British anti-vaccination propaganda.
In April 1972, "Postal History International" published an article of mine concerning anti-vaccination caricature envelopes, which has led to some correspondence with readers and the discovery of several related items. It seems appropriate, therefore, to summarise the information in these pages, in the hope that this may bring forth knowledgeable comment from others. Details of any foreign propaganda of this sort would be particularly welcome. Meanwhile, this articles summarises what is known of the Society responsible for at least some of the British envelopes, and fills in a little of the historical background. The assistance of Mr. Ritchie Bodily is gratefully acknowledged, while the historical information was culled from the Newspaper Library of the British Museum at Colindale. Certain errors in the initial article can now be corrected, notably as to the name and location of the "persecuted man of Truth".


Receiving the initial Down syndrome diagnosis: a comparison of prenatal and postnatal parent group experiences.
This study explored the preliminary experiences of parents upon learning of their child's diagnosis of Down syndrome. Qualitative data from a web-based, national survey were analyzed based on two groups: prenatal (n = 46) or postnatal (n = 115) diagnosis. Three primary categories emerged from the data analysis: prenatal screening/testing decisions by parents, the adjustment process for parents, and postdiagnosis resources and support for parents. Participants' rationale behind pursuing testing ranged from wanting to be better prepared to not pursuing testing because it was not a factor in continuing the pregnancy. Participant reactions to the diagnosis involved a range of intense preliminary emotions; participants described their extreme grief and loss experience at the initial news of the diagnosis, which also was ambiguous in nature and required differing timelines of adjustment. Finally, participants described experiences with medical professionals, information/education, and faith/religion as resources and areas of support, although not all were described as positive in nature. Participants in both groups identified having negative experiences with medical professionals during the diagnosis process. The results indicated the importance of these early experiences for parents of children with Down syndrome and emphasize providing effective education, resources, and practical information from reliable sources.


Antigen-specific memory B-cell responses to Vibrio cholerae O1 infection in Bangladesh.
Cholera, caused by Vibrio cholerae, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with V. cholerae elicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to V. cholerae infection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with V. cholerae. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to V. cholerae protein antigens. Such memory B cells could mediate anamnestic responses on reexposure to V. cholerae.


Design and experiment of a soybean shaftless spiral seed discharge and seed delivery device.
When the driven stubble-breaking and anti-blocking no-till planter operates in the Southwest China, the stubble-breaking blades will impact with the ground as they cut through the soil and straw stubble, causing the planter to vibrate. This results in poor performances of the seed discharge by seed discharger and the seed guide by the seed guide tube. Based on the principle of spiral conveying, a soybean shaftless spiral seed discharge and seed delivery device was designed. The optimum seed filling size and speed range of the spiral blade were obtained by analyzing the size, force, and motion of soybean seeds of "ZhongHuang 37". The quadratic regression orthogonal rotation test and response surface method were used to analyze the operating parameters of the shaftless spiral seed discharge and seed delivery device by joint EDEM (Discrete Element Method)-RecurDyn simulation. The optimum parameters were obtained: the spacing of spiral was 11.4 mm, spiral outer radius was 5.5 mm, spiral inner radius was 2.9 mm and rotation speed was 10.4 r·s-1. Based on simulation and optimization results, the device was trialed and its field performance was tested. The results showed that at a surface slope of 16.1°, an average surface flatness of 8.9 cm, an average planter vibration frequency of 75.2 Hz, and an average amplitude of 7.2 mm, the average seeding qualification index, multiple index, missing seeding index, and damage index of the shaftless spiral seed discharge and seed delivery device were 92.6%, 5.03%, 2.4% and 0.92%, respectively, which were in line with the local agronomic requirements. The designed soybean shaftless spiral seed discharge and seed delivery device meets the requirements of the quality of no-till seeding and can provide a reference for the design and improvement of seed discharger and seed guide tube under poor ground leveling and long-distance seed delivery conditions.


Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.
We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.


A Markerless Pose Estimator Applicable to Limbless Animals.
The analysis of kinematics, locomotion, and spatial tasks relies on the accurate detection of animal positions and pose. Pose and position can be assessed with video analysis programs, the "trackers." Most available trackers represent animals as single points in space (no pose information available) or use markers to build a skeletal representation of pose. Markers are either physical objects attached to the body (white balls, stickers, or paint) or they are defined in silico using recognizable body structures (e.g., joints, limbs, color patterns). Physical markers often cannot be used if the animals are small, lack prominent body structures on which the markers can be placed, or live in environments such as aquatic ones that might detach the marker. Here, we introduce a marker-free pose-estimator (LACE Limbless Animal traCkEr) that builds the pose of the animal de novo from its contour. LACE detects the contour of the animal and derives the body mid-line, building a pseudo-skeleton by defining vertices and edges. By applying LACE to analyse the pose of larval Drosophila melanogaster and adult zebrafish, we illustrate that LACE allows to quantify, for example, genetic alterations of peristaltic movements and gender-specific locomotion patterns that are associated with different body shapes. As illustrated by these examples, LACE provides a versatile method for assessing position, pose and movement patterns, even in animals without limbs.


The awakening of dormant neuronal precursors in the adult and aged brain.
Beyond the canonical neurogenic niches, there are dormant neuronal precursors in several regions of the adult mammalian brain. Dormant precursors maintain persisting post-mitotic immaturity from birth to adulthood, followed by staggered awakening, in a process that is still largely unresolved. Strikingly, due to the slow rate of awakening, some precursors remain immature until old age, which led us to question whether their awakening and maturation are affected by aging. To this end, we studied the maturation of dormant precursors in transgenic mice (DCX-CreERT2 /flox-EGFP) in which immature precursors were labelled permanently in vivo at different ages. We found that dormant precursors are capable of awakening at young age, becoming adult-matured neurons (AM), as well as of awakening at old age, becoming late AM. Thus, protracted immaturity does not prevent late awakening and maturation. However, late AM diverged morphologically and functionally from AM. Moreover, AM were functionally most similar to neonatal-matured neurons (NM). Conversely, late AM were endowed with high intrinsic excitability and high input resistance, and received a smaller amount of spontaneous synaptic input, implying their relative immaturity. Thus, late AM awakening still occurs at advanced age, but the maturation process is slow.


A deep intronic DLG4 variant resulting in DLG4-related synaptopathy.
The rare autosomal dominant brain disorder DLG4-related synaptopathy is caused by de novo variants in DLG4 (encoding PSD-95), the majority of which are predicted to be protein-truncating. In addition to splice site variants, a number of synonymous and missense DLG4 variants are predicted to exert their effect through altered RNA splicing, although the pathogenicity of these variants is uncertain without functional RNA studies. Here, we describe a young boy with a deep intronic DLG4 variant (c.2105+235C>T) identified using whole genome sequencing. By using reverse-transcription PCR on RNA derived from peripheral blood, we demonstrate that DLG4 mRNA expression is detectable in blood and the deep intronic variant gives rise to two alternative DLG4 transcripts, one of which includes a pseudoexon. Both alternative transcripts are out-of-frame and predicted to result in protein-truncation, thereby establishing the genetic diagnosis for the proband. This adds to the evidence concerning the pathogenic potential of deep intronic variants and underlines the importance of functional studies, even in cases where reported tissue-specific gene expression might suggest otherwise.


Melatonin or L-tryptophan accelerates healing of gastroduodenal ulcers in patients treated with omeprazole.
Melatonin and L-tryptophan (Trp) are highly gastroprotective in humans, but no study has assessed their impact on healing of chronic gastroduodenal ulcers in humans. Three groups (A, B and C) of 14 idiopathic patients in each treatment group with gastroduodenal chronic ulcers were treated with omeprazole (20 mg twice daily) combined either with placebo (group A), melatonin (group B) or with Trp (group C). The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after initiation of therapy. Plasma melatonin, gastrin, ghrelin and leptin were measured by RIA. On day 7, omeprazole by itself (group A) had not healed any ulcers, but four ulcers were healed with omeprazole plus melatonin and two with omeprazole plus tryptophan. At day 21, all ulcers were healed in patients treated with melatonin or Trp, but only 10-12 ulcers were healed in placebo-treated patients. After treatment with omeprazole plus melatonin (group B) or Trp (group C), plasma melatonin levels rose several-fold above initial values. Plasma gastrin level also rose significantly during treatment with omeprazole plus melatonin or Trp, but it was also significantly increased in patients treated with omeprazole plus placebo. Plasma ghrelin levels did not change significantly after treatment with melatonin or Trp, while plasma leptin increased significantly in patients treated with melatonin or Trp but not with placebo. We conclude that melatonin or Trp, when added to omeprazole treatment, accelerates ulcer healing and this likely depends mainly upon the significant increments in plasma melatonin.


Experiences of junior doctors who shielded during the COVID-19 pandemic.
Shielding was introduced to protect clinically extremely vulnerable people during the COVID-19 pandemic. For junior doctors who had to shield, this meant pausing in-person clinical duties to protect their health. There is limited literature regarding this, and the available evidence is predominantly surveys or blogs that describe mainly negative experiences including guilt, isolation, inadequate support and Return To Work (RTW) concerns. Exploring the experiences of this group is valuable to understand the impact on them, and their support needs moving forward. This was a qualitative study using individual semi-structured interviews. Three junior doctors were recruited using volunteer and snowball sampling. Interview transcripts were analysed using thematic analysis. Seven themes were finalised: (1) Professional value, (2) Threatened autonomy, (3) Self-motivated, (4) Educational impact, (5) Mental health, (6) Inadequate support and (7) Return To Work concerns. Participant experiences largely reflected the evidence base including increased skill and knowledge acquisition, alongside guilt, isolation and inadequate support whilst shielding and upon RTW. These findings add valuable qualitative data to a scarcity of literature. However, caution should be applied when transferring these findings to other junior doctors, noting the small sample and regional setting. A small research grant has been secured for further research with a larger sample size incorporating the supervisor perspective. These findings demonstrate that shielding was a challenging experience for these junior doctors including impacts on mental health and insufficient support. This lack of support requires further attention to refine and strengthen available support structures.


Inhibitory effects of Lemon balm (Melissa officinalis, L.) extract on the formation of advanced glycation end products.
Lemon balm (Melissa officinalis) is a medicinal herb possessing functional compounds with unexplored anti-glycative action. The anti-glycative activity of Lemon balm extract was evaluated in the bovine serum albumin (BSA)/glucose system. The level of glycation, conformational alterations and protein binding to RAGE receptors were assessed by specific fluorescence, Congo red binding assay, circular dichroism, ligand and Western blotting. Ethanol fractions of Melissa leaf exhibited the highest inhibitory effects on the formation of advanced glycation end products (AGEs) and the late stage of glycation process. Significant alteration in the secondary structure of albumin was observed upon glycation, which was mitigated by applying the herb extract. Moreover, upon treatment with balm extract, glycated albumin adopts a secondary structure impeding its detection by RAGE receptors of microglial cells. Our results represent the anti-glycative properties of Melissa extract and its application for possible treatment of AGE-associated diseases.


Plant Copper Metalloenzymes As Prospects for New Metabolism Involving Aromatic Compounds.
Copper is an important transition metal cofactor in plant metabolism, which enables diverse biocatalysis in aerobic environments. Multiple classes of plant metalloenzymes evolved and underwent genetic expansions during the evolution of terrestrial plants and, to date, several representatives of these copper enzyme classes have characterized mechanisms. In this review, we give an updated overview of chemistry, structure, mechanism, function and phylogenetic distribution of plant copper metalloenzymes with an emphasis on biosynthesis of aromatic compounds such as phenylpropanoids (lignin, lignan, flavonoids) and cyclic peptides with macrocyclizations via aromatic amino acids. We also review a recent addition to plant copper enzymology in a copper-dependent peptide cyclase called the BURP domain. Given growing plant genetic resources, a large pool of copper biocatalysts remains to be characterized from plants as plant genomes contain on average more than 70 copper enzyme genes. A major challenge in characterization of copper biocatalysts from plant genomes is the identification of endogenous substrates and catalyzed reactions. We highlight some recent and future trends in filling these knowledge gaps in plant metabolism and the potential for genomic discovery of copper-based enzymology from plants.


Microvascular anastomosis training model based on a Turkey neck with perfused arteries.
The microvascular anastomosis (MA) technique remains an important aspect of modern neurosurgical practice. Specialized training is essential for mastering the anastomosis of small vessels. To minimize animal use and to create a simple but realistic training model, we developed a pulsatile perfused arteries model based on turkey carotid arteries for microvascular anastomosis training. Approximately 10-cm-long segments of turkey necks were used as a material to set up this model. The diameter of turkey carotid arteries at the neck level was found to be between 1 and 3 mm. Both carotid arteries on the neck segment were cannulated and incorporated into a closed circulation circuit consisting of silicone tubes and an infusion pump that provided continuous arterial-like flow and pulsation during the MA training. Tubing connection with both proximal and distal ends of the carotid arteries allowed circulatory patency during vessel clamping and anastomosis creation. Different fluids ranging from simple water to various colored solutions or even whole blood could be used for vascular perfusion in this experimental setup. Fluid output was maintained between 11 and 16 ml/min. Minimum pressure was set at 80 cm/H20, and maximum pressure was set at 160 cm/H20. Mean fluid flow through the arteries was 8 to 13 ml/min. End-to-end, end-to-side, and side-to-side MA may be performed on this model. This training model provides several advantages: the materials are easily obtainable and inexpensive, pulsatile flow through the arteries is realistic, the model is easy to manage, and there is no need for special facilities for animal care or anesthesia that are required for live animals. The diameter and structure of turkey carotid arteries are essentially identical to the human cortical vessels and distal branches of the superficial temporal artery. The pulsatile perfused carotid arteries model presents a realistic MA training model. It provides an inexpensive and simple setup for educational purposes. This technique can minimize live animal and anesthesia needs for MA training. Wide use of this model may enhance and popularize MA training and education.


Disorientation for place.
The study of a patient with remarkable disorientation for place associated with an acute nondominant parietooccipital lesion raised the general question of a relationship between disorientation for place and topographical disorientation. The literature does not address this matter. The clinical findings of one case in particular are presented here in detail. Another six patients had been seen with a disproportionate disorientation for place; in each there was an acute insult to the nondominant hemisphere. Based on these cases, there is preliminary evidence of a possible relationship.


Lymphoma, leukemia, and pleiocytosis in cerebrospinal fluid: is accurate cytopathologic diagnosis possible based on morphology alone?
The differentiation of benign versus malignant hematologic processes on cerebrospinal fluid (CSF) is difficult given the significant morphologic overlap and frequently scant specimen. Our study compared the diagnostic power of cytomorphologic analyses and FC analyses in the context of CSF hematologic malignancies. We identified 32 cases of CSF submitted for cytopathologic analysis with corresponding FC data, histologic, or clinical follow-up. The slides were blinded and the study participants (one hematopathologist, two cytopathologists, and one cytotechnologist) reviewed the key slides of each case without additional information. These diagnoses were compared with the original diagnoses made in the context of clinical information and ancillary studies. The spectrum of disease ranged from acute myeloid leukemia, mantle cell lymphoma, chronic lymphocytic lymphoma, Burkitt lymphoma, large cell lymphoma, T cell lymphoma, and non-Hodgkin lymphoma. Parallel diagnoses were made in 62.5% of the cases. Interestingly, the correct diagnoses were rendered in 73% of benign cases, compared with 52% of malignant cases. Of the malignant cases, there was a higher proportion of correct diagnosis based on morphology in the acute malignancies (67%) versus the chronic malignancies (47%). The sensitivity, specificity, positive predictive value, and negative predictive value were 73, 52, 60, and 66% respectively. Features most useful for diagnosis of malignancy included cellular monotony and nuclear contour irregularity. The diagnosis of malignancy based on morphology alone is difficult in CSF. Ancillary studies such as FC analyses greatly enhance the ability to accurately distinguish between benign and malignant hematologic processes.


Influence of induced hypermagnesemia and hypocalcemia on neuromuscular blocking property of oxytetracycline in the horse.
The neurally evoked contractile response of the upper lip muscles of horses anesthetized with halothane was used to evaluate the neuromuscular blocking property of oxytetracycline which was administered intravenously at total dose rate of 21 to 28 mg/kg. This dose rate did not alter the contractile response which had a mean control value (and standard error; SE) of 1.76 plus or minus 0.22 kg. Arterial blood pressure was not affected by these dose rates. Neuromuscular blocking effect of the antibiotic occurred when it was administered during partial neuromuscular blockade which had been induced by infusion of magnesium sulfate (0.12 or 0.16 g/kg). Moderate hypocalcemia induced by infusion of sodium oxalate did not enhance the neuromuscular blocking property of this antibiotic. Since the dose rates of the oxytetracycline preparation used had a small effect on calcium concentration of equine serum (smaller than 0.3 mg/dl), calcium binding does not seem to play a major role in the neuromuscular blocking effect of this antibiotic. It was concluded that the weak neuromuscular blocking effect of oxytetracycline is not a significant etiologic factor in the acute type of adverse reaction to this antibiotic that is occasionally encountered in horses.


Thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex. Randomized, double-blind, placebo-controlled study of 100-mg oral fluconazole daily.
Recurrent oropharyngeal candidiasis is common in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex. It causes local pain and discomfort, loss of taste, and aversion to food and may lead to secondary complications. We examined, in a double-blind study, whether recurrent thrush could be prevented by prophylaxis. Twenty-five patients with one to four previous thrush episodes who had no thrush at the outset of the study were randomized to receive 100 mg of fluconazole or placebo daily for 12 weeks. If thrush occurred, prophylaxis was stopped and patients were treated conventionally, after which prophylaxis was resumed. After the randomized study, some patients were given continuous fluconazole (open phase). In the randomized study, thrush occurred in eight of 13 placebo-treated patients and none of 12 fluconazole-treated patients. Possible side effects were not different between the groups. Dermatophytosis and onychomycosis and cryptococcuria also improved in the fluconazole-treated patients, and fungal colonization was significantly decreased. One episode of thrush occurred in the open phase in an intermittently compliant patient (group total, 71.5 patient-months of fluconazole treatment); in contrast, the 25 patients also had had two episodes of Candida esophagitis, three of cryptococcosis, and 13 of dermatophytosis before entry. Subsequent to entry in the randomized trial, in 92.3 patient-months without fluconazole, there were 35 episodes of thrush, one of esophagitis, one of cryptococcemia, and one of dermatophytosis, and preexisting dermatophytosis and onychomycosis were unchanged or worsened. Individual patients observed with and without fluconazole treatment also showed its efficacy. In conclusion, thrush can be prevented in patients with acquired immunodeficiency syndrome and the acquired immunodeficiency syndrome-related complex with negligible toxic effects. Larger trials to confirm prevention of all mycoses with prophylaxis should be considered.


A promising water-in-salt electrolyte for aqueous based electrochemical energy storage cells with a wide potential window: highly concentrated HCOOK.
Recently, water-in-salt electrolytes have been widely reported because of their ability in broadening the potential window of aqueous based energy storage devices. Herein, another eco-friendly and cost-effective electrolyte, concentrated potassium formate of 40 M HCOOK where the water-to-salt molar ratio falls to 1.38 : 1, is proposed. The electrolyte demonstrates a wide potential window of up to 4 V (-2.5 to 1.5 V vs. Ag/AgCl) with a glassy carbon electrode. Compared with a CH3COOK based electrolyte, the HCOOK possesses lower stable negative potential and higher ionic conductivity. For an activated carbon based supecapacitive electrode, a low discharge potential of -2.4 V vs. Ag/AgCl can be achieved. Besides, a high capacity of 321 F g-1 is obtained at 5 A g-1 and it is still as high as 121 F g-1 at 20 A g-1. Meanwhile, typical K-battery behavior is exhibited for the KTi2(PO4)3 anode and a reversible capacity of 15 mA h g-1 can be delivered at 0.1 A g-1.


The initial validation of a novel outcome measure in severe burns- the Persistent Organ Dysfunction +Death: Results from a multicenter evaluation.
A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate "Persistent Organ Dysfunction" plus death as endpoint in burn patients and to demonstrate its statistical efficiency. This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care. In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used. POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted. Prospective cohort study, level of evidence: II.


Is medical thoracoscopy efficient in the management of multiloculated and organized thoracic empyema?.
Pleural empyema can be subdivided into 3 stages: exudative, multiloculated, and organizing. In the absence of clear septation, antibiotics plus simple drainage of pleural fluid is often sufficient treatment, whereas clear septation often requires more invasive treatment. The aim of this study was to report our experience and analyze the safety and efficacy of medical thoracoscopy in patients with multiloculated and organizing empyema. We performed a retrospective study reviewing the files of patients referred for empyema and treated by medical thoracoscopy at our department from July 2005 to February 2011. A total of 41 patients with empyema were treated by medical thoracoscopy; empyema was free flowing in 9 patients (22%), multiloculated in 24 patients (58.5%), and organized in 8 patients (19.5%). Medical thoracoscopy was considered successful without further intervention in 35 of 41 patients (85.4%): all of the 9 patients with free-flowing fluid, 22 of the 24 patients with multiloculated empyema (91.7%), and only 4 of the 8 patients with organizing effusion (50%). Our study confirms that multiloculated pleural empyema could safely and successfully be treated with medical thoracoscopy while organizing empyema can be resistant to drainage with medical thoracoscopy, requiring video-assisted thoracic surgery or open surgical decortications; among this population, the presence of separate 'pockets' not in apparent communication with each other often leads to a surgical approach.


Preparation and analysis of the nucleocapsid proteins of vesicular stomatitis virus and sendai virus, and analysis of the sendai virus leader-NP gene region.
A procedure is presented for isolating the nucleocapsid proteins, N and NP from vesicular stomatitis virus and Sendai virus respectively, in soluble form. These proteins were suitable for the determination of their blocked amino-terminal peptide sequences by gas-liquid chromatography/mass spectrometry at the low nanomole level. The N protein prepared by this procedure was previously shown to retain some of its expected biological activity. The sequence of 626 nucleotides from the 3' end of the Sendai virus genome, which includes the first one-third of the NP gene, was determined. Using this information, primer extension studies on intracellular Sendai virus mRNAs allowed the determination of the structure of the leader-NP intervening sequence and the 5' end of the NP mRNA. Comparison of the amino termini of the nucleocapsid proteins with their respective mRNA sequences revealed that these proteins are similarly processed in vivo.


The ovine corticotropin-releasing hormone stimulation test and the dexamethasone suppression test in the differential diagnosis of Cushing's syndrome.
We gave a standard dexamethasone suppression test and an ovine corticotropin-releasing hormone (CRH) stimulation test to 41 patients with adrenocorticotrophic hormone (ACTH)-dependent hypercortisolism to determine the efficacy of each test in the differential diagnosis of Cushing's syndrome. Twenty-nine of thirty-three patients with Cushing's disease and 0 of 8 patients with ectopic secretion of ACTH responded to the ovine CRH test with increased levels of cortisol. When a cortisol response was judged as positive for Cushing's disease, the CRH test had a diagnostic sensitivity, specificity, and accuracy of 88%, 100%, and 90%, respectively. Twenty-nine patients with Cushing's disease and 1 patient with ectopic secretion of ACTH responded to the dexamethasone suppression test. A combined-test strategy requiring negative results from both tests to exclude a diagnosis of Cushing's disease yielded superior sensitivity (100%) and diagnostic accuracy (98%). Thus, the ovine CRH test works as well as the standard dexamethasone suppression test in discriminating between Cushing's disease and ectopic ACTH secretion. The diagnostic power of each test is enhanced when the two tests are combined.


A zinc finger protein Tsip1 controls Cucumber mosaic virus infection by interacting with the replication complex on vacuolar membranes of the tobacco plant.
• In Cucumber mosaic virus (CMV) RNA replication, replicase-associated protein CMV 1a and RNA-dependent RNA polymerase protein CMV 2a are essential for formation of an active virus replicase complex on vacuolar membranes. • To identify plant host factors involved in CMV replication, a yeast two-hybrid system was used with CMV 1a protein as bait. One of the candidate genes encoded Tsi1-interacting protein 1 (Tsip1), a zinc (Zn) finger protein. Tsip1 strongly interacted with CMV 2a protein, too. • Formation of a Tsip1 complex involving CMV 1a or CMV 2a was confirmed in vitro and in planta. When 35S::Tsip1 tobacco (Nicotiana tabacum) plants were inoculated with CMV-Kor, disease symptom development was delayed and the accumulation of CMV RNAs and coat protein was decreased in both the infected local leaves and the uninfected upper leaves, compared with the wild type, whereas Tsip1-RNAi plants showed modestly but consistently increased CMV susceptibility. In a CMV replication assay, CMV RNA concentrations were reduced in the 35S::Tsip1 transgenic protoplasts compared with wild-type (WT) protoplasts. • These results indicate that Tsip1 might directly control CMV multiplication in tobacco plants by formation of a complex with CMV 1a and CMV 2a.


Adipose tissue and atherosclerosis: exploring the connection.
The prevalence of obesity, especially among the young, is dramatically increasing in the United States. Obesity is associated with accelerated atherosclerosis and increased rates of cardiovascular death. There are many plausible mechanisms by which an increase in adipose tissue could adversely affect the vessel wall. These include the changes in blood pressure, glucose level, lipid/lipoprotein metabolism, and systemic inflammation. In addition, factors secreted by adipose tissue may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in the vessel wall. There is general agreement that central, as opposed to peripheral, adipose tissue confers the most cardio-metabolic risk. Although the basis of this differential risk has not been not established, the pattern of gene expression and secretory products in visceral fat would be predicted to be more atherogenic compared with that in subcutaneous peripheral fat. Numerous studies have shown the beneficial effects of weight loss on markers of cardiovascular risk but fewer have demonstrated improvement in direct measures of large vessel disease. The unfolding role of adipose tissue as an important metabolic and secretory organ provides new opportunities for developing more effective approaches for preventing obesity and its atherosclerotic complications.


Does peak expiratory flow measured sitting differ from that measured standing? A cross-over study in primary care in Barbados.
Several authorities recommend measuring peak expiratory flow (PEF) standing. Limited evidence suggests that PEF obtained sitting is similar in magnitude but there are no studies in African populations. To determine in adults aged 18-60 years if PEF measured sitting differs from that measured standing. Crossover design with alternating position of initial measurement in people attending primary care clinics in Barbados. Quota sampling by age, sex, and clinic of adults aged 18-60 years was done and an interviewer-administered questionnaire was completed. PEF sitting and standing was measured with an European Union (EU) scale Mini-Wright® meter. The highest of three readings in each position was used and the difference in means tested for significance using the paired sample t-test. Characteristics of the 199 participants were 44% male; 96.5% of African descent; mean age 37 years (standard deviation [SD] 12.8); 22% with an asthma diagnosis; 23% tobacco users; and 22% marijuana users. Mean PEF standing was 438.4 versus 429.7 lmin-1 sitting, mean difference 8.7 (95% confidence interval [CI] = 3.6 to 13.8). For men, mean PEF standing was 518.7 versus 506.3 lmin-1 sitting, mean difference 12.4 (95% CI = 3.3 to 21.5). For women, mean PEF was 374.7 standing versus 368.9 lmin-1 sitting, mean difference 5.8 (95% CI = 0.11 to 11.5). A Bland-Altman plot accounting for trend and a Lin's correlation coefficient of 0.935 demonstrated good agreement between standing and sitting PEF. PEF measurements are reduced when performed sitting compared to standing. The difference is small and unlikely to alter clinical management in most cases.


Biosynthetic pathway and health benefits of fucoxanthin, an algae-specific xanthophyll in brown seaweeds.
Fucoxanthin is the main carotenoid produced in brown algae as a component of the light-harvesting complex for photosynthesis and photoprotection. In contrast to the complete elucidation of the carotenoid biosynthetic pathways in red and green algae, the biosynthetic pathway of fucoxanthin in brown algae is not fully understood. Recently, two models for the fucoxanthin biosynthetic pathway have been proposed in unicellular diatoms; however, there is no such information for the pathway in brown seaweeds to date. Here, we propose a biosynthetic pathway for fucoxanthin in the brown seaweed, Ectocarpus siliculosus, derived from comparison of carotenogenic genes in its sequenced genome with those in the genomes of two diatoms, Thalassiosira pseudonana and Phaeodactylum tricornutum. Currently, fucoxanthin is receiving attention, due to its potential benefits for human health. Therefore, new knowledge regarding the medical and nutraceutical properties of fucoxanthin from brown seaweeds is also summarized here.


Effects of BCR-ABL inhibitors on anti-tumor immunity.
In chronic myeloid leukemia (CML), BCR-ABL-mediated oncogenic signaling can be successfully targeted with the BCRABL- inhibitors imatinib, nilotinib, and dasatinib leading to complete cytogenetic (Philadelphia chromosome not detectable upon cytogenetic testing of bone marrow) and even complete molecular (BCR-ABL not detectable by PCR in peripheral blood) responses. However, CML apparently can not be cured by BCR-ABL inhibitors alone, likely due to treatment-resistance of CML stem/progenitor cells, which provokes a relapse of disease after cessation of therapy. Evidence from patients treated with allogenic stem cell transplantation or IFN-α points to an important role of anti-tumor immunity for durable control of CML disease. Data from multiple in vitro and ex vivo studies indicate that BCR-ABL inhibitors may also influence anti-tumor immunity. Varying effects on different immune effector cell subsets and of the different compounds have been reported, the latter being due to their particular and diverse potency and spectrum of target kinases. As multiple approaches presently aim to combine BCR-ABL inhibition with immunotherapeutic strategies to improve disease control in CML, immunomodulatory effects of the available BCR-ABL inhibitors may be of direct clinical relevance. Here we review the available data regarding the effects of imatinib, nilotinib, and dasatinib on dendritic cells, T cells and natural killer cells as important cellular components of anti-tumor immunity.


Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia Secondary to Stroke: A Systematic Review and Clinical Case Presentation.
Trigeminal neuralgia (TN) is a paroxysmal, unilateral, brief, shock-like pain in ≥1 divisions of the trigeminal nerve. It can result from multiple causes; however, TN secondary to stroke is very rare. We present the case of TN secondary to pontine infarction treated with incremental doses of neuropathic pain medication for >5 years before conservative management failed. He was then treated with stereotactic radiosurgery (SRS). Additionally, we conducted a systematic review using standard PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for all the cases of TN with brainstem stroke from 1976 to 2022. Our patient was an 82-year-old man. Magnetic resonance imaging demonstrated a pontine lesion consistent with stroke. The Barrow Neurological Institute (BNI) score at presentation was 5. He received a marginal dose of 60 Gy to the 80% isodose line in a single fraction to a volume of 0.05 cm3. The immediate post-treatment BNI score was 0 and remained at 0 for 3 months, when he experienced recurrence. The recurrence was treated with oxcarbazepine. His pain remained well controlled with a lower dose of oxcarbazepine, and he had no adverse effects at 1 year of follow-up with a BNI score of 3. The systemic review identified 21 case reports with a combined cohort of 25 patients with TN secondary to stroke. Only 3 patients were treated with SRS, 2 of whom reported symptom improvement at 6 months and 8 months of follow-up with no adverse events. Our case and literature review demonstrate durable and effective treatment with SRS, which can be considered a safe and effective treatment option for patients with stroke-associated TN.


Time-course of posterior parietal and occipital cortex contribution to sound localization.
It has been suggested that both the posterior parietal cortex (PPC) and the extrastriate occipital cortex (OC) participate in the spatial processing of sounds. However, the precise time-course of their contribution remains unknown, which is of particular interest, considering that it could give new insights into the mechanisms underlying auditory space perception. To address this issue, we have used event-related transcranial magnetic stimulation (TMS) to induce virtual lesions of either the right PPC or right OC at different delays in subjects performing a sound lateralization task. Our results confirmed that these two areas participate in the spatial processing of sounds. More precisely, we found that TMS applied over the right OC 50 msec after the stimulus onset significantly impaired the localization of sounds presented either to the right or to the left side. Moreover, right PPC virtual lesions induced 100 and 150 msec after sound presentation led to a rightward bias for stimuli delivered on the center and on the left side, reproducing transiently the deficits commonly observed in hemineglect patients. The finding that the right OC is involved in sound processing before the right PPC suggests that the OC exerts a feedforward influence on the PPC during auditory spatial processing.


Evaluation of the efficacies of Amphotericin B, Posaconazole, Voriconazole, and Anidulafungin in a murine disseminated infection by the emerging opportunistic Fungus Sarocladium (Acremonium) kiliense.
We evaluated and compared the efficacies of different antifungal drugs against Sarocladium kiliense (formerly Acremonium kiliense), a clinically relevant opportunistic fungus, in a murine model of systemic infection. Three clinical strains of this fungus were tested, and the therapy administered was as follows: posaconazole at 20 mg/kg of body weight (twice daily), voriconazole at 40 mg/kg, anidulafungin at 10 mg/kg, or amphotericin B at 0.8 mg/kg. The efficacy was evaluated by prolonged animal survival, tissue burden reduction, and (1→3)-β-d-glucan serum levels. In general, the four antifungal drugs showed high MICs and poor in vitro activity. The efficacy of the different treatments was only modest, since survival rates were never higher than 40% and no drug was able to reduce fungal load in all the organs for the three strains tested. Posaconazole, in spite of its high MICs (≥16 μg/ml), showed the highest efficacy. The (1→3)-β-d-glucan serum levels were equally reduced by all drugs evaluated.


Course and outcome of childhood epilepsy: a 15-year follow-up of the Dutch Study of Epilepsy in Childhood.
To study the course and outcome of childhood-onset epilepsy during 15-year follow-up (FU). We extended FU in 413 of 494 children with new-onset epilepsy recruited in a previously described prospective hospital-based study by questionnaire. Mean FU was 14.8 years (range 11.6-17.5 years). Five-year terminal remission (TR) was reached by 71% of the cohort. Course during FU was favorable in 50%, improving in 29%, and poor or deteriorating in 16%. Mean duration of seizure activity was 6.0 years (range 0-21.5 years), strongly depending on etiology and epilepsy type. Duration was <1 year in 25% of the cohort and exceeded 12 years in another 25%. Antiepileptic drugs (AEDs) were used by 86% during a mean of 7.4 years: one-third had their last seizure within 1 year of treatment, and one-third continued treatment at the end, although some had a 5-year TR. At last contact, 9% of the cohort was intractable. In multivariate analysis, predictors were nonidiopathic etiology, febrile seizures, no 3-month remission, and early intractability. Eighteen patients died; 17 had remote symptomatic etiology. Standardized mortality ratio for remote symptomatic etiology was 31.6 [95% confidence interval (CI) 18.4-50.6], versus 0.8 [95% CI 0.02-4.2] for idiopathic/cryptogenic etiology. In most children with newly diagnosed epilepsy, the long-term prognosis of epilepsy is favorable, and in particular, patients with idiopathic etiology will eventually reach remission. In contrast, epilepsy remains active in approximately 30% and becomes intractable in approximately 10%. AEDs probably do not influence epilepsy course; they merely suppress seizures. Mortality is significantly higher only in those with remote symptomatic etiology.


Characterization of carbonic anhydrase from Neisseria gonorrhoeae.
We have investigated the steady state and equilibrium kinetic properties of carbonic anhydrase from Neisseria gonorrhoeae (NGCA). Qualitatively, the enzyme shows the same kinetic behaviour as the well studied human carbonic anhydrase II (HCA II). This is reflected in the similar pH dependencies of the kinetic parameters for CO(2) hydration and the similar behaviour of the kinetics of (18)O exchange between CO(2) and water at chemical equilibrium. The pH profile of the turnover number, k(cat), can be described as a titration curve with an exceptionally high maximal value of 1.7 x 10(6) s(-1) at alkaline pH and a pK(a) of 7.2. At pH 9, k(cat) is buffer dependent in a saturable manner, suggesting a ping-pong mechanism with buffer as the second substrate. The ratio k(cat)/K(m) is dependent on two ionizations with pK(a) values of 6.4 and 8.2. However, an (18)O-exchange assay identified only one ionizable group in the pH profile of k(cat)/K(m) with an apparent pK(a) of 6.5. The results of a kinetic analysis of a His66-->Ala variant of the bacterial enzyme suggest that His66 in NGCA has the same function as a proton shuttle as His64 in HCA II. The kinetic defect in the mutant can partially be overcome by certain buffers, such as imidazole and 1,2-dimethylimidazole. The bacterial enzyme shows similar K(i) values for the inhibitors NCO(-), SCN(-) and N(3)(-) as HCA II, while CN(-) and the sulfonamide ethoxzolamide are considerably weaker inhibitors of the bacterial enzyme than of HCA II. The absorption spectra of the adducts of Co(II)-substituted NGCA with acetazolamide, NCO(-), SCN(-), CN(-) and N(3)(-) resemble the corresponding spectra obtained with human Co(II)-isozymes I and II. Measurements of guanidine hydrochloride (GdnHCl)-induced denaturation reveal a sensitivity of the CO(2) hydration activity to the reducing agent tris(2-carboxyethyl)phosphine (TCEP). However, the A(292)/A(260) ratio was not affected by the presence of TCEP, and a structural transition at 2.8--2.9 M GdnHCl was observed.


Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 pet and a highly automated analysis program.
Changes in myocardial blood flow between rest and stress states are commonly used to diagnose coronary artery disease. Relative myocardial perfusion imaging (MPI) is used routinely while myocardial blood flow quantification (MBF) may improve the sensitivity for detection of early disease. The ratio of flow at stress and rest (S/R) and their difference (S-R) have both been proposed as a means to detect regions with reduced myocardial flow reserve (MFR). In this study, we describe a highly automated method to calculate regional and global rest, stress, S/R, and S-R polar maps of the left ventricle myocardium. We measured the inter- and intra-operator variability using two randomized datasets (n = 30 each) for each of two operators (novice and expert) with correlation and Bland-Altman reproducibility coefficient (RPC%) analyses. S-R MBF had less inter-operator dependent variability than S/R (RPC% = 5.0% vs 12.6%, P < .001). While there was no difference in intra-operator variability with S-R MBF (novice vs expert RPC% = 6.4% vs 5.9%, P = ns), variability was higher in the novice-operator for S/R (RPC% = 16.8% vs 8.5% respectively, P < .001), suggesting that S-R may be preferred for detecting small changes in MFR. The novice operator's intervention pattern became more similar to that of the expert in the later dataset, emphasizing the need for adequate training and quality assurance. The proposed method results in low operator-dependent variability, suitable for routine use.


A comparative double-blind, randomised trial of a new second generation LMWH (bemiparin) and UFH in the prevention of post-operative venous thromboembolism. The Bemiparin Assessment group.
A randomised, prospective, double-blind trial was performed, to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) Bemiparin and standard unfractionated heparin (UFH), for the prophylaxis of postoperative venous thromboembolism. 300 patients scheduled to undergo elective hip arthroplasty were included. The principal outcome measures were the incidence of thromboembolic events and bleeding complications. 149 patients received 3,500 anti-Xa IU of bemiparin plus a placebo injection daily and 149 patients received 5,000 IU of UFH twice a day. The two groups were similar with respect to factors likely to affect the risk of developing post-operative venous thromboembolism (VTE) and risk of bleeding events. During the post-operative period, 34 patients developed VTE complications; 9 (7.2%) in the bemiparin group and 25 (18.7%) in the UFH group. VTE in the two groups was statistically significant (OR of 2.96; 95% CI 1.32-6.62 and p = 0.01). There were no significant differences in the frequency of bleeding complications: major bleeding requiring discontinuation of prophylaxis, (OR 1.21; 95% CI 0.36-4.05; p = 1.00), the measured median operative blood loss (p = 0.77) or the median postoperative drain loss (p = 0.97), and the number of patients who developed wound haematoma (OR 0.87; 95% CI 0.31-2.46; p = 1.00). A comparison of coagulation parameters on the preoperative day with post-operative day 2 +/- 1, day 6 +/- 1 and day of discharge showed a significantly higher AT concentration, anti-factor Xa activity and TFPI levels in the bemiparin group when compared with UFH. This study demonstrates that bemiparin, in a single daily subcutaneous dose of 3,500 anti-Xa IU in high risk patients undergoing hip arthroplasty is more effective than UFH administered twice daily at a dose of 5,000 IU in the prevention of postoperative VTE. Both agents are equally safe.


Personal health behaviors and role-modeling attitudes of physical therapists and physical therapist students: a cross-sectional study.
Physical therapists have been encouraged to engage in health promotion practice. Health professionals who engage in healthy behaviors themselves are more apt to recommend those behaviors, and patients are more motivated to change their behaviors when their health care provider is a credible role model. The purpose of this study was to describe the health behaviors and role-modeling attitudes of physical therapists and physical therapist students. This study was a descriptive cross-sectional survey. A national sample of 405 physical therapists and 329 physical therapist students participated in the survey. Participants' attitudes toward role modeling and behaviors related to physical activity, fruit and vegetable consumption, abstention from smoking, and maintenance of a healthy weight were measured. Wilcoxon rank sum tests were used to examine differences in attitudes and behaviors between physical therapists and physical therapist students. A majority of the participants reported that they engage in regular physical activity (80.8%), eat fruits and vegetables (60.3%), do not smoke (99.4%), and maintain a healthy weight (78.7%). Although there were no differences in behaviors, physical therapist students were more likely to believe that role modeling is a powerful teaching tool, physical therapist professionals should "practice what they preach," physical activity is a desirable behavior, and physical therapist professionals should be role models for nonsmoking and maintaining a healthy weight. Limitations of this study include the potential for response bias and social desirability bias. Physical therapists and physical therapist students engage in health-promoting behaviors at similarly high rates but differ in role-modeling attitudes.


Cardiac CT angiography in the emergency department.
OBJECTIVE. Nearly 8 million patients present annually to emergency departments (EDs) in the United States with acute chest pain. Identifying those with a sufficiently low risk of acute coronary syndrome (ACS) remains challenging. Early imaging is important for risk stratification of these individuals. The objective of this article is to discuss the role of cardiac CT angiography (CTA) as a safe, efficient, and cost-effective tool in this setting and review state-of-the-art technology, protocols, advantages, and limitations from the perspective of our institution's 10-year experience. CONCLUSION. Early utilization of cardiac CTA in patients presenting to the ED with chest pain and a low to intermediate risk of ACS quickly identifies a group of particularly low-risk patients (< 1% risk of adverse events within 30 days) and allows safe and expedited discharge. By preventing unnecessary admissions and prolonged lengths of stay, a strategy based on early cardiac CTA has been shown to be efficient, although potential overutilization and other issues require long-term study.


Clear cell meningiomas: three case reports with genetic characterization and review of the literature.
Intracranial clear cell meningioma is very rare. We present 3 cases of intracranial clear cell meningiomas genetically characterized by comparative genomic hybridization with a review of the literature. Patient 1 is a 38-year-old woman with a petroclival tumor. Patient 2 is a 60-year-old man with a tumor at the foramen magnum. Patient 3 is a 60-year-old man with a tumor at the posterior clinoid process. Gross total resection was performed in patients 1 and 2. Patient 1 has been free from recurrence for 10 years. Patient 2 had a tumor recurrence at 14 months after the operation. After partial resection, conventional radiotherapy was given, and there was no tumor regrowth at 2 years after radiotherapy. Subtotal resection was performed in patient 3, and no regrowth was detected for 3 months. Histologically, all tumors were composed of cells with clear cytoplasm reactive for periodic acid-Schiff and diagnosed as clear cell meningioma. The MIB-1 and p53 staining indexes were 1.8, 1.7, and 5.6 and 1.1, 1.0, and 5.5, respectively. Comparative genomic hybridization revealed no chromosomal number aberrations in patient 1, numerous losses and gains including loss of chromosome 1 in patient 2, and loss of only 22q in patient 3. Because staining indexes of MIB-1 and p53 were equivalent in 2 patient (patients 1 and 2) with a long follow-up period, the contrary clinical courses are likely associated with genetic characteristics. To the best of our knowledge, this is the first report that suggests association between tumor behavior and genetic characteristics in clear cell meningiomas.


Problematic Internet Use in Turkish High School Students: Prevalence and Related Factors.
Objectives: In this study, we sought to determine the prevalence of problematic Internet use (PIU) among high school students and identify demographic and socioeconomic factors related to PIU. Methods: Using a cross-sectional design, we conducted this study between November 2017 and January 2018 of 1412 students attending high schools in the Silivri District of Istanbul in Turkey. We administered a questionnaire inquiring about sociodemographic information, Internet use, and Young's Internet Addiction Test to participating students. Results: Among participants, 18.5% (male = 17.2%; females = 19.8%) were found to show PIU. PIU rates were higher among those with a high household income and lower among those who studied in science high schools, performed physical activities at least 2 days a week, and read at least one book a month. PIU rates were also higher among those who had their own bedrooms, phones, smartphones, Internet connections at home, and social networking accounts. Conclusion: The prevalence of PIU among the participants was 18.5%. Female sex, high household income, low physical activity, grade level, school type, reading fewer than one book per month, and Internet use experience were risk factors for PIU. PIU is considered a significant public health concern across the world, including in Turkey.


In situ monitoring of thermal crystallization of ultrathin tris(8-hydroxyquinoline) aluminum films using surface-enhanced Raman scattering.
Thermal crystallization of 3, 10, and 60 nm-thick tris(8-hydroxyquinoline)aluminum (Alq3) films is studied using surface-enhanced Raman scattering with a constant heating rate. An abrupt higher frequency shift of the quinoline-stretching mode is found to be an indication of a phase transition of Alq3 molecules from amorphous to crystalline. While the 60 nm-thick film shows the same crystallization temperature as a bulk sample, the thinner films were found to have a lower crystallization temperature and slower rate of crystallization. Non-isothermal kinetics analysis is performed to quantify kinetic properties such as the Avrami exponent constants and crystallization rates of ultrathin Alq3 films.


Mott phase at the surface of 1T-TaSe2 observed by scanning tunneling microscopy.
In this Letter we report the observation, by scanning tunneling microscopy, of a Mott metal to insulator transition at the surface of 1T-TaSe2. Our spectroscopic data compare considerably well with previous angle-resolved photoemission spectroscopy measurements and confirm the presence of a large hysteresis related to a first order process. The local character of the tunneling spectroscopy technique allows a direct visualization of the surface symmetry and provides spectroscopic measurements on the defect-free region of the sample. It follows that the electronic localization is driven purely by the enhancement of the charge density wave amplitude which drives a bandwidth controlled metal-insulator transition.


Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake.
This study examined the roles of the female sex steroids, 17beta-estradiol (E(2)) and progesterone (Prog), on glucose uptake and GLUT4 protein expression. Female Sprague-Dawley rats were either sham operated (C) or ovariectomized and treated with placebo (O), E(2) (E), Prog (P), or both hormones at physiological doses (P + E) or the same dose of Prog with a high dose of E(2) (P + HiE) via timed-release pellets inserted at the time of surgery, 15 days before metabolic testing. On the morning of day 15, animals received a 300-microCi injection (ip) of 2-deoxy-[(14)C]glucose and then either exercised on a motorized treadmill for 30 min at 0.35 m/s or remained sedentary in their cages for the same period. Basal glucose uptake was not different between the treatment groups in either the red or white quadriceps. However, glucose uptake was decreased (P < 0.05) in O, P, and P + E rats during exercise in the red quadriceps compared with C rats, whereas E and P + HiE treatment restored glucose uptake. Glycogen content in skeletal muscle followed similar trends, with no differences seen in resting animals. Postexercise red quadriceps glycogen levels were higher (P < 0.05) in the E and P + HiE rats compared with O and P. Treatment of ovariectomized rats with progesterone (P rats) decreased (P < 0.05) GLUT4 content in the red quadriceps by 21% compared with C rats. These data demonstrate that estrogen-deficient animals have a decreased ability for contraction-stimulated glucose uptake and increased glycogen use during aerobic exercise. However, changes in contraction-stimulated glucose uptake could not be explained by altered transporter protein content, since the absence of E(2) had no effect on GLUT4 protein.


Prevalence of monoclonal gammopathy of undetermined significance.
The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.


Post-learning stress reduces the misinformation effect: effects of psychosocial stress on memory updating.
Episodic memories can be modified when exposed to new and related information. This phenomenon, known as memory updating, is generally thought to be adaptive but can also lead to incorporating false information into a memory trace. Given the well-known effects of stress on episodic memory, we used a false information paradigm to investigate if acute stress during memory updating (i.e., post-learning stage) affected false memory formation. In a between-subject design, young healthy participants completed the initial phases of the misinformation experiment - they studied an event via a slideshow and then were exposed a related narrative that contained misleading information about that event. After, half of the participants were exposed to acute psychosocial stress and the other half completed a control task. Once stress levels returned to baseline, all of the participants completed the final phase of the experiment, which was a memory test for slideshow that included items containing true facts and misinformation. Participants in the stress condition showed a reduced misinformation effect and were better able to discriminate true from false information compared to control participants. This pattern of results held even when participants were tested on the same memory test after a multiple day delay, illustrating the long-lasting effects of stress on false memory formation specifically, and memory updating generally. We discuss how our results add to the understanding of the time-dependent factors that moderate stress effects on memory, and speculate how stress effects on memory updating can be positive, by limiting intrusions into encoded events, but also negative, by limiting the ability to integrate information with other concepts, harming memory generalization.


Pathophysiology of renal hemodynamics.
The high blood flow rate/gram of kidney tissue supplies mainly the renal cortex. The net effect of the interaction of the renin-angiotensin system, the kallikrein-kinin system and prostaglandins is to autoregulate renal blood flow within a narrow range. Drugs and neurogenic factors also influence renal hemodynamics. The renal circulation responds to changes in extracellular fluid volume, and in cardiac output. Renal ischemia occurs readily as these parameters decrease and prompt correction of circulatory dynamics can restore renal blood flow and prevent tubular necrosis. With hypovolemia or heart failure, angiotensin II is a mediator of efferent arteriolar constriction promoting a proportionately greater fall in renal plasma flow than in glomerular filtration rate, thereby augmenting sodium reabsorption. With renal failure, glomerulotubular balance is affected conversely promoting sodium loss. Appreciating these distinctions allows recognition of inappropriate sodium retention or loss. With such data, prognosis can be estimated more accurately and attempts to restore circulatory dynamics can be guided.


Surface modified poly(L-lactide-co-epsilon-caprolactone) microspheres as scaffold for tissue engineering.
P-15 modified poly(L-lactide-co-epsilon-caprolactone) (PLCL) microspheres were investigated as scaffolds for tissue engineering applications. PLCL copolymer was synthesized by ring opening polymerization and was composed of a soft matrix of mainly epsilon-caprolactone moieties and hard domains containing more of L-lactide units thus exhibiting a rubber like elasticity responsible for providing mechanical strength to scaffolds. Microspheres were fabricated by solvent evaporation method and surface modified with P-15, a synthetic analogue of collagen. These were then evaluated for cell adhesion, ECM formation and cell proliferation. Anchorage dependent cell lines LLCPK-1 and L6 were seeded on PLCL microspheres (unmodified surface activated microspheres) and P-15-PLCL microspheres (P-15 modified microspheres). P-15 modified microspheres showed significantly higher cell adhesion and viability than unmodified microspheres. Scanning electron microscopy also revealed copious amount of extra-cellular matrix production by P-15. Initial results of cell culture experiment on two different cell lines suggested that the growth of LLCPK-1 in a 3D environment with P-15 modified microspheres is via spreading and flattening on the surface of scaffold followed by formation of a sheet-like structure while L6 grew in the form of multilayered structures with formation of interparticulate cellular bridges. The 3D moldable nature, combined with modification of surface chemistry with cell adhesion molecules such as P-15 to enhance proliferation of epithelial cells and myoblasts, recommends further investigation of P-15-PLCL microspheres for production of an ideal scaffold for soft tissue engineering.


Efficacy of doxycycline versus azithromycin for the treatment of rectal chlamydia: a systematic review and meta-analysis.
Chlamydia trachomatis infection is the most common sexually transmitted infectious disease and carries a risk of complications. However, the optimal treatment for rectal chlamydial infection remains unclear. To compare the efficacy of doxycycline and azithromycin for the treatment of rectal chlamydia by undertaking a systematic review and meta-analysis of published data. We searched PubMed, EMBASE, Cochrane Library, Web of Science and clinicaltrials.gov databases from inception to 7 July 2021 for randomized controlled trials (RCTs) and observational studies that compared the efficacy of doxycycline and single-dose azithromycin on rectal chlamydia cure rates. Data were synthesized using a random-effects model, and subgroup analysis was conducted. All included studies were conducted in developed countries. Two RCTs and nine observational studies, with a total of 2457 patients, were analysed. Doxycycline had a higher microbiological cure rate than azithromycin (risk ratio = 1.21; 95% CI = 1.15-1.28; P < 0.05). Pooled results from two RCTs also revealed a higher microbiological cure rate for doxycycline than azithromycin (risk ratio = 1.27; 95% CI = 1.20-1.35; P < 0.05). The results remained consistent in subgroups of different study designs, countries and sexes. On the basis of our findings, we recommend doxycycline rather than azithromycin as a first-line treatment for rectal chlamydia in developed countries. More RCTs from developing countries are warranted.


On the mechanism of assembly of the aspartate transcarbamoylase from Escherichia coli.
The mechanism of subunit assembly of aspartate transcarbamoylase from Escherichia coli was studied by following the kinetics of reassociation. The isolated trimetric catalytic subunit (c3) and dimeric regulatory subunit (r2) were mixed together and formation of the dodecameric native enzyme (c6r6) was monitored by measuring changes in activity. Under appropriate conditions the reassociation was second order with respect to the c3 concentration and the effects of varying r2 concentration on the second-order rate constant were examined. An optimum R2 concentration of about 0.07 micrometer was observed. A scheme of the assembly pathways is proposed and is based on the reversible formation of c3r2n (n = 0, 1, 2 or 3) as intermediates. Various combinations of two such c3r2n species are considered as possible rate-limiting steps. This model yields an expression which relates the experimentally determined (overall) second-order rate constant to the equilibrium constant (Kd) governing the formation of c3r2n, the r2 concentration, and four coefficients which reflect the contribution of different types of assembly processes. Using previously determined values of Kd, the above expression for each r2 concentration reduces to a linear equation with four unknowns. The experimental data were subjected to multiple linear-regression analysis and values for the four coefficients were found which gave an excellent fit. Our results show that reassociation of the subunits is a fast bimolecular reaction with rate constants in excess of 10(6) M-1 s-1. Our analysis also suggests that interactions involving a total of more than three r2 subunits (e.g. the combination of c3r2 with c3r6) might contribute significantly to the overall assembly. The influence of various ligands on the reassociation rate profile was also studied. All ligands examined were partially inhibitory to the formation of native enzyme. The effects of substrates were similar to those of CTP whereas the effects of ATP were substantially different. These observations can be readily interpreted by postulating different conformational changes induced by the ligands. These changes should alter the relative orientation of the subunit contacts which must be formed in the reassociation process. The interpretation is consistent with our previous model of the allosteric mechanism.


Quantitative structure activity relationships (QSARs) and machine learning models for abiotic reduction of organic compounds by an aqueous Fe(II) complex.
Due to the increasing diversity of organic contaminants discharged into anoxic water environments, reactivity prediction is necessary for chemical persistence evaluation for water treatment and risk assessment purposes. Almost all quantitative structure activity relationships (QSARs) that describe rates of contaminant transformation apply only to narrowly-defined, relatively homogenous families of reactants (e.g., dechlorination of alkyl halides). In this work, we develop predictive models for abiotic reduction of 60 organic compounds with diverse reducible functional groups, including nitroaromatic compounds (NACs), aliphatic nitro-compounds (ANCs), aromatic N-oxides (ANOs), isoxazoles (ISXs), polyhalogenated alkanes (PHAs), sulfoxides and sulfones (SOs), and others. Rate constants for their reduction were measured using a model reductant system, Fe(II)-tiron. Qualitatively, the rates followed the order NACs > ANOs ≈ ISXs ≈ PHAs > ANCs > SOs. To develop QSARs, both conventional chemical descriptor-based and machine learning (ML)-based approaches were investigated. Conventional univariate QSARs based on a molecular descriptor ELUMO (energy of the lowest-unoccupied molecular orbital) gave good correlations within classes. Multivariate QSARs combining ELUMO with Abraham descriptors for physico-chemical properties gave slightly improved correlations within classes for NCs and NACs, but little improvement in correlation within other classes or among classes. The ML model obtained covers reduction rates for all classes of compounds and all of the conditions studied with the prediction accuracy similar to those of the conventional QSARs for individual classes (r2 = 0.41-0.98 for univariate QSARs, 0.71-0.94 for multivariate QSARs, and 0.83 for the ML model). Both approaches required a scheme for a priori classification of the compounds for model training. This work offers two alternative modeling approaches to comprehensive abiotic reactivity prediction for persistence evaluation of organic compounds in anoxic water environments.


Receptor-mediated endocytosis of biofilm-forming Enterococcus faecalis by rat peritoneal macrophages.
Enterococci are important nosocomial pathogens that are increasingly difficult to treat due to intrinsic and acquired resistance to antibiotics. Studies were taken up to identify virulence factors and to characterise pathogenic mechanisms of such infections to evaluate potential targets for treatments alternative to antibiotic therapy. This study was carried out to evaluate the contribution of extracellular polysaccharide expressed by Enterococcus faecalis to resistance to phagocytosis and survival within rat peritoneal macrophages. Six E. faecalis clinical isolates were tested for their ability to survive within rat peritoneal macrophages. Cytochalasin D, colchicine and monodansylcadaverine were used to investigate the route of enterococcal entry inside macrophages. Four of the isolates were able to produce extracellular polysaccharide and form biofilm after growth in glucose-supplemented medium, while no production could be detected in glucose deficient medium. Two isolates were polysaccharide-negative in both conditions. Isolates expressing extracellular polysaccharide were able to survive for more than 24 h compared to polysaccharide-negative bacterial cells of the same strain grown in glucose-deficient medium, which were readily cleared. Cytochalasin D virtually abolished the number of viable intracellular bacteria, after growth in either trypticase soy broth (TSB) or TSB supplemented with glucose; colchicine and monodansylcadaverine strongly affected survival of polysaccharide-positive bacteria, significantly more than that of polysaccharide-negative ones. Biofilm-forming E. faecalis survived within rat peritoneal macrophages significantly better than polysaccharide-negative isolates. Perturbators of cytoskeleton and of surface receptors turnover, indicated receptors-mediated endocytosis as the most likely route for enterococcal entry into macrophages.


Creating a Box-Cavity Defect Model in the Cortical Bone of Rat Femora.
Severe bone defects or complex fractures can result in serious complications such as nonunion or insufficient bone healing. Tissue engineering, which involves the application of cells, scaffolds, and cytokines, is considered a promising solution for bone regeneration. Consequently, various animal models that simulate bone defects play a crucial role in exploring the therapeutic potential of tissue engineering for bone healing. In this study, we established a box-shaped cortical bone defect model in the mid-femur of rats, which could serve as an ideal model for assessing the function of biomaterials in promoting bone healing. This box-shaped cortical bone defect was drilled using an oral low-speed handpiece and shaped by a lathe needle. Post-operative micro-CT analysis was immediately conducted to confirm the successful establishment of the box-cavity cortical bone defect. The femurs on the operated side of the rats were then harvested at multiple time points post-surgery (0 days, 2 weeks, 4 weeks, and 6 weeks). The healing process of each sample's defect area was evaluated using micro-CT, hematoxylin and eosin (H&E) staining, and Masson trichrome staining. These results demonstrated a healing pattern consistent with intramembranous ossification, with healing essentially complete by 6 weeks. The categorization of this animal model's healing process provides an effective in vivo method for investigating novel biomaterials and drugs that target intramembranous ossification during bone tissue defect healing.


[Clinical-morphological aspects in the diagnosis of microcarcinoma of the thyroid gland].
Retrospective analysis of clinical and morphological diagnosis of papillary microcarcinoma (PMC) of the thyroid gland in 202 patients is presented. Frequent concurrence of the tumor with different kinds of thyroid pathology, the tendency for multifocal spread are noted. The authors have tried to find out a correlation between the PMC morphological features and clinical signs.


[Research progress on the treatment improvement of HPV-associated oropharyngeal cancer].
The number of new cases of oropharyngeal cancer is increasing year by year among the world, and HPV infection is one of the risk factors for this malignant tumor. Compared with HPV-negative oropharyngeal cancer, HPV-positive patients are more sensitive to radiotherapy and have a better prognosis, but there is no accepted treatment for HPV-positive patients. Reducing treatment intensity moderately and exploring the best option to minimize side effects of treatment are urgent issues to be addressed. This article reviews the research progress on the treatment improvement of HPV-associated oropharyngeal cancer in recent years.


Inhibition of nocturnal gastric secretion in normal human volunteers by misoprostol: a synthetic prostaglandin E1 methyl ester analog.
Misoprostol (SC-29333) is a synthetic prostaglandin E1 analog that has been found to be a potent inhibitor of gastric secretion in animals. Nocturnal gastric antisecretory activity of misoprostol, in tablet form, was studied in 16 adult volunteers, under basal condition. The study was a randomized, double-blind, cross-over, comparison of placebo, and three graded doses of misoprostol (50, 100, and 200 micrograms). Misoprostol exhibited a statistically significant inhibition of total acid output only at the 200 micrograms dose and this inhibition was maintained for 3 h postadministration of the drug. The antisecretory effects of misoprostol were characterized by suppression of H+ ion but not of the volume of gastric secretion. No untoward effects were noted in the volunteers. As a consequence of the gastric antisecretory effects, the present studies indicate that misoprostol is a promising therapeutic agent for the treatment of peptic ulcer.


Point estimate and reference normality interval of MRI-derived myocardial extracellular volume in healthy subjects: a systematic review and meta-analysis.
To estimate the MRI-derived myocardial extracellular volume (ECV) in healthy subjects together with reference normality interval. The study was registered on PROSPERO and reported according to PRISMA. In October 2017, a systematic search (MEDLINE/EMBASE) was performed for articles reporting MRI-derived ECV in healthy subjects. The pooled ECV (pECV) with 95% confidence interval (CI) was calculated using the random-effect model; the normality interval was calculated as pECV ± 2 root mean square of all study standard deviations. The Newcastle-Ottawa scale was used for assessing study quality, subgroup/meta-regression analyses for technical/biological covariates, and Egger test for publication bias risk. Of 282 articles, 56 were analyzed totaling 1851 subjects with age 16-68 years, body mass index 23-28 kg/m2, and left ventricular ejection fraction 58-74%. Contrast dose varied from 0.075 to 0.200 mmol/kg. Heterogeneity was high (I2 = 92%). The pECV was 25.6% (95% CI 25.2-26.0%) with a normality interval of 19.6-31.6%. pECV was slightly increasing with age (β = 0.03%, p = 0.038) and slightly decreasing with the percentage of males (β = - 0.02%, p = 0.053). Sequence type significantly (p = 0.003) impacted on pECV: the normal interval was 19.9-31.9% for MOLLI and 20.3-33.5% for ShMOLLI. Contrast type/dose, time of acquisition, and magnetic field strength did not significantly impact pECV (p > 0.093). Quality was moderate or high in 48/56 studies (86%). No risk of publication bias (p = 0.728). Myocardial pECV in healthy subjects was 25.6%, increasing by 0.03% for each year of age. The ECV normality interval was 19.9-31.9% for MOLLI and 20.3-33.5% for ShMOLLI. • The pooled estimate of normal MRI-derived ECV based on 1851 subjects was 25.6%, slightly increasing with age and slightly decreasing with the percentage of males. • MRI-derived ECV was independent of contrast type/dose and field strength but dependent on the imaging sequence. • The modeled normality reference interval of MRI-derived ECV was 19.9-31.9% for the MOLLI sequence and 20.3-33.5% for the ShMOLLI sequence.


Long-term results of aortic valve replacement with nonviable homografts.
Between 1965 and 1972, 250 patients (186 men and 64 women; median age, 48 years) underwent aortic valve replacement with homografts preserved with beta-propiolactone (98 patients) or irradiation (152 patients); operative mortality was 6% (15 patients). Follow-up to death, reoperation, or recent evaluation was completed in 95% of patients, and median follow-up time was 11.4 years. Thromboembolic events occurred in two patients (0.21 events/100 patients/yr). Risk of reoperation was 22% at 5 years, 62% at 10 years, 85% at 15 years, and 95% at 20 years. Factors associated with increased risk of reoperation were young age, male sex, native aortic valve insufficiency, previous aortic valve surgery, history of endocarditis, and larger homograft size. Survival at 5, 10, 15, and 20 years was 85%, 66%, 53%, and 38%, respectively. Late survival was diminished in older patients and those with native aortic valve insufficiency and coronary artery disease. Aortic valve replacement with nonviable homografts has a high risk of late tissue degeneration and need for reoperation. However, the incidence of thromboemboli is minimal, and grafts can be replaced with low risk (4.5%) so that overall patient survival is similar to that observed with other bioprosthetic or mechanical heart valves.


Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort.
Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 μg/kg) above the spline knot of 0.50 μg/kg was associated with reduced birth weight (B: -191 g; 95% CI: -315, -68) and length (-0.67 cm; -1.2, -0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 μg/kg, mainly MeHg) above 1.0 μg/kg, was associated with decreased birth weight (-59 g; -115, -3.0), and length (-0.29 cm; -0.54, -0.047). Maternal Pb (median 11 μg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.


Nasal mucociliary transport in pregnancy.
Using the saccharin method, we performed tests of mucociliary function four times during pregnancy and once one month after delivery in 27 women. As the transport distance for saccharin varied from 37 to 65 mm, we used the transport speed for evaluation. Pregnancy rhinitis affects at least 20% of pregnancies. The mucociliary transport speed was higher in the group of women with pregnancy rhinitis, and was reduced during pregnancy in the group of women without that condition. We found no significant correlation between mucociliary transport speed and objectively registered nasal peak expiratory flow index. The pathophysiology of pregnancy rhinitis is not known, but is possibly multifactorial. The changes occurring in the nasal mucociliary transport system during normal pregnancy and in pregnancy rhinitis need further studies.


Dual Career of the U-23 Spanish Canoeing Team.
Canoeing is one of the sport disciplines that brings great success to Spain in international competitions and Olympic Games (of the 17 medals won in Rio in 2016, four were in this sport, including three gold). However, the journey to become an elite athlete coincides in time with the challenge of pursuing an academic education, which often involves making difficult choices in the training-university dichotomy. The aim of this research was to ascertain how the Spanish under-23 calm water canoeing team perceives their athletic and academic careers. The present study was carried out with the Spanish under-23 flat water canoeing team, the step prior to competition at the highest level. The study sample comprised the whole population, namely the entire national team, made up of 21 athletes (11 women and 10 men) with a mean age of 20.57 ± 2.64 years and 10.00 ± 3.49 years of experience. These athletes are usually based at La Cartuja High Performance Center (Seville) and combine their sports activity with studying toward a university degree. A double qualitative and quantitative methodology was used. For the first of these, an interview script was elaborated based on the theoretical model by Wylleman et al. (2013). Applicable consents were requested from the Spanish Royal Canoeing Federation, coaches and paddlers. Interviews were carried out with each athlete twice: at the beginning and at the end of the season/academic year, which were recorded and subsequently tabulated and analyzed. Concerning quantitative methodology, the ESTPORT dual career questionnaire validated by Sánchez-Pato et al. (2016) was used. The results show that for all the paddlers canoeing is very important. It is typically complicated for them to attend classes, and subject planning is usually based on their training schedules. In the second/last part of the course, it is stressful for these athletes to combine both activities and some drop out of school. During the course, though, they appreciate having another activity that allows them to escape from the training routine. In addition, they miss not having an academic tutor to guide and advise them. These student-athletes are aware that their sport causes them to miss out on many moments with family and friends due to training or competing. However, at present this is offset, largely because of their high level of performance, which makes it easier for them to obtain scholarships that provide economic support.


The role of norepinephrine in the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's disease.
The role of noradrenergic neurotransmission in normal cognitive functions has been extensively investigated, however, the involvement of noradrenergic functions in the cognitive impairment associated with schizophrenia and Alzheimer's disease has not been as intensively considered. The limited ability of atypical antipsychotics to treat the cognitive impairment of schizophrenia, and cholinomimetics to treat the cognitive impairment of Alzheimer's disease, may be related to the influence of a multiplicity of neurotransmitter abnormalities including noradrenergic dysfunction, which these treatments do not address. The evidence of noradrenergic dysfunction occurring concomitantly with dopamine dysfunction in schizophrenia and acetylcholine dysfunction in Alzheimer's disease supports therapeutic approaches using noradrenergic drugs in combination with neuroleptics and cholinesterase inhibitors, respectively, to enhance the treatment of cognitive impairment. Given the results of animal and human studies, it appears that alpha-2A agonists may be the optimal choice for this purpose.


The significance of renewable energy use for economic output and environmental protection: evidence from the Next 11 developing economies.
Increasing economic activities in developing economies raise demand for energy mainly sourced from conventional sources. The consumption of more conventional energy will have a significant negative impact on the environment. Therefore, attention of policy makers has recently shifted towards the promotion of renewable energy generation and uses across economic activities to ensure low carbon economy. Given the recent scenario, in this paper, we aim to examine the role of renewable energy consumption on the economic output and CO2 emissions of the next fastest developing economies of the world. The study employs several robust panel econometric models by using annual data from 1990 to 2012. Empirical findings confirm the significant long-run association among the variables. Similarly, results show that renewable energy consumption positively contributes to economic output and has an adverse effect on CO2 emissions. Given our findings, we suggest policy makers of those economies to initiate further effective policies to promote more renewable energy generation and uses across economic activities to ensure sustainable economic development.


Induction and regulation of crown dentinogenesis: embryonic events as a template for dental tissue repair?
Close regulation of odontoblast differentiation and subsequent secretory activity is critical for dentinogenesis during both embryogenesis and tissue repair. Some dental papilla cells achieve commitment and specific competence, allowing them to respond to epithelially derived inductive signals during the process of odontoblast differentiation. Temporo-spatial regulation of odontoblast differentiation is dependent on matrix-mediated interactions involving the basement membrane (BM). Experimental studies have highlighted the possible roles of growth factors in these processes. Regulation of functional activity of odontoblasts allows for both ordered secretion of the primary dentin matrix and maintenance of vitality and down-regulation of secretory activity throughout secondary dentinogenesis. After injury to the mature tooth, the fate of the odontoblast can vary according to the intensity of the injury. Milder injury can result in up-regulation of functional activity leading to focal secretion of a reactionary dentin matrix, while greater injury can lead to odontoblast cell death. Induction of differentiation of a new generation of odontoblast-like cells can then lead to reparative dentinogenesis. Many similarities exist between development and repair, including matrix-mediation of the cellular processes and the apparent involvement of growth factors as signaling molecules despite the absence of epithelium during repair. While some of the molecular mediators appear to be common to these processes, the close regulation of primary dentinogenesis may be less ordered during tertiary dentinogenic responses.


In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens.
Amphetamine is known to increase dopamine (DA) release by acting directly on dopamine transporters (DAT), primarily through a mechanism that is independent of impulse flow. We present evidence to show that impulse-dependent increase in DA outflow in the nucleus accumbens (NAc) is produced by amphetamine depending on genetic background. Systemic amphetamine produced higher accumbal DA release in the widely exploited C57BL/6J background than in the DBA/2J. By contrast, intra-accumbens perfusion using increasing doses of amphetamine dramatically increased DA outflow in the DBA/2J background, whereas very low DA outflow was evident in C57BL/6J mice. The fast sodium channel blocker tetrodotoxin infused through the microdialysis probe abolished accumbal DA release induced by systemic amphetamine only in the C57BL/6J background. Finally, medial prefrontal excitotoxic lesion abolished amphetamine-induced mesoaccumbens DA release in C57BL/6J mice, without significantly affecting it in the DBA/2J background. These results represent the first functional evidence in an in vivo study that amphetamine can increase DA release in the NAc mainly through an impulse-dependent mechanism regulated by prefronto-cortical glutamatergic transmission. Moreover, they point to a genetic control of impulse-dependent DA release in the accumbens, providing an exploitable tool to investigate aetiological factors involved in psychopathology and drug addiction.


Recent advances in studies on milk oligosaccharides of cows and other domestic farm animals.
Human mature milk and colostrum contain 12-13 g/L and 22-24 g/L of milk oligosaccharides respectively, and the structures of least 115 human milk oligosaccharides (HMOs) have been characterized to date. By way of comparison, bovine colostrum collected immediately post partum contains only around 1 g/L of oligosaccharides, and this concentration rapidly decreases after 48 h. It was recently recognized that HMOs have several biological functions, and this study area has become very active, as illustrated by a recent symposium, but it appears that advances in studies on the milk oligosaccharides of domestic farm animals, including cows, have been rather slow compared with those on HMOs. Nevertheless, studies on bovine milk oligosaccharides (BMOs) have progressed recently, especially in regard to structural characterization, with the development of methods termed glycomics. This review is concerned with recent progress in studies on the milk oligosaccharides of domestic farm animals, especially of BMOs and bovine glycoproteins, and it discusses the possibility of industrial utilization in the near future.


Bosentan for patients with steroid-resistant pulmonary sarcoidosis: a randomised controlled trial.
Sarcoidosis is a disorder of unknown aetiology. Most patients have steroid-responsive disease, but side effects and steroid resistance may necessitate alternative treatments. Endothelin has in-vitro fibrogenic activity and the endothelin system is activated in sarcoidosis. We studied the efficacy and safety of the endothelin receptor antagonist bosentan in sarcoidosis patients. In a prospective 12-month, double-blind, 1:1-randomised, placebo-controlled phase II trial, we assessed the effect of bosentan in patients with steroid-resistant sarcoidosis and with impaired exercise capacity and/or resting lung function. Primary endpoints were safety and overall response rate of total lung capacity, diffusion capacity, peak oxygen uptake, 6-minute walking distance and chest computed tomography score. Secondary endpoints included adverse events and quality of life. Twenty patients were randomised. Three patients discontinued the study medication prematurely. No serious drug-related adverse events occurred. At 12 months no statistically significant differences were observed in the primary endpoints including total lung capacity, diffusion capacity, 6-minute walking distance, peak oxygen uptake, and computed tomography-score. Sixty-three percent of the patients treated with bosentan showed an increase of 10% in at least one of the primary endpoints, compared with 67% in the placebo group (p = 1). There is no evidence to support efficacy of bosentan as an antifibrotic treatment for patients with steroid-resistant pulmonary sarcoidosis. Bosentan was well tolerated and no drug-related adverse effects were observed within the study population. ISRCTN registry, ISRCTN73579020.