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Objective Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early treatment. The diagnostic criteria involve clinical, laboratory, and complementary tests. This review aims to draw pediatrician attention to this diagnosis, suggesting early treatment strategies, and proposing a pediatric emergency care flowchart. Sources The PubMed/MEDLINE/WHO COVID-19 databases were reviewed for original and review articles, systematic reviews, meta-analyses, case series, and recommendations from medical societies and health organizations published through July 3, 2020. The reference lists of the selected articles were manually searched to identify any additional articles. Summary of the findings COVID-19 infection is less severe in children than in adults, but can present as MIS-C, even in patients without comorbidities. There is evidence of an exacerbated inflammatory response with potential systemic injury, and it may present with aspects similar to those of Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome. MIS-C can develop weeks after COVID-19 infection, suggesting an immunomediated cause. The most frequent clinical manifestations include fever, gastrointestinal symptoms, rash, mucous membrane changes, and cardiac dysfunction. Elevated inflammatory markers, lymphopenia, and coagulopathy are common laboratory findings. Supportive treatment and early immunomodulation can control the intense inflammatory response and reduce complications and mortality. Conclusions MIS-C associated with COVID-19 is serious, rare, and potentially fatal. The emergency department pediatrician must recognize and treat it early using immunomodulatory strategies to reduce systemic injury. Further studies are needed to identify the disease pathogenesis and establish the most appropriate treatment.

Introduction Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease characterised by pruritus and abnormal liver function tests and it has been associated with intrauterine fetal distress and stillbirth. We compared two guidelines of the management of ICP: One mandating induction at 38 weeks of gestation (Rigshospitalet and Hvidovre Hospital before 2012) and another separating ICP into a mild and severe form and only women with severe ICP were recommended induction at 38 weeks (Hvidovre Hospital after 2012). Material and methods We performed a historical cohort study at two Copenhagen Hospitals from 2004 to 2015. We included 62,937 women with singleton deliveries at Rigshospitalet and 71,015 at Hvidovre Hospital of which 971 women (1.5%) and 998 women (1.4%) were diagnosed with ICP at Rigshospitalet and Hvidovre Hospital respectively. Data was retrieved from a local medical database. For the analysis of induction and comparison of obstetrical outcomes we only included pregnancies with an ICP diagnosis and excluded women with other medical conditions that could mandate induction. Main outcome measures were induction and cesarean section rates, asphyxia and stillbirth. Results We found no changes in the rate of spontaneous labor, cesarean section and induction over the years at Rigshospitalet (p = 0.17) and Hvidovre Hospital (p = 0.38). For women with intended vaginal delivery we found no change in the final mode of delivery over the years at Rigshospitalet (p = 0.28) and Hvidovre Hospital (p = 0.57). Conclusions The two approaches to the management of mild ICP regarding the timing of induction are comparable. Women with mild ICP and their clinicians should be encouraged to engage in shared decision making when discussing timing of induction.

The aim of the present study was to evaluate the biochemical profile and reproductive performance in postpartum dairy cows with clinical metritis. The research was carried out using performed on 213 pluriparous lactating cows from two dairy herds in southeast Brazil. Dairy cows were assigned into a group of healthy cows (n = 147) and cows with metritis (n = 66). Blood samples to assess serum albumin, cholesterol, fibrinogen, calcium, gamma-glutammyltransferase (GGT), aspartate aminotransferase (AST) and β-hydroxybutyrate (BHBA) concentrations were performed on day 8 ± 2 postpartum. Metritic cows had lower (p < .05) serum albumin, cholesterol and calcium concentration, and higher (p < .05) GGT and AST activity, and BHBA and fibrinogen concentrations when compared to the healthy group. The calving-to-conception interval and services per pregnancy were higher in metritic cows (p < .01) than in healthy cows and the conception rate at first service was lower in metric group (p < .01). Variable importance in projection plots demonstrated that cholesterol was the main discriminator between metritic and healthy cows. Our results indicated alterations in the biochemical profile and impaired reproduction performance in metritic cows.

Ultimately, the diversity of research presented at this Brain Conference revealed that we are at an exciting juncture in the study of the brain: theoretical and empirical progress has afforded a view of the building blocks of dynamic computation in neural systems. The research presented provided a compelling picture of how transient neural activity can represent space, time and various features of a task, be it an abstract experimental manipulation or a naturalistic feature in a social setting such as communication or mating. The frontier is now to press forward in our understanding of how dynamic computation in the brain is flexibly controlled, and what mechanisms allow the reliable propagation of transient patterns of activity across different circuit architectures and in different environmental conditions. One of the key concepts for debate that emerged was the tension between invariance and flexibility: neural dynamics are naturally constrained by specific local connections, brain architecture and biophysical mechanisms, yet time and again throughout the meeting, researchers presented patterns of neural population activity that displayed surprisingly similar dynamics despite different model systems, different stimuli, and different tasks and global behavioral states. Continuing the search to find the fundamental mechanisms by which dynamic neural activity is flexibly controlled to produce these diverse behaviors will be an exciting next chapter for the field.

Solitary brain metastasis is defined by a single metastatic brain lesion as the only site of metastasis. The initial approach to this condition consists of radiographical evaluation to establish diagnosis, followed by assessment of functional and prognostic status. Neurologic symptom management consists of using dexamethasone and antiepileptic medications. Treatment consists of a combination of surgical and radiation therapy. Surgical treatment is indicated where there is a need for tissue diagnosis or immediate alleviation of neurologic symptoms and mass effect. Stereotactic radiosurgery has become an effective treatment modality. Whole-brain radiation therapy may have a role as an adjunctive therapy.

Background and Objectives: The incidence of novel coronavirus infection across the globe has been uneven, hitting some population subgroups harder than others. Media coverage has proffered explanations for this differential vulnerability, but psychosocial risk factors have been largely ignored. In contrast, multiple theories, medical and psychological, point to one psychosocial factor - stress - as important to the etiology of disease. They also agree that pathogenic stress arises from the particular circumstance in which adaptational demands overwhelm a person's resources, creating "stress overload" that deregulates normal functioning and increases susceptibility to illness. Assessment of stress overload is proposed as essential to understanding viral spread in the current pandemic.Methods: Studies are reviewed explicating (1) stress overload theories and relevant empirical evidence, (2) construction of a stress overload measure and related validity evidence.Results: Findings support the role of stress overload in illness and the accuracy of the measure in predicting illness.Conclusion: It is concluded that assessment of stress overload may help to explain the observed coronavirus disparities, and to identify populations at risk for imminent infection. The 10-item Stress Overload Scale-Short is offered as a potentially useful tool for researchers and clinicians working to map, and stem, the proliferation of coronavirus.

Event-related potentials (ERPs) provide a multidimensional and real-time window into neurocognitive processing. The typical Waveform-based Component Structure (WCS) approach to ERPs assesses the modulation pattern of components-systematic, reoccurring voltage fluctuations reflecting specific computational operations-by looking at mean amplitude in predetermined time-windows. This WCS approach, however, often leads to inconsistent results within as well as across studies. It has been argued that at least some inconsistencies may be reconciled by considering spatiotemporal overlap between components; that is, components may overlap in both space and time, and given their additive nature, this means that the WCS may fail to accurately represent its underlying latent component structure (LCS). We employ regression-based ERP (rERP) estimation to extend traditional approaches with an additional layer of analysis, which enables the explicit modeling of the LCS underlying WCS. To demonstrate its utility, we incrementally derive an rERP analysis of a recent study on language comprehension with seemingly inconsistent WCS-derived results. Analysis of the resultant regression models allows one to derive an explanation for the WCS in terms of how relevant regression predictors combine in space and time, and crucially, how individual predictors may be mapped onto unique components in LCS, revealing how these spatiotemporally overlap in the WCS. We conclude that rERP estimation allows for investigating how scalp-recorded voltages derive from the spatiotemporal combination of experimentally manipulated factors. Moreover, when factors can be uniquely mapped onto components, rERPs may offer explanations for seemingly inconsistent ERP waveforms at the level of their underlying latent component structure.

Introduction Literature data concerning the electrospray ionisation mass spectrometry (ESI-MS) behaviour of flavonoid 5-O-glycosides are poor and sometimes disputable. Therefore, we decided to analyse the compounds of this kind present in the bark of Prunus cerasus and Prunus avium by using high-performance liquid chromatography HPLC/ESI-MS. Objective The aim of this study is to obtain the comprehensive information about the ESI-MS(+/-) behaviour of flavonoid 5-O-glucosides, to compare their behaviour with that of their positional isomers, to confirm that the known susceptibility of flavonoid 5-O-glucosides to hydrolysis may be successfully used for their identification. Method The bark from Prunus trees was extracted with pure methanol or, in order to perform hydrolysis and extraction simultaneously, with 5% methanolic solution of hydrochloric acid. The HPLC-ESI-MS analyses were performed using a Waters model 2690 HPLC pump and Waters/Micromass ZQ2000 mass spectrometer. Results Flavonoid 5-O-glycosides were completely hydrolysed under the acid conditions used, in contrast to their positional isomers. In positive ion mode, at low cone voltage, flavonoid 5-O-glycosides yield abundant Y0 + aglycone ions, in contrast to their positional isomers. In the negative ion mode, flavonoid 5-O-glycosides do not yield [Y0 - H]-· fragment ions, in contrast to their positional isomers. When aglycone contains only two hydroxyl groups, the flavonoid 5-O-glycosides can be detected in negative ion mode, whereas their positional isomers do not yield [M - H]- ions. Conclusion It has been demonstrated that the susceptibility to hydrolysis of the analysed compounds, the abundances of respective fragment ions formed, and their ESI(-) response allow unambiguous identification of flavonoid 5-O-glycosides and their differentiation from their positional isomers.

The distance between the surface of the scalp and the surface of the grey matter of the brain is a key factor in determining the effective dose of non-invasive brain stimulation for an individual person. The highly folded nature of the cortical surface means that the depth of a particular brain area is likely to vary between individuals. The question addressed here is: what is the variability of this measure of cortical depth? Ninety-four anatomical MRI images were taken from the OASIS database. For each image, the minimum distance from each point in the grey matter to the scalp surface was determined. Transforming these estimates into standard space meant that the coefficient of variation could be determined across the sample. The results indicated that depth variability is high across the cortical surface, even when taking sulcal depth into account. This was true even for the primary visual and motor areas, which are often used in setting TMS dosage. The correlation of the depth of these areas and the depth of other brain areas was low. The results suggest that dose setting of TMS based on visual or evoked potentials may offer poor reliability, and that individual brain images should be used when targeting non-primary brain areas.

Summary The provision of high-quality health care involves many different aspects, including safety, effectiveness, efficiency, and patient centredness. In order for care to be truly patient centred requires patients’ views being sought and considered, and this may be achieved through patient-centred research. Patient-centred research is fundamentally important in contemporary health care and has many benefits; for example, it ensures that research is relevant, identifies those aspects of care that are important to patients, provides information that is important to current and future patients, and allows the integration of patients’ views regarding how services may be enhanced in the future. This paper provides an overview of how we currently involve patients in orthodontic research, what this means to the specialty and how we can enhance patient involvement in the future.

Several studies with substitution-inert polynuclear platinum(II) complexes (SI-PPC) have been carried out in recent years due to the form of DNA binding presented by these compounds. This form of bonding is achieved by molecular recognition through the formation of non-covalent structures, commonly called phosphate clamps and forks, which generate small extensions of the major and minor grooves. In this work, we use molecular dynamics simulations (MD) to study the formation of these cyclical structures between six different SI-PPCs and a double DNA dodecamer, here called 24_bp_DNA. The results showed the influence of the complex expressed on the number of phosphate clamps and forks formed. Based on the conformational characterization of the DNA fragment, we show that the studied SI-PPCs interact preferentially in the minor groove, causing groove spanning, except for two of them, Monoplatin and AH44. The phosphates of C–G pairs are the main sites for such non-covalent interactions. The Gibbs interaction energy of solvated species points out to AH78P, AH78H, and TriplatinNC as the most probable ones when coupled with DNA. As far as we know, this work is the very first one related to SI-PPCs which brings MD simulations and a complete analysis of the non-covalent interactions with a double DNA dodecamer.

We retrospectively reviewed the data of 140 female pediatric patients with rare mitochondrial diseases (MDs) confirmed using muscle biopsy. We evaluated patients who were diagnosed with central precocious puberty (PP) with early pubertal development to determine whether PP is a clinical manifestation of MDs. We also examined the clinical, auxiological, laboratory, and radiological parameters after 1 year of gonadotropin-releasing hormone treatment for central PP. Among the 140 girls with MDs, 29 had early pubertal development and underwent endocrine evaluation. Ten (7.1%) patients were diagnosed with central PP; the prevalence of central PP was higher than was that previously thought. Patients with central PP exhibited bone age advancement over 1 year and increased sex hormone levels despite their young age at diagnosis. Serum estradiol levels were significantly higher in younger patients than in older patients (P = 0.004). Patients with central PP treated with gonadotropin-releasing hormone had favorable outcomes, and their pubertal development was suppressed for 1 year. Conclusion: Central PP may be a manifestation of endocrine dysfunction in young girls with MDs.

A retrograde fibular medullary screw may be utilized in certain fractures about the ankle. The purpose of this study is to investigate the anatomic considerations of a retrograde medullary screw inserted from a lateral starting point to nearby anatomic structures about the distal fibula. Ten fresh-frozen cadaveric lower extremities were utilized. A 1.6-mm Kirschner wire was inserted into the distal fibula from a far-lateral starting point. A 3.2-mm cannulated drill bit was then inserted over the Kirschner wire. After placement of the drill bit, dissection of the lateral ankle was undertaken. The proximity of nearby anatomic structures to the drill bit was measured using calipers. A 4.5-mm cortical screw was then inserted using fluoroscopic guidance. Measurements were then taken again to assess the relationship of the screw head to adjacent structures. Mean distance from drill bit to nearby structures is as follows: Peroneus longus tendon 4.56 mm, peroneus brevis tendon 6.62 mm, sural nerve 4.13 mm, superior peroneal retinaculum 7.52 mm, inferior peroneal retinaculum 6.61 mm, anterior talofibular ligament (ATFL) 6.1 mm, calcaneofibular ligament (CFL) 6.7 mm. Average distance from 4.5-mm screw head to nearby structures is as follows: peroneus longus tendon 6.79 mm, peroneus brevis tendon 6.73 mm, ATFL 4.16 mm, CFL 5.14 mm, lateral talar process 9.41 mm. Retrograde medullary fibular screw fixation may be safely carried out through a lateral start point. Anatomic structures about the lateral ankle are nearby but not immediately adjacent to the drill bit.

The jabuticaba peel extract (JPE) contains bioactive compounds that regulate fat metabolism. Because the negative correlation between fat accumulation and bone formation in bone marrow, we hypothesized that JPE inhibits adipocyte as well as favors osteoblast differentiation of mesenchymal stromal cells (MSCs) under healthy and osteoporotic conditions, a disease that display an imbalance between adipocyte and osteoblast differentiation resulting in reduced bone mass. To test these hypotheses, bone marrow MSCs were harvested from healthy and osteoporotic rats and cultured in adipogenic and osteogenic media with three concentrations of JPE, 0.25, 5 and 10 µg/ml, and vehicle (control). After selecting the most efficient concentrations of JPE, we used them to evaluate adipocyte and osteoblast differentiation of MSCs from both sources. We observed that, in general, JPE inhibited adipocyte differentiation of MSCs with more pronounced effects in cells from healthy than osteoporotic rats. In addition, JPE increased osteoblast differentiation, exhibiting a slightly higher osteogenic potential on MSCs from osteoporotic compared to healthy condition. Our results demonstrated that JPE drives MSCs to inhibit adipocyte differentiation and toward osteoblast differentiation under healthy and osteoporotic conditions. These findings pave the way for further translational studies to investigate the therapeutic possibilities of JPE in both prevention and treatment of osteoporosis.

Purpose Spirulina has previously been reported to improve high-intensity exercise performance and hemoglobin. However, spirulina’s effect on arm cycling exercise has yet to be investigated. The purpose of this study was to investigate the responses of spirulina supplementation on hemoglobin and on oxygen uptake, RER and HR during seated arm cycling exercise. Methods In a double-blinded randomized crossover design, eleven males untrained in arm cycling ingested 6 g/day of spirulina or placebo for seven days. Seated on the Arm Crank Ergometer, each participant performed a baseline V̇O2max test, and then after supplementation, 2 × 30-min submaximal exercise bouts corresponding to 55% of their V̇O2max, followed by an incremental test to fatigue. A seven-day wash-out period was required between conditions. Oxygen uptake, RER and HR were measured continuously during exercise and hemoglobin measured prior to exercise after both conditions. Results Spirulina significantly (p Conclusion Spirulina supplementation significantly reduces oxygen uptake and HR during arm cycling submaximal exercise, allowing for an increased oxygen uptake during an incremental test to fatigue.

One of the targets of the Sustainable Development Goals is clean and affordable energy. This is also the aim of the Biofuels Act of 2007 in the Philippines. However, this law is confronted with challenges such as the limitation of lignocellulosic feedstock, specifically available for bioethanol production. The present study sought to address the issue by exploring the potential of mango seed husk (MSH), a by-product of the mango industry, in bioethanol production. MSH is considered a waste material and its utilization also permit value-addition as this can serve as an alternative and affordable source of feedstock in energy production. Two pretreatment strategies are employed to exploit the cellulose and hemicellulose content of MSH, namely, dilute acid treatment and enzymatic hydrolysis. Results show that the %H2SO4 resulting in the highest glucose concentration and yield is 4% v/v at 95 °C hydrolysis temperature, 1:10 (w/v) solid-to-solvent ratio, and 60-min hydrolysis time. For enzymatic hydrolysis using a commercial enzyme preparation, the reaction time up to 72 h did not affect glucose concentration and yield at the following conditions: 50 °C hydrolysis temperature, 150 rpm, pH 5.0, 10% solids loading, and 4% enzyme loading. This could be attributed to the lignin and non-structural compounds present in MSHs. However, a combined process strategy of dilute acid pretreatment followed by enzymatic hydrolysis in the pretreatment of MSH contributes to an increased concentration and yield of sugars in the hydrolysates, which is advantageous for bioethanol production.

The aging process is associated with many brain structural alterations. These changes are not associated with neuronal loss but can be due to cortical structural changes that may be related to white matter (WM) structural alterations. In this study, we evaluated age-related changes in WM and gray matter (GM) parameters and how they correlate for specific brain tracts in a cohort of 158 healthy individuals, aged between 18 and 83 years old. In the tract-cortical analysis, cortical regions connected by tracts demonstrated similar thinning patterns for the majority of tracts. Additionally, a significant relationship was found between mean cortical thinning rate with fractional anisotropy (FA) and mean diffusivity (MD) alteration rates. For all tracts, age was the main effect controlling diffusion parameter alterations. We found no direct correlations between cortical thickness and FA or MD, except for in the fornix, for which the subcallosal gyrus thickness was significantly correlated to FA and MD (p < 0.05 FDR corrected). Our findings lead to the conclusion that alterations in the WM diffusion parameters are explained by the aging process, also associated with cortical thickness changes. Also, the alteration rates of the structural parameters are correlated to the different brain tracts in the aging process.

Chiral discrimination in biological systems, such as L-amino acids in proteins and d-sugars in nucleic acids, has been proposed to depend on various mechanisms, and chiral discrimination by mutated enzymes mediating cancer cell signaling is important in current research. We have explored how mutated isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate which in turn is converted to d-2-hydroxyglutatrate (d-2HG) as a preferred product instead of l-2-hydroxyglutatrate (l-2HG) according to quantum chemical calculations. Using transition state structure modeling, we delineate the preferred product formation of d-2HG over l-2HG in an IDH active site model. The mechanisms for the formation of d-2HG over l-2HG are assessed by identifying transition state structures and activation energy barriers in gas and solution phases. The calculated reaction energy profile for the formation of d-2HG and l-2HG metabolites shows a 29 times higher value for l-2HG as compared to d-2HG. Results for second-order Møller-Plesset perturbation theory (MP2) do not alter the observed trend based on Density Functional Theory (DFT). The observed trends in reaction energy profile explain why the formation of D-2HG is preferred over l-2HG and reveal why mutation leads to the formation of d-2HG instead of l-2HG. For a better understanding of the observed difference in the activation barrier for the formation of the two alternative products, we performed natural bond orbital analysis, non-covalent interactions analysis and energy decomposition analysis. Our findings based on computational calculations clearly indicate a role for chiral discrimination in mutated enzymatic pathways in cancer biology.

Many developing countries currently face a double burden of malnutrition (DBM) at the household level, defined by the World Health Organization, as when a mother may be overweight or anemic, and a child or grandparent is underweight, in the same household. For the present study, we defined it as the coexistence of overweight or obesity in the mother, and at least one child under the age of 5 undernourished, within the same household. Although underweight has long been considered a major issue in South and Southeast Asia, overweight and obesity have also been identified as a growing problem. The main aim of this study was to assess the DBM at the household level and its major determinants in South and Southeast Asia. We used population-representative cross-sectional data from the Demographic and Health Survey, conducted between 2007 and 2017, for eight South and Southeast Asian countries: Bangladesh, India, Nepal, Pakistan, Myanmar, Timor, Maldives, and Cambodia. Multivariate logistic regression was performed to identify the sociodemographic factors associated with DBM. A total of 798,961 households were included in this study. The pooled prevalence of overweight or obesity for the mother and stunted child was 10.0% (95% CI: 8.0.0–12.0), for OBM and wasted child, it was 7.0% (95% confidence interval (CI): 6.0–8.0), and for overweight or obese mother (OBM) and underweight child, it was 7.0% (95% CI: 6.0–8.0). The prevalence of any of these DBM coexistences was 12.0% (95% CI: 10.0–13.0) in all households. Statistically significant positive associations (p

To assess whether the main genetic differences observed in high-grade gliomas (HGG) will present different MR imaging and MR spectroscopy correlates that could be used to better characterize lesions in the clinical setting. Seventy-nine patients with histologically confirmed HGG were recruited. Immunohistochemistry analyses for isocitrate dehydrogenase gene 1 (IDH1), alpha thalassemia mental retardation X-linked gene (ATRX), Ki-67, and p53 protein expression were performed. Tumour radiological features were examined on MR images. Metabolic profile and infiltrative pattern were assessed with MR spectroscopy. MR features were analysed to identify imaging-molecular associations. The Kaplan-Meier method and the Cox regression model were used to identify survival prognostic factors. In total, 17.7% of the lesions were IDH1-mutated, 8.9% presented ATRX-mutated, 70.9% presented p53 unexpressed, and 22.8% had Ki-67 > 5%. IDH1 wild-type tumours had higher levels of mobile lipids (p = 0.001). The tumour-infiltrative pattern was higher in HGG with unexpressed p53 (p = 0.009). Mutated ATRX tumours presented higher levels of glutamate and glutamine (Glx) (p = 0.001). An association was observed between Glx tumour levels (p = 0.038) and Ki-67 expression (p = 0.008) with the infiltrative pattern. Survival analyses identified IDH1 status, age, and tumour choline levels as independent predictors of prognostic significance. Our results suggest that IDH1-wt tumours are more necrotic than IDH1-mut. And that the presence of an infiltrative pattern in HGG is associated with loss of p53 expression, Ki-67 index, and Glx levels. Finally, tumour choline levels could be used as a predictive factor in survival in addition to the IDH1 status to provide a more accurate prediction of survival in HGG patients. • IDH1-wt tumours present higher levels of mobile lipids than IDH1-mut. • Mutated ATRX tumours exhibit higher levels of glutamate and glutamine. • Loss of p53 expression, Ki-67 expression, and glutamate and glutamine levels may contribute to the presence of an infiltrative pattern in HGG.

Jacob Cohen developed two statistical measures for judging the magnitude of effects produced by an intervention, known as Cohen’s d, appropriate for assessing scaled data, and Cohen’s h, appropriate for assessing proportions. These have been widely employed in evaluating the effectiveness of alcohol, cigarette, marijuana, and other drug prevention efforts. I present two tests to consider the adequacy of using these statistics when applied to drug use prevention programs. I used student survey data from grades 6 through 12 (N = 1,963,964) collected by the Georgia Department of Education between 2015 and 2017 and aggregated at the school level (N = 1036). I calculated effect sizes for an imaginary drug prevention program that (1) reduced 30-day alcohol, cigarette, and marijuana prevalence by 50%; and (2) maintained 30-day prevalence at a pretest level for multiple years. While both approaches to estimating intervention effects represent ideal outcomes for prevention that surpass what is normally observed, Cohen’s statistics failed to reflect the effectiveness of these approaches. I recommend including an alternative method for calculating effect size for judging program outcomes. This alternative method, Relative Reduction in Prevalence (RRP), calculates ratio differences between treatment and control group drug use prevalence at posttest and follow-up, adjusting for differences observed at pretest. RRP allows researchers to state the degree to which an intervention could be viewed as efficacious or effective that can be readily understood by practitioners.

The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis. This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure. While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host. SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic. It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature. This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease. Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode. The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms. The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic.

Due to the COVID-19 pandemic, elective medical services have had to be reduced to a minimum, which has also affected care in pain medicine. Following these drastic cutbacks, a cautious resumption of elective care is planned. This also applies to the delivery of inpatient and day-care interdisciplinary multimodal pain therapy (IMPT). Since the majority of pain medicine centers have been closed to date, the question has arisen as to whether a resumption of regular care can be easily provided under the required protective measures. To answer this question, the authors conducted a survey among patients that were in a position to make a direct comparison between IMPT under normal conditions as well as under the currently required protective measures. The survey recorded the level of disruption caused by the different protective measures in the various treatment modules. An evaluation of the questionnaires, which were completed by two patient groups and all therapists involved, revealed that interdisciplinary multimodal pain therapy is possible without significant impairments even under the required protective measures. In particular, wearing protective masks proved to be the protective measure with the greatest negative impact. However, options like the use of protective visors or relocating treatment modules to the outdoors offer practicable alternative solutions for protection. Both patient and therapist satisfaction was high despite these constraints, and personal concern regarding possible infection low.

Context Gonadotroph tumors represent approximatively one-third of anterior pituitary tumors, but despite their frequency, no medical treatment is currently recommended for them. This would be greatly needed because following surgery, which is the first-line treatment, a significant percentage of gonadotroph tumors regrow. Evidence Acquisition We performed PubMed searches in March 2020 using the term “gonadotroph” in combination with 36 different keywords related to dopamine type 2 receptor agonists, somatostatin receptor (SST) ligands, temozolomide, peptide receptor radionuclide therapy (PRRT), immunotherapy, vascular endothelial growth factor receptor (VEGFR)-targeted therapy, mammalian target of rapamycin (mTOR) inhibitors, and tyrosine kinase inhibitors. Articles resulting from these searches, as well as relevant references cited by these articles were reviewed. Evidence Synthesis SST2 analogs have demonstrated only very limited antitumor effect, while high-dose cabergoline has been more effective in preventing tumor regrowth, but still in only a minority of cases. In the setting of an aggressive gonadotroph tumor, temozolomide is the recommended medical treatment, but has demonstrated also only limited efficacy. Still, its efficacy has been so far better than that of PRRT. No case of a gonadotroph tumor treated with pasireotide, VEGFR-targeted therapy, mTOR inhibitors, tyrosine kinase inhibitors, or immune checkpoint inhibitors is reported in literature. Conclusions Gonadotroph tumors need better phenotyping in terms of both tumor cells and associated tumor microenvironment to improve their treatment. Until formal recommendations will be available, we provide the readers with our suggested approach for the management of gonadotroph tumors, management that should be discussed within multidisciplinary teams.

The influence of different chromatographic conditions and the process of spot visualization on determining the limit of detection as well as quantification (LOD and LOQ) of meloxicam by TLC-densitometric technique was estimated. Of all chromatographic conditions tested, the lowest limiting values, thus the best sensitivity, in the NP-TLC system was achieved on silica gel 60F254 and neutral aluminum oxide plates developed with the mobile phase consisting of ethyl acetate/toluene/n-butylamine (2:2:1, V/V/V). In the case of the RP-TLC method, a mixture of methanol/water (8:2, V/V) enabled densitometric detection of meloxicam at the lowest concentration level on RP-8F254 and RP-18F254 plates. Additionally, the smallest LOD value of meloxicam ensured crystalline violet and gentian violet as visualization agents on silica gel 60F254 and neutral aluminum oxide 150F254 plates, resp. Comparison of the densitometrically obtained spectra of meloxicam drug and its standard after the use of appropriate visualization agents could be a good and cheap alternative tool for the identification of meloxicam as an active pharmaceutical ingredient.

The goal of the current research was to explore the perceptions of the students in the last year of a degree in Primary Education towards technology and inclusive education. It employed a mixed method research with a combined use of qualitative and quantitative methods. The research population was comprised of 153 learners, and the quantitative sample consisted of 104 participants and the qualitative one 57. Quantitative data collection was conducted using a validated questionnaire, while the qualitative data were collected through individual semi-structured interviews. On analysing the results, it was emphasized the effectiveness of technology to design and implementation of inclusive practices. However, the results also pointed out the necessity to train students technically as well as pedagogically in the use of technological tools. Moreover, it was highlighted the lack of training in inclusive education and inclusive practices during the degree, training that students considered essential to be ready for their future careers.

The absence of evidence-based guidelines make medical disqualification (MDQ) following concussion one of the most challenging decision-making processes faced by sports medicine professionals. We aimed to compare premorbid and postmorbid factors between student-athletes that were and were not medically disqualified from sport following a concussion. Among 1832 student-athletes diagnosed with concussion within the CARE Consortium, 53 (2.9%) were medically disqualified (MDQ +) and 1779 (97.1%) were not medically disqualified (MDQ−). We used contingency tables and descriptive statistics for an initial evaluation of a broad list of premorbid and postmorbid factors. For those factors showing association with MDQ status, we calculated odds ratios and 95% confidence intervals for the odds of being MDQ + in the presence of the identified factor. History of 2 (OR: 3.2, 95% CI 1.5, 6.9) or 3 + (OR: 7.4, 95% CI 3.4, 15.9) previous concussions; 1 + headaches in past 3 months (OR: 1.8, 95% CI 1.0, 3.2); immediate removal from play (OR: 2.4, 95% CI 1.2, 4.9); alcohol (OR: 2.6, 95% CI 1.2, 5.4), tobacco (OR: 3.3, 95% CI 1.1, 9.5), or marijuana use since injury (OR: 5.4, 95% CI 1.5, 19.0); as well as prolonged recovery due to mental health alterations (OR: 5.3, 95% CI 2.0, 14.1) or motivation/malingering (OR: 7.5, 95% CI 3.3, 17.0) increased odds of being MDQ + . The MDQ + group took longer to become asymptomatic relative to the MDQ− group (MDQ + : 23.5 days, 95% CI 15.8, 31.2; MDQ−: 10.6 days, 95% CI 9.5, 11.6; p

This study aimed to quantify the penetration of hydrogen peroxide, color change evaluation, surface morphology, and composition after application of desensitizing agents before in-office bleaching. Fifty premolars were sectioned, an acetate buffer was placed in the pulp chamber and divided into five groups (n=10). In the positive control group, only the in-office bleaching gel was used, and in the negative control group, no treatment was used. Three different desensitizing agents were applied: Desensibilize KF2%® group; Mi Paste® group, and Desensibilize Nano-P® group. The bleaching procedure was carried out with 35% HP. The absorbance of the resulting solution was determined in a spectrophotometer. Color change was assessed by using a digital spectrophotometer. Four additional premolars were assigned to the same groups above for analysis under scanning electron microscope, as well as to evaluate the elemental composition with X-ray dispersive energy spectrometry. Data were subjected to ANOVA and Tukey's test (α=0.05). All products reduced the penetration of HP in the pulp chamber. Mi Paste and Nano P were the products that yielded the lowest HP penetration, which was similar to the negative control group (p

Infection with intravascular platyhelminths of the genus Schistosoma can result in the debilitating disease schistosomiasis. Schistosomes (blood flukes) can survive in the host for many years. We hypothesize that proteins on their host-interactive surface modify the worm’s external environment to help insure worm survival. Previously, we have shown that a surface ectoenzyme of Schistosoma mansoni, SmNPP5 – a nucleotide pyrophosphatase/phosphodiesterase – can cleave ADP and block platelet aggregation in vitro. In this work, we show that both adult schistosomes and recombinant SmNPP5 can cleave the exogenous purinergic signaling molecule nicotinamide adenine dinucleotide (NAD). In doing so, worms and rSmNPP5 can prevent NAD-induced apoptosis of T cells in vitro. Since regulatory T cells (Tregs) are especially prone to such NAD-induced cell death (NICD), we hypothesize that schistosome cleavage of NAD promotes Treg survival which creates a more immunologically hospitable environment for the worms in vivo. In addition to SmNPP5, schistosomes express another host-interactive NAD-degrading enzyme, SmNACE. We successfully suppressed the expression of SmNPP5 and SmNACE (singly or together) using RNAi. Only SmNPP5-suppressed worms, and not SmNACE-suppressed worms, were significantly impaired in their ability to cleave exogenous NAD compared to controls. Therefore, we contend that ectoenzyme SmNPP5 on the surface of the worm is primarily responsible for extracellular NAD cleavage and that this helps modulate the host immune environment by preventing Treg cell death.

Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth, and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic, and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multiomics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis., Graphical Abstract Graphical Abstract

This is one in a series of statistical guidelines designed to highlight common statistical considerations in behavioral medicine research. The goal is to briefly discuss appropriate ways to analyze and present data in the International Journal of Behavioral Medicine (IJBM). Collectively, the series will culminate in a set of basic statistical guidelines to be adopted by IJBM and integrated into the journal’s official Instructions for Authors, and also to serve as an independent resource. If you have ideas for a future topic, please email the Statistical Editor, Suzanne Segerstrom at segerstrom@uky.edu.

Background There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission. Methods This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20–99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care. Findings Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care. There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group. Interpretation ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.

Massive drug repurposing (or repositioning) campaigns are trying to find potential antiviral treatments for COVID-19. Many involve experimental or virtual screening of libraries of compounds previously proven safe in humans-"old drugs". In 20 years of these efforts in many other diseases, never has a new therapeutic hypothesis derived from screening of old drugs in a lab led to the drug being approved for the new indication.

From bustling business districts to vibrant cultural life, many of the things that make life in cities advantageous can be attributed to their ability to bring people together. Diverse social networks, which promote productivity and innovation, can, however, act as a vector for disease transmission during a pandemic. The social distancing and lockdown measures implemented during the COVID-19 pandemic have brought fast-paced city life to a standstill, giving citizens pause to recognise the necessity of adequate living conditions, the value of access to healthcare and the privilege of digital technology. Many of these response efforts have left the most socioeconomically disadvantaged at greater risk of catching and dying from COVID-19. They have exacerbated existing health inequalities and given rise to new ones. Many are calling for a socially just recovery, including 5 million health professionals representing over 50 countries in their open letter to the United Nations calling for ethical global leadership.1 The need for action on health inequalities was evident before the pandemic but this crisis provides an unprecedented opportunity for change and cities can be a focal point for this. While each city will require a unique recovery strategy from the pandemic, this commentary calls for a health equity approach to be universally adopted. Grounded in the Social Determinants of Health framework, this commentary suggests three ways cities could change as a result of the COVID-19 pandemic in the housing, healthcare and technology sectors. Public and urban health professionals could engage multi-level stakeholders from civil society to governments at local and national levels to improve daily living conditions, promote access to healthcare and harness the power of digital technologies to address urban health inequalities.

Aluminum (Al) contamination of parenteral nutrition (PN) solutions has been known for over 30 years. In particular, vascular intake of Al leads to its accumulation in tissues. In this study, 8 all-in-one PN solutions the aluminum concentration was analyzed by high-performance liquid chromatography. The mean Al concentration of the glucose solutions of the PN solutions combinations was 16.36 ± 8.31 µg/L, the mean Al concentration of the amino acid solutions was 4.96 ± 3.73 µg/L, and the mean Al concentration of the lipid solutions was 9.09 ± 11.23 µg/L. The Al concentration of the PN5 glucose and PN2 lipid solutions were above 25 µg/L, which is the limit set by the Food and Drug Administration (FDA). No studies in the literature have examined the Al concentrations of all-in-one PN solutions via HPLC. In two of the analyzed solutions, the Al concentration was found to be higher than the limit set by the FDA.

Predictive processing seems like a radical departure from traditional theories of information processing in the brain, but a broader view of predictions highlights many similarities with standard frameworks. Predictive processing is memory and competitive bias in a new outlook-and we should use this correspondence to advance research on both fronts.

In this work, we propose a Dynamic Difficulty Adjustment methodology to achieve automatic video game balance. The balance task is modeled as a meta game, a game where actions change the rules of another base game. Based on the model of Reinforcement Learning (RL), an agent assumes the role of a game master and learns its optimal policy by playing the meta game. In this new methodology we extend traditional RL by adding the existence of a meta environment whose state transition depends on the evolution of a base environment. In addition, we propose a Multi Agent System training model for the game master agent, where it plays against multiple agent opponents, each with a distinct behavior and proficiency level while playing the base game. Our experiment is conducted on an adaptive grid-world environment in singleplayer and multiplayer scenarios. Our results are expressed in twofold: (i) the resulting decision making by the game master through gameplay, which must comply in accordance to an established balance objective by the game designer; (ii) the initial conception of a framework for automatic game balance, where the balance task design is reduced to the modulation of a reward function (balance reward), an action space (balance strategies) and the definition of a balance space state.

Antibiotic residues are widespread in the environment and their presence is known to contribute to the propagation of antibiotic resistance. Nevertheless, knowledge on processes involved in their degradation is scattered. This second part of a two part review aims at compiling knowledge on the (bio-) degradation of antibiotics, focusing on β-lactams, macrolides, quinolones and ionophores, as well as some less common classes. Detailed metabolic and molecular aspects are discussed, as well as the role of antibiotic degraders in natural microbial communities. This exercise led to the conclusion that among the classes analyzed, the majority of antibiotics are prone to microbial cleavage or transformation.

History shows that the discovery of, and the resistance to, antibiotics go hand in hand. While knowledge of resistance mechanisms, their impact and distribution is vast, over the years, the topic of antibiotic degradation has often been overlooked and regarded as being discrete from the research on resistance. As a result, understanding of the degradation of antibiotics and the impact of antibiotic degraders on the environment and human health are, for most classes, neither thoroughly documented nor understood. Current information on the biodegradation of antibiotics is described in two review articles. This first part focuses on sulfonamides, trimethoprim, aminoglycosides, amphenicols and tetracyclines. Detailed metabolic and molecular aspects as well as the role of the degraders in natural microbial communities are discussed. An integrated analysis of the accumulated data indicates that appreciation of the interplay between resistance and degradation is quite fragmented, and closing this gap will require novel experimental approaches.

Coagulase-positive Staphylococci (CoPS) can exist as commensals in humans, companion and food-producing animals, but can cause severe or even lethal diseases. Exchange of these bacteria between humans and animals has been described. Special attention has been focused on Methicillin-Resistant Staphylococcus aureus, but other CoPS can also represent an important threat. In addition to significant antimicrobial resistance, these bacteria may carry a plethora of virulence factors - molecules that allow bacteria to establish on or within a host and increase their ability to cause disease. These virulence factors have been widely described in S. aureus but information about other species of CoPS is scarce. The aim of this paper is to review the recent literature about the virulence factors of non-aureus CoPS of animal origin. Their possible effects on human health are also described. The role and prevalence of different virulence factors including leukocidins, hemolysins, adhesins, enterotoxins, exfoliative and toxic shock syndrome toxins as well as superantigen-like proteins are addressed. The effect of these virulence factors on human health is also described. The possibility of misdiagnosis of species of CoPS has been demonstrated in human clinical samples. Prevalence of zoonotic infections could be higher than thought and medical laboratories should be aware of these other staphylococcal species. In keeping with the ‘One Health’ approach to animal and human disease, medical professionals, veterinarians and health workers should be aware of the risks derived from exposure to these bacteria in people in close contact with animals, including pet owners, farmers and veterinarians themselves.

Acute kidney injury (AKI) is a life-threatening illness that continues to have an in-hospital mortality rate of patients with AKI ranges from 20% to 50% or greater, depending on underlying conditions. However, it has only marginally declined over the past 25 years. Previous authoritative publications have been pointed out that the lack of useful biomarkers for AKI has limited progress in improving the outcomes of this disorder. The purpose of this paper is to review the recent biomarkers involved in the early detection of AKI and main reasons for the failure to identify new AKI biomarkers. So far, several new AKI biomarkers have been discovered and validated to improve early diagnosis, degree of severity, pathophysiology, differential diagnosis, prediction for major kidney adverse events (MAKE, risk groups for progressive renal failure, need for renal replacement therapy [RRT], or death). These biomarkers can be classified into functional, damage and pre-injury phase biomarkers. However, the clinical use of the studied biomarkers in AKI prediction remains unclear because large prospective multicenter trials have failed to demonstrate troponin-like diagnostic performance. Reasons for the failure to identify AKI biomarkers are the heterogeneity of AKI itself, biomarker limitations and long roads to the validation of candidates for new AKI biomarkers. In an effort to overcome these barriers to identifying new AKI biomarkers, kidney biopsy specimens should be obtained and assessed in human AKI populations. Research in this field should be carried out in a pan-social approach rather than conducted by just a few medical institutions.

A series of amino acid–sulphonamide conjugates was prepared through benzotriazole mediated coupling reactions and characterised by 1H-NMR, 13C-NMR, MS, and FTIR spectroscopic techniques as well as elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was determined against four human (h) isoforms, hCA I, hCA II, hCA VA, and hCA XII. Most of the synthesised compounds showed effective in vitro CA inhibitory properties. The new amino acid–sulphonamide conjugates showed potent inhibitory activity against hCA II, some of them at subnanomolar levels, exhibiting more effective inhibitory activity compared to the standard drug acetazolamide. Some of these sulphonamides were also found to be effective inhibitors of hCA I, hCA VA, and hCA XII, with activity from the low to high nanomolar range.

Bovine leukemia virus (BLV) is an oncogenic retrovirus of the Deltaretrovirus genus, which causes persistent infection in its natural hosts – cattle, zebu, and water buffalo with diverse clinical manifestations through the defeat of B-cells. The BLV proviral genome, along with structural genes (gag, pro, pol, and env), includes nonstructural ones (R3, G4, tax, rex, AS, pre-miRs (for miRNAs). We have shown in our previous data the association of some pre-miRs-B’ (for BLV miRNA) alleles with leukocyte (WBC – white blood cell) number in BLV-infected cows. Multifunctional properties of Tax protein have led us to an assumption that tax gene/Tax protein could have too population variations related to WBC counts. Here we report about several tax alleles/Tax protein variants, which have a highly significant association with an increase or a decrease of WBC number in BLV-infected cows. We have provided evidence that Tax A, H variants (tax b, c, d, f, e alleles) are correlated with reduced WBC counts at the level of BLV-negative groups of animals and thus could be the feature of the aleukemic (AL) form of BLV infection. We suggest this finding could be used in BLV testing for the presence of Tax A, H in the proviral DNA consider such strains of BLV as AL ones, and because of this, minimize the clinical losses due to BLV infection in cattle.

An experiment for the calculation of the degree of double bond conversion, after a polymerization reaction, of photopolymerizable liquid monomers using FTIR-ATR spectroscopy is reported. The experi...