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Nature‐derived cyclic peptides have proven to be a vast source of inspiration for advancing modern pharmaceutical design and synthetic chemistry. The focus of this Review is sunflower trypsin inhibitor‐1 (SFTI‐1), one of the smallest disulfide‐bridged cyclic peptides found in nature. SFTI‐1 has an unusual biosynthetic pathway that begins with a dual‐purpose albumin precursor and ends with the production of a high‐affinity serine protease inhibitor that rivals other inhibitors much larger in size. Investigations on the molecular basis for SFTI‐1′s rigid structure and adaptable function have planted seeds for thought that have now blossomed in several different fields. Here we survey these applications to highlight the growing potential of SFTI‐1 as a versatile template for engineering inhibitors, a prototypic peptide for studying inhibitory mechanisms, a stable scaffold for grafting bioactive peptides, and a model peptide for evaluating peptidomimetic motifs and platform technologies. [ABSTRACT FROM AUTHOR]

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The main discussion above of the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has focused substantially on the immediate risks and impact on the respiratory system; however, the effects induced to the central nervous system are currently unknown. Some authors have suggested that SARS-CoV-2 infection can dramatically affect brain function and exacerbate neurodegenerative diseases in patients, but the mechanisms have not been entirely described. In this review, we gather information from past and actual studies on coronaviruses that informed neurological dysfunction and brain damage. Then, we analyzed and described the possible mechanisms causative of brain injury after SARS-CoV-2 infection. We proposed that potential routes of SARS-CoV-2 neuro-invasion are determinant factors in the process. We considered that the hematogenous route of infection can directly affect the brain microvascular endothelium cells that integrate the blood-brain barrier and be fundamental in initiation of brain damage. Additionally, activation of the inflammatory response against the infection represents a critical step on injury induction of the brain tissue. Consequently, the virus' ability to infect brain cells and induce the inflammatory response can promote or increase the risk to acquire central nervous system diseases. Here, we contribute to the understanding of the neurological conditions found in patients with SARS-CoV-2 infection and its association with the blood-brain barrier integrity. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most prevalent cause of dementia. The main cerebral histological hallmarks are represented by parenchymal insoluble deposits of amyloid beta (Aβ plaques) and neurofibrillary tangles (NFT), intracellular filamentous inclusions of tau, a microtubule-associated protein. It is well-established that cerebrovascular dysfunction is an early feature of AD pathology, but the detrimental mechanisms leading to blood vessel impairment and the associated neurovascular deregulation are not fully understood. In 90% of AD cases, Aβ deposition around the brain vasculature, known as cerebral amyloid angiopathy (CAA), alters blood brain barrier (BBB) essential functions. While the effects of vascular Aβ accumulation are better documented, the scientific community has only recently started to consider the impact of tau on neurovascular pathology in AD. Emerging compelling evidence points to transmission of neuronal tau to different brain cells, including astrocytes, as well as to the release of tau into brain interstitial fluids, which may lead to perivascular neurofibrillar tau accumulation and toxicity, affecting vessel architecture, cerebral blood flow (CBF), and vascular permeability. BBB integrity and functionality may therefore be impacted by pathological tau, consequentially accelerating the progression of the disease. Tau aggregates have also been shown to induce mitochondrial damage: it is known that tau impairs mitochondrial localization, distribution and dynamics, alters ATP and reactive oxygen species production, and compromises oxidative phosphorylation systems. In light of this previous knowledge, we postulate that tau can initiate neurovascular pathology in AD through mitochondrial dysregulation. In this review, we will explore the literature investigating tau pathology contribution to the malfunction of the brain vasculature and neurovascular unit, and its association with mitochondrial alterations and caspase activation, in cellular, animal, and human studies of AD and tauopathies. [ABSTRACT FROM AUTHOR]

Background: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T‐cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well‐known documented conditions such as graft‐vs.‐host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. Materials and methods: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. Results and conclusion: These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T‐cell lymphoma, chronic graft‐vs.‐host disease and acute graft‐vs.‐host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus. [ABSTRACT FROM AUTHOR]

A rigorous study is presented of the physical processes related to X-Ray photoelectron spectroscopy, XPS, in the 4f level of U oxides, which, as well as being of physical interest in themselves, are representative of XPS in heavy metal oxides. In particular, we present compelling evidence for a new view of the screening of core-holes that extends prior understandings. Our analysis of the screening focuses on the covalent mixing of high lying U and O orbitals as opposed to the, more common, use of orbitals that are nominally pure U or pure O. It is shown that this covalent mixing is quite different for the initial and final, core-hole, configurations and that this difference is directly related to the XPS satellite intensity. Furthermore, we show that the high-lying U d orbitals as well as the U(5f) orbital may both contribute to the core-hole screening, in contrast with previous work that has only considered screening through the U(5f) shell. The role of modifying the U-O interaction by changing the U-O distance has been investigated and an unexpected correlation between U-O distance and XPS satellite intensity has been discovered. The role of flourite and octahedral crystal structures for U(IV) oxides has been examined and relationships established between XPS features and the covalent interactions in the different structures. The physical views of XPS satellites as arising from shake processes or as arising from ligand to metal charge transfers are contrasted; our analysis provides strong support that shake processes give a more fundamental physical understanding than charge transfer. Our theoretical studies are based on rigorous, strictly ab initio determinations of the electronic structure of embedded cluster models of U oxides with formal U(VI) and U(IV) oxidation states. Our results provide a foundation that makes it possible to establish quantitative relationships between features of the XPS spectra and materials properties. [ABSTRACT FROM AUTHOR]

The neurovascular system (NVS), which consisted of neurons, glia, and vascular cells, is a functional and structural unit of the brain. The NVS regulates blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), thereby maintaining the brain's microenvironment for normal functioning, neuronal survival, and information processing. Recent studies have highlighted the role of vascular dysfunction in several neurodegenerative diseases. This is not unexpected since both nervous and vascular systems are functionally interdependent and show close anatomical apposition, as well as similar molecular pathways. However, despite extensive research, the precise mechanism by which neurovascular dysfunction contributes to neurodegeneration remains incomplete. Therefore, understanding the mechanisms of neurovascular dysfunction in disease conditions may allow us to develop potent and effective therapies for prevention and treatment of neurodegenerative diseases. This review article summarizes the current research in the context of neurovascular signaling associated with neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We also discuss the potential implication of neurovascular factor as a novel therapeutic target and prognostic marker in patients with neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

Photoelectron and Auger peaks are central to most of the important uses of x-ray photoelectron spectroscopy (XPS), and thus, they receive the most attention in many types of analysis. Quantitative chemical analysis using XPS requires the assessment of the intensities of the photoemission peaks of the elements detected. Determination of peak intensities requires separation of the photoelectron peak signals from the background on which the peaks rest. For the determination of peak area intensities, the background is subtracted from overall signal intensity. The spectral background is also critical when peak fitting is used to determine intensities of overlapping peaks, and the model of background used in this process can impact the results. In addition to the impact on quantitative analysis, information about the depth distribution of elements in the near surface region can often be obtained by visual inspection of the background and quantified using appropriate modeling. This introductory guide provides some basic information about backgrounds in the XPS analysis, describes the types of background models that are commonly used, suggests some of their strengths and weaknesses, and provides examples of their use and misuse. Although the fundamental nature of some components of the background signals in XPS is not understood, indicating that none of the models in use are fully correct and the area is subject to active research, appropriate good practices have been established for most routine analysis. The guide describes good practices, identifies errors that frequently appear in the literature, and uses examples to demonstrate the impacts of background selections on determinations of peak intensities. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive degeneration and loss of neurons in specific regions of the central nervous system. Chronic activation of the immune cells resident in the brain, peripheral immune cell trafficking across the blood-brain barrier, and release of inflammatory and neurotoxic factors, appear critical contributors of the neuroinflammatory response that drives the progression of neurodegenerative processes in AD. As the neuro-immune network is impaired in course of AD, this review is aimed to point out the essential supportive role of innate and adaptive immune response either in normal brain as well as in brain recovery from injury. Since a fine-tuning of the immune response appears crucial to ensure proper nervous system functioning, we focused on the role of the TNF superfamily member, TNF-related apoptosis-inducing ligand (TRAIL), which modulates both the innate and adaptive immune response in the pathogenesis of several immunological disorders and, in particular, in AD-related neuroinflammation. We here summarized mounting evidence of potential involvement of TRAIL signaling in AD pathogenesis, with the aim to provide clearer insights about potential novel therapeutic approaches in AD. [ABSTRACT FROM AUTHOR]

Interstitial lung disease is a common pulmonary manifestation of connective tissue diseases and results in significant morbidity and mortality. Although all connective tissue diseases are linked by underlying autoimmunity, there is significant variability in the presentation and clinical course of interstitial lung disease associated with the different types of connective tissue diseases. In this paper, we review the prevalence, patterns, predictors, and prognosis of interstitial lung disease secondary to the most common forms of connective tissue diseases. We have also highlighted the available evidence regarding treatment options for interstitial lung disease due to different connective tissue diseases. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) plays a crucial role in maintaining the specialized microenvironment of the central nervous system (CNS). In aging, the stability of the BBB declines and the permeability increases. The list of CNS pathologies involving BBB dysfunction is growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to a host of processes resulting in progressive synaptic, neuronal dysfunction, and detrimental neuroinflammatory changes. Such processes have been implicated in different diseases, including vascular dementia, stroke, Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, hypoxia, ischemia, and diabetes mellitus. The BBB damage is also observed in tauopathies that lack amyloid-β overproduction, suggesting a role for tau in BBB damage. Tauopathies represent a heterogeneous group of around 20 different neurodegenerative diseases characterized by abnormal deposition of the MAPT in cells of the nervous system. Neuropathology of tauopathies is defined as intracellular accumulation of neurofibrillary tangles (NFTs) consisting of aggregated hyper- and abnormal phosphorylation of tau protein and neuroinflammation. Disruption of the BBB found in tauopathies is driven by chronic neuroinflammation. Production of pro-inflammatory signaling molecules such as cytokines, chemokines, and adhesion molecules by glial cells, neurons, and endothelial cells determine the integrity of the BBB and migration of immune cells into the brain. The inflammatory processes promote structural changes in capillaries such as fragmentation, thickening, atrophy of pericytes, accumulation of laminin in the basement membrane, and increased permeability of blood vessels to plasma proteins. Here, we summarize the knowledge about the role of tau protein in BBB structural and functional changes. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) is associated with neuropathological changes, including aggregation of tau neurofibrillary tangles (NFTs) and amyloid-beta plaques. Mounting evidence indicates that vascular dysfunction also plays a key role in the pathogenesis and progression of AD, in part through endothelial dysfunction. Based on findings in animal models that tau pathology induces vascular abnormalities and cellular senescence, we hypothesized that tau pathology in the human AD brain leads to vascular senescence. To explore this hypothesis, we isolated intact microvessels from the dorsolateral prefrontal cortex (PFC, BA9) from 16 subjects with advanced Braak stages (Braak V/VI, B3) and 12 control subjects (Braak 0/I/II, B1), and quantified expression of 42 genes associated with senescence, cell adhesion, and various endothelial cell functions. Genes associated with endothelial senescence and leukocyte adhesion, including SERPINE1 (PAI-1), CXCL8 (IL8), CXCL1, CXCL2, ICAM-2, and TIE1, were significantly upregulated in B3 microvessels after adjusting for sex and cerebrovascular pathology. In particular, the senescence-associated secretory phenotype genes SERPINE1 and CXCL8 were upregulated by more than 2-fold in B3 microvessels after adjusting for sex, cerebrovascular pathology, and age at death. Protein quantification data from longitudinal plasma samples for a subset of 13 (n = 9 B3, n = 4 B1) subjects showed no significant differences in plasma senescence or adhesion-associated protein levels, suggesting that these changes were not associated with systemic vascular alterations. Future investigations of senescence biomarkers in both the peripheral and cortical vasculature could further elucidate links between tau pathology and vascular changes in human AD. [ABSTRACT FROM AUTHOR]

The Americas were the last continental areas to be inhabited by modern human beings. The Jesuit Father de Acosta had already proposed in 1590 that the first peopling might have involved the use of watercraft through the north Pacific. Still today researchers are debating whether the first inhabitants of the continent arrived from the northwest or the northeast and when this occurred. What may help solve these questions is the great amount of indirect evidence suggesting the first settlers had already developed a maritime culture and very likely a seafaring technology. Implications of considering this statement as valid are that it can shed new light on old problems related to the high mobility of groups, the use of maritime and riverine resources, the location of the first settlement camps near the coast, the transportation of raw materials from very long distances, and different aspects of social organization related to technological development. Bearing these ideas in mind, watercourses should not be considered as obstacles, but on the contrary, as elements of connection. [ABSTRACT FROM AUTHOR]

Background: Scleroderma is a heterogeneous group of diseases that can be localized or systemic. Localized scleroderma is a fibrosis of the skin characterized by inflammation and thickening due to excessive collagen deposition, and systemic sclerosis (SSc) is characterized by vasculopathy, immune dysregulation and skin fibrosis. In general, the prognosis of scleroderma highly depends on the degree of visceral involvement and relates to the degree of skin fibrosis. Despite the numerous therapies used for patients with scleroderma, the disease-related morbidity and mortality are high. Studies have explored the effects of extracorporeal photopheresis (ECP) in scleroderma treatment. Originally used in the treatment of cutaneous T-cell lymphoma, ECP is an immunomodulatory procedure in which a patient's white blood cells are treated with 8-methoxypsoralen and exposed to UVA radiation to inhibit cell proliferation and induce immunosuppression.Summary: Multiple lines of evidence suggest that ECP may be a safe and possibly effective therapy for patients with scleroderma, specifically demonstrating improvement in patients with cutaneous manifestations of the disease. However, future studies assessing its role in managing visceral involvement are needed. Our review aims to examine and consolidate the results of clinical studies and propose a possible role for ECP in the management of scleroderma.Key Points: ECP may be an effective and safe procedure for the treatment of SSc. [ABSTRACT FROM AUTHOR]

Mixed connective tissue disease (MCTD) was initially described as a chronic immune-mediated disease with overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis. We conducted a cross-sectional study to describe the clinical and immunological profile of patients with MCTD and to compare the four diagnostic criteria, namely, Sharp, Kasukawa, Alarcón-Segovia, and Khan criteria. A total of 291 patients who were admitted from June 2007 to June 2017 and fulfilled the inclusion criteria were included in the study. A clinical diagnosis of MCTD was made in 111 patients, of whom 103 (92.8%) were women. The mean age at presentation was 39.3 years (SD ± 11.6). The most common organ systems that were involved were musculoskeletal system (95.5%), skin and mucosa (78.4%), and the gastrointestinal and hepatobiliary systems (56%). The maximum sensitivity was for the Kasukawa criteria with a sensitivity of 77.5% (95% CI 68.4-84.6) and specificity of 92.2% (95% CI 87-95.5). The Kahn criteria and Alarcón-Segovia criteria had the maximum specificity; the Alarcón-Segovia criteria had a sensitivity of 69.4% (95% CI 59.8-77.6) and a specificity of 99.4% (95% CI 96.5-99.9), while the Kahn criteria had a sensitivity of 52.3% (95% CI 42.6-61.7) and a specificity of 99.4% (95% CI 96.5-99.9). The sensitivity and specificity of Sharp criteria were 57.7% (95% CI 47.9-66.87) and 90% (95% CI 84.4-93.8), respectively. [ABSTRACT FROM AUTHOR]

Chalcogenide glasses have attracted considerable attention and found various applications due to their infrared transparency and other optical properties. The As–S–Se chalcogenide glass, with its large glass-formation domain and favorable nonlinear property, is a promising candidate system for tailoring important optical properties through modification of glass composition. In this context, a systematic study on ternary As–S–Se glass, chalcogen-rich versus well-studied stochiometric compositions, has been carried out using three different techniques: Raman spectroscopy, x-ray photoelectron spectroscopy, and extended x-ray absorption fine structure spectroscopy. These complementary techniques lead to a consistent understanding of the role of S/Se ratio in chalcogen-rich As–S–Se glasses, as compared to stochiometric composition, and to provide insight into the structural units (such as the mixed pyramidal units) and evidence for the existence of homopolar bonds (such as Se–Se, S–S, and Se–S), which are the possible structural origin of the high nonlinearity in these glasses. [ABSTRACT FROM AUTHOR]

With the goal of preventing unintentional fire-arm death and injury as well as widening the scope of police use of force training design, this study compared the impact of non-lethal training (NLT) ammunition and conventional ammunition (CA) on police officers' psychophysiological arousal. We assessed heart rate and parasympathetic activity while police officers engaged in a demanding fighting and shooting exercise. Based on previous research, which shows that physiological arousal in representative scenario exercises does not differ from active duty operations, this study tested and corroborated the hypothesis that simulated psychophysiological demand will be the same in using both NLT and CA. Thus, the use of NLT ammunition provides a safe alternative to training the use of issue weapons with CA, equally as representative of the active duty environment of the real world. Furthermore, this study underlines that fighting elicits high levels of physiological load that police officers need to be prepared for. [ABSTRACT FROM AUTHOR]

Investigations of police performance during acutely stressful situations have primarily focused on higher-order cognitive processes like attention, affect or emotion and decision-making, and the behavioral outcomes of these processes, such as errors in lethal force. However, behavioral outcomes in policing must be understood as a combination of both higher-order processes and the physical execution of motor skills. What is missing from extant police literature is an understanding of how physiological responses to acute stress contribute to observed decrements in skilled motor performance at the neuromuscular level. The purpose of the current paper is to fill this knowledge gap in the following ways: (1) review scientific evidence for the physiological (i.e., autonomic, endocrine, and musculoskeletal) responses to acutely stressful exposures and their influence on skilled motor performance in both human and animal models, (2) review applied evidence on occupationally relevant stress physiology and observed motor decrements in performance among police, and (3) discuss the implications of stress physiology for police training and identify future directions for applied researchers. Evidence is compelling that skill decay is inevitable under high levels of acute stress; however, robust evidence-informed training practices can help mitigate this decay and contribute to officer safety. [ABSTRACT FROM AUTHOR]

Policing is a highly stressful and dangerous profession that involves a complex set of environmental, psychosocial, and health risks. The current study examined autonomic stress responses experienced by 64 police officers, during general duty calls for service (CFS) and interactions with the public. Advancing previous research, this study utilized GPS and detailed operational police records as objective evidence of specific activities throughout a CFS. These data were then used to map officers' heart rate to both the phase of a call (e.g., dispatch, enroute) and incident factors (e.g., call priority, use-of-force). Furthermore, physical movement (i.e., location and inertia) was tracked and assisted in differentiating whether cardiovascular reactivity was due to physical or psychological stress. Officer characteristics, including years of service and training profiles, were examined to conduct a preliminary exploration of whether experience and relevant operational skills training impacted cardiovascular reactivity. Study results provide foundational evidence that CFS factors, specifically the phase of the call (i.e., arrival on scene, encountering a subject) and incident factors (i.e., call priority, weapons, arrest, use-of-force), influence physiological stress responses, which may be associated with short-term performance impairments and long-term health outcomes. Implications of research findings for operational policing, police training, and health research are discussed. [ABSTRACT FROM AUTHOR]

One of the challenges of modern engineering design is the amount of data that designers must keep track while performing system analysis and synthesis. This task is particularly important in the design process of complex systems such as novel aerospace systems where Modeling and Simulation play an essential role. The Agile philosophy stems from the field of Software Engineering and describes an approach to development in which requirements and solutions gradually develop through collaboration between self-organising cross-functional teams and end users. Agile Model-Based System Engineering (AMBSE) is the application of the Agile philosophy to Model-Based System Engineering. In this paper, AMBSE is accomplished through the application of the Object-Oriented System Engineering Method (OOSEM). OOSEM employs a top-down scenario-driven process that adopts System Modeling Language (SysML) and leverages the object-oriented paradigm to support the analysis, specification, design, and verification of systems. AMBSE assisted by mathematical modelling and safety assessment techniques is applied to the first design iterations of the main aircraft systems, allowing a comprehensive design exploration. The flight control system was chosen to illustrate the procedure in detail, emphasising the synthesis of a six-degrees-of-freedom model augmented by dynamic inversion control for a hypothetical supersonic transport aircraft satisfying class II MIL-F-8785C handling qualities. It is concluded that AMBSE presents promising properties to support future aircraft development within the current regulatory framework for aircraft design, while enabling a smooth transition from conceptual to preliminary design. [ABSTRACT FROM AUTHOR]

This paper introduces the software TiGL: TiGL is an open source geometry modeler that is used in the conceptual and preliminary aircraft and helicopter design phase. It creates full three-dimensional models of aircraft from their parametric CPACS description. Due to its parametric nature, it is typically used for aircraft design analysis and optimization. First, we present the use-case and architecture of TiGL. Then, we discuss its geometry module, which is used to generate the B-spline based surfaces of the aircraft. The backbone of TiGL is its surface generator for curve network interpolation, based on Gordon surfaces. One major part of this paper explains the mathematical foundation of Gordon surfaces on B-splines and how we achieve the required curve network compatibility. Finally, TiGL's aircraft component module is introduced, which is used to create the external and internal parts of aircraft, such as wings, flaps, fuselages, engines or structural elements. [ABSTRACT FROM AUTHOR]

The measurement of the left ventricular intervals isovolumic contraction time (IVCT), ejection time (ET), and isovolumic relaxation time (IVRT) with myocardial performance index (MPI) calculation is a method of left ventricular function assessment. The purpose of the study is to compare the results for left ventricular intervals (IVCT, ET, and IVRT) measured using three echocardiographic methods used so far (pulsed Doppler, pulsed tissue Doppler, and M-mode color tissue Doppler through the mitral valve) and evaluation of a new method of measurement, i.e. M-mode color tissue Doppler through the aortic valve. One hundred and five (105) subjects were studied, including 45 patients with arterial hypertension, 30 patients with CHD and 30 healthy subjects. Isovolumic contraction time, ejection time, and isovolumic relaxation time were measured/calculated in the three groups using these four methods. The differences in the results between patient groups using the same method, as well as the differences between data by different methods have been reported. In many comparisons, the results for IVCT and IVRT in the different groups showed a significant difference. In many cases, results obtained using different methods in specific patient groups also showed a significant difference. The ejection time shows the least differences between the methods. The measurement of left ventricular intervals using M-mode color tissue Doppler through the aortic valve is applicable in clinical practice. [ABSTRACT FROM AUTHOR]

The practices surrounding police training of complex motor skills, including the use of force, varies greatly around the world, and even over the course of an officer's career. As the nature of policing changes with society and the advancement of science and technology, so should the training practices that officers undertake at both central (i.e., police academy basic recruit training) and local (i.e., individual agency or precinct) levels. The following review is intended to bridge the gap between scientific knowledge and applied practice to inform best practices for training complex motor skills that are unique and critical to law enforcement, including the use of lethal force. We begin by providing a basic understanding of the fundamental cognitive processes underlying motor learning, from novel skill acquisition to complex behaviors including situational awareness, and decision-making that precede and inform action. Motor learning, memory, and perception are then discussed within the context of occupationally relevant stress, with a review of evidence-based training practices that promote officer performance and physiological responses to stress during high-stakes encounters. A lack of applied research identifying the neurophysiological mechanisms underlying motor learning in police is inferred from a review of evidence from various clinical populations suffering from disorders of cognitive and motor systems, including Alzheimer's and Parkinson's disease and stroke. We conclude this review by identifying practical, organizational, and systemic challenges to implementing evidence-based practices in policing and provide recommendations for best practices that will promote training effectiveness and occupational safety of end-users (i.e., police trainers and officers). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our work was to study late cardiac complications after treatment for Hodgkin's lymphoma (HL) in children and adolescents. Methods: Sixty-seven patients were examined in the long term (>5 years) after chemoradiotherapy for HL according to two different programs of treatment (groups I and II). Mean total doses of radiotherapy (RT) to the mediastinum were 37.2 and 28.9 Gy, respectively. The status of the heart was assessed at the mean age of 22.7 years with electrocardiography (ECG) and echocardiography (EchoCG). Mean terms of follow-up were 16.4 and 9.5 years for group I and group II, respectively. Results: Incidence of ECG changes was equal between the groups (88% and 90%). The prevalence of signs of valvular calcifications and fibrosis was 70.9% after mediastinal doses ≥30 Gy, and 16.6% after lower doses (p = 0.002). Those changes led to considerable valvular dysfunction in four patients. EchoCG signs of pulmonary hypertension were seen in 33.3% patients of group I versus 4.8% in group II (p = 0.047). Pericardial effusion was observed in 7.4% and 5.1%, respectively (p = 1.0). Left ventricular ejection fraction decreased slightly only in two patients (one in each group). Conclusions: The RT mediastinal dose level is the important risk factor of late heart complications. Nevertheless, the differences in the rate and severity of those complications between the groups should be viewed with caution because of differences in the age at baseline and in follow-up terms. The survivors of HL should undergo life-long regular examinations of the heart status. [ABSTRACT FROM AUTHOR]

Objective: To assess cardiac function in patients with juvenile mixed connective tissue disease (JMCTD) compared to matched controls, and to investigate possible associations between cardiac impairment and disease variables and cardiovascular risk factors.Methods: Fifty JMCTD patients (86% female) examined median 14.9 (6.6-23.0) years after disease onset were compared with 50 age- and sex-matched controls. Electrocardiogram and echocardiography [including e' as a marker for diastolic dysfunction and long-axis strain (LAS) and left ventricular (LV) ejection fraction (EF) as markers of systolic function] were performed. LV dysfunction (LVD) was defined as low EF, low LAS, or low e'. Right ventricular function was assessed with tricuspid annular plane systolic excursion (TAPSE). Cardiovascular risk factors and disease variables were assessed.Results: LVD was found in 16% of patients and 4% of controls (p = 0.035). EF and LAS were lower in patients compared to controls (6% lower, p < 0.001, and 4% lower, p = 0.044, respectively). TAPSE was 8% lower in patients versus controls (p = 0.008). No patients had signs of pulmonary hypertension. Patients had longer corrected QT time than controls (p = 0.012). LVD was associated with higher levels of apolipoprotein B, higher disease activity measured by physician's global assessment, longer prednisolone treatment, and more organ damage assessed with the Myositis Damage Index.Conclusion: Patients with JMCTD had impaired left and right ventricular function compared to matched controls after median 15 years disease duration. High disease activity and longer treatment with prednisolone were factors associated with LVD. [ABSTRACT FROM AUTHOR]

Stress has a pervasive, global, and negative influence on individual health. Stress also has negative effects on families, organizations, and communities. Current models of stress are either too general or too detailed to guide effective interventions across the spectrum of medical and social conditions that are stress-related. A new model is needed that explains how stress can have such varied effects and describes how to reduce its harm. The model must also capture both the dynamic nature of stress and its ability to persist and cause chronic effects. The model must guide those who use it in selecting effective interventions and in developing more effective interventions. Ideally, the model will be helpful to people who are experiencing stress and do not have access to professional help. The authors propose a model in an attempt to address the above concerns. The proposed model is called the Unease Modulation Model (UM Model). Briefly, the UM Model separates stress into several elements common to people's experience. The model describes how these elements interact and how those interactions lead to recurring states that are associated with health or illness. Finally, the model enables the person under stress to identify the elements where they will have the most leverage to evoke change and apply specific, effective techniques for that purpose. While the model is experiential, it is also based on mathematical theories of perception, nonlinear dynamics, neurophysiology, and cognitive psychology. In spite of this underlying sophistication, it can be used by those without a medical education. The proposed model has been taught successfully to patients in a clinical setting. The model is now being used in an international training program with police officers to address the long-term stress associated with the career and reduce decision-making errors regarding use of force. This article introduces the model by defining components based on patient descriptions of stress and integrating those into a formal structure. We then demonstrate how the model can be applied to a number of medical and psychiatric conditions. The article concludes by briefly discussing the model's application to family and societal stress-related difficulties. [ABSTRACT FROM AUTHOR]

Summary: In order to explore the discharge characteristics of aluminum‐air battery and find out the best discharge performance of aluminum‐air battery under the optimum working conditions, this paper studies discharge performances of an aluminum‐air battery under various ambient temperature and battery discharge conditions. The relationship between the temperature rise of the battery electrolyte and the discharge current density was studied by an experimental method. Effects of the electrolyte concentration and the ambient temperature on the battery discharge voltage were investigated. In addition, a novel method for calculating the efficiency of the aluminum‐air battery was proposed. Results show that the temperature of the aluminum‐air battery electrolyte gradually increases as its discharge current density increases and the electrolyte temperature rise could reach as high as 10°C after 60 minutes with a constant 35 mA cm−2 discharge current density. The specific energy and the specific capacity of the aluminum‐air battery first increase and then decrease as the current density increases. When the current density is 25 mA cm−2, the specific energy has a peak of 3105 Wh kg−1 for the condition of the chamber temperature 40°C and the electrolyte concentration 2 mol L−1 (2 M), while the specific capacity has a peak of 2207 Ah kg−1; furthermore, its efficiencies under various conditions increase first with the current density, reach a peak range of 19.6% to approximately 36% at 25 mA cm−2, and then decrease. These experimental results could be used as a technical guidance for the optimization in thermal management designs of the aluminum‐air battery under various operating conditions. Because of the high specific energy, clean, and pollution‐free, the characteristics of aluminum air batteries have received extensive attention. In the article, the relationship between the electrolyte temperature rise and the discharge current density for an aluminum‐air battery is the first available study, and a novel method is proposed to calculate the efficiency of an aluminum‐air battery, at the same time, the effects of ambient temperature on discharge voltage, specific energy, and specific capacity are fully considered. [ABSTRACT FROM AUTHOR]

Summary: Due to lack of systematic research on open‐circuit voltage (OCV) and electrolyte temperature rise characteristics of aluminum air battery, in order to explore the influential factors on the OCV and electrolyte temperature rise of aluminum air battery, in this paper, for the first time, we studied the effects of different ambient temperature conditions, different concentrations of NaOH and KOH electrolyte, and pure aluminum and aluminum alloy on the OCV and electrolyte temperature rise of aluminum air battery. Results show that the OCV of aluminum air battery is obviously affected by ambient temperature conditions, electrolyte concentration, and different anode materials. The OCV range is 1.5 to 1.8 V at 0°C under different KOH‐electrolyte concentrations when aluminum alloy is used as anode material; with the increase of ambient temperature, the OCV will rise, and the range is 1.8 to 1.95 V. The working process of aluminum air battery is accompanied by the phenomenon of heat release, and the temperature rise range of electrolyte will not exceed 7°C when aluminum alloy is used as the anode material; however, the highest temperature of the electrolyte can reach 100°C when pure aluminum is used as the negative electrode material. The results of this study will provide theoretical guidance for designing aluminum air batteries and identifying their optimal operating conditions. The open‐circuit voltage (OCV) and the electrolyte temperature rise are important parameters of aluminium‐air battery. The influence of ambient temperature on OCV and other parameters of aluminium‐air battery is obvious. In the experimental setup, the thermostatic chamber can be used to provide the specified temperature environment of aluminium‐air battery. The OCV and electrolyte temperature rise signals of aluminium‐air battery can be recorded by data acquisition system. The hydrogen generated in the experiment can be collected by using a gas collector. Highlights: This is the first systematic study of the effects of various factors on the open‐circuit voltage (OCV) of aluminum air battery.There is rare literature on the temperature rise characteristics of electrolytes for aluminum air batteries.The OCV range is 1.5 to 1.8 V at 0°C, but with the increase of ambient temperature, the OCV will rise, and the range is 1.8 to 1.95 V.The highest temperature of the electrolyte can reach 100°C when pure aluminum is used as the negative electrode material.With the increase of ambient temperature, KOH has higher OCV than NaOH. [ABSTRACT FROM AUTHOR]

Examines the effects of positive nitrogen implantation in amorphous silicon carbide films deposited on silicon substrates by relative frequency sputtering. Use of x-ray photoelectron spectroscopy and Auger electron spectroscopy; Correlation between the formation of silicon carbonitrides and the dynamical behavior of the carbon in the implanted layer; Details of the ion-induced modifications of the films.

Presents information on a study that examined electron spectroscopy for chemical analysis (ESCA) measurement results on thin SiO[sub2]/Si samples. Summary of conventional ESCA measurements; Problems associated with ESCA measurements; Conclusions.

Presents a surface analysis of bismuth-based cuprates superconductors through secondary ion mass spectrometry and X-ray photoelectron spectroscopy. Properties of cuprates superconductors; Discussion on kinetic energy distributions for secondary negative ions; Explanation for the emission of small clusters in bismuth-based cuprates.

Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc) associated with high morbidity and mortality. There are several biomarkers of SSc-PAH, reflecting endothelial physiology, inflammation, immune activation, extracellular matrix, metabolic changes, or cardiac involvement. Biomarkers associated with diagnosis, disease severity and progression have been identified, however, very few have been tested in a prospective setting. Some antinuclear antibodies such as nucleosome antibodies (NUC), anti-centromere antibodies (CENP-A/B) and anti-U3-ribonucleoprotein (anti-U3-RNP) are associated with PAH while anti-U1-ribonucleoprotein (anti-U1-RNP) is associated with a reduced PAH risk. Anti-endothelin receptor and angiotensin-1 receptor antibodies might be good markers of SSc-PAH and progression of pulmonary vasculopathy. Regarding the markers reflecting immune activation and inflammation, there are many inconsistent results. CXCL-4 was associated with SSc progression including PAH and lung fibrosis. Growth differentiation factor (GDF)-15 was associated with PAH and mortality but is not specific for SSc. Among the metabolites, kynurenine was identified as diagnostic marker for PAH, however, its pathologic role in the disease is unclear. Endostatin, an angiostatic factor, was associated with heart failure and poor prognosis. Established heart related markers, such as N-terminal fragment of A-type natriuretic peptide/brain natriuretic peptide (NT-proANP, NT-proBNP) or troponin I/T are elevated in SSc-PAH but are not specific for the right ventricle and may be increased to the same extent in left heart disease. Taken together, there is no universal specific biomarker for SSc-PAH, however, there is a pattern of markers that is strongly associated with a risk of vascular complications in SSc patients. Further comprehensive, multicenter and prospective studies are warranted to develop reliable algorithms for detection and prognosis of SSc-PAH. [ABSTRACT FROM AUTHOR]

Measurements on biological samples are often hampered by auto-fluorescence from inherent compounds in tissue or cells, limiting the achievable contrast. Both the signal of interest and the auto-fluorescence are usually detected on the Stokes side of the excitation laser. In this communication, we present two new microscopy modalities, based on the emission of a red-emitting DNA-stabilized silver nanocluster (DNA-AgNC). Its bright fluorescence can be generated on the anti-Stokes side of the readout laser, allowing easy spectral separation of the signal of interest from the Stokes side auto-fluorescence. [ABSTRACT FROM AUTHOR]

Raman spectroscopy has been playing an increasingly significant role for cell classification. Here, we introduce a novel microfluidic chip for non-invasive Raman cell natural fingerprint collection. Traditional Raman spectroscopy measurement of the cells grown in a Polydimethylsiloxane (PDMS) based microfluidic device suffers from the background noise from the substrate materials of PDMS when intended to apply as an in vitro cell assay. To overcome this disadvantage, the current device is designed with a middle layer of PDMS layer sandwiched by two MgF2 slides which minimize the PDMS background signal in Raman measurement. Three cancer cell lines, including a human lung cancer cell A549, and human breast cancer cell lines MDA-MB-231 and MDA-MB-231/BRMS1, were cultured in this microdevice separately for a period of three days to evaluate the biocompatibility of the microfluidic system. In addition, atomic force microscopy (AFM) was used to measure the Young's modulus and adhesion force of cancer cells at single cell level. The AFM results indicated that our microchannel environment did not seem to alter the cell biomechanical properties. The biochemical responses of cancer cells exposed to anti-cancer drug doxorubicin (DOX) up to 24 h were assessed by Raman spectroscopy. Principal component analysis over the Raman spectra indicated that cancer cells untreated and treated with DOX can be distinguished. This PDMS microfluidic device offers a non-invasive and reusable tool for in vitro Raman measurement of living cells, and can be potentially applied for anti-cancer drug screening. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells originally described to hamper immune responses in chronic infections. Meanwhile, they are known to be a major obstacle in cancer immunotherapy. On the other hand, MDSC can interfere with allogeneic transplant rejection and may dampen autoreactive T cell activity. Whether MDSC-Exosomes (Exo) can cope with the dangerous and potentially therapeutic activities of MDSC is not yet fully explored. After introducing MDSC and Exo, it will be discussed, whether a blockade of MDSC-Exo could foster the efficacy of immunotherapy in cancer and mitigate tumor progression supporting activities of MDSC. It also will be outlined, whether application of native or tailored MDSC-Exo might prohibit autoimmune disease progression. These considerations are based on the steadily increasing knowledge on Exo composition, their capacity to distribute throughout the organism combined with selectivity of targeting, and the ease to tailor Exo and includes open questions that answers will facilitate optimizing protocols for a MDSC-Exo blockade in cancer as well as for strengthening their therapeutic efficacy in autoimmune disease. [ABSTRACT FROM AUTHOR]

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent liver disorder worldwide, involving pathogenic mechanisms of liver sinusoidal endothelial cells (LSECs), hepatocytes and other liver cells. Here, we used a novel approach of label-free Raman confocal imaging to study primary LSECs and hepatocytes freshly isolated from the livers of mice with NAFLD induced by a high fat diet (HFD), in comparison to healthy controls. Our aim was to characterize changes in the biochemical composition in LSECs and hepatocytes that occur in a single cell at the subcellular level. LSECs from NAFLD livers displayed a significant increase in the intensity of marker bands of nuclear DNA that was not associated with changes in LSEC nucleus size. A number of changes in the cytoplasm of hepatocytes were identified. However, the most prominent change in hepatocytes was a substantial increase in the degree of unsaturation of LBs’ (lipid bodies) lipids in NAFLD, suggesting an increase in the de novo lipogenesis of unsaturated lipids. The confocal Raman imaging of single live cells isolated from the liver provided a unique tool to better understand disease-induced cell-specific changes in the biochemical phenotype of primary liver cells. [ABSTRACT FROM AUTHOR]

Copyright of Czech Rheumatology / Česká Revmatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Psoriasis is a common and chronic inflammatory disease of the skin. It may impair the physical and psychosocial function of patients and lead to decreased quality of life. Traditionally, psoriasis has been regarded as a disease affecting only the skin and joints. More recently, studies have shown that psoriasis is a systemic inflammatory disorder which can be associated with various comorbidities. In particular, psoriasis is associated with an increased risk of developing severe vascular events such as myocardial infarction and stroke. In addition, the prevalence rates of cardiovascular risk factors are increased, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome. Consequently, mortality rates have been found to be increased and life expectancy decreased in patients with psoriasis, as compared to the general population. Various studies have also shown that systemic treatments for psoriasis, including methotrexate and tumor necrosis factor-α inhibitors, may significantly decrease cardiovascular risk. Mechanistically, the presence of common inflammatory pathways, secretion of adipokines, insulin resistance, angiogenesis, oxidative stress, microparticles, and hypercoagulability may explain the association between psoriasis and cardiometabolic disorders. In this article, we review the evidence regarding the association between psoriasis and cardiovascular comorbidities, focusing on severe vascular events, cardiovascular risk factors and implications for treatment. [ABSTRACT FROM AUTHOR]

There are various fabrication methods for synthesizing nanostructures, among which plasma-based technology is strongly competitive in terms of its flexibility and friendly uses, economy, and safety. This review systematically discusses plasma techniques and the detailed interactions of charged particles, radicals, and electrons with substrate materials of, in particular, polymers for their nanostructuring. Applications employing a plasma-based nanostructuring process are explored to show the advantages and benefits that plasma treatment brings to many topical and traditional issues, and are specifically related to wettability, healthcare, or energy researches. A short perspective is also presented on strategic plans for overcoming the limitations in dimension from surface to bulk, lifetime of surface functions, and selectivity for interactions. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Raman spectroscopy is an emerging technique in bioanalysis and imaging of biomaterials owing to its unique capability of generating spectroscopic fingerprints. Imaging cells and tissues by Raman microspectroscopy represents a nondestructive and label-free approach. All components of cells or tissues contribute to the Raman signals, giving rise to complex spectral signatures. Resonance Raman scattering and surface-enhanced Raman scattering can be used to enhance the signals and reduce the spectral complexity. Raman-active labels can be introduced to increase specificity and multimodality. In addition, nonlinear coherent Raman scattering methods offer higher sensitivities, which enable the rapid imaging of larger sampling areas. Finally, fiber-based imaging techniques pave the way towards in vivo applications of Raman spectroscopy. This Review summarizes the basic principles behind medical Raman imaging and its progress since 2012. [ABSTRACT FROM AUTHOR]