Outcomes After Neuraxial or Regional Anaesthesia Instead of General Anaesthesia for Lower Limb Revascularisation Surgery: A Systematic Review and Meta-Analysis of Randomised and Non-Randomised Studies.
To determine whether receipt of neuraxial or regional anaesthesia instead of general anaesthesia for lower limb revascularisation surgery affects patient outcomes. MEDLINE, EMBASE, Evidence Based Medicine Reviews, and Google Scholar. After protocol registration, the data sources were searched for randomised and non-randomised studies comparing neuraxial or regional anaesthesia with general anaesthesia for lower limb revascularisation surgery in adults. Two investigators independently selected articles, extracted data, and assessed risks of bias. Data were pooled using random effects models. GRADE was used to assess certainty in cumulative evidence. From 10 755 citations identified, five randomised (n = 970) and 13 non-randomised (n = 96 800) studies were included. Use of neuraxial instead of general anaesthesia for lower limb revascularisation surgery was associated with no statistically significant reduction in short term (in hospital or 30 day) mortality in randomised studies (pooled odds ratio [OR] 0.77; 95% confidence interval [CI] 0.33 - 1.81; low certainty) and a statistically significant reduction in adjusted short term mortality in non-randomised studies (pooled OR 0.67; 95% CI 0.56 - 0.81; low certainty). Adults allocated to neuraxial anaesthesia in randomised studies had fewer pulmonary complications (pooled OR 0.35; 95% CI 0.16 - 0.76; low certainty). In non-randomised studies, neuraxial instead of general anaesthesia was associated with a lower adjusted odds of any morbidity (pooled OR 0.66; 95% CI 0.52 - 0.84), cardiac complications (pooled OR 0.68; 95% CI 0.58 - 0.79), pneumonia (pooled OR 0.81; 95% CI 0.64 - 1.02), prolonged mechanical ventilation (OR 0.09; 95% CI 0.002 - 0.55), and bypass graft thrombosis (OR 0.70; 95% CI 0.59 - 0.85), as well as a shorter operative duration (low certainty for all). Use of a nerve block instead of general anaesthesia was associated with a lower adjusted odds of delirium (OR 0.16; 95% CI 0.06 - 0.42) and a shorter operative duration (low certainty for both). Randomised and non-randomised data suggest that neuraxial anaesthesia for lower limb revascularisation surgery reduces morbidity and possibly mortality. Until randomised trials with a low risk of bias become available, this study supports use of neuraxial anaesthesia for these procedures where appropriate.


Stimulation of glucose transport by semicarbazide-sensitive amine oxidase activity in adipocytes from diabetic rats.
Semicarbazide-sensitive amine oxidase (SSAO) is highly expressed in adipose cells, and substrates of SSAO such as benzylamine in combination with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 recruitment in mouse 3T3-L1 adipocytes and in isolated rat adipocytes. Here we examined whether this combination of molecules also stimulates glucose transport in adipocytes from streptozotocin-induced diabetic rats and from Goto-Kakizaki diabetic rats. As previously reported, adipocytes obtained from streptozotocin-induced diabetic rats, showed a reduced stimulation of glucose transport in response to insulin. Under these conditions, the combination of benzylamine and vanadate caused a marked stimulation of glucose transport that was similar to the stimulation detected in control adipocytes. Adipocytes isolated from Goto-Kakizaki diabetic rats also showed a defective response to insulin; however, acute incubation in the presence of benzylamine and vanadate stimulated glucose transport in these cells to the same extent than in adipocytes from non-diabetic rats. These data indicate that adipocytes obtained from two different models of animal diabetes do not show resistance to the activation of glucose transport by SSAO activity, which is in contrast to the well reported resistance to insulin action. It seems to suggest that SSAO activity in combination with vanadate triggers a glucose transport-activating intracellular pathway that remains intact in the diabetic state. Further, our data support the view that the combination of benzylamine and vanadate could be an effective therapy in diabetes.


Efficacy of laser-assisted uvulopalatoplasty in obstructive sleep apnea.
Laser-assisted uvulopalatoplasty (LAUP) enlarges the oropharyngeal airway by reshaping the uvula, soft palate, and tonsillar pillars. In contrast to a uvulopalatopharyngoplasty performed in the operating room, LAUP is staged over several office visits, is less costly, is bloodless, and is not associated with velopharyngeal insufficiency or stenosis. Previous studies have documented the efficacy of LAUP in the treatment of snoring. We explore the efficacy of LAUP in the treatment of obstructive sleep apnea. Forty-eight patients comprised the study group. Each patient snored, exhibited >50% palatal collapse on Müller's maneuver, and had nocturnal polysomnography showing a respiratory disturbance index (RDI) >10. Each patient underwent LAUP until he or she reported that snoring had ceased. Of the 29 patients who underwent post-LAUP nocturnal polysomnography, 7 had RDIs <10, oxygen saturation >86%, and no cardiac arrhythmias. LAUP reduced RDI to <10 in patients with pre-LAUP apnea indexes <3 (P = 0.05) or pre-LAUP RDIs <30 (P = 0.01). The following variables did not correlate with the success of LAUP in treating obstructive sleep apnea: age, sex, pre-LAUP weight, pre-LAUP body mass index, perioperative weight change, perioperative body mass index change, pre-LAUP snoring, and post-LAUP snoring. We conclude that LAUP is an effective means of treating patients with RDIs <30.


The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern.
We have identified a Drosophila zinc-finger protein, which binds to a number of sites in the transcriptional control regions of the pair-rule gene fushi-tarazu (ftz). The expression pattern of the mRNA that encodes this protein is essentially complementary to that of ftz both prior to blastoderm formation and during germband extension. We propose that the protein may function by repressing inappropriate segmentation gene transcription during embryogenesis. The gene encoding this ftz promoter-binding protein has been named tramtrack (ttk).


Clinical symptoms of SARS-CoV-2 breakthrough infection during the Omicron period in relation to baseline immune status and booster vaccination-A prospective multicentre cohort of health professionals (SURPRISE study).
The effects of different types of pre-existing immunity on the frequency of clinical symptoms caused by the SARS-CoV-2 breakthrough infection were prospectively assessed in healthcare workers during the Omicron period. Among 518 participants, hybrid immunity was associated with symptom reduction for dizziness, muscle or limb pain and headache as compared to vaccination only. Moreover, the frequencies of dizziness, cough and muscle or limb pain were lower in participants who had received a booster vaccine dose. Thus, hybrid immunity appeared to be superior in preventing specific symptoms during breakthrough infection compared to vaccination alone. A booster vaccine dose conferred additional symptom reduction.


The intracellular mechanism of action on Escherichia coli of BF2-A/C, two analogues of the antimicrobial peptide Buforin 2.
In the present study, the antimicrobial peptides BF2-A and BF2-C, two analogues of Buforin 2, were chemically synthesized and the activities were assayed. To elucidate the bactericidal mechanism of BF2-A/C and their different antimicrobial activities, the influence of peptides to E. coli cell membrane and targets of intracellular action were researched. Obviously, BF2-A and BF2-C did not induce the influx of PI into the E. coli cells, indicating nonmemebrane permeabilizing killing action. The FITC-labeled BF2-A/C could penetrate the E. coli cell membrane and BF2-C penetrated the cells more efficiently. Furthermore, BF2-A/C could bind to DNA and RNA respectively, and the affinity of BF2-C to DNA was powerful at least over 4 times than that of BF2-A. The present results implied that BF2-A and BF2-C inhibited the cellular functions by binding to DNA and RNA of cells after penetrating the cell membranes, resulting in the rapid cell death. The structure-activity relationship analysis of BF2-A/C revealed that the cell-penetrating efficiency and the affinity ability to DNA were critical factors for determining the antimicrobial potency of both peptides. The more efficient cell-penetrating and stronger affinity to DNA caused that BF2-C displayed more excellent antimicrobial activity and rapid killing kinetics than BF2-A.


Lipodistrophy: a paradigm for understanding the consequences of "overloading" adipose tissue.
Lipodystrophies have been recognized since at least the nineteenth century and, despite their rarity, tended to attract considerable medical attention because of the severity and somewhat paradoxical nature of the associated metabolic disease that so closely mimics that of obesity. Within the last 20 yr most of the monogenic subtypes have been characterized, facilitating family genetic screening and earlier disease detection as well as providing important insights into adipocyte biology and the systemic consequences of impaired adipocyte function. Even more recently, compelling genetic studies have suggested that subtle partial lipodystrophy is likely to be a major factor in prevalent insulin-resistant type 2 diabetes mellitus (T2DM), justifying the longstanding interest in these disorders. This progress has also underpinned novel approaches to treatment that, in at least some patients, can be of considerable therapeutic benefit.


Alprenolol and bromoacetylalprenololmenthane are competitive slowly reversible antagonists at the beta 1-adrenoceptors of rat left atria.
We studied the effects of alprenolol and bromoacetylalprenololmenthane (BAAM) on rat left atria. Alprenolol and BAAM at 10(-7), 3 x 10(-7), and 10(-6) M inhibited the cardiac stimulation response slightly, which is indicative of membrane-stabilizing activity independent of beta-adrenoceptor blockade. This membrane-stabilizing activity was readily reversible. Alprenolol and BAAM also caused surmountable antagonism of isoprenaline responses, and this beta 1-adrenoceptor antagonism was slowly reversible. Inhibition of the isoprenaline responses with alprenolol and BAAM at 10(-6) M was at equilibrium after 60 min, which is indicative of reversible antagonism. We conclude that alprenolol and BAAM are competitive slowly reversible beta 1-adrenoceptor antagonists on rat left atria.


Screen-printed sensors for efficient potentiometric analysis of tolperisone hydrochloride in presence of its co-formulated drugs.
Researchers seeking for green chemistry to help safeguard and boost the economy and the environment by discovering unique ways to decrease waste and find substitutes for dangerous chemicals. In this study, a green potentiometric ion-selective electrode (ISE) was developed for measurement of tolperisone HCl (TOLP) in bulk and Pharmaceutical dosage forms in presence of diclofenac sodium and paracetamol as co-formulated drugs. This paper presents the manufacture and characterization of a disposable potentiometric ion-selective strip with an enhanced detection limit for (TOLP) measurement in its tablet dosage form either alone or in presence of the co-formulated drugs. Numerous ion pairs (IPs), such as TOLP-tetraphenylborate (TOLP-TPB), TOLP-phosphotungstic acid (TOLP-PTA), and TOLP-ammonium Reinecke (TOLP- RKT) are tested in presence of different plasticizers. The optimal potentiometric response with a near Nernstian slope of 55.949 mV/decade was achieved within a linear concentration range of 5 [Formula: see text] 10-5 - 1 [Formula: see text] 10-2 M using (PTA) and ortho nitrophenyl octyl ether (o-NPOE) as a plasticizer. The effect of the nanoparticles on the membrane stability was studied using the graphene nanoplatelets which have an effective role in the enhancement of some constructed sensors stability. Finally, the developed technique is validated for the estimation of TOLP with high accuracy and precision.


Performance of a semi-quantitative whole blood test for human heart-type fatty acid-binding protein (H-FABP).
We evaluated the accuracy of visually reading the whole blood Rapicheck H-FABP panel test using the quantitative plasma H-FABP concentration as the reference. Consecutive patients with chest pain (n = 237) who were suspected of having acute myocardial infarction were recruited. The appearance of an evident test line within 5 min was given a grade of +3 (strongly positive), appearance within 15 min +2 (moderately positive) and the appearance of a weak test line within 15 min +1 (weakly positive). The concordance rates were 91.8% for positive, 70.1% for negative and 80.2% for overall. Plasma H-FABP concentrations were above the cut-off value for 9.2% of negative (0) results. Fifty percent of weakly positive (+1) and 25.0% of moderately positive (+2) results had H-FABP concentrations lower than the cut-off value. All of the strongly positive (+3) were above the cut-off value. These results suggested that the false-positive and false-negative results of Rapicheck H-FABP were caused by over or underestimation in visual reading when the plasma H-FABP concentration was near the cut-off concentration. Low accuracy of visual reading of Rapicheck H-FABP was due to poor estimation by manual reading around the cut-off value.


Factors influencing student perceptions of high-school science laboratory environments.
Science laboratory learning has been lauded for decades for its role in fostering positive student attitudes about science and developing students' interest in science and ability to use equipment. An expanding body of research has demonstrated the significant influence of laboratory environment on student learning. Further research has demonstrated differences in student perceptions based on giftedness. To explore the relationship between giftedness and students' perceptions of their learning environment, we examined students' perceptions of their laboratory learning environment in biology courses, including courses designated for high-achieving versus regular-achieving students. In addition, to explore the relationship between students' perceptions and the extent of their experience with laboratory learning in a particular discipline, we examined students' perceptions of their laboratory learning environment in first-year biology courses versus elective biology courses that require first-year biology as a prerequisite. We found that students in high-achieving courses had a more favourable perception of all aspects of their learning environment when compared with students in regular courses. In addition, student perceptions of their laboratory appeared to be influenced by the extent of their experience in learning science. Perceptions were consistent amongst regular- and high-achieving students regardless of grade level. In addition, perceptions of students in first year and beyond were consistent regardless of grade level. These findings have critical applications in curriculum development as well as in the classroom. Teachers can use student perceptions of their learning environment to emphasize critical pedagogical approaches and modify other areas that enable enhancement of the science laboratory learning environment.


Hierarchical porous TiO2 fabricated from magnolia grandiflora petals templates for the immobilization and electrical wiring of proteins.
Hierarchical porous titanium dioxide (hp-TiO2) was prepared using natural magnolia grandiflora petals as templates and was further employed for the immobilization of horseradish peroxidase (HRP). Scanning electron microscopy (SEM) and nitrogen adsorption-desorption measurement revealed the wrinkled and porous structure of the obtained hp-TiO2. Fourier transform infrared spectroscopy (FT-IR) indicated the effective immobilization and conformation retention of HRP on hp-TiO2. HRP immobilized on hp-TiO2 exhibited direct, reversible, and surface-controlled redox reaction with the electron transfer rate constant of 5.46 s(-1). Furthermore, the immobilized HRP exhibited a wide linear detection range from 1.0 to 524.0 µM. The detection limit, based on a signal-to-noise ratio of 3, was down to 0.87 µM. The apparent Michaelis-Menten constant (Km(app)) of the immobilized HRP was 0.223 mM. In addition, the sensor possessed appreciable repeatability, reproducibility and remarkable stability for the sensitive determination of H2O2. Thus, this kind of hp-TiO2 can be used as an attractive material for immobilizing proteins and constructing biosensors.


Geometric morphometric and molecular techniques for discriminating among three cryptic species of the Anopheles barbirostris complex (diptera: culicidae) in Thailand.
Anopheles members of the Barbirostris complex are important vectors of malaria in Thailand. However, they are morphologically indistinguishable because they are closely related species. In this study, wing geometric morphometrics (GM) and DNA barcoding based on the cytochrome c oxidase subunit 1 (C O I) gene were applied to differentiate cryptic species of the Barbirostris complex in Thailand. Three cryptic species of the Barbirostris complex, Anopheles dissidens (19.44%), Anopheles saeungae (24.54%), and Anopheles wejchoochotei (56.02%) were initially identified using the multiplex polymerase chain reaction assay. DNA barcoding analyses showed low intraspecific distances (range, 0.27%-0.63%) and high interspecific distances (range, 1.92%-3.68%), consistent with the phylogenetic analyses that showed clear species groups. While wing size and shape analyses based on landmark-based GM indicated differences between three species (p < 0.05). The cross-validated reclassification revealed that the overall efficacy of wing size analysis for species identification of the Barbirostris complex was less than the wing shape analysis (56.43% vs. 74.29% total performance). Therefore, this study's results are guidelines for applying modern techniques to identify members within the Barbirostris complex, which are still difficult to distinguish by morphology-based identification and contribute to further appropriate malaria control.


A collaborative study of methods of protein evaluation: introductory paper.
The USDA's collaborative study of methods of protein quality evaluation is introduced. It was intended primarily to provide a basis for the evaluation of possibly improved procedures for the labelling of foods as a source of dietary protein. In general, the usefulness of in vitro digestibility procedures has been confirmed, but problems remained for the in vitro evaluation of heat-damaged materials and of some types of pinto beans.


[Treatment of biliary tract carcinoma with metal endoprosthesis].
The application of endoprosthesis in the surgery of biliary tract carcinoma is a very valuable method to prolong the life of cancer patients. The metalendoprosthesis with drain for continuously rinsing the bile duct to avoid incrusation showed good results in 9 patients for short survival time of 5-26 months. Two patients were treated with bifurcated Y-shape prosthesis after resection of bile duct carcinoma.


The effect of dietary selenium deficiency on the antioxidant enzyme system in the gastrointestinal tract of the rat.
The effect of selenium deficiency on the glutathione content and antioxidant enzymes in the gastrointestinal mucosa was studied. It was found that under Se-deficiency the level of glutathione increased, whereas the activity of Se-dependent glutathione peroxidase decreased. The activities of catalase and glutathione-S-transferase were unaffected. Malondialdehyde content was markedly increased in the glandular stomach of Se-deficient rats.


Isolation and expression of the retinoid X receptor from last instar nymphs and adult females of the soft tick Ornithodoros moubata (Acari: Argasidae).
Retinoid X receptors (RXR) exist broadly from invertebrates to vertebrates, and play essential roles in physiological processes of these organisms. In arthropods, RXRs form a complex with the ecdysteroid receptor (EcR) and ecdysteroids to mediate the regulation of ecdysis and reproduction. Compared to EcR, RXR and its homologue ultraspiracle (USP) are much less well understood. Therefore, we identified RXR of the soft tick Ornithodoros moubata (OmRXR) and used real-time PCR to examine the expression of OmRXR. This is the first report of RXR from a soft tick. OmRXR showed higher homology to hard tick, crustacean and vertebrate RXRs than insect RXRs and USPs. OmRXR expression was observed during molting in the last instar nymphs coinciding with EcR expression and increases in ecdysteroid titers. Tick vitellogenesis normally occurs soon after engorgement and OmRXR expression coinciding with EcR expression and ecdysteroid titers in engorged females occurred before vitellogenin (Vg) synthesis and egg maturation. The ecdysteroid/EcR/RXR complex appears to be important in the regulation of molting and vitellogenesis of soft ticks.


Radiologically-guided balloon sialoplasty for benign salivary duct obstruction: a 7-year UK service evaluation.
Obstructive sialadenitis is the most common cause of non-malignant salivary gland disorders, with salivary gland strictures being responsible for approximately 23% of all benign obstructive disease. Significant advances in minimally invasive techniques, including radiologically-guided balloon sialoplasty, offer the potential for successful treatment with reduced complications. At present there is a paucity of follow-up data regarding patient outcomes and repeat interventions in those undergoing the procedure. Patients with parotid or submandibular gland sialadenitis secondary to gland stricture were identified and underwent radiologically-guided balloon sialoplasty at Queen Alexandra Hospital, Portsmouth, UK between 2015 and 2022. Patient outcomes, complications and reintervention rates were recorded prospectively over the seven-year period and analysed retrospectively. A total of 44 patients underwent radiologically-guided balloon sialoplasty. Forty (89%) underwent sialoplasty for parotid gland disease, with a minority (n = 5) receiving an intervention for submandibular gland strictures. A total of 37 (84%) had their obstruction successfully treated (82% of parotid gland obstructions and 100% of submandibular gland obstructions). Five patients (11%) required a repeat intervention. Seventeen successfully treated patients (85%) who attended follow-up clinic appointments described complete resolution of their symptoms, with the remaining three (15%) describing a partial response. Radiologically-guided balloon sialoplasty for the treatment of benign obstructive sialadenitis secondary to a gland stricture is a safe and effective method of eliminating the obstruction and relieving patients' symptoms. Most patients were symptom free at short-term follow up, with a minority requiring a second sialoplastic intervention.


A functional near-infrared spectroscopy study on the prefrontal correlates of cognitive offloading via a personal knowledge assistant.
The saving of previously encoded information boosts both memory for subsequent information (saving-enhanced memory; SEM) as well as cognitive performance in general (saving-enhanced performance; SEP). These findings have been replicated in a setting that involves the assistance by an intelligent software that automatically structures and saves work content in an interactive sidebar. It is assumed that beneficial effects on cognitive performance due to (automatic) saving are caused by a reduction in current workload by means of cognitive offloading. We tested this assumption by measuring neural activity in the dorsolateral prefrontal cortex (DLPFC) via functional near infrared spectroscopy (fNIRS)-once after saving and once after deleting of previously collected information that had to be recalled later-on. On a behavioral level, there was a brief benefit of saving. However, cognitive offloading became most apparent on a neural level: after saving, participants showed significantly lower activation in the right DLPFC. Also, the more participants benefited from cognitive offloading, the more they were able to re-access previously collected, saved information. Thus, fNIRS results indicated reduced mental load after saving, confirming the assumption that saving triggers cognitive offloading.


Nucleotide sequence of the rrnB 16S ribosomal RNA gene from Mycoplasma capricolum.
The nucleotide sequences of the rrnB 16S ribosomal RNA gene and its 5'-and 3'-flanking regions from Mycoplasma capricolum have been determined. The coding sequence is 1521 base pairs long, being 21 base pairs shorter than that of the Escherichia coli 16S rRNA gene. The 16S rRNA sequence of M. capricolum reveals 74% and 76% identify with that of E. coli and Anacystis nidulans, respectively. The secondary structure model constructed from the M. capricolum 16S rRNA gene sequence resembles that proposed for E. coli 16S rRNA. A large stem structure can be constructed between the 5'- and 3'-flanking sequences of the 16S rRNA gene. The flanking regions are extremely rich in AT.


Heart rupture as an acute complication of cocaine abuse: A case report.
The purpose of this study is to show a very rare complication of acute cocaine poisoning, namely heart rupture. In the present case report, acute cocaine intoxication caused massive myocardial infarction, resulting in heart rupture and cardiac tamponade. A crime scene investigation found a dead body on the street in a drug dealing district. Examination of the body showed no external injuries. A thorough autopsy was performed showing massive cardiac tamponade with 510 ml of blood within the pericardium and full-thickness tissue lesion at the posterior wall of the left ventricle of 3.5 × 3 cm. Histological examination in hematoxylin and eosin was performed and confirmed the interruption of the posterior wall of the left ventricle with the presence of blood. In fact, although the correlation between cocaine and myocardial damage is well established, the relationship between heart rupture and acute cocaine intoxication is an extremely rare event. Moreover, since there are, to date, few reports of similar deaths, our report provides useful information regarding sudden death in a cocaine abuser. It is, therefore, of crucial importance to report this case to the scientific community.


The clinical laboratory evaluation of cryptococcal infections in the acquired immunodeficiency syndrome.
The medical and laboratory records were reviewed in 37 acquired immunodeficiency syndrome (AIDS) patients with cryptococcal infections. In 24 patients with the presentation of cryptococcal meningitis, the initial cerebrospinal fluid (CSF) culture was positive. The initial India ink mount demonstrated organisms in 79% of culture positive CSF specimens. After therapy the subsequent India ink mounts demonstrated 84% sensitivity and 53% specificity with respect to culture outcome. Cultures of blood, bronchoalveolar lavage fluid, and brain were more likely to be positive than cultures from other sites. The initial blood cultures were positive in eight of eight patients at presentation of cryptococcal meningitis. When the initial CSF titer was greater than 1:2, the corresponding CSF culture was always positive. A negative culture during therapy did not necessarily indicate eradication of infection. The initial cerebrospinal fluid and serum cryptococcal antigen titers varied significantly and could not be correlated with survival. In three instances when the CSF cryptococcal antigen titers and cultures were negative, a positive serum cryptococcal antigen greater than 1:8 suggested disseminated infection.


Molecular evidence for the occurrence of Pumpkin yellows virus (PuYV), a new polerovirus species associated with pumpkin plants.
In India, cucurbit aphid-borne yellows virus, a cucurbit-infecting polerovirus, is emerging in the recent past with respect to its occurrence on different crops and geographical locations. This emphasized the need for an investigation to search for the possible occurrence of the other related species Polerovirus. In this view, different cucurbit hosts exhibiting severe chlorosis, bleaching, and yellowing symptoms were collected from the Vegetable Experimental Fields of IARI, New Delhi. The samples exhibiting yellowing and bleaching symptoms were associated with small isometric virions measuring ~ 25 nm under transmission electron microscope. The RT-PCR assays using generic (covering the partial RdRp, intergenic region and partial CP region) and complete coat protein (CP) gene-specific primers confirmed the association of a polerovirus. Further, complete CP gene sequence analyses revealed the association of a distinct species of Polerovirus with the pumpkin samples. These isolates showed the CP gene sequence identities below the species demarcation limit (90%) with the corresponding gene sequences of already reported polerovirus isolates. The results of this study provide the molecular evidence for the occurrence of a new species of Polerovirus, named tentatively as Pumpkin yellows virus (PuYV) in India.


Endovascular treatment of chronic, recurrent headache secondary to chronic cerebral venous sinus thrombosis.
Headache is a clinical diagnosis linked to a number of medical and surgical disorders. A common etiology has not yet been established. It would seem that these cases can be related to some degree of cerebral venous outflow obstruction. We report 2 cases of chronic superior sagittal sinus thrombosis causing isolated intracranial hypertension. The patients were treated with intrasinus thrombolytic therapy.


[Partially French Canadians are susceptible to increased cardiovascular risk factors: A population-based retrospective cohort study].
Through various research lead in the past, it has been made evident that Quebec is home to higher rates of acute myocardial infarction (AMI) and higher prevalence of cardiovascular risk factors than other Canadian provinces. This proposed study will perform a retrospective analysis on Caucasian populations in order to analyze the cardiovascular risk factors in partially francophone populations in comparison to French and Non-French Canadians. Furthermore, we will closely analyze both genders of aforementioned populations. This population-based retrospective cohort study was achieved using the University of Ottawa Heart Institute CCTA registry. Included are Caucasian patients of all ages who came to UOHI for a CCTA between 2006 and 2018 and provided written informed consent. SPSS was used to compare the different populations (French Canadian, partially French Canadian and non-French Canadian) and sex. The PFC population more closely resembles FC, having higher incidence of cardiovascular risk factors such as smoking, dyslipidemia and type 2 diabetes. Our results suggest that PFC, like FC, may benefit from more intensive education and lifestyle modification techniques.


Comparison of diameter-based and image-based measures of surface area from gross placental pathology for use in epidemiologic studies.
Placental surface area is often estimated using diameter measurements. However, as many placentas are not elliptical, we were interested in the validity of these estimates. We compared placental surface area from images for 491 singletons from the Stillbirth Collaborative Research Network (SCRN) Study (416 live births, 75 stillbirths) to estimates obtained using diameter measurements. Placental images and diameters were obtained from pathologic assessments conducted for the SCRN Study and images were analyzed using ImageJ software. On average, diameter-based measures underestimated surface area by -5.58% (95% confidence interval: -30.23, 19.07); results were consistent for normal and abnormal shapes. The association between surface area and birthweight was similar for both measures. Thus, diameter-based surface area can be used to estimate placental surface area.


Group autonomy enhancing treatment versus cognitive behavioral therapy for anxiety disorders: A cluster-randomized clinical trial.
Although cognitive behavioral therapy (CBT) is effective in the treatment of anxiety disorders, few evidence-based alternatives exist. Autonomy enhancing treatment (AET) aims to decrease the vulnerability for anxiety disorders by targeting underlying autonomy deficits and may therefore have similar effects on anxiety as CBT, but yield broader effects. A multicenter cluster-randomized clinical trial was conducted including 129 patients with DSM-5 anxiety disorders, on average 33.66 years of age (SD = 12.57), 91 (70.5%) female, and most (92.2%) born in the Netherlands. Participants were randomized over 15-week groupwise AET or groupwise CBT and completed questionnaires on anxiety, general psychopathology, depression, quality of life, autonomy-connectedness and self-esteem, pre-, mid-, and posttreatment, and after 3, 6, and 12 months (six measurements). Contrary to the hypotheses, effects on the broader outcome measures did not differ between AET and CBT (d = .16 or smaller at post-test). Anxiety reduction was similar across conditions (d = .059 at post-test) and neither therapy was superior on long term. This was the first clinical randomized trial comparing AET to CBT. The added value of AET does not seem to lie in enhanced effectiveness on broader outcome measures or on long term compared to CBT. However, the study supports the effectiveness of AET and thereby contributes to extended treatment options for anxiety disorders.


Bacterioplankton assembly and interspecies interaction indicating increasing coastal eutrophication.
Anthropogenic perturbations impose negative effects on coastal ecosystems, such as increasing levels of eutrophication. Given the biogeochemical significance of microorganisms, understanding the processes and mechanisms underlying their spatial distribution under changing environmental conditions is critical. To address this question, we examined how coastal bacterioplankton communities respond to increasing eutrophication levels created by anthropogenic perturbations. The results showed that the magnitude of changes in the bacterioplankton community compositions (BCCs) and the importance of deterministic processes that constrained bacterial assembly were closely associated with eutrophication levels. Moreover, increasing eutrophication significantly (P < 0.001) attenuated the distance decay rate, with a random spatial distribution of BCCs in the undisturbed location. In contrast, the complexity of interspecies interaction was enhanced under moderate eutrophication levels but declined under heavy eutrophication. Changes in the relative abundances of 27 bacterial families were significantly correlated with eutrophication levels. Notably, the pattern of enrichment or decrease for a given bacterial family was consistent with its known ecological functions. Our findings demonstrate that the magnitude of changes in BCCs and underlying determinism are dependent on eutrophication levels. However, the buffer capacity of bacterioplankton community is limited, with disrupted interspecies interaction occurring under heavy eutrophication. As such, bacterial assemblages are sensitive to changes in environmental conditions and could thus potentially serve as bio-indicators for increasing eutrophication.


PEDOT/FHA nanocomposite coatings on newly developed Ti-Nb-Zr implants: Biocompatibility and surface protection against corrosion and bacterial infections.
The fabrication of bioactive polymer nanocomposite coatings with enhanced biocompatibility and surface protection has been a topic of abundant concern in orthopaedic implant applications. Herein, we electrochemically prepared a novel poly (3,4-ethylenedioxythiophene) (PEDOT) based nanocomposite coatings with different contents of fluoro hydroxyapatite (FHA) nanoparticles on a newly developed Ti-Nb-Zr (TNZ) alloy; an appropriate approach to advance the surface features of TNZ implants. FTIR, XRD, and Raman analyses of the coating confirm the successful preparation of PEDOT/FHA nanocomposite, and XPS validate the chemical interaction between FHA and PEDOT matrix. SEM and TEM examination show the uniform distribution of spherical FHA nanoparticles inside the PEDOT matrix. Hardness and contact angle measurement results showed improving in the hardness and surface wettability of the coated samples respectively. Electrochemical corrosion tests specified that the PEDOT/FHA coatings exhibit higher corrosion protection than the pure PEDOT coatings. The fabricated nanocomposite coating supports the cell adsorption and proliferation of MG-63 cells. Moreover, antibacterial studies against Gram positive and negative bacteria reveal the enhanced antibacterial performance of the coated TNZ substrates. Our results show the potential applications of PEDOT/FHA nanocomposite as a most viable coating for the orthopaedic implants.


Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation.
The tetraspanins associate with various surface molecules and with each other to build a network of molecular interactions, the tetraspanin web. The interaction of tetraspanins with each other seems to be central for the assembly of the tetraspanin web. All tetraspanins studied, CD9, CD37, CD53, CD63, CD81, CD82 and CD151, were found to incorporate [3H]palmitate. By site-directed mutagenesis, CD9 was found to be palmitoylated at any of the four internal juxtamembrane regions. The palmitoylation of CD9 did not influence the partition in detergent-resistant membranes but contributed to the interaction with CD81 and CD53. In particular, the resistance of the CD9/CD81 interaction to EDTA, which disrupts other tetraspanin/tetraspanin interactions, was entirely dependent on palmitoylation.


Successful treatment of pemphigus vegetans by addition of etretinate to systemic steroids.
Pemphigus vegetans is a rare variant of pemphigus vulgaris and is characterized by flaccid bullae, which become eroded and form vegetations or papillomatous proliferations, especially in the intertriginous areas. Oral administration of corticosteroids alone does not always induce disease remission in pemphigus vegetans. We report a 44-year-old Japanese man with pemphigus vegetans. Although corticosteroid therapy resulted in healing of the oral ulcers and skin bullae, verrucous vegetations continued to develop. In contrast, by combining corticosteroid with etretinate, verrucous vegetations improved. Thus we propose that the combination therapy of steroid and etretinate might be an effective adjunct in the therapy of pemphigus vegetans.


Autoantibodies and autoimmune disorders in SARS-CoV-2 infection: pathogenicity and immune regulation.
Coronavirus disease 2019 (COVID-19) is an infectious disease associated with the respiratory system caused by the SARS-CoV-2 virus. The aim of this review article is to establish an understanding about the relationship between autoimmune conditions and COVID-19 infections. Although majority of the population have been protected with vaccines against this virus, there is yet a successful curative medication for this disease. The use of autoimmune medications has been widely considered to control the infection, thus postulating possible relationships between COVID-19 and autoimmune diseases. Several studies have suggested the correlation between autoantibodies detected in patients and the severity of the COVID-19 disease. Studies have indicated that the SARS-CoV-2 virus can disrupt the self-tolerance mechanism of the immune system, thus triggering autoimmune conditions. This review discusses the current scenario and future prospects of promising therapeutic strategies that may be employed to regulate such autoimmune conditions.


Comparison of nitrite accumulation performance and microbial community structure in endogenous partial denitrification process with acetate and glucose served as carbon source.
Although the combination of endogenous partial denitrification (EPD) and Anammox (EPD-AMX) were developed for deep-level nitrogen removal, the effects of different carbon source were not clear. In this study, the EPD performance was investigated comparatively with acetate (EPDA) and glucose (EPDG). Results revealed that through regulating chemical oxygen demand to phosphate ratio, Candidatus_Competibacter was highly enriched in EPDA (54.2%) and EPDG (51.3%), resulting high intracellular carbon storage efficiencies (90.2% and 85.3%, respectively). More stable nitrite accumulation was observed in EPDG than EPDA. But, higher specific nitrite generated rate (rNO2, 8.25 > 7.04 mgN·gVSS-1·h-1) and nitrate-to-nitrite transformation rate (NTR, 87.9% > 85.2%) were achieved in EPDA than those in EPDG. The functional bacterium was also shifted to Defluviicoccus in both EPDA (30.6%) and EPDG (25.8%). Moreover, with whether acetate or glucose, the EPD-AMX processes could achieve the same level of total nitrogen removal efficiencies (88.7% and 91.3%, respectively) via anammox mainly (87.8% and 89.4%, respectively).


A second HD mating type sublocus of Flammulina velutipes is at least di-allelic and active: new primers for identification of HD-a and HD-b subloci.
Sexual development in Flammulina velutipes is controlled by two different mating type loci (HD and PR). The HD locus contains homeodomain (Hd) genes on two separate HD subloci: HD-a and HD-b. While the functionality of the HD-b sublocus has been largely confirmed, the status and content of the HD-a sublocus has remained unclear. To examine the function of the HD-a sublocus, genome sequences of a series of F. velutipes strains were analyzed and tested through series of amplification by specific primer sets. Furthermore, activity of di-allelic HD-a locus was confirmed by crossing strains with different combinations of HD-a and HD-b subloci. Sublocus HD-b contained a large variety of fixed Hd1/Hd2 gene pairs, while the HD-a sublocus either contained a conserved Hd2 gene or, a newly discovered Hd1 gene that was also conserved. Identification of whole HD loci, that is, the contents of HD-a and HD-b subloci in a strain, revealed that strains with similar HD-b subloci could still form normal dikaryons if the two genes at the HD-a sublocus differed. At least di-allelic HD-a sublocus, is thus indicated to be actively involved in mating type compatibility. HD-a sublocus is active and di-allelic. Using the new information on the HD subloci, primers sets were developed that specifically amplify HD-a or HD-b subloci in the majority of F. velutipes strains. In this way, unknown HD mating types of F. velutipes can now be quickly identified, and HD mating type compatibility conferred by HD-a or HD-b can be confirmed by PCR.


Elevation of fibrin degradation product (FDP) values prevents the negative conversion of serum CRP values after total knee arthroplasty.
It is essential as an orthopedic surgeon to diagnose prosthetic joint infection (PJI) at an early stage and to carry out precise treatment as well as preventing the deterioration of functional prognosis as much as possible. We suspected that PJI might have been caused because the negative conversion of creatinine reactive protein (CRP) has been prolonged after total knee arthroplasty (TKA) and patients with no serum CRP negative conversion have been treated with antibiotics to avoid the morbidity of PJI. The purpose of the present study is to investigate the factors associated with prolongation of the negative conversion of CRP, with the exclusion of PJI patients. We performed a retrospective case control study at our institution from August 2014 to August 2016. We classified the patients into two groups based on whether it required ≥20 days (Group A, n = 23) or <20 days (Group B, n = 23) for CRP levels to normalize. Serum D-Dimer and fibrin degradation product (FDP) values were measured at 1, 2, 5, 9, 12, 16, 19, 23, 26, and 30 days after TKA. Exclusion criteria include anticoagulant oral administration cases before TKA, venous thromboembolism (VTE) by postoperative lower limb venous echocardiography before and after TKA, CRP re-elevation cases, and patients with PJI. The cutoff points for D-dimer and FDP levels for screening tests were calculated from the receiver operating characteristic (ROC) curve. The ROC analysis of D- Dimer values at 30 days after TKA yielded an AUC of 0.891 (95% confidence interval (CI) 0.858-1.000), which indicates nearly an excellent test. The cutoff point of 22.1 μg/dl for FDP value (Younden Index: 22.1 μg/dl) showed a sensitivity of 81.8% (95% CI 70.1-92.8) and a specificity of 80.0% (95% CI 67.9-89.1). We revealed that CRP values of patient with an FDP level ≥22.1 μg/dl at 30 days after TKA necessarily showed negative conversion without antibiotic administration, when examining a patient with elevated serum CRP of minor criteria in the definition of PJI proposed by MSIS (other criteria do not apply). Ⅲ.


Incorporating ecosystem services to assess progress towards sustainable development goals: A case study of the Yangtze River Economic Belt, China.
To promote coordinated development of the global economy, society, and environment, The 2030 Agenda for Sustainable Development of the United Nations (UN) specifies 17 sustainable development goals (SDGs) with 169 nested targets. Studies have shown that a healthy ecological environment and stable ecosystem services (ESs) provide an important foundation for achieving the SDGs. Due to the lack of quantitative methods for assessing the contribution of ESs to SDGs, very few empirical studies have been conducted to examine how knowledge of ESs can guide regional sustainable development. From the perspective of an ES cascade, we proposed a systematic approach for quantifying progress towards environment-related SDGs in terms of ES indicators, based on the Yangtze River Economic Belt (YREB). The scores of multiple SDGs and the SDG Index increased significantly across the YREB from 2000 to 2015, mainly attributed to the improvement of food and water provisioning services. Significant spatiotemporal variation in sustainable development levels was observed between provinces within the YREB. For example, the sustainable development levels in the eastern YREB clearly trailed those in the central and western YREB, and the SDG scores and SDG Index scores declined gradually. Among 11 provincial regions in the YREB, the SDG Index scores of nine provincial regions increased gradually, whereas those of Zhejiang and Shanghai declined. Strengthening the assessment of the ES value for generating more comprehensive ES indicators and applying an integrated ES-based approach for monitoring and comparing the process of local and global sustainable development, are promising areas for future research.


Body composition and fat distribution among older Jat females: a rural-urban comparison.
The aim of the present cross-sectional study is to describe and compare age related changes in body composition and fat patterning among rural and urban Jat females of Haryana State, India. A total of 600 females (rural=300, urban=300), ranging in age from 40 to 70 years were selected by the purposive sampling method. Body weight, height, two circumferences (waist and hip) and skinfold thickness at five different sites (biceps, triceps, calf, subscapular, and supra-iliac) were taken on each participant. To study total adiposity, indices such as body mass index (BMI), grand mean thickness (GMT), total body fat and percentage fat were analyzed statistically. The fat distribution pattern was studied using waist/hip ratio, subscapular/triceps ratio and responsiveness of five skinfold sites towards accumulation of fat at different sites with advancing age. Results indicate a decline in almost every dimension including level of fatness between the mid-fourth and mid-fifth decades of life in both rural and urban females. Urban Jat females were heavier (57.36 kg vs. 56.07 kg, p>0.05) and significantly taller (1553.3mm vs. 1534.5mm, p<0.001) than their rural counterparts. Urban females also exhibited higher mean values for both the circumferences, five skinfold thicknesses as well as for lean body mass, total fat and percentage fat than the rural females. This is also evident from their higher mean values for body mass index and grand mean thickness. Waist/hip ratio values in rural and urban females showed upper body fat predominance, with urban females having relatively more abdominal fat. Results of subscapular/triceps ratio showed that rural and urban females gained proportionally similar amounts of subcutaneous fat at trunk and extremity sites until 45 years of age. Subsequently trunk skinfolds increased relatively more in thickness. The magnitude of this increase was comparatively greater in rural females up to 55 years and among urban females from 55 to 70 years. The profiles of subcutaneous fat accumulation and sensitivity of each skinfold site also revealed more fat deposition in the trunk region compared to extremities in both rural and urban females. The present study demonstrated differential rates of fat redistribution among rural and urban females.


Correction to: GABAA Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol: Genetic and Pharmacological Evidence.
The chemical name appearing in the first column of Table 1 on the 3rd row from bottom of the table is wrong.


Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review.
Transcutaneous Vagus Nerve stimulation (tVNS) may be an alternative to surgically implanted VNS for epilepsy and other diseases. However, its safety and tolerability profile is unclear. We performed a systematic review of treatment harms from tVNS in humans. A systematic published and grey literature search was carried out to identify studies which deployed tVNS in human subjects. Study authors were contacted for safety/tolerability data if these were not available in the publication. Databases were searched from 1966 to May 2017. We noted study type, population, stimulation parameters, type and prevalence of side effects and/or serious adverse events (SAE). We also noted whether side effects/SAE were considered to be related to the tVNS and the proportion of participants dropping out of studies due to side effects. 51 studies were included comprising a total of 1322 human subjects receiving tVNS. The most common side effects were: local skin irritation from electrode placement (240 participants, 18.2%), headache (47, 3.6%) and nasopharyngitis (23, 1.7%). Whilst heterogeneity in overall side effect event rates between studies was not accounted for by the frequency (Hz) or pulse width (ms) of stimulation, a minority (35 participants (2.6%)) dropped out of studies due to side effects. Overall, 30 SAE occurred but only 3 were assessed by the relevant researchers to be possibly caused by tVNS. tVNS is safe and well tolerated at the doses tested in research studies to date.


The role of sediments as a source of metals in river catchments.
Aquatic sediments are a known source of pollutants, but their impact on the quality of overlying waters is not easily quantified. Sediments are generally considered to behave as a sink for pollutants such as heavy metals in the aquatic environment, frequently acting as a source for their presence in waters, with implications for catchment management. This study aimed to calculate the contribution of sediments to metal levels in overlying waters, helping understand their role as a source of metals in river catchments. An aquivalence mass balance approach was modified to take into account both natural and anthropogenic influences and applied to assess sediment contribution in a reach of the River Yare in the UK. The rates of total metal transport from sediments to overlying waters were estimated to be 29.89 g d(-1) for cadmium (Cd), 1633.39 g d(-1) for lead (Pb), 8.29 g d(-1) for mercury (Hg) and 357.56 g d(-1) for nickel (Ni). The results from the case study demonstrated that sediments could be a significant source of metal emissions in river catchments. The calculations proposed in the paper could be useful in developing strategies for sediment management, not only to improve and/or maintain quality of sediments but also to inform the selection of measures of pollution control for the catchment.


Effect of fertilizer type on antibiotic resistance genes by reshaping the bacterial community and soil properties.
Conventional and bio-organic fertilizers play an important role in maintaining soil health and promoting crop growth. However, the effect of organic fertilizers on the prevalence of antibiotic resistance genes (ARGs) in the vegetable cropping system has been largely overlooked. In this study, we investigated the impacts of soil properties and biotic factors on ARG profiles by analyzing ARG and bacterial communities in vegetable copping soils with a long-term history of manure and bio-organic fertilizer application. The ARG abundance in the soil was significantly increased by 116% with manure application compared to synthetic NPK fertilizer application. This finding was corroborated by our meta-analysis that the longer the duration of manure application, the greater the response of increased soil ARG abundance. However, bio-organic fertilizers containing Trichoderma spp. Significantly reduced ARG contamination by 31% compared to manure application. About half of the ARG variation was explained by changes in bacterial abundance and structure, followed by soil properties. The mitigation of ARG by Trichoderma spp. Is achieved by altering the structure of the bacterial community and weakening the close association between bacteria and ARG prevalence. Taken together, these findings shed light on the contribution of bio-organic fertilizers in mitigating ARG contamination in agricultural soils, which can help manage the ecological risk posed by ARG inputs associated with manure application.


Much of the variation in breast pathology quality assurance data in the UK can be explained by the random order in which cases arrive at individual centres, but some true outliers do exist.
To investigate the role of random temporal order of patient arrival at screening centres in the variability seen in rates of node positivity and breast cancer grade between centres in the NHS Breast Screening Programme. Computer simulations were performed of the variation in node positivity and breast cancer grade with the random temporal arrival of patients at screening centres based on national UK audit data. Cumulative mean graphs of these data were plotted. Confidence intervals for the parameters were generated, using the binomial distribution. UK audit data were plotted on these control limit graphs. The results showed that much of the variability in the audit data could be accounted for by the effects of random order of arrival of cases at the screening centres. Confidence intervals of 99.7% identified true outliers in the data. Much of the variation in breast pathology quality assurance data in the UK can be explained by the random order in which cases arrive at individual centres. Control charts with confidence intervals of 99.7% plotted against the number of reported cases are useful tools for identification of true outliers.


Codon optimization and mRNA amplification effectively enhances the immunogenicity of the hepatitis C virus nonstructural 3/4A gene.
We have recently shown that the NS3-based genetic immunogens should contain also hepatitis C virus (HCV) nonstructural (NS) 4A to utilize fully the immunogenicity of NS3. The next step was to try to enhance immunogenicity by modifying translation or mRNA synthesis. To enhance translation efficiency, a synthetic NS3/4A-based DNA (coNS3/4A-DNA) vaccine was generated in which the codon usage was optimized (co) for human cells. In a second approach, expression of the wild-type (wt) NS3/4A gene was enhanced by mRNA amplification using the Semliki forest virus (SFV) replicon (wtNS3/4A-SFV). Transient tranfections of human HepG2 cells showed that the coNS3/4A gene gave 11-fold higher levels of NS3 as compared to the wtNS3/4A gene when using the CMV promoter. We have previously shown that the presence of NS4A enhances the expression by SFV. Both codon optimization and mRNA amplification resulted in an improved immunogenicity as evidenced by higher levels of NS3-specific antibodies. This improved immunogenicity also resulted in a more rapid priming of cytotoxic T lymphocytes (CTLs). Since HCV is a noncytolytic virus, the functionality of the primed CTL responses was evaluated by an in vivo challenge with NS3/4A-expressing syngeneic tumor cells. The priming of a tumor protective immunity required an endogenous production of the immunogen and CD8+ CTLs, but was independent of B and CD4+ T cells. This model confirmed the more rapid in vivo activation of an NS3/4A-specific tumor-inhibiting immunity by codon optimization and mRNA amplification. Finally, therapeutic vaccination with the coNS3/4A gene using gene gun 6-12 days after injection of tumors significantly reduced the tumor growth in vivo. Codon optimization and mRNA amplification effectively enhances the overall immunogenicity of NS3/4A. Thus, either, or both, of these approaches should be utilized in an NS3/4A-based HCV genetic vaccine.


Pathogenicity of Intronic and Synonymous Variants of ATP7B in Wilson Disease.
Wilson disease (WD) is a hereditary disorder of copper metabolism, resulting from mutations within ATP7B. Early diagnosis is essential for affected individuals. However, there are still patients with clinically suspected WD who do not have detectable pathogenic variants, which makes diagnosis difficult and delays treatment. This study included such patients from the authors' center and screened for the full-length sequence of ATP7B by next-generation sequencing. Newly identified synonymous and intronic variants were then analyzed with in silico tools. A minigene system was constructed to determine the pathogenicity of these variants in terms of splicing and blood RNA extraction, and RT-PCR experiments were performed on several patients to verify the splicing alterations. The phenotypes of the patients were also analyzed. Fourteen suspected pathogenic variants, including nine synonymous and five intronic variants, were detected in 12 patients with clinically suspected WD. Among them, four synonymous variants (c.1050G>A, c.1122C>G, c.3243G>A, and c.4014T>A) and four intronic variants (c.1543 +40G>A, c.1707+6_1707+16del, c.1870-49A>G, and c.2731-67A>G) resulted in splicing changes in ATP7B. After the above analysis, the diagnosis of WD could be confirmed in eight clinically suspected patients with WD who showed a late age of onset.


Automation of bone marrow aspirate examination using the XE-2100 automated hematology analyzer.
Attempts to analyze bone marrow aspirates have been reported with the use of several automated blood cell counters, but sufficient accuracy in examination is not acquired yet. Major problems have included difficulties in correctly differentiating various immature cells and interference by lipid in bone marrow aspirates. The goal of this study was to solve these problems to attain more accurate assessment of bone marrow aspirates with automated blood cell counters. We modified the XE-2100 Automated Hematology Analyzer (Sysmex Corporation, Kobe, Japan) to fit it for bone marrow aspirate measurement and evaluated its performance. Measurements were performed with the modified XE-2100 on 81 patient samples of bone marrow aspirates; as a reference, the manual visual method was used and flow cytometric analysis were carried out. Good correlations between results with the modified XE-2100 and the manual visual method were obtained for total nucleated cell count (TNCC; r = 0.99), erythroblast/TNCC ratio (r = 0.93), and myeloid cell/TNCC ratio (r = 0.75). When this device is used, bone marrow aspirate differentials can be determined quickly and easily. This device will be useful for preliminary examination to obtain a summary of various blood cell ratios in bone marrow aspirates before performance of microscopic examination.


NHS should carry out more gastric band surgery to help fight obesity and diabetes.
The NHS has been urged to increase the numbers of patients receiving weight loss surgery to 50,000 a year, closer to the European average, to boost health and cut costs.


Successful in vitro fertilization and embryo transfer after treatment of invasive carcinoma of the breast.
Carcinoma of the breast is the most common female malignancy and may occasionally affect women in the reproductive age group. We report a patient who had primary infertility after surgical extirpation of breast carcinoma. Successful pregnancy and delivery of a healthy baby were achieved after two cycles of IVF-ET therapy.


Source apportionment and ecological and health risk mapping of soil heavy metals based on PMF, SOM, and GIS methods in Hulan River Watershed, Northeastern China.
Heavy metals in agricultural soils not only affect the food security and soil security, but also endanger the human health through the food chain. Based on the incorporation of index analysis, positive matrix factorization (PMF), self-organizing map (SOM), and geostatistical methods, this research performed the assessment of source apportionment and ecological and health risks of soil heavy metals in Hulan River Watershed, Northeastern China. According to the Pollution Load Index (PLI), 83.08% of the soil samples were slightly or mildly polluted, and 1.54% of the soil samples were severely polluted. The ecological risk index (EI) showed that about 80.77% and 60.77% of the soil samples were beyond the low risk level for Hg and Cd, respectively. In this research, the non-carcinogenic and carcinogenic risk indices for children were higher than adult males and adult females. Four potential sources were revealed based on the PMF and SOM analysis including atmospheric deposition and industrial emission; transportation source; agricultural source; and a combination of agricultural, industrial, and natural sources. Considerable and high ecological risk from Hg existed in the area close to the coal steam-electric plant, and considerable and high ecological risk from Cd existed in the Hulan River estuary area. The eastern part of the study area experienced higher non-carcinogenic and carcinogenic risks for adults and children than the western part of the study area. The source apportionment and ecological and health risk mapping provide important role in reducing pollution sources. Zonal pollution control and soil restoration measures should be performed in the areas with high ecological and health risks.


Echocardiographic assessment of cardiac function after mild coronavirus disease 2019: A preliminary report.
While most coronavirus disease 2019 (COVID-19) cases are mild, the risk of heart dysfunction remains unknown. The objective of this observational study was to assess the impact of mild COVID-19 on heart function in a short-term follow-up using advanced echocardiography. Our study cohort comprised patients diagnosed with COVID-19 who did not require hospitalization. Speckle tracking echocardiography (STE) was used to assess heart chambers function in the 31 recovered COVID-19 patients, and the results were compared with those of the control group (28 healthy participants). Left ventricular (LV) and right ventricular (RV) systolic function was assessed using standard and STE methods and was found to be normal and comparable in both groups (LV ejection fraction [p = 0.075], LV global longitudinal strain [p = 0.123], LV global radial strain [p = 0.630], LV global circumferential strain [p = 0.069], tricuspid annular plane systolic excursion [p = 0.417], tricuspid S' peak systolic velocity [p = 0.622], and RV free wall longitudinal strain [p = 0.749]). Similarly, atrial function was not impacted when assessed using advanced STE. The heart function of patients with mild COVID-19 symptoms, assessed using standard and advanced echocardiographic methods, was observed to be normal after a short-term follow-up.


Dapagliflozin protects against doxorubicin-induced nephrotoxicity associated with nitric oxide pathway-A translational study.
Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment.


Short- and long-term outcomes of laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making: a high-volume center retrospective study with propensity score matching.
Some studies have demonstrated the short-term recovery course for patients who underwent laparoscopic gastrectomy according to preoperative computed tomography angiography (CTA) assessment. However, reports of the long-term oncological outcomes are still limited. The data of 988 consecutive patients who underwent laparoscopic or robotic radical gastrectomy between January 2014 and September 2018 were analyzed retrospectively at our center, and propensity score matching was used to eliminate bias. Study cohorts were divided into the CTA group (n = 498) and the non-CTA group (n = 490) depending on whether preoperative CTA was available. The primary and secondary endpoints were the 3-year overall survival (OS) and disease-free survival (DFS) rates and the intraoperative course and short-term outcomes, respectively. 431 patients were included in each group after PSM. Compared with the non-CTA group, the CTA group had more harvested lymph nodes and less operative time, blood loss, intraoperative vascular injury and total cost, especially in the subgroup analysis with BMI ≥ 25 kg/m2 patients. There was no difference in the 3 year OS and DFS between the CTA group and the non-CTA group. When further stratified by BMI < 25 or ≥ 25 kg/m2, the 3-year OS and DFS were significantly higher in the CTA group than in the non-CTA group in terms of BMI ≥ 25 kg/m2. Laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making has the possibility of improving short-term outcomes. However, there is no difference in the long-term prognosis, except for a subgroup of patients with BMI ≥ 25 kg/m2.


Substrate Resistance to Traction Forces Controls Fibroblast Polarization.
The mechanics of fibronectin-rich extracellular matrix regulate cell physiology in a number of diseases, prompting efforts to elucidate cell mechanosensing mechanisms at the molecular and cellular scale. Here, the use of fibronectin-functionalized silicone elastomers that exhibit considerable frequency dependence in viscoelastic properties unveiled the presence of two cellular processes that respond discreetly to substrate mechanical properties. Weakly cross-linked elastomers supported efficient focal adhesion maturation and fibroblast spreading because of an apparent stiff surface layer. However, they did not enable cytoskeletal and fibroblast polarization; elastomers with high cross-linking and low deformability were required for polarization. Our results suggest as an underlying reason for this behavior the inability of soft elastomer substrates to resist traction forces rather than a lack of sufficient traction force generation. Accordingly, mild inhibition of actomyosin contractility rescued fibroblast polarization even on the softer elastomers. Our findings demonstrate differential dependence of substrate physical properties on distinct mechanosensitive processes and provide a premise to reconcile previously proposed local and global models of cell mechanosensing.


Modification of creatine kinase by S-nitrosothiols: S-nitrosation vs. S-thiolation.
Creatine kinase is reversibly inhibited by incubation with S-nitrosothiols. Loss of enzyme activity is associated with the depletion of 5,5'-dithiobis (2-nitrobenzoic acid)-accessible thiol groups, and is not due to nitric oxide release from RSNO. Full enzymatic activity and protein thiol content are restored by incubation of the S-nitrosothiol-modified protein with glutathione. S-nitroso-N-acetylpenicillamine, which contains a more sterically hindered S-nitroso group than S-nitrosoglutathione, predominantly modifies the protein thiol to an S-nitrosothiol via a transnitrosation reaction. In contrast, S-nitrosoglutathione modifies creatine kinase predominantly by S-thiolation. Both S-nitroso-N-acetylpenicillamine and S-nitrosoglutathione modify bovine serum albumin to an S-nitroso derivative. This indicates that S-thiolation and S-nitrosation are both relevant reactions for S-nitrosothiols, and the relative importance of these reactions in biological systems depends on both the environment of the protein thiol and on the chemical nature of the S-nitrosothiol.


Tight-junction tightness of Necturus gall bladder epithelium is not regulated by cAMP or intracellular Ca2+. II. Impedance measurements.
In the preceding publication we have reported that, contrary to the prevailing opinion in the literature, the tight-junction tightness of Necturus gall bladder epithelium is not up-regulated by cAMP-mediated or by Ca(2+)-mediated stimulation. This conclusion was based on our observation that the stimulant-induced increase in transepithelial resistance (Rt) occurred only when the lateral intercellular spaces were allowed to collapse, which suggested that the increase reflected primarily or exclusively the increasing resistance of the lateral spaces (Rlis) rather than the postulated increase in tight-junction resistance (Rj). An alternative explanation could have been that the constancy of Rt after space dilatation reflected an increase Rj that was masked by a concomitant fall in apical and basolateral cell membrane resistances Ra and Rbl. To decide between those possibilities we have performed impedance measurements with transepithelial and intracellular microelectrodes on Necturus gall bladder epithelium. Applying previously developed analysis procedures, the measurements readily showed that elevation of intracellular Ca2+ concentration increased Rlis, but left Rj as well as Ra and Rbl quasi constant. Experiments with forskolin, theophylline or isobutylxanthine, on the other hand, were less clear. These stimulants activated an apical Cl- conductance, which drastically reduced Ra and apparently caused low-frequency polarization effects that could not be accounted for by the classical epithelial equivalent circuit. After elimination of the polarization phenomena by uni- or bilateral substitution of Cl- by isethionate or sulphate, however, we were able to demonstrate that Rj remains constant under cAMP-mediated stimulation irrespective of whether the lateral spaces are kept open or are allowed to collapse. We conclude that the tight-junction resistance of Necturus gall bladder epithelium is not controlled by intracellular Ca2+ or by cAMP-mediated stimulation.


The standardization of 188W/188Re by 4pi beta liquid scintillation spectrometry with the CIEMAT/NIST 3H-standard efficiency tracing method.
The massic activity of a solution containing 188W in equilibrium with its daughter, 188Re, has been standardized by the National Institute of Standards and Technology using 4pi beta liquid scintillation counting with efficiency tracing using the CIEMAT NIST method. Confirmatory measurements were carried out with gamma-ray spectrometry using high purity germanium detectors and a 4pi gamma NaI(Tl) system. A calibration factor of 1.68 MBq pA(-1) +/-0.03 MBq pA(-1) (expanded, k = 2, uncertainty) for the 188W in the solution was determined, along with correction factors for activity determinations using Capintec dose calibrators. A half-life value of 69.78 d +/- 0.05 d (standard uncertainty) was determined by measurement in the NIST 4pi gamma ionization chamber and is consistent with currently recommended values.


Physical activity from menarche-to-first pregnancy and risk of breast cancer: the California teachers study.
A longer menarche-to-first pregnancy window of susceptibility (WOS) is associated with increased breast cancer risk. Whether physical activity, an established preventive risk factor, during the menarche-to-first pregnancy WOS offsets breast cancer risk overall or for specific molecular subtypes is unclear. We examined the prospective association between physical activity during the menarche-to-first pregnancy WOS and breast cancer risk in the California Teachers Study (N = 78,940). Recreational physical activity at multiple timepoints were recalled at cohort entry, and converted to metabolic equivalent of task hours per week (MET-hrs/wk). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed 5,157 invasive breast cancer cases over 21.6 years of follow-up. Longer menarche-to-first pregnancy WOS (≥ 20 vs. < 15 years) was associated with higher breast cancer risk (HR = 1.23, 95% CI = 1.13-1.34). Women with higher physical activity level during menarche-to-first pregnancy had lower risk of invasive breast cancer (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.89, 95% CI = 0.83-0.97) and triple-negative subtype (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.53, 95% CI = 0.32-0.87). No association was observed for luminal A-like and luminal B-like subtypes. Higher physical activity level was associated with lower breast cancer risk among women with moderate (15-19 years) menarche-to-first pregnancy intervals (≥ 40 vs. < 9 MET-hrs/wk: HR = 0.80, 95% CI = 0.69-0.92), but not with short (< 15 years) or long (≥ 20 years) intervals. Physical activity during a WOS was associated with lower breast cancer risk in our cohort. Understanding timing of physical activity throughout the life course in relationship with breast cancer risk maybe important for cancer prevention strategies.


Kinetic study by pulse radiolysis of the lactate dehydrogenase-catalyzed chain oxidation of nicotinamide adenine dinucleotide by HO2 and O2-RADICALS.
The lactate dehydrogenase-catalyzed chain oxidation of NADH (LDH-NADH) by the superoxide radicals, HO2 and O2, has been studied with pulse radiolysis in the pH range between 4.5 and 9.0. The rate constants for the oxidation of the LDH-NADH by HO2 and O2 determined at 23 degrees are 1.2 times 10-6 M(-1) s(-1) and 3.6 times 10-4 M(-1) s(-1), respectively. The latter represents an activation of over 1000-fold by the enzyme. A chain reaction mechanism consistent with the results from these kinetic studies has been proposed.


The relationship between prolactin levels and clinical ratings in manic patients treated with oral and intravenous test doses of haloperidol.
Twelve manic patients were treated for 2 weeks with oral haloperidol; in 6 patients treatment commenced with intravenous haloperidol, and intravenous 'test' doses were given after 1, 3-5 and 14 days of oral medication. From 24 hours to 14 days baseline serum prolactin levels rose towards a plateau, as did the improvement in clinical ratings. After the first intravenous test doses of haloperidol, prolactin levels peaked at 1 hour; however, they fell to a low point at 24 hours, and no response to further test doses was seen for 3-5 days. The response tended to return at 14 days. The mechanisms underlying the changes in prolactin levels, and in clinical state, are discussed.


Characterization and purification of a protein binding to the cis-acting element for brain-specific exon 1 of the mouse aromatase gene.
The functional differences between male and female brains commit to the existence of androgen that the testis secretes during the perinatal period. Androgen exerts its action on the brain after conversion to estrogen by brain aromatase. The aromatase appears in some neural nuclei such as in the hypothalamus and amygdala, and has been indicated to be involved in the expression of sexuality by the results of neurobehavioral analyses involving aromatase-knockout mice. We analyzed the brain-specific promoter in order to clarify the control mechanism for the expression of brain aromatase, which is deeply concerned in the sexual differentiation of the brain. The 202bp upstream region of brain-specific exon 1 contains at least three kinds of cis-acting elements, Arom-Aalpha, -Abeta and -B. In particular, the binding activities as to the Abeta sequence show a tissue-specific pattern. Gel shift analysis revealed that the Abeta binding factor recognizes the TTGGCCCCT sequence. Abeta binding activity is detectable at the perinatal stage, but is undetectable at the adult stage in the brain. Furthermore, a protein which binds to the Abeta sequence was purified from the fetal mouse brain. The molecular mass of the Abeta binding protein was estimated to be 49kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.


Association of musculoskeletal complaints and gliptin use: review of spontaneous reports.
Gliptins are new oral antidiabetic drugs that increase insulin levels through dipeptidyl peptidase-4 inhibition. Recently, the association of serious musculoskeletal (MSk) adverse effects with the gliptin use has been suggested. The aim is to describe and analyze the characteristics of spontaneous reports related to these adverse effects and gliptin use. All spontaneous reports with MSk disorders associated with gliptins gathered in the Spanish pharmacovigilance database until May 2012 were described and analyzed using a case/non-case method. Gliptins were reported as the suspected drug in 332 cases: 208 involved sitagliptin, 115 vildagliptin, and nine saxagliptin. In 34 patients (10.2% of total reports with gliptins), MSk reactions were described (22 women [64.7%] and 12 men [35.3%]). Their mean age was 65.1 years; 41.2% were younger than 65 years. Only seven cases were serious, but the gliptin had to be withdrawn in 22 patients because of intolerance and/or persistence of MSk discomfort, and patients recovered after its discontinuation. A positive re-challenge was observed in two cases. In seven cases, the patients were on previous chronic treatment with statins, and began to present MSk complaints shortly after starting a gliptin. The reporting odds ratio (ROR) for myalgia and arthralgia were strongly associated with gliptin use (ROR 1.96 [95% CI 1.12-3.43], p < 0.05 and ROR 2.69 [95% CI 1.38-5.24], p < 0.05, respectively). Musculoskeletal disorders are adverse reactions strongly associated with gliptins that, despite not being serious, may impair the treatment adherence in patients with type 2 diabetes. Future observational studies could confirm these findings.


Idiosyncratic media exposures during a pandemic and their link to well-being, cognition, and behavior over time.
Over the past two decades of research, increased media consumption in the context of collective traumas has been cross-sectionally and longitudinally linked to negative psychological outcomes. However, little is known about the specific information channels that may drive these patterns of response. The current longitudinal investigation uses a probability-based sample of 5,661 Americans measured at the onset of the COVID-19 pandemic to identify a) distinct patterns of information-channel use (i.e., dimensions) for COVID-related information, b) demographic correlates of these patterns, and c) prospective associations of these information channel dimensions with distress (i.e., worry, global distress, and emotional exhaustion), cognition (e.g., beliefs about the seriousness of COVID-19, response efficacy, and dismissive attitudes), and behavior (e.g., engaging in health-protective behaviors and risk-taking behaviors) 6 mo later. Four distinct information-channel dimensions emerged: journalistic complexity; ideologically focused news; domestically focused news; and nonnews. Results indicate that journalistic complexity was prospectively associated with more emotional exhaustion, belief in the seriousness of the coronavirus, response efficacy, engaging in health-protective behaviors, and less dismissiveness of the pandemic. A reliance on conservative-leaning media was prospectively associated with less psychological distress, taking the pandemic less seriously, and engaging in more risk-taking behaviors. We discuss the implications of this work for the public, policy makers, and future research.


Assessment of the distal anastomosis of coronary artery bypass grafts with a 2D T2-weighted turbo spin echo sequence and correlation to conventional coronary angiography.
The aim of the study was to evaluate the patency of the distal anastomoses of coronary artery bypass grafts and to detect graft stenoses and occlusions with a magnetic resonance (MR) spin echo sequence. One hundred and eighty-five patients with 481 distal anastomoses were examined with a 1.5 T MR scanner and coronary angiography. A 2-dimensional T2-weighted breath-hold half-Fourier acquisition single-shot turbo spin echo sequence (Haste) was performed. All images were evaluated independently by a radiologist and cardiologist and compared to the conventional coronary angiography. The observers were blinded to the coronary angiography findings, but informed in regard to the surgical graft anastomosis. With the Haste sequence, 76% of the distal anastomoses were recognized (368/481). Forty-five of 52 (87%) stenoses and all occlusions were identified. The sensitivity and specificity for the evaluation of the distal anastomosis with the spin echo sequence was 87% and 96%. Twenty-four percent of the distal anastomoses were not identified due to a poor image quality or motion artefacts. Using the Haste sequence, a reliable assessment of graft patency of the distal anastomosis is possible. Further improvements of the spatial resolution and the image quality are necessary to recommend this MR technique for routine clinical use.


Inhibition of the thromboplastin response of endothelial cells in vitro.
Confluent monolayers of human umbilical vein endothelial cells in culture responded with a 5-fold increase in thromboplastin (tissue factor) synthesis when exposed to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) (50 ng/ml) or endotoxin (ETX) (25 micrograms/ml) for 16 hr. This induced thromboplastin synthesis was markedly inhibited by exposure of the cells to two different phosphodiesterase inhibitors, methylisobutylxanthine (MIX) and rac-4(3-butoxy-4-methoxybenzyl)-2-imidazole idinone (RO-20-1724) and to the transmethylation inhibitors 3-deazaadenosine (DZA) and 1-homocysteine thiolactone (Hcy) in combination. It was slightly (TPA) or not at all (ETX) inhibited upon exposure of the cells to the intracellular calcium antagonist 8-(N,N-diethylamino)-octyl 3,4, 5-trimethoxybenzoate hydrochloride (TMB-8). However, in the presence of MIX TMB-8 had a moderate additional inhibitory effect on TPA-induced thromboplastin response. The thromboplastin response of endothelial cells in vitro thus probably depends on transmethylation events for its full expression. It is also strongly modulated by the intracellular level of cAMP.


Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations.
Systemic lupus erythematosus (SLE) is an autoimmune disease with known genetic, epigenetic, and environmental risk factors. To assess the role of DNA methylation in SLE, we collected CD4+ T-cells, CD19+ B-cells, and CD14+ monocytes from 49 SLE patients and 58 controls, and performed genome-wide DNA methylation analysis with Illumina Methylation 450 microarrays. We identified 166 CpGs in B-cells, 97 CpGs in monocytes, and 1,033 CpGs in T-cells with highly significant changes in DNA methylation levels (p < 1 × 10(-8)) among SLE patients. Common to all three cell-types were widespread and severe hypomethylation events near genes involved in interferon signaling (type I). These interferon-related changes were apparent in patients collected during active and quiescent stages of the disease, suggesting that epigenetically-mediated hypersensitivity to interferon persists beyond acute stages of the disease and is independent of circulating interferon levels. This interferon hypersensitivity was apparent in memory, naïve and regulatory T-cells, suggesting that this epigenetic state in lupus patients is established in progenitor cell populations. We also identified a widespread, but lower amplitude shift in methylation in CD4+ T-cells (> 16,000 CpGs at FDR < 1%) near genes involved in cell division and MAPK signaling. These cell type-specific effects are consistent with disease-specific changes in the composition of the CD4+ population and suggest that shifts in the proportion of CD4+ subtypes can be monitored at CpGs with subtype-specific DNA methylation patterns.


Using Technology to Limit the Impacts of Isolation on Youth in Inpatient Psychiatry Units.
The COVID-19 pandemic has been identified as a mental health crisis for children and adolescents in America.1 Social isolation and loneliness during the pandemic present a significant challenge. A rapid systematic review published in this journal found that social isolation correlates with depression and anxiety and may heighten the risk of disorder onset.2 Specifically in an infectious disease context, research on the H1N1 influenza pandemic showed that children in North America required to quarantine were 5 to 30 times more likely to meet criteria for posttraumatic stress disorder than children not under these restrictions.2.


EPR studies of the dynamics and phase behaviour of dithiadiazolyl radicals derived from mesogenic precursors.
A series of liquid-crystalline materials based on 4-substituted cyanobiphenyls, RC(6)H(4)C(6)H(4)CN (R = C(5)H(11), C(6)H(13), C(7)H(15), C(8)H(17) and C(12)H(25), commonly referred to as 5CB, 6CB, 7CB, 8CB and 12CB, respectively) were functionalised to give the corresponding dithiadiazolyl organic radicals RC(6)H(4)C(6)H(4)CNSSN(*) (compounds 1(*), 2(*), 3(*), 4(*) and 5(*), respectively). EPR spectra of n-C(12)H(25)C(6)H(4)C(6)H(4)CNSSN(*) (5(*)) reveal that it adopts a dimeric diamagnetic structure in the solid state with a small number of paramagnetic defect sites. Variable temperature electron paramagnetic resonance (EPR) studies reveal a thermally activated rotation about the molecular long axis at temperatures above 314 K. The energy barrier to rotation about the phenylene-dithiadiazolyl bond was estimated as 25 kJ mol(-1) using density functional theory (DFT). At elevated temperatures thermal annealing was also observed, quenching the sample's paramagnetism.


Single-cell differences in matrix gene expression do not predict matrix deposition.
Mesenchymal stem cells (MSCs) display substantial cell-to-cell heterogeneity, complicating their use in regenerative medicine. However, conventional bulk assays mask this variability. Here we show that both chondrocytes and chondrogenically induced MSCs exhibit substantial mRNA expression heterogeneity. Single-molecule RNA FISH to measure mRNA expression of differentiation markers in single cells reveals that sister cell pairs have high levels of mRNA variability, suggesting that marker expression is not heritable. Surprisingly, this variability does not correlate with cell-to-cell differences in cartilage-like matrix production. Transcriptome-wide analysis suggests that no combination of markers can predict functional potential. De-differentiating chondrocytes also show a disconnect between mRNA expression of the cartilage marker aggrecan and cartilage-like matrix accumulation. Altogether, these quantitative analyses suggest that sorting subpopulations based on these markers would only marginally enrich the progenitor population for 'superior' MSCs. Our results suggest that instantaneous mRNA abundance of canonical markers is tenuously linked to the chondrogenic phenotype at the single-cell level.


Generation of 520 mW pulsed blue light by frequency doubling of an all-fiberized 978 nm Yb-doped fiber laser source.
Pulsed blue light at 489 nm has been generated by second-harmonic-generation of a nanosecond pulsed master-oscillator power amplifier system based on a short Yb(3+) doped single-mode fiber amplifier at 978 nm and an external-cavity diode laser as seed source. The Yb(3+)-doped fiber was core-pumped by a W type Nd(3+) doped double-clad fiber laser operating on the transition near 930 nm ((4)F(3/2)→(4)I(9/2)). 520 mW of average power was generated at 489 nm using a periodically poled MgO:LiNbO(3), corresponding to a conversion efficiency of 34%.


1-{3-[(7-Fluoro-9H-pyrimido[4,5-b]indol-4-yl)(meth-yl)amino]-piperidin-1-yl}propan-1-one.
The title compound, C19H22FN5O, has been synthesized as an inhibitor of glycogen synthase kinase-3β. Two mol-ecules inter-act via two N-H⋯N hydrogen bonds, forming centrosymmetric dimers.


Sensitization of HT29 colorectal cancer cells to vemurafenib in three-dimensional collagen cultures.
The extracellular matrix to which cancer cells adhere affects cellular sensitivity to anticancer drugs. We sought to examine the changes in sensitivity of colorectal cancer cells carrying the BRAF V600E mutation to vemurafenib cultured in three-dimensional (3D) collagen-I gels, while also identifying the signaling pathways involved in these changes. HT29 colorectal cancer cells were cultured in conventional tissue culture (TC) plastic plates or in collagen-I gels. The HT29 cells demonstrated approximately 10-fold higher sensitivity to vemurafenib in 3D-collagen-I gels compared with those cultured on conventional TC plastic plates. Furthermore, in cells cultured on TC plastic, vemurafenib was found to augment tyrosine phosphorylation of focal adhesion kinase (FAK), while 3D-cultured cells expressed lower levels of FAK and vemurafenib did not affect its tyrosine phosphorylation, suggesting that FAK contributes to vemurafenib resistance. However, pharmacological inhibition of FAK did not sensitize the cells to vemurafenib. Also, the level of tyrosine-phosphorylated epidermal growth factor receptor (EGFR)/ERBB2 family proteins was found to be lower in cells cultured in 3D-collagen gel compared with those in cells cultured on TC plastic. Afatinib, an inhibitor of the EGFR/ERBB family of kinases, sensitized the cells to higher concentrations of vemurafenib, implying their participation in vemurafenib resistance. Adhesion to collagen-I gel but not to the collagen-I-coated plastic surface sensitized the cells, suggesting that the rigidity of the media rather than adherence to collagen-I may be important for cellular sensitivity to vemurafenib.


Integrated Cu-Au stereo microelectrode arrays and microfluidic channels for the electrochemical detection of glucose.
Noble and transition metal nanomaterials are widely used in glucose sensing. However, the fabrication of these sensors still suffers from complex nanomaterial synthesis process and unstable nanomaterial loading on sensing surfaces. Herein, a Cu-Au bimetallic microelectrode array was prepared via local electrochemical deposition and electrochemical reduction without the need for templates and additional nanomaterial preparation processes. Based on the COMSOL computational fluid study, the obtained microelectrode arrays combined with microfluidic channels allow the continuous and rapid detection of glucose. Large number of active sites on the surface of 3D nano-arrays contributes to excellent sensing performance for glucose, with good linear detection ranges in 10 µM to 4 × 102 µM and 4 × 102 µM to 4 × 105 µM, and a low detection limit of 284 nM. The feasibility of sensor in real sample was verified by detecting glucose in beverages with good recoveries ranging from 95.50% to 104.31%.


Passive electrical properties and voltage dependent membrane capacitance of single skeletal muscle fibers.
The passive membrane capacitance and conductance of isolated single muscle fibers were investigated using a vaseline gap method. The results obtained with this method are consistent with those obtained using the microelectrode technique. It was confirmed that the membrane capacitance of skeletal muscle consisted of a large capacitance of tubular membrane (7-10 microF/cm2) and a much smaller capacitance of surface membrane (1-2 microF/cm2). The relative time constants of these two components vary from one sample to another, resulting in one time and two time constant behaviors. Secondly, the capacitance of isolated skeletal muscle fibers was investigated during hyper- and depolarizing pulses, using the transient bridge technique with the vaseline gap method. Measurements were performed at two frequencies, i.e. 500 Hz and 20 kHz. It was found that the membrane capacitance increased by 15-20% with depolarizations. The voltage dependent membrane capacitance was not affected by the addition of tetrodotoxin in bathing solution blocking sodium current and muscle contraction. Also, blocking both Na and K current did not have an appreciable effect on the non-linear behavior of membrane capacitance. The origin of voltage dependent capacitance in muscle membrane appears to be distributed among several non-linear ionic processes such as Na and K currents and the flux of Ca and Cl ions and their accumulation.


Microdrive and method for single unit recording in the active rat.
A technique for recording single unit activity in the active rat with microelectrodes is described. The microdrive used is small and light enough to be carried in a well that is chronically implanted on the head of the rat. The device permits standard microelectrodes to be lowered without rotation, a feature which reduces chance of damage to the fine tips and to the brain tissue. The microdrive itself may be rotated in the well and several penetrations in a single preparation are possible. The electrodes used are capable of recording unit activity of high amplitude and stability. Units may be held for minutes or hours depending on the intensity of the rat's behavior.


Diagnosis of subarachnoid hemorrhage.
The ideal therapy and neurocritical care for patients with aneurysmal subarachnoid hemorrhage (SAH) follows from an early and accurate diagnosis. However, approximately 30% of patients with SAH are misdiagnosed at their initial visit to a physician. This article explores the reasons for this alarming error rate: failure to understand the full spectrum of presentation of SAH and failure to know the limitations of the major diagnostic tests (computed tomography of the brain and lumbar puncture [LP]). I suggest a strategy for selecting which patients with headache require evaluation beyond history and physical examination and how that evaluation should proceed. Other diagnostic issues are also discussed, such as use of magnetic resonance scanning and angiography for diagnosis, distinguishing the traumatic LP from true SAH, the concept of warning bleeds, and the LP-first diagnostic strategy.


Evaluation and recommendations from a study of a critical-care waiting room.
The intensive care unit (ICU) waiting room is a dynamic place that influences the satisfaction of families of critically ill patients. Waiting-room comfort and amenities are important, because families often spend a great deal of nonvisiting time there. A quality improvement evaluation of the ICU waiting room at Lehigh Valley Hospital, Allentown, PA, was conducted. Methods included distribution of an 18-item family survey, ethnographic observations, interviews, and assessment of the physical environment. Findings suggest that the role of the receptionist and access to food and other services were important to families and influenced their assessment of the quality of services provided by the ICU.


Therapeutic inhibition of breast cancer bone metastasis progression and lung colonization: breaking the vicious cycle by targeting α5β1 integrin.
At diagnosis, 10 % of breast cancer patients already have locally advanced or metastatic disease; moreover, metastasis eventually develops in at least 40 % of early breast cancer patients. Osteolytic bone colonization occurs in 80-85 % of metastatic breast cancer patients and is thought to be an early step in metastatic progression. Thus, breast cancer displays a strong preference for metastasis to bone, and most metastatic breast cancer patients will experience its complications. Our prior research has shown that the α5β1 integrin fibronectin receptor mediates both metastatic and angiogenic invasion. We invented a targeted peptide inhibitor of activated α5β1, Ac-PHSCN-NH2 (PHSCN), as a validated lead compound to impede both metastatic invasion and neovascularization. Systemic PHSCN monotherapy prevented disease progression for up to 14 months in Phase I clinical trial. Here, we report that the next-generation construct, Ac-PhScN-NH2 (PhScN), which contains D-isomers of histidine (h) and cysteine (c), is greater than 100,000-fold more potent than PHSCN at blocking basement membrane invasion. Moreover, PhScN is also up to 10,000-fold more potent than PHSCN at inhibiting lung extravasation and colonization in athymic mice for both MDA-MB-231 metastatic and SUM149PT inflammatory breast cancer cells. Furthermore, we show that systemic treatment with 50 mg/kg PhScN monotherapy reduces established intratibial MDA-MB-231 bone colony progression by 80 %. Thus, PhScN is a highly potent, well-tolerated inhibitor of both lung colonization and bone colony progression.