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Twenty years of the International Society for Pediatric and Adolescent Diabetes Science Schools programs: Assessment of their impact on the participants' personal careers and networking development. The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success. All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities. One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004-2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014-2019), participants indicated that the program was valuable/useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards. From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities.

The use of infrared thermography to noninvasively measure the surface temperature of polar bears during bouts of social play. Infrared thermography or thermal imagery is a noninvasive tool that can be used to measure the temperature of surfaces. Typically, thermal imagery is used for construction or military purposes but is increasingly used as a noninvasive tool in wildlife studies. We investigated the use of thermal imagery to measure surface temperature changes as a proxy for energetic expenditure. We measured the surface temperature of polar bear (Ursus maritimus) eyes, while immobilized, to determine whether the eye is a thermal window that can accurately indicate internal temperature. We found a significant difference (2.68 ± 0.41°C) between the surface temperature of the eye measured with thermal imagery and the internal rectal temperature. Additionally, we measured surface temperature changes in polar bears after bouts of social play as a proxy for energy expenditure. Mean temperature of the eye increased by 1.34 ± 0.43°C after social play, indicating that this activity increased energy expenditure. During the fasting season, polar bears rely on fat stores, and any energy expenditure beyond what is required to travel may be costly to their survival, particularly in years of low resource availability. We conclude that thermal imagery is a useful tool to noninvasively investigate the energetics of social play.

Effect of timber removal on the total nutrient fluxes from a freshwater-supplying forested watershed. Effects of 18% thinning on nutrient fluxes were investigated in a broadleaf forest. Streamflow and suspended sediment were sampled during the calibration and treatment periods for the treatment and control watersheds to determine total nutrient fluxes through bedload sediment and runoff. Streamflow was measured, and water samples were collected from the streams of the watersheds. The volume of the bedload deposited in both weirs' pools was measured, and sediment deposits were sampled at the ends of the calibration and treatment periods. Water and sediment samples were analyzed for calcium (Ca2+ ), magnesium (Mg2+ ), Kjeldahl nitrogen (KN), sodium (Na+ ), potassium (K+ ), iron (Fe3+ ), and sulfur (S2- ). Results showed that there was only a significant increase in KN loss from 0.01 kg/ha to 0.10 kg/ha and from 0.04 kg/ha to 2.41 kg/ha in the second and the third post-treatment years, respectively (P < 0.05). Thinning was not intensive to change nutrient outflow in the study site. PRACTITIONER POINTS: The 18% thinning was not intensive enough to increase the total nutrient flux, deteriorate water chemical quality, and hence threaten aquatic life in the stream water. Significant increases were found only in KN outflow after timber removal. If there is no information about the effect of timber harvest on nutrient loss in a specific watershed, the application of evenly distributed low-intensity timber harvest may be a good option to protect stream water quality in forested watersheds. Further investigations are needed about the effects of various timber harvest intensities on physical water quality (odor, color, turbidity, taste, temperature, etc.) and biological characteristics (population and biodiversity of aquatic organisms) of the stream water for making better water management plans.

Empirical and Authoritative Classification of Neuropsychiatric Syndromes in Neurocognitive Disorders. Neuropsychiatric symptoms of neurocognitive disorders have been classified into higher-order constructs, often called neuropsychiatric syndromes. As with the general psychopathology literature, these classifications have been achieved through two approaches: empirical and authoritative. The authoritative approach relies on expert panels that condense the available evidence into operational criteria, whereas the empirical approach uses statistical methods to discover symptom patterns and possible hierarchies formed by them. In this article, the author reviews the strengths and weaknesses of both approaches using general psychopathology literature as a reference point. The authoritative approach, influenced by the DSM, has led to several sets of criteria, which could aid clinical trials, diagnostics, and communication. However, unknown reliability and the complex relationships between empirical evidence and published criteria may limit the utility of current criteria. The empirical approach has been used to explore syndrome structures on the basis of rating scales for neuropsychiatric symptoms. The structures suggested in these studies have not been replicated easily and have been limited by either small sample sizes, restricted breadth of neuropsychiatric assessment, or both. Suggestions for further development of both approaches are offered. First, neuropsychiatric symptoms and syndromes need to be studied with measures of broad scope and in large samples. These requirements are prerequisites not only for eliciting highly informative empirical classifications but also for understanding these symptoms at a more nuanced level. Second, both approaches could benefit from more transparency. Finally, the reliability of the available authoritative criteria should be examined.

rTMS/iTBS and Cognitive Rehabilitation for Deficits Associated With TBI and PTSD: A Theoretical Framework and Review. Rehabilitation of cognitive and psychosocial deficits resulting from traumatic brain injury (TBI) continues to be an area of concern in health care. Commonly co-occurring psychiatric disorders, such as major depressive disorder and posttraumatic stress disorder, create additional hurdles when attempting to remediate cognitive sequelae. There is increased need for procedures that will yield consistent gains indicative of recovery of function. Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation, has potential as an instrument that can be tailored to aid cognitive processes and support functional gains. The use of iTBS enables direct stimulation of desired neural systems. iTBS, performed in conjunction with behavioral interventions (e.g., cognitive rehabilitation, psychotherapy), may result in additive success in facilitating cognitive restoration and adaptation. The purpose of this theoretical review is to illustrate how the technical and physiological aspects of iTBS may enhance other forms of neurorehabilitation for individuals with TBI. Future research on combinatorial iTBS interventions has the potential to translate to other complex neuropsychiatric conditions.

Reasoning for whistleblowing in health care. Whistleblowing is recognised as part of solving wrongdoing. It requires individual reasoning as it is a potentially complicated process with a risk of possible negative consequences for oneself. Knowledge on how individuals reason for whistleblowing in healthcare context is lacking. This study aimed to create a theoretical construct to describe individual reasoning for whistleblowing. The methodology was grounded theory, with 244 nurses as informants. The data consisted of nurses' written narratives in response to a wrongdoing situation presented in a video vignette. To ensure the heterogeneity of the population and variation in nurses' professional expertise, experiences and geographical locations in health care to capture the multidimensionality of the responses, nurses were invited to participate, and data were collected electronically from the membership register of the Finnish Nurses' Association on a national level. Constant comparison was used to analyse the open data. The core category of the theoretical construct, 'The formation of morally courageous intervening', was discovered, reflecting individual's values and beliefs. It forms mentally as an integration of cognition and emotion for recognising one's own strengths and limits to act to do the right thing despite the risk of negative consequences for oneself. The core category consists of three dimensions of reasoning: (1) Reasoning Actors, (2) Reasoning Justifications and (3) Reasoning Activities, their categories and three patterns of reasoning connecting the dimensions and their categories with each other: (I) Individual Reasoning, (II) Collaborative Reasoning and (III) Collective Reasoning. The theoretical construct indicate that reasoning is a multidimensional phenomenon. In future, a theoretical construct could be further developed. In health care, managers could use the theoretical construct to support employees in their whistleblowing.

A Neuropsychiatric and Neuroimaging Study of Unilateral and Bilateral Striatal Ischemic Lesions. Neuropsychiatric disorders after striatal territory stroke have not been studied systematically. The investigators aimed to study the spectrum of cognitive and behavioral disorders following striatal infarcts. Different aspects of cognitive functions, including executive, frontal lobe, memory, visuospatial, language, and semantic processing, were assessed among patients with striatal infarct. Structural MRI data sets were obtained 3 months after stroke to delineate affected territories of the striatum. MRIcroGL software was used to acquire multiple layers of images, generate volume renderings, and draw volumes of interest. To determine the brain locus most frequently affected in patients with distinct cognitive disorders, ischemic area distributions in patients with cognitive dysfunction versus those without cognitive impairment were contrasted. Among 60 patients in this study, six different striatal infarction types were significantly associated with seven different cognitive categories (p<0.001). Unilateral caudate lesion was characterized by attention, planning, and executive disorders (38%), and unilateral lentiform infarct was characterized by executive (36%) and frontal (36%) dysfunctions. Bilateral caudate infarcts caused impairments in frontal and executive functions (75%), as well as in autobiographical (50%) and episodic (50%) memory. In those with bilateral caudate plus lentiform infarcts, all components of frontal and executive functions were dramatically impaired. The anteromedial striatum was affected more frequently in patients with language impairment compared with patients with other types of cognitive dysfunction (p<0.001). Following striatal stroke, a wide range of frontal-like cognitive impairments occurred, along with impaired working memory, declarative memory, executive function, speech fluency, and motor function.

White Matter Microstructure and Gray Matter Volume in Cannabis-Induced Psychosis and Schizophrenia With Cannabis Use. This study explored the differences in white matter (WM) microstructural integrity and gray matter (GM) volume between cannabis-induced psychosis (CIP) and schizophrenia with cannabis use (SZC). This cross-sectional study with convenience sampling involved three groups of 20 participants each (CIP, SZC, and a control group without substance use), matched on age, handedness, and education. CIP and SZC were diagnosed with the Psychiatric Research Interview for Substance and Mental Disorders. Diffusion tensor and kurtosis imaging were done, and fractional anisotropy (FA), mean diffusivity, and mean kurtosis were estimated. GM volume was measured with voxel-based morphometry. Group comparisons revealed comparable age at initiation and duration and frequency of cannabis use between participants in the SZC and CIP groups. Participants with SZC had lower FA than controls in the anterior and retrolenticular internal capsule limbs, cingulate gyrus hippocampal formation, fornix, and superior fronto-occipital fasciculus (all p<0.05). Participants with CIP had lower FA than controls in the left fornix and right superior fronto-occipital fasciculus but higher FA than those with SZC in the left corticospinal tract (all p<0.05). On morphometry, participants with CIP had greater cerebellar GM volume than those with SZC and greater inferior frontal gyrus volumes than controls (all p<0.05). Widespread WM microstructural abnormalities were observed in participants with SZC, and fewer but significant WM disruptions were observed in those with CIP. Better WM integrity in some WM fiber tracts and greater GM volumes in crucial brain areas among those with CIP may have prevented the transition to schizophrenia.

Long-term risk of cardiovascular disease mortality among classic Hodgkin lymphoma survivors. The temporal trend of cardiovascular disease (CVD) mortality in patients with classic Hodgkin lymphoma (cHL) throughout follow-up remains unclear. This study aimed to assess this temporal trend in patients with cHL. This multicenter cohort included 15,889 patients with cHL diagnosed between 1983 and 2015, covering all ages. The proportional mortality ratio, cumulative incidence of cause-specific mortality accounting for competing risk, standard mortality ratio, and absolute excess risk were analyzed. Among patients in stage I and stage II cHL, the proportional mortality ratio for CVD exceeded that for cHL, after approximately 60 or 120 months of follow-up, respectively. For almost all the patients with stage I or stage II disease, the cumulative incidence of CVD mortality exceeded that of cHL and other neoplasms over time. In recent decades, the risk of cHL mortality declined sharply, but the risk of CVD mortality among patients with cHL declined quite slowly or even remained unchanged among some populations. Patients with stage I or stage II disease experienced a higher risk of CVD mortality than the general population in almost all follow-up intervals. The absolute excess CVD risk among patients in stage I reached 48.5. The risk of CVD mortality exceeded that of cHL and other neoplasms and became the leading cause of death over time, among patients with stage I or stage II disease. More effective measures should be taken to reduce the risk of CVD mortality. Among patients with stage I and stage II classic Hodgkin lymphoma (cHL), the proportional mortality ratio of cardiovascular disease (CVD) exceeded that of cHL after approximately 60 or 120 months of follow-up, respectively. For almost all the patients with stage I or stage II disease, the cumulative incidence of CVD mortality exceeded that of cHL and other neoplasms over time. In the past several decades, the risk of cHL mortality declined sharply, but the risk of CVD mortality among patients with cHL declined quite slowly or even unchanged among some populations. CVD exceeded cHL and has become the leading cause of death over time.

Instruments used to measure dating violence: A systematic review of psychometric properties. To identify, synthesize and evaluate the psychometric properties of instruments that measure dating violence (DV). Psychometric systematic literature review. The databases SCOPUS, PubMed, CINAHL, PsychINFO, and Web of Science were searched up to December 2021. We evaluated the psychometric properties of the instruments included and their methodological quality using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and Terwee's quality criteria. The Modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to rate the best available evidence. The entire process was carried out by three independent reviewers. The review was registered at PROSPERO (registry number CRD42020161137). A total of 35 studies evaluated 29 instruments measuring DV. Most studies reported data on content validity, structural validity and internal consistency. No studies tested measurement error and responsiveness. Only one instruments tested cross-cultural validity. It is of interest that the data reported for content validity were the worst evaluated, despite the fact that content validity is one of the key properties in developing and validating the measuring instrument. There are a significant number of instruments published in this field, and it is important to evaluate and show their psychometric properties to help select evidence-based instruments. After carrying out the evaluation following the COSMIN guidelines, the authors of this study recommend that the three most suitable instruments are CADRI, WAS/Chinese version and PMWI-SF/Portuguese version (in that order). Identifying and evaluating DV is the first step in designing effective interventions. To achieve this, it is necessary to have validated instruments with suitable psychometric properties. To date, this is the only published systematic review evaluating the psychometric properties of instruments that measure DV which reports on their methodological qualities. The results we found show a growing trend in developing new instruments, with the most suitable approach being to make a cross-cultural adaptation and validation of the instrument that best suits the value to be measured. In this way, data can be compared between different countries and standardized health care plans and policies designed to achieve better health outcomes. This study may help future researchers to choose the most suitable instrument for their research.

Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients. Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.

Cu-Zn SOD suppresses epilepsy in pilocarpine-treated rats and alters SCN2A/Nrf2/HO-1 expression Copper-zinc superoxide dismutase (Cu-Zn SOD) is downregulated in epilepsy, however, the role of Cu-Zn SOD in epilepsy remains unclear. Based on the pilocarpine hydrochloride-induced rat model of epilepsy, cortical-striatum brain slices of rats were examined based on field excitatory post-synaptic potentials. Pathological changes were observed by transmission electron microscope. Also using SH-SY5Y cells, flow cytometry and TUNEL staining were applied to investigate cell apoptosis, and ELISA was applied to detect SOD activity. In addition, qRT-PCR and western blot were performed to detect SCN2A/Nrf2/HO-1 gene and protein expression levels, respectively. Cu-Zn SOD over-expression suppressed epilepsy in vivo. In addition, Cu-Zn SOD knockdown notably decreased SOD activity and induced apoptosis in SH-SY5Y cells. Moreover, Cu-Zn SOD silencing decreased the levels of SCN2A, Nrf2 and HO-1. Lastly, Cu-Zn SOD was shown to modulate the NaV1.2/Nrf2/HO-1 axis in rats. In this model, Cu-Zn SOD attenuated epilepsy and was shown to alter the expression level of proteins of the NaV1.2 /Nrf2/HO-1 signalling pathway, indicating that Cu-Zn SOD might be a target for the treatment of epilepsy.

Epileptiform abnormalities in the disconnected hemisphere are common in seizure-free patients after hemispherectomy The spectrum of EEG abnormalities in the disconnected hemisphere in seizure-free patients after hemispherectomy has not been well characterized. Fifty consecutive patients who were seizure-free following hemispheric disconnection were identified. Data on preoperative clinical, EEG and neuroimaging findings and postoperative EEG findings and antiseizure medication status were collected. Forty-seven patients (94%) had functional hemispherectomy, and three (6%) had more extensive tissue resection of the posterior quadrant or frontal region along with hemispheric disconnection. Etiologies included: residual effects from vascular lesions including perinatal stroke in 35 patients, Rasmussen encephalitis in six, malformation of cortical development in seven, and Sturge-Weber syndrome in two. Pre-operative EEG showed focal epileptiform discharges in the affected hemisphere in 26 patients and in both hemispheres in 19. Eleven patients had diffuse bisynchronous epileptiform discharges. Postoperative EEGs at six to 12 months after surgery showed slowing and attenuation of physiological rhythms on the operated side in all patients. Thirty-four patients (68%) had epileptiform discharges exclusively from the operated hemisphere, six (12%) had bilateral independent epileptiform discharges, nine (18%) had no epileptiform discharges on either side, and one (2%) had epileptiform discharges from the contralateral hemisphere only. Lateralized periodic discharges from the operated hemisphere were noted in three patients (6%). EEG seizures from the operated hemisphere without clinical signs were noted in four patients (8%). After a median follow-up of three years, 30 patients (60%) were off all antiseizure medications, including 8/9 (89%) patients with no epileptiform discharges, 20/34 (59%) patients with postoperative epileptiform discharges from the operated hemisphere, and 2/7 (28%) patients with contralateral discharges. The majority of patients who are seizure-free after disconnective hemispherectomy will continue to show epileptiform discharges in the operated hemisphere. The presence of such discharges should not preclude tapering, nor prompt restarting of antiseizure medication in seizure-free patients.

Microevolutionary variation in molar morphology of Onychomys leucogaster decoupled from genetic structure. In neutral models of quantitative trait evolution, both genetic and phenotypic divergence scale as random walks, producing a correlation between the two measures. However, complexity in the genotype-phenotype map may alter the correlation between genotypic and phenotypic divergence, even when both are evolving neutrally or nearly so. Understanding this correlation between phenotypic and genetic variation is critical for accurately interpreting the fossil record. This study compares the geographic structure and scaling of morphological variation of the shape of the first lower molar of 77 individuals of the northern grasshopper mouse Onychomys leucogaster to genome-wide SNP variation in the same sample. We found strong genetic structure but weak or absent morphological structure indicating that the scaling of each type of variation is decoupled from one another. Low PST values relative to FST values are consistent with a lack of morphological divergence in contrast to genetic divergence between groups. This lack of phenotypic structure and the presence of notable within-sample phenotypic variance are consistent with uniform selection or constraints on molar shape across a wide geographic and environmental range. Over time, this kind of decoupling may result in patterns of phenotypic stasis masking underlying genetic patterns.

Choice matters: Pupils' stress regulation, brain development and brain function in an outdoor education project. Education outside the classroom (EOtC) is considered beneficial to children's physical and mental health. Especially, stress resilience has been linked to nature experience. This study experimentally explored the effects of pupils' autonomy support (AUT) and physical activity (PA) on their biological stress responses and brain development in EOtC. The study comprised 48 fifth and sixth graders. The intervention consisted of one day/week taught in a forest over one school year. Structural magnetic resonance imaging (MRI) was conducted at the beginning and the end of the school year, functional MRI under a stress condition at the end. Regions of interest were amygdala, hippocampus and the anterior cingulate cortex (ACC). All other measures were obtained at the beginning, at mid-term and at the end of the school year. PA was measured using accelerometry. Cortisol levels were obtained three times during the examined school days. AUT was measured with a paper-based survey. Data were analysed using Bayesian multivariate models. EOtC students exhibit more efficient regulation of biological stress-reactivity and show a reduction of cortisol over the day associated with light PA in the forest. Cortisol is further associated with amygdala activation in the stress condition. Cerebral structural change is best explained by age; however, AUT has a positive direct effect on the maturation of the ACC, which is stronger in EOtC. Our results support the idea that autonomy supportive teaching fosters cerebral maturation and that EOtC can have a positive effect on biological stress regulation.

Predictors of post COVID complications in patients admitted with moderate to severe COVID symptoms: A single center, prospective, observational study. While the world was still busy battling active COVID-19 infections, a large subset of patients started showing prolonged symptoms or developing complications following an initial recovery from COVID-19. Post covid complications range from mild symptoms such as fatigue, headache, shortness of breath to serious, life threatening conditions like opportunistic infections, deep venous thrombosis, pulmonary embolism, pneumothorax and lung fibrosis. A single center, prospective, observational study was carried out in a tertiary respiratory care institute in North India from June 2021 to August 2021 where 224 cases of previously treated COVID-19/ongoing symptomatic COVID-19 (those patients who were manifesting symptoms beyond 4 weeks), were enrolled and followed up for a period of 3 months to estimate the prevalence of persistent symptoms, complications and any risk factors associated with it. Data analysis was done using SPSS software version 21. Univariate and multivariate analysis done among risk factors and outcome variables. ROC was done on predictor variables and area under curve (AUC) calculated. p value less than 0.05 was considered significant. Among the 24.6% symptomatic patients at follow up, the most common symptom was fatigue (51.8%) followed by dyspnea (43.8%) and anxiety (43.3%). Among the complications of COVID-19, the most common according to our study was fibrosis (15.2%), followed by pulmonary thromboembolism (PTE) (12.1%), echocardiographic abnormalities (11.2%) and pulmonary mucormycosis (5.4%). Female gender, presence of comorbidities, requirement of non-invasive or invasive ventilation during hospital stay emerged as independent risk factors for complications following COVID-19. This study brings forth the huge morbidity burden that COVID-19 brought upon seemingly cured individuals and lists the risk factors associated with persistence of symptoms and complications. This would help to better streamline health resources and standardize follow up guidance of COVID-19 patients.

Rapid progression of pulmonary artery dilatation in pulmonary hypertension. We report the case of a 47-year-old woman who was admitted to the cardiac department for worsening dyspnea. The last chest computed tomography (CT) showed a rapid increase in pulmonary artery dimension (65 mm in 2019, 76 mm in 2021). The symptoms reported by the patient were due to important extrinsic compression of the left main coronary artery (LMCA). In this case, it is very difficult to choose the best therapeutic strategy. In the end, we decided to treat the left main coronary for prevention. After 3 months no new clinical symptoms have developed.

Coeliac and cardiovascular disease: a possible relationship between two apparently separate conditions. Coeliac disease (CD) is an autoimmune condition with a high prevalence among general population and multisystemic involvement: a more complex scene than a merely gastrointestinal disease. Therefore, an early diagnosis and treatment with a gluten-free diet is mainly important to reduce mortality and comorbidities. Together with autoimmune diseases (as Hashimoto thyroiditis, insulin-dependent diabetes mellitus, autoimmune liver disease and connective tissue diseases), also an accelerated progression of atherosclerosis and a higher prevalence of heart disease have been reported in coeliacs. In the present paper we tried to collect from literature the emergent data on the probable relationship between coeliac and cardiovascular disease, focusing on pathophysiological bases of vascular injury. Data and opinions on the development of cardiovascular risk in patients with CD are conflicting. However, the major evidence supports the theory of an increased cardiovascular risk in CD, due to many mechanisms of myocardial injury, such as chronic malabsorption, abnormalities of intestinal permeability, and direct immune response against self-proteins. The conclusions that come from these data suggest the utility of a careful cardiovascular follow up in coeliac patients.

The emergent role of mitochondrial RNA modifications in metabolic alterations. Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases. In the light of current knowledge about the involvement, the association between mitochondrial RNA modifications and diseases arises from studies focusing on mutations in both mitochondrial and nuclear DNA genes encoding enzymes involved in such modifications. Here, we review the current evidence available for mitochondrial RNA modifications and their role in metabolic disorders, and we also explore the possibility of using them as promising targets for prevention and early detection. Finally, we discuss future directions of mitochondrial epitranscriptomics in these metabolic alterations, and how these RNA modifications may offer a new diagnostic and theragnostic avenue for preventive purposes. This article is categorized under: RNA Processing > RNA Editing and Modification.

Weak population differentiation and high diversity in Salsola tragus in the inland Pacific Northwest, USA. Salsola tragus is a widespread and problematic weed of semi-arid wheat production globally, and in the inland Pacific Northwest region of the USA. The species exhibits high levels of phenotypic diversity across its range and, at least in California USA, previous work has described cryptic diversity comprising a multi-species complex. Such cryptic diversity could suggest the potential for a differential response to management inputs between groups, and have important implications for the spread of herbicide resistance or other adaptive traits within populations. We used a genotyping-by-sequencing approach to characterize the population structure of S. tragus in the inland Pacific Northwest. Our results indicated that the population in this region is comprised of a single, tetraploid species (S. tragus sensu latu) with weak population structure on a regional scale. Isolation-by-distance appears to be the primary pattern of structure, but an independent set of weakly differentiated clusters of unknown origin were also apparent, along with a mixed mating system and high levels of largely unstructured genetic diversity. Despite considerable phenotypic variability within S. tragus in the region, agronomic weed managers can likely consider it as a single entity across the region, rather than a collection of cryptic subgroups with possible differential responses to management inputs or agroecosystem conditions. A lack of strong barriers to migration and gene flow mean that adaptive traits, such as herbicide resistance, can be expected to spread rapidly through populations across the region. © 2022 Society of Chemical Industry.

Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL-37, in a psoriasis mimicking microenvironment. Psoriasis is an autoimmune disease driven by a Th17 response linked to the antimicrobial peptide (AMP) LL-37 that has been connected to the induction and chronicity of psoriasis. We show that keratinocytes secrete various immune biomarkers with a direct link to psoriasis immunopathogenesis. Under pro-inflammatory microenvironmental conditions, LL-37 was found to regulate keratinocyte secretion of various immune biomarkers (eg C-X-C motif chemokine ligand (CXCL)8 and interleukin (IL)-1β) and alter extracellular signal-regulated kinase (ERK)1/2 signalling. However, during neutral conditions LL-37 induced a different pattern of keratinocyte immune biomarker secretion (eg vascular endothelial growth factor, CXCL8 and IL-6). Thus, an interesting pattern emerged regarding the immunomodulatory effects of LL-37 on keratinocytes; in general, expression of immune biomarkers that were upregulated in a Th1-like microenvironment was downregulated in the presence of LL-37. In contrast, LL-37 reinforced the Th17 response. In active psoriatic skin lesions, LL-37 expression was found to be significantly upregulated, which was also evident from the unique diffuse epidermic expression pattern not found in healthy skin. Finally, successful phototherapy of psoriasis patients converted this LL-37 inflammatory psoriatic skin pattern into a more localized basal layer expression as found in healthy controls. Thus, these findings demonstrate that LL-37 has a significant role in skin immune homeostasis and that its interplay with keratinocytes may have a more direct role in the immunopathogenesis of psoriasis than previously thought.

Effectiveness of telehealth-based exercise interventions on pain, physical function and quality of life in patients with knee osteoarthritis: A meta-analysis. The objective of the study was to evaluate the effectiveness of telehealth-based exercise intervention on pain, physical function and quality of life in patients with knee osteoarthritis. A systematic review and meta-analysis of randomised controlled trials (RCTs). Six databases (PubMed, Embase, Cochrane Library, CINAHL, PEDro and Web of Science Core Collection) were searched for relevant randomised controlled trials published from database inception to 3 June 2021. Reviewers independently screened the literature, extracted data and used the Cochrane Collaboration Risk of Bias Tool for quality assessment. A meta-analysis and subgroup analyses, stratified by control condition, intervention duration and delivery type, were conducted by Revman 5.4. The study was reported in compliance with PRISMA statement. A total of 9 independent RCTs with 861 participants were included. The meta-analysis showed that the telehealth-based exercise interventions significantly reduced pain in KOA patients (SMD = -0.28, 95% CI [-0.49, -0.08], p < .01) and produced similar effects to controls in terms of physical function and quality of life. Subgroup analysis revealed that telehealth-based exercise interventions were superior to the use of exercise booklet and usual care in terms of pain and physical function and were similar to face-to-face exercise treatment; a long-term (>3 months) intervention and the use of web and smartphone APPs to deliver exercise interventions were associated with better pain relief and physical function. Telehealth-based exercise intervention is an effective strategy for KOA management during the COVID-19 epidemic, and it is significantly better than usual care in reducing knee pain and improving physical function and was able to achieve the effects of traditional face-to-face exercise treatment. Although the duration and type of delivery associated with the effect of the intervention have been identified, patient preference and acceptability need to be considered in practice.

Synthesis and anticancer activity of novel Eugenol derivatives against breast cancer cells. Eugenol chemically known as 4-allyl-2-methoxyphenol is a major phenolic component of Syzigium aromaticum and associated with significant biological activities. In the present work, new eugenol 1,2,3-triazole derivatives have been synthesized, characterized using NMR, mass spectrometry, IR, and elemental analysis and screened for their anticancer activity against breast cancer cells. Compound 9, namely 3-(4-((4-allyl-2-methoxyphenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N'-(4-methylbenzoyl) benzohydrazide was found to be the most potent candidate and better than eugenol in exhibiting cytotoxicity with IC50 6.91 and 3.15 μM, comparable to Doxorubicin with IC50 6.58 and 3.21 μM against MDA-MB-231 and MCF-7 cells, respectively. Furthermore, compound 9 treated MCF-7 cells as observed by propidium iodide staining significantly increased cell population of S phase and G2 phase to 43.64% and 35.19%, respectively therefore arresting cell cycle at G2 and S phase. These results indicate that eugenol linked 1,2,3-triazole ring could be used as anticancer leads for the treatment of this deadly diseases.

What Ethical Dilemmas Do Social Workers Face in the Healthcare Area in Spain? The purpose of the article is to identify the types of ethical dilemmas that Spanish social workers face in the healthcare arena (health centers, hospitals and mental health). A quantitative methodology was chosen using the questionnaire prepared by Eileen J. Ain. The questionnaire has been translated and adapted for Social Work in Spain. The statistical analysis shows the correlation between the different areas of intervention in Social Work and the most significant ethical dilemmas that such professionals have to solve (autonomy, confidentiality and informed consent). This article is an essential study on Social Work at the national level that emphasizes the importance of the ethics of Social Work in the Healthcare area.

First report of transfusing low-titer cold-stored type O whole blood to an extremely-low-birth-weight neonate after acute blood loss. Multiple reports suggest that cold-stored low-titer type O whole blood (LTOWB) is becoming a preferred transfusion product for resuscitating massive hemorrhage across trauma, obstetrical, and pediatric services. However, we know of no reports of using this product for emergency transfusion of newborn infants after acute severe hemorrhage. We report our experience with emergency transfusion of re-warmed LTOWB using a fluid warmer for the resuscitation of a hypotensive 25-week gestation neonate following acute and severe placental abruption. The transfusion was tolerated well, without evidence of hemolysis or other complications. This is the first report of which we are aware of transfusing warmed LTOWB to a preterm neonate. Our positive experience leads us to speculate that this product could have a role for neonates following acute severe blood loss.

Long-Duration Progressive Supranuclear Palsy: Clinical Course and Pathological Underpinnings. To identify the clinical characteristics of the subgroup of benign progressive supranuclear palsy with particularly long disease duration; to define neuropathological determinants underlying variability in disease duration in progressive supranuclear palsy. Clinical and pathological features were compared among 186 autopsy-confirmed cases with progressive supranuclear palsy with ≥10 years and shorter survival times. The 45 cases (24.2%) had a disease duration of ≥10 years. The absence of ocular motor abnormalities within the first 3 years from disease onset was the only significant independent clinical predictor of longer survival. Histopathologically, the neurodegeneration parameters in each survival group were paralleled anatomically by the distribution of neuronal cytoplasmic inclusions, whereas the tufted astrocytes displayed anatomically an opposite severity pattern. Most interestingly, we found significantly less coiled bodies in those who survive longer, in contrast to patients with less favorable course. A considerable proportion of patients had a more "benign" disease course with ≥10 years survival. They had a distinct pattern and evolution of core symptoms compared to patients with short survival. The inverted anatomical patterns of astrocytic tau distribution suggest distinct implications of these cell types in trans-cellular propagation. The tempo of disease progression appeared to be determined mostly by oligodendroglial tau, where the high degree of oligodendroglial tau pathology might affect neuronal integrity and function on top of neuronal tau pathology. The relative contribution of glial tau should be further explored in cellular and animal models. ANN NEUROL 2022;92:637-649.

Application of biological variation and sigma metrics to evaluate the performance of HbA1c in external quality assessment. It is crucial to improve the accuracy of HbA1c measurement as its essential role in diabetes diagnosis and treatment. We aimed to establish the biological variation (BV) and sigma metrics (SM) models and apply the models to evaluate the analytical performance of HbA1c in external quality assessment (EQA) program. Data of HbA1c EQA (2021) and internal quality control (IQC) (March-August 2021) were collected. The group-specific bias and coefficient of variance (CV) were computed for measuring systems with laboratory number >9 in EQA program. The analytical bias and CV for individual laboratory were estimated from EQA and IQC data. The CV% and bias% were plotted in the BV-SM models for performance evaluation of measuring system and individual laboratory. Totally, 380 laboratories participated in EQA program. The overall inter-laboratory CV of five EQA samples ranged from 3.02% to 3.63%. There were five measuring systems that met the minimum performance for 5/5 samples: Arkary, Primus, Roche, Mindray and Tosoh, but none of them achieved the optimum performance. Half of the 196 laboratories that reported IQC and EQA results simultaneously achieved 3σ and minimum performance limits. Further analysis indicated that 88.8%, and 31.6% of the laboratories met the minimum performance for bias and CV, respectively. The biological variation and sigma metrics are appropriate quality management models for evaluating the performance of HbA1c in EQA program. The intra-laboratory and inter-laboratory imprecision need to be improved in order to achieve the required analytical goals for diabetes diagnosis.

Timeliness of Point-of-Care Viral Load Results Improves Human Immunodeficiency Virus Monitoring in Nigeria. Human immunodeficiency virus (HIV) viral load (VL) monitoring is critical for antiretroviral therapy (ART) management. Point-of-care (POC) VL testing has been reported to be feasible and preferred over standard-of-care (SOC) testing in many low- and middle-income country settings where rapid results could improve patient outcomes. The timeliness of receipt of VL results was evaluated in an open-label, randomized, controlled trial among patients newly initiating ART. Clinical outcomes with POC VL monitoring using Cepheid Xpert vs SOC VL at Jos University Teaching Hospital and Comprehensive Health Centre Zamko in Nigeria were assessed. We determined time between specimen collection and recording of VL in patient charts, receipt of results, and ART switch for those who met virologic failure criteria. Between April 2018 and October 2019, we screened 696 ART-naive individuals; 273 were randomized to POC and 268 to SOC HIV-1 VL testing. Participants in the POC arm received VL results significantly faster than those in the SOC arm (0.1 median days, interquartile range [IQR], 0.1-0.2 vs 143.1 days, IQR, 56.0-177.1, respectively; P < .0001). Participants in the POC arm with confirmed virologic failure vs those in the SOC arm were switched more rapidly to a second-line regimen (0 median days, IQR, 0-28 vs 66 days, IQR, 63-123, respectively; P = .03). POC VL testing resulted in significant improvement in the timeliness of VL result receipt by patients and use for effective HIV clinical management. In patients experiencing VL failure, POC monitoring enabled prompt switching to second-line ART regimens. NCT03533868.

Arresting Aqueous Swelling of Layered Graphene-Oxide Membranes with H3O+ and OH- Ions. Over the past decade, graphene oxide (GO) has emerged as a promising membrane material with superior separation performance and intriguing mechanical/chemical stability. However, its practical implementation remains very challenging primarily because of its undesirable swelling in an aqueous environment. Here, we demonstrated that dissociation of water molecules into H3O+ and OH- ions inside the interlayer gallery of a layered GO membrane can strongly affect its stability and performance. We reveal that H3O+ and OH- ions form clusters inside the GO laminates that impede the permeance of water and salt ions through the membrane. Dynamics of those clusters is sensitive to an external ac electric field, which can be used to tailor the membrane performance. The presence of H3O+ and OH- ions also leads to increased stability of the hydrogen bond (H-bond) network among the water molecules and the GO layers, which further reduces water permeance through the membrane, while crucially imparting stability to the layered GO membrane against undesirable swelling.

WSe2 as Transparent Top Gate for Infrared Near-Field Microscopy. Independent control of carrier density and out-of-plane displacement field is essential for accessing novel phenomena in two-dimensional (2D) material heterostructures. While this is achieved with independent top and bottom metallic gate electrodes in transport experiments, it remains a challenge for near-field optical studies as the top electrode interferes with the optical path. Here, we characterize the requirements for a material to be used as the top-gate electrode and demonstrate experimentally that few-layer WSe2 can be used as a transparent, ambipolar top-gate electrode in infrared near-field microscopy. We carry out nanoimaging of plasmons in a bilayer graphene heterostructure tuning the plasmon wavelength using a trilayer WSe2 gate, achieving a density modulation amplitude exceeding 2 × 1012 cm-2. The observed ambipolar gate-voltage response allows us to extract the energy gap of WSe2, yielding a value of 1.05 eV. Our results provide an additional tuning knob to cryogenic near-field experiments on emerging phenomena in 2D materials and moiré heterostructures.

Comparative efficacy of sedation or analgesia methods for reduction of anterior shoulder dislocation: A systematic review and network meta-analysis. We performed a network meta-analysis (NMA) to compare the efficacy and safety of intravenous sedation (IVS), intraarticular anesthetic injection (IAA), and peripheral nerve block (PNB) as sedation or analgesia methods for the reduction of anterior shoulder dislocation. We included randomized controlled trials (RCTs) comparing different sedation or analgesia methods for anterior shoulder dislocation reduction. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ICTRP, ClinicalTrials.gov, and Google Scholar databases were searched in October 2021. We conducted a random-effects NMA within a frequentist framework. We evaluated the confidence in each outcome using the CINeMA tool. Sixteen RCTs (957 patients) were included. Regarding the primary outcomes, the three methods might result in little to no difference in the immediate success rate of reduction and patient satisfaction. The IAA method had a shorter emergency department length of stay than that of the IVS method (mean difference [MD] -107.88 min, 95% confidence interval [CI] -202.58 to -13.18). In the secondary outcomes, the IAA method had a lower pain score than that of the PNB method (standardized MD -1.83, 95% CI -3.64 to -0.02). The IAA and PNB methods might require a longer time for reduction than that of the IVS method (MD 5.3 min, 95% CI 2.4 to 10.36; MD 15.25, 95% CI 5.49 to 25.01). The three methods might result in little to no difference in the number of reduction attempts and total success rate of reduction. However, the confidence ratings for all treatment comparisons were very low. IAA and PNB had no adverse respiratory events. The results of our NMA indicated that three sedation or analgesia methods (IVS, IAA, and PNB) might result in little to no difference in the success rate of reduction and patient satisfaction. IAA and PNB had no adverse respiratory events.

Leveraging epigenetics to enhance the efficacy of cancer-testis antigen: a potential candidate for immunotherapy. Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.

Effect of Xuanwei Ham Proteins with Different Ripening Periods on Lipid Metabolism, Oxidative Stress, and Gut Microbiota in Mice. Consumption of dry-cured ham may have a cardiovascular disease preventive capacity. However, whether ham protein in the maintenance of health and prevention of disease is dependent on ripening periods need to be clarified. Fifty C57BL/6 mice consume a diet that contains either Casein, raw ham protein (XWH0), or Xuanwei ham protein after 1-, 2-, or 3-years of maturation (XWH1, XWH2, or XWH3) for 4 weeks. Results show that longer ripening periods in the Xuanwei ham groups are negatively correlated with body weight gain, adipose tissue weight, total cholesterol (TC), and triglycerides levels in serum and liver, and these proteins intake could maintain liver health, reduce lipid deposition and oxidative stress, regulate lipid metabolism-related genes expression, alter the gut microbiota, and promote short-chain fatty acid production. Remarkably, XWH3 intake maintains lower TC and low-density lipoprotein cholesterol levels in serum and has high antioxidative activity as well. This regulation of lipid metabolism and oxidative stress may be related to the AMPK/Nrf2 signaling. Xuanwei ham dietary proteins that have endured a specific ripening period may have preventive effects on metabolic syndrome, which provide a basis for new ideas for nutritional health interventions.

A Systematic Review of Occupational Therapy-Related Interventions for Pediatric Chronic Pain. Occupational therapists have distinct value providing pediatric chronic pain interventions (e.g., pain management, normalizing sensory responses, increasing participation); however, limited evidence exists. This review appraised empirical studies on occupational therapy pediatric chronic pain management. Three reviewers independently screened 2,401 titles, 250 abstracts, and 71 full-text sources for studies published in English, after 2008, and with sample sizes >10, participants <18 years, with chronic pain >3 months, and outcomes related to pain/function. Studies were assessed for risk of bias. The review included 23 studies on psychological, interprofessional, virtual/telehealth, or biomechanical management, demonstrating significant decreases in pain/disability. Most studies had high risk of bias for lack of randomization and control groups, and homogeneous sampling. The occupational therapists' role in chronic pain interventions is still unclear. Research including larger, heterogenous samples is warranted to examine occupational therapy's specific role providing pain interventions as part of a team.

Age and neurocognition are associated with credibility evaluations of health websites. The internet has become a common means by which many older adults seek out health information. The prevalence of misinformation on the internet makes the search for accurate online health information a more complex and evaluative process. This study examined the role of age and neurocognition in credibility evaluations of credible and non-credible health websites. Forty-one older adults and fifty younger adults completed a structured credibility rating task in which they evaluated a series of webpages displaying health information about migraine treatments. Participants also completed measures of neurocognition, internet use, and health literacy. Results suggested that older adults rated non-credible health websites as more credible than younger adults, but the age groups did not differ in their ratings of credible sites. Within the full sample, neurocognition was associated with credibility ratings for non-credible health websites, whereas health literacy was related to the ratings of credible sites. Findings indicate that older adults may be more likely to trust non-credible health websites than younger adults, which may be related to differences in higher-order neurocognitive functions. Future work might examine whether cognitive-based supports for credibility training in older adults can be used to improve the accuracy with which they evaluate online health information.

All or nothing? A second look at partial levator avulsion. To define associations between partial levator trauma and symptoms and signs of pelvic organ prolapse (POP). This was a retrospective study of 3484 women attending a tertiary urogynecology unit for symptoms of pelvic floor dysfunction between January 2012 and February 2020. All women underwent a standardized interview, clinical pelvic organ prolapse quantification (POP-Q) examination and tomographic ultrasound imaging of the pelvic floor. Women with full levator avulsion were excluded from analysis. Partial levator avulsion was quantified using the tomographic trauma score (TTS), in which slices 3-8 are scored bilaterally for abnormal insertions. Binomial multiple logistic regression was analyzed independently for the outcome variables prolapse symptoms, symptom bother and objective prolapse on clinical examination and imaging, with age and body mass index as covariates. Two continuous outcome variables, prolapse bother score and hiatal area on Valsalva, were analyzed using multiple linear regression. Of the 3484 women, ultrasound data were missing or incomplete in 164 due to lack of equipment, clerical error and/or inadequate image quality. Full levator avulsion was diagnosed in 807 women, leaving 2513 for analysis. TTS ranged from 0-10, with a median of 0. Partial trauma (TTS > 0) was observed in 667/2513 (26.5%) women. All subjective and objective measures of POP were associated significantly with TTS, most strongly for cystocele. Associations were broadly linear and similar for all slice locations but disappeared after accounting for hiatal area on Valsalva. Partial avulsion is associated with POP and prolapse symptoms. This association was strongest for cystocele, both on POP-Q and ultrasound imaging. The effect of partial avulsion on POP and prolapse symptoms is explained fully by its effect on hiatal area. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Perineuronal Nets: Subtle Structures with Large Implications. Perineuronal nets (PNNs) are specialized structures of the extracellular matrix that surround the soma and proximal dendrites of certain neurons in the central nervous system, particularly parvalbumin-expressing interneurons. Their appearance overlaps the maturation of neuronal circuits and the closure of critical periods in different regions of the brain, setting their connectivity and abruptly reducing their plasticity. As a consequence, the digestion of PNNs, as well as the removal or manipulation of their components, leads to a boost in this plasticity and can play a key role in the functional recovery from different insults and in the etiopathology of certain neurologic and psychiatric disorders. Here we review the structure, composition, and distribution of PNNs and their variation throughout the evolutive scale. We also discuss methodological approaches to study these structures. The function of PNNs during neurodevelopment and adulthood is discussed, as well as the influence of intrinsic and extrinsic factors on these specialized regions of the extracellular matrix. Finally, we review current data on alterations in PNNs described in diseases of the central nervous system (CNS), focusing on psychiatric disorders. Together, all the data available point to the PNNs as a promising target to understand the physiology and pathologic conditions of the CNS.

Short Communication: Restrictions in care following the COVID-19 pandemic severely impacted Machado-Joseph disease patients: a study in the Azores Islands, Portugal. This qualitative study describes how the restrictions imposed by the COVID-19 pandemic impacted on Machado-Joseph disease (MJD) patients and their care, in the island of São Miguel (the Azores, Portugal). In-person semi-structured interviews were conducted with 11 participants, including patients, family members, healthcare professionals, and care providers. Main findings highlighted the key role played by the local association in psychosocial and healthcare for MJD patients and families, and the adverse effects on their care following the onset of the COVID-19 pandemic. In particular, hindered access to the day-care centre increased isolation and had a negative impact on mental health and disease progression. For persons with a progressive and severe neurological disease, there is no "back to normal." Future restrictive measures ensuing need to be accompanied by a careful definition of daily care routines for patients.

Healthcare Resource Utilization and Direct Cost of Patients with Atopic Dermatitis in Dubai, United Arab Emirates: A Retrospective Cohort Study. Atopic dermatitis (AD) data are scarce in Dubai [United Arab Emirates (UAE)]. Therefore, this study aimed at understanding real-world healthcare resource utilization (HCRU) and related costs, specialties, treatment landscape, consultation-based prevalence and incidence, and patient characteristics. This retrospective, longitudinal, insurance e-claims (Dubai Private Insurance-insured expatriates) database studied AD in Dubai between 1 January 2014 and 31 March 2020. Two cohorts of patients based on treatment status as the eligibility criteria were selected from 442,956 patients with at least two AD diagnosis claims: treated AD [mild to moderate (10,134 patients) and moderate to severe (3515 patients)] and untreated or on drugs not included in the treated AD cohort (10,806 patients). Across treated AD (mild to moderate and moderate to severe) and untreated AD cohorts, mean age was ~ 29 years; the majority were from dermatology (65-44%) and pediatrics (29-32%) specialty. Key HCRU cost contributors were hospitalizations and outpatient visits in both the treated AD groups. Mean annual disease-specific HCRU cost per patient was highest for the moderate-to-severe treated (531.5 USD) cohort, followed by the mild-to-moderate treated (378.4 USD) cohort, and lowest for the untreated (144.0 USD) cohort; patients with AD with any infection, asthma, or allergic rhinitis showed a similar trend. However, AD-diagnosed patients with Staphylococcus infection had the highest mean HCRU cost among the mild-to-moderate treated AD cohort, followed by the moderate-to-severe treated AD cohort. This study indicated AD to be a common skin disease with a prevalence rate of 4-5% in Dubai (UAE), with the majority of patients (about 90%) being treated by specialists. However, there is a significant underuse of newer innovative therapies (including biologics). Also, disease severity (moderate-to-severe AD) was associated with high direct medical cost, which could be controlled by early intervention. Furthermore, AD treatment choice could focus on major direct HCRU cost contributors such as hospitalizations, comorbid conditions, and infections. The online version contains supplementary material available at 10.1007/s13555-022-00769-z.

Impact of the use of the Red Lotus Critical Health Promotion Model as a pedagogical framework on health promotion graduates' professional practice: A mixed methods study. The Red Lotus Critical Health Promotion Model (RLCHPM) is designed to support critical health promotion practice. This study investigated the impact of the use of the RLCHPM as a pedagogical framework for competency-based university curricula on the practice of graduates from health promotion programs from an Australian regional university. A mixed methods study was undertaken, including an online survey of all 195 graduates from 2008 to 2016, followed by semi-structured interviews with a subset of respondents. There were 95 survey respondents and 10 interviewees. More than half of the survey respondents reported that the model impacted health promotion programs they are involved in, however, less than a quarter felt it impacted workplace policies. The impact was significantly higher for those with higher levels of knowledge about, confidence in using, and perception of utility of the RLCHPM, and stronger alignment of their practice with critical health promotion values and principles. Graduates' embodiment of the model's values and principles in practice enhanced the impact of the model. Factors that limited the impact included participants' implicit use of components of the model without explicit reference to the model, and the incongruence between participants' professional practice ideals and those of their workplace context. The use of the RLCHPM as a pedagogical framework for university health promotion programs positively impacted graduates' practice within the Australian context. SO WHAT?: The RLCHPM could be used as a pedagogical framework in universities to develop competency-based critical health promotion curricula to enable graduates to progress critical health promotion practice.

Pharmacological management of chronic heart failure. Chronic heart failure is a progressive and life-limiting syndrome that is caused by a failure of the heart to pump blood around the body effectively. It frequently leads to a range of distressing symptoms, such as breathlessness, fatigue and fluid retention. Chronic heart failure can be caused by a variety of cardiac diseases, but is commonly linked to coronary heart disease and hypertension. In response to these, the body initiates a series of compensatory mechanisms, which ultimately become maladaptive, and the manipulation of these mechanisms is the cornerstone of pharmacological management of the condition. This article explains the compensatory mechanisms that occur in chronic heart failure and outlines the medicines commonly used in its management.

Quantum chemistry study of the multiphoton absorption in enhanced green fluorescent protein at the single amino acid residue level. The chromophore (CRO) of fluorescent proteins (FPs) is embedded in a complex environment that is a source of specific interactions with the CRO. Understanding how these interactions influence FPs spectral properties is important for a directed design of novel markers with desired characteristics. In this work, we apply computational chemistry methods to gain insight into one-, two- and three-photon absorption (1PA, 2PA, 3PA) tuning in enhanced green fluorescent protein (EGFP). To achieve this goal, we built EGFP models differing in: i) number and position of hydrogen-bonds (h-bonds) donors to the CRO and ii) the electric field, as approximated by polarizable force field, acting on the CRO. We find that h-bonding to the CRO's phenolate oxygen results in stronger one- and multiphoton absorption. The brighter absorption can be also achieved by creating more positive electric field near the CRO's phenolate moiety. Interestingly, while individual CRO - environment h-bonds usually enhance 1PA and 2PA, it takes a few h-bond donors to enhance 3PA. Clearly, response of the absorption intensity to many-body effects depends on the excitation mechanism. We further employ symmetry-adapted perturbation theory (SAPT) to reveal excellent (2PA) and good (3PA) correlation of multiphoton intensity with electrostatic and induction interaction energies. This points to importance of accounting for mutual CRO - environment polarization in quantitative calculations of absorption spectra in FPs.

Full-array channel discrimination in cochlear implants: validation and clinical application. We sought to validate our proposed tool for estimating channel discrimination of cochlear implant (CI) users along the full electrode array and to assess associations between place-pitch discrimination and speech perception. In two tests, participants identified one stimulus (probe) as the odd-one-out compared with two reference stimuli. Probe stimuli were evoked using dual electrode stimulation characterised by the current steering coefficient α. The first test measured psychometric functions (PFs) on pre-defined contacts, with just a noticeable difference (JNDα) as the outcome variable. The second test estimated channel discrimination on the full electrode array, yielding a discrimination score of Dα. We measured speech perception as free-field consonant-vowel-consonant phoneme recognition scores. We included 25 adults with at least 6 months of CI experience. JNDα and Dα scores measured on the same contact correlated significantly (rs = 0.64, p < 0.001). Mean JNDα and speech perception scores showed significant relationships in quiet and in noise. Dα correlated strongly with JNDα scores obtained with the PFs. For poor performers, the full-array test may underestimate JNDα. The full-array pitch discrimination test could be a helpful clinical tool, such as for fitting regions of lesser pitch discrimination ability.

Health care workers' mental health in the face of COVID-19: a systematic review and meta-analysis. Healthcare workers are leading the way in treating patients with coronavirus disease 2019 (COVID-19). Due to the high levels of psychological stress, this group is more likely to experience psychological issues. These psychological problems in healthcare providers include depression, anxiety, insomnia, stress and post-traumatic stress disorder (PTSD). The goal of this systematic review and meta-analysis was to find out how common these problems were in the face of COVID-19. On 20 February 2022, systematic searches were conducted in the PubMed, Cochrane Library, Scopus, EMBASE, Science Direct, Web of Science and ProQuest databases. Two authors selected articles based on search keywords. As a last step, articles about the prevalence of psychological problems among healthcare workers in the face of COVID-19 were looked at and analysed for five different outcomes. The initial search yielded 18,609 articles. After reviewing the titles, abstracts and full texts of the articles, 44 were chosen for the final analysis and 29 were subjected to a meta-analysis. Insomnia, anxiety, depression, PTSD and stress are among the psychological issues faced by healthcare workers. Furthermore, the highest pooled prevalence of depression, anxiety, insomnia, PTSD and stress was 36% (95% confidence interval (CI) 24-50%), 47% (95% CI 22-74%), 49% (95% CI 28-70%), 37% (95% CI 19-59%) and 27% (95% CI 6-69%). In this meta-analysis, insomnia was found to be the most common mental health problem, followed by anxiety, PTSD, depression and stress in healthcare workers in the face of the COVID-19 pandemic. Generally, the pooled prevalence of these mental health problems was higher among physicians, nurses and older staff in the subgroup analysis. As a result, health policymakers and managers of the health care system should think about effective interventions to promote mental health, paying particular attention to these two groups.Key pointsStudies conducted in China reported more mental problems than in other countries.Health policymakers and health system managers should hold training programs to promote healthcare workers' mental health with a particular focus on more vulnerable groups.The prevalence of PTSD, stress, anxiety, depression and insomnia were higher among physicians, nurses and older staff.Health systems at both national and local levels have to take older physicians, nurses and healthcare providers into consideration while designing interventions.

Lived experiences of being cared for by ambulance clinicians when experiencing breathlessness-A phenomenological study. Breathlessness is a serious and distressing symptom and a common reason why patients require prehospital care by ambulance clinicians. However, little is known about how patients experience this care when they are in a state of breathlessness. The aim of this study is to describe the lived experiences of being cared for by ambulance clinicians when experiencing breathlessness. Fourteen lifeworld interviews were conducted with patients who experienced breathlessness and were cared for by ambulance clinicians. The interviews were analysed using a qualitative phenomenological approach. The essential meaning of being cared for by ambulance clinicians when experiencing breathlessness is described in two ways: existential humanising care, in which the experience is that of being embraced by a genuine presence or existential dehumanising care, in which feeling exposed to an objectifying presence is the main experience. This meaning has four constituents: surrendering to and trusting in the care that will come; being exposed to an objectifying presence is violating; being embraced by a genuine presence is relieving; and knowing is dwelling. The findings reveal that the ability of ambulance clinicians to provide existential humanising and trustful care, which is the foundation of professional judgement, was essential in how patients responded to and handled the overall situation when breathlessness.

PRNP gene polymorphism frequencies for comparing possible vulnerability to BSE in Chinese bovine population. Among the numerous transmissible spongiform encephalopathies (TSEs), bovine spongiform encephalopathy (BSE) is the most well-known TSEs. It is a potential Creutzfeldt-Jakob (CJD) disease mutation that can be transferred through cattle to humans. In several animals, the prion protein gene (PRNP) is recognized to take active part in TSE vulnerability or tolerance. Previous studies have found indels polymorphism in PRNP gene promoter and intron1 region linked to BSE vulnerability. It's linked with 23 bp indels polymorphism in putative promoter and 12 bp indel in intron 1 of the PRNP gene. The aim of this study was to compare the allele, genotype and haplotype frequencies of PRNP indel polymorphisms in Zhongdian Yak (Bos grunniens) (YK), Zhongdian Yellow cattle (Bos taurus) (YC) and Zhongdian Yakow (Bos primigenius taurus × Bos grunniens) (PK) with worldwide reported healthy or affected BSE cattle, in order to assess their potential resistance to BSE. A comparison of Chinese bovine populations with healthy and BSE-affected German and Swiss cattle from globally was conducted, and result indicating significant difference (p < .001) between healthy and affected cattle. Additionally, as compared to prior studies with Chinese bovine population, the significant results were found. In this study, the allelic frequency D23 finding high deletion in all analyzed Chinese bovine species, and haplotype D12-D23 exhibited a less significant inclination toward susceptibility to BSE.

The force-from-lipid principle and its origin, a 'what is true for E. coli is true for the elephant' refrain. The force-from-lipid (FFL) principle states that it is the lateral stretch force from the lipid membrane that ultimately opens mechanosensitive (MS) channels, not the external tether nor the internal cytoskeleton. Piezo channels for certain touch or proprioception and the hair-cell channels for hearing or balance apparently obey this principle, which is based on the idea that the lipid bilayer is an amphipathic compartment with a distinct internal force-distribution profile. Physical stretch or insertion of chemical impurities alters this profile, driving channel shape change to conform to the new environment. Thus, FFL governs all dynamic proteins embedded in membrane, including Kv's and TRPs. This article retraces the humble origin of the FFL concept. Paramecium research first created the mind set and the resources to electrically explore other microbial membranes. Patch clamp revealed MS-channel activities from yeast and E. coli spheroplasts. Despite formidable obstacles against interdisciplinary research, the E. coli MS-channel protein, MscL, was purified through fractionation by following its activity, much like enzyme purification. Reconstituted into a simple lipid bilayer, pure MscL retains mechanosensitivity, thus firmly establishing the FFL principle in 1994. The relatively simple MscL and its functional cousin MscS soon became ideal models for detailed analyses. Like the DNA-RNA-protein 'central dogma' or ATP synthesis, FFL is a fundamental principle, which appeared early in evolution, retained in all cellular life forms, and is expected to contribute to future molecular research on sensations, homeostasis, and embryonic development.

Conversation success in one-to-one and group conversation: a group concept mapping study of adults with normal and impaired hearing. The concept of conversation success is undefined, although prior work has variously related it to accurate exchange of information, alignment between interlocutors, and good management of misunderstandings. This study aimed (1) to identify factors of conversation success and (2) to explore the importance of these factors in one-to-one versus group conversations. Group concept mapping method was applied. Participants responded to two brainstorming prompts ("What does 'successful conversation' look like?" and "Think about a successful conversation you have taken part in. What aspects of that conversation contributed to its success?"). The resulting statements were sorted into related clusters and rated in importance for one-to-one and group conversation. Thirty-five adults with normal and impaired hearing. Seven clusters were identified: (1) Being able to listen easily; (2) Being spoken to in a helpful way; (3) Being engaged and accepted; (4) Sharing information as desired; (5) Perceiving flowing and balanced interaction; (6) Feeling positive emotions; (7) Not having to engage coping mechanisms. Three clusters (1, 2, and 4) were more important in group than in one-to-one conversation. There were no differences by hearing group. These findings emphasise that conversation success is a multifaceted concept.

Active muscle stiffness is reduced during rapid unloading in muscles from TtnΔ112-158 mice with a large deletion to PEVK titin. Evidence suggests that the giant muscle protein titin functions as a tunable spring in active muscle. However, the mechanisms for increasing titin stiffness with activation are not well understood. Previous studies have suggested that during muscle activation, titin binds to actin, which engages the PEVK region of titin, thereby increasing titin stiffness. In this study, we investigated the role of PEVK titin in active muscle stiffness during rapid unloading. We measured elastic recoil of active and passive soleus muscles from TtnΔ112-158 mice characterized by a 75% deletion of PEVK titin and increased passive stiffness. We hypothesized that activated TtnΔ112-158 muscles are stiffer than wild-type muscles as a result of the increased stiffness of PEVK titin. Using a servomotor force lever, we compared the stress-strain relationships of elastic elements in active and passive muscles during rapid unloading and quantified the change in stiffness upon activation. The results show that the elastic modulus of TtnΔ112-158 muscles increased with activation. However, elastic elements developed force at 7% longer lengths and exhibited 50% lower active stiffness in TtnΔ112-158 soleus muscles than in wild-type muscles. Thus, despite having a shorter, stiffer PEVK segment, during rapid unloading, TtnΔ112-158 soleus muscles exhibited reduced active stiffness compared with wild-type soleus muscles. These results are consistent with the idea that PEVK titin contributes to active muscle stiffness; however, the reduction in active stiffness of TtnΔ112-158 muscles suggests that other mechanisms compensate for the increased PEVK stiffness.

Gender-related differences in changes of estimated bleeding risk in patients on dual antiplatelet therapy: the RE-SCORE multicenter prospective registry. The risk of bleeding as predicted by the PRECISE-DAPT score can vary over time after percutaneous coronary intervention (PCI). We sought to compare the predictive ability of the PRECISE-DAPT score calculated at baseline and reassessed during follow-up in male and female patients undergoing PCI. The RE-SCORE was a multicenter, prospective registry including patients undergoing PCI treated with dual antiplatelet therapy (DAPT) for 1 year. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding. The PRECISE-DAPT score was determined for each patient at the time of PCI and at 1, 4 and 8-month follow-up visits or before the occurrence of an endpoint event. A total of 480 patients undergoing PCI were included. At baseline, median PRECISE-DAPT score was similar in males (23.2 [IQR 20.1-24.2]) and females (23.4 [IQR 20.2-25.3]; p = .22). During follow-up, an increase in the PRECISE-DAPT occurred significantly more often in females (44%) than in males (23%; p < .001). The discrimination of the PRECISE-DAPT score calculated at baseline was marginal in both males (c-index = 0.59, 95% CI: 0.51-0.65) and females (c-index = 0.55, 95% CI: 0.49-0.60). The discriminative ability of the score reassessed at follow-up was excellent in females (c-index = 0.84; 95% CI: 0.77-0.91) but remained modest in males (c-index = 0.61; 95% CI: 0.55-0.70). The bleeding predictive ability of the PRECISE-DAPT score can vary over time, more commonly in females than males. The discrimination of the score calculated during follow-up appeared improved in females but remained modest in males.Clinical Trial Registration - ClinicalTrials.gov Identifier: NCT03526614.

Coach perceptions of FA youth heading guidance: an online survey. Concerns surrounding the safety of heading within football led the English Football Association (FA) to implement guidelines for youth football participants in February 2020. Information on coach perceptions of guidelines can help to evaluate their suitability.From aninitial 1383 clubs emailed, a total of 351 respondents from English teams spanning ages U12-U18 completed an online survey between August 2020 and January 2021. Questions included their familiarity with and perceptions of youth guidelines, as well as how they approach heading within training. Information was also gathered on perceived heading frequency within training and matches. 31.1% of respondents were either unaware of guidelines or how they relate to their team. Only 4.8% of respondents did not agree with guidelines. For most respondents (60.1%), heading frequency in training was low (between 0 and 5 headers for the whole team per session), with 71.1% of respondents reporting that heading exposure would stay the same in response to guidelines. Most participants were aware of and agree with FA youth heading guidelines, however the majority think their training will not be influenced by guidelines, questioning their applied usefulness. Regardless of guidelines, coach reported heading frequency within training and matches appears to be low.

Famalismo Primero and Puerta Cerrada in Self-Managing Diabetes Among Hispanics: A Qualitative Meta-Synthesis. Type 2 diabetes (T2D) prevalence is increasing at concerning rates for Hispanics. Researchers have attempted to understand why through quantitative or qualitative studies. This meta-synthesis examines qualitative studies concerning barriers and facilitators that Hispanics face while managing their diabetes. Noblit and Hare's (1988) defined method of analysis was used to synthesize 15 qualitative studies on Hispanics' diabetes self-management. Findings revealed two themes: (a) famalismo primero and (b) puerta cerrada, translating to family first and closed door, respectively. In famalismo primero, Hispanics with T2D prioritize family, and receive support, motivation, and knowledge from them first; puerta cerrada is tied to barriers such as cost of services and patient-provider relationships. Inclusion of family in diabetes self-management provides support and motivation for Hispanics. Hispanics experience barriers to access health care that may interfere with diabetes self-management, which need to be addressed to promote health equity.

Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients. G protein-coupled receptor 183 (GPR183) has been indicated to mediate the migration and localisation of immune cells in T cell-dependent antibody responses. Systemic lupus erythematosus (SLE) is a canonical autoimmune disease involving B cell-mediated tolerance destruction and excessive pathogenic autoantibody production, in which multiple GPCRs play a role. To date, there has been no systematic study regarding the expression of GPR183 in lymphocyte subsets of SLE patients. In this research, firstly, we observed the expression trends of GRP183 in various T and B cell subsets in human tonsil tissues. These lymphocyte subsets include CD4+, CD8+, naïve T, effector T, Tfh, activated Tfh, Th1, Th2, Th17, Treg, CD19+CD27-, CD19+CD27+, naïve B, germinal centre B, memory B, and plasma cells. Further, compared with healthy controls (HCs), GPR183 expression levels in above peripheral blood lymphocyte subsets of patients with SLE were reduced overall. The differential expression of GPR183 expression between inactive and active SLE patients indicates that GPR183 expression may be concerned with the disease activity of SLE. This was further confirmed through the strong negative correlation with SLEDAI score and positive correlation with serum complement protein C3, C4 and C1q levels. Further receiver operating characteristic (ROC) curve analysis revealed that GPR183 expression in circulating CD27-IgD+ B cells may be beneficial in distinguishing between inactive and active SLE patients. In addition, type I interferon stimulation could down-regulate the expression of GPR183 in peripheral blood T and B cell subsets. Aberrant expression of GPR183 may provide some novel insights into disease activity prediction and underlying pathogenesis of SLE.

Novel and PCR ready rapid DNA isolation from Drosophila. Isolation of genomic DNA is an initial step in molecular biology techniques. The quality of isolated DNA depends on procedures and chemicals, as well as source and types of the sample used. Several existing procedures are expensive and time consuming. In this study, we isolated high quality genomic DNA with an inexpensive and least time consuming procedure using Drosophila melanogaster flies, larvae, and pupae. Drosophila melanogaster samples were collected from pre-cultured bottles, and genomic DNA was extracted using a proposed novel and PCR-ready method from three different pools of flies [PF1, PF2, and PF3], similarly from larvae and pupae [PL1, PL2, PL3, PP1, PP2, and PP3, respectively]. Isolated genomic DNA was subjected to PCR amplification with different dilutions using the COI gene and further amplicons were used for RAPD and DNA sequencing. The high quality of isolated genomic DNA was confirmed by 0.8% agarose gel electrophoresis and the purity and quantity of the DNA isolated from single fly, larva and pupa was similar to the purity and quantity of the DNA isolated using the NucleoSpinR Tissue kit method. Isolated genomic DNA was successfully amplified when the template was diluted in the ratio of 1:10. Further successful RAPD amplification and sequencing analysis of the COI gene confirms the efficiency of the downstream application of the proposed novel method. The present Novel and PCR ready rapid DNA isolation method will be potentially beneficial, and it can be successfully used for quick isolation of high molecular weight DNA from Drosophila flies larvae and pupae for DNA barcoding, identification of new species, genotyping, RAPD analysis, etc. Moreover, it can also be easily scaled up for bulk preparations.

Relationship between fear of COVID-19 and premenstrual syndrome in Turkish university students. Premenstrual syndrome (PMS) has been reported to be related to psychological distress. The COVID-19 pandemic has globally caused heightened levels of stress, anxiety, and fear. There is no sufficient evidence regarding the impact of the fear of COVID-19 on PMS and related symptoms. Therefore, this study examined the association of the fear of COVID-19 with PMS among Turkish university students. The sample of this cross-sectional study consisted of 829 Turkish university students. Data were collected online using the Questionnaire Form, the Premenstrual Syndrome Scale (PMSS), and the Fear of COVID-19 Scale (FCoV-19S). The prevalence of PMS was 73 percent. The most common symptoms were fatigue, irritability, appetite changes, and depression. Participants had a moderate fear of COVID-19 (mean FCoV-19S: 20.48 ± 5.96). Most participants stated that the pandemic did not affect the menstrual cycle length (72.5 percent) and bleeding (79.6 percent). Participants who noted that the pandemic impacted the length of their menstrual cycles and bleeding had a significantly higher mean FCoV-19S score than those who did not (p = .000). Moreover, FCoV-19S scores were positively correlated with PMS scores, PMS-related discomfort, and dysmenorrhea VAS scores (p < .001). This study revealed that the fear of COVID-19 affected PMS and menstrual cycle-related symptoms in Turkish university students.

Efficacy of ascorbic acid and different sources of orange peel on growth performance, gene expression, anti-oxidant status and microbial activity of growing rabbits under hot conditions. Orange peel and its extract are good sources of phenols and vitamin C that can be used as powerful antioxidants and antibacterial. The effects of dietary ascorbic acid (AA), orange peel powder (OPP) and orange peel extract (OPE) supplementations on growth performance, blood biochemicals, gene expression and antioxidant status of growing rabbits under hot conditions were investigated. A total of 80 weaned Giant Flander male rabbits, five weeks old (606.25 ± 10.08 g), were randomly assigned to four groups. The first group received untreated diet (control group). The other groups received diets supplemented with 0.5 g AA/kg diet, 2% OPP and 500 mg OPE/kg diet. The lowest feed conversion ratio (FCR) was recorded by rabbits consumed diet supplemented with AA. Supplementations of OPP and OPE reduced blood plasma total cholesterol, low density lipoprotein and very-low density lipoprotein concentrations. The tested diets reduced triglycerides, total lipids, hydrogen peroxide, malondialdehyde levels, Staphylococcus aureus and Escherichia coli of the rabbits cecum. Supplementation of OPE improved activities of superoxide dismutase gene (6.1475) and insulin-like growth factor-1 (9.2108). Conclusively, dietary supplementation of OPE improved rabbit performance through improving antioxidant enzyme activities as well as upregulation of insulin-like growth gene. Additionally, OPP and OPE (2% and 500 mg/kg diet, respectively) had antibacterial effects for growing rabbits under hot conditions.

Pediatric Rehabilitation Therapy and Physiotherapy Education in China. To explore the pediatric rehabilitation curriculum, clinical placement, faculty characteristics, facilitators and barriers to curriculum implementation, and satisfaction of graduates of entry-level programs of rehabilitation therapy and physiotherapy in China. Two online cross-sectional surveys were conducted. With stratified random sampling, faculty were contacted to provide information on pediatric rehabilitation education in Survey A. In Survey B, the satisfaction of 2019 graduates was collected. Fifty-three faculty members (response rate 96.4%) completed Survey A and 154 graduates (response rate 85.6%) completed Survey B. There were variations in pediatric rehabilitation curriculum setting, clinical placement, and faculty characteristics. The key facilitator to implementation was a stand-alone pediatric course. The insufficient number of teachers was identified as the major barrier. The median satisfaction level of all 2019 graduates for curricular setting, faculty and placement was 4 (satisfied). The satisfaction level of 2019 graduates of programs accredited by the World Physiotherapy was statistically higher than that of graduates of non-accredited programs in curricular setting and faculty. The results support the need for faculty development and guidelines on minimum standards for entry-level pediatric rehabilitation education in China.

Constitutively-expressed and induced immune effectors in the house fly (Musca domestica) and the transcription factors that may regulate them. Insects possess both infection-induced and constitutively expressed innate immune defences. Some effectors, such as lysozymes and antimicrobial peptides (AMPs), are constitutively expressed in flies, but expression patterns vary across tissues and species. The house fly (Musca domestica L.) has an impressive immune repertoire, with more effector genes than any other flies. We used RNA-seq to explore both constitutive and induced expression of immune effectors in flies. House flies were fed either Pseudomonas aeruginosa or Escherichia coli, or sterile control broth, and gene expression in the gut and carcass was analysed 4 h post-feeding. Flies fed either bacterium did not induce AMP expression, but some lysozyme and AMP genes were constitutively expressed. Prior transcriptome data from flies injected with bacteria also were analysed, and these constitutively expressed genes differed from those induced by bacterial injection. Binding sites for the transcription factor Myc were enriched upstream of constitutively expressed AMP genes, while upstream regions of induced AMPs were enriched for NF-κB binding sites resembling those of the Imd-responsive transcription factor Relish. Therefore, we identified at least two expression repertoires for AMPs in the house fly: constitutively expressed genes that may be regulated by Myc, and induced AMPs likely regulated by Relish.

X-ray Photoelectron Spectroscopy and Diffuse Reflectance Infrared Fourier Transform Spectroscopy Insight into the Pathways of Manganese Oxalate Thermal Decomposition to MnO and MnCO3. X-ray photoelectron spectroscopy (XPS) and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) were employed to study the isothermal decomposition of MnC2O4 under ultrahigh vacuum and N2 environmental conditions, respectively. High-resolution core-level XP spectra, X-ray-induced Auger spectra, and infrared spectra were obtained as a function of annealing time. In XPS studies, the time-dependent thermal decomposition characteristics were elucidated by analyzing surface composition, chemical shifts, satellites in the Mn 2p3/2 and Mn LMV bands, and Auger parameters for Mn and O. Functional groups developing during the ongoing reaction were identified by DRIFTS from characteristic vibrations. For the first time, the isothermal decomposition of manganese oxalate was shown to proceed via two pathways involving nucleation and accumulation of MnO and MnCO3. The kinetics of the decomposition in vacuum could be described by the Prout-Tompkins or/and by the Avrami-Erofeev models. The results obtained by XPS, DRIFTS, and ex situ XRD allowed concluding that the final product of oxalate decomposition was composed of MnO and MnCO3 or/and unidentate/polydentate carbonate structures populating the surface of the sample. A substantial formation of graphitic carbon was also observed and associated with interface chemical reactivities between the MnO particles and the supporting gold foil.

In Situ Imaging of Endogenous Hydrogen Peroxide Efflux from Living Cells via Bipolar Gold Nanoelectrode Array and Electrochemiluminescence Technology. The integration of a closed bipolar electrode (c-BPE) array and electrochemiluminescence (ECL) detection received a boost in applications in the detection of cell adhesion and disease-related biomarkers. This work proposed a gold nanorod array based c-BPE-ECL system to realize an in situ image of endogenous hydrogen peroxide (H2O2) efflux from living cells and parallel analysis of endogenous H2O2 released from multiple cells by converting electrochemical signals into optical signals. The gold nanorod array with high density was prepared by a repeating chronopotentiometry procedure with anodic aluminum oxide (AAO) membrane as a template. The c-BPE array was fabricated by assembling poly(dimethylsiloxane) (PDMS) chips on both sides of the gold nanorod array. When an appropriate driving potential is applied, H2O2 generated from living cells at the sensing pole was reduced on the gold nanorod, triggering the oxidation of the ECL reagent at the reporting pole, which allowed the detection of H2O2 released from living cells. Under phorbol myristate acetate (PMA) stimulation, H2O2 released from living HeLa, HepG2, MCF-7, and LO2 cells was determined to be 47, 32.4, 25.7, and 6.3 μM, respectively. This indicated that the amount of H2O2 released from PMA-stimulated cancer cells was significantly higher than that from the stimulated normal cells. This work presented a new approach for in situ imaging of H2O2 released from living cells and could also be used to detect other electrochemically active or non-electrochemically active molecules through simple cell surface modification, which may have potential applications in cell apoptosis study and disease diagnosis.

Application of finite element analysis to tissue differentiation and bone remodelling approaches and their use in design optimization of orthopaedic implants: A review. Post-operative bone growth and long-term bone adaptation around the orthopaedic implants are simulated using the mechanoregulation based tissue-differentiation and adaptive bone remodelling algorithms, respectively. The primary objective of these algorithms was to assess biomechanical feasibility and reliability of orthopaedic implants. This article aims to offer a comprehensive review of the developments in mathematical models of tissue-differentiation and bone adaptation and their applications in studies involving design optimization of orthopaedic implants over three decades. Despite the different mechanoregulatory models developed, existing literature confirm that none of the models can be highly regarded or completely disregarded over each other. Not much development in mathematical formulations has been observed from the current state of knowledge due to the lack of in vivo studies involving clinically relevant animal models, which further retarded the development of such models to use in translational research at a fast pace. Future investigations involving artificial intelligence (AI), soft-computing techniques and combined tissue-differentiation and bone-adaptation studies involving animal subjects for model verification are needed to formulate more sophisticated mathematical models to enhance the accuracy of pre-clinical testing of orthopaedic implants.

Decoupled evolution of the cranium and mandible in carnivoran mammals. The relationship between skull morphology and diet is a prime example of adaptive evolution. In mammals, the skull consists of the cranium and the mandible. Although the mandible is expected to evolve more directly in response to dietary changes, dietary regimes may have less influence on the cranium because additional sensory and brain-protection functions may impose constraints on its morphological evolution. Here, we tested this hypothesis by comparing the evolutionary patterns of cranium and mandible shape and size across 100+ species of carnivoran mammals with distinct feeding ecologies. Our results show decoupled modes of evolution in cranial and mandibular shape; cranial shape follows clade-based evolutionary shifts, whereas mandibular shape evolution is linked to broad dietary regimes. These results are consistent with previous hypotheses regarding hierarchical morphological evolution in carnivorans and greater evolutionary lability of the mandible with respect to diet. Furthermore, in hypercarnivores, the evolution of both cranial and mandibular size is associated with relative prey size. This demonstrates that dietary diversity can be loosely structured by craniomandibular size within some guilds. Our results suggest that mammal skull morphological evolution is shaped by mechanisms beyond dietary adaptation alone.

Structural Characterization of Dendriplexes In Vacuo: A Joint Ion Mobility/Molecular Dynamics Investigation. The combination between ion mobility mass spectrometry and molecular dynamics simulations is demonstrated for the first time to afford valuable information on structural changes undergone by dendriplexes containing ds-DNA and low-generation dendrimers when transferred from the solution to the gas phase. Dendriplex ions presenting 1:1 and 2:1 stoichiometries are identified using mass spectrometry experiments, and the collision cross sections (CCS) of the 1:1 ions are measured using drift time ion mobility experiments. Structural predictions using Molecular Dynamics (MD) simulations showed that gas-phase relevant structures, i.e., with a good match between the experimental and theoretical CCS, are generated when the global electrospray process is simulated, including the solvent molecule evaporation, rather than abruptly transferring the ions from the solution to the gas phase. The progressive migration of ammonium groups (either NH4+ from the buffer or protonated amines of the dendrimer) into the minor and major grooves of DNA all along the evaporation processes is shown to compact the DNA structure by electrostatic and hydrogen-bond interactions. The subsequent proton transfer from the ammonium (NH4+ or protonated amino groups) to the DNA phosphate groups allows creation of protonated phosphate/phosphate hydrogen bonds within the compact structures. MD simulations showed major structural differences between the dendriplexes in solution and in the gas phase, not only due to the loss of the solvent but also due to the proton transfers and the huge difference between the solution and gas-phase charge states.

Adherence to Oxidative Balance Scores is Associated with a Reduced Risk of Breast Cancer; A Case-Control Study. We aimed to examine whether anthropometric indices, dietary factors, and nutrient intakes of women with and without breast cancer (BrCa) are associated with the oxidative balance score (OBS). This case-control study was carried out among 253 patients with BrCa and 267 healthy subjects aged >18 years. The OBS was calculated by using the following 13 dietary and non-dietary anti- and prooxidant components: dietary antioxidants (selenium, fiber, β-carotene, vitamin D, vitamin C, vitamin E, and folate), dietary prooxidants (iron and saturated and polyunsaturated fatty acids), and nondietary anti- (physical activity) and prooxidants (smoking and obesity). The binary logistic regression was used to determine the association OBS with BrCa. After adjusting for potential confounders in the final model, there was evidence that the odds of BrCa decreased with increasing categories of the OBS (OR = 0.53, 95% CI 0.28 - 0.98; P-trend = 0.021). When we made stratified analysis by menopausal status, OBS was inversely associated with odds of BrCa in premenopausal women after adjusting for potential confounders. No significant association was found between OBS and odds of BrCa among post-menopausal women. Our data suggest that OBS scores were associated with decreased BrCa risk in the overall population.

Resilience, perceived social support and professional quality of life among medical social workers during COVID-19 pandemic in Mainland China: A cross-sectional survey. As COVID-19 rapidly overwhelmed the world in 2020, medical social workers have fought against the disease on the front lines as a member of medical teams, but little is known about the impact of the pandemic on their mental health. This study investigated the resilience, perceived social support and professional quality of life of medical social workers in Mainland China under the influence of the COVID-19 pandemic. An online questionnaire survey was applied to 319 respondents and the results showed that informal support was positively related with compassion satisfaction (r = 0.67, p < .01) and negatively correlated with job burnout (r = -0.51, p < .01) while formal support was positively associated with compassion satisfaction (r = 0.61, p < .01) and negatively associated with job burnout (r = -0.44. p < .01). Resilience was positively correlated with compassion satisfaction (r = 0.56, p < .01) and negatively correlated with job burnout (r = -0.49, p < .01). Nevertheless, neither perceived social support nor resilience was associated with secondary traumatic stress. The regression results further highlighted the role of informal social support on job burnout. Measures should be taken to enhance the professional quality of life for medical social workers during a public health crisis .

Food yeasts: occurrence, functions, and stress tolerance in the brewing of fermented foods. With the rapid development of systems biology technology, there is a deeper understanding of the molecular biological mechanisms and physiological characteristics of microorganisms. Yeasts are widely used in the food industry with their excellent fermentation performances. While due to the complex environments of food production, yeasts have to suffer from various stress factors. Thus, elucidating the stress mechanisms of food yeasts and proposing potential strategies to improve tolerance have been widely concerned. This review summarized the recent signs of progress in the variety, functions, and stress tolerance of food yeasts. Firstly, the main food yeasts occurred in fermented foods, and the taxonomy levels are demonstrated. Then, the main functions of yeasts including aroma enhancer, safety performance enhancer, and fermentation period reducer are discussed. Finally, the stress response mechanisms of yeasts and the strategies to improve the stress tolerance of cells are reviewed. Based on sorting out these related recent researches systematically, we hope that this review can provide help and approaches to further exert the functions of food yeasts and improve food production efficiency.

Unauthorized Pelvic Exams are Sexual Assault. The pelvic exam is used to assess the health of female reproductive organs and so involves digital penetration by a physician. However, it is common practice for medical students to acquire experience in administering pelvic exams by performing them on unconscious patients without prior authorization. In this article, we argue that such unauthorized pelvic exams (UPEs) are sexual assault. Our argument is simple: in any other circumstance, unauthorized digital penetration amounts to sexual assault. Since there are no morally significant differences between UPEs and other instances of digital penetration, UPEs are sexual assault. So, insofar as one is against sexual assault, one should be against UPEs.

Sustainable multi-trait selection index based on production, reproduction, and health traits for genetic improvement of Murrah buffaloes. Selection of Murrah buffaloes based on production, reproduction, and health traits play an important role in sustainable genetic improvement. With the aim to construct an index comprising of production, reproduction and health traits of Murrah buffaloes, the production and reproduction data during a 50-year span (1971-2020) and for health traits data of 27 years (1994-2020) were analyzed. Various three, four, five, and six trait combinations of production, reproduction, and health traits were explored for construction of performance indices. The income and expenditure method was used to calculate relative economic values (REV) for traits under consideration. A total of 37 performance indices were constructed using a multi-trait combination of production, reproduction, and health traits. Out of 37 indices, the (ADMY-PY-DO-AFC-FF) based index was identified as the best, with 78%, 2%, and 20% weightage given to production, reproduction, and female fertility, respectively. Furthermore, when REVs of traits were increased by 25% and 50%, there was no change observed in the relative importance of traits in the best index, indicating that the index was robust to substantial increases in economic values. Therefore, it is recommended that the above constructed composite selection index can be employed in selection of female buffaloes to achieve sustainable genetic gain.

Targeting the Receptor-Binding Motif of SARS-CoV-2 with D-Peptides Mimicking the ACE2 Binding Helix: Lessons for Inhibiting Omicron and Future Variants of Concern. The COVID-19 pandemic continues to spread around the world, with several new variants emerging, particularly those of concern (VOCs). Omicron (B.1.1.529), a recent VOC with many mutations in the spike protein's receptor-binding domain (RBD), has attracted a great deal of scientific and public interest. We previously developed two D-peptide inhibitors for the infection of the original SARS-CoV-2 and its VOCs, alpha and beta, in vitro. Here, we demonstrated that Covid3 and Covid_extended_1 maintained their high-affinity binding (29.4-31.3 nM) to the omicron RBD. Both D-peptides blocked the omicron variant in vitro infection with IC50s of 3.13 and 5.56 μM, respectively. We predicted that Covid3 shares a larger overlapping binding region with the ACE2 binding motif than different classes of neutralizing monoclonal antibodies. We envisioned the design of D-peptide inhibitors targeting the receptor-binding motif as the most promising approach for inhibiting current and future VOCs of SARS-CoV-2, given that the ACE2 binding interface is more limited to tolerate mutations than most of the RBD's surface.

Hierarchical Composite Nanoarchitectonics with a Graphitic Core, Dendrimer and Fluorocarbon Domains, and a Poly(ethylene glycol) Shell as O2 Reservoirs for Reactive Oxygen Species Production. Graphene oxide (GO), single-walled carbon nanohorn (CNHox), and nitrogen-doped CNH (N-CNH) were functionalized with fluorinated poly(ethylene glycol) (F-PEG) and/or with a fluorinated dendrimer (F-DEN) to prepare a series of assembled nanocomposites (GO/F-PEG, CNHox/F-PEG, N-CNH/F-PEG, N-CNH/F-DEN, and N-CNH/F-DEN/F-PEG) that provide effective multisite O2 reservoirs. In all cases, the O2 uptake increased with time and saturated after 10-20 min. When graphitic carbons (GO and CNHox) were coated with F-PEG, the O2 uptake doubled. The O2 loading was slightly higher in N-CNH compared to CNHox. Notably, coating N-CNH with F-DEN or F-PEG, or with both F-DEN and F-PEG, was more effective. The best performance was obtained with the N-CNH/F-DEN/F-PEG nanocomposite. The O2 uptake kinetics and mechanisms were analyzed in terms of the Langmuir adsorption equation based on a multibinding site assumption. This allowed the precise determination of multiple oxygen binding sites, including on the graphitic structure and in the dendrimer, F-DEN, and F-PEG. After an initial rapid, relatively limited release, the amount of O2 trapped in the nanomaterials remained high (>95%). This amount was marginally lower for the functionalized composites, but the oxygen stored was reserved for longer times. Finally, it is shown that these systems can generate singlet oxygen after irradiation by a light-emitting diode, and this production correlates with the amount of O2 loaded. Thus, it was anticipated that the present nanocomposites hierarchically assembled from components with different characters and complementary affinities for oxygen can be useful as O2 reservoirs for singlet oxygen generation to kill bacteria and viruses and to perform photodynamic therapy.

Polydopamine/SiO2 Hybrid Structured Superamphiphobic Fabrics with Good Photothermal Behavior. In recent years, photothermal materials that can convert light into heat energy have attracted extensive attention. In this work, we report a simple and effective approach to construct a self-cleaning photothermal superamphiphobic fabric. Dopamine (DA) can self-polymerize into polydopamine (PDA) and adhere to the surface of cotton fabric as a secondary reaction platform. Then, SiO2 nanoparticles were in situ grown on the PDA@fabric surface by the sol-gel method. The PDA clusters can not only provide good photothermal conversion performance but also be integrated with SiO2 to create micro-nano rough structures. Finally, the surface of SiO2 was modified by the long chain of fluorosilane to decrease the fabric surface energy, resulting in superamphiphobicity. The contact angles of water, ethylene glycol, and pump oil on the modified fabric surface could reach 161.1, 158.1, and 142.2°, respectively, making the fabric resistant to contamination by water, common beverages, and oil. Due to the adhesion of the PDA layer, the strong binding force between the fabric and SiO2 particles enabled the modified fabric to withstand various chemical and mechanical attacks, showing excellent mechanical robustness and harsh environmental stability. More importantly, the surface temperature of the modified fabric could be increased from 19.6 to 37.0 °C, which is close to the human body temperature, under the irradiation of simulated sunlight (I = 15 A, 300 s). The photothermal superamphiphobic fabrics with self-cleaning properties show great promise in the photothermal conversion field.

Cutaneous eyelid melanoma with lacrimal sac metastasis: the potential role of lacrimal fluid as a metastatic pathway. Here we present a patient with cutaneous eyelid melanoma patient with lacrimal sac metastasis. Clinicopathological findings in this case support the theory that lacrimal fluid can be a metastatic pathway for tumour cells. Dermatologists should be aware of the possibility that cutaneous eyelid melanoma may involve the nasolacrimal system and should examine it during the perioperative period and in postoperative follow-up.

Health from Brazilian Amazon food wastes: Bioactive compounds, antioxidants, antimicrobials, and potentials against cancer and oral diseases. Brazilian Amazon contains over 30,000 plant species and foods rich in bioactive compounds such as terpenes, phenolic acids, alkaloids, and flavonoids, of potential health benefits (antioxidant, antimicrobial, antiparasitic, anticancer, gastroprotection, prebiotic effects, among others). The existence of residues from non-edible parts of plants (leaves, roots, stems, branches, barks) or fruit wastes (peel, bagasse, seeds) in the agri-food industry and its supply chain is an important challenge in food loss and waste management. In this critical review several Amazon species, focusing on extracts/essential oils from nonedible parts or wastes, were analyzed in terms of phytochemicals, biological activity, and underlying mechanisms. We hope this review emphasizes the importance of Amazon's sustainability initiatives on population health due to the potential shown against cancer, infectious diseases, and prevention of oral diseases. It is urgent to think about the conversion of amazon food wastes and co-products into high-added-value raw materials to develop novel drugs, food packaging systems, or nutraceutical foods.

MiR-424-5p targets HSP90AA1 to facilitate proliferation and restrain differentiation in skeletal muscle development. MiR-424-5p was found to be a potential regulator in the proliferation, migration, and invasion of various cancer cells. However, the effects and functional mechanism of miR-424-5p in the process of myogenesis are still unclear. Previously, using microRNA (miRNA) sequencing and expression analysis, we discovered that miR-424-5p was expressed differentially in the different skeletal muscle growth periods of Xuhuai goats. We hypothesized that miR-424-5p might play an important role in skeletal muscle myogenesis. Then, we found that the proliferation ability of the mouse myoblast cell (C2C12 myoblast cell line) was significantly augmented, whereas the C2C12 differentiation was repressed after increasing the expression of miR-424-5p. Mechanistically, HSP90AA1 presented a close interrelation with miR-424-5p, which was predicted as a target gene in the progression of skeletal muscle myogenesis, using transcriptome sequencing, dual luciferase reporter gene detection, and qRT-PCR. The silencing of HSP90AA1 obviously increased C2C12 proliferation and diminished differentiation, which is consistent with the ability of miR-424-5p in C2C12. Altogether, our findings indicated the role of miR-424-5p as a novel potential regulator via HSP90AA1 during muscle myogenesis progression.

Aqueous Dual-Electrolyte Full-Cell System for Improving Energy Density of Sodium-Ion Batteries. Sodium-ion batteries (SIBs) are regarded as one of the most promising candidates for next-generation energy storage devices and have been gradually grasping market share for their low cost and similar reaction mechanism and production process as compared to lithium-ion batteries. However, the low energy density of SIBs restricts their practical applications. For example, regular full cells of a Prussian blue cathode and NASICON anode have only a low discharge capacity (about 77 mA h/g at 1 C). Taking into account the compatibility of the electrolyte and electrode materials, a novel strategy for a viable aqueous dual-electrolyte sodium-ion battery (ADESIB) has been proposed using Na2SO4 solution as the anolyte and redox-active sodium hexacyanoferrate Na4Fe(CN)6 solution as the catholyte to accommodate a NASICON NaTi2(PO4)3 anode and Prussian blue Na2NiFe(CN)6 cathode. The capacity of Na+ ion deinsertion/insertion electrodes combined with the redox chemistry of the Na4Fe(CN)6 catholyte thus enhances overall charge storage and energy density. The ADESIB delivers a capacity of about 113 mA h/g at 1 C, showing a 43% improvement over batteries with a regular single Na2SO4 electrolyte. Additionally, the dual-electrolyte full-cell system is proved to reach a 84.7% capacity retention after 1000 cycles, mainly due to the synergy of the electrolytes in both sides. This pioneering research proposes an aqueous dual-electrolyte sodium-ion full cell, showing potential applications in a new sodium-ion full battery system.

Construction of a LiF-Rich and Stable SEI Film by Designing a Binary, Ion-, and Electron-Conducting Buffer Interface on the Si Surface. Stabilizing a solid electrolyte interface (SEI) film on the Si surface is a prerequisite for realizing silicon (Si) anode applications. Interfacial engineering is one of the effective strategies to construct stable SEI films on Si surfaces and improve the electrochemical performance of the Si anodes. This work develops a silver (Ag)-decorated mucic acid (MA) buffer interface on the Si surface and the obtained Si@MA*Ag anode retains 1567 mAh g-1 after 500 cycles at 2.1 A g-1 and exhibits 1740 mAh g-1 at 126 A g-1, which are significantly higher than those of the bare Si anode of 247 and 145 mAh g-1 under the same conditions, respectively. Analysis indicates that the improved electrochemical performance is because of the depressed volume effect of the Si particles and the sustained integrity of the electrode laminate during cycling, the enhanced lithium diffusion on the Si surface, and the improved electronic conductivity of the Si anode, as well as the facilitated formation of inorganic components in the SEI film.

Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10-12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile. NCT03759379.

Systemic sclerosis mortality trends in Spain from 1980 to 2019: age-period-cohort and joinpoint analysis. Systemic sclerosis (SSc) is an autoimmune chronic rheumatic disease with a high mortality rate, which continues to be a challenge for clinicians today. To assess changes in mortality trends in the Spanish SSc population between 1980 and 2019, taking into account the independent effects of sex, age, time period and birth cohort. SSc death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for the overall population and for each sex (male, female) and age group (5-year groups). Significant changes in mortality trends were identified by joinpoint regressions. An age-period-cohort (APC) analysis and potential years of life lost (PYLL) analysis were performed to identify the burden of SSc. Age-standardized mortality rates due to SSc increased from 1.87 (95% CI 1.00-3.02) per 1 000 000 inhabitants between 1980 and 1984, to 2.47 (95% CI 1.74-3.02) per 1 000 000 inhabitants between 2015 and 2019. The relative risk of mortality fell in all groups in cohorts born after 1990. The PYLL rates showed a gradual rise for both sexes. There was an increase in overall SSc mortality in Spain during the 39 years evaluated, although there was a progressive drop for men.

Acupuncture and osteopathic medicine for atopic dermatitis: a three-armed, randomized controlled explorative clinical trial. Patients with atopic dermatitis (AD) frequently use acupuncture (ACU) and osteopathic medicine (OM), although their therapeutic benefits are unclear. To investigate the effectiveness of ACU and OM in patients with AD. In a three-armed, single-centre, randomized controlled open explorative clinical trial, adult patients with AD received ACU, OM or no study intervention (control group; CG) plus routine care. Outcomes included disease severity (SCORing Atopic Dermatitis; SCORAD), itching intensity (visual analogue scale; VAS), frequency of topical corticosteroid (TCS) use over 7 days and cost-effectiveness. Endpoints were analysed by analysis of covariance adjusted for the respective baseline value and TCS use. Overall, 121 patients (92 women, 29 men) with a mean ± SD age of 31.4 ± 10.5 years were randomized. After 12 weeks, the adjusted means (95% CI) for ACU, OM and control were, respectively, 22.3 (18.3-26.3), 26.4 (22.6-30.2) and 23.7 (19.9-27.5) for SCORAD (P = 0.32); 27.9 (19.5-36.4), 35.0 (26.9-43.0) and 42.3 (34.7-50.0) for VAS itching (P < 0.05); and 2.3 (0.8-3.9), 1.9 (0.4-3.5) and 4.3 (2.6-6.0), for TCS use (P = 0.10). ACU and OM were not cost-effective compared with the CG. Although no differences in disease severity were found, our findings indicate that ACU might reduce itching in patients with AD. Furthermore, ACU and OM showed a trend towards reducing TCS use.

Computational modelling of ankle-foot orthosis to evaluate spatially asymmetric structural stiffness: Importance of geometric nonlinearity. An ankle-foot orthosis (AFO) constructed as a single piece of isotropic elastic material is a commonly used assistive device that provides stability to the ankle joint of patients with spastic diplegic cerebral palsy. The AFO has asymmetric stiffness that restricts plantarflexion during the swing phase while it is flexible to allow dorsiflexion during the stance phase with a large deflection, including buckling originating from geometric nonlinearity. However, its mechanical implications have not been sufficiently investigated. This study aims to develop a computational model of an AFO considering geometric nonlinearity and examine AFO stiffness asymmetry during plantarflexion and dorsiflexion using physical experiments. Three-dimensional AFO mechanics with geometric nonlinearities were expressed using corotational triangle-element formulations that obeyed Kirchhoff-Love plate theory. Computational load tests for plantarflexion and dorsiflexion, using idealised AFOs with two different ankle-region designs (covering or not covering the apexes of the malleoli), showed that plantarflexion moment-ankle angle relationships were linear and dorsiflexion moment-ankle angle relationships were nonlinear; increases in dorsiflexion led to negative apparent stiffness of the AFO. Both ankle-region designs resisted both plantarflexion and dorsiflexion, and out-of-plane elastic energy was locally concentrated on the lateral side, resulting in large deflections during dorsiflexion. These findings give insight into appropriate AFO design from a mechanical viewpoint by characterising three-dimensional structural asymmetry and geometric nonlinearity.

DNA-Templated Ultracompact Optical Antennas for Unidirectional Single-Molecule Emission. Optical antennas are nanostructures designed to manipulate light-matter interactions by interfacing propagating light with localized optical fields. In recent years, numerous devices have been realized to efficiently tailor the absorption and/or emission rates of fluorophores. By contrast, modifying the spatial characteristics of their radiation fields remains challenging. Successful phased array nanoantenna designs have required the organization of several elements over a footprint comparable to the operating wavelength. Here, we report unidirectional emission of a single fluorophore using an ultracompact optical antenna. The design consists of two side-by-side gold nanorods self-assembled via DNA origami, which also controls the positioning of the single-fluorophore. Our results show that when a single fluorescent molecule is positioned at the tip of one nanorod and emits at a frequency capable of driving the antenna in the antiphase mode, unidirectional emission with a forward to backward ratio of up to 9.9 dB can be achieved.

Behavioral and psychosocial predictors of self-efficacy for managing chronic disease among people living with HIV: forgiveness, life perspective, and social support. HIV medication can help people living with HIV (PLWH) live longer, but many PLWH still report difficulty managing their disease and report engaging in harmful behaviors to themselves and others, which have adverse downstream consequences. Self-efficacy is predictive of positive health behaviors and outcomes, and it is modifiable through interventions. While existing studies overwhelmingly examine self-efficacy among PLWH, much fewer studies focus on self-efficacy for managing HIV, including self-efficacy for managing physical and psychological health problems caused by HIV-common problems that PLWH experience. Additionally, only limited literature on other-forgiveness and life perspective among PLWH exists. Thus, we further examine predictors of self-efficacy for managing HIV. We hypothesize that other-forgiveness, positive life perspective, and social support significantly predict self-efficacy for managing HIV after controlling for demographic variables. The results show that the overall multiple linear regression model significantly accounted for 38% of the variance in self-efficacy for managing HIV. Additionally, other-forgiveness was as powerful at predicting self-efficacy as social support; moreover, positive life perspective was a significant and the most powerful predictor of self-efficacy. These findings indicate that other-forgiveness and positive life regard may be as important, if not more so, than social support to chronic disease management.

Responses of soil fauna communities to the individual and combined effects of multiple global change factors. Soil fauna plays a key role in regulating biogeochemical cycles, but how multiple global change factors (GCFs) may affect faunal communities remains poorly studied. We conducted a meta-analysis using 1154 observations to evaluate the individual and combined effects of elevated CO2 , nitrogen (N) addition, warming, increased rainfall and drought on soil fauna density and diversity. Here we show that, overall, individual and combined effects of GCFs had negligible effects on soil fauna density and diversity, except that density was negatively affected by drought (-27.4%) and positively affected by increased rainfall individually (+24.9%) and in combination with N addition (+67.3%) or warming (+70.4%). GCF effects varied among taxonomic groups both in magnitude and direction. Variables such as latitude, elevation and experimental setting significantly impacted both individual and combined effects. Our results suggest that soil fauna density is affected by changed rainfall regimes, while diversity is resistant against individual and combined effects of multiple GCFs.

Chemical Imaging of Lipid Segregation: Determining Different Length Scales of Heterogeneity with Compressive-Sensing Sum Frequency Generation Microscopy and Brewster Angle Microscopy. Membranes of various phospholipids may separate into different domains at micrometer length scales at the air-water interface. A significant challenge is to visualize the molecular organization and obtain chemical information on this surface. Langmuir-Blodgett monolayers of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) on fused silica were investigated with compressive sensing sum frequency generation (SFG) microscopy. Before and after mixing, SFG spectra for DSPC and DLPC revealed significant differences, indicating a structural change. Brewster angle microscopy images show phase separations that directly correlate the morphology of phospholipid mixtures with SFG images. Exploiting vibrational contrast in SFG images, exchange between the two phases was discovered, and quantitative thermodynamic analysis of lipid compositions in liquid-condensed and liquid-expanded (LE) phases was provided. Local SFG spectra reveal significant differences from one another, indicating the heterogeneity resulting from domain areas with distinct molecular orientation and conformation. Further heterogeneity across the domain boundary was presented on a finer scale, revealing an effect on DLPC due to the condensed phase DSPC, and the terminal methyl of DLPC perturbs the ordering of DSPC in the LE phase. This work demonstrates the heterogeneity of a two-dimensional binary lipid system mainly due to the aliphatic chain length and transition temperature difference.

[Fewer overtriaged children with PEPP compared to RETTS-p at a Swedish pediatric emergency department]. Pediatric Priority Process (PEPP) is a triage system derived from the South African Triage Scale. It was developed by healthcare professionals at the Queen Silvia Children's hospital in Gothenburg. PEPP is a four-level triage system with two parts: vital parameters and warning symptoms. The aim of the study was to compare the amount of overtriage and the specificity for children in need of hospitalization in PEPP compared to RETTS-p. Our study shows that PEPP yields significantly fewer children with a high priority and has a higher specificity than RETTS-p. Senior triage nurses judged PEPP to have a higher accuracy, and the system triages children in need of supplemental oxygen higher than RETTS-p. We conclude that PEPP has high patient safety, and the next step is to implement it at our pediatric emergency department and to continue research for further validation.

[A simple home remedy for heartburn led to a life-threatening rupture of the stomach]. A middle-aged male who suffered from heartburn ingested 1 tablespoon of bicarbonate dissolved in water to relieve symptoms. Minutes afterwards he debuted with severe abdominal pain. Upon arrival at hospital 35 minutes later he was septic with peritonitis. Surgery without preoperative radiology was contemplated. However, a promptly available CT-scan interpreted by a radiologist revealed small amounts of pneumoperitoneum. During laparotomy findings were minor and the anticipated perforation could not be localized. However, after extensive air insufflation with a gastroscope a perforation below the gastroesophageal junction was detected. This case illustrates how a seemingly harmless home remedy resulted in a life-threatening condition. During night-time in Sweden, primary radiological services are often only offered digitally by remote radiologists. Such a remote organization at our hospital might have resulted in omitting CT to avoid delay, but with an increased risk of misdiagnosing our patient.

[Urogenital Ureaplasma urealyticum can cause invasive infection in immunosuppressed patients]. Ureaplasma urealyticum (Uu) is a bacterium without a cell wall, which makes it difficult to culture. Uu colonizes the lower genitourinary tract and is transmitted through sexual contact. The presence of Uu is higher in persons with immunosuppressive disease or treatment. Moreover, these persons are at increased risk of developing invasive Uu infections. We present a case concerning a 47-year-old female with multiple sclerosis treated with Rituximab. She first presented with a urinary tract infection and bartholinitis. Despite treatment with antibiotics and surgical procedures, the infection disseminated and led to intra-abdominal abscesses and empyema. Repeated cultures were negative, which prolonged the time to diagnosis and accurate treatment. Uu was detected with 16S rRNA PCR assays during the course of the disease but was interpreted as non-pathogenic Finally, Uu was suspected as the causing agent, treatment with doxycycline was initiated, and the patient recovered after nine months of disease.

[Proactive work with patient safety in psychiatry, Patient safety in Real time in Psychiatry]. Traditionally, work with patient safety has mainly been focused on examining and learning from incidents retrospectively. Proactive methods to support and evaluate patient safety as work-as-done in real time are needed. Patient safety in Real time in Psychiatry (PiRiP), combining systematic reviews of inpatient records and interviews with inpatients and staff, can be such a method. We have evolved and tested this approach in psychiatric wards in Region Jönköping County and Region Västernorrland. We found that discussion and reflection with staff about the patients' views of care and treatment, observed strengths, risks and possibilities of improvement were of value to increase awareness and knowledge of how performance of daily work relates to patient safety. PiRiP adheres to the basic principles of patient safety as described in the national action plan for patient safety.

General Backward Model to Identify the Source for Contaminants Undergoing Non-Fickian Diffusion in Water. Pollutant source identification (PSI) has been conducted for four decades for tracking Fickian diffusive pollutants, while PSI for non-Fickian diffusion, well-documented in aquifers and rivers, requires novel, predictive models. To enable PSI for non-Fickian diffusive pollutants, this study derived a general backward model using the fractional-adjoint approach in sensitivity analysis for dissolved contaminants with transport governed by the spatiotemporal fractional advection-dispersion equation (fADE). The backward fADE contains a self-adjoint time-fractional term for subdiffusion and direction-dependent, non-self-adjoint space-fractional terms for superdiffusion. Field applications showed that the resultant backward location probability density function identified the point source location in all three test cases, one alluvial aquifer and two rivers. The backward model and boundary conditions derived in this study made it possible to reliably and efficiently backtrack pollutants (and may include other constituents, such as bedload) undergoing mixed sub- and superdiffusion in natural aquatic systems. The classical PSI model, however, underestimated the source location since it did not account for solute retention and preferential flow. In addition, the measured tracer snapshots (if available before PSI) can enhance the parameter predictability and improve the applicability of backward fADE PSI. Most importantly, a spatially variable dispersion coefficient is needed in the backward fADE since PSI is most likely scale dependent in natural hydrologic systems.

Atomised intranasal dexmedetomidine versus oral melatonin in prevention of emergence delirium in children undergoing ophthalmic surgery with sevoflurane: A randomised double-blind study. Melatonin and dexmedetomidine have both been used as a premedication to decrease emergence delirium in children. The effectiveness of oral melatonin, compared with atomised intranasal dexmedetomidine, in this role is not well studied. To study the efficacy of pre-operative atomised intranasal dexmedetomidine versus oral melatonin in children scheduled for ophthalmic surgery under sevoflurane. A prospective, randomised, double-blind trial. Ophthalmic surgery in a university teaching hospital, April 2021 to October 2021. A total of 120 children undergoing ophthalmic surgery with sevoflurane anaesthesia. Children were randomised to receive pre-operative intranasal dexmedetomidine 2 μg/kg via an atomiser device (dexmedetomidine group) or oral melatonin 0.5 mg kg -1 (melatonin group), 45 min before surgery. The primary outcome was the incidence of emergence delirium assessed by the Paediatric Anaesthesia Emergence Delirium scale. Secondary outcomes included pre-operative sedation, quality of inhalational induction, postoperative sedation and pain. The incidence of emergence delirium was lower in the dexmedetomidine group than in the melatonin group (17 versus 37%, relative risk 0.45, 95% CI: 0.24 to 0.88; P = 0.01). Children in the dexmedetomidine group were more sedated following premedication and in the postanaesthesia care unit ( P < 0.05). Postoperative pain scores were lower in the dexmedetomidine group than in the melatonin group: 0 [0 to 3] versus 2.5 [0-4], ( P = 0.01). The requirement for and dose of rescue fentanyl analgesia postoperatively was comparable between the two groups. Atomised intranasal dexmedetomidine significantly reduced emergence delirium in paediatric opthalmic procedures under sevoflurane anaesthesia compared to oral melatonin. Clinical Trials Registry of India CTRI/2021/03/032388 ( www.ctri.nic.in ).

Red Light or Green Light? Netflix Series' Squid Game Influence on Young Adults' Gambling-Related Beliefs, Attitudes and Behaviors, and the Role of Audience Involvement. Media exposure for dark consumption products mostly shows glamorized and positive portrayals, rarely showing the negative consequences of consuming those products. However, the Netflix series Squid Game addresses the issue of gambling in its most extreme forms and shows the negative consequences related to it in a shocking manner, which begs the question whether watching the series could act as a preventive tool to increase risk perceptions, de-normalize gambling and reduce gambling behavior. A pre-registered survey study (N = 271) examined whether watching the Netflix series Squid Game affected young adults' (18 to 35 years old) gambling intentions and play behavior through risk perceptions, subjective norms and attitudes toward gambling, and what role audience involvement plays. Although the results show that watching Squid Game increased young adults' subjective norms of gambling (i.e. belief that significant others approve of the behavior in question) and further increased their positive attitudes toward gambling and gambling intention, the study also found an important impact of audience involvement. Audiences who were more involved with the series saw greater risks of gambling and perceived gambling to be less common. This resulted in more negative attitudes toward gambling and further less gambling intention and more motivation to change gambling behavior due to watching Squid Game.

Strategic application of liposomal system to R-α-lipoic acid for the improvement of nutraceutical properties. R-α-lipoic acid (RLA) and dihydrolipoic acid (DHLA), a reduced form of RLA, are potent endogenous antioxidants that can reduce oxidative damage. Despite their numerous nutraceutical potentials, clinical applications of RLA are still limited due to its poor solubility and stability problems. This study aimed to develop an RLA-loaded liposome (LIP/RLA) for the improvement of nutraceutical properties. LIP/RLA was developed by a typical solvent injection method. Uniform liposomes of LIP/RLA were observed by transmission electron microscopy, and the mean particle size was calculated to be ∼150 nm from the data of dynamic light scattering. LIP/RLA could prevent the degradation of RLA even under acidic conditions (pH 1.2) possibly due to the encapsulation of RLA into the liposomal structure. In the release test under pH6.8 with lipase, LIP/RLA showed relatively rapid release of RLA, possibly due to the lipolysis of phospholipids by lipase. After the oral administration of LIP/RLA (10 mg-RLA/kg, p.o.) in rats, the systemic exposures of RLA and DHLA increased by 2.8- and 5.8-fold, respectively. In a rat model of acute hepatic injury induced by carbon tetrachloride (CCl4) (0.7 mL-CCl4/kg, p.o.), orally dosed LIP/RLA (3 mg-RLA/kg, p.o.) resulted in 78.7% and 86.4% reductions of plasma alanine aminotransferase, and aspartate aminotransferase, respectively; however, RLA was found to be less effective possibly due to the poor oral absorption. The RLA-loaded liposomal system might be a promising carrier for poorly water-soluble materials with poor stability under acidic conditions, as well as RLA, to improve their oral absorption and nutraceutical properties.

Advanced clinical practice in paediatric haematology and oncology: developing a capability document. Specialist roles have been developed to provide holistic care to children and young people with cancer, one of which is the advanced clinical practitioner (ACP) in paediatric oncology and haematology. A survey showed that paediatric oncology and haematology ACPs in the UK work in a wide variety of roles and that their numbers vary greatly between treatment centres. The survey also confirmed the need for a national standardised framework delineating the knowledge, skills and expertise required of ACPs working in paediatric oncology and haematology. This article describes the development of a capability document to support and standardise advanced practice in paediatric oncology and haematology. The document reflects the advanced level of critical thinking, autonomy and decision-making required of ACPs and has been endorsed by the Children's Cancer and Leukaemia Group and by the Royal College of Nursing. It is hoped that it will support ACPs to consistently deliver high-quality, safe care for the benefit of children and young people with cancer and their families.

Physicochemical characterization of particulate matter in a cement production plant. Employees working in cement production plants are exposed to airborne particulate matter (PM) which may lead to lung function impairments and airway symptoms. The PM consists of raw materials, clinker and additives which vary depending on cement blend. The aim of this work was to characterize the thoracic fraction of PM with regard to size, phase composition and mixing state. Both stationary and personal impactors were used to collect size-fractionated samples in a cement production plant in Norway. Stationary samples were measured with aerosol particle counters and collected with a 13-stage cascade impactor, which were stationed at three locations of the cement production plant: at the raw meal mill, clinker conveyor belt and cement mill. Sioutas cascade impactors, and thoracic and respirable dust samplers were used in parallel for personal sampling. Additionally, particles for electron microscopy were collected with the stationary cascade impactor for size-fractionated single particle characterization. Gravimetric measurements and element compositions of the samples from the stationary impactors show that the PM mass is dominated by calcium-rich particles of size >1 μm. The size distribution results of stationary and personal impactors were similar. Characterization of single particles reveals that limestone is the dominating material in the raw meal mill, whereas clinker and limestone dominate at the clinker conveyor belt and at the cement mill. The element composition of clinker PM did not change with particle size. The PM collected on impactor stages with aerodynamic diameter cut-offs below 0.56 μm was dominated by soot and volatile secondary particles at the three locations. The number of ultrafine particles of the cement related compounds was low. Air concentrations of PM in personal respirable and thoracic samples ranged from 0.14-10 mg m-3 to 0.37-9.5 mg m-3, respectively. Considerable local variations exist, both in composition and air concentration of the PM.

Azide-Locked Prodrug Co-Assembly into Nanoparticles with Indocyanine Green for Chemophotothermal Therapy. Fabrication of self-delivery drug systems can surmount low drug bioavailability and achieve a precise therapeutic process. In this study, a hydrogen sulfide-responsive (H2S) small molecule prodrug was synthesized by linking two chemotherapy drugs, camptothecin (CPT) and gemcitabine (GT), using a reductive disulfide bond simultaneously with a lock GT strategy using a H2S-responsive azide group (denoted as N3-GT-CPT). The ingenious design endows the easy coprecipitation peculiarity of the prodrug with clinical indocyanine green (ICG) via a combined interaction force of hydrophobic, π-π stacking, and electrostatic interactions of anions and cations, thus producing a more stable and multifunctional therapeutic nanosystem. Considering the great photothermal and imaging ability of ICG, the obtained nanosystem showed an excellent therapeutic ability against colon tumors in vitro and in vivo with selective response to intercellular H2S, thus offering a good combination-based multiple therapy for treatment of tumors.

Charge effect of water-soluble porphyrin derivatives as a prototype to fight infections caused by Acinetobacter baumannii by aPDT approaches. In the last decade, Acinetobacter baumannii has emerged as a pathogen associated with infections in intensive care units worldwide, especially due to its ability to resist an extensive list of antibiotics. In this context, porphyrins have emerged as an important strategy in photodynamic therapy, since they are a group of tetrapyrrolic compounds with important photochemical and photobiological activities. In this study, the antimicrobial photodynamic activity of meso-tetra(4-N-methyl-pyridyl)porphyrin (H2TMePyP+) and meso-tetra(4-sulfonatophenyl)porphyrin (H2TPPS‒) was evaluated against A. baumannii by minimum inhibitory concentration (MIC), anti-biofilm activity, and the interaction with antibiotics after exposure to white-light LED irradiation. The cationic derivative H2TMePyP+ was more potent (MIC = 0.61 µM) than H2TPPS‒, with anti-biofilm activity and increased the antimicrobial activity of ciprofloxacin and amikacin. Given these findings, the tetra-cationic porphyrins can be assumed as prototypes to optimize and develop new agents by promoting oxidative stress and inducing free radical production.

ACUTE PANCREATITIS in HELSINKI in 2016-2018: INCIDENCE, ETIOLOGY and RISK FACTORS - analysis of 1378 acute pancreatitis episodes in a Finnish normal population. Updated population-based studies on acute pancreatitis (AP) in Finland are lacking. Our aim was to evaluate the current data for AP in Helsinki. We performed an electronic health care records (EHRs) search on AP patients treated at Helsinki University Hospital between the years 2016 - 2018. Incidence was calculated, etiological and potential risk factors, as well as severity of AP were documented and analyzed. Between 2016 and 2018 we found 1378 AP episodes on 1084 patients, 35% of the patients had several AP episodes, i.e., recurrent AP (RAP). The domicile-adjusted incidence was 42.2/100 000. 47% of the patients had alcohol etiology (59% men, 27% women) and 23% had biliary etiology, 21% were idiopathic and 2.9% were post-ERCP pancreatitis. 13.1% of the patients had passed at the end of September 2021. 45% of the patients were currently smoking, 11% were ex-smokers, and the highest percentage of smokers was in the group of alcohol-caused AP with 74% ever-smokers. Biliary AP had the highest amount of overweight patients. 24% of the patients used anticoagulation (AC) medication, and the percentage was significantly higher with idiopathic AP (48%). RAP, female sex and normal BMI associated with a mild form of AP. Incidence of AP and the percentage of alcohol etiology are lower than earlier reported for Finland although still higher than in other Nordic countries. Smoking and the use of AC medication associate with AP.

Can different physical education programs produce specific developments in psychological responses and cognitive functions? An ecological intervention in school-age children. The aim of this study was to investigate the effects of physical education (PE) class contents on 6-8 years school-age children's perceived exertion, psychological responses and cognitive functions. These dimensions were measured in 135 children (6.61 ± 0.58 years) before and after an 8-week different PE intervention programs [i.e. balance intervention program (BIP), game based program (GBP) or drama learning program (DLP)]. With regard to the physical exertion, higher perceived exertion was found in BIP than in GBP and DLP (p < .01, ES = -0.5 to -1.0, small to moderate). Regarding cognitive functions, children of the GBP and the DLP significantly improved some of the cognitive functions test scores (p < .01 or 0.05, ES = 0.5 to 1.5, small to large). These results lead us to think that physical activity could be an effective tool for improving children's cognitive functions.

Bicyclol alleviates high-fat diet-induced hepatic ER stress- and autophagy-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in mice. Non-alcoholic fatty liver disease (NAFLD) is a manifestation of the metabolic syndrome in the liver, and non-alcoholic steatohepatitis (NASH) represents its advanced stage. Bicyclol has protective activity against NAFLD in mice; however, the effect of bicyclol on high-fat diet (HFD)-induced NASH and its underlying molecular mechanism remains unknown particularly anti-endoplasmic reticulum (ER) stress and autophagic machinery potentials. Therefore, the present study was performed to investigate the protective effect and underlying mechanisms of bicyclol action on NAFLD/NASH. Mice were fed an HFD to induce NAFLD/NASH, and bicyclol was administered as a treatment. Biochemistry and histopathological assays were performed to evaluate the effects of bicyclol on NAFLD/NASH. Moreover, the levels of hepatic ER stress- and autophagy-related markers were determined by western blotting. The present results revealed that bicyclol exerted significant protective effects against HFD-induced NAFLD/NASH. This activity was evidenced by the decrease in elevated serum transaminase and hepatic triglyceride levels, and the attenuation of negative histopathological changes. Bicyclol considerably alleviated hepatic inflammation and apoptosis. The protein expression of ER stress-related markers, including C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), was downregulated by the bicyclol treatment in HFD-induced mice. However, the protein expression of autophagy-related markers (LC3 and Beclin 1) was upregulated by the treatment with bicyclol. Bicyclol protected HFD-induced NASH, and partly due to its ability of reducing ER stress and promoting autophagy.

Curative high-dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure. To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.