Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis.
Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X(1), P2X(2), P2X(3), P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and P2Y(4) are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2X(2), P2X(1)) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X(1) expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.


Reversal of deficits in aged skeletal muscle during disuse and recovery in response to treatment with a secrotome product derived from partially differentiated human pluripotent stem cells.
Aged individuals are at risk to experience slow and incomplete muscle recovery following periods of disuse atrophy. While several therapies have been employed to mitigate muscle mass loss during disuse and improve recovery, few have proven effective at both. Therefore, the purpose of this study was to examine the effectiveness of a uniquely developed secretome product (STEM) on aged skeletal muscle mass and function during disuse and recovery. Aged (22 months) male C57BL/6 were divided into PBS or STEM treatment (n = 30). Mice within each treatment were assigned to either ambulatory control (CON; 14 days of normal cage ambulation), 14 days of hindlimb unloading (HU), or 14 days of hindlimb unloading followed by 7 days of recovery (recovery). Mice were given an intramuscular delivery into the hindlimb muscle of either PBS or STEM every other day for the duration of their respective treatment group. We found that STEM-treated mice compared to PBS had greater soleus muscle mass, fiber cross-sectional area (CSA), and grip strength during CON and recovery experimental conditions and less muscle atrophy and weakness during HU. Muscle CD68 +, CD11b + and CD163 + macrophages were more abundant in STEM-treated CON mice compared to PBS, while only CD68 + and CD11b + macrophages were more abundant during HU and recovery conditions with STEM treatment. Moreover, STEM-treated mice had lower collagen IV and higher Pax7 + cell content compared to PBS across all experimental conditions. As a follow-up to examine the cell autonomous role of STEM on muscle, C2C12 myotubes were given STEM or horse serum media to examine myotube fusion/size and effects on muscle transcriptional networks. STEM-treated C2C12 myotubes were larger and had a higher fusion index and were related to elevated expression of transcripts associated with extracellular matrix remodeling. Our results demonstrate that STEM is a unique cocktail that possesses potent immunomodulatory and cytoskeletal remodeling properties that may have translational potential to improve skeletal muscle across a variety of conditions that adversely effect aging muscle.


Fifth-order susceptibility unveils growth of thermodynamic amorphous order in glass-formers.
Glasses are ubiquitous in daily life and technology. However, the microscopic mechanisms generating this state of matter remain subject to debate: Glasses are considered either as merely hyperviscous liquids or as resulting from a genuine thermodynamic phase transition toward a rigid state. We show that third- and fifth-order susceptibilities provide a definite answer to this long-standing controversy. Performing the corresponding high-precision nonlinear dielectric experiments for supercooled glycerol and propylene carbonate, we find strong support for theories based on thermodynamic amorphous order. Moreover, when lowering temperature, we find that the growing transient domains are compact--that is, their fractal dimension d(f) = 3. The glass transition may thus represent a class of critical phenomena different from canonical second-order phase transitions for which d(f) < 3.


Health Inequalities.
Health inequalities are embedded in a complex array of social, political, and economic inequalities. Responding to health inequalities will require systematic action targeting all the underlying ("upstream") social determinants that powerfully affect health and well-being. Systemic inequalities are a major reason for the rise of modern populism that has deeply divided polities and infected politics, perhaps nowhere more so than in the United States. Concerted action to mitigate shocking levels of inequality could be a powerful antidote to nationalist populism. A basic yet critical start to addressing health inequalities is to recognize them, which demands improving data collection and analysis. Certainly, global indicators show vast progress in reducing poverty and extending life. Yet aggregate health data mask a deeper reality: health gains have disproportionately benefited the well-off, leaving the poor and middle-class behind.


Biosynthesis and characterization of lipid-linked sugars and glycoproteins in aorta.
A particulate enzyme from bovine aorta catalyzes the incorporation of mannose from GDP-D-[14C]mannose into three products as follows: 1. Most of the radioactivity which is incorporated in short term incubations is into a product that is soluble in CHCl3/CH3OH (2/1, v/v). This product was purified by chromatography on DEAE-cellulose and Sephadex LH-20. The purified glycolipid was stable to alkaline saponification but released [14C]mannose when subjected to mild acid hydrolysis (1/2 = 7 min at 100 degrees in 0.01 N HCl). The purified glycolipid had the same mobility on silica gel plates in an acidic, basic, or neutral solvent system as did glycolipid had the same mobility on silica gel plates in an acidic, basic, or neutral solvent system as did authentic dolichyl mannopyranosyl phosphate. The synthesis of the 14C-mannolipid was reversed by the addition of GDP and Mg2+. 2. [14C]mannose is also incorporated, although at a slower rate into products which are soluble in CHCl3/CH3OH/H2O (1/1/0.3, v/v). When the 1/10.3 soluble material was chromatographed on Avicel plates, it gave rise to three distinct radioactive bands which appear to be lipid-linked oligosaccharides. Mild acid hydrolysis of the 1/10.3 soluble material released water-soluble, neutral 14C-oligosaccharides which eluted from Sephadex G-50 in two or three peaks between the standards cytochrome c and GDP-mannose...


Potential application of spice and herb extracts as natural preservatives in cheese.
This study investigated the antibacterial efficiency of five spice and herb extracts (cinnamon stick, oregano, clove, pomegranate peel, and grape seed) against Listeria monocytogenes, Staphylococcus aureus, and Salmonella enterica in cheese at room temperature (~ 23°C). The lipid oxidation (thiobarbituric acid-reactive substances) of cheese was periodically tested by oxidative analyses. The results showed that all five plant extracts were effective against three foodborne pathogens in cheese. Treatments with these extracts increased the stability of cheese against lipid oxidation. Clove showed the highest antibacterial and antioxidant activity. The reduction of foodborne pathogen numbers and the inhibition of lipid oxidation in cheese indicated that the extracts of these plants (especially clove) have potential as natural food preservatives.


The owner-animal-environment triad in the treatment of canine periodontal disease.
In a perfect world, all veterinarians and veterinary dental technicians would understand periodontal disease as well as the dental specialist. They would all be able to recognize the early signs of periodontal disease and recommend treatment to prevent its progression. The owners would have the financial resources, time, and desire to maintain their pet's oral health. The dogs would all be calm and compliant with home care and have no particular anesthetic risks. Unfortunately, this is not a perfect world. Some veterinarians do not understand periodontal disease any better that I understand cosmic string theory. Some owners have limited financial resources and are not particularly committed to their pet's oral health. Some animals will not tolerate any type or manner of home care. Given that animals, their mouths, and their owners come in an infinite variety of shapes and sizes (figuratively and literally), how can we talk about the treatment of periodontal disease as if it is a single condition with a single treatment, or even only a few treatment options? Each owner, animal, and its environment must be assessed on an individual basis to develop a treatment plan that is reasonable and attainable based on the unique circumstances of each case. So, what should be the goal when treating periodontal disease? Is it the preservation of all teeth at all costs? Is it the preservation of important teeth if the costs can be kept reasonable? I would suggest that the overriding goal of periodontal treatment should be the elimination and prevention of oral infection and oral pain. In the domestic environment, dogs have no real need to defend territory. They have no need to prehend and kill live prey animals. In short, the domesticated pet dog does not need teeth at all. This may seem like an odd statement for a veterinary dentist to make, but I feel quite strongly that a dog is far better off having no teeth than having bad teeth. My preference is that a dog should have a full set of healthy, functional teeth, but preserving bad teeth in the face of a poor or questionable prognosis serves no positive purpose.


Important Topics for Fostering Research Integrity by Research Performing and Research Funding Organizations: A Delphi Consensus Study.
To foster research integrity (RI), it is necessary to address the institutional and system-of-science factors that influence researchers' behavior. Consequently, research performing and research funding organizations (RPOs and RFOs) could develop comprehensive RI policies outlining the concrete steps they will take to foster RI. So far, there is no consensus on which topics are important to address in RI policies. Therefore, we conducted a three round Delphi survey study to explore which RI topics to address in institutional RI policies by seeking consensus from research policy experts and institutional leaders. A total of 68 RPO and 52 RFO experts, representing different disciplines, countries and genders, completed one, two or all rounds of the study. There was consensus among the experts on the importance of 12 RI topics for RPOs and 11 for RFOs. The topics that ranked highest for RPOs concerned education and training, supervision and mentoring, dealing with RI breaches, and supporting a responsible research process (e.g. through quality assurance). The highest ranked RFO topics concerned dealing with breaches of RI, conflicts of interest, and setting expectations on RPOs (e.g. about educating researchers about RI). Together with the research policy experts and institutional leaders, we developed a comprehensive overview of topics important for inclusion in the RI policies of RPOs and RFOs. The topics reflect preference for a preventative approach to RI, coupled with procedures for dealing with RI breaches. RPOs and RFOs should address each of these topics in order to support researchers in conducting responsible research.


Clinical, histopathological, and in silico pathogenicity analyses in a pedigree with familial amyloidosis of the Finnish type (Meretoja syndrome) caused by a novel gelsolin mutation.
Familial amyloidosis of the Finnish type (FAF) is an inherited amyloidosis arising from mutations in the gelsolin protein (GSN). The disease includes facial paralysis, loose skin, and lattice corneal dystrophy. To date, FAF has been invariably associated with substitution of Asp214 in GSN. We describe the clinical, histopathological, and genetic features of a family with FAF due to a novel GSN mutation. Five affected adult individuals in a three-generation FAF pedigree were included in the study. Histopathological analysis was performed on an eyelid skin biopsy from one patient. Genetic analysis included next-generation sequencing (NGS) and Sanger sequencing for confirmation of the GSN variant. Several tools for in silico analysis of pathogenicity for the novel variant and to predict the effect of the amino acid replacement on protein stability were used. Three older adult affected patients exhibited corneal lattice dystrophy, cutis laxa, and facultative peripheral neuropathy. Two younger adult individuals presented only with corneal amyloid deposits. NGS identified a heterozygous GSN c.1631T>G transversion, predicting a novel p.Met544Arg mutation. All in silico tools indicated that p.Met544Arg is deleterious for GSN functionality or stability. The results expand the molecular spectrum of GSN-linked systemic amyloidosis. The novel p.Met544Arg pathogenic variant is predicted to affect gelsolin function, presumably by impairing a potential calcium-sensitive, actin-binding region.


Piperazine ferulate ameliorates the development of diabetic nephropathy by regulating endothelial nitric oxide synthase.
Diabetic nephropathy (DN) is among the most common complications of diabetes mellitus. The disorder is associated with a decrease in the activity of the nitric oxide synthase/nitric oxide system. Piperazine ferulate (PF) is widely used for the treatment of kidney disease in China. The aim of the present study was to examine the effects of PF on streptozotocin (STZ)‑induced DN and the underlying mechanism of this process. STZ‑induced diabetic mice were intragastrically administered PF (100, 200 and 400 mg/kg/body weight/day) for 12 weeks. At the end of the treatment period, the parameters of 24‑h albuminuria and blood urea nitrogen, creatinine and oxidative stress levels were measured. Hematoxylin and eosin staining, periodic acid‑Schiff staining and electron microscopy were used to evaluate the histopathological alterations. mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were measured by quantitative polymerase chain reaction and western blotting, respectively. PF significantly decreased blood urea nitrogen and creatinine levels and 24‑h albuminuria, and it alleviated oxidative stress, improved glomerular basement membrane thickness and caused an upregulation in eNOS expression and activity levels in diabetic mice. In addition, high glucose decreased eNOS expression levels, whereas PF caused a reversal in the nitric oxide (NO) levels of glomerular endothelial cells. The present results suggested that PF exhibited renoprotective effects on DN. The mechanism of its action was associated with the regulation of eNOS expression and activity.


Tracing odor-induced activation in the olfactory bulbs of mice using manganese-enhanced magnetic resonance imaging.
Ithas previously been demonstrated that it is possible to map active regions of the brain using MRI relying on the fact that Mn(2+) ion enters excitable cells through voltage-gated calcium channels and is an excellent relaxation agent. In addition, Mn(2+) has been shown to trace neuronal connections in the mouse olfactory and visual systems, enabling MRI neuronal tract tracing. The purpose of the present studies was to determine if these two properties could be combined to trace Mn(2+) from sites of activation in the olfactory epithelium to the olfactory bulb thereby localizing regions within the olfactory bulb that respond to a particular odor. Mice were exposed to an aerosolized solution containing either a high pheromone content odor (male mouse urine) or amyl acetate plus MnCl(2). In both cases the odors caused a localized T(1) MRI enhancement in the olfactory epithelium and bulb that was dependent upon the presence of Mn(2+). The high pheromone containing solution caused enhancement in the anatomically correct location of the accessory olfactory bulb. Amyl acetate also caused T(1)-weighted MRI enhancement in specific regions of the olfactory bulb. These areas showing activation agree well with previous 2-deoxyglucose and BOLD fMRI results in the rat. Using manganese-enhanced MRI (MEMRI) it should be possible to rapidly map a variety of odors. Furthermore, since the effects of activation are imaged after the activation protocol it should be possible to take the time to obtain very high resolution images and make MEMRI maps from awake behaving animals.


The family in the family medicine literature.
The degree to which the family medicine literature articulates unique family practice approaches and perspectives that are distinct from other primary care specialties has not been well studied. To determine how often a family practice perspective is included in clinical articles in the family medicine literature, we performed a family medicine journal review. We reviewed 173 original research articles, review articles, and case reports from four family medicine journals from the year 2000: American Family Physician, Journal of Family Practice, Journal of the American Board of Family Practice, and Archives of Family Medicine. Each article was scored by independent reviewers as to whether the article discussed family aspects of care or family context. A total of 9.3% of clinical articles discussed family aspects of care; an additional 17.3% made some limited mention of the family or social context. Female first authors were 2.5 times more likely to have demonstrated a family practice perspective. Articles published in the American Family Physician and review articles were most likely to discuss family medicine perspectives, but these differences were not statistically significant. Unique family medicine approaches and perspectives are not discussed commonly in clinical articles in the family medicine literature.


Studies on the cell wall of Schizophyllum commune. Permethylation and enzymic hydrolysis.
Two polysaccharide fractions S-glucan were isolated from the cell walls of Schizophyllumcommune. S-Glucan is primarily a linear 1,3-alpha-glucan with occasional 1,6-alphalinkages as shown by permethylation and partial acid hydrolysis. The glucan fraction also contains a small amount of xylose. The R-glucan fraction is a mixture of two polysaccharides, chitin and a highly branched glucan with linear 1,6-beta and 1,3-beta segments and 1,6-beta branching. This conclusion is based on permethylation studies and enzymic hydrolyses.


Update on research-based interventions for anxiety in patients with cancer.
Anxiety may begin at the moment a person is diagnosed with cancer and may fluctuate throughout the cancer trajectory as physical illness improves or declines. The purpose of this article is to present current evidence for nurses to implement interventions to reduce anxiety in patients who have cancer. The PubMed and CINAHL® databases were searched to identify relevant citations addressing interventions that treat or prevent anxiety symptoms in patients with cancer. Based on available evidence, the interventions addressed herein are categorized according to the Putting Evidence Into Practice (PEP®) rating schema. Interventions include pharmacologic and nonpharmacologic approaches to care, and meet criteria for three PEP categories: likely to be effective, effectiveness not established (the largest category of results), or effectiveness unlikely.


Investigation of preconcentration strategies for the trace analysis of multi-residue pesticides in real samples by capillary electrophoresis.
In this work, on-line preconcentration strategies were investigated for the multi-residue analysis of pesticides in drinking water and vegetables using micellar electrokinetic chromatography. Among the on-line strategies, sweeping and stacking with reverse migration of micelles (SRMM), with and without the insertion of a plug of water before sample injection, were contrasted. A new version of SRMM was also introduced. The modification consisted of momentarily applying a positive voltage at the inlet vial right after sample has been injected, increasing the efficiency by which the analytes are captured. Nine pesticides from different classes, carbendazim (benzimidazole), simazine, atrazine, propazine and ametryn (triazine), diuron and linuron (urea), carbaryl and propoxur (carbamate), were baseline separated in less than 6 min with a electrolyte composed of 20 mmol l(-1) phosphate buffer at pH 2.5, containing 25 mmol l(-1) sodium dodecyl sulfate and 10% methanol. Limits of detection (LODs) in the order of 2-46 microg l(-1) for the pesticides under investigation were obtained solely using the on-line strategies. Enrichment factors of 3-18-fold were obtained. These factors were computed as the improvement of the concentration LODs with respect to the reference condition (injection of 10 s at 2.5 kPa pressure). The proposed methodologies were applied to the analysis of pesticides in complex matrices such as carrot extracts where the detection of 2.5 microg l(-1) was illustrated. By combining off-line solid-phase extraction and the proposed on-line strategies, the detection of pesticides in drinking water at the 0.1 microg l(-1) level was conceived.


Digging deep into the pockets of orphan nuclear receptors: insights from structural studies.
Nuclear receptors comprise a large family of proteins that shares a common structure and mechanism of action. Members of this family, first cloned 20 years ago, are regulated by small lipophilic signaling molecules such as steroid hormones, retinoids and thyroid hormone. More recently, the characterization of proteins that resemble nuclear receptors (referred to as orphan receptors) has resulted in the determination of novel signaling pathways. However, many orphan-receptor ligands remain unidentified, and recent structural studies of the binding domains for orphan-receptor ligands suggest that not all of these receptors use ligand binding in a classical way. Notably, it is now evident that some orphan receptors lack the capacity for ligand binding, which suggests that they are regulated by alternative, ligand-independent mechanisms.


Binding Features and Functions of ATG3.
Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related (ATG) genes are indispensable for autophagosome formation. ATG3 is one of the key genes involved in autophagy, and its homologs are common in eukaryotes. During autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, contributing to phagophore elongation. ATG3 has also been found to participate in many physiological and pathological processes in an autophagy-dependent manner, such as tumor occurrence and progression, ischemia-reperfusion injury, clearance of pathogens, and maintenance of organelle homeostasis. Intriguingly, a few studies have recently discovered the autophagy-independent functions of ATG3, including cell differentiation and mitosis. Here, we summarize the current knowledge of ATG3 in autophagosome formation, highlight its binding partners and binding sites, review its autophagy-dependent functions, and provide a brief introduction into its autophagy-independent functions.


Micro-RNA Binding Site Polymorphisms in the WFS1 Gene Are Risk Factors of Diabetes Mellitus.
The absolute or relative lack of insulin is the key factor in the pathogenesis of diabetes mellitus. Although the connection between loss of function mutations of the WFS1 gene and DIDMOAD-syndrome including diabetes mellitus underpins the significance of wolframin in the pathogenesis, exact role of WFS1 polymorphic variants in the development of type 1 and type 2 diabetes has not been discovered yet. In this analysis, 787 patients with diabetes and 900 healthy people participated. Genotyping of the 7 WFS1 SNPs was carried out by TaqMan assays. Association study was performed by χ2-test in combination with correction for multiple testing. For functional analysis, the entire 3' UTR of the WFS1 gene was subcloned in a pMIR-Report plasmid and relative luciferase activities were determined. Linkage disequilibrium analysis showed a generally high LD within the investigated region, however the rs1046322 locus was not in LD with the other SNPs. The two miR-SNPs, rs1046322 and rs9457 showed significant association with T1DM and T2DM, respectively. Haplotype analysis also confirmed the association between the 3' UTR loci and both disease types. In vitro experiments showed that miR-185 reduces the amount of the resulting protein, and rs9457 miRSNP significantly influences the rate of reduction in a luciferase reporter assay. Genetic variants of the WFS1 gene might contribute to the genetic risk of T1DM and T2DM. Furthermore demonstrating the effect of rs9457 in binding of miR-185, we suggest that the optimal level of wolframin protein, potentially influenced by miR-regulation, is crucial in normal beta cell function.


An Examination of Personalized Approaches in the Management of Ankle Fractures: A Thorough Evaluation of Soft Tissue Factors, Treatment Methods, and Patient Adherence.
This study offers a thorough analysis of tibial pilon fractures, accounting for patient compliance, diverse treatment options, and soft tissue implications. The article discusses varied treatment pathways, ranging from single-stage interventions to two-stage methods for open fractures by presenting seven clinical cases. The emphasis is on the intricate interplay of trauma intensity, bone damage, and adjacent soft tissue in dictating treatment plans and patient outcomes. The challenges posed by non-compliant patients rejecting advised treatments are underscored, illuminating the inherent risks. Drawing from varied patient demographics, comorbidities, and fracture types, a comprehensive guide for clinicians emerges. The findings underscore the importance of a tailored, patient-centric approach, considering the multifaceted nature of ankle fractures, local soft tissue health, patient's overall well-being, and their adherence to the proposed treatment regimen.


Assessment and clinical relevance of the dynamic parameters of ventricular repolarization in patients with grade I left ventricular diastolic dysfunction 1.
Imbalance in ventricular repolarization parameters are related to increased risk of severe arrhythmia and sudden cardiac death. There is limited research regarding markers to detect patients at risk in this early stage. We aimed to assess the influence of grade I left ventricular diastolic dysfunction on repolarization parameters in asymptomatic patients. Ambulatory patients with grade I left ventricular diastolic dysfunction were studied and compared with a control group. We assessed the QT dispersion circadian variation, heart rate variability in the time and frequency domains, and dynamics of QT using a 12-lead Holter. In the diastolic dysfunction group, 8 (30%) patients had QT dispersion > 80 ms. One (3.8%) patient presented premature ventricular complex > 10/h. The comparison between the 2 groups showed that the difference between the standard deviation of normal-to-normal intervals and low frequency power in both groups was statistically significant. We therefore conclude that increased parameters of ventricular repolarization and depressed heart rate variability reflect an imbalance in autonomic responses in patients with grade I left ventricular diastolic dysfunction without cardiovascular symptoms, enabling the identification of patients that are at a higher risk for cardiovascular events.


Hospital-sponsored primary care: I. Organizational and financial effects.
Findings are presented from a seven-year (1976-83) evaluation of the Community Hospital Program (CHP), a national demonstration program sponsored by the Robert Wood Johnson Foundation to assist 54 community hospitals in improving the organization of access to primary care. Upon grant expiration, 66 per cent of hospital-sponsored group practices continued under some form of hospital sponsorship; over 90 per cent developed or were planning to develop spin-off programs; and new physicians were recruited and retained in the community. About 9 per cent of hospital admissions were accounted for by group physicians and grantee hospitals experienced a greater annual increase in their market share of admissions than competing hospitals in the area. While only three of the groups generated sufficient revenue to cover expenses during the grant period, 21 additional groups broke even during the first post-grant year. Productivity and cost per visit compared favorably with most other forms of care. Hospitalization rates from the hospital-sponsored practices were somewhat lower than those for other forms of care. Medical director leadership and involvement and the organization design of the practice were among several key factors associated with higher performing practices. The ability of such joint hospital-physician ventures to meet the needs of the poor and elderly in a time of Medicare and Medicaid cutbacks is discussed along with suggestions for targeting future initiatives in primary care.


Validation of a Prediction Model for Vaginal Birth after Cesarean Delivery Reveals Unexpected Success in a Diverse American Population.
Objective To investigate the validity of a prediction model for success of vaginal birth after cesarean delivery (VBAC) in an ethnically diverse population. Methods We performed a retrospective cohort study of women admitted at a single academic institution for a trial of labor after cesarean from May 2007 to January 2015. Individual predicted success rates were calculated using the Maternal-Fetal Medicine Units Network prediction model. Participants were stratified into three probability-of-success groups: low (<35%), moderate (35-65%), and high (>65%). The actual versus predicted success rates were compared. Results In total, 568 women met inclusion criteria. Successful VBAC occurred in 402 (71%), compared with a predicted success rate of 66% (p = 0.016). Actual VBAC success rates were higher than predicted by the model in the low (57 vs. 29%; p < 0.001) and moderate (61 vs. 52%; p = 0.003) groups. In the high probability group, the observed and predicted VBAC rates were the same (79%). Conclusion When the predicted success rate was above 65%, the model was highly accurate. In contrast, for women with predicted success rates <35%, actual VBAC rates were nearly twofold higher in our population, suggesting that they should not be discouraged by a low prediction score.


Comparing the Ecological Stoichiometry in Green and Brown Food Webs - A Review and Meta-analysis of Freshwater Food Webs.
The framework of ecological stoichiometry was developed primarily within the context of "green" autotroph-based food webs. While stoichiometric principles also apply in "brown" detritus-based systems, these systems have been historically understudied and differ from green ones in several important aspects including carbon (C) quality and the nutrient [nitrogen (N) and phosphorus (P)] contents of food resources for consumers. In this paper, we review work over the last decade that has advanced the application of ecological stoichiometry from green to brown food webs, focusing on freshwater ecosystems. We first review three focal areas where green and brown food webs differ: (1) bottom-up controls by light and nutrient availability, (2) stoichiometric constraints on consumer growth and nutritional regulation, and (3) patterns in consumer-driven nutrient dynamics. Our review highlights the need for further study of how light and nutrient availability affect autotroph-heterotroph interactions on detritus and the subsequent effects on consumer feeding and growth. To complement this conceptual review, we formally quantified differences in stoichiometric principles between green and brown food webs using a meta-analysis across feeding studies of freshwater benthic invertebrates. From 257 datasets collated across 46 publications and several unpublished studies, we compared effect sizes (Pearson's r) of resource N:C and P:C on growth, consumption, excretion, and egestion between herbivorous and detritivorous consumers. The meta-analysis revealed that both herbivore and detritivore growth are limited by resource N:C and P:C contents, but effect sizes only among detritivores were significantly above zero. Consumption effect sizes were negative among herbivores but positive for detritivores in the case of both N:C and P:C, indicating distinct compensatory feeding responses across resource stoichiometry gradients. Herbivore P excretion rates responded significantly positively to resource P:C, whereas detritivore N and P excretion did not respond; detritivore N and P egestion responded positively to resource N:C and P:C, respectively. Our meta-analysis highlights resource N and P contents as broadly limiting in brown and green benthic food webs, but indicates contrasting mechanisms of limitation owing to differing consumer regulation. We suggest that green and brown food webs share fundamental stoichiometric principles, while identifying specific differences toward applying ecological stoichiometry across ecosystems.


Application of a nonradioactive pulsed electron source for ion mobility spectrometry.
Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. Common ion mobility spectrometers work by employing a radioactive source to provide electrons with high energy to ionize analytes in a series of chemical reactions. General security as well as regulatory concerns related to radioactivity result in the need for a different ionization source which on the other hand produces ions in a similar manner as a radioactive source since the ion chemistry is well-known. Here we show the application of a novel nonradioactive source that produces spectra similar to those obtained with radioactive tritium sources. Using this source in a pulsed mode offers the additional advantage of selecting certain analytes by their recombination time and thus significantly increasing the selectivity. The successful isolation of a target signal in the presence of contaminants using a pulsed electron beam or more precisely the difference in recombination times will be demonstrated for the case of dimethyl-methylphosphonate (DMMP) showing the potential of this source to reduce the possibility for false-positive detection of corresponding chemical warfare agents (CWA) by IMS.


Clinical use of hematopoietic growth factors in the myelodysplastic syndromes.
Recent advances in the molecular genetics of myelodysplastic syndromes (MDS) have shed new light on the pathogenesis of MDS allowing a better understanding of the defects of differentiation of the transformed clone and suppression of normal hematopoiesis. The clinical hematologist, however, continues to be challenged with the treatment of patients with MDS. Pancytopenia and defective function of neutrophils and platelets lead to a high risk of infectious and hemorrhagic complications. The progression to acute myeloid leukemia adds to morbidity and mortality. Supportive care including red blood cell and platelet transfusions are still the cornerstone of therapeutic management. While prophylactic administration of G-CSF or GM-CSF cannot be recommended, treatment of febrile neutropenia might benefit from administration of G-CSF in addition to antibiotics. Administration of high-dose erythropoietin will improve erythropoiesis in around 20% of the patients, mainly in those with rather preserved erythroid function and no or low transfusion need. Coadministration of erythropoietin with either G-CSF or GM-CSF could increase the response rate. Allogeneic stem cell transplantation still is the only curative treatment and prolongs survival. Intensive chemotherapy for advanced MDS is possible with an acceptably low rate of early death and a complete remission rate between 45% to 60%, while initial results of autologous transplantation are promising.


Acquired Brown's syndrome in a patient with combined lichen sclerosus et atrophicus and morphoea.
A 49-year-old woman with generalised lichen sclerosus et atrophicus and morphoea developed bilateral Brown's syndrome. Some of the skin lesions were in the vicinity of the trochlea. A characteristic feature of morphoea is subcutaneous fibrosis, so we postulate that the cause of the Brown's syndrome was mechanical tethering of the superior oblique tendon by deep subdermal fibrosis. Histopathological diagnosis was made from biopsies of similar lesions on the patient's face.


First report of human infection caused by Curvularia warraberensis, manifesting as invasive sinusitis with intracranial involvement.
Curvularia species are saprophytic dematiaceous fungi commonly isolated from environmental sources. Most often, they are responsible for allergic fungal rhinosinusitis, an intense, allergic inflammatory sinus disease in immunocompetent individuals. Though invasive infections are rare and more commonly observed in immunocompromised patients, recent reports indicate an increasing trend of invasive sinusitis caused by Curvularia species in immunocompetent hosts. Over the past few years, new species of the genus Curvularia are increasingly being recognized as human pathogens. Here, we report the first human infection caused by Curvularia warraberensis, a cryptic species of Curvularia primarily described as an endophyte in Australian grasses. The 33-year-old female presented with chronic invasive sinusitis of the sphenoid and ethmoid sinuses that progressed to involve the pituitary gland, mid-brain, the facial-vestibulocochlear nerve complex, and basilar artery. The patient underwent endoscopic sinus surgery. Histopathology, microscopic examination and culture of biopsy tissues revealed a dematiaceous fungus that was identified as C. warraberensis, based on sequencing the internal transcribed spacer (ITS) and large subunit (LSU) regions of ribosomal DNA. Antifungal susceptibility testing (AFST) showed low minimum inhibitory concentrations (MICs) for amphotericin B (1 µg/mL), itraconazole (0.25 µg/mL) and posaconazole (0.125 µg/mL). Accurate identification and AFST are crucial for making treatment decisions as some Curvularia species demonstrate variable susceptibility to antifungal agents. The patient died despite combined surgical and medical intervention owing to late presentation and delay in initiating antifungal therapy. A high index of suspicion together with an early diagnosis and aggressive treatment may improve the outcome in such cases.


Theoretical study of the nontraditional enol-based photoacidity of firefly oxyluciferin.
A theoretical analysis of the enol-based photoacidity of oxyluciferin in water is presented. The basis for this phenomenon is found to be the hydrogen-bonding network that involves the conjugated photobase of oxyluciferin. The hydrogen-bonding network involving the enolate thiazole moiety is stronger than that of the benzothiazole phenolate moiety. Therefore, enolate oxyluciferin should be stabilized versus the phenolate anion. This difference in strength is attributed to the fact that the thiazole moiety has more potential hydrogen-bond acceptors near the proton donor atom than the benzothiazole moiety. Moreover, the phenol-based excited-state proton transfer leads to a decrease in the hydrogen-bond acceptor potential of the thiazole atoms. The ground-state enol-based acidity of oxyluciferin is also studied. This phenomenon can be explained by stabilization of the enolate anion through strengthening of a bond between water and the nitrogen atom of the thiazole ring, in an enol-based proton-transfer-dependent way.


Renal autotransplantation: an alternative to standard renal revascularization procedures.
From January 1978 through December 1987, 22 patients underwent 23 renal autotransplantation procedures for the treatment of renovascular hypertension through the retroperitoneal approach. The causes of the renal artery stenosis were as follows: atherosclerosis (15), fibromuscular dysplasia (6), and Takayasu's arteritis (1). Indications for renal autotransplantation were as follow: disease extending into the renal artery branches (10), stenosis of multiple renal arteries (6), atherosclerotic aorta in high-risk patients (4), and stenosis of renal artery in children (2). The mean preoperative blood pressure of 205 +/- 6/109 +/- 3 mm Hg decreased significantly to 139 +/- 4/77 +/- 2 mm Hg (p less than 0.001). The serum creatinine decreased significantly from a mean preoperative level of 2.2 +/- 0.8 mg/dl to a mean postoperative level of 1.4 +/- 0.4 mg/dl (p less than 0.05). Eleven patients with preoperative renal dysfunction had a significant decrease in the serum creatinine from a mean preoperative level of 3.4 +/- 0.3 mg/dl to a mean postoperative level of 1.9 +/- 0.2 mg/dl (p less than 0.001). One operative death occurred as a result of myocardial infarction. There were three postoperative complications, none of which affected the ultimate result in blood pressure or renal function. This experience demonstrates that in selected patients, renal autotransplantation is an excellent alternative in the surgical treatment of renovascular hypertension.


Facility-based surveillance for emerging infectious diseases; diagnostic practices in rural West African hospital settings: observations from Ghana.
The aim of this study was to better understand the effectiveness of Integrated Disease Surveillance and Response (IDSR) facility-based surveillance in detecting newly emerging infectious diseases (EIDs) in rural West African settings. A six-month ethnographic study was undertaken in 2012 in the Techiman Municipality of the Brong-Ahafo Region of Ghana, aimed at documenting the trajectories of febrile illness cases of unknown origin occurring within four rural communities. Particular attention was paid to where these trajectories involved the use of formal healthcare facilities and the diagnostic practices that occurred there. Seventy-six participants were enrolled in the study, and 24 complete episodes of illness were documented. While participants routinely used hospital treatment when confronted with enduring or severe illness, the diagnostic process within clinical settings meant that an unusual diagnosis, such as an EID, was unlikely to be considered. Facility-based surveillance is unlikely to be effective in detecting EIDs due to a combination of clinical care practices and the time constraints associated with individual episodes of illness, particularly in the resource-limited settings of rural West Africa, where febrile illness due to malaria is common and specific diagnostic assays are largely unavailable. The success of the 'One Health' approach to EIDs in West Africa is predicated on characterization of accurately diagnosed disease burdens. To this end, we must address inefficiencies in the dominant approaches to EID surveillance and the weaknesses of health systems in the region generally.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'.


Humerus shaft fractures in young children: accident or abuse?
We performed a retrospective review of 34 humerus shaft fractures (HSFs) in children younger than 3 years to determine the frequency of child abuse in young children with this injury. Data were obtained from hospital records (including previous and subsequent emergency, clinic, and inpatient notes), radiographs, and county childprotective services. Cases were reviewed independently by four physicians and were classified as probable abuse, probable not abuse, and indeterminate. Only 18% were classified as probable abuse. The history and findings other than the fracture itself were critical in establishing cause. Neither age nor fracture pattern is pathognomonic of abuse, but suspicion should remain high. A detailed history, complete physical examination, and appropriate radiographic investigation are required in every case either to make the diagnosis of abuse or to avoid the trauma of a false accusation.


Kappa opioids and the modulation of pain.
Pain is a complex sensory experience, involving cognitive factors, environment (setting, society, and culture), experience, and gender and is modulated significantly by the central nervous system (CNS). The mechanisms by which opioid analgesics work are understood, but this class of drugs is not ideal as either an analgesic or anti-hyperalgesic. Accordingly, considerable effort continues to be directed at improved understanding of nociceptor function and development of selective analgesics that do not have the unwanted effects associated with opioid analgesics. The purpose of this paper is to provide a review of the role of KOP receptors in the modulation of pain and highlight several chemotypes currently being explored as peripherally restricted KOP ligands. A growing body of literature has shown that KOP receptors are implicated in a variety of behavioral pain models. Several different classes of peripherally restricted peptidic and nonpeptidic KOP agonists have been identified and show utility in treating painful conditions. The pharmacological profile of KOP agonists in visceral pain models suggest that peripherally restricted KOP agonists are potentially useful for a variety of peripheral pain states. Further, clinical investigation of peripherally restricted KOP agonists will help to clarify the painful conditions where KOP agonists will be most effective.


Crude versus case-mix-adjusted control charts for safety monitoring in thyroid surgery.
Patient-safety monitoring based on health-outcome indicators can lead to misinterpretation of changes in case mix. This study aimed to compare the detection of indicator variations between crude and case-mix-adjusted control charts using data from thyroid surgeries. The study population included each patient who underwent thyroid surgery in a teaching hospital from January 2006 to May 2008. Patient safety was monitored according to two indicators, which are immediately recognisable postoperative complications: recurrent laryngeal nerve palsy and hypocalcaemia. Each indicator was plotted monthly on a p-control chart using exact limits. The weighted κ statistic was calculated to measure the agreement between crude and case-mix-adjusted control charts. We evaluated the outcomes of 1405 thyroidectomies. The overall proportions of immediate recurrent laryngeal nerve palsy and hypocalcaemia were 7.4% and 20.5%, respectively. The proportion of agreement in the detection of indicator variations between the crude and case-mix-adjusted p-charts was 95% (95% CI 85% to 99%). The strength of the agreement was κ = 0.76 (95% CI 0.54 to 0.98). The single special cause of variation that occurred was only detected by the case-mix-adjusted p-chart. There was good agreement in the detection of indicator variations between crude and case-mix-adjusted p-charts. The joint use of crude and adjusted charts seems to be a reasonable approach to increase the accuracy of interpretation of variations in outcome indicators.


[ST segment depression during recovery after treadmill exercise test in stable patients with previous myocardial infarction].
The significance of exercise-induced ST segment depression is well known while limited data are available on the clinical/prognostic power of ST depression occurring only during recovery. Aim of the study was to clarify the clinical/prognostic value of "recovery only" ST depression in stable patients late from myocardial infarction (AMI) and to determine whether the addition of recovery data to exercise parameters improves the interpretation of exercise test. From a population of 766 consecutive patients (mean age: 57.2 +/- 8.6 yrs.; male: 89%) who underwent a Bruce Treadmill test at least 1 year after a Q wave AMI and whose exercise data were prospectively entered in the database of our Institution, 4 different Groups were identified: 1) 99 patients with a negative exercise test; 2) 53 patients with "exercise only" ST depression; 3) 140 patients with "exercise and recovery" ST depression; 4) 31 patients with "recovery only" ST depression. The main clinical and exercise data and a cardiac follow-up (average mean length: 1530 +/- 600 day) were evaluated by one-way analysis of variance, Bonferroni T-test, chi-square, relative risk (RR) with 95% confidence intervals (CI), Kaplan-Meler method and log-rank. Baseline clinical parameters were similar in the 4 Groups except for older age in Group 3 compared to Group 2 (< 0.05) and higher prevalence of anterior AMI in Group 4 compared to others (= 0.004). Patients with exercise and recovery ST depression or with "recovery only" ST depression had significantly less exercise tolerance than patients with negative exercise test or "exercise only" ST depression [exercise duration (< 0.05, Group 1 vs. 3, vs. 4; Group 2 vs. 3), peak rate pressure product (< 0.05), maximal heart rate (< 0.05; Group 1 vs. 2; vs. 3; vs. 4)]. Exercise-induced ST depression was higher and angina was significantly more frequent in patients with exercise and recovery ST depression as well as an high Mark's risk score (< 0.001). Only patients with exercise and recovery ST depression demonstrated significantly higher risk of overall mortality (RR: 1.35, CI: 1.04-1.74), unstable angina (RR: 1.34, CI: 1.09-1.65) or revascularisation procedures (RR: 1.51, CI: 1.25-1.83). Relative risk of patients with "recovery only" ST depression was similar to that of subjects with "exercise only" ST depression. In stable patients with old Q wave AMI, "recovery only" ST depression is rate, but does represent a true sign of ischemia. It could be associated with indirect indexes of worse ventricular function. The prognostical power of "recovery only" ST depression is mild, although similar to that of "exercise only" ST depression. Moreover the presence of ST depression not only during exercise but also during the recovery phase identifies patients with more severe prognosis. Therefore the inclusion of findings from the recovery phase in the analysis of the exercise test could increase the predictive power of the test itself.


Cloning and Partial Characterization of a Cold Shock Domain-Containing Protein Gene from the Dinoflagellate Scrippsiella trochoidea.
CSPs, cold shock domain (CSD) containing proteins, are demonstrated to be involved in low temperature responses and various cellular processes under normal growth conditions. Here, we used the cosmopolitan, toxic, and resting cyst-producing dinoflagellate Scrippsiella trochoidea as a representative harmful algal bloom-forming dinoflagellate to investigate the expression patterns of CSP in vegetative cells in response to temperature shocks and in resting cysts, with an objective to probe the possible function of CSP in dinoflagellates. The full-length cDNA of a CSP gene from S. trochoidea (StCSP) was obtained which has a solely N-terminal CSD with conserved nucleic acids binding motifs. The qPCR results together indicated StCSP expression was not modulated by temperature at the transcriptional level and implied this gene may not be associated with temperature stress responses in S. trochoidea as the gene's name implies. However, we observed significantly higher StCSP transcripts in resting cysts (newly formed and maintained in dormancy for different periods of time) than that observed in vegetative cells (at exponential and stationary stages), indicating StCSP is actively expressed during dormancy of S. trochoidea. Taking together our recent transcriptomic work on S. trochoidea into consideration, we postulate that StCSP may play roles during encystment and cyst dormancy of the species.


Prevalence of HIV testing and associated factors among young men who have sex with men (MSM) in Bangkok, Thailand.
Without the safety and effective vaccine for HIV the HIVvoluntary counseling testing (VCT) has been documented as a central component ofcomprehensive HIV prevention strategies targeting individual risk reduction by modified high risk behaviors. However, the coverage of HIV testing among men who have sex with men (MSM) is suboptimal. Moreove, the information regarding to factors associated with HIV testing among young Thai MSM are limited and not well understood. This study aimed to evaluate the prevalence and factors associated with HIV testing among young MSM in Bangkok, Thailand. A cross-sectional study was conducted in Bangkok. Descriptive statistics were presented with crude- and adjusted-odds ratios with 95% confidence interval and the logistic regression models were used to identify factors associated with prior HIV testing. Fifty-six participants were enrolled into study and 51.8% of men previously had an HIV test. After adjusting for potential confounders, logistic regression revealed that older age was positively associated with HIV testing (AOR = 14.4, 95% CI 1.88-111.22) while perceived at low riskfor HIV infection was inversely association with HIV testing (AOR = 0.1, 95% CI 0.02-0.94). Young MSM in Thailand are at risk for HIV infection and uptake of HIV testing is suboptimal. Understanding the motivators and barriers to HIV testing are essential to planning and improving the effective HIVprevention interventions-relevance to HIV-serostatus.


[Protective effect of TGF-beta-Smads signal-based oxymatrine on myocardial fibrosis induced by acute myocardial infarction in rats].
To study the protective effect of oxymatrine (OMT) on myocardial fibrosis induced by acute myocardial infarction in rats and its effect on TGF-beta-Smads signal pathway. Arteria coronaria ligation-induced acute myocardial infarction model was established in rats. The survived rats were randomly allotted into the model group, 50, 25, 12.5 mg x kg(-1) OMT groups, the 50 mg x kg(-1) captopril group, and the Sham-operated group which was treated as the model group without the arteria coranaria ligation. After 8 weeks of ligation, myocardial fibrosis was detected by HE and Masson staining, and the RT-PCR method were used to detect the expression of mRNA of TGF-beta-Smads signal system. The histopathological examination showed decrease in cardiocytes, deposition of extra-cellular matrix, and increase of collagen contents after 8 weeks of ligation. RT-PCR results showed that mRNA expressions of TGF-beta1, TbetaR1, Smad2, Smad3 and Smad4 significantly increased, but mRNA expression of Smad7 is remarkable lower than the sham-operated group. Treatment with OMT for 8 weeks could remarkably inhibit myocardial fibrosis, decrease mRNA expressions of TGF-beta1, TbetaR1, Smad2, Smad3, and Smad4, and increase mRNA expressions of Smad7. OMT has the inhibitory effect on the experimental myocardial fibrosis induced by AMI in rats. Its mechanism may be closely related to TGF-beta-Smads signal system.


Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells.
Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC. MC were isolated from wild type (WT) and Itga8-/- mice. Latex beads were coated with matrix components. Apoptosis was induced by cisplatin in macrophages and in DiI-stained MC. After coincubation of latex beads or apoptotic cells with MC, the phagocytosis rate was detected in WT and Itga8-/- MC via fluorescence microscopy and FACS analysis. Itga8-/- MC showed reduced phagocytosis of matrix-coated beads and apoptotic cells compared to WT MC. Reduction of stress fibers was observed in Itga8-/- compared to WT MC. Inhibition of cytoskeletal reorganization by inhibition of Rac1 or ROCK during phagocytosis significantly decreased the rate of phagocytosis by WT MC but not by Itga8-/- MC. The expression of Itga8 facilitates phagocytosis in MC, likely mediated by Itga8-cytoskeleton interactions. An impairment of MC phagocytosis might thus contribute to a delayed glomerular regeneration in Itga8-/- mice.


Diversification of transmission modes and the evolution of mutualism.
In order for mutualism to evolve, some force must align the interests of the two interacting partners. Vertical transmission can fill this role, but it is still unknown whether mutualism can be stable when vertically transmitted symbionts can evolve toward horizontal transmission. In this article, we investigate how symbionts' transmission mode and virulence should evolve, depending on the relationship between these two traits. We show that pathogens that reduce their host's fecundity can have more complex evolutionary dynamics than those that increase mortality. In some cases, runaway evolution of virulence can drive the host population extinct. In most cases, evolutionary branching results in the differentiation of avirulent, vertically transmitted symbionts from virulent, contagious pathogens. The population of symbionts then becomes polymorphic, and because the least virulent symbionts are the most frequent, the average virulence of symbionts is much lower than it would be in a monomorphic population. When the link between transmission and virulence results from correlated mutational changes and not from fixed constraints, vertically transmitted symbionts do not simply lose virulence; they evolve toward mutualism. We show that the force that stabilizes mutualism in such situations is the competition for transmission between symbionts.


The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects.
The incretin hormone glucagon-like peptide-1 (GLP-1) is capable of ameliorating glucose-dependent insulin secretion in subjects with diabetes. However, its very short half-life (1.5-5 min) in plasma represents a major limitation for its use in the clinical setting. The present study was designed to characterize the duration of the effect of GLP-1 in the Zucker diabetic fatty (ZDF) rat. ZDF rats were subjected to a 48 h infusion of human GLP-1 (30 pmol/kg per min), followed by an i.p. glucose tolerance test (IPGTT) (1 g/kg body weight), 2 h after removing the infusion pump. At 15 min from the beginning of the test, GLP-1-treated animals had lower plasma glucose levels (442+/-38 mg/dl) than saline-infused controls (583+/-63 mg/dl, P<0.01). This was reflected in the higher insulin levels attained in the GLP-1-treated animals (1999+/-163 vs 1250+/-51 pmol/l, GLP-1 vs saline respectively, P<0.01). Repetition of the IPGTT on day 3, 9 and 16 from the removal of the infusion pump revealed a surprising lasting 'memory' of the exposure to GLP-1. Indeed, the best insulin secretory response was observed approximately 1 week after discontinuation of the GLP-1 infusion, and lasted up to 3 weeks from the early exposure to GLP-1. Detection of fasting plasma levels of GLP-1 during the 3 weeks of the experiment showed a very rapid decline, consistent with the data reported by others. Our findings provide evidence for a long-lasting beneficial effect of GLP-1 that persists for weeks even when the circulating levels of GLP-1 are back to normal.


Establishment of the Lotus japonicus Gene Expression Atlas (LjGEA) and its use to explore legume seed maturation.
Lotus japonicus is a model species for legume genomics. To accelerate legume functional genomics, we developed a Lotus japonicus Gene Expression Atlas (LjGEA), which provides a global view of gene expression in all organ systems of this species, including roots, nodules, stems, petioles, leaves, flowers, pods and seeds. Time-series data covering multiple stages of developing pod and seed are included in the LjGEA. In addition, previously published L. japonicus Affymetrix data are included in the database, making it a 'one-stop shop' for transcriptome analysis of this species. The LjGEA web server (http://ljgea.noble.org/) enables flexible, multi-faceted analyses of the transcriptome. Transcript data may be accessed using the Affymetrix probe identification number, DNA sequence, gene name, functional description in natural language, and GO and KEGG annotation terms. Genes may be discovered through co-expression or differential expression analysis. Users may select a subset of experiments and visualize and compare expression profiles of multiple genes simultaneously. Data may be downloaded in a tabular form compatible with common analytical and visualization software. To illustrate the power of LjGEA, we explored the transcriptome of developing seeds. Genes represented by 36 474 probe sets were expressed at some stage during seed development, and almost half of these genes displayed differential expression during development. Among the latter were 624 transcription factor genes, some of which are orthologs of transcription factor genes that are known to regulate seed development in other species, while most are novel and represent attractive targets for reverse genetics approaches to determine their roles in this important organ.


[The future of catheterization in acquired heart valve diseases].
The value of routine catheterization and angiography in the investigation of acquired valvular disease is currently under debate. In many cases, echocardiography provides enough information, even for pre-operative assessment of the heart disease. However, the pre-operative assessment of the valvular disease requires an estimation of the severity of the valvular lesion and a study of left ventricular performance. In older patients, associated coronary artery disease also has to be evaluated. Finally, in patients who have been treated surgically, the disorders related to recurrence of their valvular disease or to the dysfunction of their valvular prosthesis also have to be identified. Each of these aspects has to be considered; this requires a very thorough clinical evaluation of the symptoms and signs and a combination of investigations, consisting of echocardiography, haemodynamic studies and angiography.


Anterior internal capsule volumes increase in patients with schizophrenia switched from typical antipsychotics to olanzapine.
Abnormalities in connectivity are thought to contribute to the symptoms of schizophrenia. Accumulating evidence suggests that antipsychotic medication affects both subcortical and cortical grey and white matter volumes. The goal of this study was to investigate the effects of antipsychotic medication on two white matter tracts: a subcortical-cortical tract, the anterior and posterior limbs of the internal capsule; and a cortical-cortical tract, the corpus callosum. Magnetic resonance imaging was conducted on 10 chronic schizophrenia patients treated with typical antipsychotics and 20 healthy controls at baseline. Patients were switched to olanzapine and both groups were rescanned after 1 year. At baseline, the volume of the anterior limb of the internal capsule was 24% smaller in typical-treated patients than controls (p = 0.009). Patients treated with greater amounts of chlorpromazine-equivalent daily dosage had smaller anterior internal capsule volumes at baseline (r = -0.65, p = 0.04). At follow-up, after being switched to olanzapine, there were no significant differences between patients and controls. Patients with schizophrenia had a significant 25% increase in anterior internal capsule volume from baseline to follow-up compared with controls (p = 0.04). These effects were most prominent in the anterior limb of the internal capsule, which consists of fronto-thalamic pathways, and were not statistically significant in the posterior limb of the internal capsule or corpus callosum. Olanzapine may be effective in normalizing fronto-thalamic structural connectivity in schizophrenia.


Associations between Plasma Antibody Levels against Porphyromonas gingivalis and Atrial Fibrillation among Community-Dwelling Older Individuals in Japan: A Cross-Sectional Study.
To investigate the association between plasma antibody levels against Porphyromonas gingivalis (PG) and atrial fibrillation (AF) history in community-dwelling older individuals in Japan. This study was a subset of the Uonuma cohort study, including 3091 participants aged 60-79 years. Data were collected, including AF history as a dependent variable, plasma immunoglobulin G antibody levels against PG as an independent variable, and previously reported AF risk factors and demographic information as covariates. The median age of the participants was 69 years. Of the 3091 participants, 1411 (45.6%) were men, and 56 (1.8%) had an AF history. AF prevalence was significantly higher in participants with higher antibody levels against PG than in those with lower antibody levels (3.0% vs 1.4%; p = 0.005). Multivariable logistic regression analysis showed that participants with higher antibody levels against PG had twofold higher odds of having AF (odds ratio = 2.13; 95% confidence interval = 1.23-3.69). Restricted cubic spline analysis indicated a nonlinear relationship between antibody levels against PG and AF history. Plasma antibody levels against PG were associated with AF history in community-dwelling older individuals in Japan.


[Recent developments in the treatment of chronic hepatitis B and C].
Chronic hepatitis B and C are life-threatening diseases, treated with variable success. Peginterferon-alpha is one of the standard therapies for chronic hepatitis B as well as C. To prevent the development of resistant viruses, combination treatment is preferable to monotherapy. Therefore, in chronic hepatitis B virus peginterferon-alpha combined with nucleoside inhibitors is used. The treatment of chronic hepatitis C virus with a combination of peginterferon-alpha and ribavirine can be improved by new protease inhibitors.


Subtract Before You Add: Toward the Development of a De-Implementation Approach in School-Based Speech Sound Therapy.
It is often difficult for school-based speech-language pathologists (SLPs) to prioritize implementing new practices for children with speech sound disorders (SSDs), given burgeoning caseloads and the myriad of other workload tasks. We propose that de-implementation science is equally as important as implementation science. De-implementation science is the recognition and identification of areas that are of "low-value and wasteful." Critically, the idea of de-implementation suggests that we first remove something from a clinician's workload before requesting that they learn and implement something new. Situated within the Sustainability in Healthcare by Allocating Resources Effectively (SHARE) framework, we review de-implementation science and current speech sound therapy literature to understand the mechanisms behind continuous use of practices that are no longer supported by science or legislation. We use vignettes to highlight real-life examples that clinicians may be facing in school-based settings and to provide hypothetical solutions, resources, and/or next steps to these common challenges. By focusing on Phase 1 of the SHARE framework, we identified four primary practices that can be de-implemented to make space for new evidence-based techniques and approaches. These four practices were determined based on an in-depth review of SLP-based survey research: (a) overreliance on speech sound norms for eligibility determinations, (b) the omission of phonological processing skills within evaluations, (c) homogeneity of service delivery factors, and (d) the use of only one treatment approach for all children with SSDs. De-implementation will take work and may lead to some difficult discussions. Implementing a framework, such as SHARE, can guide SLPs toward a reduction in workloads and improved outcomes for children with SSDs.


Inferring Molecular Processes Heterogeneity from Transcriptional Data.
RNA microarrays and RNA-seq are nowadays standard technologies to study the transcriptional activity of cells. Most studies focus on tracking transcriptional changes caused by specific experimental conditions. Information referring to genes up- and downregulation is evaluated analyzing the behaviour of relatively large population of cells by averaging its properties. However, even assuming perfect sample homogeneity, different subpopulations of cells can exhibit diverse transcriptomic profiles, as they may follow different regulatory/signaling pathways. The purpose of this study is to provide a novel methodological scheme to account for possible internal, functional heterogeneity in homogeneous cell lines, including cancer ones. We propose a novel computational method to infer the proportion between subpopulations of cells that manifest various functional behaviour in a given sample. Our method was validated using two datasets from RNA microarray experiments. Both experiments aimed to examine cell viability in specific experimental conditions. The presented methodology can be easily extended to RNA-seq data as well as other molecular processes. Moreover, it complements standard tools to indicate most important networks from transcriptomic data and in particular could be useful in the analysis of cancer cell lines affected by biologically active compounds or drugs.


Mitral annular disjunction in myxomatous mitral valve disease: a relevant abnormality recognizable by transthoracic echocardiography.
Mitral annular disjunction (MAD) consists of an altered spatial relation between the left atrial wall, the attachment of the mitral leaflets, and the top of the left ventricular (LV) free wall, manifested as a wide separation between the atrial wall-mitral valve junction and the top of the LV free wall. Originally described in association with myxomatous mitral valve disease, this abnormality was recently revisited by a surgical group that pointed its relevance for mitral valve reparability. The aims of this study were to investigate the echocardiographic prevalence of mitral annular disjunction in patients with myxomatous mitral valve disease, and to characterize the clinical profile and echocardiographic features of these patients. We evaluated 38 patients with myxomatous mitral valve disease (mean age 57 ± 15 years; 18 females) and used standard transthoracic echocardiography for measuring the MAD. Mitral annular function, assessed by end-diastolic and end-systolic annular diameters, was compared between patients with and without MAD. We compared the incidence of arrhythmias in a subset of 21 patients studied with 24-hour Holter monitoring. MAD was present in 21 (55%) patients (mean length: 7.4 ± 8.7 mm), and was more common in women (61% vs 38% in men; p = 0.047). MAD patients more frequently presented chest pain (43% vs 12% in the absence of MAD; p = 0.07). Mitral annular function was significantly impaired in patients with MAD in whom the mitral annular diameter was paradoxically larger in systole than in diastole: the diastolic-to-systolic mitral annular diameter difference was -4,6 ± 4,7 mm in these patients vs 3,4 ± 1,1 mm in those without MAD (p < 0.001). The severity of MAD significantly correlated with the occurrence of non-sustained ventricular tachycardia (NSVT) on Holter monitoring: MAD›8.5 mm was a strong predictor for (NSVT), (area under ROC curve = 0.74 (95% CI, 0.5-0.9); sensitivity 67%, specificity 83%). There were no differences between groups regarding functional class, severity of mitral regurgitation, LV volumes, and LV systolic function. MAD is a common finding in myxomatous mitral valve disease patients, easily recognizable by transthoracic echocardiography. It is more prevalent in women and often associated with chest pain. MAD significantly disturbs mitral annular function and when severe predicts the occurrence of NSVT.


Aortic Endovascular Stent IIIb Endoleak Combined With Sealed Aneurysm Rupture Mimicking a Paravertebral Retroperitoneal Tumor.
The aim of this paper is to present the unique case of a sealed ruptured abdominal aortic aneurysm (AAA) with simultaneous type IIIb endoleak of an endovascular stent, mimicking a paravertebral retroperitoneal tumor. A 75-year-old male was referred to the tumor service of our tertiary orthopaedic department suffering from intractable low back pain with an onset of six months. He had undergone repair of an infrarenal AAA with an endovascular stent 5 years ago. Imaging studies depicted a large retroperitoneal mass adjacent to L2 and L3 vertebrae. The stent's metal cage had no signs of wear or migration. The pathology report of a CT-guided core-needle biopsy he had undergone before his referral raised suspicion about possible AAA rupture. CT-angiography confirmed the existence of a ruptured AAA, accompanied by retroperitoneal blood loss and a (possibly) failed stent. The IIIb eroded stent was openly removed and a Y-type allograft was used to repair the defect. The patient reported immediate relief and was uneventfully discharged. He demised 4 years later due to reasons unrelated to the hereby reported condition. Increased awareness is warranted when dealing with anterior lumbar spine or retroperitoneal lesions. A close cooperation between a vascular and an orthopaedic/spine surgeon must always be sought.


Quantitative and dynamic assessment of the contribution of the ER to phagosome formation.
Phagosomes were traditionally thought to originate from an invagination and scission of the plasma membrane to form a distinct intracellular vacuole. An alternative model implicating the endoplasmic reticulum (ER) as a major component of nascent and maturing phagosomes was recently proposed (Gagnon et al., 2002). To reconcile these seemingly disparate hypotheses, we used a combination of biochemical, fluorescence imaging, and electron microscopy techniques to quantitatively and dynamically assess the contribution of the plasmalemma and of the ER to phagosome formation and maturation. We could not verify even a transient physical continuity between the ER and the plasma membrane, nor were we able to detect a significant contribution of the ER to forming or maturing phagosomes in either macrophages or dendritic cells. Instead, our data indicate that the plasma membrane is the main constituent of nascent and newly formed phagosomes, which are progressively remodeled by fusion with endosomal and eventually lysosomal compartments as phagosomes mature into acidic, degradative organelles.


Stereotactic radiotherapy for wet age-related macular degeneration: current perspectives.
Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID) showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger randomized controlled trial (STAR) is underway.


Epidemiology and genetics of CTX-M extended-spectrum β-lactamases in Gram-negative bacteria.
CTX-M enzymes, the plasmid-mediated cefotaximases, constitute a rapidly growing family of extended-spectrum β-lactamases (ESBLs) with significant clinical impact. CTX-Ms are found in at least 26 bacterial species, particularly in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. At least 109 members in CTX-M family are identified and can be divided into seven clusters based on their phylogeny. CTX-M-15 and CTX-M-14 are the most dominant variants. Chromosome-encoded intrinsic cefotaximases in Kluyvera spp. are proposed to be the progenitors of CTX-Ms, while ISEcp1, ISCR1 and plasmid are closely associated with their mobilization and dissemination.


Oculopathologic findings in flavivirus-infected gallinaceous birds.
Using eye samples of nine 9-week-old experimentally West Nile virus (WNV)-infected red-legged partridges (Alectoris rufa), time course of lesions and WNV antigen appearance in ocular structures were examined. In addition, eye samples of 6 red-legged partridges and 3 common pheasants (Phasianus colchicus) naturally infected with Bagaza virus (BAGV) were used to study lesions and flavivirus antigen distribution in relation to apparent blindness in the former. The rapid onset of microscopic lesions and early presence of viral antigen in the eye of experimentally WNV-infected partridges, prior to the central nervous system involvement, suggested hematogenous spread of the virus into the eye. BAGV-infected partridges had a more pronunced inflammatory reaction and more widespread flavivirus antigen distribution in the retina compared with pheasants and experimentally fatally WNV-infected partridges. Our results suggest that flavivirus replication and development of lesions in ocular structures of gallinaceous game birds vary with the specific virus and host species involved.


Ultrafast proton transfer of three novel quinone cyanine photoacids.
Steady-state and time-resolved emission techniques were used to study the photoprotolytic properties of three recently synthesized strong quinone cyanine photoacids (QCy7 and its sulfonated derivatives). The rate coefficient of the excited-state proton transfer (ESPT), k(PT), of the three dyes is roughly 1.5 × 10(12) s(-1), a high value that is comparable to the solvation dynamics rate of large polar organic molecules in H(2)O and D(2)O. It is twice as fast as the proton transfer rate between two adjacent water molecules in liquid water. We found that, as expected, two of the sulfonated photoacids geminately recombines with the proton at an elevated rate. The accelerated geminate recombination process of the sulfonated derivatives is different from a simple diffusion process of protons. The ESPT rate coefficient of these molecules is the highest recorded thus far.


Sedentariness and increased visceral adiposity in adult perinatally iron-deficient rats.
Perinatal iron deficiency (PID) adversely programs offspring resulting in alterations in adult cardiometabolic function. Increased visceral adiposity is the proposed culprit for these sequelae, and may be potentiated by decreased physical activity. Herein, we determined (i) the effect of PID on visceral adipose tissue (VAT) and locomotor activity, and (ii) whether increased VAT is associated with blood pressure responsiveness to increased dietary sodium. Dams were fed a low iron diet (<10 mg/kg Fe) prior to and throughout gestation. From 12 to 35 weeks of age, locomotor activity (assessed by radiotelemetry) in PID offspring was 25% lower compared with control offspring (P<0.001). At 36 weeks of age, PID offspring had 15% more VAT than controls (P<0.05). Furthermore, the elevation of mean arterial pressure (by radiotelemetry) in response to increased sodium intake was approximately twofold greater in the PID offspring (P<0.05). PID results in increased visceral adiposity, which was associated with enhanced blood pressure responsiveness to dietary salt, perhaps due to programmed sedentary behavior.


The Role of Dietary Experience in the Development of Eating Behavior during the First Years of Life.
Infants are born equipped to ingest nutrients, but because of the transitions in the mode of feeding in the first years (from "tube" feeding in utero to eating table foods with the family), they have to learn how, what and how much to eat. Eating behavior established during early years may follow throughout childhood; therefore, it is fundamental to understand the most important drivers of the early development of eating behavior. Beyond the first flavor discoveries during the gestational and lactation periods (through the infant's exposure to flavors from foods of the mother's diet), the most important phases for learning food preferences and appetite control may be the beginning of complementary feeding (CF). Infants discover the sensory (texture, taste and flavor) and nutritional properties (energy density) of foods that will ultimately compose their adult diet. This brief review shows that several feeding practices influence the development of eating behavior: breastfeeding; repeating the presentation of a food, even if it seems initially disliked; introducing a variety of different foods rapidly in the CF process; offering foods in an appropriate way to make their sensory characteristics appealing to infants. More research is needed to understand in a combined way the effectiveness and long-term effect of these practices to promote healthy eating behaviors.


Staphylococcus aureus binding to Seraph® 100 Microbind® Affinity Filter: Effects of surface protein expression and treatment duration.
Extracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria. The aim of this study was to analyse the binding activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity. To test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells. The Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration.


A Continuous Extension of Gene Set Enrichment Analysis using the Likelihood Ratio Test Statistics Identifies VEGF as a Candidate Pathway for Alzheimer's disease.
Alzheimer's disease involves brain pathologies such as amyloid plaque depositions and hyperphosphorylated tau tangles and is accompanied by cognitive decline. Identifying the biological mechanisms underlying disease onset and progression based on quantifiable phenotypes will help understand the disease etiology and devise therapies. Our objective was to identify molecular pathways associated with AD biomarkers (Amyloid-β and tau) and cognitive status (MMSE) accounting for variables such as age, sex, education, and APOE genotype. We introduce a novel pathway-based statistical approach, extending the gene set likelihood ratio test to continuous phenotypes. We first analyzed independently each of the three phenotypes (Amyloid-β, tau, cognition), using continuous gene set likelihood ratio tests to account for covariates, including age, sex, education, and APOE genotype. The analysis involved a large sample size with data available for all three phenotypes, allowing for the identification of common pathways. We identified 14 pathways significantly associated with Amyloid-β, 5 associated with tau, and 174 associated with MMSE. Surprisingly, the MMSE outcome showed a larger number of significant pathways compared to biomarkers. A single pathway, vascular endothelial growth factor receptor binding (VEGF-RB), exhibited significant associations with all three phenotypes. The study's findings highlight the importance of the VEGF signaling pathway in aging in AD. The complex interactions within the VEGF signaling family offer valuable insights for future therapeutic interventions.


The Status of Affected Infraorbital Nerve and Inferior Alveolar Nerve in Patients With Jaw Fibrous Dysplasia: A Clinical and Radiographic Evaluation.
The affected infraorbital nerve (IFBN) and inferior alveolar nerve (IFAN) status in patients with jaw fibrous dysplasia has not been definitely depicted. In this study, the authors try to explore the status of affected IFBN and IFAN in patients with jaw fibrous dysplasia. Ten patients with jaw fibrous dysplasia were included in this study. The complaints of numbness in the IFBA and IFAN innervated area were asked and recorded, and careful clinical examination was performed to evaluate the touch sense, pain sense, pressure sense, and temperature sense in the IFBA and IFAN innervated areas. Computed tomography scans also were performed to evaluate the imaging characteristics of affected IFBA and IFAN. The results showed that 1 patient with maxillary lesion showed complaints of slight numbness, and clinical examination showed that the patient exhibited slight insensitive in pain sense. In addition, 1 patient with mandibular lesion showed relative obvious complaints of numbness, and clinical examination showed that the patient exhibited slight insensitive in pain sense and temperature sense, but not serious. All other patients exhibited no numbness in the IFBA and IFAN innervated area. Although the position and morphology changed in some patients, all neural canal of affected IFBA or IFAN existed and showed no invasion of lesion. Taking these findings together, it further confirmed that evaluation of the function of IFBAN and IFAN is necessary for patients with jaw fibrous dysplasia, and the affected IFBAN and IFAN may should be reserved in most patients with jaw fibrous dysplasia when resecting or recontouring the lesion.


Expression of Ia antigens on freshly dissociated mouse thyroid follicles demonstrated by immunofluorescence.
Iak antigens were detected by indirect immunofluorescence on CBA mouse thyroid follicles. Isolated thyroid follicles, free of lymphocyte contamination, were obtained by collagenase treatment and mechanical disruption; they were then cytocentrifuged on glass slides. This material was incubated with polyclonal or monoclonal anti Iak antibodies followed by FITC-conjugated F(ab')2. Subsequent microscopic observations of these open thyroid follicles revealed that Iak antigens were spontaneously expressed. Labelling was distributed preferentially on the thyrocyte cell surface and, to a lesser extent, on intracellular organelles. Conversely, nuclei were never stained. In some cases, labelling was mottled. Ia antigens may have been previously unobserved because, beside autoimmune disorders they are present in such small amounts that detection is very difficult. The fact that Ia expression is independent of morphological signs of spontaneous autoimmune thyroiditis (particularly, lymphocyte infiltration of follicles), raises the problem of correlation between the autoimmune disorders and Ia expression.


A descriptive quantitative study of 7- and 8-year-old children's outdoor recreation, cold exposure and symptoms in winter in Northern Finland.
In Finland, children spend a lot of time outdoors in winter. Outdoor recreation in winter has a wide variety of effects on children's well-being. Although children are a subgroup that is vulnerable to cold exposure, remarkably little research has been done on the subject. The aim of this study was to describe children's outdoor recreation, cold exposure and symptoms in winter in Northern Finland. This was a descriptive quantitative study. The participants consisted of 30 children aged 7-8 years who were living in the provinces of Lapland and Northern Ostrobothnia in Finland. Data were collected by using electronic data-logging thermometers fixed on children's outerwear for a month. The thermometers recorded the environmental temperature every five minutes and from that temperature data, we were able to discern the exact amount and duration of children's outdoor recreation. In addition, information on the children's cold symptoms was collected with structured daily entries. Cold weather was not an obstacle to children's outdoor activities in Finland. However, the duration of outdoor recreation shortened when the outdoor air temperature decreased. There were no significant differences between boys and girls in terms of time spent outdoors. Remarkably, every child reported symptoms associated with cold. Almost half of the children reported experiencing respiratory symptoms and some children also experienced cold pain and numbness. The results of this study illustrate the many and varied effects that cold exposure can have on children's health and well-being. In order to prevent negative health effects of cold exposure on children, structured prevention strategies are needed: therefore, children's exposure to cold should be studied more. Future research should also bring out more the positive health effects of outdoor recreation on children's growth and development..


[Study of Equilibrium Control System during a Lowering at Arousal Level].
Contingent negative variation (CNV) is an event-related potential proportional to vigilance degree. A CNV graph shows an inverted U-shape, and this bioreaction disappears after falling below a threshold of vigilance degree. Previous studies have shown that the event-related potential gained with time decreases with sleep deprivation, and a decrease in the vigilance degree has been confirmed using Flicker values (FV) and the Stanford Sleepiness Scale (SSS) score. The minimum integrated value was recorded 24 h after the onset of sleep deprivation. In a present study, we used 36-h sleep deprivation. The FVs, SSS scores, and stabilograms were obtained every 90 min for 52 h, except for the 12 h of sleep. We herein examine whether the biocontrol system is changed by sleep deprivation. The time sequences in FV and SSS score showed that the degree of vigilance markedly decreased 22.5 h after the onset of this experiment, which supported CNV disappearance with sleep deprivation. The sway value with subjects' eyes closed was greatest 22.5 h after the onset of this experiment. Furthermore, there were no significant differences between the sway value during the above-mentioned sleep deprivation and that after 12 h of sleep. We considered that the equilibrium function and vigilance after 36-h sleep deprivation did not recover markedly well with sleep of sufficient duration. That is, the biocontrol process in the subconscious still proceeds after awakening. In this study, we focused on bioprocessing, especially the equilibrium function, during sleep deprivation and investigated the relationship between the equilibrium function and sleep deprivation. We obtained evidence supporting CNV disappearance after sleep deprivation for 36 h. The equilibrium control system without CNV was compared with that with CNV.


Loss of fumarylacetoacetate hydrolase causes light-dependent increases in protochlorophyllide and cell death in Arabidopsis.
Fumarylacetoacetate hydrolase (FAH) catalyses the final step of the tyrosine degradation pathway, which is essential to animals but was of unknown importance in plants until we found that mutation of Short-day Sensitive Cell Death1 (SSCD1), encoding Arabidopsis FAH, results in cell death under short-day conditions. The sscd1 mutant accumulates succinylacetone (SUAC), an abnormal metabolite caused by loss of FAH. Succinylacetone is an inhibitor of δ-aminolevulinic acid (ALA) dehydratase (ALAD), which is involved in chlorophyll (Chl) biosynthesis. In this study, we investigated whether sscd1 cell death is mediated by Chl biosynthesis and found that ALAD activity is repressed in sscd1 and that protochlorophyllide (Pchlide), an intermediate of Chl biosynthesis, accumulates at lower levels in etiolated sscd1 seedlings. However, it was interesting that Pchlide in sscd1 might increase after transfer from light to dark and that HEMA1 and CHLH are upregulated in the light-dark transition before Pchlide levels increased. Upon re-illumination after Pchlide levels had increased, reactive oxygen species marker genes, including singlet oxygen-induced genes, are upregulated, and the sscd1 cell death phenotype appears. In addition, Arabidopsis WT seedlings treated with SUAC mimic sscd1 in decline of ALAD activity and accumulation of Pchlide as well as cell death. These results demonstrate that increase in Pchlide causes cell death in sscd1 upon re-illumination and suggest that a decline in the Pchlide pool due to inhibition of ALAD activity by SUAC impairs the repression of ALA synthesis from the light-dark transition by feedback control, resulting in activation of the Chl biosynthesis pathway and accumulation of Pchlide in the dark.


Detergent effects on the light-harvesting chlorophyll A/B-protein complex crystallization revealed by fluorescence depolarization.
Detergent effects on the pre-crystallization of light-harvesting chlorophyll a/b-protein complex (LHCII) were investigated through the fluorescence depolarization method. Stable LHCII crystals were formed in the media containing Triton X-100 (TX) or n-nonyl-beta-D-glucopyranoside (NG) and the crystallization efficients were dependent on their concentrations. The second virial coefficient of crystallizing system, estimated by the fluorescence depolarization analysis of LHCII, showed the most harmonious value under the condition yielding the most efficient crystallization of LHCII to suggest that some specific molecular interaction leading to the crystal growth would be induced according to the concentration of TX or NG.


Socioeconomic deprivation and serious ocular trauma in Scotland: a national prospective study.
To identify the population at risk of serious ocular trauma by exploring relationships with socioeconomic factors. National, prospective, population-based, cross-sectional and follow-up study. Patients with serious ocular trauma requiring hospital admission in Scotland. Case definition and ascertainment-cases of serious ocular trauma necessitating admission to hospital under the care of a consultant ophthalmologist were identified using the British Ophthalmological Surveillance Unit reporting scheme. Using the postcode of residence, we assigned a Scottish Index of Multiple Deprivation (SIMD) score, SIMD quintile ( 0%-20% most deprived; 20%-40%, 40%-60%, 60%-80%, 80%-100% least deprived areas), geographical access score as well as the estimated travel time to the nearest general practitioner (GP) practice using either car or public transport for each patient. Population estimates were obtained from the General Register Office for Scotland. Serious ocular trauma requiring hospital admission. A total of 104 patients (85.6% male) were reported as being admitted with ocular trauma with a median age of 32 years (IQR 24-54). There was a trend for increasing incidence of serious ocular injury with increasing socioeconomic deprivation (p=0.034). Patients from the most deprived areas (SIMD: 0%-20%) were twice as likely to sustain ocular injury compared with those from the least deprived (SIMD: 80%-100%) areas (relative risk: 2.19, 95% CI 1.02 to 4.81). There was no significant difference in the drive/public transport time to GP practices across the SIMD quintiles. Increasing socioeconomic deprivation was associated with a higher incidence of serious ocular injury. Targeted interventions are needed to address inequality in eye healthcare in deprived areas.