Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.
Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during the critical period of the central nervous system ontogeny.


Factors Associated with Sport-Related Post-concussion Headache and Opportunities for Treatment.
The purpose of this review is to (1) describe factors both pre- and post-injury that are associated with post-concussion headache, (2) describe the influence of post-concussion headache on recovery following concussion, and (3) provide potential post-concussion treatment options that may reduce the burden of headache, as well as other symptoms to facilitate recovery. Various factors may be associated with post-concussion headache presentation. These may include pre-injury or historical factors such as sex, family and self-history of headache and migraine, concussion history, and mood disorders. In addition, post-injury presentation factors for consideration may include injury mechanism, symptom clusters, cervicogenic dysfunction, and post-concussion physiologic dysfunction. Despite this complex interplay of factors, many treatment options may improve headache symptoms and recovery post-concussion including rehabilitation programs focusing on deficits such as visual-vestibular dysfunction, sub-symptom threshold exercise, and potential pharmacological interventions. Concussion is a complex injury that results in a variety of sequelae with headache being one of the most common. Understanding factors related to post-concussion headache presentation and the available options for treatment may improve patient care and outcomes post-concussion.


DNA damage response and mutagenesis in mouse embryonic stem cells.
Mutation in embryonic stem (ES) cells can potentially compromise multiple cell lineages and affect the well-being of subsequent generations. Thus, ES cells require sensitive mechanisms to maintain genomic integrity. One mechanism involves suppression of mutation. A complementary mechanism is to regulate the cell cycle checkpoint and facilitate cell death. Here, we describe the detailed protocols we have used to investigate DNA damage response and mutagenesis in mouse ES cells.


[Effects of resveratrol on hippocampal astrocytes and expression of TNF-α in Alzheimer's disease model rate].
To explore the effects of resveratrol on astrocyte and TNF-α in hippocampus of Alzheimer's disease (AD) model rats. Sixty rats were randomly divided into six groups: sham control group, model group, resveratrol 20, 40, 80 mg/kg group, and estradiol valerate group (0.8 mg/kg). The model of AD was established by ovariectomy combined injection of D-galactose (100 mg/kg). Twelve weeks later, the heart perfusion in vivo was done and then the hippocampus was fixed. Additionally, the changes of hippocampal astrocytes and TNF-α expression were detected by immunohistochemistry. The levels of glial fibrillary acidic protein (GFAP) and TNF-α in the model group were significantly higher than those of the sham control group (P < 0.01). No marked difference in the production of GFAP was observed between the resveratrol 20 mg/kg group and the model group (P > 0.05). However, the resveratrol 40, 80 mg/kg and estradiol valerate treated groups showed a decrease in the expression of GFAP compared with the model group (P < 0.01). Moreover, with the increasing of resveratrol concentration, the expression of GFAP decreased gradually. The levels of TNF-α decreased markedly in Res 20, 40, 80 mg/kg and estradiol valerate group compared with the model group (P < 0.01). These results suggest that the activation of astrocytes and the secretion of TNF-α can be inhibited by Res in AD rats.


Roles for Arc in metabotropic glutamate receptor-dependent LTD and synapse elimination: Implications in health and disease.
The Arc gene is robustly transcribed in specific neural ensembles in response to experience-driven activity. Upon induction, Arc mRNA is transported to dendrites, where it can be rapidly and locally translated by activation of metabotropic glutamate receptors (mGluR1/5). mGluR-induced dendritic synthesis of Arc is implicated in weakening or elimination of excitatory synapses by triggering endocytosis of postsynaptic AMPARs in both hippocampal CA1 and cerebellar Purkinje neurons. Importantly, CA1 neurons with experience-induced Arc mRNA are susceptible, or primed for mGluR-induced long-term synaptic depression (mGluR-LTD). Here we review mechanisms and function of Arc in mGluR-LTD and synapse elimination and propose roles for these forms of plasticity in Arc-dependent formation of sparse neural representations of learned experience. We also discuss accumulating evidence linking dysregulation of Arc and mGluR-LTD in human cognitive disorders such as intellectual disability, autism and Alzheimer's disease.


All in a day's work: an observational study to quantify how and with whom doctors on hospital wards spend their time.
To quantify time doctors in hospital wards spend on specific work tasks, and with health professionals and patients. Observational time and motion study. 400-bed teaching hospital in Sydney. 19 doctors (seven registrars, five residents, seven interns) in four wards were observed between 08:30 and 19:00 for a total of 151 hours between July and December 2006. Proportions of time in categories of work; proportions of tasks performed with health professionals and patients; proportions of tasks using specific information tools; rates of multitasking and interruptions. The greatest proportions of doctors' time were in professional communication (33%; 95% CI, 29%-38%); social activities, such as non-work communication and meal breaks (17%; 95% CI, 13%-21%), and indirect care, such as planning care (17%; 95% CI, 15%-19%). Multitasking involved 20% of time, and on average, doctors were interrupted every 21 minutes. Most tasks were completed with another doctor (56%; 95% CI, 55%-57%), while 24% (95% CI, 23%-25%) were undertaken alone and 15% (95% CI, 15%-16%) with a patient. Interns spent more time completing documentation and administrative tasks, and less time in direct care than residents and registrars. The time interns spent documenting (22%) was almost double the time they were engaged in direct patient care. Two-thirds of doctors' time was consumed by three work categories: professional communication, social activities and indirect care. Doctors on wards are interrupted at considerably lower rates than those in emergency and intensive care units. The results confirm interns' previously reported dissatisfaction with their level of administrative work and documentation.


The effect of endovascular revascularization of common iliac artery occlusions on erectile function.
To determine the incidence of erectile dysfunction in patients with common iliac artery (CIA) occlusive disease and the effect of revascularization on erectile function using the sexual health inventory for males (SHIM) questionnaire. All patients (35 men; mean age 57 ± 5 years; range 42-67 years) were asked to recall their sexual function before and 1 month after iliac recanalization. Univariate and multivariate analyses were performed to determine variables effecting improvement of impotence. The incidence of impotence in patients with CIA occlusion was 74% (26 of 35) preoperatively. Overall 16 (46%) of 35 patients reported improved erectile function after iliac recanalization. The rate of improvement of impotence was 61.5% (16 of 26 impotent patients). Sixteen patients (46%), including seven with normal erectile function before the procedure, had no change. Three patients (8%) reported deterioration of their sexual function, two of whom (6%) had normal erectile function before the procedure. The median SHIM score increased from 14 (range 4-25) before the procedure to 20 (range 1-25) after the procedure (P = 0.005). The type of recanalization, the age of the patients, and the length of occlusion were related to erectile function improvement in univariate analysis. However, these factors were not independent factors for improvement of erectile dysfunction in multivariate analysis (P > 0.05). Endovascular recanalization of CIA occlusions clearly improves sexual function. More than half of the patients with erectile dysfunction who underwent endovascular recanalization of the CIA experienced improvement.


Single-centre experience of genitourinary complications of epidermolysis bullosa.
Epidermolysis bullosa (EB) is a heterogeneous skin disorder that is sometimes associated with genitourinary involvement. We report our experience with the urological problems seen in these patients. Dermatology and nephro-urology databases were used to identify EB patients with urological problems, between 1980 and 2004. In total, five patients, all male, were identified, and the hospital records were reviewed. Genitourinary complications of EB present difficult challenges. The disorder can lead to urothelial blistering and strictures that can result in obstruction throughout the urinary tract. In addition, urethral instrumentation and surgical reconstruction in patients with EB has a high complication rate and should be avoided whenever possible.


Photodynamic disinfection and its role in controlling infectious diseases.
Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.


Trabecular bone score as a more sensitive tool to evaluate bone involvement in MEN1-related primary hyperparathyroidism.
The skeletal involvement of MEN1-related PHPT (MHPT) is not exactly the same as that of sporadic PHPT (SHPT). Trabecular bone score (TBS) as a texture parameter has been reported to reflect trabecular bone damage. This study aimed to compare the clinical characteristics, especially the skeletal involvement, between MHPT and SHPT patients. The clinical characteristics were retrospectively collected in 120 MHPT patients and compared to 360 SHPT patients in the same period. Dual-energy X-ray absorptiometry (DXA) were conducted in some MHPT patients, in whom bone mineral density (BMD) and calculated TBS derived from lumbar spine DXA images were compared with SHPT patients. Although the duration of disease in MHPT group was longer, the age at hospital visit was significantly lower than that in SHPT group (43.5 [31.5, 52.0] vs 52.0 [40.5, 61.0], P < 0.001). The proportion of skeletal involvement in MHPT group was significantly lower. However, in the subgroup of MHPT cases (n = 86) with data of BMD, there was no significant difference in skeletal involvement from SHPT cases matched for gender and age. While the BMD and TBS in lumbar spine of MHPT patients were lower than those of SHPT patients (BMD: 0.91 ± 0.18 g/cm2 vs. 1.01 ± 0.17 g/cm2; TBS: 1.22 ± 0.14 vs. 1.29 ± 0.11, P < 0.001). According to TBS, among 34 MHPT patients with normal BMD, 15 patients had bone microstructure damage. The cancellous bone microarchitecture was more severely damaged in MHPT patients according to TBS, which suggested that TBS could be a sensitive supplemental index in addition to BMD to identify bone-involvement risk in MHPT patients.


Mechanisms of transport of Na, Cl, and K in the human colon.
Ionic transport across isolated, stripped, human colonic mucosa was studied in vitro using a modified short circuit current technique. Electrical potential difference and short circuit current were dependent on the presence of sodium ions in the mucosal bathing solution and were unaffected by addition of 10 mM glucose to the solution. Ouabain (10(-3) M) added to the serosal reservoir abolished both potential difference and short circuit current. Isotopic flux measurements across short-circuited colonic mucosa showed a net active sodium absorption which accounted for the observed short circuit current and was unaffected by 10 mM glucose. Chloride was also actively absorbed and this was unaffected by removal of sodium from the bathing solutions. Ouabain abolished net sodium absorption but had no effect on chloride absorption. There was a net active secretion of potassium which was abolished in sodium-free buffer. We conclude that sodium is actively absorbed via a rheogenic process which is not stimulated by glucose; chloride is actively absorbed via a nonelectrogenic process, not linked to sodium transport, and probably involving a Cl-HCO3- exchange; and postassium is actively secreted possibly via a Na+K+ exchange.


One-pot synthesis of layered mesoporous ZSM-5 plus Cu ion-exchange: Enhanced NH3-SCR performance on Cu-ZSM-5 with hierarchical pore structures.
Hierarchical ZSM-5 zeolite with meso- and micro-pore structures was successfully prepared through a facile one-pot hydrothermal synthesis method using bifunctional template. After copper ion-exchange, it was applied for the selective catalytic reduction of NO with NH3 (NH3-SCR). Compared with conventional Cu-ZSM-5 catalyst containing only micropores, the hierarchical catalyst with ca. 2 wt.% Cu loading displayed significantly improved catalytic performance. Particularly, the hierarchical zeolite catalyst also displayed excellent hydrothermal stability and sulfur resistance that exhibited great potential in practical application. Characterization techniques such as XRD, N2 physisorption, temperature programmed desorption/reduction (TPD/TPR) and in situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS) were comprehensively used to reveal the relationship between zeolite structure and catalytic properties. It was concluded that the hierarchically porous structure could not only improve the mass transfer of reactant/product but also provide larger specific surface area, higher surface acidity, larger NO adsorption capacity. And we found that bidentate nitrate species was more active in Cu-ZSM-5-meso than Cu-ZSM-5-C, which were all beneficial to the NH3-SCR reaction. This work can provide a guideline to design other high performance hierarchical zeolites with different crystalline structures (such as CHA, LTA) for efficient catalytic NOx removal processes.


A novel function of protein kinase B as an inducer of the mismatch repair gene hPMS2 degradation.
Human DNA mismatch repair (MMR) proteins correct DNA errors, which normally occur during DNA replication. Defects of MMR genes result in genomic instability and carcinogenesis. However, the mechanism of MMR proteins regulation has not yet been clearly explored, especially for the member of MutL-related protein, human post meiotic segregation increased 2 (hPMS2). In this study, an inverse correlation between hPMS2 level and activated Akt was detected in nine tumor cell lines by western blot. The negative regulation of hPMS2 expression by activated Akt was further verified by functional experiments manipulating Akt activity using siRNA targeting Akt, Akt Inhibitor I, Akt/PKB Signaling Inhibitor-2 (API-2) and Insulin-like Growth Factor-I (IGF-1). In addition, protein complex immunoprecipitation assays and protein stability assays using cycloheximide revealed that activated Akt (P-Akt1 S473) could bind to hPMS2 directly and induce hPMS2 degradation. Moreover, results of immunofluorescence assays showed blocking Akt activity resulted in accumulation of hPMS2 protein in nucleus. These observations indicate that activated Akt is the upstream signaling regulating hPMS2 expression, stability and nuclear localization, providing a novel insight into the regulation of hPMS2 in cancer cells.


Results of elective duodenal ulcer surgery in women: comparison of truncal vagotomy and antrectomy, gastric selective vagotomy and pyloroplasty, proximal gastric vagotomy.
This study provides a retrospective comparative analysis of results in 90 women patients who underwent three different elective operations for intractable duodenal ulcer disease. Group I (30 patients) underwent truncal vagotomy/antrectomy (TV + A); group II (30 patients) gastric selective vagotomy/pyloroplasty (GSV + P); and Group III proximal gastric vagotomy (PGV). There were no operative deaths among the 90 patients. No patient after TV + A has developed a recurrent ulcer. Two recurrent ulcers developed after GSV + P, and one gastric ulcer occurred after PGV. Dumping, diarrhea, and reflux gastritis were lower after PGV than with TV + A and GSV + P. Follow-up studies have been from six months to ten years. The clinical results among the three groups of women patients compare favorably with results obtained in a recent prospective randomized study using the identical operative procedures in three groups of men patients operated upon for intractability. There was no statistically significant difference between women and men after similar operative procedures, but the postgastrectomy sequelae were less after PGV in both women and men patients.


A design for life: prokaryotic metal-binding MerR family regulators.
The MerR family of metal-binding, metal-responsive proteins is unique in that they activate transcription from unusual promoters and coordinate metals through cysteine (and in the case of ZntR, histidine) residues. They have conserved primary structures yet can effectively discriminate metals in vivo.


Prostacyclin producing activity of human umbilical blood vessels in adrenergic innervated and non-innervated portions.
The present experiment was performed in order to clarify the significance of prostacyclin (PGI2) in the regulation of human umbilical blood flow. Distribution of adrenergic nerve fibers in umbilical cord was examined by means of a modification of the glyoxylic acid fluorescence histochemical technique. PGI2 producing activity in various portions of umbilical blood vessels was measured by platelet bioassay. Adrenergic nerve fibers were observed only in the region surrounding umbilical arteries at the fetal end of the cord. PGI2 producing activity of umbilical arteries was significantly lower in the innervated region than in the non-innervated region. There were no significant regional differences in umbilical vein which has no adrenergic innervation. The relationship between vascular PGI2 producing activity and adrenergic innervation, and the significance of PGI2 in the regulation of human umbilical blood flow are discussed.


ROCK2-induced metabolic rewiring in diabetic podocytopathy.
Loss of podocytes is a common feature of diabetic renal injury and a key contributor to the development of albuminuria. We found that podocyte Rho associated coiled-coil containing protein kinase 2 (ROCK2) is activated in rodent models and patients with diabetes. Mice that lacked ROCK2 only in podocytes (PR2KO) were resistant to albuminuria, glomerular fibrosis, and podocyte loss in multiple animal models of diabetes (i.e., streptozotocin injection, db/db, and high-fat diet feeding). RNA-sequencing of ROCK2-null podocytes provided initial evidence suggesting ROCK2 as a regulator of cellular metabolism. In particular, ROCK2 serves as a suppressor of peroxisome proliferator-activated receptors α (PPARα), which rewires cellular programs to negatively control the transcription of genes involved in fatty acid oxidation and consequently induce podocyte apoptosis. These data establish ROCK2 as a nodal regulator of podocyte energy homeostasis and suggest this signaling pathway as a promising target for the treatment of diabetic podocytopathy.


Gender differences in active musculoskeletal stiffness. Part I. Quantification in controlled measurements of knee joint dynamics.
Active females demonstrate increased risk for musculoskeletal injuries relative to equivalently-trained males. Although gender differences in factors such as passive laxity, skeletal geometry and kinematics have been examined, the effect of gender on active muscle stiffness has not been reported. Stiffness of the active quadriceps and hamstrings musculature were recorded during isometric knee flexion and extension exertions from twelve male and eleven female subjects. A second-order biomechanical model of joint dynamics was used to quantify stiffness from the transient motion response to an angular perturbation of the lower-leg. Female subjects demonstrated reduced active stiffness relative to male subjects at all torque levels, with levels 56-73% of the males. Effective stiffness increased linearly with the torque load, with stiffness increasing at a rate of 3.3 Nm/rad per unit of knee moment in knee flexion exertions (hamstrings) and 6.6 Nm/rad per unit of knee moment extension exertions (quadriceps). To account for gender differences in applied moment associated with leg mass, regressions analyses were completed that demonstrated a gender difference in the slope of stiffness-versus-knee moment relation. Further research is necessary to identify the cause of the observed biomechanical difference and implications for controlling injury.


Effect of cholera toxin and prostaglandins on the rat choroid plexus in vitro.
The present study was performed to measure the effects of cholera toxin (CT) and prostaglandins (PG) on choroid plexus cyclic AMP accumulation. Choroid plexuses, isolated from Sprague-Dawley rats, were incubated in Krebs-Ringer bicarbonate buffer containing either CT (10 microgram/ml), heat inactivated CT, prostaglandins, or appropriate controls. After a minimum incubation period of 60 min with CT, cyclic AMP accumulation (pmol/mg protein) in treated incubates (58.10 +/- 6.43, n = 6) was 4 times that in controls (14.-5 +/- 1.4, n = 6). This large increase was only seen when theophylline (10 mM) was in the incubation mixture 3--10 min prior to the end of the incubation period. The increase in cyclic AMP accumulation was dose responsive and was irreversible after 5 min of incubation. Of the 5 prostaglandins studied, only PGE2 resulted in an increase in cyclic AMP accumulation. Cyclic AMP levels were 29.64 +/- 2.5 in controls and 57.57 +/- 3.5 in plexus which had been incubated with PGE2 (20 microgram/ml) for 1 min, and this increase was dose responsive.


Optimization of a sequential extraction procedure for trace elements in Arctic PM10.
In this work, a two-step sequential extraction scheme for the determination of trace elements in Arctic PM10 samples was optimized by using two certified reference materials (CRMs). By means of an experimental design for qualitative variables, the five most common extracting solutions for particulate matter (PM) sequential extraction (high purity water (HPW), 0.032 M HNO3, 0.022 M HCl, 0.11 M CH3COOH, and 0.012 M CH3COOH/CH3COONH4 buffer) and two different extraction methods (stirring and ultrasounds) were compared. The purpose of the study was the identification of the procedure which gives the best estimation of the anthropogenic portion of the elements present in PM10 samples. The use of ultrasounds instead of stirring induced a low but significant decrease of the extraction of all the elements and a decrease in the repeatability of the procedure. Diluted HNO3 was the extractant which allowed to maximize the extraction of anthropogenic elements (As, Cd, Pb, Zn) with respect to crustal ones (Al, Si, Ti). The optimized procedure proved successful in avoiding contaminations and, therefore, suitable to be applied to PM samples having extremely low concentrations, such as samples collected in polar or other remote areas. The chosen procedure was applied to ten Arctic PM10 samples, allowing for a better identification of their sources. Indeed, it was possible to hypothesize that even though the concentrations of As, Cd, K, Mg, Mn, and Ni in spring and summer were different, their mobility and, therefore, their chemical form in the analyzed PM10 samples were probably similar. Graphical abstract.


Economic impact of predominant ticks and tick-borne diseases on Indian dairy production systems.
As per 20th livestock census, India possessing 193.46 million cattle and 109.85 million buffaloes in organized and unorganized sectors. These animals are suffering from tick infestation almost throughout the year causing both direct and indirect losses. Repeated use of chemical acaricides for tick management resulted in the establishment of acaricide resistant tick populations, insecticide residues in livestock products and environmental pollution. In the present study, analysis of the data generated during 1990-2021 revealed pooled prevalence of infestations in cattle and buffaloes was 53% [95% CI = 47-60%] and 38% [95% CI = 28-49%], respectively. Based on peripheral blood smear examination the prevalence of theileriosis, babesiosis and anaplasmosis in cattle is estimated as 17% [95% CI = 12-24%], 4% [95% CI = 3-6%] and 5% [95% CI = 3-7%], respectively, while in buffalo the prevalence of infection is estimated as 7% [95% CI = 2-21%], 2% [95% CI = 0-5%] and 8% [95% CI = 2-36%],respectively.To estimate economic impact, both direct (reduction in milk production, cost of treatment, leather depreciation) and indirect (milk loss and treatment cost) losses were taken into consideration. Loss of milk production was predicted as 13.91, 56.91 and 85.34L/cross-bred cow/lactation in low, moderate and high tick infestation conditions, respectively. Whereas, 20.10, 7.01L milk/buffalo/lactation in Hyalomma spp. and Rhipicephalus spp. infestation was estimated. Similarly,the estimated loss of milk production due to clinical theileriosis, babesiosis and anaplasmosis was 57.96, 30.96 and 59.22L, respectively. The cumulative (milk loss, treatment cost and leather loss) loss due to tick infestation was calculated as 46199.31 million INR (USD595.07 million) while due to TBDs 14877.15 million INR (USD191.15 million) = 61076.46 million INR (USD787.63 million). The data provided base line information for the policy maker to develop strategies at government level so that the significantly high cumulative loss of 787.63 million USD due to ticks and tick borne diseases (TTBDs) can be minimized.


catena-Poly[[(1,10-phenanthroline-κ(2) N,N')copper(II)]-μ-2,2'-iminodibenzoato-κ(4) O,O':O'',O'''].
The structure of the title compound, [Cu(C14H9NO4)(C12H8N2)] n , consists of zigzag polymeric chains along the c axis. The asymmetric unit contains one Cu(II) atom which is coordinated by one 2,2'-imino-dibenzoate ligand and a one phenanthroline unit. Two intra-molecular N-H⋯O hydrogen bonds occur. The supra-molecular structure is characterized by weak C-H⋯O hydrogen bonds and π-π stacking inter-actions, forming a three-dimensional supramolecular network. The shortest centroid-centroid distances between neighbouring phenanthroline aromatic rings and 2,2'-imino-dibenzoate rings are 3.684 (1) and 3.640 Å, respectively. The shortest intra-chain Cu⋯Cu distance is 7.2885 (9) and the shortest Cu⋯Cu distance between Cu atoms in different chains is 7.1103 (6) Å.


Eye-fixation patterns in homonymous hemianopia and unilateral spatial neglect.
Eye-fixation patterns while viewing simple patterns were quantitatively analysed in homonymous hemianopic subjects with or without unilateral spatial neglect (USN), using an eye camera. Hemianopic subjects without USN used the strategy to look at the hemianopic side of the patterns longer in order to compensate for their visual field defect. However, those with USN lacked this compensatory eye-fixation pattern.


Dual substrate model for novel approach towards a kinetic study of acetylcholinesterase inhibition by diazinon.
Limited reports as compared to other insecticides appear in the literature for acetylcholinesterase (AChE) inhibition by diazinon. In the current study, new kinetic parameters of AChE inhibition by diazinon have been investigated. The assay was done with bovine retinal AChE using two different substrate (ASCh) concentrations in the absence and presence of diazinon (0.08-1.28 mM). The optical density was monitored up to 25 min (reaction time) for the assay. New kinetic parameters k'(oms), K'(sms), k(oms), K(sms), K'(asms) and K(asms) ) were calculated from these experimental data.


Distinguishing artificial spin ice states using magnetoresistance effect for neuromorphic computing.
Artificial spin ice (ASI) consisting patterned array of nano-magnets with frustrated dipolar interactions offers an excellent platform to study frustrated physics using direct imaging methods. Moreover, ASI often hosts a large number of nearly degenerated and non-volatile spin states that can be used for multi-bit data storage and neuromorphic computing. The realization of the device potential of ASI, however, critically relies on the capability of transport characterization of ASI, which has not been demonstrated so far. Using a tri-axial ASI system as the model system, we demonstrate that transport measurements can be used to distinguish the different spin states of the ASI system. Specifically, by fabricating a tri-layer structure consisting a permalloy base layer, a Cu spacer layer and the tri-axial ASI layer, we clearly resolve different spin states in the tri-axial ASI system using lateral transport measurements. We have further demonstrated that the tri-axial ASI system has all necessary required properties for reservoir computing, including rich spin configurations to store input signals, nonlinear response to input signals, and fading memory effect. The successful transport characterization of ASI opens up the prospect for novel device applications of ASI in multi-bit data storage and neuromorphic computing.


Survival and migration of transplanted male glia in adult female mouse brains monitored by a Y-chromosome-specific probe.
A Y-chromosome-specific probe and in situ hybridization technology have been used to monitor the survival and migration of neonatal male glia isografted to the left cerebral hemisphere of adult female mice. More than 95% of the cultured donor glia were glial fibrillary acidic protein (GFAP)-positive astrocytes. By 4 weeks, large numbers of transplanted glia were found in both cerebral hemispheres; the extent of glial migration was greatest in white matter tracts. This method provides a new way of identifying all surviving donor cells within the brains of immunologically compatible hosts.


Synchrotron radiation circular dichroism spectroscopy of oligonucleotides at millimolar concentrations.
Circular dichroism spectroscopy of nucleic acids has been traditionally performed at sample concentrations orders of magnitude lower than what occur in biological systems. While recent work from us demonstrated the flexibility of an adjustable sample cell that allowed for successful recording of CD spectra of an 18- and a 21-mer double stranded DNA sequences at around 1 mM, sample concentrations beyond 1 mM present a challenge for standard benchtop CD spectrometers. In the present work, the synchrotron radiation circular dichroism (SRCD) spectra were recorded for d(CG)9 and a mixed 18-mer double stranded DNA at 1, 5, and 10 mM in 100 mM or 4 M NaCl. SRCD of low molecular weight salmon DNA was also measured at a 10 mg/ml concentration. These results represent the first report of CD spectra of DNA samples measured at concentrations comparable to those found in the nucleus. The results suggest that dsDNA maintain very similar structures at concentrations up to tens of mg/ml, as evident by the very similar CD patterns in this concentration range. Furthermore, the SRCD allowed for the recording of CD patterns of DNA in the far UV region, which is not readily accessible by standard benchtop CD spectropolarimeters. These far UV signals appear to be quite characteristic of DNA structures and are sensitive to sample conditions.


Manual dexterity in late childhood is associated with maturation of the corticospinal tract.
Despite the important role of manual dexterity in child development, the neurobiological mechanisms associated with manual dexterity in childhood remain unclear. We leveraged fixel-based analysis (FBA) to examine the longitudinal association between manual dexterity and the development of white matter structural properties in the corticospinal tract (CST). High angular diffusion weighted imaging (HARDI) data were acquired for 44 right-handed typically developing children (22 female) aged 9-13 across two timepoints (timepoint 1: mean age 10.5 years ± 0.5 years, timepoint 2: 11.8 ± 0.5 years). Manual dexterity was assessed using the Grooved Pegboard Test, a widely used measure of manual dexterity. FBA-derived measures of fiber density and morphology were generated for the CST at each timepoint. Connectivity-based fixel enhancement and mixed linear modelling were used to examine the longitudinal association between manual dexterity and white matter structural properties of the CST. Longitudinal mixed effects models showed that greater manual dexterity of the dominant hand was associated with increased fiber cross-section in the contralateral CST. Analyses further demonstrated that the rate of improvement in manual dexterity was associated with the rate of increase in fiber cross-section in the contralateral CST between the two timepoints. Our longitudinal data suggest that the development of manual dexterity in late childhood is associated with maturation of the CST. These findings significantly enhance our understanding of the neurobiological systems that subserve fine motor development and provide an important step toward mapping normative trajectories of fine motor function against microstructural and morphological development in childhood.


Standing out from the crowd: cancer stem cells in hepatocellular carcinoma.
Cancer stem cells (CSCs) drive solid tumor formation. In this issue of Cancer Cell, Zhao and colleagues indentify the calcium channel α2δ1 subunit as a new functional hepatocellular carcinoma (HCC) CSC biomarker, which is vital for CSC biology as blocking α2δ1 in combination with doxorubicin treatment hinders HCC tumor formation.


An Integrated Ecological Modeling System for Assessing Impacts of Multiple Stressors on Stream and Riverine Ecosystem Services within River Basins.
We demonstrate a novel, spatially explicit assessment of the current condition of aquatic ecosystem services, with limited sensitivity analysis for the atmospheric contaminant mercury. The Integrated Ecological Modeling System (IEMS) forecasts water quality and quantity, habitat suitability for aquatic biota, fish biomasses, population densities, productivities, and contamination by methylmercury across headwater watersheds. We applied this IEMS to the Coal River Basin (CRB), West Virginia (USA), an 8-digit hydrologic unit watershed, by simulating a network of 97 stream segments using the SWAT watershed model, a watershed mercury loading model, the WASP water quality model, the PiSCES fish community estimation model, a fish habitat suitability model, the BASS fish community and bioaccumulation model, and an ecoservices post-processer. Model application was facilitated by automated data retrieval and model setup and updated model wrappers and interfaces for data transfers between these models from a prior study. This companion study evaluates baseline predictions of ecoservices provided for 1990 - 2010 for the population of streams in the CRB and serves as a foundation for future model development.


Planned cesarean versus planned vaginal delivery at term: comparison of newborn infant outcomes.
The purpose of this study was to examine neonatal outcomes among women with a planned cesarean and a planned vaginal delivery at term. This prospective survey was conducted on 18,653 singleton deliveries that represent 24 maternity units during a 6-month period. The data were retrieved from the Medical Birth Registry of Norway and analyzed according to intended mode of delivery. Compared with planned vaginal deliveries, planned cesarean delivery increased transfer rates to the neonatal intensive care unit from 5.2% to 9.8% (P < .001). The risk for pulmonary disorders (transient tachypnea of the newborn infant and respiratory distress syndrome) rose from 0.8% to 1.6% (P = .01). There were no significant differences in the risks for low Apgar score and neurologic symptoms. A planned cesarean delivery doubled both the rate of transfer to the neonatal intensive care unit and the risk for pulmonary disorders, compared with a planned vaginal delivery.


Sexual preference of meiotic recombination within the H-2 complex.
The recombination frequency between the H-2K and H-2D marker loci in male mice was measured using heterozygotes that carry the H-2wm7 haplotype derived from the Japanese wild mouse and common H-2 haplotypes derived from inbred mice. Previous mating experiments in which backcross progeny of heterozygous females were screened demonstrated that the H-2wm7 displays marked enhancement of recombination within the H-2 complex. In contrast to recombination in female mice, no enhancement of recombination was observed during male meiosis in the present study. Thus, it appeared that enhancement of recombination is specific to female mice. A genealogical study of recombination indicated that the postmeiotic stage is not involved in the generation of sexual preference of enhancement of recombination, suggesting that the preference is meiotic-drive and that a female-specific mechanism is involved in meiotic recombination mediated by the H-2wm7 haplotype.


Cognitive control during audiovisual working memory engages frontotemporal theta-band interactions.
Working memory (WM) maintenance of sensory information has been associated with enhanced cross-frequency coupling between the phase of low frequencies and the amplitude of high frequencies, particularly in medial temporal lobe (MTL) regions. It has been suggested that these WM maintenance processes are controlled by areas of the prefrontal cortex (PFC) via frontotemporal phase synchronisation in low frequency bands. Here, we investigated whether enhanced cognitive control during audiovisual WM as compared to visual WM alone is associated with increased low-frequency phase synchronisation between sensory areas maintaining WM content and areas from PFC. Using magnetoencephalography, we recorded neural oscillatory activity from healthy human participants engaged in an audiovisual delayed-match-to-sample task. We observed that regions from MTL, which showed enhanced theta-beta phase-amplitude coupling (PAC) during the WM delay window, exhibited stronger phase synchronisation within the theta-band (4-7 Hz) to areas from lateral PFC during audiovisual WM as compared to visual WM alone. Moreover, MTL areas also showed enhanced phase synchronisation to temporooccipital areas in the beta-band (20-32 Hz). Our results provide further evidence that a combination of long-range phase synchronisation and local PAC might constitute a mechanism for neuronal communication between distant brain regions and across frequencies during WM maintenance.


Mediation of arsenic oxidation by Thiomonas sp. in acid-mine drainage (Carnoulès, France).
To isolate, identify, and characterize heterotrophic bacteria in acid-mine drainage that mediate oxidation of As(III). Samples of acid-mine drainage were collected over a period of 14 months. Heterotrophic and non-obligatory acidophilic bacteria in the samples were cultured on a solid medium (pH 7.0-7.2), and three strains were isolated. The three different strains belong to the genus Thiomonas, and have more than 99% homology with the group Ynys1. Culturing in mineral media demonstrated that the isolated strains used thiosulphate as an energy source, and oxidized iron in the presence of thiosulphate. However, none of the strains were able to oxidize arsenic in the presence of thiosulphate, nor could they use iron or arsenic alone as an energy source. In vitro experiments demonstrated that two of the Thiomonas strains were able to oxidize more than 90% of the As(III) present in the acid-mine drainage, whereas no abiotic oxidation of arsenic occurred. Two strains of newly identified Thiomonas sp. found in acid-mine drainage are capable of oxidizing arsenic. These results represent the first reported oxidation of arsenic by Thiomonas sp. Biologically mediated oxidation and subsequent immobilization of arsenic is of great interest for the remediation of contaminated mine sites.


Force levels of fiber-reinforced composites and orthodontic stainless steel wires: a 3-point bending test.
The purpose of this study was to evaluate the force levels of 2 sizes (diameters, 0.6 and 1.2 mm) of fiber-reinforced composites (FRCs) (Ever Stick; Stick Teck Ltd, Turku, Finland) compared with orthodontic stainless steel wires (sections, 0.016, 0.018, 0.017 x 0.025, and 0.019 x 0.026 in) under the same testing conditions. The samples were divided into 12 groups, each consisting of 10 specimens. Each sample was evaluated with a 3-point bending test on a universal testing machine. The FRC groups were light-cured by hand with a halogen curing unit (Optilux 501; SDS Kerr, Danbury, Conn) for 40 seconds. Groups 1 through 6 were tested at 1-mm deflection, and groups 7 through 12 at 2-mm deflection. The results of ANOVA indicated significant differences among the various groups (P = .000). The post-hoc test showed that the 2-mm deflection groups had significantly higher load values than the 1-mm deflection groups (P = .000). The highest force levels were recorded with the 1.2-mm FRCs, followed by the 0.019 x 0.026-in stainless steel wires. No significant differences were found between the 0.6-mm FRCs and the 0.017 x 0.025-in wires. The lowest load values were reported with the 0.016-in stainless steel wires. The 1.2-mm FRCs showed higher load values than the other stainless steel wires and the FRCs, whereas no significant difference was found between the 0.6-mm FRCs and the 0.017 x 0.025-in stainless steel wires. Thus, FRCs can be considered a viable esthetic alternative to full-size stainless steel wires to rigidly join dental segments to form anchorage units or units for active tooth movement.


Preparation and properties of a cephalosporin acetylesterase adsorbed onto bentonite.
A cephalosporin acetylesterase produced by Bacillus subtilis was immobilized by adsorption onto bentonite. The immobilized enzyme (E(I)) and the soluble enzyme (E(S)) exhibited Michaelis-Menton kinetics with 7-aminocephalosporanic acid (7-ACA): K(m) = 2.8 x 10(-3) M and K(m) = 3.2 x 10(-3) M, respectively. Similar kinetics were observed with 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin), but the K(m) value measured with E(I) (3.7 x 10(-3) M) was less than one-half that measured with this substrate and E(S). The reduction in K(m) value was correlated with the ability of bentonite to adsorb cephalothin. The reaction products, acetate and deacetyl-7-ACA, were weak competitive inhibitors of E(S) and E(I). The K(i) values for E(I) were 5.0 x 10(-2) M for acetate and 3.6 x 10(-2) M for deacetyl-7-ACA. Similar values were measured with E(S) and these substrates. E(I) retained about 80% of its initial activity after 3 weeks of storage in solution at 25 C. However, the enzyme dissociated from the bentonite particles during the deacetylation reaction. This dissociation was minimized by cross-linking E(I) with glutaraldehyde or bis-dimethyladipimidate, or by adding Al(OH)(3) to the suspension. With the latter addition, E(I) was stabilized so that it could be reused nine times before one-half of the initial activity was lost.


Global burden of major gastrointestinal cancers and its association with socioeconomics, 1990-2019.
To understand the impact of common cancers of the gastrointestinal tract and help to formulate evidence-based policy, we evaluate the relationship between the burden of GI tract cancers and socioeconomics. Data on GI tract cancer burden were obtained from the Global Burden of Disease (GBD) 2019 including mortality and incidence rates. According to the Socio-demographic Index (SDI) level, country and territory, and sex, etc., the data were further stratified. The association between the burden of GI tract cancer and socioeconomics, indicated by SDI, was described. Uncertainty analysis was estimated using bootstrap draw. In 2019, five major cancers of the gastrointestinal tract led to an age-standardized incidence rate (ASIR) of 61.9 (95% CI 56.1-67.6) per 100 000 person-years. From 1990 to 2019, five common tumors of the gastrointestinal tract related age-standardized death rates (ASDRs) decreased by -22.7% (-31.1 to -13.5). For the five common tumors, ASIRs and ASDRs were both higher in males than those in females. Globally, Mongolia, and several East Asia countries exhibited the highest ASIRs in 2019. The high SDI, and high-middle SDI locations recorded the highest incidence rate and death rate of colon and rectum cancer and pancreatic cancer. On the contrary, the low-middle SDI, and low SDI locations possessed the highest incidence rate and death rate of stomach cancer and esophageal cancer. There is a profound association between socioeconomics and burden of common cancers of the gastrointestinal tract. It would be helpful for the high SDI, and high-middle SDI locations to pay special attention to the screening of colon and rectum cancer and pancreatic cancer while the low-middle SDI, and low SDI locations should pay more attention to the screening of stomach cancer and esophageal cancer.


A continental-scale soil evaporation dataset derived from Soil Moisture Active Passive satellite drying rates.
This manuscript describes an observationally-based dataset of soil evaporation for the conterminous U.S. (CONUS), gridded to a 9 km resolution for the time-period of April 2015-March 2019. This product is termed E-SMAP (Evaporation-Soil Moisture Active Passive) in which soil evaporation is estimated from the surface layer, defined by the SMAP sensing depth of 50 mm, between SMAP overpass intervals that are screened on the basis of precipitation and SMAP quality control flags. Soil evaporation is estimated using a water balance of the surface soil that we show is largely dominated by SMAP-observed soil drying. E-SMAP soil evaporation is on average 0.72 mm day-1, which falls within the range of soil evaporation estimates (0.17-0.89 mm day-1) derived from operational land surface models and an alternative remote sensing product. E-SMAP is independent from existing soil evaporation estimates and therefore has the potential to improve understanding of evapotranspiration partitioning and model development.


Conservative management of juvenile spongiotic gingivitis: a series of ten cases.
Introduction This case series highlights the condition juvenile spongiotic gingivitis; how to recognise it, where it lies in a list of differential diagnoses and why conservative management is the authors' recommended treatment.Case series The authors present ten cases that were successfully managed conservatively on the Joint Oral Medicine Paediatric Dentistry Clinic at Guy's and St Thomas' NHS Foundation Trust over a six-year period. Follow-ups reached up to 5 years and 11 months to date, with no adverse outcomes observed in any of the cases.Conclusion The pathogenesis of this benign condition and its ideal management is not well understood. Recurrence can occur after surgical treatment and the condition is likely to spontaneously resolve or regress with age. Therefore, particularly in asymptomatic cases, conservative management is recommended.


Acid-base disorders in critically ill neonates.
To study acid-base imbalance in common pediatric diseases (such as sepsis, bronchopneumonia, diarrhea, birth-asphyxia etc.) in neonates. An observational study was conducted in an emergency room of a tertiary teaching care hospital in Haryana, India. Fifty neonates (from first hour to one month) attending pediatric emergency services with various ailments. Blood gas analysis, electrolytes, plasma lactate, and plasma albumin were estimated in neonates. Metabolic acidosis was the most common acid-base disorder. Hyperlactatemia was observed in more than half of such cases. Birth asphyxia was another common disorder with the highest mortality in neonates followed by bronchopneumonia and sepsis. Significant correlation between mortality and critical values of lactate was observed. Birth asphyxia with high-lactate levels in neonates constituted major alterations in acid-base disorders seen in an emergency room of a tertiary teaching care hospital. Plasma lactate concentration measurement provides an invaluable tool to assess type of metabolic acidosis in addition to predicting mortality in these neonates.


Correction to: Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model.
An amendment to this paper has been published and can be accessed via the original article.


Molecular characterization of a novel chitinase from Bacillus thuringiensis subsp. kurstaki.
The present work aims to study a new chitinase from Bacillus thuringiensis subsp. kurstaki. BUPM255 is a chitinase-producing strain of B. thuringiensis, characterized by its high chitinolytic and antifungal activities. The cloning and sequencing of the corresponding gene named chi255 showed an open reading frame of 2031 bp, encoding a 676 amino acid residue protein. Both nucleotide and amino acid sequences similarity analyses revealed that the chi255 is a new chitinase gene, presenting several differences from the published chi genes of B. thuringiensis. The identification of chitin hydrolysis products resulting from the activity, exhibited by Chi255 through heterologous expression in Escherichia coli revealed that this enzyme is a chitobiosidase. Another chitinase named Chi255 belonging to chitobiosidase class was evidenced in B. thuringiensis subsp. kurstaki and was shown to present several differences in its amino acid sequence with those of published ones. The functionality of Chi255 was proved by the heterologous expression of chi255 in E. coli. The addition of the sequence of chi255 to the few sequenced B. thuringiensis chi genes might contribute to a better investigation of the chitinase 'structure-function' relation.


Potential of Mortierellaceae for polyunsaturated fatty acids production: mini review.
The health benefits of polyunsaturated fatty acids (PUFAs) have encouraged the search for rich sources of these compounds. However, the supply chain of PUFAs from animals and plants presents environmental concerns, such as water pollution, deforestation, animal exploitation and interference in the trophic chain. In this way, a viable alternative has been found in microbial sources, mainly in single cell oil (SCO) production by yeast and filamentous fungi. Mortierellaceae is a filamentous fungal family world-renowned for PUFA-producing strains. For example, Mortierella alpina can be highlighted due to be industrially applied to produce arachidonic acid (20:4 n6), an important component of infant supplement formulas. Thus, the state of the art of strategies to increase PUFAs production by Mortierellaceae strains is presented in this review. Firstly, we have discussed main phylogenetic and biochemical characteristics of these strains for lipid production. Next, strategies based on physiological manipulation, using different carbon and nitrogen sources, temperature, pH and cultivation methods, which can increase PUFA production by optimizing process parameters are presented. Furthermore, it is possible to use metabolic engineering tools, controlling the supply of NADPH and co-factors, and directing the activity of desaturases and elongase to the target PUFA. Thus, this review aims to discuss the functionality and applicability of each of these strategies, in order to support future research for PUFA production by Mortierellaceae species.


Breastfeeding exposure is associated with better knowledge of and attitudes toward BF in Kuwaiti women.
Breastfeeding (BF) has many benefits for both infants and mothers. However, despite evidence in support of BF, its prevalence has remained low in Kuwait. The purpose of this study was to (1) assess and describe BF attitudes and knowledge among women at a college campus; (2) evaluate BF exposures and sociodemographic factors associated with attitudes toward BF; (3) determine the association between BF knowledge and attitudes. This survey was a cross-sectional descriptive study conducted from February to April 2016. A convenience sample of 330 women (students, faculty and staff) from the College of Life Sciences (CLS) at Kuwait University participated in the survey. Most of the participants respected women who breast fed (81.8%). Some participants believed that BF a baby is painful (43.3%), makes the breasts sag (35.8%), and restricts the mothers' freedom (51.5%). Additionally, 47.6% of the participants reported that they would feel embarrassed if they saw a woman BF her baby. Acceptability of BF in public was low and most participants preferred BF only around friends and family (52.4%). A statistically significant positive association was observed between BF knowledge and attitudes (R2=6.5%, p<0.001); however, the relationship was not independent and was also associated with nationality and having been breast fed as a baby (R2=10.3%, p=0.021). BF knowledge is important to encourage positive BF attitudes, and both are enforced with family values and practice across generations.


A cad-gfpmut3 plasmid construct in Escherichia coli for gene induction-based quantification of lysine in acid hydrolysates of feedstuffs.
To generate an inducible plasmid-borne cad-gfpmut3 transcriptional fusion and develop a method for quantification of total lysine. The cad-gfpmut3 transcriptional fusion was constructed by cloning the cad promoter (Pcad) upstream of a promotorless gfpmut3 located on a high-copy plasmid. The construct was electroporated into Escherichia coli ZK126 and the transformed strain was subsequently used to quantify lysine in feed ingredients. Lysine standard curves based on gene induction of the bacterial cells were used for estimating acid hydrolysate lysine concentrations in four feed ingredients. Except for sorghum, no substantial differences were observed when the data for lysine in soybean (2 x 49 +/- 0 x 37%), cottonseed (1 x 82 +/- 0 x 15%), and meat and bone meal (2 x 31 +/- 0 x 24%) generated by the newly developed construct were compared with previously published data. Using the cad-gfpmut3 fusion, feed derived lysine induction was measured easily and accurately, and could be a useful tool for the estimation of lysine in acid hydrolysates of feed ingredients. The described approach for lysine quantification in feed ingredients represents a cost- and time-efficient method offering rapid and accurate lysine quantification of multiple samples.


[Activation of satellite cells in the intercostal muscles of patients with chronic obstructive pulmonary disease].
The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) display evidence of structural damage in parallel with signs of adaptation. We hypothesized that this can only be explained by the simultaneous activation of satellite cells. The aim of this study was to analyze the number and activation of those cells along with the expression of markers of microstructural damage that are frequently associated with regeneration. The study included 8 patients with severe COPD (mean [SD] forced expiratory volume in 1 second, 33% [9%] of predicted) and 7 control subjects in whom biopsies were performed of the external intercostal muscle. The samples were analyzed by light microscopy to assess muscle fiber phenotype, electron microscopy to identify satellite cells, and real-time polymerase chain reaction to analyze the expression of the following markers: insulin-like growth factor 1, mechano growth factor, and embryonic and perinatal myosin heavy chains (MHC) as markers of microstructural damage; Pax-7 and m-cadherin as markers of the presence and activation of satellite cells, respectively; and MHC-I, IIa, and IIx as determinants of muscle fiber phenotype. The patients had larger fibers than healthy subjects (54 [6] vs 42 [4] microm(2); P< .01) with a similar or slightly increased proportion of satellite cells, as measured by ultrastructural analysis (4.3% [1%] vs 3.7% [3.5%]; P>.05) or expression of Pax-7 (5.5 [4.1] vs 1.6 [0.8] arbitrary units [AU]; P< .05). In addition, there was greater activation of satellite cells in the patients, as indicated by increased expression of m-cadherin (3.8 [2.1] vs 1.0 [1.2] AU; P=.05). This was associated with increased expression of markers of microstructural damage: insulin-like growth factor 1, 0.35 (0.34) vs 0.09 (0.08) AU (P< .05); mechano growth factor, 0.45 (0.55) vs 0.13 (0.17) AU (P=.05). The intercostal muscles of patients with severe COPD show indirect signs of microstructural damage accompanied by satellite cell activation. This suggests the presence of ongoing cycles of lesion and repair that could partially explain the maintenance of the structural properties of the muscle.


Sidechain-linked inhibitors of HIV-1 protease dimerization.
There is a great need for alternative modes of inhibition for the design of anti-HIV therapies, due to the increased resistance of HIV to currently approved drugs. A novel strategy for generating potent dimerization inhibitors of HIV-1 protease is described based on sidechain-linked interfacial peptides. In a number of cases the activity of these agents against HIV-1 protease was found to be among the most potent reported, with inhibitory constants in the low nM range.


The influence of the patients' ethnicity, socio-demographic conditions and strain on psychiatric diagnoses given at an outpatient clinic.
Although psychiatric diagnoses are influenced by cultural and social conditions, with large global variations, the ICD and DSM systems are applied worldwide. The aims of this study were to describe the distribution of different ethnic patient groups in psychiatric outpatient services and the influence of ethnicity, demographic conditions and social strain on psychiatric diagnoses. An entire year's cohort of psychiatric outpatients (n = 839) in an outpatient register was divided into nine groups, according to country of birth. The proportion of each group in the outpatient population was compared with its corresponding proportion in the catchment area. In order to examine the relationship between socio-demographic variables and strain on the one hand, and DSM-III-R diagnoses on the other, stepwise logistic regression analyses were carried out. Swedes were the only group under-represented as outpatients (P < 0.001). Africans ran a higher risk (OR = 5.55, 95% CI = 2.56-12.04) than other ethnic groups of receiving a diagnosis of psychotic disorder--except schizophrenia--and Greek patients were more likely to receive a diagnosis of somatoform disorder (OR = 8.81, 95% CI = 4.41-17.59). Swedes were twice as likely to receive a diagnosis of personality disorder (OR = 2.16, 95% CI = 1.55-3.15). Schizophrenia was related to male gender (OR = 1.75, 95% CI = 1.04-2.94) and affective disorders to age >40 years (OR = 1.71, 95% CI = 1.22-2.40). Ethnicity has a strong impact on how diagnoses are given in cross-cultural settings. We could not confirm earlier findings of under-representation of ethnic minorities in outpatient services.


Continual planning and scheduling for managing patient tests in hospital laboratories.
Hospital laboratories perform examination tests upon patients, in order to assist medical diagnosis or therapy progress. Planning and scheduling patient requests for examination tests is a complicated problem because it concerns both minimization of patient stay in hospital and maximization of laboratory resources utilization. In the present paper, we propose an integrated patient-wise planning and scheduling system which supports the dynamic and continual nature of the problem. The proposed combination of multiagent and blackboard architecture allows the dynamic creation of agents that share a set of knowledge sources and a knowledge base to service patient test requests.


What activates the human mirror neuron system during observation of artificial movements: bottom-up visual features or top-down intentions?
In a recent study we could show that during observation of artificial object movements a similar cortical network, including the areas of the so-called human mirror neuron system (hMNS), was activated as during the observation of hand movements. The present study investigated whether activation of the hMNS during the observation of artificial object movements depends more on the visual features of the movements (buttom-up), or, by manipulating the task instructions, on the intentional goal of an observer (top-down). Using a factorial design we recorded the hemodynamic responses in 20 healthy participants while they watched arbitrary artificial object movements following two types of movement trajectories (smooth vs. discontinuous). In one part of the experiment participants had to detect color changes of two objects (color task) and in another part they had to judge whether the movement pattern of two objects could be performed with human hands (simulation task). We found stronger activation in the hMNS during the simulation than during the color task for both types of movement trajectories. In contrast, the color task activated the left ventral-occipital area (human V4). A direct comparison of smooth vs. discontinuous movement trajectories revealed significant effects neither in the structures of the hMNS nor in human V4. The present findings suggest that it is not a specific visual feature, such as a smooth biological movement trajectory, that activates the hMNS. Rather, the hMNS seems to respond when an observed movement is matched to a motor representation triggered by the intentional goal of the observer.


Exploring bacterial insertion sequences with ISfinder: objectives, uses, and future developments.
We describe here the use of the ISfinder database and its associated software. ISfinder was conceived -initially as a comprehensive database for prokaryotic insertion sequences (ISs). It now includes software for visualising complete and partial IS copies in whole genomes (ISbrowser) and for high-quality genome annotation (Insertion Sequence Semi-automatic Genome Annotation).


Disparities in primary and emergency health care among "off-reserve" Indigenous females compared with non-Indigenous females aged 15-55 years in Canada.
Access to primary care protects the reproductive and non-reproductive health of females. We aimed to quantify health care disparities among "off-reserve" First Nations, Métis and Inuit females, compared with non-Indigenous females of reproductive age. We used population-based data from cross-sectional cycles of the Canadian Community Health Survey (2015-2020), including 4 months during the COVID-19 pandemic. We included all females aged 15-55 years. We measured health care access, use and unmet needs, and quantified disparities through weighted and age-standardized absolute prevalence differences compared with non-Indigenous females. We included 2902 First Nations, 2345 Métis, 742 Inuit and 74 760 non-Indigenous females of reproductive age, weighted to represent 9.7 million people. Compared with non-Indigenous females, Indigenous females reported poorer health and higher morbidity, yet 4.2% (95% confidence interval [CI] 1.8% to 6.6%) fewer First Nations females and 40.7% (95% CI 34.3% to 47.1%) fewer Inuit females had access to a regular health care provider. Indigenous females waited longer for primary care, more used hospital services for nonurgent care, and fewer had consultations with dental professionals. Accordingly, 3.2% (95% CI 0.3% to 6.1%) more First Nations females and 4.0% (95% CI 0.7% to 7.3%) more Métis females reported unmet needs, especially for mental health (data for Inuit females not reported owing to high variability). During reproductive age, Indigenous females in Canada face many disparities in health care access, use and unmet needs. Solutions aimed at increasing access to primary care are urgently needed to advance health care reconciliation.


Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review.
The aim of this article is to conduct a literature review on first-generation TRK inhibitors (TRKi), namely entrectinib and larotrectinib, to describe the most common adverse events (AEs) and their management in adults. A search strategy was conducted in MEDLINE, EMBASE, and Google Scholar using a list of predetermined keywords. Peer-reviewed articles written in English and published through June 2021 were included. Articles covered included randomized clinical trials and expert recommendations, as well as patent and other types of reviews. The discussed AEs include weight gain and withdrawal pain, as well as neuromuscular, central nervous system (dysesthesias and peripheral sensory neuropathies, dizziness and ataxia, and dysgeusia), gastrointestinal (nausea, vomiting, and diarrhea), and respiratory symptoms. Additionally, several AEs encountered with entrectinib specifically (cognitive and vision disorders, congestive heart failure, QTc elongation, and skeletal fractures) are discussed. First, an overall mechanism of action explaining these AEs is presented. Then, for each AE, incidence and severity are stated and followed by practical management recommendations. While nearly all AEs were reversible upon TRKi suspension, the proposed managements are mainly constituted of pharmacological and non-pharmacological interventions. With the estimated growth of gene sequencing in the coming years, it is foreseeable that TRKi will take a larger position in the oncologic therapeutic arsenal. Therefore, adequate management of AEs associated with TRKi in adults should be a prime focus.


Medication Adherence in Children and Adolescents with Acne Vulgaris in Medicaid: A Retrospective Study Analysis.
The objectives of the study were to evaluate and compare medication adherence associated with acne drugs in children and adolescents with acne vulgaris. Data from MarketScan Medicaid enrollees with acne vulgaris were included if patients were ages 6 to 17 years on the index date, had at least one acne-related medication claim, and were enrolled in Medicaid during January 2004 to December 2007. The adherence rate was measured using the medication possession ratio. The medication possession ratio was dichotomized to categorize patients as adherent (≥0.8) or nonadherent (<0.8). Multivariate logistic regressions were used for analyses of the medication possession ratio. Of 20,039 eligible patients, 2,860 patients were children and 17,179 patients were adolescent. Approximately 6.96% of children and 16.75% of adolescents had at least one acne-related medication refill. The mean adherence rate to acne medication was significantly different between children (0.22) and adolescents (0.32). In addition, only 3.71% of children were adherent to acne medication while 13.38% of adolescents were adherent. After controlling for covariates, adolescents were 2.06 times more likely to get an acne-related medication refilled and were 2.40 times more likely to be adherent to acne-related medication. The analyses also showed that acne-related medication adherence was associated with the patient's characteristics and acne medication type. Neither patient population was considered adherent to acne-related medications, nor was there a significant difference between the two patient populations. This study also revealed that medication type is a contributing factor towards adherence. Health care providers should strive to educate patients on the importance of medication adherence.


Field induced rotational viscosity of ferrofluid: effect of capillary size and magnetic field direction.
In the present investigation we report the effect of capillary diameter and the direction of applied magnetic field on the rotational viscosity of water and kerosene based ferrofluids. We found that changes in the field induced rotational viscosity are larger in the case of water based magnetic fluid than that of kerosene based fluid. The field induced rotational viscosity is found to be inversely proportional to the capillary diameter and it falls exponentially as a function of the angle between the direction of field and vorticity of flow. Magnetophoretic mobility and hydrodynamic volume fraction of nanomagnetic particles are determined for above cases.


Cyclophosphamide, adriamycin and platinum (CAP) combination chemotherapy, a new effective approach in the treatment of disseminated breast cancer. Preliminary report.
The prospective controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination (CAP), compared with the combination including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFVP), in untreated metastatic breast cancer. One hundred and twenty-three patients (greater than 2 cycles) were evaluated: 61 on the CAP, and 62 on the CMFVP schedule. An objective response (CR + PR) to CAP combination chemotherapy was achieved in 72% of patients (43/61), with a high rate (36%) of complete remissions. In terms of metastatic site, the response rate appeared to be particularly high in soft tissue and visceral organ (lung, liver) metastases. In the CMFVP group, an objective response was noted in 26 of 62 patients (42%), with 16% complete remissions. The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen (P less than 0.01). The duration of remissions was 6-28 + months (means = 14) for the CAP, and 4-15 + months (mean = 9) for the CMFVP schedule. Toxic side effects were more pronounced in the CAP group, particularly myelosuppression, with anemia prevailing. Side effects of CMFVP treatment were moderate. In 39 CMFVP previously treated cases, CAP was administered as second-line treatment, and an objective response was observed in 51% of cases (20/39). Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer.


Prolonged response to exemestane following multiple surgical resections and hormonal therapies in a patient with recurrent endometrial stromal sarcoma.
Endometrial stromal sarcomas (ESSs) are rare, indolent tumors with high recurrence rates. Management includes surgery and hormonal therapy given high estrogen and progesterone receptor (ER/PR) expression. A pre-menopausal patient with stage II ESSs (ER +/PR +) underwent primary surgery followed by adjuvant megestrol. Recurrence in the bladder/upper vagina (ER +/PR -) was diagnosed one year later and treated with anterior pelvic exenteration and adjuvant letrozole. Two years later she recurred and was treated with radical surgery and adjuvant exemestane therapy (tumor ER strongly +/PR +). The patient then had a five-year disease free interval before being diagnosed with her third recurrence (ER +). Exemestane treatment for ESSs can lead to a prolonged response, even in the setting of progression after prior aromatase inhibitor treatment.


Fat accumulates preferentially in the right rather than the left liver lobe in non-diabetic subjects.
To examine the distribution of liver fat (LFAT) in non-diabetic subjects and test whether the fat in the right as compared to the left lobe correlates better with components of the metabolic syndrome or not. In this cross sectional study, we determined LFAT by 1H-MRS in the right lobe (LFAT%MRS), and by MRI (LFAT%MRI) in four regions of interest (ROIs 1-4, two in the right and two in the left lobe) in 97 non-diabetic subjects (age range 22-74 years, BMI 18-41kg/m2) and compared the accuracy of LFATMRI in the different ROIs in diagnosing non-alcoholic fatty liver disease (NAFLD) using areas under the receiver operator characteristic (AUROC) curves. 38% of the subjects had NAFLD (LFAT%MRS). LFAT%MRI was significantly higher in the right (5.7±0.5%) than the left (5.1±0.4%) lobe (p<0.02). The AUROC for LFAT%MRI in the right lobe for diagnosing NAFLD was significantly better than that in the left lobe. The relationships between several metabolic parameters and LFAT%MRI in the left lobe were significantly worse than those for LFAT%MRS while there was no difference between LFAT%MRS and right lobe ROIs. Liver right lobe contains more fat and correlates better with components of the metabolic syndrome than the left in non-diabetic subjects.


Sleep disruption, use of sleep-promoting medication and circadian desynchronization in spaceflight crewmembers: Evidence in low-Earth orbit and concerns for future deep-space exploration missions.
The spaceflight environment presents unique demands on human physiology; among those demands, is sleep. Sleep loss and circadian desynchronization is a major concern for future deep- exploration plans, including long-term crewed missions to the Moon and Mars. Analyze evidence of sleep disruption in crewmembers during low-Earth orbit missions, identify the use of sleep-promoting medication among crewmembers and deepen the comprehension of challenges to sleep physiology for future missions to the Moon and Mars. Evidence consistently indicates a loss of sleep and circadian rhythm disruption during low-Earth orbit missions. Sleep duration is shortened especially the night before a critical operation and during circadian-misaligned sleep episodes. The prevalence of sleep-promoting medication ranges between 71% and 78%; medication is more frequently taken on circadian-misaligned sleep episodes. Regarding the Moon, Apollo astronauts had variable sleep duration. For some, sleep was restful while others had poor-quality sleep. Many reported fatigue and errors due to the lack of rest. A loss of the 24-h light/dark might be expected due to the Moon's complex illumination characteristics. Regarding Mars, one main challenge will consist in synchronizing the circadian clock to a Martian day (24.65 h).


Role of Cervical Vestibular Evoked Myogenic Potentials (cVEMP) as Outcome-Measure of Glycerol Test.
Diagnosis of Meniere's disease is mainly clinical although many tests have been studied for efficacy in diagnosis of Meniere's disease. Glycerol test is a functional test to identify hydrops in Meniere's disease and can be done with PTA, Speech audiometry, otoacoustic emission, EcochG and cVEMP as its outcome measures. The study aimed to compare two outcome measures of glycerol test to identify Meniere's disease; to determine whether the stage of Meniere's disease affected glycerol outcomes; and to attempt to identify independent variables that could predict outcomes of glycerol test. 26 ears of 20 Meniere's disease participants were evaluated using PTA-based and cVEMP-based glycerol tests. Each test identified ten of 26 ears with Meniere's disease; and high agreement was noted in the two outcome measures. The stage of Meniere's disease based on four frequency hearing threshold average was not associated with outcome of glycerol test, but staging of Meniere's disease based on symptom duration was associated with glycerol test results. As the duration of symptoms increased there was lesser chance of positive outcomes on glycerol test; but intermediate stages of Meniere's disease showed positive outcomes. Variables such as age, gender, severity of hearing loss, duration of symptoms and pre-glycerol cVEMP measurements could not predict glycerol test outcomes. PTA-based and cVEMP- based glycerol tests hold promise in the test battery for identification of Meniere's disease. Positive findings on the test lead to confirmatory diagnosis but a negative glycerol test does not rule out Meniere's disease.


Preformed and de novo DSA are associated with T-cell-mediated rejection in pediatric liver transplant recipients requiring clinically indicated liver biopsy.
Despite growing interest about the impact of donor-specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single-center chart review of children (0-16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient- and donor-characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow-up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty-eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6-7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS.


Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.
Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease. Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein. Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05). Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.


MUC-1 mucin in normal human salivary glands detected by HMFG-1 and HMFG-2 monoclonal antibodies.
The aim of this study was to determine the immunoexpression of normal salivary gland cells using two human milk fat globule membrane protein antibodies (HMFG-1 and HMFG-2). Paraffin-embedded, 5 microm-thick slides from parotid and submandibular gland tissues were cut and immunostained with monoclonal antibodies HMFG-1 and HMFG-2 against MUC1 protein. HMFG antigens were found in secretory epithelial cells and ductal cells lining the striated and intercalated ducts in the intraductal secretion material, and sometimes in the myoepithelial cells. Our results suggest that HMFG-1 and HMFG-2 proteins may play a role in normal salivary gland function, mainly in the manufacturing and secretion of saliva.


Validating the Incorporation of 13C and 15N in a Shorebird That Consumes an Isotopically Distinct Chemosymbiotic Bivalve.
The wealth of field studies using stable isotopes to make inferences about animal diets require controlled validation experiments to make proper interpretations. Despite several pleas in the literature for such experiments, validation studies are still lagging behind, notably in consumers dwelling in chemosynthesis-based ecosystems. In this paper we present such a validation experiment for the incorporation of 13C and 15N in the blood plasma of a medium-sized shorebird, the red knot (Calidris canutus canutus), consuming a chemosymbiotic lucinid bivalve (Loripes lucinalis). Because this bivalve forms a symbiosis with chemoautotrophic sulphide-oxidizing bacteria living inside its gill, the bivalve is isotopically distinct from 'normal' bivalves whose food has a photosynthetic basis. Here we experimentally tested the hypothesis that isotope discrimination and incorporation dynamics are different when consuming such chemosynthesis-based prey. The experiment showed that neither the isotopic discrimination factor, nor isotopic turnover time, differed between birds consuming the chemosymbiotic lucinid and a control group consuming a photosynthesis-based bivalve. This was true for 13C as well as for 15N. However, in both groups the 15N discrimination factor was much higher than expected, which probably had to do with the birds losing body mass over the course of the experiment.


Is sirolimus responsible for proteinuria?
Sirolimus (SRL) is suspected to induce proteinuria. We retrospectively studied proteinuria in a population of liver (n = 29) and kidney transplant (n = 30) recipients switched to SRL with progressive diminution or withdrawal of calcineurin inhibitors (CNI). We also observed estimated glomerular filtration rate (GFR), modification of treatment with antiproteinuric drugs, and changes in concentration of SRL. Collection of data started 3 months before SRL introduction at a mean follow-up of 21 months. Following SRL introduction, proteinuria was not detected in the 28 liver transplant patients, and was stable in the two others. In the kidney transplant group, proteinuria did not occur in 12 patients, remained stable in three, and was slightly increased in 14 (0.57 +/- 0.93 g/d vs 1.83 +/- 1.26 g/d). For all patients, eGFR remained stable; there was no difference in management of antiproteinuric drugs. As suspected, cyclosporin (CsA) and tacrolimus (FK) serum concentrations were decreased. We observed a significant correlation between the variation of proteinuria and the variation of serum concentration of CsA or FK (respectively, P = .001 and P = .007). On the other hand, we did not find any correlation between variation in proteinuria and concentration of SRL. This retrospective study suggests that in our cohort of liver transplant patients without previous renal damage, SRL did not provoke proteinuria. On the other hand, the slight aggravation of proteinuria in a subgroup of kidney transplant patients seems to be linked to the hemodynamic renal effects due to CNI withdrawal.


Mycoplasma gallisepticum-induced alterations in chicken red blood cells.
Incubation of Mycoplasma gallisepticum with washed chicken red blood cells for 1 hr or 5 hr resulted in altered red blood cell surface morphology and perforations of the cells.


Poly[octa-carbonyl-heptakis-(tetra-hydro-furan)-diironmanganesedisodium(2 Mn-Fe)].
The reaction of Na2Fe(CO)4 with an excess of MnCl2 in tetra-hydro-furan (THF) produced {Fe2Mn(C4H8O)2Na2(C4H8O)5(CO)8] n or C36H56Fe2MnNa2O15. The compound is a xenophilic dianion with short iron-manganese bond lengths of 2.6274 (10) and 2.6294 (10) Å. The sodium cations of the dianion are coordinated to THF ligands and have isocarbonyl inter-actions forming a polymeric (two-dimensional) structure in the crystal. One of the THF mol-ecules was modeled with the carbon atoms being statistically disordered.


Hybridization chain reaction for regulating surface capacitance of organic photoelectrochemical transistor toward sensitive miRNA detection.
Photon-enabled bioelectronics has long been pursued in modern electronics due to their non-contact, remote-control, and even self-powered function interfacing the biological world with semiconductor devices. The debuting organic photoelectrochemical transistor (OPECT) relies on the photovoltage generated by the semiconductors to modulate the channel conductance, which enables light-fueled operation at zero gate bias. Inspired by the insulating nature of macrobiomolecules and surface capacitance mechanism, herein we demonstrate the biological regulation of the surface capacitance towards new OPECT biodetection, which was exemplified by a CdS quantum dots/TiO2 nanotubes photoanode accommodating hybridization chain reaction (HCR) amplification with the target of biomarker miRNA-17. Formation of the non-conducting DNA layer from the miRNA-17-oriented HCR could decrease the surface capacitance and increase the corresponding fractional potential drop, shifting the transfer curve horizontally to higher gate voltage and thus producing different drain currents. The OPECT biosensor exhibited a linear relationship with the miRNA-17 concentration on the logarithmic axis in the range from 1 pm. to 10 μm with a detection limit of 1 pm. This work not only represented a generic methodology of miRNA detection, but also provided a universal mechanism for the operation of advanced OPECT bioanalytics.


σ-GeH and Germyl Cationic Pt(II) Complexes.
The low electron count Pt(II) complexes [Pt(NHC')(NHC)][BArF] (where NHC is a N-heterocyclic carbene ligand and NHC' its metalated form) react with tertiary hydrogermanes HGeR3 at room temperature to generate the 14-electron platinum(II) germyl derivatives [Pt(GeR3)(NHC)2][BArF]. Low-temperature NMR studies allowed us to detect and characterize spectroscopically some of the σ-GeH intermediates [Pt(η2-HGeR3)(NHC')(NHC)][BArF] that evolve into the platinum-germyl species. One of these compounds has been characterized by X-ray diffraction studies, and the interaction of the H-Ge bond with the platinum center has been analyzed in detail by computational methods, which suggest that the main contribution is the donation of the H-Ge to a σ*(Pt-C) orbital, but backdonation from the platinum to the σ*(Ge-H) orbital is significant. Primary and secondary hydrogermanes also produce the corresponding platinum-germyl complexes, a result that contrasts with the reactivity observed with primary silanes, in which carbon-silicon bond-forming reactions have been reported. According to density functional theory calculations, the formation of Pt-Ge/C-H bonds is both kinetically and thermodynamically preferred over the competitive reaction pathway leading to Pt-H/C-Ge bonds.


Fractal dimension of K1735 mouse melanoma clones and spheroid invasion in vitro.
An in vitro tumour-host confrontation method to investigate the invasion behaviour of cancer has been applied to K1735 mouse melanomas. Fluorescently labelled spheroids of cancer cells and host cells were confronted and the temporal course of cancer invasion into the host was investigated using confocal laser scanning microscopy. To improve the quantitative data of this method, the boundary images of the fluorescently labelled confrontation pairs were treated as fractals. The physical and mathematical framework for determination of the fractal capacity dimension is widely used in biology and medicine and has proved to be a very useful tool for describing the cancer invasion process. The fractal capacity dimension determination was carried out by dilation of the binary boundaries of the objects, which were treated as an estimate of the Minkowski-Bouligand dimension. The fractal dimension correlated well with the degree of invasion of the K1735-M2 clone. Control experiments, with host-host confrontations and various K1735 clones with reduced invasiveness, support these results.


Early predictors of remission in children and adolescents with new-onset epilepsy: A prospective study.
This study aims to identify predictive factors of a two-year remission (2YR) in a cohort of children and adolescents with new-onset seizures based on baseline clinical characteristics, initial EEG and brain MRI findings. A prospective cohort of 688 patients with new onset seizures, initiated on treatment with antiseizure medication was evaluated. 2YR was defined as achieving at least two years of seizure freedom during the follow-up period. Multivariable analysis was performed and recursive partition analysis was utilized to develop a decision tree. The median age at seizure onset was 6.7 years, and the median follow-up was 7.4 years. 548 (79.7%) patients achieved a 2YR during the follow up period. Multivariable analysis found that presence and degree of intellectual and developmental delay (IDD), epileptogenic lesion on brain MRI and a higher number of pretreatment seizures were significantly associated with a lower probability of achieving a 2YR. Recursive partition analysis showed that the absence of IDD was the most important predictor of remission. An epileptogenic lesion was a significant predictor of non-remission only in patients without evidence of IDD, and a high number of pretreatment seizures was a predictive factor in children without IDD and in the absence of an epileptogenic lesion. Our results indicate that it is possible to identify patients at risk of not achieving a 2YR based on variables obtained at the initial evaluation. This could allow for a timely selection of patients who require close follow-up, consideration for neurosurgical intervention, or investigational treatments trials.


Simulation for Teaching on Racial Microaggressions and Bystander Intervention - A Theory-Based Guide for Health Profession Education.
Microaggressions are words or behaviour that "subtly and unconsciously express a prejudiced attitude", and racial microaggressions express these attitudes towards people from racial minority groups. The "Bystander Effect" is when the presence of other people means that an individual is less likely to offer assistance or get involved in a situation - bystander intervention training aims to inform about the best ways to avoid this, equipping students with the necessary strategies. In health profession education, teaching on microaggressions and bystander intervention can be done with the use of simulation. Simulated patients (SPs) and environments would be the most appropriate modality of simulation to use, as roleplay would be central. This guide focuses on how to use simulation for teaching on racial microaggressions and bystander training for healthcare students including tips on preparing the students and SPs, planning for the implementation of the simulation training, setting ground rules, showing different scenarios, checking student understanding throughout, using debriefs and course evaluation feedback, and signposting students to available support afterwards. These are topics which are particularly relevant because there have been calls in recent years for healthcare education to be more inclusive and representative of current issues, as the COVID-19 pandemic and resurgence of the Black Lives Matter movement have highlighted curriculum gaps. So teaching students about this early is a good start, and simulation is an effective teaching method to help with this.


Molecular characteristics and biological activities of anionic macromolecules from Codium fragile.
Water-soluble anionic macromolecules isolated from Codium fragile and fractionated using ion-exchange chromatography were investigated to determine their molecular characteristics and immunostimulating activity. The crude molecules and fractions (F1, F2, and F3) consisted mostly of carbohydrates (44.1-80.5%), sulfates (3.2-22.2%) and proteins (3.0-15.7%) with small amounts of uronic acids (1.1-4.2%), and included different levels of mannose (91.3-18.7%), glucose (62.7-8.6%) and galactose (37.5-59.5%). These molecules contained one or two subfractions with molecular weights (Mw) ranging from 148×10(3) to 4879×10(3)g/mol. The crude, F1 and F2 stimulated RAW264.7 cells to produce considerable amounts of pro-inflammatory mediator nitric oxide (NO) and cytokines. The treatment of sample molecules facilitated the degradation of Iκ-B and phosphorylation of MAPK in RAW264.7 cells, suggesting that they might stimulate RAW264.7 cells through the activation of NF-κB and MAPK pathway. Proteins in fraction F2 were essential to possess its bioactivity and its main backbone was composed of mixed linkages of (1→3)-α and β-d-mannan.


Attentional control in dysphoria: an investigation using the antisaccade task.
We examined inhibitory mechanisms in dysphoria using direct measures of attentional control. Dysphoric and non-dysphoric participants performed standard and delayed versions of the antisaccade and prosaccade tasks with facial expressions as stimuli. Results showed higher error rates in the standard antisaccade task than in the delayed tasks, with the dysphoric group having higher error rates in response to emotional facial expressions, in particular happy expressions. Our findings indicate impaired attentional processing in response to emotional facial expressions, in particular happy expressions, in dysphoria. Implications for understanding the mechanisms underlying attentional control in dysphoria are discussed.


GPCR large-amplitude dynamics by 19F-NMR of aprepitant bound to the neurokinin 1 receptor.
Comparisons of G protein-coupled receptor (GPCR) complexes with agonists and antagonists based on X-ray crystallography and cryo-electron microscopy structure determinations show differences in the width of the orthosteric ligand binding groove over the range from 0.3 to 2.9 Å. Here, we show that there are transient structure fluctuations with amplitudes up to at least 6 Å. The experiments were performed with the neurokinin 1 receptor (NK1R), a GPCR of class A that is involved in inflammation, pain, and cancer. We used 19F-NMR observation of aprepitant, which is an approved drug that targets NK1R for the treatment of chemotherapy-induced nausea and vomiting. Aprepitant includes a bis-trifluoromethyl-phenyl ring attached with a single bond to the core of the molecule; 19F-NMR revealed 180° flipping motions of this ring about this bond. In the picture emerging from the 19F-NMR data, the GPCR transmembrane helices undergo large-scale floating motions in the lipid bilayer. The functional implication is of extensive promiscuity of initial ligand binding, primarily determined by size and shape of the ligand, with subsequent selection by unique interactions between atom groups of the ligand and the GPCR within the binding groove. This second step ensures the wide range of different efficacies documented for GPCR-targeting drugs. The NK1R data also provide a rationale for the observation that diffracting GPCR crystals are obtained for complexes with only very few of the ligands from libraries of approved drugs and lead compounds that bind to the receptors.