Genome Editing in Chlamydomonas reinhardtii Using Cas9-gRNA Ribonucleoprotein Complex: A Step-by-Step Guide.
Genome editing technologies have provided opportunities to manipulate literally any genomic location, opening new avenues for reverse genetics-based improvements. Among them, CRISPR/Cas9 is the most versatile tool for genome editing applications in prokaryotes and eukaryotes. Here, we provide a guide to successfully carry out high-efficiency genome editing in Chlamydomonas reinhardtii using preassembled CRISPR/Cas9-gRNA ribonucleoprotein (RNP) complexes.


Detection of significantly high vitreous concentrations of fatty acid-binding protein 4 in patients with proliferative diabetic retinopathy.
The fatty acid-binding protein4 (FABP4) and vascular endothelial growth factor A (VEGFA) play key roles in the metabolic and cardiovascular diseases, and proliferative diabetic retinopathy (PDR), respectively. To identify FABP4 in vitreous fluid in PDR, vitreous concentrations of FABP4 (V-FABP4) and VEGFA (V-VEGFA) from PDR (n = 20) and non-PDR (n = 20) patients were determined by Enzyme-Linked ImmunoSorbent Assays. The data, which included height and weight, systemic blood pressures, several blood biochemical parameters and blood flow at the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) were collected. The levels of V-FABP4 and V-VEGFA were significantly higher in PDR patients than in non-PDR patients (P < 0.001) with a high positive correlation (r = 0.72, P < 0.001) between them. The findings were not affected by body mass index values and the presence of vitreous hemorrhaging. Among the clinical parameters, V-FABP4 correlated positively with creatinine and negatively with age and aspartate transaminase (AST) levels, while V-VEGFA correlated positively with fasting plasma glucose and hemoglobin A1c (HbA1c) levels but negatively with AST. Multiple regression analyses indicated that V-VEGFA, or V-FABP4, AST and HbA1c were independent predictors of V-FABP4 or V-VEGFA, respectively. Both were negatively correlated, but more evident in V-FABP4, with the ONH ocular blood flow.


Simulating the trade effects of the COVID-19 pandemic: Scenario analysis based on quantitative trade modelling.
The WTO Global Trade Model, a quantitative trade model, is employed to project the impact on the global economy of the COVID-19 pandemic. Because of the profound uncertainty about the duration of the pandemic and the containment measures, three scenarios are constructed, V-shaped, U-shaped and L-shaped recovery, corresponding with a duration of the pandemic of 3 months, 6 months and more than a year. The pandemic and containment measures are assumed to lead to a general reduction of labour supply, a rise in trade costs, and reductions in both demand and supply in sectors most affected by the containment measures. GDP and trade are projected to fall by, respectively, 5% and 11% in the V-shaped and L-shaped scenarios and trade by, respectively, 8% and 20%. The response of trade to the reduction in GDP, measured by the trade-to-GDP elasticity, is projected to rise as the crisis lasts longer. The reason is that a longer duration will lead to a larger drop in spending on durables which are highly tradable.


Pheophorbide a: a photosensitizer with immunostimulating activities on mouse macrophage RAW 264.7 cells in the absence of irradiation.
Pheophorbide a (Pa) has been proposed to be a potential photosensitizer for the photodynamic therapy of human cancer. However, the immunomodulatory effect of Pa, in the absence of irradiation, has not yet been investigated. The present study revealed that Pa possessed immunostimulating effect on a murine macrophages cell line RAW 264.7. Pa could significantly stimulate the growth of RAW 264.7 cells with the maximum effect at 1.0μM after 24, 48 and 72 h of treatment (all p<0.05). Besides, intracellular mitogen activated protein kinases (MAPK) including extracellular signal-regulated kinase (ERK) and p38 MAPK were activated by Pa treatment in a dose-dependent manner. The activation of ERK and p38 MAPK was found to be related to the Pa-induced intracellular reactive oxygen species. Furthermore, Pa could significantly induce the release of interleukine-6 and tumour necrosis factor-α, and enhance the phagocytic activity of RAW 264.7 cells (all p<0.05). The present work is the first report to demonstrate the potential immunomodulatory effect of Pa on macrophages, apart from its well-studied anti-tumour activity.


Challenges Faced by Rural Primary Care Providers When Caring for COPD Patients in the Western United States.
Rural chronic obstructive pulmonary disease (COPD) patients have worse outcomes and higher mortality compared with urban patients. Reasons for these disparities likely include challenges to delivery of care that have not been explored. To determine challenges faced by rural primary care providers when caring for COPD patients. Rural primary care providers in 7 primarily western states were asked about barriers they experienced when caring for COPD patients. A total of 71 rural primary care medical providers completed the survey, of which 51% were physicians and 49% were advanced practice providers (APPs). A total of 61% used Global Initiative for Chronic Obstructive Lung Disease or American Thoracic Society/European Respiratory Society guidelines as an assessment and treatment resource. The presence of multiple chronic conditions and patient failure to recognize and report symptoms were the greatest barriers to diagnose COPD. A total of 89% of providers used spirometry to diagnose COPD, but only 62% were satisfied with access to spirometry. Despite recommendations, 41% of providers never test for alpha-1 antitrypsin deficiency. A total of 87% were comfortable with their ability to assess symptoms, but only 11% used a guideline-recommended assessment tool. Although most providers were satisfied with their ability to treat symptoms and exacerbations, only 66% were content with their ability to prevent exacerbations. Fewer providers were happy with their access to pulmonologists (55%) or pulmonary rehabilitation (37%). Subgroup analyses revealed differences based on provider type (APP versus physician) and location (Colorado and Kansas versus other states), but not on population or practice size. Rural providers face significant challenges when caring for COPD patients that should be targeted in future interventions to improve COPD outcomes.


Depression of glutathione by cold-restraint in mice.
The effects of cold-restraint as a physiological stressor on the glutathione (GSH) content of the liver and other tissues were examined in male mice. Mice of the ICR, NIH, ND/4, and B6C3F1 strains subjected to cold-restraint for 2 or 3 h experienced a loss of hepatic GSH concentrations ranging from approximately 15 to 50%. Though 3 of these strains (ICR, NIH, and B6C3F1) experienced hypothermia as result of the cold-restraint treatment, with average decreases in core body temperature ranging from 3.3 to 9.8 degrees C, hepatic GSH levels were depressed in the ND/4 mouse in the absence of changes in core body temperature. The ability of cold-restraint as a stressor to diminish hepatic GSH therefore could not be attributed simply to hypothermia. The decrease in hepatic GSH from cold-restraint in ND/4 mice was paralleled by a decrease in non-protein sulfhydryl (NPSH) content of the liver. In addition to its effects on liver GSH and NPSH concentrations, 1.5 h of cold-restraint stress significantly depressed plasma, heart, kidney, and lung NPSH concentrations. The extent of NPSH depression was equivalent to the GSH depression in the liver, heart, and kidney, despite the observation that the normal contribution of GSH to total NPSH content in these tissues ranged from a high of 89% (liver) to a low of 49% (heart). These results with cold-restraint in the ND/4 mouse suggest that other stressors may significantly depress cellular concentrations of GSH and other thiols, and may thereby render the affected tissues more susceptible to the toxicity of free radicals, electrophilic xenobiotic metabolites, or reactive oxygen species.


Antibiotic resistance patterns of Vibrio mimicus isolated from human and environmental sources in Bangladesh.
Twenty-five environmental and 19 clinical strains of Vibrio mimicus were tested for antibiotic susceptibility patterns. Environmental strains were resistant to streptomycin, kanamycin, and trimethoprim-sulfamethoxazole; clinical strains were susceptible. Environmental strains showed variable resistance to ampicillin (44%), but clinical strains were susceptible. All strains tested were susceptible to chloramphenicol and gentamicin.


Contraindications can damage your health--is metformin a case in point?
Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a long list of contraindications precludes millions of patients with type 2 diabetes from using it. This is largely due to the historical experience of lactic acidosis with phenformin, despite the fact that metformin does not predispose to this when compared with other therapies. Contraindications such as old age, renal impairment and cardiac insufficiency are increasingly disregarded in clinical practice, yet there is no evidence that the incidence of lactic acidosis has changed. Metformin has been shown to improve metabolic control without causing lactic acidosis in elderly patients with multiple comorbidities, including explicit contraindications, and its use in patients with type 2 diabetes over the age of 70 with mild renal impairment did not produce a clinically relevant increase in plasma lactate. There is no correlation between levels of metformin and lactate in patients with lactic acidosis, and its prognosis is mainly related to the causal hypoxic underlying disease and comorbidities. These findings raise doubts about the pathogenetic significance of metformin in lactic acidosis. We propose that advanced age per se, mild renal impairment and compensated heart failure can no longer be upheld as contraindications for metformin. A clear re-definition of contraindications to metformin will enable more physicians to prescribe within guidelines.


The HIF-1α/miR-26a-5p/PFKFB3/ULK1/2 axis regulates vascular remodeling in hypoxia-induced pulmonary hypertension by modulation of autophagy.
Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which may cause right heart failure and even death. Accumulated evidence confirmed that microRNA-26 family play critical roles in cardiovascular disease; however, their function in PAH remains largely unknown. Here, we investigated the expression of miR-26 family in plasma from PAH patients using quantitative RT-PCR, and identified miR-26a-5p as the most downregulated member, which was also decreased in hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) autophagy models and lung tissues of PAH patients. Furthermore, chromatin immunoprecipitation (ChIP) analysis and luciferase reporter assays revealed that hypoxia-inducible factor 1α (HIF-1α) specifically interacted with the promoter of miR-26a-5p and inhibited its expression in PASMCs. Tandem mRFP-GFP-LC3B fluorescence microscopy demonstrated that miR-26a-5p inhibited hypoxia-induced PAMSC autophagy, characterized by reduced formation of autophagosomes and autolysosomes. In addition, results showed that miR-26a-5p overexpression potently inhibited PASMC proliferation and migration, as determined by cell counting kit-8, EdU staining, wound-healing, and transwell assays. Mechanistically, PFKFB3, ULK1, and ULK2 were direct targets of miR-26a-5p, as determined by dual-luciferase reporter gene assays and western blots. Meanwhile, PFKFB3 could further enhance the phosphorylation level of ULK1 and promote autophagy in PASMCs. Moreover, intratracheal administration of adeno-miR-26a-5p markedly alleviated right ventricular hypertrophy and pulmonary vascular remodeling in hypoxia-induced PAH rat models in vivo. Taken together, the HIF-1α/miR-26a-5p/PFKFB3/ULK1/2 axis plays critical roles in the regulation of hypoxia-induced PASMC autophagy and proliferation. MiR-26a-5p may represent as an attractive biomarker for the diagnosis and treatment of PAH.


Molecular characterization of ascaridoid parasites from captive wild carnivores in China using ribosomal and mitochondrial sequences.
Despite the public health importance of toxocariasis/toxascariasis, only a few species of these ascaridoid parasites from wild canine and feline carnivores have been studied at the molecular level so far. Poor understanding of diversity, host distribution and the potential (zoonotic) transmission of the ascaridoid species among wild animals negatively affects their surveillance and control in natural settings. In this study, we updated previous knowledge by profiling the genetic diversity and phylogenetic relationships of ascaridoid species among eleven wild canine and feline animals on the basis of a combined analysis of the ribosomal internal transcribed spacer region (ITS) gene and the partial mitochondrial cytochrome c oxidase subunit 2 (cox2) and NADH dehydrogenase subunit 1 (nad1) genes. In total, three genetically distinct ascaridoid lineages were determined to be present among these wild carnivores sampled, including Toxocara canis in Alopex lagopus and Vulpes vulpes, Toxocara cati in Felis chaus, Prionailurus bengalensis and Catopuma temmincki and Toxascaris leonina in Canis lupus, Panthera tigris altaica, Panthera tigris amoyensis, Panthera tigris tigris, Panthera leo and Lynx lynx. Furthermore, it was evident that T. leonina lineage split into three well-supported subclades depending on their host species, i.e. wild felids, dogs and wolves and foxes, based on integrated genetic and phylogenetic evidence, supporting that a complex of T. leonina other than one species infecting these hosts. These results provide new molecular insights into classification, phylogenetic relationships and epidemiological importance of ascaridoids from wild canids and felids and also highlight the complex of the taxonomy and genetics of Toxascaris in their wild and domestic carnivorous hosts.


Diagnostic Performance of FibroTouch Ultrasound Attenuation Parameter and Liver Stiffness Measurement in Assessing Hepatic Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.
To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.


Cascade generalized predictive control strategy for boiler drum level.
This paper proposes a cascade model predictive control scheme for boiler drum level control. By employing generalized predictive control structures for both inner and outer loops, measured and unmeasured disturbances can be effectively rejected, and drum level at constant load is maintained. In addition, nonminimum phase characteristic and system constraints in both loops can be handled effectively by generalized predictive control algorithms. Simulation results are provided to show that cascade generalized predictive control results in better performance than that of well tuned cascade proportional integral differential controllers. The algorithm has also been implemented to control a 75-MW boiler plant, and the results show an improvement over conventional control schemes.


Developing oral drug delivery systems using formulation by design: vital precepts, retrospect and prospects.
Over the past few decades, the domain of drug formulations has metamorphosed from the conventional tablets and capsules to advanced and intricate drug delivery systems (DDS), both temporal and spatial. Formulation development of the oral DDS, accordingly, cannot be adequately accomplished using the traditional 'trial and error' approaches of one variable at a time. This calls for the adoption of rational, systematized, efficient and cost-efficient strategies using 'design of experiments (DoE)'. The recent regulatory guidelines issued by the key federal agencies to practice 'quality by design (QbD)' paradigms have coerced researchers in industrial milieu, in particular, to use experimental designs during drug product development. This review article describes these principles of DoE and QbD as applicable to drug delivery development using a more apt expression, that is, 'formulation by design (FbD)'. The manuscript describes the overall FbD methodology along with a summary of various experimental designs and their application in formulating oral DDS. The article also acts as a ready reckoner for FbD terminologies and methodologies. Select literature and an extensive FbD case study have been included to provide the reader with a comprehensive portrayal of the FbD precept. FbD is a holistic concept of formulation development aiming to design more efficacious, safe, economical and patient-compliant DDS. With the recent regulatory quality initiatives, implementation of FbD has now become an integral part of drug industry and academic research.


Protection against cerebral infarction by Withaferin A involves inhibition of neuronal apoptosis, activation of PI3K/Akt signaling pathway, and reduced intimal hyperplasia via inhibition of VSMC migration and matrix metalloproteinases.
Stroke is a major public health concern with high rates of morbidity and mortality worldwide. Cerebral ischemia and infarction are commonly associated with stroke. Currently used medications, though effective, are also associated with adverse effects. Development of effective neuroprotective agents with fewer side effects would be of clinical value. We evaluated the effects of Withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera, on experimentally induced cerebral infarction. The ability of WA to inhibit neuroapoptosis and modulate vascular smooth muscle cell (VSMC) migration and PI3K/Akt signaling was assessed. Separate groups of Sprague Dawley rats were subjected to cerebral occlusion and reperfused for 24h. WA treatment (25, 50 or 100mg/kg bodyweight) significantly reduced the infarct area in a carotid ligation model; WA reduced intimal hyperplasia and proliferating cell nuclear antigen (PCNA)-positive cell counts. Western blotting analysis revealed significantly suppressed PI3K/Akt signaling following cerebral ischemia/reperfusion injury. WA supplementation was found to downregulate apoptotic pathway proteins. WA suppressed PTEN and enhanced p-Akt and GSK-3β levels and elevated mTORc1, cyclinD1 and NF-κB p65 expression, suggesting activation of the PI3K/Akt pathway. In vitro studies with PDGF-stimulated A7r5 cells revealed that WA exposure severely downregulated matrix metalloproteinases (MMP)-2 and -9 and inhibited migration of A7r5 cells. Additionally, WA reduced the proliferation of A7r5 cells significantly. WA exerted neuroprotective effects by activating the PI3K/Akt pathway, modulating the expression of MMPs, and inhibiting the migration of VSMCs.


Integral microalgae-bacteria model (BIO_ALGAE): Application to wastewater high rate algal ponds.
An integral mechanistic model describing the complex interactions in mixed algal-bacterial systems was developed. The model includes crucial physical, chemical and biokinetic processes of microalgae as well as bacteria in wastewater. Carbon-limited microalgae and autotrophic bacteria growth, light attenuation, photorespiration, temperature and pH dependency are some of the new features included. The model named BIO_ALGAE was built using the general formulation and structure of activated sludge models (ASM), and it was implemented in COMSOL Multiphysics™ platform. Calibration and validation were conducted with experimental data from two identical pilot HRAPs receiving real wastewater. The model was able to simulate the dynamics of different components in the ponds, and to predict the relative proportion of microalgae (58-68% in average of total suspended solids (TSS) and bacteria (30-20% in average of TSS). Microalgae growth resulted strongly influenced by the light factor fL(I), decreasing microalgae concentrations from 40 to 60%. Furthermore, reducing the influent organic matter concentration of 50% and 70%, model predictions indicated that microalgae production increased from (8.7gTSSm-2d-1 to 13.5gTSSm-2d-1) due to the new distribution of particulate components. The proposed model could be an efficient tool for industry to predict the production of microalgae, as well as to design and optimize HRAPs.


RNA targeting by DNA binding drugs: structural, conformational and energetic aspects of the binding of quinacrine and DAPI to A-form and H(L)-form of poly(rC).poly(rG).
A key step in the rational design of new RNA binding small molecules necessitates a complete elucidation of the molecular aspects of the binding of existing molecules to RNA structures. This work focuses towards the understanding of the interaction of a DNA intercalator, quinacrine and a minor groove binder 4',6-diamidino-2-phenylindole (DAPI) with the right handed Watson-Crick base paired A-form and the left-handed Hoogsteen base paired H(L)-form of poly(rC).poly(rG) evaluated by multifaceted spectroscopic and viscometric techniques. The energetics of their interaction has also been elucidated by isothermal titration calorimetry. Results of this study converge to suggest that (i) quinacrine intercalates to both A-form and H(L)-form of poly(rC).poly(rG); (ii) DAPI shows both intercalative and groove-binding modes to the A-form of the RNA but binds by intercalative mode to the H(L)-form. Isothermal calorimetric patterns of quinacrine binding to both the forms of RNA and of DAPI binding to the H(L)-form are indicative of single binding while the binding of DAPI to the A-form reveals two kinds of binding. The binding of both the drugs to both conformations of RNA is exothermic; while the binding of quinacrine to both conformations and DAPI to the A-form (first site) is entropy driven, the binding of DAPI to the second site of A-form and H(L)-conformation is enthalpy driven. Temperature dependence of the binding enthalpy revealed that the RNA-ligand interaction reactions are accompanied by small heat capacity changes that are nonetheless significant. We conclude that the binding affinity characteristics and energetics of interaction of these DNA binding molecules to the RNA conformations are significantly different and may serve as data for the development of effective structure selective RNA-based antiviral drugs.


Interaction of stress and alcohol on discriminating fear from safety and reward in male and female rats.
Stressful events can have lasting and impactful effects on behavior, especially in terms of appropriate fear regulation and reward seeking. Our prior work in rats has shown baseline sex differences in fear expression and sucrose seeking in a discriminative reward-fear-safety conditioning task. The objectives of the current study were to determine how prior stress may affect alcohol consumption across a reward-fear-safety learning task, and how prior alcohol history may interact with stress to impact learning in this task. Male and female Long Evans rats were given home cage intermittent 24 h access to both water and alcohol for 5 weeks. A subset of rats then received exposure to stress (15 unsignaled footshocks), while remaining unstressed rats received context exposure without shock. One week later, all rats were trained on the same reward-fear-safety cue task while having continuous home cage access to both water and alcohol. All rats increased consumption (g/kg/24 h) across the 5 weeks of intermittent access, with females showing higher consumption levels. Stress exposure did not alter alcohol consumption in the week following stress, but did increase home cage alcohol consumption during later reward-fear-safety cue learning. Stress in both sexes also elevated freezing levels to the reward cue resulting in decreased sucrose seeking and was positively correlated with home cage alcohol consumption. While stress increased drinking in both males and females, the effects of stress were particularly pronounced in females, indicating our results could be capturing a higher propensity for females to display stress-induced drinking.


Brain-heart interactions are modulated across the respiratory cycle via interoceptive attention.
Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far. In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans. In Study 1, we compared HEP activity for heartbeats occurred during inhalation and exhalation in 40 volunteers at rest. We found higher HEP amplitude during exhalation, compared to inhalation, over fronto-centro-parietal areas. This suggests increased brain-heart interactions and improved cortical processing of the heartbeats during exhalation. Further analyses revealed that this effect was moderated by heart rate changes. In Study 2, we tested the respiratory phase-dependent modulation of HEP activity in 20 volunteers during Exteroceptive and Interoceptive conditions of the Heartbeat Detection (HBD) task. In these conditions, participants were requested to tap at each heartbeat, either listened to or felt, respectively. Results showed higher HEP activity and higher detection accuracy at exhalation than inhalation in the Interoceptive condition only. Direct comparisons of Interoceptive and Exteroceptive conditions confirmed stronger respiratory phase-dependent modulation of HEP and accuracy when attention was directed towards the interoceptive stimuli. Moreover, HEP changes during the Interoceptive condition were independent of heart physiology, but were positively correlated with higher detection accuracy at exhalation than inhalation. This suggests a link between optimization of cortical processing of cardiac signals and detection of heartbeats across the respiratory cycle. Overall, we provide data showing that respiration shapes cardiac interoception at the neurophysiological and behavioural levels. Specifically, exhalation may allow attentional shift towards the internal bodily states.


Dual inversion recovery ultrashort echo time (DIR-UTE) imaging and quantification of the zone of calcified cartilage (ZCC).
To develop ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques to image the zone of calcified cartilage (ZCC), and quantify its T2*, T1 and T1ρ. In this feasibility study a dual inversion recovery UTE (DIR-UTE) sequence was developed for high contrast imaging of the ZCC. T2* of the ZCC was measured with DIR-UTE acquisitions at progressively increasing TEs. T1 of the ZCC was measured with saturation recovery UTE acquisitions at progressively increasing saturation recovery times. T1ρ of the ZCC was measured with spin-locking prepared DIR-UTE acquisitions at progressively increasing spin-locking times. The feasibility of the qualitative and quantitative DIR-UTE techniques was demonstrated on phantoms and in six cadaveric patellae using a clinical 3 T scanner. On average the ZCC has a short T2* ranging from 1.0 to 3.3 ms (mean ± standard deviation = 2.0 ± 1.2 ms), a short T1 ranging from 256 to 389 ms (mean ± standard deviation = 305 ± 45 ms), and a short T1ρ ranging from 2.2 to 4.6 ms (mean ± standard deviation = 3.6 ± 1.2 ms). UTE MR based techniques have been developed for high resolution imaging of the ZCC and quantitative evaluation of its T2*, T1 and T1ρ relaxation times, providing non-invasive assessment of collagen orientation and proteoglycan content at the ZCC and the bone cartilage interface. These measurements may be useful for non-invasive assessment of the ZCC, including understanding the involvement of this tissue component in osteoarthritis.


Long-term imatinib diminishes ovarian reserve and impacts embryo quality.
Tyrosine kinase inhibitors (TKIs) such as imatinib are commonly used chemotherapeutics, but the effects of long-term treatments on reproductive outlook for cancer survivors are unknown. The purpose of this study was to examine the effects of long-term imatinib treatments on follicle development and embryo quality. Since prospective studies are not possible in healthy humans, we have incorporated a commonly used mouse model. Adult female mice were treated with daily IP injections of imatinib for 4-6 weeks. Liquid chromatography-mass spectrometry was used to measure imatinib in serum and ovarian tissues. At the end of treatments, females were superovulated and mated to yield fertilized embryos. Oocytes and embryos were collected from oviducts, assessed for development by microscopy, and fertilized embryos were cultured in vitro. Blastocysts were fixed and stained for differential cell counts. Long-term imatinib treatments caused a shift in follicle development, with imatinib-treated females having fewer primordial follicles, but an increase in primary and secondary follicles (P < 0.05). There was no effect on ovulation or fertilization rates. However, blastocysts from imatinib-treated females had fewer total cells (P < 0.05) and a significant shift from inner cell mass to increased trophectoderm cells. This pilot study indicates that long-term TKI treatments may have significant impact on ovarian reserve and embryo developmental capacity. More studies are needed in other model systems to determine the long-term impact of TKIs in patients. Knowing the potential effects of chemotherapeutics on reproductive outlook is critical for quality of life and more research is needed.


Corrigendum: Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer's disease in the preclinical stage.
[This corrects the article DOI: 10.4103/1673-5374.337053].


Retrospective analysis of safety of ultrasound-guided percutaneous liver biopsy in the 21st century.
Ultrasound-guided percutaneous liver biopsy is a standard procedure, but it might be burdened with serious adverse events, mainly hemorrhagic. Literature lacks recent studies taking into account new ultrasound machines, more sensitive to tiny vessels and the evolution of the bioptic technique, including ultrasound guidance in all instances. Hence, the primary aim of this study was to evaluate complication rates of ultrasound-guided percutaneous liver biopsy in a recent population. Secondary aims were to evaluate if the experience of operator is a determinant of risk of complication and to identify other potential risk factors. We evaluated 800 procedures carried out in one hospital in the period 2010-2018. Complication rate resulted in 4%, with the occurrence of moderate hemorrhagic complications in 0.75%. No cases of severe events or death were registered. A higher risk of bleeding was found to be associated with less experienced operators, while the need to perform multiple needle insertions increased the probability of adverse events. The present findings confirmed ultrasound-guided percutaneous liver biopsy to be a substantially safe procedure with a low risk of overall adverse events and bleeding in particular, especially when performed by expert operators.


Improving interprofessional communication: Conceptualizing, operationalizing and testing a healthcare improvisation communication workshop.
Communication errors are a leading cause of adverse events in the acute and ambulatory healthcare setting. We now understand that communication within and across professions and patients is a complex achievement with numerous barriers, including cultural, educational, and structural hurdles. Improvisation has been identified as an approach with great potential to develop communication skills for multi-disciplinary healthcare students. We report on the interdisciplinary conceptualization, operationalization, and effectiveness testing of a novel educational healthcare improvisation communication workshop. Prospective pre-post test experimental. University of California, Irvine. Total of 158 nursing, medicine, and population health students. We conceptualized improvisation through the constructs of presence, trust, and acceptance to develop workshop activities, then used the Kirkpatrick Learning Framework to test the workshop's feasibility, learning outcomes, and preliminary behavior changes. Participants rated the feasibility of the workshop highly. Pre-post workshop effectiveness testing showed significant increases in communication and collaboration competencies. Qualitative data suggested workshop activities were powerful learning modality because they were premised by introducing their conceptual underpinning and providing tangible examples via the video and debrief. Qualitative data also suggested preliminary behavior changes post workshop. We have developed and tested a communication teaching modality with strong conceptual grounding and empirical evidence of its efficacy in engaging healthcare students in collaborative communication, with documented evidence of learning that health educators can use in their courses. Future research is needed (and currently underway) to generate the evidence that the workshop can be adopted and sustained within a multi-school curriculum, which includes testing the feasibility of cross-school curriculum logistics (i.e. cross-listing the course to meet different school registrar policies, teaching workload sharing across faculty, etc.), as well as continued effectiveness testing.


Immunization with homologous oxidized low density lipoprotein reduces neointimal formation after balloon injury in hypercholesterolemic rabbits.
In this study we tested the hypothesis that immunization with homologous oxidized low density lipoprotein (oxLDL) would inhibit the neointimal response to balloon injury in hypercholesterolemic rabbits. Immunization with homologous oxLDL has been shown to markedly reduce aortic atherosclerosis in LDL receptor-deficient as well as cholesterol-fed rabbits; however, the effect of this strategy on the balloon injury-induced neointimal lesion is unknown. New Zealand White rabbits were immunized with 280 microg of homologous native LDL (n = 5), copper-oxidized LDL (n = 5) or phosphate buffer as control (n = 5) and fed a 1% cholesterol diet. Rabbits were reimmunized after 3 weeks, and balloon injury of the right ileofemoral artery was performed 1 week later. Four weeks after balloon injury, rabbits were killed, and the neointimal lesion area was measured by computerized morphometry after perfusion fixation of the arteries. Circulating antibodies against oxLDL were measured by enzyme-linked immunosorbent assay. In comparison with the control animals, those immunized with oxLDL had a 58% reduction in the neointimal area (0.53 +/- 0.13 vs. 1.27 +/- 0.26 mm2; p = 0.01). The group immunized with native LDL had a 19% reduction in the neointimal area compared with the control group (p = NS). Circulating cholesterol levels and antibody titers against oxLDL were comparable in the three groups. There was a trend toward reduced immunoreactivity for T cells and oxLDL in the neointima of oxLDL-immunized animals. Hypercholesterolemic rabbits immunized with homologous oxLDL have a markedly reduced neointimal area after balloon injury despite severe hypercholesterolemia. Together with previous work, these data suggest that an immunization strategy (vaccination) against atherosclerosis and restenosis warrants further investigation.


Modulation of epidermal growth factor receptor tyrosine phosphorylation by tumor necrosis factor.
The effects of tumor necrosis factor (TNF) on epidermal growth factor (EGF) receptor tyrosine phosphorylation were investigated in Swiss 3T3 cells, which are sensitive to TNF action. At cytotoxic levels, TNF produced an appreciable inhibition of EGF-induced autophosphorylation of the receptor. A similar inhibition was detected even after prolonged treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) which produces down-regulation of protein kinase C (PKC). According to this finding, TNF does not induce phosphorylation of the 80 kDa PKC-specific substrate. These results support the hypothesis that the inhibition of EGF receptor tyrosine phosphorylation is not mediated via stimulation of PKC activity in intact Swiss 3T3 cells.


Barriers to Completion of Research Projects Among Orthopaedic Trainees.
It is a requirement of the Australian Orthopaedic Association (AOA) training program that surgical education training (SET) trainees demonstrate competency in clinical or basic science research as part of their teaching curriculum. The aim of this study is to identify barriers in completing research by the Victorian and Tasmanian Region AOA SET trainees. We designed a short qualitative survey which was distributed to all Victorian and Tasmanian orthopaedic trainees through the AOA. The survey consisted of 18 questions most of which were based on a 5-point Likert scale with options to add comments based on individual experience. Thirty-two (61%) orthopaedic trainees responded to the survey. Two did not give consent for their data to be used. Trainees were more likely to abandon their research projects if they had insufficient time to complete a project (p = 0.01), had fewer opportunities to take part in research (p = 0.011), were unable to complete a research project within their hospital rotation (p = 0.024), and did not have access to funding (p = 0.025). A large amount of research is abandoned by trainees. The barriers to research completion are similar to those found in the literature, however, not all barriers identified in the literature were found to be barriers to the Victorian and Tasmanian Orthopaedic trainees. By identifying barriers to research completion within training programs, we hope to assist efficiency and help improve the likelihood of project completion as well as assist mentors in their guidance of trainees while conducting research.


RT-PCR for detection of all seven genotypes of Lyssavirus genus.
The Lyssavirus genus includes seven species or genotypes named 1-7. Rabies genotypes correlate with geographical distribution and specific hosts. Co-circulation of different lyssaviruses, imported cases, and the presence of unknown viruses, such as Aravan, Khujand, Irkut and West Caucasian Bat Virus, make it necessary to use generic methods able to detect all lyssaviruses. Primer sequences were chosen from conserved regions in all genotypes in order to optimise a generic RT-PCR. Serial dilutions of 12 RNA extracts from all seven Lyssavirus genotypes were examined to compare the sensitivity of the RT-PCR standardised in this study with a published RT-PCR optimised for EBLV1 detection and capable of amplifying RNA from all seven lyssaviruses. All seven genotypes were detected by both RT-PCRs, however, the sensitivity was higher with the new version of the test. Twenty samples submitted for rabies diagnosis were tested by the new RT-PCR. Eight out of 20 samples from six dogs, one horse and one bat were found positive, in agreement with immunofluorescence results. Seven samples from terrestrial mammals were genotype 1 and one from a bat was genotype 5. In conclusion, this method can be used to complement immunofluorescence for the diagnosis of rabies, enabling the detection of unexpected lyssaviruses during rabies surveillance.


A Call to Action for Philanthropy in North Carolina Health Care.
The conversation about how we create and maintain health has evolved. We have now clearly expanded our thinking beyond an exclusive focus on traditional medical care, and philanthropy can play an important role.


Renal nutrients uptake and brush-border membrane enzymes in cholesterol-fed guinea pigs.
The effect of dietary cholesterol load on the reabsorption of nutrients and the enzyme and chemical characteristics of renal brush-border membrane (BBM) was evaluated in guinea pigs. The transport of D-glucose and amino acids into the renal BBM vesicles of experimental animals was significantly (P less than 0.001) decreased. Vmax of leucine aminopeptidase decreased without alteration in Km; however, both the Km and Vmax of alkaline phosphatase and maltase decreased in renal membrane in response to cholesterol load. The alterations in the chemical architecture of the membrane could possibly be responsible for the observed aberrations in the kidneys of cholesterol-fed animals.


Generalized quasiperiodic epileptiform activity in sleep is associated with cognitive impairment in children with drug-resistant focal lesional epilepsy.
To evaluate the impact of generalized quasiperiodic epileptiform discharges ("hurdles") observed in non-rapid eye movement (NREM) sleep on cognitive function in children with intractable focal epilepsy. "Hurdles" pattern does not meet the criteria of the electrical status epilepticus in slow-wave sleep (ESES). In a retrospective analysis, 24 patients with "hurdles" and their 24 peers matched for demographic and epilepsy-related variables were compared in terms of neuropsychological domains and electroencephalography (EEG)-derived quantifiers. Both "hurdles" and controls were children between 2 and 19 years of age who had intractable focal epilepsy evaluated as candidates of resective epilepsy surgery. Full-scale intelligence quotient/developmental quotient (FSIQ/DQ) (P = .002) and visuoconstructional skills (P = .004) were significantly lower in children with "hurdles" compared to controls. Patients with "hurdles" presented with higher interictal spike indexes in sleep (P < .001, median difference -0.9, 95% confidence interval [CI] -1.4, -0.6) and wakefulness (P < .001, median difference -0.3, 95% CI -0.5, -1). Relative time of sleep spindles in NREM sleep was significantly reduced (P < .001, median difference 0.1, 95% CI 0.0, 0.1) in the "hurdles" group. The time proportion of sleep spindles represented a significant positive (P = .008) and spike index of generalized spikes in sleep a significant negative explanatory variable (P = .004) of FSIQ/DQ scores. The proportion of seizure-free patients 2 years after epilepsy surgery did not differ significantly between the two groups (P = .19). Although the "hurdles" pattern does not fulfill the criteria of ESES, it is associated with a pronounced cognitive dysfunction. Disturbed sleep structure marked by reduced sleep spindles and generalized spiking in sleep is associated with worse cognitive performance. Despite having a generalized nature, we did not find a lower probability of postsurgical seizure freedom in patients with "hurdles" pattern.


Masson tumor (intravascular papillary endothelial hyperplasia) arising in a superficial temporal artery aneurysm.
Masson tumor (intravascular papillary endothelial hyperplasia) is a rare proliferation of endothelial cells within the wall of a vessel, often thought to represent an aberrant resolution of a thrombosis. We describe the unique case of a 75-year-old man who presented to the clinic with a tender, spontaneous aneurysmal dilation of his left superficial temporal artery (STA). Only 8% of all STA aneurysms are believed to be spontaneous true aneurysms, with the majority being post-traumatic pseudoaneurysms. After successful surgical resection, pathologic examination demonstrated a Masson tumor within an STA aneurysm. This paper describes a case in which both rare entities were discovered and briefly outlines the diagnostic and therapeutic modalities available.


Molecular characteristics and clinical outcomes of elderly patients with IDH-wildtype glioblastomas: comparative study of older and younger cases in Kansai Network cohort.
Aging is a known negative prognostic factor in glioblastomas (GBM). Whether particular genetic backgrounds are a factor in poor outcomes of elderly patients with GBM warrants investigation. We aim to elucidate any differences between older and younger adult patients with IDH-wildtype GBM regarding both molecular characteristics and clinical outcomes. We collected adult cases diagnosed with IDH-wildtype GBM from the Kansai Network. Clinical and pathological characteristics were analyzed retrospectively and compared between older (≥ 70 years) and younger (≤ 50 years) cases. Included were 92 older vs. 33 younger cases. The older group included more patients with preoperative Karnofsky performance status score < 70 and had a shorter survival time than the younger group. MGMT promoter was methylated more frequently in the older group. TERT promoter mutation was more common in the older group. There were significant differences in DNA copy-number alteration profiles between age groups in PTEN deletion and CDK4 amplification/gain. In the older group, no molecular markers were identified, but surgical resection was an independent prognostic factor. Age-specific survival difference was significant in the MGMT methylated and TERT wildtype subgroup. Elderly patients have several potential factors in poor prognosis of glioblastomas. Varying molecular profiles may explain differing rates of survival between generations.


Toxic megacolon. An analysis of 70 cases.
The clinical features and outcome of 70 patients treated for toxic megacolon between 1970 and 1984 in five university-affiliated hospitals were determined. There were 35 women and 35 men with a mean age of 39 +/- 0.2 years. Toxic megacolon occurred at the initial episode of colitis in 43 patients (61 percent). Only five patients had a specific colitis: salmonellosis, two; ischemic, two; and pseudomembranous, one. Of the 65 remaining patients with nonspecific colitis, six had to be operated on without delay because of peritonitis. In the remaining 59 patients, toxic megacolon was cured with intensive medical management in nine (15 percent), improved temporarily in 14 (24 percent), and remained unchanged in 36 (61 percent). The postoperative mortality rate was 11 percent for all patients (6/56), 4 percent for patients without perforation (2/50) compared with 27 percent for patients with perforation (4/15). None of the patients who underwent surgery within five days of medical treatment died. When toxic megacolon was complicated by hemorrhage (nine patients) or peritonitis (eight patients), the mortality rate increased to 33 percent and 27 percent, respectively. A one-stage proctocolectomy was performed in 19 patients (32 percent). Of 32 patients in whom the rectum was retained, successful restoration of continuity was possible in only seven (22 percent) within 12 months after surgery. In well-selected patients, a plea is made for rectal preservation to offer an alternative to permanent ileostomy.


Family structure and obesity in early childhood.
This study informs family and child health research by using longitudinal Fragile Families data to assess how family structure and transitions are associated with changes in children's BMI and weight status between ages three and five. Concerns in family structure literature about biases due to selectivity are reduced through the use of change score models and by controlling for parental BMI. The findings indicate unhealthy BMI gain and an increased risk of becoming overweight/obese among children living with a mother who recently dissolved a union or had been living without a partner for at least 2years compared with those in stable married parent families. Children with single mothers who entered a new union had significantly healthier BMI trajectories than those whose mothers remained single or recently became single. These results suggest the importance of two-parent family contexts for children's healthy physical development, and that single mothers may need additional support to better manage their children's BMI.


Lifestyle, stress, and blood pressure in a southern black community.
The effects of lifestyle incongruity on blood pressure were examined in research in an African-American community in the southern United States. Lifestyle incongruity is defined as the extent to which a high status style of life (based on possession of material goods and exposure to mass media) exceeds an individual's occupational class. In a sample of 186 25- to 55-year-olds, higher arterial blood pressure was related to higher lifestyle incongruity, especially among persons aged 40-55. These effects were independent of perceived chronic social role stressors, a self-report diagnosis of hypertension, age, sex, body mass, and skin color. Future research should examine more closely those social and psychological factors that might moderate the risk associated with lifestyle incongruity.


Increased arterial expression of a glycosylated haptoglobin isoform after balloon dilation.
Haptoglobin is a novel cell migration factor that is expressed in arteries after sustained flow changes and involved in arterial restructuring. Arterial restructuring is the major determinant of arterial shrinkage after balloon dilation. Although the function of extrahepatic haptoglobin expression is not yet understood, local haptoglobin expression may provide the tissue with functionally different haptoglobin due to post-translational modifications. We hypothesized that haptoglobin expression is increased during arterial restructuring after balloon dilation and compared glycosylation patterns between arterial and liver haptoglobin. Arterial haptoglobin expression was studied in rabbits at 0, 2, 7, 14 and 28 days after balloon dilation (n=36) using real-time polymerase chain reaction, Western blotting and in situ hybridization. Two-dimensional gel electrophoresis and lectin affinity blotting were used to identify liver and arterial haptoglobin glycoforms. Arterial haptoglobin mRNA (5.7-fold, P=0.01) and protein levels (1.4-fold, P=0.01) were increased after balloon dilation whereas liver haptoglobin expression remained constant. Haptoglobin was expressed in the adventitia of balloon dilated rabbit arteries, which was confirmed in human atherosclerotic arteries. Comparison between liver and arterial haptoglobin demonstrated the expression of artery-specific haptoglobin glycoforms. This study demonstrates that arterial haptoglobin expression is increased early after balloon dilation whereas liver haptoglobin expression does not change. Furthermore, arterial haptoglobin consists of an unique set of glycoforms compared to haptoglobin produced in the liver.


In vitro analysis of neuron-glial cell interactions during cellular migration.
We used time-lapse microscopy to study the in vitro migration of neuronal cells from developing chick ciliary ganglion. These cells, when dissociated and cultured in a chemically defined medium, are able to migrate and to associate into clusters. We focused our attention on the study of the distribution of neuronal velocity components. Quantitative analysis of cell trajectories allowed us to demonstrate that, in many cells, velocities are well described by the Langevin equation, when deterministic components of the forces acting on the cells are taken into account. We also have shown that the majority of neurons whose movement is not purely random migrate in association with glial cells. We conclude that glial cells, by guiding neurons during migration, play an important role in the cell organization in vitro.


Paralysis of occipitofrontalis in a borderline case of leprosy.
A patient with neuritic leprosy developed borderline skin lesions. Later, another skin lesion developed on the left side of the forehead with clinical involvement of the supraorbital branch of the ophthalmic division of the trigeminal nerve. Simultaneously, paralysis of the occipitofrontalis and mild paresis of orbicularis oculi occurred.


Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987.
A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma.


Neuroprotection by JM-1232(-) against oxygen-glucose deprivation-induced injury in rat hippocampal slice culture.
JM-1232(-) (JM) is a novel isoindoline derivative with sedative and hypnotic activities that are mediated by binding to the benzodiazepine site of the Gamma-aminobutyric acid type A (GABAA) receptor. Although the neuroprotective effects of other GABAA receptor agonists are well known, there is no published report regarding JM. Thus, we examined the effects of JM on neurons exposed to oxygen-glucose deprivation (OGD) using rat hippocampal slice cultures. Hippocampal slices were assigned to either control or JM-administered groups. To assess the neuroprotective effects of JM from necrotic changes, we measured the fluorescence of propidium iodide and compared the cell mortality 24h following OGD between the control and JM-administered groups. We also verified that the effects of JM were mediated by GABAA receptors by adding flumazenil, a benzodiazepine receptor antagonist, in the same experimental settings. JM, at concentrations of 250 and 500 µM, significantly reduced cell mortality in pyramidal neurons after OGD; however, flumazenil did not inhibit this effect. To analyze more immediate effects of JM, we next measured the fluorescence of Oregon Green 488 BAPTA-1 during the OGD and re-oxygenation periods, and evaluated changes in intracellular Ca(2+) in single CA1 pyramidal neurons. JM reduced the elevation of intracellular Ca(2+) concentration during OGD, and this effect was antagonized by flumazenil. These findings indicate that JM suppressed the elevation of intracellular Ca(2+) concentration during OGD through GABAA receptors, but its neuroprotective effects from necrotic changes also involve other unknown mechanisms.


Hectogram-scale synthesis of [Aib8 , Arg34 ]-GLP-1 (7-37) by liquid-phase fragment condensation.
Based on small-scale synthesis (0.3 g), a 100-g scale-up synthesis of crude [Aib8 , Arg34 ]-glucagon-like peptide-1 (GLP-1) (7-37) was completed. The crude [Aib8 , Arg34 ]-GLP-1 (7-37) was purified using a dynamic axial compression column 200 (DAC-200). Approximately 61 g of [Aib8 , Arg34 ]-GLP-1 (7-37) with a purity of >99% was obtained through one-step reverse-phase chromatography. The purification yield was approximately 92%. The yield from the total reaction was approximately 60%. In summary, we developed an economical and environmentally friendly route to the synthesis and purification of crude [Aib8 , Arg34 ]-GLP-1 (7-37), laying a foundation for subsequent industrial production.


The effect of a wearable device prompting high school students aged 17-18 years to break up periods of prolonged sitting in class.
Increasingly, evidence shows that prolonged sedentary behavior factors into the health equation on its own, unrelated to weight and periods of intense exercise. In schools, students are required to sit for long periods of time. To investigate whether reminders (via a wearable device) to change posture, can change students' behavior and impact their subjective wellbeing. Ten students of ages 17 to 18 years at a public high school in Bellevue, Washington, USA. To monitor students' behaviors, specially designed wearable devices recorded periods of sitting, standing and moving of participants throughout the school day for one week. During the second week of the study session, reminders were given via the devices providing vibration feedback after 20 minutes of uninterrupted sitting. Subjective wellbeing was evaluated through a daily questionnaire. The reminders given by the devices were effective in changing students' behavior. Students took significantly more breaks from sitting during the week with reminders. However, changes in subjective well-being were inconclusive. The reminders were effective in changing students' behavior, demonstrating that behavior can be changed through individual feedback. Further study is required to explore benefits of such breaks on students' subjective wellbeing, but other studies suggest that such breaks improve their physical health.


Association between epicardial adipose tissue and blood pressure: A systematic review and meta-analysis.
Epicardial adipose tissue has been reported to be associated with the development of cardiometabolic disease. Whether this is true for hypertension and non-dipper blood pressure remains controversial. Here, we conducted a systemic review and meta-analysis to evaluate the association between EAT and blood pressure. Pubmed, Embase, and Web of Science were searched for relevant papers. Studies reported on the difference of EAT thickness between hypertensive and normotensive patients, or those recorded odds ratio (OR) between EAT and hypertension were included. The standard mean difference (SMD) and ORs were extracted and pooled using a random-effects model respectively. We further assessed the effect of EAT on circadian rhythm of blood pressure by combining multiple-adjusted ORs for non-dipper blood pressure. Seven studies with an overall sample of 1089 patients reported the mean difference of EAT thickness between hypertensive and normotensive patients, and the hypertensive patients had higher EAT (SMD = 1.07; 95% CI: 0.66-1.48; I2 = 89.2%) compared with controls. However, the pooled association between EAT and hypertension from two studies was not significant (OR = 1.65, 95%CI 0.62-4.68; I2 = 87.5%). The summary risk effect of EAT on non-dipper blood pressure from six studies comprising1208 patients showed that each 1 mm increment of EAT was associated with a 2.55-fold risk of non-dipper blood pressure. Hypertensive patients tend to present higher EAT thickness near the right ventricular wall and increased EAT thickness might be associated with high risk of non-dipper blood pressure. Future researches are warranted to determine the causal link between EAT and hypertension and the underlying mechanism.


Biota: sediment partitioning of aluminium smelter related PAHs and pulp mill related diterpenes by intertidal clams at Kitimat, British Columbia.
The question of polycyclic aromatic hydrocarbon (PAH) bioavailability and its relationship to specific PAH sources with different PAH binding characteristics is an important one, because bioavailability drives PAH accumulation in biota and ultimately the biochemical responses to the PAH contaminants. The industrial harbour at Kitimat (British Columbia, Canada) provides an ideal location to study the bioavailability and bioaccumulation of sediment hydrocarbons to low trophic level biota. Samples of soft shell clams (Mya arenaria) and intertidal sediment collected from multiple sites over six years at various distances from an aluminium smelter and a pulp and paper mill were analysed for 106 PAHs, plant diterpenes and other aromatic fraction hydrocarbons. Interpretation using PAH source ratios and multivariate data analysis reveals six principal hydrocarbon sources: PAHs in coke, pitch and emissions from anode combustion from the aluminium smelter, vascular plant terpenes and aromatised terpenes from the pulp and paper mill, petroleum PAHs from shipping and other anthropogenic activities and PAHs from natural plant detritus. Harbour sediments predominantly contain either pitch or pyrogenic PAHs from the smelter, while clams predominantly contain plant derived PAHs and diterpenes from the adjacent pulp mill. PAHs from the smelter have low bioavailability to clams (Biota-Sediment Accumulation Factors; BSAFs <1 for pitch and coke; <10 for anode combustion, decreasing to ∼0.1 for the mass 300 and 302 PAHs), possibly due to binding to pitch or soot carbon matrices. Decreases in PAH isomer ratios between sediments and clams likely reflect a combination of variation in uptake kinetics of petroleum PAHs and compound specific metabolism, with the importance of petroleum PAHs decreasing with increasing molecular weight. Plant derived compounds exhibit little natural bioaccumulation at reference sites, but unsaturated and aromatised diterpenes released from resins by industrial pulping processes are readily accumulated by the clams (BSAFs >500). Thus while most of the smelter associated PAHs in sediments may not be bioavailable to benthic organisms, the plant terpenes (including retene, totarol, ferruginol, manool, dehydroabietane and other plant terpenes that form the chemical defence mechanism of conifers) released by pulp mills are bioavailable and possess demonstrated toxic properties. The large scale release of plant terpenes by some of the many pulp mills located in British Columbia and elsewhere represents a largely undocumented risk to aquatic biota.


Perceptual learning for speech: Is there a return to normal?
Recent work on perceptual learning shows that listeners' phonemic representations dynamically adjust to reflect the speech they hear (Norris, McQueen, & Cutler, 2003). We investigate how the perceptual system makes such adjustments, and what (if anything) causes the representations to return to their pre-perceptual learning settings. Listeners are exposed to a speaker whose pronunciation of a particular sound (either /s/ or /integral/) is ambiguous (e.g., halfway between /s/ and /integral/). After exposure, participants are tested for perceptual learning on two continua that range from /s/ to /integral/, one in the Same voice they heard during exposure, and one in a Different voice. To assess how representations revert to their prior settings, half of Experiment 1's participants were tested immediately after exposure; the other half performed a 25-min silent intervening task. The perceptual learning effect was actually larger after such a delay, indicating that simply allowing time to pass does not cause learning to fade. The remaining experiments investigate different ways that the system might unlearn a person's pronunciations: listeners hear the Same or a Different speaker for 25 min with either: no relevant (i.e., 'good') /s/ or /integral/ input (Experiment 2), one of the relevant inputs (Experiment 3), or both relevant inputs (Experiment 4). The results support a view of phonemic representations as dynamic and flexible, and suggest that they interact with both higher- (e.g., lexical) and lower-level (e.g., acoustic) information in important ways.


A randomized trial of race-related stress among African Americans with chronic kidney disease.
African Americans progress from early to late-stage chronic kidney disease (CKD) at a rate that is three times that of Whites. Given research that implicates social stress in poor kidney outcomes, there is a need to examine whether race-related stress contributes to these disparities. Through experimental manipulation, this study sought to determine whether acute race-related stress was associated with autonomic arousal and an inflammatory marker, which are well-established pathways to poor kidney outcomes. Further we tested the hypothesis that expectations of racism may moderate this relationship. Fifty-two African American patients along the CKD continuum were randomized to recall a general or race-related stressful experience. Before, during, and after the recall, patients' blood pressure and Interleukin-6 (IL-6) were monitored. Prior to the experimental manipulation, participants completed self-reported measures of expectations of racism. Across both study conditions, change in self-reported distress from baseline to stress was associated with both systolic and diastolic reactivity (both ps <.01), but not change in IL-6 responses (all ps > 0.05). A significant interaction revealed that those who were randomized to recall a race-related stressor demonstrated less diastolic blood pressure reactivity (F=4.80, p<.05) if they scored lower in expectations of racism as compared to those who scored high. Moreover, those who were randomized to the race-related stressor demonstrated greater increase in IL-6 from 45 to 90 min post-recall than those who recalled a general stressor (F=6.35, p<.05). Acute race-related stress may be associated with autonomic arousal and inflammatory response among African American patients along the CKD continuum, suggesting the need to further understand its role in racial disparities in CKD progression.


Octreotide's role in the management of sulfonylurea-induced hypoglycemia.
The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published from 1965 to 2008 using combinations of the terms octreotide, antidote, sulfonylurea, overdose, poisoning, and toxicity was performed. References from identified articles were reviewed for additional sources. Animal studies, case reports, case series, and randomized controlled trials were evaluated. An animal model of sulfonylurea overdose demonstrates that octreotide reduces the number of refractory sulfonylurea-induced hypoglycemic episodes. Published case reports describe the use of octreotide to prevent recurrent hypoglycemia after sulfonylurea overdose. A retrospective case series demonstrates that administration of octreotide decreases the need for supplemental dextrose boluses as well as hypoglycemic events. Two prospective, controlled trials determined that octreotide and supplemental dextrose increase blood glucose concentrations with fewer hypoglycemic events. Based on animal and human data, there is sufficient evidence to recommend the use of octreotide with supplemental dextrose for the treatment of sulfonylurea-induced hypoglycemia.


Non-melanoma Skin Cancer Treated by Contact High-dose-rate Radiotherapy (Brachytherapy): A Mono-institutional Series and Literature Review.
Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules. All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources. Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%. cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.


Shared Decision Making in an Integrated Mental Health and Vocational Rehabilitation Intervention: Stakeholder Practices and Experiences.
A Danish integrated mental health care and vocational intervention was developed to support the return-to-work process for people with common mental disorders. Shared decision making was a core element of the intervention to ensure a person-centred approach. The study aim is to describe how shared decision making was practiced and experienced and to discuss its potential in this integrated care context. Shared decision making practice and experience was studied in participant observation (n = 20), interviews (n = 12), focus groups interviews (n = 2), and shared plan documents (n = 12). Research methods and analyses were guided by theoretically defined ideals of shared decision making. Shared decision making constituted a general value rather than a structured method in practice. Clients experienced a more person-centred collaboration with professionals, compared to the regular vocational system. Contextual factors regarding vocational legislation and the intervention design influenced the decision latitude. Shared decision making has the potential to support a person-centred approach in integrated services. However, we recommend clarifying decisions applicable for shared decision making, to ensure thorough training, develop and test decision aids, and ensure supportive organisational conditions for shared decision making in interprofessional collaboration.


Pembrolizumab for metastatic adrenocortical carcinoma with high mutational burden: Two case reports.
In the setting of metastatic or locally advanced adrenocortical carcinoma, a limited number of therapies are available and their efficacy is generally below modest. The backbone of treatment remains surgery, even for metastatic disease, whenever it is possible, and mitotane. Chemotherapy can be used with limited results. A small subset of patients with adrenocortical carcinoma may have high mutational burden and harbor mutations in mismatch-repair genes. We report a 40-year old and a 28-year-old female patients with metastatic adrenocortical carcinoma refractory to multiple treatments. Next-generation sequencing detected high mutational burden (>10 mutations/megabase) in both patients, one of them with MSH2 mutation. They were treated with pembrolizumab (100 to 200 mg every 3 weeks). The patient harboring a MSH2 mutation experienced a long-term complete response after pembrolizumab, while the patient with high mutational burden and absence of mismatch repair deficiency did not have any response. To the best of our knowledge, this is the first report in the literature of a durable complete response after pembrolizumab in a patient with metastatic adrenocortical carcinoma. Differences in therapy sequencing, possibly abscopal effect related to multiple previous radiotherapy exposition, predictive values of high mutational burden and mutations in mismatch-repair genes are discussed.


IBIsCO: a molecular dynamics simulation package for coarse-grained simulation.
IBIsCO is a parallel molecular dynamics simulation package developed specially for coarse-grained simulations with numerical potentials derived by the iterative Boltzmann inversion (IBI) method (Reith et al., J Comput Chem 2003, 24, 1624). In addition to common features of molecular dynamics programs, the techniques of dissipative particle dynamics (Groot and Warren, J Chem Phys 1997, 107, 4423) and Lowe-Andersen dynamics (Lowe, Europhys Lett 1999, 47, 145) are implemented, which can be used both as thermostats and as sources of friction to compensate the loss of degrees of freedom by coarse-graining. The reverse nonequilibrium molecular dynamics simulation method (Müller-Plathe, Phys Rev E 1999, 59, 4894) for the calculation of viscosities is also implemented. Details of the algorithms, functionalities, implementation, user interfaces, and file formats are described. The code is parallelized using PE_MPI on PowerPC architecture. The execution time scales satisfactorily with the number of processors.


Ultrasound diagnosis of a twin gestation with concordant body stalk anomaly. A case report.
Concordant body stalk anomaly in an 18-week twin gestation was diagnosed by ultrasound and confirmed by pathologic examination after elective termination of pregnancy. The ultrasonographic presentation of this rare anomaly and its embryogenesis are discussed.


Injuries Among Immigrants Treated in Primary Care in Madrid, Spain.
This study compared the injury incidence rates by sex in adult immigrant and native population attended in primary care in the Community of Madrid, Spain. Cross-sectional study of injuries registered in the primary care electronic medical record in 2012. Crude and age-adjusted incidence rates by sex, region of birth and type of injury were calculated. Poisson regression was performed. In both sexes, the highest crude injury incidence rate was found in immigrants from North Africa, followed by the native population. After controlling for age and socioeconomic-status, the highest risk of injury in immigrants was observed in burns in women from North-African (79%) and in foreign body injuries in men from Latin America and Caribbean, Sub-Saharan and North Africa and Central and Eastern Europe (61-123%). The analysis by region of origin has identified people from North Africa as a particularly vulnerable group.


MRF: a tool to overcome the barrier of inconsistent genome annotations and perform comparative genomics studies for the largest animal DNA virus.
The genome of the largest known animal virus, the white spot syndrome virus (WSSV) responsible for huge economic losses and loss of employment in aquaculture, suffers from inconsistent annotation nomenclature. Novel genome sequence, circular genome and variable genome length led to nomenclature inconsistencies. Since vast knowledge has already accumulated in the past two decades with inconsistent nomenclature, the insights gained on a genome could not be easily extendable to other genomes. Therefore, the present study aims to perform comparative genomics studies in WSSV on uniform nomenclature. We have combined the standard mummer tool with custom scripts to develop missing regions finder (MRF) that documents the missing genome regions and coding sequences in virus genomes in comparison to a reference genome and in its annotation nomenclature. The procedure was implemented as web tool and in command-line interface. Using MRF, we have documented the missing coding sequences in WSSV and explored their role in virulence through application of phylogenomics, machine learning models and homologous genes. We have tabulated and depicted the missing genome regions, missing coding sequences and deletion hotspots in WSSV on a common annotation nomenclature and attempted to link them to virus virulence. It was observed that the ubiquitination, transcription regulation and nucleotide metabolism might be essentially required for WSSV pathogenesis; and the structural proteins, VP19, VP26 and VP28 are essential for virus assembly. Few minor structural proteins in WSSV would act as envelope glycoproteins. We have also demonstrated the advantage of MRF in providing detailed graphic/tabular output in less time and also in handling of low-complexity, repeat-rich and highly similar regions of the genomes using other virus cases. Pathogenic virus research benefits from tools that could directly indicate the missing genomic regions and coding sequences between isolates/strains. In virus research, the analyses performed in this study provides an advancement to find the differences between genomes and to quickly identify the important coding sequences/genomes that require early attention from researchers. To conclude, the approach implemented in MRF complements similarity-based tools in comparative genomics involving large, highly-similar, length-varying and/or inconsistently annotated viral genomes.


Identification of an O-linked repetitive glycan chain of the polar flagellum flagellin of Azospirillum brasilense Sp7.
This is the first report to have identified an O-linked repetitive glycan in bacterial flagellin, a structural protein of the flagellum. Studies by sugar analysis, Smith degradation, (1)H and (13)C NMR spectroscopy, and mass spectrometry showed that the glycan chains of the polar flagellum flagellin of the plant-growth-promoting rhizobacterium Azospirillum brasilense Sp7 are represented by a polysaccharide with a molecular mass of 7.7 kDa, which has a branched tetrasaccharide repeating unit of the following structure:


Melanocyte-stimulating hormone affects melanogenic differentiation of quail neural crest cells in vitro.
Quail neural crest cells were treated in vitro with alpha-melanocyte-stimulating hormone (alpha-MSH) or dibutyryl cyclic AMP (dbcAMP) plus theophylline. These treatments increased the proportion of melanocytes to total cells in crest cell outgrowth cultures. Pigmentation of neural crest cell clusters proceeded more rapidly when cultures were treated with alpha-MSH or dbcAMP plus theophylline than when untreated. In clonal cell cultures, the proportion of pigmented colonies to total colonies was increased by MSH treatment. From these results, MSH seems not only to accelerate melanogenic differentiation but also to affect the state of commitment of neural crest cells to melanogenic differentiation in vitro, and this action of MSH appears to be mediated by cAMP.


Model-based evidence for the relevance of microbial community variability to the efficiency of the anaerobic reductive dechlorination of TCE.
The composition of mixed dechlorinating communities varies considerably in field and laboratory conditions. Dechlorinators thrive alongside with distinctive populations that help or hinder dechlorination. The variability of the composition of dechlorinating communities inevitably precludes a firm consensus regarding the optimal strategies for biostimulation. This lack of consensus motivated a model-based approach for the investigation of how the variability of the composition of a microbial community impacts the electron donor supply strategies for accelerating chloroethene removal. To this end, a kinetic model accounting for dechlorination in conjunction with cooperative and competing processes was developed. Model parameters were estimated using a multi-experiment, multi-start algorithm and data from research previously performed with two generations of a methane-producing, Dehalococcoides mccartyi-dominated consortium. The two generations of the consortium functioned comparably under maintenance conditions but performed divergently under high electron donor surpluses. The multi-experiment, multi-start algorithm overcame the hurdles of poor parameter identifiability and offered a probable cause for the different behaviors exhibited by each of the two generations of the chloroethene-degrading consortium: modest differences in the make-up of non-dechlorinators, which were minority populations, significantly influenced the fate of the offered electron donor.


Single kidney and ureteral atresia in a newborn girl: a treatment concept.
To demonstrate a rare case of urological pathology, we report a combination of a single kidney and ureteral atresia. The treatment concept and outcome are outlined. Antenatal ultrasound had revealed urinary ascites which lead to caesarean section in the 34th gestational week. Persisting anuria was confirmed postnatally and peritoneal dialysis started on the second day of life. Subsequent laparotomy revealed ureteral atresia after 3 cm of patent ureter. We created an ileum conduit after discussing various other therapeutic options. A follow up of 12 months has shown steady function of the stoma with stable renal parameters. An ileal conduit represents a good option if high drainage is necessary in early childhood.


In vitro antifungal activity of epigallocatechin 3-O-gallate against clinical isolates of dermatophytes.
Previously, we reported that epigallocatechin 3-O-gallate (EGCg) has growth-inhibitory effect on clinical isolates of Candida species. In this study, we investigated the antifungal activity of EGCg and antifungal agents against thirty-five of dermatophytes clinically isolated by the international guidelines (M38-A2). All isolates exhibited good susceptibility to EGCg (MIC₅₀, 2-4 μg/mL, MIC₉₀, 4-8 μg/mL, and geometric mean (GM) MICs, 3.36-4 μg/mL) than those of fluconazole (MIC₅₀, 2-16 μg/mL, MIC₉₀, 4-32 μg/mL, and GM MICs, 3.45-25.8 μg/mL) and flucytosin (MIC₅₀, MIC₉₀, and GM MICs, >64 μg/mL), although they were less susceptible to other antifungal agents, such as amphotericin B, itraconazole, and miconazole. These activities of EGCg were approximately 4-fold higher than those of fluconazole, and were 4 to 16-fold higher than flucytosin. This result indicates that EGCg can inhibit pathogenic dermatophyte species. Therefore, we suggest that EGCg may be effectively used solely as a possible agent or combined with other antifungal agents for antifungal therapy in dermatophytosis.


Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia.
Because of its long latency, slow growing nature, and high prevalence, prostate cancer is the best model for chemoprevention. High-grade prostate intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer. Chemoprevention with lycopene has shown definite results in prostate cancer. We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing prostate cancer from developing in this vulnerable group of patients. A total of 40 patients with HGPIN were randomized into 2 groups: one received 4 mg lycopene twice a day for one year, and the other was periodically followed up. Total follow-up was one year. Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an inverse relationship between lycopene and prostate-specific antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for a longer period without any adverse reaction. Lycopene is an effective chemopreventive agent in the treatment of HGPIN, with no toxicity and good patient tolerance.


[Growth and regeneration of the eye of the larvae ofAeshna cyanea Müll. (Odonata, Anisoptera)].
The growth of the eye inAeshna cyanea has been studied by several experiments involving removal, regeneration and heterotopic grafts.The results show that the ommatidia do not develop from any stemcells that are permanent during the whole larval life. In fact the ommatidia grow by progressive recruitment of vertex epidermal cells on a level with a transitory zone (the eye budding zone) which progress through this epidermis.The eye budding zone regenerates only from the competent cells of the vertex in contact with differentiated ommatidia. Contact between ommatidia and epidermal cells from another area does not allow regeneration of the eye.The results are discussed and we propose an hypothesis explaining the larval eye's growth by means of these findings on its regeneration.


Sex-specific gene expression patterns in head and neck squamous cell carcinomas.
The head and neck squamous cell carcinomas (HNSCCs) have higher incidence rates in men, but the reasons are still obscure. This study aimed to investigate the sex-specific gene expression patterns and predict the regulatory mechanisms. Data including clinical, survival, RNA-seq, miRNA, and methylation information were derived from The Cancer Genome Atlas (TCGA). A total of 131 paired male and female cases were included based on propensity score matching. We concentrated on the prognostic values of the sex-specific pathways enriched by differentially expressed genes (DEGs) and predicted the potential regulatory mechanisms from immune cell infiltration, ceRNA regulatory network, methylation, and differential coexpression analysis. Compared with females, males exhibited a lower activity of immune-related functions and higher activities of mitochondrial and ubiquitination functions. The pathway activities were associated with the prognosis of males but less relevant to females. We extracted eight pathways with sex-biased survival patterns, of which five were about down-regulated immune functions, and three were up-regulated pathways (GTP biosynthetic, DNA polymerase, and spliceosomal complex assembly). The five immune pathways were moderately or strongly correlated with the proportion of macrophages. We identified six over-expressed lncRNAs that might be involved in the regulation of the three up-regulated pathways. These lncRNAs exhibited a lower methylation density in males, which might account for their over-expression. For HNSCCs, males were characterized by immunosuppression. It was a sign of unfavorable prognosis and might be associated the proportion of macrophages. LncRNAs and methylation might be involved in the regulation of these pathways.


Diffusion of microcystins (cyanobacteria hepatotoxins) from the reservoir of Isahaya Bay, Japan, into the marine and surrounding ecosystems as a result of large-scale drainage.
In the artificial reservoir of the Isahaya reclaimed land, Nagasaki, Japan, algal blooms have become an annual event, dominated primarily by the microcystin (MC) producing cyanobacteria Microcystis aeruginosa. Although the majority of MCs are either degraded by bacteria or washed out to sea, some remain in the sediment of the reservoir and bay throughout the year. As a result, they also accumulate in aquatic organisms (mullet, oyster, etc.) that inhabit the reservoir and surrounding areas, as well as midge flies that spend their larval period in the bottom of the reservoir. Accordingly, MCs also accumulate in the predators of these organisms, allowing the toxin to spread from the hydrosphere to terrestrial ecosystems. The most effective method for resolving this potentially dangerous condition is to introduce seawater into the reservoir by opening the drainage gates at high tide.


Cystic metastatic cerebral neuroblastoma.
Intracerebral neuroblastoma is an exceedingly rare manifestation of intracranial neuroblastoma and has been described as a solid lesion. Cystic metastatic intracerebral neuroblastoma has not been described. We report a case of histologically proven metastatic intracerebral neuroblastoma presenting in a cystic form 1 year after diagnosis and treatment of a solid intra-abdominal neuroblastoma. The imaging and clinical appearance of this case was indistinguishable from that of intracerebral cystic lesions caused by infection or inflammation. It has been suggested that, due to more aggressive treatment of neuroblastoma, patients are surviving longer and consequently intracranial involvement is becoming more frequent. It is important to be aware of this cystic manifestation of the disease.


Long-term metal fume exposure assessment of workers in a shipbuilding factory.
This study aims to assess the metal fume exposure of welders and to determine exposure rates for similar exposure groups in a shipyard through the use of Near-field/Far-field (NF/FF) mathematical model and Bayesian decision analysis (BDA) technique. Emission rates of various metal fumes (i.e., total chromium (Cr), iron (Fe), lead (Pb), manganese (Mn), and nickel (Ni)) were experimentally determined for the gas metal arc welding and flux cored arc welding processes, which are commonly used in shipyards. Then the NF/FF field model which used the emission rates were further validated by welding simulation experiment, and together with long-term operation condition data obtained from the investigated shipyard, the predicted long-term exposure concentrations of workers was established and used as the prior distribution in the BDA. Along with the field monitoring metal fume concentrations which served as the likelihood distribution, the posterior decision distributions in the BDA were determined and used to assess workers' long-term metal exposures. Results show that the predicted exposure concentrations (Cp) and the field worker's exposure concentrations (Cm) were statistically correlated, and the high R2 (= 0.81-0.94) indicates that the proposed surrogate predicting method by the NF and FF model was adequate for predicting metal fume concentrations. The consistency in both prior and likelihood distributions suggests the resultant posterior would be more feasible to assess workers' long-term exposures. Welders' Fe, Mn and Pb exposures were found to exceed their corresponding action levels with a high probability (= 54%), indicating preventive measures should be taken immediately. The proposed approach provides a universal solution for conducting exposure assessment with usual limited number of personal exposure data.


Off-on phosphorescence assay of heparin via gold nanoclusters modulated with protamine.
A sensitive and selective phosphorescence "turn-off-on" nanosensor to detect heparin by gold nanoclusters (Au-NCs) modulated with protamine was developed. The carboxyl groups on the surface of Au-NCs can interact with amino groups in protamine via electrostatic interactions and hydrogen bonding to induce the aggregation of Au-NCs, which results in the photoluminescence to "turn-off". However, in the presence of heparin, protamine prefers to combine with heparin to release Au-NCs, which results in the photoluminescence to "turn-on". The photoluminescence lifetime measurements demonstrate that the photoluminescence belongs to phosphorescence, and that the quenching progress is dynamic. The concentration of heparin can be determined by measuring the Au-NCs phosphorescence recovery. The linear response range was obtained from 0.006 to 25.0 μg mL(-1) with the detection limit of 6 ng mL(-1). Moreover, the proposed phosphorescence nanosensor was used to detect heparin in fetal bovine serum samples with satisfactory results.


Marinobacterium alkalitolerans sp. nov., with nitrate reductase and urease activity isolated from green algal mat collected from a solar saltern.
A novel Gram-staining-negative, rod-shaped, 0.6-0.8 µm wide and 2.0-3.0 µm in length, motile bacterium designated strain AK62T, was isolated from the green algal mat collected from saltpan, Kakinada, Andhra Pradesh, India. Colonies on ZMA were circular, off-white, shiny, moist, translucent, 1-2 mm in diameter, flat, with an entire margin. The major fatty acids include C16:0, C18:1 ω7c, and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c and/or iso-C14:0 3-OH). Polar lipids include diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid, three unidentified phospholipids, and one unidentified lipid. Polyamine includes Spermidine. The DNA G + C content of the strain AK62T was 58.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain AK62T was closely related to the type strains Marinobacterium sediminicola, Marinobacterium coralli and Marinobacterium stanieri with a pair-wise sequence similarity of 96.9, 96.6 and 96.6%, respectively, forming a distinct branch within the genus Marinobacterium and clustered with M. stanieri, M. sediminicola, M. coralli and M. maritimum cluster. Strain AK62T shares average nucleotide identity (ANIb, based on BLAST) of 78.44, 76.69, and 76.95% with M. sediminicola CGMCC 1.7287T, M. stanieri DSM 7027T, and Marinobacterium halophilum Mano11T respectively. Based on the observed phenotypic, chemotaxonomic characteristics, and phylogenetic analysis, strain AK62T is described in this study as a novel species in the genus Marinobacterium, for which the name Marinobacterium alkalitolerans sp. nov. is proposed. The type strain of M. alkalitolerans is AK62T (= MTCC 12102T = JCM 31159T = KCTC 52667T).


Maternal reactions to a child with epilepsy: Depression, anxiety, parental attitudes and family functions.
The goal of this study was to investigate how the disease and treatment of epilepsy affected the psychological profile (depression and anxiety) of mothers whose children had epilepsy, as well as these mothers' attitudes towards their children and their family relationships. Both the case and control groups consisted of 50 children and their mothers. All mothers were asked to complete the Beck Depression Inventory, State-Trait Anxiety Inventory, Parental Attitude Research Instrument and Family Assessment Device. Mothers whose children had epilepsy scored significantly higher in depression and state anxiety compared to the mothers of the control group. The mothers of children diagnosed with epilepsy also failed to develop supportive and friendly relationships with their children. In addition, these mothers scored significantly higher in the Attitude of Hostility and Rejection, Marital Discordance and Authoritarian Attitude as compared to the mothers of the control group. This cross-sectional study demonstrated that, for the mothers of children who had epilepsy, the illness might have an adverse effect on their lives and their family relationships.


Photoprotection and skin irritation effect of hydrogels containing hydroalcoholic extract of red propolis: A natural pathway against skin cancer.
The use of natural products in sunscreen formulations as a prophylactic measure against skin cancer is receiving special attention attributed to the photoprotective and antioxidant properties of their chemical components. In this work, we describe the development of topical hydrogel formulations containing hydroalcoholic extract of red propolis (HERP), and the evaluation of the dermal sensitizing effect of the developed products. Sunscreen formulations composed of HERP in different concentrations (1.5, 2.5 or 3.5% w/w) alone or in combination with a chemical (octyl methoxycinnamate) and/or physical (titanium dioxide) filters were developed using poloxamer 407 as gel basis. The preliminary and accelerated stability tests, texture analysis and spreadability tests were performed. All formulations revealed to be stable in preliminary stability assessment. The formulations containing HERP 1.5 and 2.5% alone or associated with the filters showed intense modifications during accelerated stability test, which were confirmed by rheological analyses. The incorporation of HERP and filters in the poloxamer hydrogel decreased the toughness of product (p < 0.05) and the formulation containing HERP alone presented the lowest adhesivity (p < 0.001). The incorporation of HERP in the hydrogel decreased the poloxamer transition temperature, showing different rheological behavior with the increase of HERP concentration. The developed formulations were stable, exhibited non-Newtonian and pseudoplastic behavior, showing in vivo skin compatibility and no skin irritancy.


Review article: prevention, diagnosis and management of COVID-19 in the IBD patient.
The current COVID-19 pandemic, caused by SARS-CoV-2, has emerged as a public health emergency. All nations are seriously challenged as the virus spreads rapidly across the globe with no regard for borders. The primary management of IBD involves treating uncontrolled inflammation with most patients requiring immune-based therapies. However, these therapies may weaken the immune system and potentially place IBD patients at increased risk of infections and infectious complications including those from COVID-19. To summarise the scale of the COVID-19 pandemic, review unique concerns regarding IBD management and infection risk during the pandemic and assess COVID-19 management options and drug interactions in the IBD population. A literature review on IBD, SARS-CoV-2 and COVID-19 was undertaken and relevant literature was summarised and critically examined. IBD patients do not appear to be more susceptible to SARS-CoV-2 infection and there is no evidence of an association between IBD therapies and increased risk of COVID-19. IBD medication adherence should be encouraged to prevent disease flare but where possible high-dose systemic corticosteroids should be avoided. Patients should exercise social distancing, optimise co-morbidities and be up to date with influenza and pneumococcal vaccines. If a patient develops COVID-19, immune suppressing medications should be withheld until infection resolution and if trial medications for COVID-19 are being considered, potential drug interactions should be checked. IBD patient management presents a challenge in the current COVID-19 pandemic. The primary focus should remain on keeping bowel inflammation controlled and encouraging medication adherence.