Proteins of the kidney microvillar membrane. Purification and properties of carboxypeptidase P from pig kidneys.
Carboxypeptidase P has been purified by immunoaffinity chromatography from pig kidneys. A single-step assay with Z-Pro-Met (where Z represents benzyloxycarbonyl) as substrate was used, methionine being determined by using L-amino acid oxidase and horseradish peroxidase. The enzyme constitutes about 1.5% of the kidney microvillar proteins. Triton X-100-solubilized and papain-released forms of the enzyme were isolated. The former had an apparent subunit Mr of 135 000, and the latter form contained two polypeptide chains of Mr 128 000 and 95 000. The undenatured forms were dimeric proteins. In common with other microvillar hydrolases, carboxypeptidase P was a glycoprotein and each subunit contained one Zn atom. MnCl2 (1 mM) in the assay was necessary for maximum activity; in its absence, 0.5 mM-ZnSO4 produced a limited activation, but was inhibitory at higher concentrations. The Km for Z-Pro-Met, in the presence of MnCl2, was 4.1 mM, and the kcat. for freshly prepared enzyme was 1230 min-1. The enzyme lost activity during storage at -20 degrees C. In a limited survey of peptides, hydrolysis was observed only with substrates containing a proline, alanine or glycine residue in the P1 position, and these included angiotensins II and III. The best substrate in this series was Val-Ala-Ala-Phe.


Peri-ovulatory endocrine regulation of the prostanoid pathways in the bovine uterus at early dioestrus.
We hypothesised that different endocrine profiles associated with pre-ovulatory follicle (POF) size would impact on uterine prostanoid pathways and thereby modulate the histotroph composition. Beef cows (n=15 per group) were hormonally manipulated to have small (SF-SCL group) or large (LF-LCL group) pre-ovulatory follicles (POF) and corpora lutea (CL). Seven days after induction of ovulation, animals were slaughtered and uterine tissues and flushings were collected for quantification of prostanoids. The POF and CL size and the circulating progesterone concentrations at Day 7 were greater (P<0.05) in the LF-LCL cows than in the SF-SCL group, as expected. The abundance of 5 out of 19 genes involved in prostanoid regulation was different between groups. Transcript abundance of prostaglandin F2α, E2 and I2 synthases was upregulated (P<0.05) and phospholipase A2 was downregulated (P<0.05) in endometrium of the LF-LCL group. No difference (P>0.1) in prostanoid concentrations in the endometrium or in uterine flushings was detected between groups. However, prostaglandin F2α and E2 concentrations in the uterine flushings were positively correlated with the abundance of transcripts for prostaglandin endoperoxide synthase 2 (0.779 and 0.865, respectively; P<0.002). We conclude that endometrial gene expression related to prostanoid synthesis is modulated by the peri-ovulatory endocrine profile associated with POF size, but at early dioestrus differences in transcript abundance were not reflected in changes in prostanoid concentrations in the uterine tissue and fluid.


[Use of poly-beta-oxybutyric acid by Yersinia pseudotuberculosis and Listeria monocytegenes bacteria at various temperatures].
A comparative investigation of the intracellular content of poly-beta-hydroxybutyric acid showed that Yersinia pseudotuberculosis strains accumulated, on the average, lower amounts of this reserve substance than Listeria monocytogenes strains. The intracellular pool of poly-beta-hydroxybutyric acid was responsible for the growth of the bacteria at low temperatures (4-6 degrees C) in the absence of any exogenous carbon and energy source.


Tools for Enhancement and Quality Improvement of Peer Assessment and Clinical Care in Endocrinology and Metabolism.
Members of the College of Physicians and Surgeons of Ontario Endocrinology and Metabolism Peer Review Network have been involved in a quality improvement project to help standardize the peer assessment of physicians practicing in endocrinology and metabolism. This has included developing state-of-the-art summaries of common endocrine problems by Canadian experts in endocrinology and metabolism. These tools have been developed in response to the educational needs, as identified by peer reviewers, of practicing endocrinologists in Ontario. These pedagogical tools aim not only to standardize the documentation of the clinical performance of endocrinologists but also to make the process more transparent and to improve the quality of patient care in Ontario. This article summarizes the project and also provides the tools developed for the endocrinology and metabolism section of the College of Physicians and Surgeons of Ontario.


Localization and properties of respiratory neurons in the rostral pons of the newborn rat.
The distribution and discharge pattern of respiratory neurons in the 'pneumotaxic center' of the rostral pons in the rat has remained unknown. We performed optical recordings and whole-cell patch clamp recordings to clarify respiratory neuron activity in the rostral pons of a brainstem-spinal cord preparation from a newborn rat. Inspiratory nerve activity was recorded in the 4th cervical nerve and used as a trigger signal for optical recordings. Respiratory neuron activity was detected in the limited region of the rostral-lateral pons. The main active region was presumed to be primarily the Kölliker-Fuse nucleus. The location of respiratory neurons was further confirmed by Lucifer Yellow staining after conducting whole-cell recordings. From a membrane potential analysis of the respiratory neurons in the rostral pons, the respiratory neurons were divided into four types: inspiratory neuron (71.9%), pre-inspiratory neuron (5.3%), post-inspiratory neuron (19.3%), and expiratory neuron (3.5%). A noticeable difference between pontine and medullary respiratory neurons was that post-inspiratory neurons were more frequently encountered in the pons. Application of a mu-opioid agonist, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, transformed the burst pattern of post-inspiratory neurons into that of pre-inspiratory neurons. The electrical stimulation of the sensory root of the trigeminal nerve induced three types of responses in 85% of pontine respiratory neurons: inhibitory postsynaptic potentials (42.7%), excitatory postsynaptic potentials (37.7%) and no response (15.1%). Our findings provide the first evidence in the rat for the presence of respiratory neurons in the rostral pons, with localization in the lateral region approximately overlapping with the Kölliker-Fuse nucleus.


Activation of trans geometry in bifunctional mononuclear platinum complexes by a non-bulky methylamine ligand.
In order to shed light on the mechanism that underlies activity of bifunctional mononuclear Pt(II) analogs of transplatin we examined in the present work a DNA binding mode of the analog of transplatin, namely trans-[Pt(CH3NH2)2Cl2], in which NH3 groups were replaced only by a small, non-bulky methylamine ligand. This choice was made because we were interested to reveal the role of the bulkiness of the amines used to substitute NH3 in transplatin to produce antitumor-active Pt(II) drug. The results indicate that trans-[Pt(CH3NH2)2Cl2] forms a markedly higher amount of more distorting intrastrand cross-links than transplatin which forms in DNA preferentially less distorting and persisting monofunctional adducts. Also importantly, the accumulation of trans-[Pt(CH3NH2)2Cl2] in tumor cells was considerably greater than that of transplatin and cisplatin. In addition, the results of the present work demonstrate that the replacement of ammine groups by the non-bulky methylamine ligand in the molecule of ineffective transplatin results in a radical enhancement of its activity in tumor cell lines including cisplatin-resistant tumor cells. Thus, activation of the trans geometry in bifunctional mononuclear Pt(II) complexes can be also accomplished by replacement of ammine groups in transplatin by non-bulky methylamine ligands so that it is not limited only to the replacement by relatively bulky and stereochemically more demanding amino ligands.


Spatial and Temporal Analysis of Populations of the Sudden Oak Death Pathogen in Oregon Forests.
Sudden oak death caused by the oomycete Phytophthora ramorum was first discovered in California toward the end of the 20th century and subsequently emerged on tanoak forests in Oregon before its first detection in 2001 by aerial surveys. The Oregon Department of Forestry has since monitored the epidemic and sampled symptomatic tanoak trees from 2001 to the present. Populations sampled over this period were genotyped using microsatellites and studied to infer the population genetic history. To date, only the NA1 clonal lineage is established in this region, although three lineages exist on the North American west coast. The original introduction into the Joe Hall area eventually spread to several regions: mostly north but also east and southwest. A new introduction into Hunter Creek appears to correspond to a second introduction not clustering with the early introduction. Our data are best explained by both introductions originating from nursery populations in California or Oregon and resulting from two distinct introduction events. Continued vigilance and eradication of nursery populations of P. ramorum are important to avoid further emergence and potential introduction of other clonal lineages.


iPTT(2 L)-CNN: A Two-Layer Predictor for Identifying Promoters and Their Types in Plant Genomes by Convolutional Neural Network.
A promoter is a short DNA sequence near to the start codon, responsible for initiating transcription of a specific gene in genome. The accurate recognition of promoters has great significance for a better understanding of the transcriptional regulation. Because of their importance in the process of biological transcriptional regulation, there is an urgent need to develop in silico tools to identify promoters and their types timely and accurately. A number of prediction methods had been developed in this regard; however, almost all of them were merely used for identifying promoters and their strength or sigma types. Owing to that TATA box region in TATA promoter that influences posttranscriptional processes, in the current study, we developed a two-layer predictor called iPTT(2L)-CNN by using the convolutional neural network (CNN) for identifying TATA and TATA-less promoters. The first layer can be used to identify a given DNA sequence as a promoter or nonpromoter. The second layer is used to identify whether the recognized promoter is TATA promoter or not. The 5-fold crossvalidation and independent testing results demonstrate that the constructed predictor is promising for identifying promoter and classifying TATA and TATA-less promoter. Furthermore, to make it easier for most experimental scientists get the results they need, a user-friendly web server has been established at http://www.jci-bioinfo.cn/iPPT(2L)-CNN.


Phase retrieval, error reduction algorithm, and Fienup variants: a view from convex optimization.
The phase retrieval problem is of paramount importance in various areas of applied physics and engineering. The state of the art for solving this problem in two dimensions relies heavily on the pioneering work of Gerchberg, Saxton, and Fienup. Despite the widespread use of the algorithms proposed by these three researchers, current mathematical theory cannot explain their remarkable success. Nevertheless, great insight can be gained into the behavior, the shortcomings, and the performance of these algorithms from their possible counterparts in convex optimization theory. An important step in this direction was made two decades ago when the error reduction algorithm was identified as a nonconvex alternating projection algorithm. Our purpose is to formulate the phase retrieval problem with mathematical care and to establish new connections between well-established numerical phase retrieval schemes and classical convex optimization methods. Specifically, it is shown that Fienup's basic input-output algorithm corresponds to Dykstra's algorithm and that Fienup's hybrid input-output algorithm can be viewed as an instance of the Douglas-Rachford algorithm. We provide a theoretical framework to better understand and, potentially, to improve existing phase recovery algorithms.


Treatment of dyslipidaemias with fluvastatin.
In many patients with primary hyperlipidaemia the statins have become the drugs of choice when diet alone has failed. Despite the availability of different potencies of the statins, the dosages prescribed in most countries appear to be aimed at producing a reduction in levels of low-density lipoprotein cholesterol (LDL-C) of about 25%. Fluvastatin is the newest member of this class of agent and the first completely synthetic compound. In dose-finding studies, fluvastatin has produced statistically significant (P < 0.001) reductions in LDL-C levels when used in dosages of 20 mg (21%) and 40 mg (27.4%), thus placing it within the range generally required of other statins; additional studies have shown that the efficacy of fluvastatin is unaffected by gender and age. Moreover, fluvastatin produces the maximum reduction in LDL-C levels within 6 weeks and maintains this efficacy during long-term treatment (LDL-C levels have been reported to fall by 27.4% over 2 years with fluvastatin 40 mg/day). In high-risk patients the LDL-C-lowering effect of fluvastatin 40 mg/day is maintained when compared with low-risk patients (26.6% vs 24.8%). A similar pattern has been observed in hypertensive patients, irrespective of the antihypertensive agent used to control blood pressure. Fluvastatin has been found to produce better LDL-C-lowering effects than bezafibrate and come instances has exhibited an advantage over other statins. In addition to lowering LDL-C levels by the required amount, 20 and 40 mg (the equivalent of pravastatin 20 mg) dosages of fluvastatin significantly reduce levels of total cholesterol and triglycerides and increase high-density lipoprotein cholesterol levels.


Prolonged grief symptomatology following violent loss: the mediating role of meaning.
Background: Prolonged Grief Disorder (PGD) is over-represented among those who have lost loved ones to violent causes. To tailor PGD interventions for this vulnerable population it is critical to examine the aetiology of PGD specifically in the context of violent death bereavement. Previous studies have suggested that violent loss increases symptoms of PGD by hindering the mourner's ability to make meaning of the death or its aftermath. However, these studies have relied on cross sectional data that preclude genuine prediction and have not differentiated among specific themes of meaning. Objective: This study aimed to identify specific themes of meaning that mediate the detrimental impact of violent loss on subsequent emergence of PGD symptomatology among the violently bereft. Method: A longitudinal, prospective design (N = 171) was used to assess violent loss and themes of meaning an average of six months post-loss allowing for prediction of PGD symptoms an average of eight months later. Results: Violent loss had a significant indirect effect on PGD symptomatology when meaning themes focusing on sense of peace and continuing bonds served as mediators. Conclusions: This study demonstrates the mediating role that specific meaning themes play in the development of PGD symptomatology following violent loss. These findings highlight the potential benefits of applying a meaning-based intervention approach with the violently bereft.


Should Dentists Mandatorily Wear Ear Protection Device to Prevent Occupational Noise-induced Hearing Loss? A Randomized Case-Control Study.
Dentists are constantly exposed to high-frequency noise at their workplace that increases the risk of occupational noise-induced hearing loss (ONIHL). Even though dentists acknowledge about the noisy dental workplace, hearing protection devices or ear protection devices (EPD) are not commonly used by dentists. No study has yet provided any evidence on how effective EPDs can be in reducing the temporary threshold shift and damage to the outer, middle and inner ears. The aim of this article is to evaluate and compare the changes in the hearing acuity and temporary threshold shift (TTS) in dentists who wear EPDs when compared with those who do not use EPDs. Sixty-four dental clinicians were randomly divided into two groups: Group 1 (performed ultrasonic scaling without EPDs) and Group 2 (performed ultrasonic scaling with EPDs). Their hearing threshold was checked by using pure tone audiometry, stapedial acoustic reflexes, and otoacoustic emission (OAE) before and after 45 mins of ultrasonic scaling. The intergroup and intragroup comparison was done. All the outcome measures from pre- and post-scaling across the ears, groups, and frequencies among groups were done using mixed-effects analysis of variance. A P-value of less than 0.05 was considered to be statistically significant. EPDs were effective in reducing the immediate TTSs. Immediately upon exposure to high-frequency noise, the alterations in the hearing threshold and stapedial reflex OAE were less in the group that used EPDs. EPDs should be mandatorily worn by dentists to prevent accumulation of temporary shifts in the hearing acuity, which in long-term can lead to permanent hearing loss.


[Activated charcoal as first-choice therapy in poisoning].
In gastrointestinal detoxication, three methods are possible: ipecac induced emesis, gastric lavage and administration of activated charcoal. The method of treatment predominantly used in the Netherlands is gastric lavage in combination with activated charcoal. Published evidence suggests that activated charcoal not preceded by gastric emptying is preferred. Additional advantages of using activated charcoal alone as the method of choice for gastrointestinal decontamination are patient friendliness, low cost and time saving because quick intervention by general practitioners is possible.


Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.
There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.


Regurgitant flow field characteristics of the St. Jude bileaflet mechanical heart valve under physiologic pulsatile flow using particle image velocimetry.
The regurgitant flow fields of clinically used mechanical heart valves have been traditionally studied in vitro using flow visualization, ultrasound techniques, and laser Doppler velocimetry under steady and pulsatile flow. Detailed investigation of the forward and regurgitant flow fields of these valves can elucidate a valve's propensity for blood element damage, thrombus formation, or cavitation. Advances in particle image velocimetry (PIV) have allowed its use in the study of the flow fields of prosthetic valves. Unlike other flow field diagnostic systems, recent work using PIV has been able to relate particular regurgitant flow field characteristics of the Bjork-Shiley Monostrut valve to a propensity for cavitation. In this study, the regurgitant flow field of the St. Jude Medical bileaflet mechanical heart valve was assessed using PIV under physiologic pulsatile flow conditions. Data collected at selected time points prior to and after valve closure demonstrated the typical regurgitant jet flow patterns associated with the St. Jude valve, and indicated the formation of a strong regurgitant jet, in the B-datum plane, along with twin vortices near the leaflets. Estimated ensemble-average viscous shear rates suggested little potential for hemolysis when the hinge jets collided. However, the vortex motion near the occluder tips potentially provides a low-pressure environment for cavitation.


Slow late myocardial clearance of thallium: a characteristic phenomenon in coronary artery disease.
We extended the quantitative seven-pinhole method to follow the dynamics of thallium redistribution after exercise. We observed a pattern of slow late thallium clearance that appears to be characteristic of myocardium supplied by obstructed coronary arteries. In 28 subjects, quantitative thallium scintigrams (seven-pinhole tomography, circumferential count profiles) and blood samples for thallium concentration were taken immediately, 2 hours and 4 hours after maximal treadmill exercise. Twenty subjects had coronary artery disease (CAD) and eight were normal. The rate of thallium clearance from the blood (TCB) was compared with the rate of thallium clearance from each segmental region of myocardium (TCM, derived by ratioing corresponding segments of the absolute circumferential count profiles) between the 2- and 4-hour images. In seven of the eight normal subjects, TCM exceeded TCB in all regions of all images (specificity 88%). Seventeen of the 20 CAD patients had at least one region where TCM was less than TCB (sensitivity 85%). Of the 13 patients with multivessel CAD, 11 had multiple regions with TCM less than TCB. Using this criterion, we detected 31 of 39 obstructed coronary arteries. Of the 37 regions that were abnormal by this analysis, 30 corresponded to obstructed coronary arteries. In contrast, while conventional circumferential count profile analysis also was abnormal in 17 of the 20 CAD patients, it diagnosed multivessel CAD in only five of the 13 patients that had it. These results show that slow late thallium clearance from myocardium is characteristic of regions of myocardium supplied by diseased coronary arteries and that observation of this phenomenon may improve diagnostic sensitivity for the presence of multivessel CAD.


Monitoring prednisolone and prednisone in saliva: a population pharmacokinetic approach in healthy volunteers.
Prednisolone (PLN) is a widely used corticosteroid in a variety of immune-mediated diseases. Treatment regimes generally consist of empirically derived treatment doses, whereas therapeutic response among patients is highly variable. Drug monitoring of serum PLN levels might support a more rational approach to dose selection, yet is invasive and laborious. In analogy to cortisol, salivary PLN may offer a good alternative for serum PLN, being a representative approximation of free serum PLN. The aims of this study were to evaluate the correlation between free serum and salivary PLN levels and to quantify this relationship within a population pharmacokinetic model. PLN and prednisone (PN) concentrations were measured in 396 samples from 19 healthy volunteers after oral ingestion of 80 mg PLN. Measurements in serum, ultrafiltrate, and saliva were performed with a recently validated liquid chromatography tandem mass spectrometry method. Population pharmacokinetic analysis was performed with nonlinear mixed effect modeling using NONMEM. Salivary PLN levels correlated well with free serum PLN levels (r = 0.931, P < 0.01). A weaker correlation was found for PN (r = 0.318, P < 0.01), which may be explained by the finding that salivary PN levels mainly seemed to consist of PLN enzymatically converted to PN. Total and free serum PLN concentrations decreased over time after drug administration and showed a nonlinear mutual relationship, consistent with concentration-dependent protein binding. Modeled PLN pharmacokinetics corresponded with previous reports. Low to moderate interindividual variability was found for V/F and CL/F (coefficients of variation were 13.8% and 14.6%, respectively). Free and salivary PLN showed a nonlinear relationship with total PLN. An equation predicting free serum levels from salivary levels was successfully derived from the data. This study is the first to describe the relationship between salivary and (free) serum PLN using a population pharmacokinetic model. Salivary PLN was found to be a reliable predictor of free and total serum PLN in healthy volunteers. The results of this study encourage further exploration of the use of saliva as a noninvasive and feasible method for drug monitoring of PLN.


[PET-FDG in thyroid cancer with high thyroglobulin levels and negative 131-I scan. A case report].
The value of whole body PET-FDG in the evaluation of metastases has been demonstrated in a wide variety of tumors. In this report, we present the case of a patient with antecedent of papillary thyroid carcinoma, who was operated twelve years ago, and submitted to an ablative dose of residual thyroid tissue through 131I, being the levels of thyroglobulin normals. After twelve years of evolution, the patient refers bag pain and respiratory trouble, appearing in the CT image suspicious of metastases in right pulmonary base. The levels of thyroglobulin were shown increased, being the 131I scan negative. A whole body PET-FDG study was performed in order to exclude metastases of his malignant process, showed multiple high FDG uptake focus in brain, cerebellum, neck, chest, lymphatic nodes and bone, suggestive of dedifferentiated disease These findings were confirmed subsequently in the clinic evolution. Therefore, whole-body PET-FDG is a complementary diagnostic technique for study patients with CDT (Thyroid Differentiated Carcinoma) with 131I scan negative and rising thyroglobulin levels.


Mapping European research networks providing health data: results from the InfAct Joint Action on health information.
Research networks offer multidisciplinary expertise and promote information exchange between researchers across Europe. They are essential for the European Union's (EU) health information system as providers of health information and data. The aim of this mapping exercise was to identify and analyze EU research networks in terms of health data collection methods, quality assessment, availability and accessibility procedures. A web-based search was performed to identify EU research networks that are not part of international organizations (e.g., WHO-Europe, OECD) and are involved in collection of data for health monitoring or health system performance assessment. General characteristics of the research networks (e.g., data sources, representativeness), quality assessment procedures, availability and accessibility of health data were collected through an ad hoc extraction form. Fifty-seven research networks, representative at national, international or regional level, were identified. In these networks, data are mainly collected through administrative sources, health surveys and cohort studies. Over 70% of networks provide information on quality assessment of their data collection procedures. Most networks share macrodata through articles and reports, while microdata are available from ten networks. A request for data access is required by 14 networks, of which three apply a financial charge. Few networks share data with other research networks (8/49) or specify the metadata-reporting standards used for data description (9/49). Improving health information and availability of high quality data is a priority in Europe. Research networks could play a major role in tackling health data and information inequalities by enhancing quality, availability, and accessibility of health data and data sharing across European networks.


Room-temperature ferromagnetic CoSe2 nanoplates synthesized by chemical vapor deposition.
Among novel two-dimensional (2D) materials, transition metal dichalcogenides (TMDs) with 3d magnetic elements have been extensively researched owing to their unique magnetic, electric, and photoelectric properties. As an important member of TMDs, CoSe2 is an interesting material with controversial magnetic properties, hitherto there are few reports related to the magnetism of CoSe2 materials. Here, we report the synthesis of CoSe2 nanoplates on Al2O3 substrates by chemical vapor deposition (CVD). The CVD-grown CoSe2 nanoplates exhibit three typical morphologies (regular hexagonal, hexagonal, and pentagonal shapes) and their lateral sizes and thickness of CoSe2 nanoplates can reach up to hundreds of microns and several hundred nanometers, respectively. The electric-transport measurement shows a metallic feature of CoSe2 nanoplates. Furthermore, the slanted hysteresis loop and nonzero remnant magnetization of the CoSe2 nanoplates confirm the ferromagnetism in the temperature range of 5 to 400 K. This work provides a novel platform for designing CoSe2-based spintronic devices and studying related magnetic mechanisms.


Mathematical modeling of the infectious spread and outbreak dynamics of avian influenza with seasonality transmission for chicken farms.
A compartmental model with a time-varying contact rate, the seasonality effect, and its corresponding nonautonomous model are investigated. The model is developed based on the six compartments: susceptible, latent, infected, asymptomatic, treated, and recovered individuals. We determine the effective reproduction number for this nonautonomous system, and analytic discussion shows that at least one positive periodic solution exists for R0>1. The model is simulated using the RK-45 numerical method, and the parameter values for the model are taken from the available literature. From the numerical results, we observe that the degree of seasonality and vaccine efficacy significantly impact the amplitude of the epidemic curve. The latent-infected phase plane shows that periodic solutions exhibit a period-doubling bifurcation as the amplitude of seasonality increases. Finally, the model outcome was compared with the actual field data and found to be consistent.


Plasminogen improves lung lesions and hypoxemia in patients with COVID-19.
Lungs from patients with coronavirus disease 2019 (COVID-19) have shown typical signs of acute respiratory distress syndrome (ARDS), formation of hyaline membrane mainly composed of fibrin and 'ground-glass' opacity. Previously, we showed plasminogen itself is a key regulator in fibrin degradation, wound healing and infection. We aimed to investigate whether plasminogen can improve lung lesions and hypoxemia of COVID-19. Thirteen clinically moderate, severe or critical COVID-19 patients were treated with atomization inhalation of freeze-dried plasminogen. Levels of their lung lesions, oxygen saturation and heart rates were compared before and after treatment by computed tomography scanning images and patient monitor. After plasminogen inhalation, conditions of lung lesions in five clinically moderate patients have quickly improved, shown as the decreased range and density of 'ground glass' opacity. Improvements of oxygen saturation were observed in six clinically severe patients. In the two patients with critical conditions, the oxygen levels have significantly increased from 79-82% to 91% just about 1 h after the first inhalation. In 8 of 13 patients, the heart rates had slowed down. For the five clinically moderate patients, the difference is even statistically significant. Furthermore, a general relief of chest tightness was observed. Whereas it is reported that plasminogen is dramatically increased in adults with ARDS, this study suggests that additional plasminogen may be effective and efficient in treating lung lesions and hypoxemia during COVID-19 infections. Although further studies are needed, this study highlights a possible hope of efficiently combating this rapid epidemic emergency.


UK Nurses Delivering Physical Activity Advice: What Are the Challenges and Possible Solutions? A Qualitative Study.
There are a multitude of health benefits gained from regular physical activity (PA). Currently, PA advice implementation from NHS nurses is inadequate despite their ever-increasing role in lifestyle and preventive medicine. By assessing their knowledge of current PA guidance, this study proposed to investigate the issues with regular PA advice being given and expand upon nurses' proposed barriers and solutions. A qualitative approach using semi structured interviews was undertaken between March and August 2023 involving 13 NHS nurses. Thematic analysis was undertaken using Braun and Clarke's six step approach. Four themes and fifteen subthemes emerged as barriers and solutions in delivering PA advice. Intrinsic barriers included a lack of nurse knowledge on the topic and PA being seen as an afterthought. Extrinsic barriers included time pressures and a lack of staff engagement. Solutions involved increasing staff awareness of guidelines through teaching, policy, encouraging staff to be active and optimising PA advice delivery through a piecemeal approach and utilising online and visual resources. This study displayed an insight into nurses' thoughts on their consultations with patients regarding PA, and proposed several barriers and solutions. Further work is needed to improve nurses' PA knowledge and to assess the proposed strategies to improve its delivery.


Disruption of smooth muscle gap junctions attenuates myogenic vasoconstriction of mesenteric resistance arteries.
Communication between vascular smooth muscle (VSM) cells via low-resistance gap junctions may facilitate vascular function by synchronizing the contractile state of individual cells within the vessel wall. We hypothesized that inhibition of gap junctional communication would impair constrictor responses of mesenteric resistance arteries. Immunohistochemical experiments revealed positive staining for connexin 37 (Cx37) in both endothelium and smooth muscle of rat mesenteric arterioles, whereas connexin 43 (Cx43) immunoreactivity was not detected in the mesenteric vasculature. Administration of the gap junction inhibitory peptide Gap27, which targets Cx37 and Cx43, significantly diminished myogenic vasoconstriction (8.6 +/- 3.8% of passive diameter at 100 Torr) and changes in vessel wall intracellular [Ca2+] of mesenteric resistance arteries compared with vessels treated with either vehicle (physiological saline solution) (33.5 +/- 6.1%) or a control peptide (32.1 +/- 6.5%). Administration of 18alpha-glycyrrhetinic acid, structurally distinct from Gap27, also significantly attenuated myogenic constriction compared with its vehicle control (DMSO) (9.6 +/- 3.2% vs. 23.8 +/- 4.6%). In contrast, phenylephrine-induced vasoconstriction was not altered by gap junction blockers. Attenuated myogenic vasoconstriction resulting from inhibition of gap junctions persisted after disruption of the endothelium. In additional experiments, VSM cell membrane potential was recorded in mesenteric resistance arteries pressurized to 20 or 100 Torr. VSM membrane potential was depolarized at 100 Torr compared with 20 Torr. However, VSM cells in arteries treated with Gap27 were significantly hyperpolarized (-48.6 +/- 1.4 mV) at the higher pressure compared with vehicle (-41.4 +/- 1.5 mV) and Gap20-treated (-38.4 +/- 0.7 mV) vessels. Our findings suggest that inhibition of smooth muscle gap junctions attenuates pressure-induced VSM cell depolarization and myogenic vasoconstriction.


Impact of hard vs. soft wheat and monensin level on rumen acidosis in feedlot heifers.
Many feedlot finishing diets include wheat when the relative wheat prices are low. This study was conducted to examine the responses in ruminal pH and fermentation as well as site and extent of digestion from substituting soft or hard wheat for barley grain and to determine whether an elevated monensin concentration might decrease indicators of ruminal acidosis in feedlot heifers. Five ruminally cannulated beef heifers were used in a 5 × 5 Latin square with 2 × 2 + 1 factorial arrangement. Treatments included barley (10% barley silage, 86% barley, 4% supplement, with 28 mg monensin/kg DM) and diets where barley was substituted by either soft or hard wheat with either 28 or 44 mg monensin/kg diet DM. Intake of DM was not affected by grain source, whereas increasing monensin with wheat diets reduced (P < 0.02) DMI. Mean ruminal pH was lower (P < 0.04) and durations of pH < 5.8 and pH < 5.5 greater (P < 0.03) for wheat than for barley diets. However, ruminal pH was not affected by wheat type or monensin level. Total VFA concentrations were greater (P < 0.03) for wheat than barley diets with no effect of wheat type. The molar proportion of propionate was greater (P < 0.04), whereas butyrate (P < 0.01) and ratio of acetate to propionate tended to be lower (P < 0.09), with the high as compared to low level of monensin. Replacing barley with wheat in finishing diets did not affect the duodenal flow or the digestibility of OM, likely as a result of greater (P < 0.01) NDF digestion from barley offsetting the increased (P < 0.03) supply of digested starch from wheat. Feeding soft vs. hard wheat delivered a greater (P < 0.03) duodenal supply of OM and nonammonia N with no differences in total tract nutrient digestion. The increased monensin concentration decreased the flow of OM (P < 0.01), total N (P < 0.05), and microbial protein (P < 0.05) to the small intestine due to decreased DMI. These results indicated that hard and soft wheat exhibited digestive characteristics similar to barley, but ruminal pH measurements indicate that compared with barley, wheat increased the risk of ruminal acidosis. Although an increased level of monensin had limited impact on ruminal indicators of acidosis, an increase in propionate would be expected to improve efficiency of feed use by heifers fed wheat-based finishing diets.


Geometries and bond energies of the He-MX, Ne-MX, and Ar-MX (M = Cu, Ag, Au; X = F, Cl) complexes.
Calculations on the He...MX, Ne...MX, and Ar...MX (M = Cu, Ag, Au; X = F, Cl) complexes at the CCSD and CCSD(T) levels of theory have been carried out. The geometries of the Ar-MF complexes are in good agreement to those determined via microwave spectroscopy. The RG...MX (RG = He, Ne, and Ar) dissociation energies for these complexes have been evaluated by extrapolation to the complete basis set limit. The importance of the inclusion of diffuse functions to the determined dissociation energies of these complexes are discussed with comparison to recent work. For the He...CuF and He...AuF complexes, the dissociation energies have been found to be significant, at approximately 26 kJ mol(-1), while the bonding in the chlorine analogues is only approximately 15 kJ mol(-1). The bonding between the helium and the metal atoms in the He...CuF and He...AuF complexes has been investigated by using an atoms-in-molecules (AIM) analysis together with an evaluation of the dipole/induced-dipole and ion/induced-dipole interactions. This analysis has shown that the bonding in these complexes is slightly covalent in nature. For the He...AgF and Ne...MF (M = Cu, Ag, Au) complexes the dissociation energy is much smaller and the AIM analysis shows the bonding is more electrostatic in nature. Calculations have also been carried out on He...AgCl and Ne...MCl (M = Cu, Ag, Au) complexes for the first time in addition to the Ar...MX (M = Cu, Ag, Au; X = F, Cl) complexes. The RG...MCl complexes are found to be more weakly bound than the corresponding RG...MF complexes as a result of the difference in electronegativity of the halogen. For each complex, bond lengths, rotational constants, and harmonic vibrational frequencies have also been evaluated.


Early detection of cardiac involvement in Miyoshi myopathy: 2D strain echocardiography and late gadolinium enhancement cardiovascular magnetic resonance.
Miyoshi myopathy (MM) is an autosomal recessive distal myopathy characterized by early adult onset. Cardiomyopathy is a major clinical manifestation in other muscular dystrophies and an important prognostic factor. Although dysferlin is highly expressed in cardiac muscle, the effect of dysferlin deficiency in cardiac muscle has not been studied. We hypothesized that early myocardial dysfunction could be detected by 2D strain echocardiography and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Five consecutive MM patients (3 male) in whom we detected the DYSF gene mutation and age-matched healthy control subjects were included. None of the patients had history of cardiac disease or signs and symptoms of overt heart failure. Patients were studied using 2D strain echocardiography and CMR, with 2D strain being obtained using the Automated Function Imaging technique. All patients had preserved left ventricular systolic function. However, segmental Peak Systolic Longitudinal Strain (PSLS) was decreased in 3 patients. Global PSLS was significantly lower in patients with MM than in control subjects (p = 0.005). Basal anterior septum, basal inferior septum, mid anterior, and mid inferior septum PSLS were significantly lower in patients with MM than in control subjects (P < 0.0001, < 0.0001, 0.038 and 0.003, respectively). Four patients showed fibrosis by LGE. The reduced PSLS lesion detected by 2D strain tended to be in the same area as that which showed fibrosis by LGE. Patients with MM showed subclinical involvement of the heart. 2D strain and LGE are sensitive methods for detecting myocardial dysfunction prior to the development of cardiovascular symptoms. The prognostic significance of these findings warrants further longitudinal follow-up.


An immunofluorescence test for detection of serum antibody to rodent coronaviruses.
An indirect immunofluorescence test, using cultured cells infected with two strains of mouse hepatitis virus, was developed for detection of antibody to rodent coronaviruses. The immunofluorescence test detected serum antibody to mouse hepatitis virus and rat sialodacryoadenitis virus earlier than the neutralization test. In the case of mouse hepatitis virus, the results of the immunofluorescence test closely paralleled those obtained with a commercially available enzyme-linked immunosorbent assay.


Nature and autonomy: an organizational view of social and neurobiological aspects of self-regulation in behavior and development.
The concepts of self-regulation and autonomy are examined within an organizational framework. We begin by retracing the historical origins of the organizational viewpoint in early debates within the field of biology between vitalists and reductionists, from which the construct of self-regulation emerged. We then consider human autonomy as an evolved behavioral, developmental, and experiential phenomenon that operates at both neurobiological and psychological levels and requires very specific supports within higher order social organizations. We contrast autonomy or true self-regulation with controlling regulation (a nonautonomous form of intentional behavior) in phenomenological and functional terms, and we relate the forms of regulation to the developmental processes of intrinsic motivation and internalization. Subsequently, we describe how self-regulation versus control may be characterized by distinct neurobiological underpinnings, and we speculate about some of the adaptive advantages that may underlie the evolution of autonomy. Throughout, we argue that disturbances of autonomy, which have both biological and psychological etiologies, are central to many forms of psychopathology and social alienation.


A Computational Theory of Mindfulness Based Cognitive Therapy from the "Bayesian Brain" Perspective.
Mindfulness Based Cognitive Therapy (MBCT) was developed to combine methods from cognitive behavioral therapy and meditative techniques, with the specific goal of preventing relapse in recurrent depression. While supported by empirical evidence from multiple clinical trials, the cognitive mechanisms behind the effectiveness of MBCT are not well understood in computational (information processing) or biological terms. This article introduces a testable theory about the computational mechanisms behind MBCT that is grounded in "Bayesian brain" concepts of perception from cognitive neuroscience, such as predictive coding. These concepts regard the brain as embodying a model of its environment (including the external world and the body) which predicts future sensory inputs and is updated by prediction errors, depending on how precise these error signals are. This article offers a concrete proposal how core concepts of MBCT-(i) the being mode (accepting whatever sensations arise, without judging or changing them), (ii) decentering (experiencing thoughts and percepts simply as events in the mind that arise and pass), and (iii) cognitive reactivity (changes in mood reactivate negative beliefs)-could be understood in terms of perceptual and metacognitive processes that draw on specific computational mechanisms of the "Bayesian brain." Importantly, the proposed theory can be tested experimentally, using a combination of behavioral paradigms, computational modelling, and neuroimaging. The novel theoretical perspective on MBCT described in this paper may offer opportunities for finessing the conceptual and practical aspects of MBCT.


Herd factors influencing free fatty acid concentrations in bulk tank milk.
Free fatty acid (FFA) concentrations can be elevated in raw milk due to improper handling and management at the dairy farm, and high concentrations of FFA can lead to off flavors in milk. This study aimed to describe how the herd production system, milking system, feeding and technological factors impact on FFA concentrations in bulk tank milk. FFA concentrations in bulk milk samples from 259 organic and 3326 conventional herds were analyzed by FT-IR during one year. The FFA content was significantly lower in bulk milk from organic than conventional herds. This was most evident during the summer half-year when the organic cows graze pasture. Bulk milk from automatic milking systems (AMS) and tie-stalls contained greater concentrations of FFA than any other milking parlor systems. In AMS, high milking frequency was found to be the most significant contributor to elevated FFA content in milk. Moreover, a strong interaction was found between milking interval and production system (organic vs. conventional). The technical factors, pre-cooling, onset time for cooling after milk inlet, contact between milk and agitation also impacted on the FFA concentration, whereas other technical factors including centrifugal pump type, length and height of pumping line and type of AMS manufacturer were found to be without significant effect on FFA. Feeding variables, based on feeding plans and evaluation, only explained a small part of the variation in bulk milk FFA. Overall, this study demonstrated that AMS compared to other milking system contributes significantly to increased FFA concentration in bulk tank milk, and within AMS high milking frequency contributes to increased FFA concentration.


Immunosuppressive effects of an HLA class I-derived peptide in a rat cardiac allograft model.
B7.75-84, a 10-amino-acid peptide derived from the HLA-B7 molecule, prolongs rat heterotopic cardiac allograft survival time (GST) when used with cyclosporine in the Lewis-to-ACI strain combination. We evaluated the ability of B7.75-84 to prolong GST in other strain combinations without cyclosporine and studied the effect of B7.75-84 on the immune response in the Wistar-Furth (WF)-to-ACI strain combination. GST was markedly prolonged in most low-responder (ACI) recipients but only slightly prolonged in the high-responder (Lewis) recipient. Cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) limiting dilution assays (LDA) were performed 10 days after cardiac allografts from WF donors were placed in ACI recipients treated with B7.75-84. HTL-LDA assays at 10 days posttransplant showed a slight decrease in HTL precursor frequency and a decrease in their IL-2 production in B7.75-84 treated recipients with prolonged GST in response to donor antigen as well as third-party (Lewis) antigen. CTL-LDA assays at day 10 showed no difference in CTL precursor frequency among treated recipients but did show a significant decrease in CTL killing activity against donor cells in recipients with prolonged GST. No significant difference in CTL killing activity was seen against third- party cells. Antibody analysis was performed at day 8 in treated recipients. Serum from B7.75-84-treated recipients with prolonged graft survival generally showed no detectable IgG antibody response against donor MHC class I antigen. All B7.75-84 treated recipients showed a strong IgM response against donor antigen regardless of allograft outcome. Our results suggest that the immunosuppressive effect of B7.75-84 in rats is greater using a low-responder RT1 haplotype. Furthermore, B7.75-84 induces a nonspecific decrease in HTL function while producing a donor-specific decrease in CTL function and a diminished antidonor MHC class I IgG response.


Induction of Escherichia coli O157:H7 into the viable but non-culturable state by chloraminated water and river water, and subsequent resuscitation.
Induction of culturable Escherichia coli O157:H7 cells into a viable but non-culturable (VBNC) state by chloraminated tap water was carefully investigated; as many as 90% of initial cells entered into a VBNC state within 15 min, compared with 14% in river water within 14 weeks. To understand what specific stresses may induce E. coli O157:H7 into a VBNC state, chloraminated tap water, autoclaved river water, and media with known ingredients (PBS buffer and deionized water) at 4°C or 25°C were used to examine induction efficiency. Chloramination alone, or the combination of starvation with either low temperature or osmotic pressure, induced E. coli O157:H7 into a VBNC state, while starvation alone did not induce the bacteria into a VBNC state within 1.5 years. The mRNA of the rfbE and fliC genes was detected in the 10-month-old VBNC cells induced by river water, confirming the viability of E. coli O157:H7 VBNC cells. The VBNC cells induced by chloraminated water and the 10-month-old VBNC cells induced by river water were first resuscitated using autoinducers produced by E. coli O157:H7 itself in a serum-based medium; the VBNC cells of bovine isolates recovered more efficiently compared with those of clinical isolates. These results demonstrate a potential health risk of VBNC E. coli O157:H7 in environmental water and the utility of monitoring viable E. coli O157:H7 including VBNC cells based on the mRNA of the rfbE and fliC genes.


Clinical and roentgenographic aspects of pseudogout: a study of 50 cases and a review.
Pseudogout, defined as recurrent acute arthritis due to intrasynovial deposition of calcium pyrophosphate dihydrate crystals, is a relatively common arthritic disorder of the elderly. The clinical and roentgenographic aspects of 50 cases of pseudogout in hospitalized patients are reviewed in this paper. Oligoarticular and polyarticular episodes were observed in half of these patients. Antecedent problems included infection, trauma, surgery and vascular events. Consistent with previous reports, most patients had roentgenographic evidence of chondrocalcinosis. A third had asymptomatic capsular or periarticular calcific deposits or both, and a third had pyrophosphate arthropathy, a progressive, destructive, accelerated form of osteoarthritis. An attack of pseudogout may offer a clue to the presence of an unsuspected metabolic disease, such as primary hyperparathyroidism or idiopathic hemochromatosis.


Combined action of nisin and carvacrol on Bacillus cereus and Listeria monocytogenes.
Nisin, a small antimicrobial protein, was tested for its bactericidal action against Listeria monocytogenes and Bacillus cereus and a typical biphasic reduction of the viable count was observed. The reduction was most fast during the first 10 min of exposure, while the viable count remained stable in the last part of the exposure period. Bacillus cereus was more sensitive towards nisin than L. monocytogenes and the inhibitory effect of nisin was stronger towards cells cultivated and exposed at 8 degrees C than towards cells cultivated and exposed at 20 degrees C. Combining nisin with sublethal doses of carvacrol resulted in an increased reduction in the viable count of both organisms, indicating synergy between nisin and carvacrol. Addition of lysozyme as a third preservative factor increased the synergistic effect between nisin and carvone, especially in the last part of the exposure period.


Graphene hydrogels deposited in nickel foams for high-rate electrochemical capacitors.
Graphene hydrogel/nickel foam composite electrodes for high-rate electrochemical capacitors are produced by reduction of an aqueous dispersion of graphene oxide in a nickel foam (upper half of figure). The micropores of the hydrogel are exposed to the electrolyte so that ions can enter and form electrochemical double-layers. The nickel framework shortens the distances of charge transfer. Therefore, the electrochemical capacitor exhibits highrate performance (see plots).


Large H2O solubility in dense silica and its implications for the interiors of water-rich planets.
Sub-Neptunes are common among the discovered exoplanets. However, lack of knowledge on the state of matter in [Formula: see text]O-rich setting at high pressures and temperatures ([Formula: see text]) places important limitations on our understanding of this planet type. We have conducted experiments for reactions between [Formula: see text] and [Formula: see text]O as archetypal materials for rock and ice, respectively, at high [Formula: see text] We found anomalously expanded volumes of dense silica (up to 4%) recovered from hydrothermal synthesis above ∼24 GPa where the [Formula: see text]-type (Ct) structure appears at lower pressures than in the anhydrous system. Infrared spectroscopy identified strong OH modes from the dense silica samples. Both previous experiments and our density functional theory calculations support up to 0.48 hydrogen atoms per formula unit of ([Formula: see text])[Formula: see text] At pressures above 60 GPa, [Formula: see text]O further changes the structural behavior of silica, stabilizing a niccolite-type structure, which is unquenchable. From unit-cell volume and phase equilibrium considerations, we infer that the niccolite-type phase may contain H with an amount at least comparable with or higher than that of the Ct phase. Our results suggest that the phases containing both hydrogen and lithophile elements could be the dominant materials in the interiors of water-rich planets. Even for fully layered cases, the large mutual solubility could make the boundary between rock and ice layers fuzzy. Therefore, the physical properties of the new phases that we report here would be important for understanding dynamics, geochemical cycle, and dynamo generation in water-rich planets.


Polarization dependence of non-linear gain compression factor in semiconductor optical amplifier.
We investigate the power and the polarization dependence of the intraband dynamics in a bulk semiconductor optical amplifier using both a 2.5-ps pump-probe experimental set-up in contra-propagation and a theoretical model. Our model is based on the rate equations and takes into account the polarization dependence of the gain. By comparing experimental and computational results we are able to highlight the dependences of the intraband dynamics and to extract the non-linear gain compression factor as a function of both pulse energy and polarization of the injected pulses.


Preliminary X-ray characterization and phasing of a type II cohesin domain from the cellulosome of Acetivibrio cellulolyticus.
The N-terminal type II cohesin from the cellulosomal ScaB subunit of Acetivibrio cellulolyticus was crystallized in two different crystal systems: orthorhombic (space group P2(1)2(1)2(1)), with unit-cell parameters a = 37.455, b = 55.780, c = 87.912 A, and trigonal (space group P3(1)21), with unit-cell parameters a = 55.088, b = 55.088, c = 112.553 A. The two crystals diffracted to 1.2 and 1.9 A, respectively. A selenomethionine derivative was also crystallized and exhibited trigonal symmetry (space group P3(1)21), with unit-cell parameters a = 55.281, b = 55.281, c = 112.449 A and a diffraction limit of 1.97 A. Initial phasing of the trigonal crystals was successfully performed by the SIRAS method using Cu Kalpha radiation with the selenomethionine derivative as a heavy-atom derivative. The structure of the orthorhombic crystal form was solved by molecular replacement using the coordinates of the trigonal form.


The handwriting performance of children with NF1.
The objective of this study was to analyze the process and product of handwriting among children with Neurofibromatosis Type 1 (NF1) in comparison to those of Typically Developing (TD) children. Children with NF1 are at risk for some cognitive deficits, a wide range of deficits in perceptual skills and, motor and visual-motor integration skills which may interfere with handwriting competency, which is an essential ingredient for success at school. Participants were 30 NF1 children and 30 age and gender matched TD children, between the ages 8 and 16.08. The handwriting performance of children with NF1 was evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI), for copying text and free style writing tasks, using: (1) Computerized Penmanship Evaluation Tool (ComPET) to assess mechanical aspects of the writing process. (2) The Hebrew Handwriting Evaluation (HHE) to examine product legibility. (3) The Six-Trait Writing Model to judge the quality of the written product. Significant differences between the NF1 children and the control group were found in the process and product measures. Significant correlations were found between the VMI, the ComPET, the HHE and the Six-Trait Writing Model variables for both groups. We suggest a possible relationship between executive dysfunction and poor performance in handwriting.


Is Kalamchi and MacEwen Group I avascular necrosis of the femoral head harmless in developmental dysplasia of the hip?
The aim of this clinical study was to evaluate the influence of Kalamchi and MacEwen group I avascular necrosis of the femoral head (AVN) on the radiographic and clinical outcomes in developmental dysplasia of the hip (DDH). Preoperative and follow-up (at 2-3, 4-6, 7-9 and 10-15 years of age) Sharp's acetabular angles (AA) and the final Wiberg's center-edge angles (CEA) and proximal femoral center-trochanter distances (CTD) of 13 hips with group I AVN (AVN group) were compared with measurements of 22 hips without AVN (control group). All hips were initially treated by the same soft tissue surgical procedure (posteromedial limited surgery) under the age of 18 months and were completely followed up to at least 10 years of age. Radiographic diagnosis of group I AVN was made between 6 and 12 months postoperatively. The period for complete radiographic recovery of group I ischemic changes was between 2 to 4.5 years. Preoperative mean AA values of both groups were similar. However, the mean AA was found to be worse in the AVN group than in the control group during follow-up. Control group hips had a better mean CEA and higher number of hips having normal CTD than the AVN group, at latest follow-up. In conclusion, when compared with uncomplicated hips, group I ischemic changes retard acetabular development and have quantitative unfavorable effects on lateral femoral head coverage and proximal femoral anatomy in DDH. In addition, the healing process in group I AVN patients is extended.


Evaluation of marginal sealing ability of self-adhesive flowable composite resin in Class II composite restoration: An in vitro study.
The aim of this study is to evaluate the marginal sealing ability of self-adhesive flowable composite resin when used as a liner in Class II composite restoration with and without aging. A total of 120 standardized Class II tooth preparations with gingival margins 1 mm coronal and apical to cementenamel junction (CEJ) were prepared on 60 extracted permanent mandibular molars and were randomly divided into eight equal Groups: Group 1: cavities coronal to CEJ and restored with Dyad flow liner + Herculite ultra, Group 2: same as Group 1 but cavities margins apical to CEJ, Group 5: cavities coronal to CEJ and restored with only Herculite ultra, and Group 6: same as Group 5 but cavities apical to CEJ. Groups 3,4,7,8 were similar to Groups 1,2,5,6, respectively, but were aged for 6 months. After thermocycling, microleakage testing was done using 0.5% basic fuchsin dye. At cervical level, Group 5 exhibited statistically lower (P = 0.006) microleakage than Group 6, and Group 1 showed lesser microleakage than Group 5 (P = 0.162). Group 2 exhibited significantly less microleakage than Group 6 (P = 0.002). Increased microleakage was observed in aging Groups; however, the difference with nonaging Groups was not statistically significant (P > 0.005). Margins of the cavity in cementum can be better sealed by placing self-adhesive liner and is not affected by aging.


Tazarotene induces apoptosis in human basal cell carcinoma via activation of caspase-8/t-Bid and the reactive oxygen species-dependent mitochondrial pathway.
Previous studies suggest that tazarotene, a new member of the acetylenic class of RARβ/γ selective retinoids which is approved to treat a variety of skin diseases, exhibits an anti-proliferative effect in human basal cell carcinoma (BCC) by triggering caspase-dependent apoptosis. However, the detailed molecular mechanisms underlying the anti-tumor activity of tazarotene are poorly understood. This study aims at investigating the molecular mechanisms of tazarotene-induced apoptosis in human BCC cells. Our results are the first to demonstrate that tazarotene induces mitochondria-dependent cleavage of caspase-9 and -3 and PARP in BCC cells by producing reactive oxygen species (ROS) and activating caspase-8 through both ROS and death receptor signaling. These events are accompanied by a decrease in BCL-2 and BCL-xl anti-apoptotic proteins as well as by survivin and XIAP, two IAP family members. Furthermore, our results presented for the first time that tazarotene triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the caspase-8-truncated Bid signaling pathway. Collectively, these data provide insights into the molecular mechanisms underlying tazarotene-induced apoptosis in human BCC cells, suggesting that this compound is a potential anti-skin cancer drug.


Use of Simulation Based Training to Enhance Cardiac Auscultation Proficiency.
This article was migrated. The article was marked as recommended. Cardiopulmonary auscultation is an important skill for medical professionals with deficiencies being well documented with broad implications on healthcare. Providing ideal bedside auscultatory teaching presents many difficulties. Simulation has been used as a means to improve cardiac auscultatory training and circumvent some of these limitations. We studied the use of Harvey © simulation in teaching cardiac murmurs and whether there was improvement in short term knowledge, as well as testing long term knowledge retention, as measured through a standardized test. From 2014-2019, 124 medical students in their 2 nd and 3 rd year of school (during the clinical portion of medical school curriculum) rotating through an Internal Medicine rotation completed a 2 hour training course on cardiac auscultation using Harvey © to identify six common cardiac murmurs. The session contained a pretest, didactic session, and posttest. 124 students participated in the auscultatory training session. Of them, 42 (34%) underwent the session a second time at an average of 1.29 months from their first session. There was statistically significant improvement between tests. Notably, the most often missed murmurs were mitral stenosis and benign (innocent) flow murmur. As shown in our study, simulation based cardiac auscultatory education is feasible and likely beneficial in medical education as it can be delivered to a large group of trainees and overcomes the challenges of bedside teaching.


N-(4-Methoxybenzylidene)-N'-(2-pyridyl)hydrazine.
Molecules of the title compound (alternative name p-methoxybenzaldehyde 2-pyridylhydrazone), C(13)H(13)N(3)O, adopt an E configuration about the azomethine C=N double bond. Molecules are almost planar, the dihedral angle between the pyridine and methoxyphenyl rings being only 6.19 (12) degrees. Pairwise N-H.N hydrogen bonds [R(2)(2)(8) in graph-set notation] link centrosymmetrically related molecules into discrete pairs.


Associations Between Macrophage Colony-Stimulating Factor and Monocyte Chemotactic Protein 1 in Plasma and First-Time Coronary Events: A Nested Case-Control Study.
Myeloid cells play a central role in atherosclerosis. We investigated the associations between the plasma levels of growth factors and chemokines that regulate myeloid cell homeostasis and function and the risk of first-time acute coronary events in middle-aged persons. We measured baseline plasma levels of macrophage colony-stimulating factor; monocyte chemotactic protein 1; C-C motif chemokine ligands 3, 4, and 20; C-X-C motif chemokine ligands 1, 6, and 16; and C-X3-C motif chemokine ligand 1 in 292 participants who had a coronary event during follow-up and 366 controls matched for age, sex, and time of inclusion who remained event free. Study participants were recruited from the Malmö Diet and Cancer Study population cohort and had no previous history of coronary artery disease. We found a strong independent negative association between macrophage colony-stimulating factor and incident coronary events in a forward stepwise Cox proportional hazards model including all biomarkers alongside the classic Framingham risk factors (age, sex, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure), diabetes mellitus, and medication. Conversely, monocyte chemotactic protein 1 had the strongest independent positive association with the outcome. The addition of macrophage colony-stimulating factor and monocyte chemotactic protein 1 significantly improved the predictive ability of a model including traditional risk factors alone (C statistic 0.81 [95% CI 0.78-0.84] versus 0.67 [95% CI 0.63-0.71]; net reclassification index 0.52 [0.42-0.62]; P<0.001). The combined model led to a 54% net downclassification of participants who did not have a coronary event during follow-up and was particularly effective in the intermediate-risk group. High levels of macrophage colony-stimulating factor and low levels of monocyte chemotactic protein 1 in plasma characterize middle-aged persons at low risk to develop clinically manifested coronary artery disease.


Exploration of internet use: profile and preferences of transition-aged adolescents with spina bifida.
A pilot study was conducted to learn about the Internet usage of adolescents with spina bifida. The purpose of this study is to investigate the feasibility for developing an online health care transition intervention. Use of the Internet was examined in a convenience sample of 50 adolescents with spina bifida in the Spina Bifida Clinic at Children's Hospital, Los Angeles. Participants were between 14 to 18 years of age. Data are reported as percentages and frequency distributions. Ninety-two percent of adolescents with spina bifida used the Internet, and of those, 87% used it at home, with an average rate of 2.4 hours per dat. The majority of adolescents used the Internet for homework purposes (83%). Leisure activities, such as listening to music (76%), playing games (70%), meeting new friends/social networking (63%), and watching YouTube videos (61%), were also reported. Most participants have never used the Internet to obtain spina bifida information (67%) or to meet other adolescents with spina bifida (85%). Internet application as an outreach tool for education and transition planning should be further explored in future studies. Given the widespread reported access to the Internet among our participants, results suggest that a Web-based outreach tool for education and health care transition planning have the potential to be accessible and beneficial to adolescents with spina bifida with the facilitated support of health care professionals.


Predicting the decrease of conjugated bilirubin with extracorporeal albumin dialysis MARS using the predialysis molar ratio of conjugated bilirubin to albumin.
Extracorporeal albumin dialysis with the molecular adsorbent recirculating system (MARS) machine is a new supportive intervention for patients with liver failure. It removes bilirubin and other albumin-bound toxins from the patient and has been shown by preliminary studies of liver failure patients to be beneficial. Our study examines the ability of predialysis molar ratio of bilirubin to albumin to predict the decrease of bilirubin by MARS. We had 5 patients and results from 29 treatments. The results showed a significant correlation between the predialysis molar ratio of bilirubin (total and conjugated) to albumin to the reduction in bilirubin (total and conjugated): R(2) = 0.27 and 0.62 respectively, P <.005 for both. There was no significant correlation with the predialysis molar ratio of unconjugated bilirubin to albumin to the reduction in unconjugated bilirubin. The ratio of change in total bilirubin (micromol/L) to the predialysis molar ratio of total bilirubin to albumin and the ratio of change in conjugated bilirubin (micromol/L) to the predialysis molar ratio of conjugated bilirubin to albumin were 6.2 (+/- 4.2) and 10.8 (+/- 4.3), respectively (mean (+/- SD)). The results enable us to predict the likely reduction in bilirubin (especially conjugated) after each MARS treatment and also suggest to us that albumin infusion before MARS treatment may reduce the efficacy of bilirubin removal. Whether this ratio applies to other albumin-bound toxins remains open for investigation.


Zoonotic potential and molecular epidemiology of Giardia species and giardiasis.
Molecular diagnostic tools have been used recently in assessing the taxonomy, zoonotic potential, and transmission of Giardia species and giardiasis in humans and animals. The results of these studies have firmly established giardiasis as a zoonotic disease, although host adaptation at the genotype and subtype levels has reduced the likelihood of zoonotic transmission. These studies have also identified variations in the distribution of Giardia duodenalis genotypes among geographic areas and between domestic and wild ruminants and differences in clinical manifestations and outbreak potentials of assemblages A and B. Nevertheless, our efforts in characterizing the molecular epidemiology of giardiasis and the roles of various animals in the transmission of human giardiasis are compromised by the lack of case-control and longitudinal cohort studies and the sampling and testing of humans and animals living in the same community, the frequent occurrence of infections with mixed genotypes and subtypes, and the apparent heterozygosity at some genetic loci for some G. duodenalis genotypes. With the increased usage of multilocus genotyping tools, the development of next-generation subtyping tools, the integration of molecular analysis in epidemiological studies, and an improved understanding of the population genetics of G. duodenalis in humans and animals, we should soon have a better appreciation of the molecular epidemiology of giardiasis, the disease burden of zoonotic transmission, the taxonomy status and virulences of various G. duodenalis genotypes, and the ecology of environmental contamination.


Enhanced tonic GABAA inhibition in typical absence epilepsy.
The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired gamma-aminobutyric acid (GABA)-ergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABA(A) receptor-dependent 'tonic' inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT-1 in the genetic models tested, and GAT-1 is crucial in governing seizure genesis. Extrasynaptic GABA(A) receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABA(A) receptors is sufficient to elicit both electrographic and behavioral correlates of seizures in normal rats. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic importance and highlight potential therapeutic targets for the treatment of absence epilepsy.


Dinitrochlorobenzene-induced colitis in the guinea-pig: studies of colonic lamina propria lymphocytes.
Dinitrochlorobenzene-induced colitis in guinea-pigs may be immunologically mediated: animals must be presensitised to dinitrochlorobenzene to develop colitis, sensitivity can be passively transferred by lymphocytes and the injury can be mitigated by immunosuppression. In this study, we examined lamina propria lymphocytes isolated from colons of animals with dinitrochlorobenzene-induced colitis, and appropriate controls. Lamina propria lymphocytes from colitis animals have a greater percentage of rabbit erythrocyte-rosetting cells (T cells) (20.1 +/- 3.0 vs 2.3 +/- 0.8, p less than .01) and a greater capacity to mediate mitogen-induced cellular cytotoxicity with phytohaemagglutinin than lamina propria lymphocytes from normal colon (% specific cytoxicity = 29.4 +/- 8.7 vs 5.0 +/- 4.5, P less than .005). There was no difference in the percentage of rosetting cells or cytotoxicity index of spleen or mesenteric lymph node lymphocytes between the colitis animals and controls. These data suggest that there are changes in the distribution and functional characteristics of lamina propria lymphocytes which correlate with mucosal cell injury in the dinitrochlorobenzene-colitis model.


Tuberculosis drug discovery and emerging targets.
Current tuberculosis (TB) therapies take too long and the regimens are complex and subject to adverse effects and drug-drug interactions with concomitant medications. The emergence of drug-resistant TB strains exacerbates the situation. Drug discovery for TB has resurged in recent years, generating compounds (hits) with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review proposes strategies for generating improved hits and leads that could help achieve this goal.


Relationship between serum and free interstitial concentrations of cefodizime and cefpirome in muscle and subcutaneous adipose tissue of healthy volunteers measured by microdialysis.
Microdialysis is a suitable method to monitor unbound concentrations of antimicrobial drugs in the interstitial tissue space which is the site of many infections. The aim of this investigation was to examine whether free tissue levels of cefodizime (81% plasma protein binding) and cefpirome (10% plasma protein binding) in muscle and subcutaneous adipose tissue of healthy volunteers obtained by microdialysis are consistent with the extent of their respective plasma protein binding. Healthy volunteers were given cefodizine and cefpirome at a single intravenous 2-g dose in a randomized crossover design. Microdialysis probes were inserted into a medial vastus muscle and into the periumbilical subcutaneous layer. After calibration of the probe, samples of serum and microdialysis fluid were obtained and drug concentrations were measured using a microagar diffusion-bioassay. There was a reasonable agreement between plasma protein binding data and the tissue penetration of both cephalosporins (AUC0-infinity tissue, free/AUC0-infinity serum, total-ratios) into the interstitial fluid of the muscle tissue, but not for the subcutaneous tissue layer. Furthermore, the serum and tissue concentrations of both drugs were fitted to an open two-compartment body model. The measured free-tissue concentrations were compared with calculated unbound concentrations in the peripheral compartment. Good agreement was observed for the free muscle concentrations, but unbound concentrations in the subcutaneous tissue was somewhat higher (cefpirome) or lower (cefodizime) than predicted. This may be due to the different lipophilicities of the two compounds.


MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents.
MMSET/WHSC1 is a histone methyltransferase (HMT) overexpressed in t(4;14)+ multiple myeloma (MM) patients, believed to be the driving factor in the pathogenesis of this MM subtype. MMSET overexpression in MM leads to an increase in histone 3 lysine 36 dimethylation (H3K36me2), and a decrease in histone 3 lysine 27 trimethylation (H3K27me3), as well as changes in proliferation, gene expression and chromatin accessibility. Prior work linked methylation of histones to the ability of cells to undergo DNA damage repair. In addition, t(4;14)+ patients frequently relapse after regimens that include DNA damage-inducing agents, suggesting that MMSET may play a role in DNA damage repair and response. In U2OS cells, we found that MMSET is required for efficient non-homologous end joining as well as homologous recombination. Loss of MMSET led to loss of expression of several DNA repair proteins, as well as decreased recruitment of DNA repair proteins to sites of DNA double-strand breaks (DSBs). By using genetically matched MM cell lines that had either high (pathological) or low (physiological) expression of MMSET, we found that MMSET-high cells had increased damage at baseline. Upon addition of a DNA-damaging agent, MMSET-high cells repaired DNA damage at an enhanced rate and continued to proliferate, whereas MMSET-low cells accumulated DNA damage and entered cell cycle arrest. In a murine xenograft model using t(4;14)+ KMS11 MM cells harboring an inducible MMSET shRNA, depletion of MMSET enhanced the efficacy of chemotherapy, inhibiting tumor growth and extending survival. These findings help explain the poorer prognosis of t(4;14) MM and further validate MMSET as a potential therapeutic target in MM and other cancers.


Origins of number sense. Large-number discrimination in human infants.
Four experiments investigated infants' sensitivity to large, approximate numerosities in auditory sequences. Prior studies provided evidence that 6-month-old infants discriminate large numerosities that differ by a ratio of 2.0, but not 1.5, when presented with arrays of visual forms in which many continuous variables are controlled. The present studies used a head-turn preference procedure to test for infants' numerosity discrimination with auditory sequences designed to control for element duration, sequence duration, interelement interval, and amount of acoustic energy. Six-month-old infants discriminated 16 from 8 sounds but failed to discriminate 12 from 8 sounds, providing evidence that the same 2.0 ratio limits numerosity discrimination in auditory-temporal sequences and visual-spatial arrays. Nine-month-old infants, in contrast, successfully discriminated 12 from 8 sounds, but not 10 from 8 sounds, providing evidence that numerosity discrimination increases in precision over development, prior to the emergence of language or symbolic counting.


Construction and functional study of pGN, a mammary gland-specific expression plasmid.
The aim of this study was to construct a mammary gland-specific expression vector, pGN, and to validate its function in expressing growth hormone (GH) both in vitro and in vivo. First, the GH gene was amplified and inserted downstream of the b-casein 5'-arm. Next, the neo gene was cloned downstream of the b-casein 3'-arm as a selection marker. To analyze the bioactivity of the pGN plasmid, we expressed pGN in a Bcap-37 cell line and in the goat mammary gland. Quantitative PCR analysis revealed that the expression of GH mRNA in the pGN-transfected group was higher than that of the control group in Bcap-37 cells. Results of a radioimmunoassay and an enzyme-linked immunosorbent assay demonstrated that the pGN-transfected group expressed much more GH protein than the non-transfected group (P < 0.05). Upon injection of the pGN plasmid into the goat mammary gland, GH mRNA and growth hormone receptor mRNA expressions increased 2-fold. In vivo analyses revealed that GH protein expression was higher in the injected group than in the control group. Together, these results strongly demonstrated that the pGN plasmid was constructed correctly and exhibited favorable bioactivity in efficiently expressing GH both in vitro and in vivo.


Algorithms, clinical practice guidelines, and standardized clinical assessment and management plans: evidence-based patient management standards in evolution.
In this issue, Farias and colleagues describe how to develop a clinical care pathway by using a structured, continuous learning process embedded within the day-to-day delivery of care. Their method is called Standardized Clinical Assessment and Management Plans (SCAMPs). A care pathway, such as a SCAMP, includes multiple decision points and related recommendations. The SCAMP process can test the validity of each decision point if clinicians document patient data and record their reasoning when they deviate from the recommended action at a decision point. The unique feature of SCAMPs is that they encourage dissent, unlike clinical practice guidelines (CPGs), algorithms, and bundled electronic health record protocols, which are designed to be followed. If a clinician deviates from the recommended action at a decision point, an explanation is required. This feedback, which should explain why a patient does not precisely "fit" the logic of the care pathway, may lead the SCAMP developers to modify the decision point. The authors of this Commentary argue that SCAMPs and CPGs, two approaches to developing clinical standards of care, are fundamentally equivalent. The key link between them is the recently described process of deconstructing a CPG into the many steps that are necessary to consistently apply it to clinical practice. The SCAMP process puts these steps to the test of daily practice. The Commentary ends with a list of foundational principles for developing standards of clinical care. These principles should apply to care pathways, algorithms, practice guidelines, or SCAMPs.


Explainable AI approach with original vegetation data classifies spatio-temporal nitrogen in flows from ungauged catchments to the Great Barrier Reef.
Transfer of processed data and parameters to ungauged catchments from the most similar gauged counterpart is a common technique in water quality modelling. But catchment similarities for Dissolved Inorganic Nitrogen (DIN) are ill posed, which affects the predictive capability of models reliant on such methods for simulating DIN. Spatial data proxies to classify catchments for most similar DIN responses are a demonstrated solution, yet their applicability to ungauged catchments is unexplored. We adopted a neural network pattern recognition model (ANN-PR) and explainable artificial intelligence approach (SHAP-XAI) to match all ungauged catchments that flow to the Great Barrier Reef to gauged ones based on proxy spatial data. Catchment match suitability was verified using a neural network water quality (ANN-WQ) simulator trained on gauged catchment datasets, tested by simulating DIN for matched catchments in unsupervised learning scenarios. We show that discriminating training data to DIN regime benefits ANN-WQ simulation performance in unsupervised scenarios ( p< 0.05). This phenomenon demonstrates that proxy spatial data is a useful tool to classify catchments with similar DIN regimes. Catchments lacking similarity with gauged ones are identified as priority monitoring areas to gain observed data for all DIN regimes in catchments that flow to the Great Barrier Reef, Australia.


Light propagation in dry and wet softwood.
Light propagation in dry and wet softwood (silver fir) was investigated experimentally and theoretically. The spatially and time resolved reflectance from softwood was measured. Light propagation was modeled with Monte Carlo simulations considering the microstructure of softwood. By comparing the spatially resolved reflectance we found that all characteristics of the experimentally obtained iso-intensity contour lines were recovered by the theory. In addition, the reduced scattering and the absorption coefficients were determined in the time domain by fitting a solution of the diffusion equation to Monte Carlo simulations and to measurements. Good qualitative agreement was obtained between the experimentally and theoretically derived optical properties.


Mapping the ecosystem service delivery chain: Capacity, flow, and demand pertaining to aesthetic experiences in mountain landscapes.
Accounting for the spatial connectivity between the provision of ecosystem services (ES) and their beneficiaries (supply-benefit chain) is fundamental to understanding ecosystem functioning and its management. However, the interrelationships of the specific chain links within ecosystems and the actual benefits that flow from natural landscapes to surrounding land have rarely been analyzed. We present a spatially explicit model for the analysis of one cultural ecosystem service (aesthetic experience), which integrates the complete ecosystem service delivery chain for Puez-Geisler Nature Park (Italy): (1) The potential service stock (ES capacity) relies on an expert-based land use ranking matrix, (2) the actual supply (ES flow) is based on visibility properties of observation points along recreational routes, (3) the beneficiaries of the service (ES demand) are derived from socioeconomic data as a measure of the visitation rate to the recreation location, and (4) the supply-demand relationship (ES budget) addresses the spatially explicit oversupply and undersupply of ES. The results indicate that potential ES stocks are substantially higher in core and buffer zones of protected areas than in surrounding land owing to the specific landscape composition. ES flow maps reveal service delivery to 80% of the total area studied, with the highest actual service supply to locations with long and open vistas. ES beneficiary analyses show the highest demand for aesthetic experiences in all-season tourist destinations like Val Badia and Val Gardena, where both recreational amenity and overnight stays are equally high. ES budget maps identify ES hot and cold spots in terms of ES delivery, and they highlight ES undersupply in nature protection buffer zones although they are characterized by highest ES capacity. We show how decision/policy makers can use the presented methodology to plan landscape protection measures and develop specific regulation strategies for visitors based on the ES delivery chain concept.


Cultured human vascular smooth muscle cells with functional thromboxane A2 receptors: measurement of U46619-induced 45calcium efflux.
Thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) are potent vasoconstrictors whose contractile effects are mediated by increases in cellular calcium. Stable analogues of these compounds have shown calcium ionophore activity at high concentrations. To determine if effects of TXA2/PGH2 analogues on 45Ca2+ fluxes are receptor mediated, the effects of the stable TXA2/PGH2 mimetic U46619 and the TXA2/PGH2 receptor antagonist I-PTA-OH on 45Ca/+ fluxes in cultured human vascular smooth muscle cells were studied. The smooth muscle cells were cultured from human saphenous vein explants, and they retained the morphologic and immunologic characteristics of vascular smooth muscle cells. U46619 stimulated 45Ca2+ efflux in a dose-dependent manner with an EC50 of 398 +/- 26 nM (n = 4). The maximal 45Ca2+ efflux in response to U46619 (5 microM) was significantly greater (p = 0.006) than the 45Ca2+ efflux induced by KCl (40 mM). I-PTA-OH inhibited the U46619-induced 45Ca2+ efflux but had no effect on KCl-induced 45Ca2+ efflux. These results suggest that the effects of U46619 in increasing vascular smooth muscle cell calcium efflux are receptor mediated. Furthermore, vascular smooth muscle cells with functional TXA2/PGH2 receptors were cultured from human saphenous veins and provide a potentially useful in vitro system for the further study of TXA2/PGH2 receptor-mediated phenomena in human vascular tissue.


Mechanical chiral resolution.
Mechanical interactions of chiral objects with their environment are well-established at the macroscale, like a propeller on a plane or a rudder on a boat. At the colloidal scale and smaller, however, such interactions are often not considered or deemed irrelevant due to Brownian motion. As we will show in this tutorial review, mechanical interactions do have significant effects on chiral objects at all scales, and can be induced using shearing surfaces, collisions with walls or repetitive microstructures, fluid flows, or by applying electrical or optical forces. Achieving chiral resolution by mechanical means is very promising in the field of soft matter and to industry, but has not received much attention so far.


An effect of walking exercise applying the theory of planned behavior in people at risk of hypertension.
To investigate an effectiveness of walking exercise program applying the Theory of Planned Behavior in people at risk of hypertension in Samut Sakorn province. The present study is a quasi-experimental research. The inclusion criteria were people aged 35-59 years old, systolic blood pressure 120-139 mmHg, and diastolic blood pressure 80-89 mmHg. Participants were randomly selected into the experimental group (n = 34) and the comparison group (n = 34). The experimental group received activities including health information, benefits of walking exercise, group discussion in exercise barriers, modeling and experience exchange, walking exercise practice, and practice on using walking monitoring booklet at the baseline and the 2nd week, whereas the comparison group received only health information and the booklet practice at the beginning of the intervention. Data were collected by self-administered questionnaires at the baseline, 2nd week, and 6th week. Statistical analysis was performed using Chi-square, Independent t-test, and repeated measures ANOVA. The experimental group made significant improvements in attitude towards walking exercise, perceived behavior control, subjective norm, walking exercise intention, and walking exercise over time (p < 0.05). However, no statistically significant differences between the experimental and the comparison groups were found in subjective norm, systolic and diastolic blood pressure from baseline to the 6th week. The experimental group had a significant higher mean difference score of attitude towards walking exercise, perceived behavior control, walking exercise intention, walking exercise, weight, and BMI compared to those in the comparison group (p < 0.05). Subjective norm scores in the experimental group were more likely to increase from baseline to the 6th week, but not a significant difference. Walking exercise programs applying the Theory of Planned Behavior should be recommended in people at risk of hypertension. Health professionals should also be motivated to practice with this program.


The dual origin of the yeast mitochondrial proteome.
We propose a scheme for the origin of mitochondria based on phylogenetic reconstructions with more than 400 yeast nuclear genes that encode mitochondrial proteins. Half of the yeast mitochondrial proteins have no discernable bacterial homologues, while one-tenth are unequivocally of alpha-proteobacterial origin. These data suggest that the majority of genes encoding yeast mitochondrial proteins are descendants of two different genomic lineages that have evolved in different modes. First, the ancestral free-living alpha-proteobacterium evolved into an endosymbiont of an anaerobic host. Most of the ancestral bacterial genes were lost, but a small fraction of genes supporting bioenergetic and translational processes were retained and eventually transferred to what became the host nuclear genome. In a second, parallel mode, a larger number of novel mitochondrial genes were recruited from the nuclear genome to complement the remaining genes from the bacterial ancestor. These eukaryotic genes, which are primarily involved in transport and regulatory functions, transformed the endosymbiont into an ATP-exporting organelle.


Transcription of a cis-acting, noncoding, small RNA is required for pilin antigenic variation in Neisseria gonorrhoeae.
The strict human pathogen Neisseria gonorrhoeae can utilize homologous recombination to generate antigenic variability in targets of immune surveillance. To evade the host immune response, N. gonorrhoeae promotes high frequency gene conversion events between many silent pilin copies and the expressed pilin locus (pilE), resulting in the production of variant pilin proteins. Previously, we identified a guanine quartet (G4) structure localized near pilE that is required for the homologous recombination reactions leading to pilin antigenic variation (Av). In this work, we demonstrate that inactivating the promoter of a small non-coding RNA (sRNA) that initiates within the G4 forming sequence blocks pilin Av. The sRNA promoter is conserved in all sequenced gonococcal strains, and mutations in the predicted transcript downstream of the G4 forming sequence do not alter pilin Av. A mutation that produces a stronger promoter or substitution of the pilE G4-associated sRNA promoter with a phage promoter (when the phage polymerase was expressed) produced wild-type levels of pilin Av. Altering the direction and orientation of the pilE G4-associated sRNA disrupted pilin Av. In addition, expression of the sRNA at a distal site on the gonococcal chromosome in the context of a promoter mutant did not support pilin Av. We conclude that the DNA containing the G-rich sequence can only form the G4 structure during transcription of this sRNA, thus providing a unique molecular step for the initiation of programmed recombination events.


[Epidemiology of infectious diseases in children in the old states of the Federal Republic of Germany].
This study was done to describe the epidemiology of infectious diseases in children living in the old countries of the Federal Republic of Germany. After an intensive search for literature, data about notifiable diseases, data from insurance agencies and a random test from 700 charts of a general pediatrician were reviewed and analysed in a standardized way for their validity. No single review article on this topic was found. Estimates about the frequency of some specific infectious diseases as well as data about notifiable diseases proved to be unreliable and not useful from a scientific point of view. Published insurance data suggested, that infectious diseases may contribute comparatively little to the morbidity of the population. In contrast, chart analysis revealed that every second visit at a pediatrician's office was prompted by an infectious disease. It is concluded, that there are only insufficient and unreliable data about the epidemiology of infectious diseases in children in the western part of the FRG and that this unsatisfying situation could be changed by using the technique of representative evaluation.