[The Nephrological Aspects of the Use of Rivaroxaban and Other Direct Peroral Anticoagulants in Non-Valvular Atrial Fibrillation].
Chronic kidney disease (CKD) is a powerful cardiovascular risk factor, its presence is accompanied by an increased risk of hospitalization for exacerbation of chronic heart failure (CHF), adverse outcomes in myocardial infarction, and cardiovascular mortality. Among the adverse events, an increased risk of atrial fibrillation (AF) should be noted. This article contains discussion of current approaches to the treatment of AF in patients with different stages of CKD, data on benefits of certain direct oral anticoagulants, as well as comparative characteristics of therapy with direct oral anticoagulants and warfarin. Pharmacokinetics and pharmacodynamics of direct oral anticoagulants, which determine the features of therapy in CKD, are also considered.


Cellular Manipulation Using Rolling Microrobots.
Many biomedical applications, such as targeted drug delivery or cell manipulation, are well suited for the deployment of microrobots, untethered devices that are capable of carrying out tasks at the microscale. One biocompatible means of driving microrobots relies on magnetic actuation. In particular, microrobots driven using rotating fields rather than magnetic field gradients are especially practical for real-word applications. Many biological applications involve enclosed environments, such as blood vessels, in which surfaces are abundant, therefore, surface rolling is a particularly pertinent method of transportation. In this paper we demonstrate manipulation and transportation of cells using two types of magnetically driven rolling microrobots. We find that the microrobots are able to manipulate the cells by physically pushing or by first adhering to the cells and then carrying them. Microrobots spinning at high rates also can transport cells via the induced fluid flows.


Vitamin D receptor as an intestinal bile acid sensor.
The vitamin D receptor (VDR) mediates the effects of the calcemic hormone 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We show that VDR also functions as a receptor for the secondary bile acid lithocholic acid (LCA), which is hepatotoxic and a potential enteric carcinogen. VDR is an order of magnitude more sensitive to LCA and its metabolites than are other nuclear receptors. Activation of VDR by LCA or vitamin D induced expression in vivo of CYP3A, a cytochrome P450 enzyme that detoxifies LCA in the liver and intestine. These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer.


Chemotherapeutic Drugs: DNA Damage and Repair in Glioblastoma.
Despite improvements in therapeutic strategies, glioblastoma (GB) remains one of the most lethal cancers. The presence of the blood-brain barrier, the infiltrative nature of the tumor and several resistance mechanisms account for the failure of current treatments. Distinct DNA repair pathways can neutralize the cytotoxicity of chemo- and radio-therapeutic agents, driving resistance and tumor relapse. It seems that a subpopulation of stem-like cells, indicated as glioma stem cells (GSCs), is responsible for tumor initiation, maintenance and recurrence and they appear to be more resistant owing to their enhanced DNA repair capacity. Recently, attention has been focused on the pivotal role of the DNA damage response (DDR) in tumorigenesis and in the modulation of therapeutic treatment effects. In this review, we try to summarize the knowledge concerning the main molecular mechanisms involved in the removal of genotoxic lesions caused by alkylating agents, emphasizing the role of GSCs. Beside their increased DNA repair capacity in comparison with non-stem tumor cells, GSCs show a constitutive checkpoint expression that enables them to survive to treatments in a quiescent, non-proliferative state. The targeted inhibition of checkpoint/repair factors of DDR can contribute to eradicate the GSC population and can have a great potential therapeutic impact aiming at sensitizing malignant gliomas to treatments, improving the overall survival of patients.


Physicochemical effects in the representation of molecular structures for drug designing.
After the identification of a biological target, drug design is to analyze the relationships between the structure of potential ligands and their biological activity. A hierarchy of structure representation is presented here considering either the constitution of a molecule, its 3D structure, or the molecular surface. At each level, a variety of physicochemical effects can be accounted for. Furthermore, the special requirements of learning algorithm, such as neural networks, are taken into consideration. Application to problems from combinatorial chemistry, lead identification, high-throughput screening, and prediction of ADME-Tox properties are given.


Protein-losing enteropathy following the Fontan procedure in a child with intestinal lactase deficiency treated with lactose-free diet.
A 12-year-old girl presented with a protein-losing enteropathy. Symptoms started 4 weeks after undergoing the Fontan procedure at the age of 1.5 years for mitral atresia, ventricular septal defect, and double-outlet right ventricle. Upon referral for 3 weeks of rehabilitation after multiple interventional measures and drug treatments, she appeared in a dystrophic state, with decreased plasma protein and electrolyte levels along with occasional tetanic convulsions. Blood glucose levels after a lactose tolerance test were markedly reduced. The introduction of a lactose-free diet was quickly effective, with plasma protein and electrolyte levels raised to normal levels, and the girl's body weight increased without ascites or oedema. Molecular genetic examination revealed a homozygous C/C13910 polymorphism in the LCT gene. Protein-losing enteropathy in the Fontan circulation may be provoked by lactase deficiency and should therefore be ruled out to exclude this rather common condition.


Current poliovirus vaccines.
Most of the poliovirus vaccine distributed in the United States since 1962 has been of the live, oral type ( OPV ). Production problems have not been a major concern for the manufacturer. The statistics compiled by various authorities since the product was introduced relative to paralytic disease following the administration of OPV are discussed and recommendations for the use of OPV are cited.


Survival probability and prognostic factors for breast cancer patients in Vietnam.
Breast cancer is becoming a public health problem in Vietnam. The mortality to incidence ratio of the disease was ranked second among the most common cancers in women. This study estimates the survival probability at 1, 3, and 5 years following diagnosis and determines prognostic factors for breast cancer mortality in Vietnam. A survival analysis was conducted based on retrospective data from Hue Central Hospital and the Cancer Registry in Ho Chi Minh City. Using the Kaplan-Meier method, the survival probability of patients with breast cancer was estimated at 1, 3, and 5 years following diagnosis. The covariates among prognostic factors for survival time were studied using an extended Cox proportion hazards model, including time-dependent predictors. Overall survival rates at 1, 3, and 5 years following diagnosis were 0.94, 0.83 and 0.74 respectively. Marital status, education level, stage at diagnosis, and hormone therapy were prognostic factors for mortality. For the stage at diagnosis, the relation to the risk of death for breast cancer was 1.32 (95% CI, 1.22-1.41). Married women faced a risk of death nearly 1.59 times higher than unmarried women (95% CI, 1.09-2.33). Women with higher levels of education and who received hormone therapy had approximately 10% (hazard ratio [HR]: 0.92; 95% CI, 0.89-0.96) and 80% (HR: 0.22; 95% CI, 0.12-0.41) risk reduction of death respectively, compared with those classified as illiterate and those without hormone therapy. The 5-year survival probability of breast cancer was lower in Vietnam than in countries with similar distributions of the stage at diagnosis. Screening programs and related support policies should be developed to increase the life expectancy of women with breast cancer in Vietnam.


Papilliferous Keratoameloblastoma: A Rare Case Report.
Ameloblastoma is true odontogenic tumor of epithelial origin, which is described as locally aggressive with varying chances of recurrence. It is believed to derive from enamel organ, remnants of dental lamina, lining of odontogenic cysts, or basal cells of oral epithelium. Radiologically, it may present as unilocular or multilocular radiolucency commonly. Although conventional ameloblastoma presents typical histological features as described by Vickers and Gorlin, few unusual variants have been reported with different histological patterns. However, the clinical and biological behavior of these lesser known variants has not been established yet due to the scarcity of cases reported. Here, we report an extremely rare case of papilliferous ameloblastoma in a young male patient with 2-year follow-up and presenting with unusual histological presentation than conventional ameloblastoma.


Re-Evaluating the Effects of Obesity on Cancer Immunotherapy Outcomes in Renal Cancer: What Do We Really Know?
Obesity has reached global epidemic proportions and its effects on interactions between the immune system and malignancies, particularly as related to cancer immunotherapy outcomes, have come under increasing scrutiny. Although the vast majority of pre-clinical murine studies suggest that host obesity should have detrimental effects on anti-tumor immunity and cancer immunotherapy outcomes, the opposite has been found in multiple retrospective human studies. As a result, acceptance of the "obesity paradox" paradigm, wherein obesity increases cancer risk but then improves patient outcomes, has become widespread. However, results to the contrary do exist and the biological mechanisms that promote beneficial obesity-associated outcomes remain unclear. Here, we highlight discrepancies in the literature regarding the obesity paradox for cancer immunotherapy outcomes, with a particular focus on renal cancer. We also discuss multiple factors that may impact research findings and warrant renewed research attention in future studies. We propose that specific cancer patient populations may be affected in fundamentally different ways by host obesity, leading to divergent effects on anti-tumor immunity and/or immunotherapy outcomes. Continued, thoughtful analysis of this critical issue is therefore needed to permit a more nuanced understanding of the complex effects of host obesity on cancer immunotherapy outcomes in patients with renal cancer or other malignancies.


Botulinum as a Toxin for Treating Post-herpetic Neuralgia.
We aimed to study the curative effects of botulinum A toxin (BTX-A) on the treatment of post-herpetic neuralgia (PNH). We enrolled 58 PNH patients and treated them with hypodermic injection of BTX-A in Xiangyang No.1 People's Hospital, Hubei University of Medicine, Hubei, China. We measured and compared the Visual Analog Score (VAS), Neuropathy Pain Scale (NPS), Quality of Life Scale (SF-36) score, PNH seizure severity degree, seizure duration, frequency of attack and the use of painkillers before and after treatment. We used SPSS13 software package for statistical analysis. Values were expressed by mean± standard deviation. P<0.05 indicated a significant difference and P<0.01 indicated an obvious significant difference. Attack frequency, attack duration and attack severity were all significantly lower after treatment (P<0.01). The use of painkillers reduced after treatment (P<0.01) and we observed very few adverse reactions associated with BTX-A injection. The use of BTX-A for treating post-herpetic neuralgia produced very promising results with very few adverse reactions. BTX-A can be considered as a valid approach in the treatment of PNH, especially in patients that do not respond well to painkillers.


Expression rate of vinculin isoforms in human aortocoronary saphenous vein grafts.
Aortocoronary bypass conduits derived from saphenous veins usually develop diffuse intimal thickening, one of the major causes of haemodynamically relevant graft stenosis. To elucidate the role of smooth muscle cell proliferation in late graft failure, specimens from highly stenotic or occluded vein grafts implanted into the arterial circulation for more than 5 years were tested for their expression rate of meta-vinculin. Since the cytoskeletal protein meta-vinculin is present exclusively in contractile smooth muscle cells, the determination of the relative amounts of meta-vinculin (150 kDa) and its low-molecular weight isoform vinculin (130 kDa) allows characterization of the phenotypic status of smooth muscle cells. Using immunoblotting techniques, the quantitative relation of meta-vinculin in tissue samples obtained from autoptic vein grafts (n=10) was measured and compared with those of native saphenous veins (n=6). In vein grafts, the fractional meta-vinculin content of the total vinculin immunoreactivity ranged from 32%-46% (mean 39.6%), whereas the range was 39%-53% (mean 46.7%) in native veins. By applying Student's t-test, a statistical significance was not demonstrated suggesting that the majority of smooth muscle cells in intimal thickenings consisted of a contractile phenotype. Immunohistochemically, the vinculin immunoreactivity in the intimal layer of vein grafts was reduced as compared to native saphenous veins. The distribution of vinculin in grafted veins closely resembled that in arteriosclerotic coronary arteries with intimal thickening. Hence, our biochemical data demonstrate parallels between the pathogenesis of late vein graft stenosis and degenerative arteriosclerotic lesions.


The acidocalcisome vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi.
Polyphosphate is a polymer of inorganic phosphate found in both prokaryotes and eukaryotes. Polyphosphate typically accumulates in acidic, calcium-rich organelles known as acidocalcisomes, and recent research demonstrated that vacuolar transporter chaperone 4 catalyzes its synthesis in yeast. The human pathogens Trypanosoma brucei and T. cruzi possess vacuolar transporter chaperone 4 homologs. We demonstrate that T. cruzi vacuolar transporter chaperone 4 localizes to acidocalcisomes of epimastigotes by immunofluorescence and immuno-electron microscopy and that the recombinant catalytic region of the T. cruzi enzyme is a polyphosphate kinase. RNA interference of the T. brucei enzyme in procyclic form parasites reduced short chain polyphosphate levels and resulted in accumulation of pyrophosphate. These results suggest that this trypanosome enzyme is an important component of a polyphosphate synthase complex that utilizes ATP to synthesize and translocate polyphosphate to acidocalcisomes in insect stages of these parasites.


What have we learned form monogenic forms of severe insulin resistance associated with PCOS/HAIRAN?
Whatever the origin of severe insulin resistance (primary insulin receptors defects or lipodystrophies), in vivo hyperinsulinemia has been clearly shown to promote ovarian growth and androgen synthesis independently of gonadotropins. In lipodystrophic syndromes, the endocrine deficiency of adipose tissue has been shown to play important pathophysiological roles in metabolic alterations. In particular leptin is decreased, contributing to the ectopic lipid storage in non-adipose cells, which inhibits insulin signalling (lipotoxicity). Finally, polycystic ovary syndrome (PCOS) features are not always present in insulin resistance syndromes with lipodystrophy. This is in favour of an aggravating, but not a primary role of post-receptor insulin resistance on ovary dysfunctions.


Expertise with unfamiliar objects is flexible to changes in task but not changes in class.
Perceptual expertise is notoriously specific and bound by familiarity; generalizing to novel or unfamiliar images, objects, identities, and categories often comes at some cost to performance. In forensic and security settings, however, examiners are faced with the task of discriminating unfamiliar images of unfamiliar objects within their general domain of expertise (e.g., fingerprints, faces, or firearms). The job of a fingerprint expert, for instance, is to decide whether two unfamiliar fingerprint images were left by the same unfamiliar finger (e.g., Smith's left thumb), or two different unfamiliar fingers (e.g., Smith and Jones's left thumb). Little is known about the limits of this kind of perceptual expertise. Here, we examine fingerprint experts' and novices' ability to distinguish fingerprints compared to inverted faces in two different tasks. Inverted face images serve as an ideal comparison because they vary naturally between and within identities, as do fingerprints, and people tend to be less accurate or more novice-like at distinguishing faces when they are presented in an inverted or unfamiliar orientation. In Experiment 1, fingerprint experts outperformed novices in locating categorical fingerprint outliers (i.e., a loop pattern in an array of whorls), but not inverted face outliers (i.e., an inverted male face in an array of inverted female faces). In Experiment 2, fingerprint experts were more accurate than novices at discriminating matching and mismatching fingerprints that were presented very briefly, but not so for inverted faces. Our data show that perceptual expertise with fingerprints can be flexible to changing task demands, but there can also be abrupt limits: fingerprint expertise did not generalize to an unfamiliar class of stimuli. We interpret these findings as evidence that perceptual expertise with unfamiliar objects is highly constrained by one's experience.


[Short-acting insulin analogs].
Patients with diabetes mellitus type I usually are treated with a multiple injection regimen comprising rapid-acting insulin before meals and intermediate-acting insulin at bedtime. Recently, the rapid-acting insulin analogue insulin LISPRO was introduced on the Dutch market. This form of insulin is very rapidly taken up into the bloodstream from the subcutaneous tissue. The advantages of the use of insulin LISPRO are the comfort of injecting the insulin just before a meal, the more rapid correction of incidental hyperglycaemia and the slightly lower incidence of (nocturnal) hypoglycaemia in comparison with conventional rapid-acting insulin. There is no argument in favour of switching diabetics to insulin LISPRO if they are well-controlled with normal rapid-acting insulin and have few episodes of hypoglycaemia. In some persons the duration of action of insulin LISPRO may be too short, leading to preprandial hyperglycaemia. This can be avoided by using a second injection of intermediate-acting insulin, either before breakfast or before lunch.


[Problems of railway medicine at the Pirogov Congresses. Report 2: Organization of medical care for resettlers].
The article is devoted to the problems of medical and sanitary support for the transportation of resettlers by rail in Russia at the beginning of the 20th century. The basis for the performed historical reconstruction was the materials of the railway medicine section of the congresses of the Society of Russian Physicians in memory of N. I. Pirogov.


New mechanistic insights into the motile-to-sessile switch in various bacteria with particular emphasis on Bacillus subtilis and Pseudomonas aeruginosa: a review.
A biofilm is a complex assemblage of microbial communities adhered to a biotic or an abiotic surface which is embedded within a self-produced matrix of extracellular polymeric substances. Many transcriptional regulators play a role in triggering a motile-sessile switch and in consequently producing the biofilm matrix. This review is aimed at highlighting the role of two nucleotide signaling molecules (c-di-GMP and c-di-AMP), toxin antitoxin modules and a novel transcriptional regulator BolA in biofilm formation in various bacteria. In addition, it highlights the common themes that have appeared in recent research regarding the key regulatory components and signal transduction pathways that help Bacillus subtilis and Pseudomonas aeruginosa to acquire the biofilm mode of life.


[Mutation of penicillin-binding protein genes and antimicrobial susceptibility of Haemophilus influenzae isolated from spinal fluid or blood in children].
Between September 1999 and August 2001, we studied serotypes to capsular antigen, beta-lactamase production, mutation of penicillin binding protein (PBP) genes by PCR method, and antimicrobial susceptibilities of 13 strains of Haemophilus influenzae isolated from spinal fluid or blood in children. Diseases of patients were meningitis in 11, pneumonia in 1, and laryngitis in 1. The age range of the patients was from 26 days to 5 years. The serotypes of all strains were b. Four of the 13 strains were beta-lactamase-positive. The mutation of genes of pbp3 was revealed from 4 isolates and 2 of the strains were beta-lactamase-positive. MICs of ampicillin to beta-lactamase-negative strains ranged from 0.125 to 1 microgram/ml and those to beta-lactamase-positive were more than 32 micrograms/ml. MICs of 2 strains of beta-lactamase-negative and mutation-positive were 0.5 and 1 microgram/ml. The excellent active antimicrobials in our study was cefotaxime (MIC90 0.06 microgram/ml), meropenem (MIC90 0.125 microgram/ml), ceftazidime (MIC90 0.25 microgram/ml), and cefepime (MIC90 0.25 microgram/ml).


Asynchronous e-learning with technology-enabled and enhanced training for continuing education of nurses: a scoping review.
Asynchronous e-learning has become the mainstream choice since the transformation of learning formats by the coronavirus disease-19 pandemic. This scoping review aimed to examine the technologies used in asynchronous e-learning for the continuing education of clinical nurses and their modes of delivery and effectiveness. This scoping review covered the period between 2011 and 2023. Six databases were searched for relevant studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) protocol. Sixty articles met the inclusion criteria. There was a noticeable trend toward using diverse technology-enabled and enhanced training (TEET) options after 2017. The enabling technological approaches, such as interactive online modules (25 articles) and video modules (25 articles), are described in the articles. The most commonly used enhancing technologies were scenario-based learning (nine articles), resource access (eight articles), computer simulation or virtual reality (three articles), and gamification (three articles). Among the outcomes, knowledge acquisition was the most commonly examined outcome (41 articles). Notably, many interactive TEET modules were used in asynchronous e-learning. There were few studies on gamification, computer simulation or virtual reality, and scenario-based learning (techniques to enhance intrinsic motivation further). However, the adoption of asynchronous e-learning with advanced TEET options is anticipated to increase in the future. Therefore, objective outcome measures are required to determine the effects of such learning methods on knowledge acquisition and behavioral changes.


[Depressive states at the stage of broad clinical presentations of anorexia nervosa in adolescents].
To specify psychopathological features and dynamics of depression developed at the stage of broad clinical presentations of anorexia nervosa (AN) in adolescent patients. Authors studied 61 young women, aged from 14 to 18 years, mean age 16.6 ± .9 years. Depressive states manifested during the first year of AN in all patients. Two variants of depressive episodes were described. The first variant was characterized by asthenic/depressive, somatic and autonomic presentations, with the leading role of exogenous/organic and somatogenic factors. In the second variant, affective disorders were characterized by the anxiety affect concomitant with adynamia, dysphoria and melancholia that most probably may be caused by endogenous constitutional/biological factors. The follow-up data (0,5-6 years) indicated that most of the patients with the second variant of depressive episodes had recurrent depressive states. During the course of disease, eating disorders acquired an atypical character and gradually decreased while the affective pathology became dominating. Depressive symptomatology in AN patients of pubertal age corresponded to main mechanisms of development of the clinical picture and dynamics of adolescent depression as atypical depressive triad, predominance of anxiety and asthenic/adynamic affect, a trend towards protracted course and substantial frequency of dysmorphophobic symptoms and over-valued ideas.


Idiopathic sudden sensorineural hearing loss and acute low-tone sensorineural hearing loss: a comparison of the results of a nationwide epidemiological survey in Japan.
The aim of this study was to investigate the differences between idiopathic sudden sensorineural hearing loss (SSNHL), and acute low-tone sensorineural hearing loss (ALHL) using the results of a nationwide survey database in Japan and to analyze the variables associated with their clinical features and the severity of hearing impairment, treatment, and prognosis. Participants were patients registered between April 2014 and March 2016 in a multicenter epidemiological survey database involving 30 university hospitals and medical centers across Japan. Statistical analysis was performed to clarify the factors associated with their clinical characteristics and the severity of hearing impairment, treatment, and prognosis. Idiopathic SSNHL and ALHL differed significantly in terms of male-to-female ratio, age distribution, and time from onset to start of treatment. The treatment methods and hearing prognosis also differed markedly between the two diseases. A majority (92%) of idiopathic SSNHL patients were administered some type of corticosteroid, while half of the ALHL patients received corticosteroids and a diuretic agent. The results suggested that idiopathic SSNHL and ALHL belonged to different categories of inner ear disease.


Interleukin 6 is a negative regulator of the acute phase alpha 1-inhibitor III gene.
The broad-range proteinase inhibitor alpha 1-inhibitor III (alpha 1I3), a member of the complement C3/alpha 2-macroglobulin protein family, is the prototype of a negatively regulated acute phase protein. During an acute inflammatory reaction alpha 1I3 plasma protein and liver mRNA concentrations are decreased three- to fourfold in rats, and in chronic inflammations the protein concentration is reduced between ten- and 20-fold. In search of a cell culture model to study the regulation of the alpha 1I3 gene by mediators of inflammation, five well-established rat hepatoma cell lines were examined. All five lines constitutively expressed the gene, a marker for a highly differentiated hepatic phenotype, although at less than one-tenth the level of its expression in vivo. In the three hepatoma lines FAZA, FTO2B and FAO1, alpha 1I3 mRNA was decreased by treatment with interleukin 6 (IL6) and glucocorticoids. Among these lines untreated FAO1 cells produced the highest constitutive concentrations of alpha 1I3 mRNA and in FAO1 cells alpha 1I3 mRNA concentrations were decreased up to fourfold in a dose-responsive and time-dependent manner after treatment with IL6 alone or with combinations of IL6 and the synthetic glucocorticoid dexamethasone. Thus, IL6 alone was sufficient to negatively regulate alpha 1I3 mRNA levels in hepatoma cells with similar characteristics as occur during an inflammatory response in the liver. A number of other acute phase mRNA species, including alpha 1-acid glycoprotein, T2-kininogen, gamma-fibrinogen and alpha 2-macroglobulin were induced to higher levels by the same hormonal treatments in FAO1 cells. The fourfold reduction of alpha 1I3 mRNA concentrations in FAO1 cells could be reversed by treatment with 1 microM of a water-soluble derivative of forskolin, an activator of the cyclic AMP pathway. Thus, the effect of IL6 on the expression of the alpha 1I3 gene may involve the activation of the cyclic AMP pathway. In contrast, T2 kininogen mRNA levels were not altered by treatment of FAO1 cells with forskolin, suggesting that IL6 may act on this gene through a different mechanism.


Light-enabled reversible self-assembly and tunable optical properties of stable hairy nanoparticles.
The ability to dynamically organize functional nanoparticles (NPs) via the use of environmental triggers (temperature, pH, light, or solvent polarity) opens up important perspectives for rapid and convenient construction of a rich variety of complex assemblies and materials with new structures and functionalities. Here, we report an unconventional strategy for crafting stable hairy NPs with light-enabled reversible and reliable self-assembly and tunable optical properties. Central to our strategy is to judiciously design amphiphilic star-like diblock copolymers comprising inner hydrophilic blocks and outer hydrophobic photoresponsive blocks as nanoreactors to direct the synthesis of monodisperse plasmonic NPs intimately and permanently capped with photoresponsive polymers. The size and shape of hairy NPs can be precisely tailored by modulating the length of inner hydrophilic block of star-like diblock copolymers. The perpetual anchoring of photoresponsive polymers on the NP surface renders the attractive feature of self-assembly and disassembly of NPs on demand using light of different wavelengths, as revealed by tunable surface plasmon resonance absorption of NPs and the reversible transformation of NPs between their dispersed and aggregated states. The dye encapsulation/release studies manifested that such photoresponsive NPs may be exploited as smart guest molecule nanocarriers. By extension, the star-like block copolymer strategy enables the crafting of a family of stable stimuli-responsive NPs (e.g., temperature- or pH-sensitive polymer-capped magnetic, ferroelectric, upconversion, or semiconducting NPs) and their assemblies for fundamental research in self-assembly and crystallization kinetics of NPs as well as potential applications in optics, optoelectronics, magnetic technologies, sensory materials and devices, catalysis, nanotechnology, and biotechnology.


High internal resistance to CO(2) uptake by submerged macrophytes that use HCO(3) (-): measurements in air, nitrogen and helium.
Previous studies have shown that in water the affinity of submerged macrophytes for CO(2) is higher for species restricted to CO(2) than for species with an additional ability to use bicarbonate. We measured slopes of CO(2) uptake versus CO(2) concentration in the gas phase in air, nitrogen and helium for pairs of species, having or lacking the ability to use bicarbonate, but with similar leaf morphology. For species restricted to CO(2), the slope in nitrogen and helium was 1.5 times and 3.2 times greater than in air. The increased slope in nitrogen results from a suppression of photorespiration. The further increase in helium reflects the increased rate of diffusion of CO(2) and shows that, even in gas, external diffusion through the boundary layer is a significant hindrance to CO(2) uptake. In contrast, in species able to use bicarbonate, the uptake slope was not affected by gas composition, suggesting that photorespiration is absent or photorespired CO(2) is efficiently trapped and that internal resistance is high relative to external resistance. Elodea canadensis specimens grown under high concentrations of CO(2) de-regulated their ability to use bicarbonate, and slopes of CO(2) uptake in helium were significantly greater than in air or nitrogen. Overall, these results are consistent with the notion that while a high affinity for CO(2) will maximise carbon uptake in species restricted to CO(2), for species able to use bicarbonate, a high internal resistance would reduce loss of CO(2) and help maintain high concentrations of CO(2) at the site of fixation.


[Influence of acute hemorrhage on erythrodieresis].
Influence of acute hemorrhage on peritoneal and splenic macrophages function and NO production was studied. Interaction of peritoneal and splenic macrophages with autologous erythrocytes was examined the day after the hemorrhage. Concentration of nitrate ions: the stable metabolites of nitric oxide, was measured in peritoneal lavage, splenic cells suspension, blood, as well as in supernatant of peritoneal and splenic macrophages before and after hemorrhage. The data obtained suggest that splenic macrophages of intact rats are more active than peritoneal ones. After hemorrhage peritoneal macrophages activity increases, whereas splenic macrophages remain unchanged. Concentration of nitrate ions is significantly reduced after hemorrhage.


Evaluation of volume changes following lateral window maxillary sinus floor elevation using Minics software.
Significant volume changes at the site of lateral window maxillary sinus floor elevation have been reported 6 months postoperatively, with stabilization thereafter. However, at present, there is no consensus regarding the gold standard to assess the shape and volume of the bone graft site after implantation. This study aimed to analyze volume changes in the lateral window maxillary sinus floor elevation region using Minics software. We analyzed 40 patients who underwent lateral window maxillary sinus floor elevation surgery at the Stomatology Department of Binhaiwan Central Hospital, Dongguan, China between 2017 and 2020. Twenty patients underwent lateral window maxillary sinus floor elevation with simultaneous implantation, while 20 patients underwent lateral window maxillary sinus floor elevation with delayed implantation 6 months later. Minics software was used for three-dimensional analysis of the elevation site on the day after surgery (T1) and 6 months after surgery (T2) in both groups. The elevation site volume was reduced 6 months after lateral window maxillary sinus floor elevation. The differences in the length, width, height from the tip, and volume of the implant between T1 and T2 were statistically significant. The length, width, height, and volume of the lateral window maxillary sinus floor elevation region were reduced using Minics software, suggesting that the volume of the elevation site should be enlarged as much as possible during the operation to prevent volume shrinkage.


Action Video Game Experience Related to Altered Large-Scale White Matter Networks.
With action video games (AVGs) becoming increasingly popular worldwide, the cognitive benefits of AVG experience have attracted continuous research attention over the past two decades. Research has repeatedly shown that AVG experience can causally enhance cognitive ability and is related to neural plasticity in gray matter and functional networks in the brain. However, the relation between AVG experience and the plasticity of white matter (WM) network still remains unclear. WM network modulates the distribution of action potentials, coordinating the communication between brain regions and acting as the framework of neural networks. And various types of cognitive deficits are usually accompanied by impairments of WM networks. Thus, understanding this relation is essential in assessing the influence of AVG experience on neural plasticity and using AVG experience as an interventional tool for impairments of WM networks. Using graph theory, this study analyzed WM networks in AVG experts and amateurs. Results showed that AVG experience is related to altered WM networks in prefrontal networks, limbic system, and sensorimotor networks, which are related to cognitive control and sensorimotor functions. These results shed new light on the influence of AVG experience on the plasticity of WM networks and suggested the clinical applicability of AVG experience.


PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy.
Cryo-electron tomography (cryo-ET) is emerging as a revolutionary method for resolving the structure of macromolecular complexes in situ. However, sample preparation for in situ Cryo-ET is labour-intensive and can require both cryo-lamella preparation through cryo-focused ion beam (FIB) milling and correlative light microscopy to ensure that the event of interest is present in the lamella. Here, we present an integrated cryo-FIB and light microscope setup called the Photon Ion Electron microscope (PIE-scope) that enables direct and rapid isolation of cellular regions containing protein complexes of interest. Specifically, we demonstrate the versatility of PIE-scope by preparing targeted cryo-lamellae from subcellular compartments of neurons from transgenic Caenorhabditis elegans and Drosophila melanogaster expressing fluorescent proteins. We designed PIE-scope to enable retrofitting of existing microscopes, which will increase the throughput and accuracy on projects requiring correlative microscopy to target protein complexes. This new approach will make cryo-correlative workflow safer and more accessible.


First-principle insight into the structural, electronic, elastic and optical properties of Cs-based double perovskites Cs2XCrCl6 (X = K, Na).
This study communicates the theoretical investigations on the cubic double perovskite compounds Cs2XCrCl6 (X = K or Na). Density functional theory (DFT) calculations were carried out using the TB-mBJ approximation. These compounds were found to be stable in the cubic perovskite structure having lattice constants in the range of 10.58-10.20. The stability of the investigated materials was assessed by the Gold-Schmidt tolerance method, which resulted in the tolerance factor values of 0.891 and 0.951 for Cs2KCrCl6 and Cs2NaCrCl6, respectively. The calculated values of the elastic constants C11, C12, and C44 of the cubic compounds studied by our research team confirm the elastic stability. The values of the formation energies were also calculated for both the compounds and were found in the range from -2.1 to -2.3. The electronic behavior of the presently investigated materials was examined by inspecting their band structures and the density of states. It was observed that both the materials have half-metallic nature. To check the suitability of the studied compounds in optical applications, we determined the real and imaginary parts of their respective dielectric functions, absorption coefficients, optical conductivities, refractive index, and reflectivity as a function of a wide range of incident photon energies up to 40 eV.


FKBP5 genotype-dependent DNA methylation and mRNA regulation after psychosocial stress in remitted depression and healthy controls.
Polymorphisms in the FK506 binding protein 5 (FKBP5) gene have been shown to influence glucocorticoid receptor sensitivity, stress response regulation, and depression risk in traumatized subjects, with most consistent findings reported for the functional variant rs1360780. In the present study, we investigated whether the FKBP5 polymorphism rs1360780 and lifetime history of major depression are associated with DNA methylation and FKBP5 gene expression after psychosocial stress. A total of 116 individuals with a positive (n = 61) and negative (n = 55) lifetime history of major depression participated in the Trier Social Stress Test. We assessed plasma cortisol concentrations, FKBP5 mRNA expression, and CpG methylation of FKBP5 intron 7 in peripheral blood cells. Genotype-dependent plasma cortisol response to psychosocial stress exposure was observed in healthy controls, with the highest and longest-lasting cortisol increase in subjects with the TT genotype of the FKBP5 polymorphism rs1360780, and healthy controls carrying the T risk allele responded with a blunted FKBP5 mRNA expression after psychosocial stress. No genotype effects could be found in remitted depression. The FKBP5 rs1360780 polymorphism is associated with plasma cortisol and FKBP5 mRNA expression after psychosocial stress in healthy controls but not in remitted depression. Preliminary results of the DNA methylation analysis suggest that epigenetic modifications could be involved.


Neurological and psychiatric practitioners' views on Alzheimer's disease and treatment thereof.
General views of practitioners shape medical routine. This study surveyed general views of neurological and psychiatric practitioners in Germany on Alzheimer's disease (AD). 850 surveys were distributed and 637 (75%) recovered. 36% of practitioners reported not having used therapies for medical conditions other than dementia in patients with AD for reasons of limited compliance in these patients. Efficacy of antidementia drugs (donepezil, galantamine, memantine, rivastigmine) was rated on a 5-point scale (very good, good, satisfactory, sufficient, insufficient) regarding memory, attention and concentration, aggression, depression, activities of daily living, and dependency on caregivers. 87% of practitioners reported an at least satisfactory effect on at least 2 domains. Practitioners estimated that about 20% of caregivers are treated for psychiatric disorders such as depression. Practitioners that were more aware of caregivers' needs for psychiatric treatment more frequently reported positive feedback of caregivers concerning improvement of the patients in everyday life. Nursing home admission was estimated to result from both progression of dementia and diminished forces of the caregivers. Neurological and psychiatric practitioners perceive antidementia drugs as effective in multiple domains in AD. Appreciation of the overall success of treatment requires consideration of the patient-caregiver dyad.


Direct stimulation of nucleoside triphosphatase activity in human ovarian nuclear membranes by human chorionic gonadotropin.
We previously reported that nuclei isolated from ovaries of premenopausal women contain binding sites for hCG/human LH (hLH). This study was undertaken to determine the possible functional significance of these nuclear binding sites. Upon addition to isolated ovarian (mostly luteal cells) nuclear membranes, hCG and hLH stimulated nucleoside triphosphatase (NTPase), an enzyme involved in nucleocytoplasmic transfer of mRNA, but not Mg2+-ATPase or NADH cytochrome c reductase activities, in a concentration-dependent manner. Heat-denatured hCG, isolated alpha- and beta-subunits of hCG, human FSH, PRL, and porcine relaxin had no effect on the enzyme. Addition of hCG antiserum blocked hCG's ability to stimulate NTPase activity. cAMP, which is a second messenger in hCG- and hLH-stimulated steroidogenesis, had no effect on NTPase activity. These results, which demonstrate that hCG acts on human ovarian nuclei directly, raise the possibility that internalized hCG might influence nuclear function(s) before it is eventually degraded in the lysosomes of ovarian cells.


Using evidence to demonstrate the value of nursing.
This article explores the position of nursing in relation to the evidence-based medicine (EBM) and clinical effectiveness (CE) initiatives. It argues that both activities are based on at least three implicit assumptions. By exploring these assumptions nurses can become more involved in evidence-based practice and clinical effectiveness activities.


[Studies on the pharmacokinetic-pharmacodynamic model of ketoprofen beta-CD inclusion complex in rabbits].
A simple HPLC-UV method was established to determine concentrations of ketoprofen (KP) in rabbit plasma following oral administration. Twelve rabbits were selected and divided into three groups. KP beta-CD inclusion complex suspension, KP entity suspension (in 0.5% CMC-Na) and 0.5% CMC-Na suspension (as a placebo group) were administered orally to the three groups of rabbits, respectively. Differences in the pharmacokinetics-pharmacodynamics (PK-PD) parameters between KP beta-CD inclusion complex and KP entity were examined. The results indicate that the established HPLC-UV method could be used to assay the concentrations of KP in rabbit plasma with good precision. The distribution phase T1/2 alpha of the complexated KP was 0.4 h, while that of the KP entity was 0.56 h, KP in beta-CD inclusion complex could be absorbed more rapidly. The early effect values of the KP inclusion complex were higher than those of the KP entity. The maximal antipyretic effect occurred after the peak of plasma concentration. The phenomenon indicates that the effect compartment of ketoprofen is in the peripheral compartment.


Deconstructing Cancer Patient Information Seeking in a Consumer Health Library Toward Developing a Virtual Information Consult for Cancer Patients and Their Caregivers: A Qualitative, Instrumental Case Study.
Cancer patients and their caregivers want information about their disease and are interested in finding health information online. Despite the abundance of cancer information online, it is often fragmented, its quality is highly variable, and it can be difficult to navigate without expert-level knowledge of the cancer system. The Patient & Family Library at the Princess Margaret Cancer Centre offers a broad collection of high-quality cancer health information and staff are available to help patrons refine their questions and explore information needs that they may not have considered. The purpose of this research study was to deconstruct patrons' information-seeking behaviors in the library to assess the feasibility of replicating the services provided in the library through a Web app, extending the service beyond the walls of the cancer centre. The specific aims of this research were to understand (1) how patrons approach information seeking in the library (interface design), (2) how patrons communicate their informational needs (information categorization and metadata requirements), and (3) what resources are provided to address the patrons' information needs (collection development). We employed a qualitative, instrumental case study to deconstruct patrons' health information-seeking behavior. The study population included patients, the librarian, and library volunteers. Ethnographic observation was conducted at the library over 3 days and key informant interviews with library staff were conducted to address the first aim. A closed card-sorting activity was conducted to address the second aim and the library shift logs and Search Request Forms (SRFs) were reviewed to address the third aim. A total of 55 interactions were recorded during the ethnographic observation and nine semistructured interviews were conducted during the key informant interviews. Seven library patron personas were identified: (1) Newbie, (2) Seasoned, (3) Direct, (4) Window Shopper, (5) Collector, (6) Information Seeker, and (7) Distressed. A total of 83 participants completed the closed card-sorting exercise. The participants' conceptual clusters within the similarity matrix overlapped with the groupings created by the librarian, with a few differences. A total of 161 entries in the library shift log and 65 SRFs were analyzed to determine what resources were given to patrons. Most resources that patrons received were available online (61%), although almost half of these required special access (47%). The study findings suggest it is possible to replicate library functions in a Web app with a few exceptions that cannot be replicated online. These elements include access to journal articles or other content behind paywalls and the librarian's ability to encourage further discussion through empathy and active listening. Discussion with the librarian could serve to refine and predict needs through observing information seekers and to provide immediate connection to spiritual care and psychosocial support for patrons in distress.


Modified Tail Vein and Penile Vein Puncture for Blood Sampling in the Rat Model.
Blood samples are required in most experimental animal designs to assess various hematological parameters. This paper presents two procedures for blood collection in rats: the lateral tail vein puncture and the dorsal penile vein puncture, which offer significant advantages over other previously described techniques. This study shows that these two procedures allow for fast sampling (under 10 min) and yield sufficient blood volumes for most assays (202 μL ± 67.7 μL). The dorsal penile vein puncture must be done under anesthesia, whereas the lateral tail vein puncture can be done on a conscious, restrained animal. Alternating these two techniques, therefore, enables blood draw in any situation. While it is always recommended for an operator to be assisted during a procedure to ensure animal welfare, these techniques require only a single operator, unlike most blood sampling methods that require two. Moreover, whereas these previously described methods (e.g., jugular stick, subclavian vein blood draw) require extensive prior training to avoid harm to or death of the animal, tail vein and dorsal penile vein puncture are rarely fatal. For all these reasons, and according to the context (e.g., for studies including male rats, during the perioperative or immediate postoperative period, for animals with thin tail veins), both techniques can be used alternately to enable repeated blood draws.


Genetic upregulation of BK channel activity normalizes multiple synaptic and circuit defects in a mouse model of fragile X syndrome.
Single-channel recordings in CA3 pyramidal neurons revealed that large-conductance calcium-activated K(+) (BK) channel open probability was reduced by loss of fragile X mental retardation protein (FMRP) and that FMRP acts on BK channels by modulating the channel's gating kinetics. Fmr1/BKβ4 double knockout mice were generated to genetically upregulate BK channel activity in the absence of FMRP. Deletion of the BKβ4 subunit alleviated reduced BK channel open probability via increasing BK channel open frequency, but not through prolonging its open duration. Genetic upregulation of BK channel activity via deletion of BKβ4 normalized action potential duration, excessive glutamate release and short-term synaptic plasticity during naturalistic stimulus trains in excitatory hippocampal neurons in the absence of FMRP. Genetic upregulation of BK channel activity via deletion of BKβ4 was sufficient to normalize excessive epileptiform activity in an in vitro model of seizure activity in the hippocampal circuit in the absence of FMRP. Loss of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), yet the mechanisms underlying the pathophysiology of FXS are incompletely understood. Recent studies identified important new functions of FMRP in regulating neural excitability and synaptic transmission via both translation-dependent mechanisms and direct interactions of FMRP with a number of ion channels in the axons and presynaptic terminals. Among these presynaptic FMRP functions, FMRP interaction with large-conductance calcium-activated K(+) (BK) channels, specifically their auxiliary β4 subunit, regulates action potential waveform and glutamate release in hippocampal and cortical pyramidal neurons. Given the multitude of ion channels and mechanisms that mediate presynaptic FMRP actions, it remains unclear, however, to what extent FMRP-BK channel interactions contribute to synaptic and circuit defects in FXS. To examine this question, we generated Fmr1/β4 double knockout (dKO) mice to genetically upregulate BK channel activity in the absence of FMRP and determine its ability to normalize multilevel defects caused by FMRP loss. Single-channel analyses revealed that FMRP loss reduced BK channel open probability, and this defect was compensated in dKO mice. Furthermore, dKO mice exhibited normalized action potential duration, glutamate release and short-term dynamics during naturalistic stimulus trains in hippocampal pyramidal neurons. BK channel upregulation was also sufficient to correct excessive seizure susceptibility in an in vitro model of seizure activity in hippocampal slices. Our studies thus suggest that upregulation of BK channel activity normalizes multi-level deficits caused by FMRP loss.


Cardiorespiratory Fitness in Internal Medicine Residents: Are Future Physicians Becoming Deconditioned?
Previous studies have shown a falloff in physicians' physical activity from medical school to residency. Poor fitness may result in stress, increase resident burnout, and contribute to mortality from cardiovascular disease and other causes. Physicians with poor exercise habits are also less likely to counsel patients about exercise. Prior studies have reported resident physical activity but not cardiorespiratory fitness age. The study was conducted in 2 residency programs (3 hospitals) to assess internal medicine residents' exercise habits as well as their cardiorespiratory fitness age. Data regarding physical fitness levels and exercise habits were collected in an anonymous cross-sectional survey. Cardiopulmonary fitness age was determined using fitness calculator based on the Nord-Trøndelag Health Study (HUNT). Of 199 eligible physicians, 125 (63%) responded to the survey. Of respondents, 11 (9%) reported never having exercised prior to residency and 45 (36%) reported not exercising during residency (P < .001). In addition, 42 (34%) reported exercising every day prior to residency, while only 5 (4%) reported exercising daily during residency (P < .001), with 99 (79%) participants indicating residency obligations as their main barrier to exercise. We found residents' calculated mean fitness age to be 5.6 years higher than their mean chronological age (P < .001). Internal medicine residents reported significant decreases in physical activity and fitness. Residents attributed time constraints due to training as a key barrier to physical activity.


Mutational analysis of the conserved cysteines of the rat P2X2 purinoceptor.
P2X receptors are ATP-gated cation channels that are widely expressed in the brain. The extracellular domains of all seven P2X receptors contain 10 conserved cysteines, which could form disulfide bonds or binding sites for transition metals that modulate P2X receptors. To test whether these cysteines are critical for receptor function, we studied wild-type rat P2X(2) receptors and 10 mutant P2X(2) receptors, each containing an alanine substituted for a cysteine. Nine mutants were functional but had reduced maximum currents compared with wild-type P2X(2) expressed in either Xenopus oocytes or human embryonic kidney (HEK) 293 cells. The 10th mutant (C224A) did not respond to ATP when expressed in oocytes and gave very small currents in HEK 293 cells. Seven mutants (C113A, C124A, C130A, C147A, C158A, C164A, and C214A) showed rightward shifts (9- to 30-fold) in their ATP concentration-response relationships and very little potentiation by zinc. In contrast, C258A and C267A had EC(50) values similar to those of wild-type P2X(2) and were potentiated by zinc. Acidic pH potentiated wild-type and all mutant receptor currents. Despite the loss of zinc potentiation in seven mutants, these cysteines are unlikely to be exposed in the zinc-binding site, because [2-(trimethylammonium)ethyl] methanethiosulfonate bromide did not prevent zinc potentiation of wild-type receptor currents. On the basis of correlations in the maximum current, EC(50), zinc potentiation, and pH potentiation, we suggest that the following cysteine pairs form disulfide bonds: C113-C164, C214-C224, and C258-C267. We also suggest that C124, C130, C147, and C158 form two disulfide bonds, but we are unable to assign specific cysteine pairs to these two bonds.


NextPBM: a platform to study cell-specific transcription factor binding and cooperativity.
High-throughput (HT) in vitro methods for measuring protein-DNA binding have become invaluable for characterizing transcription factor (TF) complexes and modeling gene regulation. However, current methods do not utilize endogenous proteins and, therefore, do not quantify the impact of cell-specific post-translational modifications (PTMs) and cooperative cofactors. We introduce the HT nextPBM (nuclear extract protein-binding microarray) approach to study DNA binding of native cellular TFs that accounts for PTMs and cell-specific cofactors. We integrate immune-depletion and phosphatase treatment steps into our nextPBM pipeline to characterize the impact of cofactors and phosphorylation on TF binding. We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity, and show how PU.1 affinity correlates with enhancer status and the presence of cooperative and collaborative cofactors. We describe how nextPBMs, and our accompanying computational framework, can be used to discover cell-specific cofactors, screen for synthetic cooperative DNA elements, and characterize TF cooperativity.


The value of an oath of professional conduct: process, content, or both?
...I would suggest that the major objectives of studying the Hippocratic Oath or other pertinent oaths and codes are fourfold. First, studying oaths and codes pertaining to medical conduct and standards enables students to learn about historical changes and cultural influences. Second, choosing an oath or developing one for recitation at graduation enables students to engage in conceptual and moral reasoning. Third, the deliberations and discussions involving students enable them to practice interactional, communication skills about highly charged issues. Fourth, the identified limitations of the Hippocratic Oath or other pertinent oaths and codes enable students to appreciate the value of the broader principles that support medical ethics... The remainder of this commentary is divided into two parts. In the first part, recommendations for an educational program are presented. In the second part, recommendations for future research in this area are offered.


ZnI2-Mediated β-Galactosylation of C2-Ether-Type Donor.
Conventional glycosylation with galactosyl donors having C-2 benzyl (Bn) ether-type functionality often leads to anomeric mixtures, due to the anomeric and steric effects that stabilize the 1,2-cis-α- and 1,2-trans-β-glycosides, respectively. Herein we report a versatile ZnI2-directed β-galactosylation approach employing a 4,6-O-tethered and 2-O-Bn galactosyl donor for the stereoselective and efficient synthesis of β-O-galactosides. With a broad substrate scope, the reaction tolerates a wide range of functional groups and complex molecular architectures, providing stereocontrolled β-galactosides in moderate to excellent yields. The practicality of this transformation is demonstrated through the synthesis of a tetrasaccharide arabinogalactan fragment with high stereoselectivity.


The cultural sustainability in English as foreign language textbooks: Investigating the cultural representations in English language textbooks in China for senior middle school students.
In the age of globalization, studies of cultural representations in foreign language textbooks take account of cultural sustainability. This article reports on a case study of cultural representations in two English language textbook series that are widely used in senior high schools in China. The study investigated whether the cultural representations in these textbooks contribute to the development of local cultural sustainability. Content analysis was employed to examine the texts used in these textbooks, with references to the synergy of the theoretical frameworks of cultural sustainability and world Englishes. The study results indicate that there is an imbalanced cultural representation with respect to the categories of international cultures and national culture in these textbooks. The results point to the cultures of the inner circle countries (BANA: Britain, Australasia, and North America) being predominant, while the representation of Chinese culture has a low profile. As these textbooks are an important learning and teaching resource in China, they have the potential to play a significant role in influencing learners' worldviews as they develop their understanding of different cultures. The imbalanced presentation of culture may in turn lead to a biased worldview where learners, rather appreciating cultural diversity, may instead discriminate against certain cultures. The implications for redressing the imbalance in cultural representation and cultural sustainability are discussed.


[Faster detection of Vibrio parahaemolyticus in foods by FQ-PCR technique].
To establish a rapid and accurate qualitative and quantitative method to detect Vibrio parahaemolyticus in food. Primers and Taqman probe were designed according to the sequence of gyrase gene of Vibrio parahaemolyticus. The PCR fragment was cloned into PTM vector and was used as positive template for establishing the criterion curve. The simulated samples, made from negative food samples with Vibrio parahaemolyticus positive strain, were used to evaluate the sensitivity of the PCR reaction. 8 Vibrio parahaemolyticus standard strains and other 24 negative strains (8 strains were Vibrionaceae other than Vibrio parahaemolyticus, the rest 16 strains were none-Vibrionaceae) were treated in the same way to evaluate the specificity. All samples were detected with PE7000 sequence detection system and DA620 fluorescene detection system. FQ-PCR method had good specificity and high sensitivity. All 8 strains of Vibrio parahaemolyticus tested showed positive results while all other 24 strains were negative (8 strains were Vibrionaceae, 16 strain were from different). The correlation was 0.9871 between the concentration of positive template and the quantitative curve circular threshold. The threshold for detecting Vibrio parahaemolyticus in pure culture is 10 cfu/ml, and the threshold is as low as 2 cfu/ml with 16 simulative samples after these samples were incubated for a period of time. By direct quantitative detection for uncultured 16 food samples, the threshold is 100 cfu/g. FQ-PCR method has high sensitivity and specificity, and it is a handy and rapid detection method. Comparing with regular PCR method, it is not easily contaminated in operation, and can achieve high sensitivity and specificity with domestic instruments. FQ-PCR method has potential and applied value for detection of pathogenic bacteria in food.


Meta-meta-analysis: A paradigm in the case of surgical publications.
Meta-analyses are considered to provide level I-II evidence. Based on this premise, several statements have been developed to standardize guidelines and optimize results. The purpose of this study was to investigate the quality of the information delivered by meta-analyses. Meta-analyses published in Annals of Surgery during an 11-year period were reviewed whereas individual publications of each meta-analysis were assessed. An Excel database encompassing 29 parameters was constructed based on the Quality of Reporting of Meta-analyses (QUOROM) statement. The present study included 31 consecutive meta- analyses. The number of meta-analyses conforming with each of the parameters considered was as follows: information obtained from more than 2 databases 23/31; language of publication exclusively English 25/31; defined population, intervention, and principal outcomes 31/31; study design encompassing review of randomised controlled trials (RCTs) 10/31; quality assessment of contributing publications 10/31; handling of missing data 10/31; assessment of statistical heterogeneity 30/31; subgroup analysis 23/31; assessment of publication bias 26/31; agreement on selection and validity assessment 22/31; simple summary results 28/31; data available to calculate effect size and confidence interval 27/31; key findings summarized 30/31; clinical inferences based on internal and external validity 24/31; description of potential biases in the review process 23/31; future research agenda suggested 18/31. Evidence derived from meta-analyses must be interpreted with caution. Although QUOROM guidelines were observed, quality assessments showed considerable variability.


EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS.
Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors.


Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program.
Pax3/7-dependent stem cells play an essential role in skeletal muscle development. We now show that Fgfr4 lies genetically downstream from Pax3 and is a direct target. In chromatin immunoprecipitation (ChIP)-on-chip experiments, Pax3 binds to a sequence 3' of the Fgfr4 gene that directs Pax3-dependent expression at sites of myogenesis in transgenic mouse embryos. The activity of this regulatory element is also partially dependent on E-boxes, targets of the myogenic regulatory factors, which are expressed as progenitor cells enter the myogenic program. Other FGF signaling components, notably Sprouty1, are also regulated by Pax3. In vivo manipulation of Sprouty expression reveals that FGF signaling affects the balance between Pax-positive progenitor cells and committed myoblasts. These results provide new insight into the Pax-initiated regulatory network that modulates stem cell maintenance versus tissue differentiation.


Low frequency sound spatial encoding within an enclosure using spherical microphone arrays.
In a spherical coordinate system, interior sound field can be expressed in terms of a series of Fourier-Bessel expansions. The process that obtains the expansion coefficients by use of a microphone array (e.g., a spherical microphone array) is called spatial encoding. Until now spatial encoding has mainly been examined in a free field or a diffuse field which can be modeled as a sum of plane waves. For spatial encoding within an enclosure at low frequencies, special challenges would be encountered in two aspects. First, the expansions are influenced by array configurations. Second, an acoustic mode based model instead of a plane wave based one should be considered. This study focuses on these challenges. Different kinds of array configurations were compared specifically at low frequencies, and the spatial encoding for the cylindrical cavity modes was investigated. It was found that the spherical array with cardioid microphones was optimal when kr<1, the cavity modes can be effectively represented by only a sparse subset of expansion coefficients and a good reproduction can be achieved even outside the spherical valid region, which demonstrates an effective alternative way to describe the cylindrical cavity modes and can be implemented efficiently in practice.


Aurora A kinase activity is required to maintain an active spindle assembly checkpoint during prometaphase.
During the prometaphase stage of mitosis, the cell builds a bipolar spindle of microtubules that mechanically segregates sister chromatids between two daughter cells in anaphase. The spindle assembly checkpoint (SAC) is a quality control mechanism that monitors proper attachment of microtubules to chromosome kinetochores during prometaphase. Segregation occurs only when each chromosome is bi-oriented with each kinetochore pair attached to microtubules emanating from opposite spindle poles. Overexpression of the protein kinase Aurora A is a feature of various cancers and is thought to enable tumour cells to bypass the SAC, leading to aneuploidy. Here, we took advantage of a chemical and chemical-genetic approach to specifically inhibit Aurora A kinase activity in late prometaphase. We observed that a loss of Aurora A activity directly affects SAC function, that Aurora A is essential for maintaining the checkpoint protein Mad2 on unattached kinetochores and that inhibition of Aurora A leads to loss of the SAC, even in the presence of nocodazole or Taxol. This is a new finding that should affect the way Aurora A inhibitors are used in cancer treatments.This article has an associated First Person interview with the first authors of the paper.


Computation and visualization of three-dimensional soft tissue motion in the orbit.
This work presents a method to measure the soft tissue motion in three dimensions in the orbit during gaze. It has been shown that two-dimensional (2-D) quantification of soft tissue motion in the orbit is effective in the study of orbital anatomy and motion disorders. However, soft tissue motion is a three-dimensional (3-D) phenomenon and part of the kinematics is lost in any 2-D measurement. Therefore, T1-weighted magnetic resonance (MR) imaging volume sequences are acquired during gaze and soft tissue motion is quantified using a generalization of the Lucas and Kanade optical flow algorithm to three dimensions. New techniques have been developed for visualizing the 3-D flow field as a series of color-texture mapped 2-D slices or as a combination of volume rendering for display of the anatomy and scintillation rendering for the display of the motion field. We have studied the performance of the algorithm on four-dimensional volume sequences of synthetic motion, simulated motion of a static object imaged by MR, an MR-imaged rotating object and MR-imaged motion in the human orbit during gaze. The accuracy of the analysis is sufficient to characterize motion in the orbit and scintillation rendering is an effective visualization technique for 3-D motion in the orbit.


Combining antipsychotics; is this strategy useful?
Antipsychotic drugs are commonly combined in psychiatric practice in an attempt to treat schizophrenia. Such practice is widespread, despite the lack of explicit endorsement by many of the main regulatory bodies. There are varying rationales behind combining these potent drugs-either to augment the effect of a drug whose action alone is inadequate for patients with treatment resistant schizophrenia (TRS), or to improve the side effects seen due to treatment. Augmentations are most frequently observed with clozapine, a drug reserved for use when other antipsychotic medications have failed. Several drugs have been chosen as adjuvants, including aripiprazole, sulpiride, amisulpiride and risperidone. A small number of RCTs (randomized controlled trials) have been performed but, despite this data and numerous case reports showing positive changes in symptomatology, Cochrane reviews of available studies have been unable to definitively confirm the efficacy of these combinations, frequently citing the need for larger, longer term, prospective studies.Evidence for benefits of combination therapy on side effects is also inadequate. Some RCTs and case series have shown they can positively alter side effects due to drugs such as clozapine, e.g. metabolic side effects. However, despite many of the combinations being relatively well tolerated, there is some evidence they can cause adverse effects of their own. More evidence is essential as, on the current data alone, it is not possible to make a firm recommendation on the efficacy and safety of antipsychotic combinations. In addition it is vital that the importance of a fair trial of monotherapy at adequate dosages is reinforced to clinicians, so that patients are not put onto these relatively unknown treatment strategies unnecessarily.


Glycoprotein enrichment in Moloney leukemia virus structural proteins released from interferon-treated cells.
Interferon treatment of Moloney-leukemia-virus-infected cells (3T3/MLV) leads to the formation of virus particles enriched with viral structural glycoproteins, in addition to the inhibition of virus production. A preferential inhibitory effect on incorporation of RNA and proteins rather than glycoproteins was found in the released virus particles from interferon-treated cells. Enrichment in 70,000- and 45,000-dalton glycoprotein (gP-70, gP-45) in these particles was further demonstrated by polyacrylamide analysis of viral proteins pulse-labeled with [3H]-leucine. Viral glycoproteins released as soluble antigens were also determined. A 40% reduction was found in gP-70 and gP-45 released from interferon-treated cells. Radioimmunoprecipitation of pulse-chase-labeled cellular viral proteins showed no effect of interferon on the formation of viral structural 30,000-, 15,000- to 12,000-dalton proteins, and gP-70 and gP-45 from their respective precursors. The uncoordinate effect of interferon inhibition on viral 30,000-dalton protein and gP-70 is discussed.


The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC.
The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.


Factors controlling carbon distribution on reforested minelands and regenerating clearcuts in Appalachia, USA.
Increasing carbon (C) storage in soils of degraded lands, such as surface coal mines, is of interest because of its potential role in mitigating increases in atmospheric CO2. While it has been shown that reforesting degraded lands can significantly increase C storage in soils, there are limited studies addressing what processes control soil C in these systems. A study was initiated with the following objectives: 1) quantify the amount of soil C accumulating on reforested mine lands; and 2) examine several biological processes that govern the amount of C sequestered into soil (decomposition, soil respiration and microbial dynamics). A chronosequence approach was used to examine C changes with time in reforested mine lands (years 1, 3, and 8) and unmined regenerating clear-cuts (years 4, 12 and 20). From a C perspective, our results indicated that the young reforested mines (ages 1 and 3) differed significantly from the older mines (age 8) and all regenerating clear-cuts for all parameters examined. However, after 8 years litterfall, microbial biomass C and nitrogen (N), microbial activity, litter decomposition and CO2 efflux were similar on the mine as that found on the 12-year-old naturally regenerating clear-cut. Although soil organic C (SOC) content was lower on the reforested mines than the regenerating forests, rates of SOC accumulation were greater on the mine sites, likely because the young mine lands were initially devoid of SOC and conditions were suitable for rapid sequestration.


Obesity is associated with an altered HDL subspecies profile among adolescents with metabolic disease.
We aimed to determine the risk factors associated with the depletion of large HDL particles and enrichment of small HDL particles observed in adolescents with T2D. Four groups of adolescents were recruited: 1) lean insulin-sensitive (L-IS), normal BMI and no insulin resistance; 2) lean insulin-resistant (L-IR), normal BMI but insulin resistance (fasting insulin levels ≥ 25 mU/ml and homeostatic model assessment of insulin resistance ≥ 6); 3) obese insulin-sensitive (O-IS), BMI ≥ 95th percentile and no insulin resistance; and 4) obese insulin-resistant (O-IR), BMI ≥ 95th percentile and insulin resistance. Plasma was separated by using gel-filtration chromatography to assess the HDL subspecies profile and compared with that of obese adolescents with T2D (O-T2D). Large HDL subspecies were significantly lower across groups from L-IS > L-IR > O-IS > O-IR > O-T2D (P < 0.0001); small HDL particles were higher from L-IS to O-T2D (P < 0.0001); and medium-sized particles did not differ across groups. The contributions of obesity, insulin resistance, and diabetes to HDL subspecies profile were between 23% and 28%, 1% and 10%, and 4% and 9%, respectively. Obesity is the major risk factor associated with the altered HDL subspecies profile previously reported in adolescents with T2D, with smaller contributions from insulin resistance and diabetes.


Diffuse lymphoplasmacytic infiltration of the small intestine with damage to nerve plexus. A cause of intestinal pseudo-obstruction.
We describe the clinicopathologic characteristics of three patients with chronic intestinal pseudo-obstruction and malabsorption. The patients were young women (average age, 25 years) who presented with abdominal pain, nausea, vomiting, diarrhea, and weight loss that led to extreme inanition and death in two patients despite multiple treatment schemes. The evolution of the process averaged 8 years. No case manifested evidence of malignant lymphoproliferative progression. Histologically, a diffuse lymphoplasmacytic infiltrate that affected all the layers of the intestinal wall was observed in full-thickness biopsy specimens. The proliferating lymphocytes were small and mixed with mature plasma cells that proved to be polyclonal on immunohistochemical analysis. An outstanding finding in all three cases was extensive damage to submucosal and myenteric nerve plexus associated with a lymphoid infiltrate. Quantification of the myenteric plexus by using immunohistochemical and morphometric techniques also revealed a marked reduction in their number. We concluded that diffuse lymphoplasmacytic infiltration of the small intestine associated with damage to the intestinal nerve plexus constitutes a specific disorder that is different from other diseases that produce intestinal pseudo-obstruction.


Coronal limb alignment and indications for high tibial osteotomy in patients undergoing revision ACL reconstruction.
Failed ACL reconstruction frequently is accompanied by irreparable medial meniscal tear and/or visible osteoarthritis (OA) in the medial tibiofemoral joint. Thus, assessment for the presence of varus malalignment is important in caring for patients in whom revision ACL reconstruction is considered. We determined whether patients undergoing revision ACL reconstruction (1) have more frequent varus malalignment coupled with more severe degrees of medial meniscal injury and/or medial tibiofemoral OA, and (2) would meet potential indications for high tibial osteotomy more frequently than patients undergoing primary ACL reconstruction. We compared 58 patients undergoing revision ACL reconstruction and 116 patients undergoing primary ACL reconstruction. The mechanical tibiofemoral angle and the weight loading line (%) of the knee were measured. Additionally, radiographic degrees of OA in the tibiofemoral joints, and meniscal conditions were assessed. Then, proportions of potential candidates for high tibial osteotomy between the two groups were compared based on the following indications: (1) weight loading line less than 5%, (2) weight loading line less than 25% and medial tibiofemoral OA Kellgren-Lawrence Grade 3 or greater, or (3) weight loading line less than 25% and Kellgren-Lawrence Grade 2 medial tibiofemoral OA plus subtotal or total medial meniscectomy status. The revision ACL reconstruction group had more frequent varus malalignment in terms of proportion of knees with more varus mechanical tibiofemoral angle than varus 5° (19% versus 8%, p = 0.029) and knees with weight loading line less than 25% (22% versus 9%, p = 0.011). This group also had more frequent high-grade injury of the medial meniscus (34% versus 16%, p = 0.007) and tended to have more frequent higher-grade radiographic OA at the medial tibiofemoral joint (19% versus 9%, p = 0.076). The percentage of patients meeting potential indications for high tibial osteotomy was greater in this group (14% versus 2%, p = 0.003). We found that many patients undergoing revision ACL surgery may be reasonable candidates for concurrent high tibial osteotomy to address concomitant alignment and OA issues in the medial compartment. However, whether that additional intervention is offset by added risk and morbidity should be the focus of a future study, as it cannot be answered by a study of this design.


Analytical results for fundamental time-delayed feedback systems subjected to multiplicative noise.
We study the stochastic behavior of fundamental time-delayed feedback systems subjected to multiplicative noise. We derive exact results for the first and second moments and the autocorrelation function. For a particular class of systems we show how the variance depends on the amplitude of the multiplicative noise. Furthermore, we identify parameter regions of stationary solutions with finite and infinite variances. Finally, we suggest that delay-induced Lévy flights may occur in time-delayed feedback systems involving multiplicative noise.


Sleep apnea and hypothyroidism.
Thyroid deficiency states are now a well recognized cause of the sleep apnea syndrome. The spectrum of disease ranges from mild, asymptomatic hypothyroidism to severe myxedema, and the disorder is associated with both obstructive and central types of sleep apnea. A variety of factors may be involved, including upper airway obstruction with or without obesity, and alterations in ventilatory drive. The definitive therapy is thyroid hormone replacement, which has been shown to diminish or completely eliminate apneic episodes and arterial oxygen desaturation, as well as to effect many improvements in sleep patterns and overall sleep efficiency. The incidence of thyroid deficiency states in patients with sleep apnea syndrome is not known, but it seems reasonable to evaluate thyroid function in all patients. Thyroid replacement therapy seems logical for the treatment of sleep apnea in patients with previously unrecognized subclinical hypothyroidism. Much remains to be learned about the diagnosis and treatment of sleep apnea syndromes associated with thyroid hormone deficiency, and further studies are needed.


Retroviral transfer of the p16INK4a cDNA inhibits C6 glioma formation in Wistar rats.
BACKGROUND: The p16INK4A gene product halts cell proliferation by preventing phosphorylation of the Rb protein. The p16INK4a gene is often deleted in human glioblastoma multiforme, contributing to unchecked Rb phosphorylation and rapid cell division. We show here that transduction of the human p16INK4a cDNA using the pCL retroviral system is an efficient means of stopping the proliferation of the rat-derrived glioma cell line, C6, both in tissue culture and in an animal model. C6 cells were transduced with pCL retrovirus encoding the p16INK4a, p53, or Rb genes. These cells were analyzed by a colony formation assay. Expression of p16INK4a was confirmed by immunohistochemistry and Western blot analysis. The altered morphology of the p16-expressing cells was further characterized by the senescence-associated beta-galactosidase assay. C6 cells infected ex vivo were implanted by stereotaxic injection in order to assess tumor formation. RESULTS: The p16INK4a gene arrested C6 cells more efficiently than either p53 or Rb. Continued studies with the p16INK4a gene revealed that a large portion of infected cells expressed the p16INK4a protein and the morphology of these cells was altered. The enlarged, flat, and bi-polar shape indicated a senescence-like state, confirmed by the senescence-associated beta-galactosidase assay. The animal model revealed that cells infected with the pCLp16 virus did not form tumors. CONCLUSION: Our results show that retrovirus mediated transfer of p16INK4a halts glioma formation in a rat model. These results corroborate the idea that retrovirus-mediated transfer of the p16INK4a gene may be an effective means to arrest human glioma and glioblastoma.


5-HT(2A/2C) receptor-mediated hypopnea in the newborn rat: relationship to Fos immunoreactivity.
Previous data derived from anesthetized, decerebrate, or in vitro preparations suggested that 5-HT(2) receptor activation might be responsible for respiratory dysfunction. Such a mechanism has not yet been documented in the intact animal, but might be of clinical relevance to the apneic spells of the premature infant. In the present investigation on conscious newborn rats we analyzed the respiratory response to the activation of 5-HT(2A/2C) receptors by the agonist 1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and we delineated central structures possibly involved in this response, using Fos expression as a marker of neuronal activation. We demonstrated that intraperitoneal injection of 5 mg/kg DOI produced a long-lasting decrease in respiratory frequency and tidal volume, which could be blocked by the antagonist ritanserin. Fos immunohistochemistry suggested that the rostral ventrolateral medulla and the lateral paragigantocellular nucleus might have a key role in the respiratory response to 5-HT(2) receptor activation. In addition, double immunostaining for Fos and tyrosine hydroxylase suggested that the contribution of catecholaminergic neurons to this response might be modest and indirect.


The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study.
Pathogenic variations in the OTOF gene are a common cause of hearing loss. To refine the natural history and genotype-phenotype correlations of OTOF-related auditory neuropathy spectrum disorders (ANSD), audiograms and distortion product otoacoustic emissions (DPOAEs) were collected from a diverse cohort of individuals diagnosed with OTOF-related ANSD by comprehensive genetic testing and also reported in the literature. Comparative analysis was undertaken to define genotype-phenotype relationships using a Monte Carlo algorithm. 67 audiograms and 25 DPOAEs from 49 unique individuals positive for OTOF-related ANSD were collected. 51 unique OTOF pathogenic variants were identified of which 21 were missense and 30 were loss of function (LoF; nonsense, splice-site, copy number variants, and indels). There was a statistically significant difference in low, middle, and high frequency hearing thresholds between missense/missense and LoF/missense genotypes as compared to LoF/LoF genotypes (average hearing threshold for low, middle and high frequencies 70.9, 76.0, and 73.4 dB vs 88.5, 95.6, and 94.7 dB) via Tukey's test with age as a co-variate (P = 0.0180, 0.0327, and 0.0347, respectively). Hearing declined during adolescence with missense/missense and LoF/missense genotypes, with an annual mid-frequency threshold deterioration of 0.87 dB/year and 1.87 dB/year, respectively. 8.5% of frequencies measured via DPOAE were lost per year in individuals with serial tests. Audioprofiling of OTOF-related ANSD suggests significantly worse hearing with LoF/LoF genotypes. The unique pattern of variably progressive OTOF-related autosomal recessive ANSD may be amenable to gene therapy in selected clinical scenarios.


Protein tyrosine phosphatases mediate cell readhesion in alveolar epithelial cells mechanically separated from in vitro matrix.
Alveolar epithelial type II cells are the progenitor cells for restoring the alveolar epithelial barrier after acute lung injury. During repair of lung injury, the alveolar epithelial type II cells reepithelialize denuded air spaces, a process that involves breaking and reforming cell adhesions. A novel technique of mechanical separation of cultured alveolar epithelial cells from in vitro matrix was used to examine the intracellular signals that result when alveolar epithelial cell adhesions are broken. The results show that the tyrosine phosphorylation levels of focal adhesion kinase, paxillin, and pp60(src) decreased immediately after mechanical separation of the cells. Levels returned to nearly normal by 24 h after mechanical separation. Paxillin and pp60(scr) coprecipitated with focal adhesion kinase regardless of their phosphorylation state. Interestingly, the tyrosine phosphorylation level of the mitogen-activated protein kinase, p42(erk2), increased 15 min after mechanical separation. Preincubation of cell monolayers with phenylarsine oxide, a protein tyrosine phosphatase inhibitor, blocked the decrease in tyrosine phosphorylation levels of focal adhesion kinase, paxillin and pp60(src). Phenylarsine oxide incubation also prevented readhesion of mechanically separated cells at 24 h, but genistein, a tyrosine kinase inhibitor, had no effect. We conclude that protein tyrosine phosphatases are activated immediately after cultured alveolar epithelial cells are mechanically separated from in vitro matrix, and their activation is required for alveolar epithelial cell readhesion.


Thermodynamics of quantum information scrambling.
Scrambling of quantum information can conveniently be quantified by so-called out-of-time-order correlators (OTOCs), i.e., correlators of the type 〈[W_{τ},V]^{†}[W_{τ},V]〉, whose measurements present a formidable experimental challenge. Here we report on a method for the measurement of OTOCs based on the so-called two-point measurement scheme developed in the field of nonequilibrium quantum thermodynamics. The scheme is of broader applicability than methods employed in current experiments and provides a clear-cut interpretation of quantum information scrambling in terms of nonequilibrium fluctuations of thermodynamic quantities, such as work and heat. Furthermore, we provide a numerical example on a spin chain which highlights the utility of our thermodynamic approach when understanding the differences between integrable and ergodic behaviors. We also discuss how the method can be used to extend the reach of current experiments.


The construction of help during radiotherapy: Redefining informal care.
This study will explore how help is constructed during and following radiotherapy for patients with cancer. Grounded theory methods were used in the study to explore the way in which family members and friends constructed a role for themselves in relation to patients receiving radiotherapy. A total of 22 helpers were interviewed. Patients were being treated for a range of cancers including breast, prostate, colorectal, and head and neck. Respondents in this study consistently defined themselves as "helpers" rather than "carers." While radiotherapy as a treatment modality was mostly seen as noninvasive, the cancer diagnosis cast a long shadow over the lives of helpers and patients creating a separation in longstanding relationships. Helpers experienced this separation as "otherness." Help became an important vehicle for bridging this separation. Individuals developed different ways of knowing about the patient as the basis for providing help. Two different types of help were identified in this study: the behind the scenes, largely invisible work that helpers undertook to help the patient without their knowledge and the explicit visible help that was much more commonly negotiated and discussed between helpers and patients. The study provides the basis for a greater understanding on the part of professionals into the impact of diagnosis and radiotherapy treatment on family and friends. In doing so, the study identifies opportunities for the experience of helpers to be recognised and supported by professionals.


Dilated cardiomyopathy in children: determinants of outcome.
To determine the outcome of dilated cardiomyopathy presenting in childhood and the features that might be useful for prognostic stratification. Supraregional paediatric cardiology unit. Retrospective analysis. The natural history of dilated cardiomyopathy in children is not well characterised. Previous studies have shown a variable relation between age at presentation and outcome, and sudden death has been infrequent. Retrospective study of 63 consecutive patients with idiopathic dilated cardiomyopathy presenting between 1979 and 1992. Survival curves were constructed by the Kaplan-Meier method. Age at diagnosis ranged from 1 day to 15 years (median 12 months) and follow up ranged from 1 day to 13 years (median 19 months). Actuarial survival from presentation was 79% at one year (95% confidence interval (95% CI) 66%-88%) and 61% (44%-74%) at five years. Univariate analysis showed that mural thrombus, left ventricular end diastolic pressure > 20 mm Hg, and age at presentation > 2 years were predictors of adverse outcome, but on multivariate analysis only age at presentation was significant. Left ventricular echocardiographic indices either did not improve or deteriorated in 36 children (17 of whom died, four suddenly, and three were transplanted), partially improved in 16 (three of whom died, all suddenly), and returned to normal in 11 (all of whom have survived). Older age at presentation and lack of improvement in systolic function are associated with an adverse outcome, and early transplantation should be considered in these patients. There is a persistent risk of late sudden death in those children in whom echocardiographic dimensions remain abnormal.


Regulation of relative abundance of arterivirus subgenomic mRNAs.
The subgenomic (sg) mRNAs of arteriviruses (order Nidovirales) form a 5'- and 3'-coterminal nested set with the viral genome. Their 5' common leader sequence is derived from the genomic 5'-proximal region. Fusion of sg RNA leader and "body" segments involves a discontinuous transcription step. Presumably during minus-strand synthesis, the nascent RNA strand is transferred from one site in the genomic template to another, a process guided by conserved transcription-regulating sequences (TRSs) at these template sites. Subgenomic RNA species are produced in different but constant molar ratios, with the smallest RNAs usually being most abundant. Factors thought to influence sg RNA synthesis are size differences between sg RNA species, differences in sequence context between body TRSs, and the mutual influence (or competition) between strand transfer reactions occurring at different body TRSs. Using an Equine arteritis virus infectious cDNA clone, we investigated how body TRS activity affected sg RNA synthesis from neighboring body TRSs. Flanking sequences were standardized by head-to-tail insertion of several copies of an RNA7 body TRS cassette. A perfect gradient of sg RNA abundance, progressively favoring smaller RNA species, was observed. Disruption of body TRS function by mutagenesis did not have a significant effect on the activity of other TRSs. However, deletion of body TRS-containing regions enhanced synthesis of sg RNAs from upstream TRSs but not of those produced from downstream TRSs. The results of this study provide considerable support for the proposed discontinuous extension of minus-strand RNA synthesis as a crucial step in sg RNA synthesis.


[Thrombosis in patients with malignancy].
Thrombosis traditionally considered as a complication of cardiovascular disease, however, this problem until recently was rarely taken into account in the presence of cancer. Although the association between cancer and thrombosis has been known almost 150 years ago, awareness of the impact of thrombotic complications have increased only now. Cancer is an independent major risk factor for venous thromboembolism (VTE), which is the leading cause of death of cancer patient. The incidence of VTE is steadily increasing in these patients. Thrombotic events have a significant impact on the quality of life of patients, and are associated with worsening of their short-term and long-term survival. The objective of this review is to summarize modern views on pathophysiology, as well as to outline new approaches to risk assessment, prevention and treatment of thrombosis in cancer patients.


Towards a Humanized Mouse Model of Liver Stage Malaria Using Ectopic Artificial Livers.
The malaria liver stage is an attractive target for antimalarial development, and preclinical malaria models are essential for testing such candidates. Given ethical concerns and costs associated with non-human primate models, humanized mouse models containing chimeric human livers offer a valuable alternative as small animal models of liver stage human malaria. The best available human liver chimeric mice rely on cellular transplantation into mice with genetically engineered liver injury, but these systems involve a long and variable humanization process, are expensive, and require the use of breeding-challenged mouse strains which are not widely accessible. We previously incorporated primary human hepatocytes into engineered polyethylene glycol (PEG)-based nanoporous human ectopic artificial livers (HEALs), implanted them in mice without liver injury, and rapidly generated human liver chimeric mice in a reproducible and scalable fashion. By re-designing the PEG scaffold to be macroporous, we demonstrate the facile fabrication of implantable porous HEALs that support liver stage human malaria (P. falciparum) infection in vitro, and also after implantation in mice with normal liver function, 60% of the time. This proof-of-concept study demonstrates the feasibility of applying a tissue engineering strategy towards the development of scalable preclinical models of liver stage malaria infection for future applications.


Maintaining Good Oral Health With Fluoridated Water.
Community water fluoridation (CWF) has been a public health measure against tooth decay since 1945. Strong evidence supports the use of CWF in reduction in caries risk in the pediatric population, and numerous studies also show benefit in adults. CWF remains an important contributor to oral health despite the availability and widespread use of other fluoride-containing dental products. The efficacy, safety, and optimal use of CWF will be discussed.