. Responses of cyanobacteria in the planktonic (i.e., cell density, in vivo chlorophyll a and phycocyanin concentrations) and benthic (percent coverage) phases after a 14 d incubation were evaluated in treatments and controls. The HAB-forming cyanobacteria present after a 14 d incubation were: Aphanizomenon, Dolichospermum, Microcystis, Nostoc, and Planktonthrix. Successive treatments of copper sulfate (CuSulfate) followed by sodium carbonate peroxyhydrate (PeroxiSolid) (second algaecide applied after 24 h) as well as repeat applications of a single algaecide, PeroxiSolid (second treatment applied after 24 h) resulted in statistically significant (p ≤ 0.05; α = 0.05) declines in cell density relative to untreated controls. Planktonic cyanobacteria responses measured in terms of phycocyanin concentrations were strongly correlated with cyanobacteria density measurements (Pearson’s correlation coefficient (r) = 0.89). Chlorophyll a concentrations and percent benthic coverage did not correlate with planktonic cyanobacteria density measurements (r = 0.37 and −0.49, respectively) and therefore, were unreliable metrics for cyanobacterial responses in this study. These data provide initial evidence of the efficacy of algaecides for treating overwintering cells in sediments and contribute to our overarching hypothesis that proactive treatments may delay the onset and intensity of HABs in impacted waterbodies.

Abstract Background Muscle mitochondrial decline is associated with aging‐related muscle weakness and insulin resistance. FoxO transcription factors are targets of insulin action and deletion of FoxOs improves mitochondrial function in diabetes. However, disruptions in proteostasis and autophagy are hallmarks of aging and the effect of chronic inhibition of FoxOs in aged muscle is unknown. This study investigated the role of FoxOs in regulating muscle strength and mitochondrial function with age. Methods We measured muscle strength, cross‐sectional area, muscle fibre‐type, markers of protein synthesis/degradation, central nuclei, glucose/insulin tolerance, and mitochondrial bioenergetics in 4.5‐month (Young) and 22–24‐month‐old (Aged) muscle‐specific FoxO1/3/4 triple KO (TKO) and littermate control (Ctrl) mice. Results Lean mass was increased in Aged TKO compared with both Aged Ctrl and younger groups by 26–33% (P

Abstract Coral reefs are highly threatened environs subject to ongoing unprecedented degradation as a result of anthropogenic activities. Given the existential threat to coral reef ecosystems, extractive industries that make use of coral reef resources, are facing significant public and political pressure to quantify and justify their environmental impact. In Australia, hundreds of thousands of live scleractinian (hard) corals are harvested annually directly from the wild to supply the growing international marine aquarium trade. Many of the most popular and high value aquarium corals are believed to be slow growing, which would make them particularly vulnerable to over-fishing. Corals present a number of unique challenges for fisheries management, not least of which, is the marked variation in the size of corals, which may be harvested in whole or in part. This issue is further compounded because harvest limits are typically weight-based, but there is very limited information on the standing biomass of corals in targeted stocks. Herein, we describe size-weight relationships for some of Australia’s most heavily targeted coral species (Catalaphyllia jardinei, Duncanopsammia axifuga, Euphyllia glabrescens, Homophyllia cf. australis, Micromussa lordhowensis, Trachyphyllia geoffroyi), which allows estimation of standing biomass from transect surveys. This work represents an important first step in the development of ecologically sound management strategies by bridging the gap between catch reporting and stock assessments.

Magdalena Massalska,1 Marzena Ciechomska,1 Ewa Kuca-Warnawin,1 Tomasz Burakowski,1 Anna Kornatka,1 Anna Radzikowska,1 Dariusz Pawlak,2 Barbara Muz,3 Adrianna Loniewska-Lwowska,4 Andrzej Palucha,5 Pawel Maldyk,6,7 Wlodzimierz Maslinski1 1Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, 02-637, Poland; 2Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, 15-222, Poland; 3Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine, St. Louis, MO, 63108, USA; 4Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, 02-106, Poland; 5Genomed S.A. Ponczowa 12, Warsaw, 02-971, Poland; 6Department of Rheumoorthopaedic Surgery, National Institute of Geriatrics, Rheumatology, and Rehabilitation (NIGRiR), Warsaw, 02-637, Poland; 7Clinical Department of Orthopaedic and Traumatology of Locomotor System, Enfant-Jesus Clinical Hospital, Warsaw, 02-005, PolandCorrespondence: Magdalena Massalska, Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Spartanska 1, Warsaw, 02-637, Poland, Tel/Fax +48 22 670 94 94, Email magdalena.massalska@spartanska.plBackground: Rheumatoid arthritis (RA) is a chronic autoimmune disease with systemic inflammation finally resulting in damaged joints. One of the RA development models suggests bone marrow (BM) as a place of inflammation development further leading to disease progression. We aimed to investigate the potential of CTLA-4-Fc molecule in inducing tolerogenic milieu in BM measured as indoleamine 2,3-dioxygenase (IDO) expression, CD4+Foxp3+ Treg induction, and T cell activation control. The expression of IDO-pathway genes was also examined in monocytes to estimate the tolerogenic potential in the periphery.Methods: Bone marrow mononuclear cells (BMMC) were stimulated by pro-inflammatory cytokines and CTLA-4-Fc. Next IDO expression, CD4+CD69+ and CD4+Foxp3+ percentage were estimated by PCR and FACS staining, respectively. Enzymatic activity of IDO was confirmed by HPLC in BM plasma and blood plasma. Genes expressed in IDO-pathway were analyzed by NGS in peripheral monocytes isolated from RA patients and healthy controls.Results: We found that CTLA-4-Fc and IFN-γ stimulation results in IDO production by BMMC. CTLA-4-Fc induced tryptophan catabolism can inhibit mitogen-induced CD4+ T cells activation without influencing CD8+ cells, but did not control CD25 nor Foxp3 expression in BM cells. Significantly higher expression of selected IDO-pathway genes was detected on peripheral monocytes isolated from RA as compared to healthy controls.Conclusion: This study sheds light on some immunosuppression aspects present or induced in BM. The potential of IDO-mediated pathways were confirmed in the periphery, what may represent the promising candidates for therapeutic strategies in RA.Keywords: rheumatoid arthritis, bone marrow, CTLA-4-Fc, indoleamine 2,3- dioxygenase, CD4+Foxp3+, monocytes

Collections of silent film music constitute valuable sources for historical research on the musical practice in the silent film era. The musical prints preserved in the Mirskey Collection were previously used by the author to reconstruct a score for the movie A Kiss for Cinderella (1925, dir. Herbert Brenon). This article describes the historical context considered during the reconstruction and discusses the workflow applied by Nek Mirskey (Bronisław Mirski) as a musical director of movie theatres. A comparative analysis of sheet music from the Mirskey Collection accompanied by handwritten notes, original cue sheet compiled by James Bradford for the Paramount Pictures, and a digitised copy of the film, have led to conclusions that are applicable not only to Mirskey's methods of compiling scores, but also to the more general rules for the development of musical accompaniments to silent films in the 1920s.

The green transition unfolding on a global scale is much less studied at the regional level, although its outcomes and management are strongly place-specific. This article presents a comparative study of green transition strategies in the Silesian Voivodeship (Poland) and the Khanty-Mansiysk Autonomous Okrug (KMAO) – Ugra (Russia), based on a qualitative content analysis of regional legislation and strategies. The regions share common specialisation in fossil fuel mining and have inherited some features of post-socialist economies. Research shows three common features of green transition policies in the studied regions. Firstly, much attention is paid to the dissemination of information about green transition and its benefits. Secondly, research on various green subjects and educational programmes for green market requirements are developed. Thirdly, it is planned for renewables to have a larger proportion in regional energy mixes. By mid-century, both regions are expected to reach climate neutrality, although by using different paths of development. Coal mines are planned to be closed down in the Silesian Voivodeship by 2050, while the KMAO – Ugra will retain its oil-mining specialisation but diversify it with hydrogen production.

Rectal cancer constitutes around one-third of all colorectal cancers. New markers are required to optimize the treatment. Extramural vascular invasion (EMVI) is a magnetic resonance imaging (MRI)-based negative prognostic marker. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) are blood-based systemic inflammatory response markers with proven prognostic value in many cancers, including CRC. We hypothesized whether there is a relationship between LMR, NLR, PLR and the presence of EMVI on pre-treatment MRI in patients with locally advanced rectal cancer (LARC). We conducted a retrospective analysis of 371 patients with LARC treated in the Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland between August 2016 and December 2021. One hundred eighty-four patients were found eligible for the study. A correlation between the extension of the tumour, nodal status, clinical stage of the disease and the presence of EMVI was found (p < 0.001). The pre-treatment level of neutrophils, platelets and carcinoembryonic antigen (CEA) was significantly higher in the EMVI-positive population (p = 0.041, p = 0.01, p = 0.027, respectively). There were no significant differences regarding the level of LMR, NLR and PLR between the EMVI-positive and EMVI-negative population. LMR, NLR and PLR do not differentiate patients in terms of EMVI; neither of these parameters is a good predictor of the status of EMVI in LARC.

Abstract Background Dipylidium caninum is the causal agent of dipylidiasis affecting mainly cats and dogs worldwide. Human cases of dipylidiasis are rare, and the diagnosis is prevalently based on morphological features of the parasite. Here we report the diagnosis of dipylidiasis through morphological and molecular characterization of D. caninum infecting an 11-month-old boy in Cajicá, Colombia. Methods Fresh faecal samples were obtained from the infant, and morphological identification of the parasite was performed through faecal smears. DNA was extracted from proglottids and used in PCR analyses for amplification of a 653-bp fragment of the nuclear ribosomal RNA (rRNA) encoding the 28S rRNA gene. A phylogeny study to better characterize the obtained DNA sequence was inferred using the maximum likelihood method and the Tamura-Nei model. Results After morphological and molecular analyses, D. caninum was identified as the etiological agent causing the infection in the infant. Results of phylogenetical analyses showed that the obtained sequence clusters within the feline genotype clade. After the diagnosis of the parasite, effective treatment with praziquantel was administered to the infant. Conclusions This is the third human case of dipylidiasis reported in Colombia, and the first study in South America to provide a molecular identification of D. caninum. Graphical abstract

The main goal of this paper is to empirically examine the effects of related and unrelated variety on per employee income in Polish NUTS 2 regions, and the resulting income inequality. The study is based on regional panel data for the 2003–2018 period using the GMM estimator system. The positive effect of related variety on per employee income and the negative effect of unrelated variety on per employee income are reported. Our simulation results show that regional income inequality could be reduced by promoting related variety in eastern regions of the country.

Pawel Kiper,1 Ewa Przysi&eogon;&zdot;na,2 B&lstrok;a&zdot;ej Cie&sacute;lik,1 Katarzyna Broniec-Siekaniec,3 Aleksandra Kuci&nacute;ska,3 Jaros&lstrok;aw Szczygie&lstrok;,4,5 Katarzyna Turek,6 Robert Gajda,7,8 Joanna Szczepa&nacute;ska-Gieracha2 1Healthcare Innovation Technology Lab, IRCCS San Camillo Hospital, Venezia, Italy; 2Faculty of Physiotherapy, University School of Physical Education in Wroclaw, Wroclaw, Poland; 3“REPTY” Upper Silesian Rehabilitation Centre, Tarnowskie Góry, Poland; 4Humanitas University in Sosnowiec, Sosnowiec, Poland; 5Neurorehabilitation Department, District Hospital, Zawiercie, Poland; 6The Karol Lipi&nacute;ski Academy of Music in Wroclaw, Wroc&lstrok;aw, Poland; 7Gajda-Med District Hospital in Pultusk, Pu&lstrok;tusk, Poland; 8Department of Kinesiology and Health Prevention, Jan Dlugosz University in Cz&eogon;stochowa, Cz&eogon;stochowa, PolandCorrespondence: Pawel Kiper, IRCCS San Camillo Hospital, Alberoni 70, Venezia, 30126, Italy, Tel +390412207157, Email pawel.kiper@hsancamillo.itPurpose: Depressive symptoms constitute an important group of mental problems that alter the course of post-stroke rehabilitation by reducing quality of life, physical activity, social functioning, and interpersonal relationships. Although several studies have shown the efficacy of virtual reality (VR) in the motor treatment of poststroke patients, there is a lack of studies that would also evaluate the impact of VR on psychological aspects. Thus, we investigated the effectiveness of immersive VR therapy on both functional activity and depressive symptoms in stroke survivors.Patients and Methods: We conducted a single blind, randomized controlled trial comparing VR therapy with Schultz’s Autogenic Training (SAT). Patients randomized to the VR group received treatment in an immersive VR therapeutic garden with elements of psychotherapy and physical activity of the upper extremities, whereas patients in the control group received SAT. Additionally, patients in both groups received standard neurological rehabilitation. The full research cycle lasted six weeks. We used Geriatric Depression Scale, Generalized Self-Efficacy Scale, Acceptance of Illness Scale, Visual Analogue Scale of pain, Hospital Anxiety and Depression Scale, Barthel Index, Lawton Instrumental Activities of Daily Living Scale and Rivermead Motor Assessment for outcome assessment. This trial was registered with ClinicalTrials.gov (NCT03830372).Results: We assessed 60 patients and randomly assigned to the VR or control group. The VR group showed a significant reduction in depressive symptoms (ηp2 = 0.13, p < 0.01) compared to SAT. The applied VR therapy significantly increased the sense of self-efficacy and the level of acceptance of the illness; however, this effect was similar to that obtained with the standard intervention. We did not observe statistically significant changes in the functional parameters of post-stroke patients.Conclusion: The use of VR therapy combined with neurological rehabilitation had a positive effect on improving mood and reducing depressive symptoms in post-stroke patients.Keywords: stroke, depressive symptoms, virtual reality, mental health, neurorehabilitation

Abstract Peru was the first country where pfhrp2 and pfhrp3 gene deletions were detected despite the fact that rapid diagnostics tests are not commonly used for confirmatory malaria diagnosis. This context provides a unique scenario to study the dynamics of pfhrp2 and pfhrp3 gene deletions without apparent RDTs selection pressure. In this study we characterized the presence of pfhrp2 and pfhrp3 genes on 325 P. falciparum samples collected in Iquitos and surrounding communities between 2011 and 2018 in order to understand the dynamics of gene deletion prevalence, potential associations with clinical symptomatology and parasite genetic background. P. falciparum presence was confirmed by microscopy and PCR of 18 s rRNA, pfmsp1 and pfmsp2. Gene deletions were assessed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCRs. Confirmation of absence of HRP2 expression was assessed by ELISA of HRP2 and pLDH. Genotyping of 254 samples were performed using a panel of seven neutral microsatellite markers. Overall, pfhrp2 and pfhrp3 dual gene deletions were detected in 67% (217/324) parasite samples. Concordance between pfhrp2 deletion and negligible HRP2 protein levels was observed (Cohen's Kappa = 0.842). Prevalence of gene deletions was heterogeneous across study sites (adjusted p

Abstract Background Colombia is ranked very high among countries with the highest numbers of endemic Leishmania species (n = 9) causing human disease. Although much effort has been devoted to generating simple and specific tools for Leishmania species identification, challenges remain in the discrimination of species belonging to the Leishmania (Viannia) guyanensis complex: L. (V.) guyanensis and L. (V.) panamensis. Methods A set of seven reference strains of species belonging to the L. (Leishmania) and L. (Viannia) subgenera, clinical strains from human cases of cutaneous leishmaniasis (CL; n = 26) and samples collected from sylvatic mammals and sand flies (n = 7) from endemic areas in Colombia were analyzed in this study. The heat-shock protein 70 gene (hsp70) was amplified by PCR from DNA extracted from logarithmic-phase promastigotes or tissue samples, and the PCR products were sequenced. Sequence alignment was performed against a set of previously published and curated sequences, and phylogenetic analysis based on the maximum-likelihood and Bayesian inference approaches was conducted. Haplotype diversity among strains and species of the L. (V.) guyanensis complex was explored using a median-joining network. Results Sequencing of the hsp70 gene for L. (Viannia) spp. typing was comparable to species identification using isoenzyme electrophoresis or monoclonal antibodies. Complete species matching was found, except for one sylvatic sample with an identity yet unsolved. Among the L. (V.) panamensis clinical strains, two distinctive phylogenetic clusters were found to correlate with two different zymodemes: L. (V.) panamensis Z2.2 and Z2.3. Analysis of samples from sylvatic environments identified novel records of naturally infected wild mammal and sand fly species. Conclusions Our results support the adequacy of hsp70 gene sequencing as a single-locus approach for discrimination of L. (Viannia) spp., as well as for exploring the genetic diversity within the L. (V.) guyanensis complex. Graphical Abstract

Developments in modern times have grown rapidly, this can be seen from the rapid development. Along with the increasing scale of development in the world of construction, more and more concrete is needed effectively, practically, and in the future. The strength of concrete is strongly influenced by the quality of the materials, admixtures, the working process, and the curing of the concrete. Concrete with the addition of an accelerator has higher compressive strength, this is due to the accelerator reaction which can accelerate the binding process and the development of the initial compressive strength of the concrete. Concrete with direct immersion treatment has large compressive strength. There are several methods of treating concrete, including watering and high temperature. This study used a fixed accelerator proportion of 3 % of the weight of cement with a test time of 7 and 28 days. The treatment method used is open space, immersion, high temperature at temperatures of 25 ºC, 30 ºC, 35 ºC, 40 ºC and 45 ºC. From the results of the research, there are differences in characteristics between normal concrete and concrete with the addition of an accelerator. Concrete with a high-temperature treatment method at a temperature of 45 ºC produces the highest strong pressure. This is caused by the higher the treatment temperature, the higher the rate of hydration process that affects the compressive strength of the concrete.

Abstract Rising ocean temperatures are threatening marine species and populations worldwide, and ectothermic taxa are particularly vulnerable. Echinoderms are an ecologically important phylum of marine ectotherms and shifts in their population dynamics can have profound impacts on the marine environment. The effects of warming on echinoderms are highly variable across controlled laboratory‐based studies. Accordingly, synthesis of these studies will facilitate the better understanding of broad patterns in responses of echinoderms to ocean warming. Herein, a meta‐analysis incorporating the results of 85 studies (710 individual responses) is presented, exploring the effects of warming on various performance predictors. The mean responses of echinoderms to all magnitudes of warming were compared across multiple biological responses, ontogenetic life stages, taxonomic classes, and regions, facilitated by multivariate linear mixed effects models. Further models were conducted, which only incorporated responses to warming greater than the projected end‐of‐century mean annual temperatures at the collection sites. This meta‐analysis provides evidence that ocean warming will generally accelerate metabolic rate (+32%) and reduce survival (−35%) in echinoderms, and echinoderms from subtropical (−9%) and tropical (−8%) regions will be the most vulnerable. The relatively high vulnerability of echinoderm larvae to warming (−20%) indicates that this life stage may be a significant developmental bottleneck in the near‐future, likely reducing successful recruitment into populations. Furthermore, asteroids appear to be the class of echinoderms that are most negatively affected by elevated temperature (−30%). When considering only responses to magnitudes of warming representative of end‐of‐century climate change projections, the negative impacts on asteroids, tropical species and juveniles were exacerbated (−51%, −34% and −40% respectively). The results of these analyses enable better predictions of how keystone and invasive echinoderm species may perform in a warmer ocean, and the possible consequences for populations, communities and ecosystems.

Introduction: Dysfunction of the endothelium impairs its’ protective role and promotes inflammation and progression of vascular diseases. Activated Protein C (APC) elicits endothelial cytoprotective responses including barrier stabilization, anti-inflammatory and anti-apoptotic responses through the activation of the G protein-coupled receptor (GPCR) protease-activated receptor-1 (PAR1) and is a promising therapeutic. Despite recent advancements in developing new Activated protein C variants with clinical potential, the mechanism by which APC/PAR1 promotes different cytoprotective responses remains unclear and is important to understand to advance Activated protein C and new targets as future therapeutics. Here we examined the mechanisms by which APC/PAR1 attenuates cytokine-induced pro-inflammatory vascular cell adhesion molecule (VCAM-1) expression, a key mediator of endothelial inflammatory responses.Methods: Quantitative multiplexed mass spectrometry analysis of Activated protein C treated endothelial cells, endothelial cell transcriptomics database (EndoDB) online repository queries, biochemical measurements of protein expression, quantitative real-time polymerase chain reaction (RT-qPCR) measurement of mRNA transcript abundance, pharmacological inhibitors and siRNA transfections of human cultured endothelial cells.Results: Here we report that Activated Protein C modulates phosphorylation of tumor necrosis factor (TNF)-α signaling pathway components and attenuates of TNF-α induced VCAM-1 expression independent of mRNA stability. Unexpectedly, we found a critical role for the G protein-coupled receptor co-receptor sphingosine-1 phosphate receptor-1 (S1PR1) and the G protein receptor kinase-2 (GRK2) in mediating APC/PAR1 anti-inflammatory responses in endothelial cells.Discussion: This study provides new knowledge of the mechanisms by which different APC/PAR1 cytoprotective responses are mediated through discrete β-arrestin-2-driven signaling pathways modulated by specific G protein-coupled receptor co-receptors and GRKs.

Functional foods, drug delivery systems, and cosmetics are the main areas of application for multiphase systems, where the use of naturally derived compounds is preferred. Hence, this study aimed to assess the possibility of using natural surfactants and saponin-rich extracts to produce emulsions containing antibacterial and antioxidant cinnamon and clove essential oils (EOs). The analyses of nanoparticles using dynamic light scattering showed that the addition of plant extracts to solutions allows one to obtain stable emulsions and decreased zeta potential (< −40 mV) and droplet size (

Inflammasomes are multiprotein signaling platforms in the cytosol that senses exogenous and endogenous danger signals and respond with the maturation and secretion of IL-1β and IL-18 and pyroptosis to induce inflammation and protect the host. The inflammasome best studied is the Nucleotide-binding oligomerization domain, leucine-rich repeat-containing family pyrin domain containing 3 (NLRP3) inflammasome. It is activated in a two-step process: the priming and the activation, leading to sensor NLRP3 oligomerization and recruitment of both adaptor ASC and executioner pro-caspase 1, which is activated by cleavage. Moreover, NLRP3 inflammasome activation is regulated by posttranslational modifications, including ubiquitination/deubiquitination, phosphorylation/dephosphorylation, acetylation/deacetylation, SUMOylation and nitrosylation, and interaction with NLPR3 protein binding partners. Moreover, the connection between it and metabolism is receiving increasing attention in this field. In this review, we present the structure, functions, activation, and regulation of NLRP3, with special emphasis on regulation by mitochondrial dysfunction-mtROS production and metabolic signals, i.e., metabolites as well as enzymes. By understanding the regulation of NLRP3 inflammasome activation, specific inhibitors can be rationally designed for the treatment and prevention of various immune- or metabolic-based diseases. Lastly, we review current NLRP3 inflammasome inhibitors and their mechanism of action.

O presente estudo objetivou sintetizar e analisar a produção científica sobre as características do desenvolvimento motor (DM) em crianças com Transtorno do Espectro Autista (TEA), por meio de revisão sistemática de literatura. Neste sentido, foram selecionadas as bases de dados Eric/Thesaurus, Web of Science, SciELO, Scopus, ASP/EBsco e Redalyc. Para a identificação dos artigos nas bases de dados, foram elencados os descritores “Child Development”; “Autism Spectrum Disorder”; “Motor Skills Disorder”; “Motor Development” bem como seus termos em português. Por abranger áreas de saúde e educação, estes descritores foram identificados entre os Descritores em Ciências da Saúde (DeCS) da BVS e Thesaurus (Eric). A amostra final foi composta por cinco estudos que apresentaram dados de diferentes baterias de avaliação motora. Os resultados caracterizaram o DM em crianças com TEA como atípico, apresentando déficits significativos em todas às áreas motoras, sendo a coordenação fina, o equilíbrio e o esquema corporal, os mais pronunciados.

Background Locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC) is associated with significant morbidity and mortality. To target upregulated ErbB dimer expression in this cancer, we developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) approach named T4 immunotherapy. Patient-derived T-cells are engineered by retroviral transduction to coexpress a panErbB-specific CAR called T1E28ζ and an IL-4-responsive chimeric cytokine receptor, 4αβ, which allows IL-4-mediated enrichment of transduced cells during manufacture. These cells elicit preclinical antitumor activity against HNSCC and other carcinomas. In this trial, we used intratumoral delivery to mitigate significant clinical risk of on-target off-tumor toxicity owing to low-level ErbB expression in healthy tissues.Methods We undertook a phase 1 dose-escalation 3+3 trial of intratumoral T4 immunotherapy in HNSCC (NCT01818323). CAR T-cell batches were manufactured from 40 to 130 mL of whole blood using a 2-week semiclosed process. A single CAR T-cell treatment, formulated as a fresh product in 1–4 mL of medium, was injected into one or more target lesions. Dose of CAR T-cells was escalated in 5 cohorts from 1×107−1×109 T4+ T-cells, administered without prior lymphodepletion.Results Despite baseline lymphopenia in most enrolled subjects, the target cell dose was successfully manufactured in all cases, yielding up to 7.5 billion T-cells (67.5±11.8% transduced), without any batch failures. Treatment-related adverse events were all grade 2 or less, with no dose-limiting toxicities (Common Terminology Criteria for Adverse Events V.4.0). Frequent treatment-related adverse events were tumor swelling, pain, pyrexias, chills, and fatigue. There was no evidence of leakage of T4+ T-cells into the circulation following intratumoral delivery, and injection of radiolabeled cells demonstrated intratumoral persistence. Despite rapid progression at trial entry, stabilization of disease (Response Evaluation Criteria in Solid Tumors V.1.1) was observed in 9 of 15 subjects (60%) at 6 weeks post-CAR T-cell administration. Subsequent treatment with pembrolizumab and T-VEC oncolytic virus achieved a rapid complete clinical response in one subject, which was durable for over 3 years. Median overall survival was greater than for historical controls. Disease stabilization was associated with the administration of an immunophenotypically fitter, less exhausted, T4 CAR T-cell product.Conclusions These data demonstrate the safe intratumoral administration of T4 immunotherapy in advanced HNSCC.

Herein, we present a dataset based on the RNA-Seq analysis of liver tissue from bovine female fetuses at day 83 of gestation. The findings were reported in the main article, “Periconceptual maternal nutrition affects fetal liver programming of energy- and lipid-related genes” [1]. These data were generated to investigate the effects of periconceptual maternal vitamin and mineral supplementation and rates of body weight gain on the transcript abundance of genes associated with fetal hepatic metabolism and function. To this end, crossbred Angus beef heifers (n = 35) were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial design. The main effects tested were vitamin and mineral supplementation (VTM or NoVTM – at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low (LG – 0.28 kg/d) or moderate (MG – 0.79 kg/d) – from breeding to day 83). The fetal liver was collected on day 83 ± 0.27 of gestation. After total RNA isolation and quality control, strand-specific RNA libraries were prepared and sequenced on the Illumina® NovaSeq 6000 platform to generate paired-end 150-bp reads. After read mapping and counting, differential expression analysis was performed with edgeR. We identified 591 unique differentially expressed genes across all six vitamin-gain contrasts (FDR ≤ 0.1). To our knowledge, this is the first dataset investigating the fetal liver transcriptome in response to periconceptual maternal vitamin and mineral supplementation and/or the rate of weight gain. The data described in this article provides genes and molecular pathways differentially programming liver development and function.