Non-invasive model of neuropathogenic Escherichia coli infection in the neonatal rat.
Investigation of the interactions between animal host and bacterial pathogen is only meaningful if the infection model employed replicates the principal features of the natural infection. This protocol describes procedures for the establishment and evaluation of systemic infection due to neuropathogenic Escherichia coli K1 in the neonatal rat. Colonization of the gastrointestinal tract leads to dissemination of the pathogen along the gut-lymph-blood-brain course of infection and the model displays strong age dependency. A strain of E. coli O18:K1 with enhanced virulence for the neonatal rat produces exceptionally high rates of colonization, translocation to the blood compartment and invasion of the meninges following transit through the choroid plexus. As in the human host, penetration of the central nervous system is accompanied by local inflammation and an invariably lethal outcome. The model is of proven utility for studies of the mechanism of pathogenesis, for evaluation of therapeutic interventions and for assessment of bacterial virulence.


Comparing perceptual and preferential decision making.
Perceptual and preferential decision making have been studied largely in isolation. Perceptual decisions are considered to be at a non-deliberative cognitive level and have an outside criterion that defines the quality of decisions. Preferential decisions are considered to be at a higher cognitive level and the quality of decisions depend on the decision maker's subjective goals. Besides these crucial differences, both types of decisions also have in common that uncertain information about the choice situation has to be processed before a decision can be made. The present work aims to acknowledge the commonalities of both types of decision making to lay bare the crucial differences. For this aim we examine perceptual and preferential decisions with a novel choice paradigm that uses the identical stimulus material for both types of decisions. This paradigm allows us to model the decisions and response times of both types of decisions with the same sequential sampling model, the drift diffusion model. The results illustrate that the different incentive structure in both types of tasks changes people's behavior so that they process information more efficiently and respond more cautiously in the perceptual as compared to the preferential task. These findings set out a perspective for further integration of perceptual and preferential decision making in a single ramework.


The antiosteoporotic activity of central-icaritin (CIT) on bone metabolism of ovariectomized rats.
Central-icaritin (CIT) is a flavonoid aglycone first discovered in our laboratory, which is an isomeric aglycone of icaritin (IT). We wanted to know whether CIT also had anti-osteoporosis activity. In this study, CIT was investigated in an ovariectomized rat (OVX) model. Fifty-six 6-month old female Sprague-Dawley rats were randomly assigned to sham operated group (Sham) and six OVX subgroups (n=8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), icaritin (IT, 40 mg/kg body weight/day), estradiol valerate (EV, 100 μg/kg body weight/day) or CIT (10, 20, and 40 mg/kg body weight/day) for 12 weeks, respectively. Then, the serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone immunohistochemistry and related protein and gene expressions were evaluated. In OVX rats, the increases of body weight, HOP, AKP, and TRACP5b levels, and the decreases of uterus wet weight, femurs weight, BMD, serum OPG/RANKL and OCN were significantly inhibited by CIT treatment. Micro-CT analysis results showed that CIT apparently enhanced trabecular bone compared with the OVX group (p<0.05). Total femur BMD and biomechanical strength of tibia were significantly improved (p<0.05) after 12 weeks of CIT administration. In addition, the CIT administration also significantly enhanced the OPG expression, whereas reduced the RANKL expression in femurs according to RT-PCR, western blot assays and immunohistochemical evaluation. CIT had the antiosteoporotic activity, and its antiosteoporotic effects in OVX rats may be stronger than that of IT.


Association between Tuberculosis, Statin Use, and Diabetes: A Propensity Score-Matched Analysis.
Statins have anti-inflammatory and immunomodulatory properties that may affect the development of tuberculosis (TB). We assessed the association between use of statins and the risk of active TB by propensity score matching. Furthermore, we analyzed the impact of statins on TB in patients according to the presence or absence of diabetes. The study was based on the National Health Insurance database and its subset database of the "medical checkup" population of South Korea. We identified 123,468 statin users and 439,546 non-statin users. After propensity score matching, 28,018 statin users and the same number of non-statin users were finally analyzed. The development of active TB was monitored in these matched pairs over 11 years. In the propensity score-matching analysis, the number of active TB cases was 30 in 30,303 person-years (0.99 per 1,000 person-years; 95% CI, 0.64-1.35) in the statin users and 235 in 167,857 person-years (1.40 per 1,000 person-years; 95% CI, 1.22-1.58) in the non-statin users. Statin users had a significantly lower risk of TB than non-statin users: hazard ratio (HR) 0.67 (95% CI, 0.46-0.98) (P = 0.04). A subgroup analysis showed that statin use reduced the risk of TB in subjects without diabetes, but not in patients with diabetes: HRs were, respectively, 0.28 (95% CI, 0.13-0.60) (P = 0.001) and 1.05 (95% CI, 0.66-1.67) (P = 0.84). There is epidemiologic evidence that statin decreases the risk of active TB. However, the protective effect of statins against TB is attenuated by diabetes.


Assessing acceptance and social skills with peers in childhood. Current issues.
This article reviews current strategies for assessing social skills with peers in childhood, highlighting contemporary unresolved issues in identifying children who need intervention, selecting target behaviors, and assessing treatment outcome. Sociometric measures of peer acceptance are also considered. Although many current measures of social skills have adequate evidence of reliability and convergent validity, assessment could benefit from (a) increased documentation that the content of measures assesses important skills in relating to peers, (b) improved methods for assessing social behavior in specific interpersonal situations, and (c) more empirical evidence that indirect assessment methods (self-report, peer assessment, and teacher report) and analogue observations reflect in vivo behavior.


Two adult familial cases of selective hypoaldosteronism due to insufficiency of conversion of corticosterone to aldosterone.
A 57-year-old woman (case 1) and her daughter aged 29 (case 2) with hyperkalemia exhibited subnormal plasma aldosterone (ALD) in the face of elevated plasma renin activity. Their physical findings were normal. Their arterial blood gas analysis showed that metabolic acidosis and renal function of these cases were slightly impaired. Urinary 17-OHCS and 17-KS excretions in these cases were normal. Baseline levels of corticosterone (B) and 18-hydroxycorticosterone (18-OH-B) were clearly elevated. Plasma deoxycorticosterone (DOC), B and 18-OH-B as well as cortisol remarkable increased after ACTH injection, but the increase in plasma ALD was very small. Angiotensin II infusion in case 1 resulted in a clear rise in plasma 18-OH-B but in slight depletion of B, and no increase in ALD. 9-alpha-fludrocortisone acetate treatment was performed in case 1. Serum potassium was normalized and blood pressure elevated from 82/52 to 120/78 mmHg. Arterial blood gas analysis was corrected. We concluded that these two cases with subnormal plasma ALD and hyperreninemia may exist as a congenital and familial abnormality of the final step of aldosterone boisynthesis due to the impairment of the conversion of B to ALD.


Our experience in the treatment of Malignant Fibrous Hystiocytoma of the larynx: clinical diagnosis, therapeutic approach and review of literature.
Hereditary spherocytosis (HS) and Chronic myelocytic leukemia (CML) are both life threatening hemotologic diseases. They are rarely seen to occur simultaneously in one individual patient. Here we demonstrate a case of HS associated with CML in this study. The patient is a young female, diagnosed with HS in 2005, and was given partial embolization of the splenic artery. She got significant remission after the procedure. In 2008, she was found abnormal in blood routine test, after bone marrow routine, chromosome and fusion gene tests, she was diagnosed with CML (chronic phase). She did not receive regular treatment until 3 months prior, and is currently being treated with Dasatimib. She achieved hematological remission, but had no significant improvement in chromosome and fusion gene figures. Due to her severe condition of hemolysis, a splenectomy or an allogeneic hematopoietic stem cell transplantation is considered.


Different Clinicopathologic and Computed Tomography Imaging Characteristics of Primary and Acquired EGFR T790M Mutations in Patients with Non-Small-Cell Lung Cancer.
Although patients with primary and acquired epidermal growth factor receptor (EGFR) T790M positive non-small-cell lung cancer (NSCLC) respond to osimertinib treatment, the optimal treatment strategy differs for these two groups of patients. This study aimed to compare the clinicopathologic and computed tomography (CT) imaging characteristics between primary and acquired EGFR T790M mutations in patients with NSCLC before treatment. We enrolled two groups of patients with primary or acquired EGFR T790M mutation NSCLC (n = 103 per group) from January 2012 to December 2019. We analyzed their clinicopathologic and CT characteristics and differences between the groups. The groups were further categorized based on 21L858R and 19del to exclude the effect of coexistent mutations. Primary, compared to acquired, T790M mutation tends to coexist with 21L858R (P < 0.001), exhibiting earlier tumor stage (P < 0.001), higher differentiation (P = 0.029), higher proportion of lepidic subtype adenocarcinoma (P < 0.001), and significant associations with some CT features (multiple primary lung cancers, ground-glass opacity, air bronchogram, and vacuole sign [all P < 0.001]). The combined model, composed of clinicopathologic and conventional CT signature and CT-radiomic signature, showed good discriminative ability with the area under the receiver operating characteristic curve 0.90 and 0.91 in the training and validation datasets, respectively. The T790M mutation contributed to these differences independently of coexistent mutations. We identified clinicopathologic and CT imaging differences between primary and acquired T790M mutations. These findings provide insights into developing future personalized T790M mutation status-based theranostic strategies.


Phase Transitions in Definite Total Spin States of Two-Component Fermi Gases.
Second-order phase transitions have no latent heat and are characterized by a change in symmetry. In addition to the conventional symmetric and antisymmetric states under permutations of bosons and fermions, mathematical group-representation theory allows for non-Abelian permutation symmetry. Such symmetry can be hidden in states with defined total spins of spinor gases, which can be formed in optical cavities. The present work shows that the symmetry reveals itself in spin-independent or coordinate-independent properties of these gases, namely as non-Abelian entropy in thermodynamic properties. In weakly interacting Fermi gases, two phases appear associated with fermionic and non-Abelian symmetry under permutations of particle states, respectively. The second-order transitions between the phases are characterized by discontinuities in specific heat. Unlike other phase transitions, the present ones are not caused by interactions and can appear even in ideal gases. Similar effects in Bose gases and strong interactions are discussed.


Wastewater surveillance facilitates climate change-resilient pathogen monitoring.
Traditional disease surveillance systems are ill-equipped to handle climate change-driven shifts in pathogen dynamics. If paired with wastewater surveillance, a cost-effective and scalable approach for generating high-resolution health data, such next-generation systems can enable effective resource allocation and delivery of targeted interventions.


Computer assisted surgery evaluation of femoral component rotation in well-balanced and well-aligned total knee arthroplasty using gap technique.
Using computer assisted surgery (CAS) to assess femoral component rotation in well-balanced, well-aligned total knee arthroplasty (TKA) implanted with Posterior Cruciate Ligament (PCL) excision type prosthesis using gap technique. Using CAS, well-balanced TKA was defined by both flexion/extension and medial/lateral gap difference of less than 2 mm and well-aligned TKA was defined by final mechanical axis within +/- 3 degrees deviation and flexion contracture of less than 5 degrees without hyper extension. Femoral component rotation was determined by posterior condylar axis versus proximal tibia resection plane. The present study analyzed data from January 1, 2009 to September 30, 2009. Out of 65 knees, 34 knees (14 fixed and 20 mobile bearing prosthesis) were considered well-balanced and well-aligned. Mean femoral component rotation was 2.12 +/- 3.38 degrees. Seven knees were within 2-4 degrees external rotation. There was no statistically significant difference of femoral component rotation between fixed and mobile bearing. Wide range of femoral component rotation occurred in well-aligned and well-balanced TKA using PCL excision type prosthesis.


[Molecules involved in characteristics of naive/memory B cells].
Memory B cells, which carry immunoglobulin somatic hypermutations, generate immunoglobulins rapidly and vigorously in the secondary immune response. We recently highlighted studies confirming that CD27 surface antigen is a memory B-cell marker. By using the memory B-cell marker, peripheral blood B cells were clearly distinguished into naive and memory B cells. The B cells are further separated to three populations by the expressions of CD27 and IgD: IgD+CD27- naive B cells (circulating B cell 1: cB1), IgD+CD27+ unclass-switched memory B cells (cB2, so-called IgM memory B cells) and IgD-CD27+ class-switched memory B cells (cB3, switched memory B cells). Here we show molecules which are involved in characteristics of naive/memory B cells and their functions. This functionally distinct B cell subset and molecules involved in the subset may represent an important mechanism by which quiescent human B cells can initiate and propagate rapid and vigorous immune memory responses, and regulate the synthesis of low/high affinity antibodies.


The uncoupling effect of diacylglycerol on gap junctional communication of mammalian heart cells is independent of protein kinase C.
Possible regulatory effects on cell-to-cell communication of a synthetic diacylglycerol, an activator of protein kinase C (PKC), were examined in pairs of synchronously beating ventricular myocytes of neonatal rats in primary culture. Junctional communication was estimated by measuring either the rate constant of dye diffusion, with the fluorescence recovery after photobleaching technique, or the cell-to-cell electrical conductance with a double whole-cell voltage clamp. The addition of a freshly prepared emulsion of 1-oleoyl-2-acetyl-sn-glycerol (OAG, 100 micrograms/ml), either in the bath or in the solution filling the patch pipet, was seen to interrupt intercellular communication within approximately 8 to 10 min. This effect is neither mimicked by stimulation of PKC by a phorbol ester, nor prevented by PKC inhibitors, making it unlikely that, in these cells, PKC activation could induce intercellular uncoupling. During OAG exposures, the intracellular calcium concentration was very modestly increased (by a factor 1.5 to 2), which does not suffice to account for uncoupling. OAG might trigger interruption of cell-to-cell communication by a mechanism analogous to that of other lipophilic molecules (such as aliphatic alcohols or long chain unsaturated fatty acids) which interfere with gap junctions.


Folate during reproduction: the Canadian experience with folic acid fortification.
Folate has received international attention regarding its role in the risk-reduction of birth defects, specifically neural tube defects (NTDs). In 1998, health officials in Canada, like the United States, mandated the addition of folic acid to white flour and select grain products to increase the folate intake of reproductive-aged women. Subsequent to this initiative there has been an increase in blood folate concentrations in Canada and a 50% reduction in NTDs. Many countries, including Korea, have not mandated folic acid fortification of their food supply. Reasons vary but often include concern over the masking of vitamin B(12) deficiency, a belief that folate intakes among womenare adequate, low priority relative to other domestic issues, and the philosophy that individuals have the right not to consume supplemental folic acid if they so choose. Prior to folic acid fortification of the food supply in Canada, the folate intakes of women were low, and their blood folate concentrations while not sufficiently low to produce overt signs of folate deficiency (eg. anemia) were inconsistent with a level known to reduce the risk of an NTD-affected pregnancy. The purpose of this article is to describe the role of folate during the periconceptional period, pregnancy, and during lactation. The rationale for, and history of recommending folic acid-containing supplements during the periconceptional period and pregnancy is described as is folic acid fortification of the food supply. The impact of folic acid fortification in Canada is discussed, and unresolved issues associated with this policy described. While the incidence of NTDs in Canada pre-folic acid fortification were seemingly higherthan that of Korea today, blood folate levels of Korean women are strikingly similar. We will briefly explore these parallels in an attempt to understand whether folic acid fortification of the food supply in Korea might be worth consideration.


Risks of invasive pneumococcal disease in children with underlying chronic diseases.
The risk of invasive pneumococcal disease is increased among children with some chronic diseases. The objective of this study was to quantify the risk of invasive pneumococcal disease in a wide range of chronic diseases. Cases of invasive pneumococcal disease among children (aged 0-17 years) were identified from 1977 through 2005 by using a national surveillance program in Denmark. Rate ratios were assessed in a case-control study by using 10 age- and gender-matched controls per case. Chronic diseases were defined a priori. Among 1655 children with invasive pneumococcal disease, 19% had a history of chronic disease, according to our definition, versus 5% of controls. An increased risk of invasive pneumococcal disease was observed for children followed >30 days after initial hospital contact for a chronic disease, but it was also increased in children with >or=5 hospital contacts for any other reason. Children with a history of cancer, chronic renal disease, splenectomy, and transplantation were particularly susceptible to invasive pneumococcal disease. Adjusted for number of hospital contacts, the risk for children with other types of chronic disease was 1.4-fold more than for those with hospital contacts for any reason. Cancer, chronic renal diseases, splenectomy, and transplantation were strongly associated with an increased risk of invasive pneumococcal disease in children. For children with other chronic diseases, their excess risk seemed to be attributable mostly to frail children having repeated hospital contact rather than their underlying condition.


Efficacy of a rise in C-reactive protein serum levels as an early indicator of sepsis in burned children.
C-Reactive protein serum levels were measured in 57 pediatric patients with 3% to 92% total body surface area burns to determine whether a defined rise in C-reactive protein serum levels could indicate sepsis earlier in burn patients. A rise in C-reactive protein serum levels was defined as an increase of at least 3 mg/dL for 2 days or 10 mg for 1 day. Increases the first 2 days after the burn or the day after surgery were excluded, since these injuries increase C-reactive protein serum levels. Patients were defined as septic when they were on systemic antibiotics and exhibited at least two of 16 specific clinical parameters. C-Reactive protein serum levels correctly predicted sepsis 82% of the time (efficiency=82%). Nonseptic patients generally did not show increased C-reactive protein serum levels (specificity=69%). When sepsis did occur, it always was preceded by increased C-reactive protein (sensitivity=100%), and the increased C-reactive protein occurred 2.3+/-0.5 days before the patient was deemed septic clinically. Hence, a defined rise in C-reactive protein serum levels can predict sepsis sooner in burned children.


[Emotional reactions of psychiatric staff to violent patients].
Approximately 10% of psychiatric patients are violent and their violence is often directed towards the treating staff. Up to half of all psychiatrists have been physically assaulted at some time during their careers. Emotional reactions of the psychiatric staff to assault by patients vary, and include fear, anger and helplessness. Psychological defense mechanisms employed include projection, denial and isolation. For the staff, these reactions are a source of distress and a cause of burn-out. Anger can lead to nontherapeutic interventions such as counter-aggression.


Kidney disease in Aboriginal Australians: a perspective from the Northern Territory.
This article outlines the increasing awareness, service development and research in renal disease in Aboriginal people in Australia's Northern Territory, among whom the rates of renal replacement therapy (RRT) are among the highest in the world. Kidney failure and RRT dominate the intellectual landscape and consume the most professional energy, but the underlying kidney disease has recently swung into view, with increasing awareness of its connection to other chronic diseases and to health profiles and trajectories more broadly. Albuminuria is the marker of the underlying kidney disease and the best treatment target, and glomerulomegaly and focal glomerulosclerosis are the defining histologic features. Risk factors in its multideterminant genesis reflect nutritional and developmental disadvantage and inflammatory/infectious milieu, while the major putative genetic determinants still elude detection. A culture shift of "chronic disease prevention" has been catalyzed in part by the human pain, logistic problems and great costs associated with RRT. Nowadays chronic disease management is the central focus of indigenous primary care, with defined protocols for integrated testing and management of chronic diseases and with government reimbursed service items and free medicines for people in remote areas. Blood pressure, cardiovascular risk and chronic kidney disease (CKD) are all mitigated by good treatment, which centres on renin-angiotensin system blockade and good metabolic control. RRT incidence rates appear to be stabilizing in remote Aboriginal people, and chronic disease deaths rates are falling. However, the profound levels of disadvantage in many remote settings remain appalling, and there is still much to be done, mostly beyond the direct reach of health services.


The role of magnesium in the aetiology and prevention of caries: some new findings and implications.
While some epidemiological studies seem to indicate that a high intake of magnesium should be associated with a low prevalence of dental caries, the results of experimental studies are mainly equivocal. Magnesium is probably not bound to the apatite lattice of dental enamel or dentine, or it is bound to a small degree only. It is mainly located in the hydration layer of the apatite crystallites. In the dental caries process it is preferentially dissolved together with the carbonate of the mineral phase. It is not known to what extent feasible dietary changes can modify tooth magnesium content during pre-eruptive tooth development. Animal experiments indicate that the elevation of dietary magnesium alone after tooth eruption has no definite capacity to modify the occurrence of dental caries. When fed in combination with small fluoride supplements in the diet magnesium and fluoride may support each other in preventing various calcium salt imbalances such as dental caries, arteriosclerosis and nephrocalcinosis. Although some recent in vitro findings indicate that extra magnesium in the fluid environment of cariogenic streptococci may protect them against the inhibitory action of fluoride, such magnesium changes do not seem possible in the human mouth under present or envisaged dietary conditions.


Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis.
Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.


Left Ventricular Assist Device Driveline Infections: The Achilles' Heel of Destination Therapy.
Heart failure is a chronic progressive disease that affects millions of people in the United States. Although medical management of heart failure has helped improve quality of life and survival, end-stage heart failure ultimately requires a heart transplant or long-term left ventricular assist device (LVAD) support. With more patients awaiting transplant, the demand for hearts outweighs the supply of donor hearts. The use of LVADs is increasing in patients with advanced heart failure as a treatment option for those awaiting a heart transplant or as a long-term solution if they are ineligible for a transplant. Although the LVAD is a marvel of modern medicine, infection is a cause of concern because today's LVADs are powered externally through a percutaneous driveline that can be a major source of infection.


Reflection on a patient's airway management during a ward-based resuscitation.
The bag-valve-mask (BVM) system is a common adjunct used during adult resuscitation to ventilate the lungs and deliver oxygen to patients in cardiopulmonary arrest. Gastric inflation, regurgitation and aspiration are well-documented complications of BVM ventilation, which can have serious consequences for patients. The aim of this paper is to review the cause of gastric inflation, regurgitation and aspiration during BVM ventilation and to consider techniques that have been suggested to reduce these problems. Using a reflective model, the author revisits an actual cardiac arrest, and within a structured framework considers the event itself, the context of the event and looks at ways in which practice could be improved in future. It is clear from the evidence that a reduction in peak airway pressure can reduce the risk of gastric inflation, regurgitation and aspiration. A review of the available research strongly suggests that in expert hands, the most effective means of reducing peak airway pressure is by reducing tidal volume by using a smaller bag. Although the evidence, as presented, for a reduction in bag size is convincing, there appears to be a problem that less regular users do not appear to be able to produce effective tidal volumes when using a smaller bag. If a reduced bag size is standardized, further research using a diverse group of health care workers with the BVM is required before a clear policy can be achieved. It is likely that training and practice will be shown to be important for nursing staff expected to use the smaller BVM.


Multidisciplinary assessment of children with developmental coordination disorder: using the ICF framework to inform assessment.
The aim of this study was to describe relationships in young children with motor coordination problems between measures of motor, functional, self-efficacy, and communication administered by a multidisciplinary team and the fit of these measures within the framework of the International Classification of Functioning, Disability and Health (ICF) (World Health Organisation, 2001). Sixty children, 40 males and 20 females, with mean age 72.5 months (SD= 11.4 months) referred to a university physiotherapy clinic met the inclusion criteria for developmental coordination disorder (DCD). Each measure provided a different perspective of performance when considered within the framework of the ICF. The findings suggest caution when using the Movement Assessment Battery for Children (M-ABC) for the purpose of diagnosis with young referred children, since 25 of the 60 children scored > 15th percentile, despite demonstrating motor deficits at home and school. Further research is needed to address assessment at the participation level. Viewing children from the multiple perspective of each discipline highlights the range of challenges faced by children with DCD.


Relationship between liver histopathological changes and HBsAg in 111 patients treated by long-term hemodialysis.
We studied liver biopsies performed between January 1972 and June 1980 in 111 patients receiving regular dialysis treatment. Biopsies were performed either because of suspected liver disease (61 patients) or routinely during abdominal surgery or kidney transplantation (50 patients). Repeat biopsies were done in 14 cases. Hepatitis B virus markers, assayed every 3 months during the observation period, were detected at some time in 71 patients (64%); 51 remained persistently positive. Histological examination showed normal liver in 39 cases, lobular hepatitis in 15, chronic persistent hepatitis in 36 and chronic active hepatitis in 21. All patients with chronic active hepatitis were chronic HBsAg carriers, and repeated biopsies showed aggravation only in these patients. The course was remarkably asymptomatic, with lesions leading to fibrosis despite the lack of histopathological patterns of severe necrosis and/or inflammation, which were conspicuously absent in this series.


Role of neurofilament aggregation in motor neuron disease.
A major question in the pathogenesis of motor neuron disease is why motor neurons are selectively susceptible to mutations in widely expressed gene products. Reexamination of motor neuron degeneration due to alterations of neurofilament (NF) expression suggests that disruption of assembly with aggregation of the light neurofilament (NFL) protein may be an upstream event and contributing factor leading to the preferential degeneration of motor neurons. The implications of these findings are that aggregation of NFL is not only a triggering mechanism to account for the hallmark aggregates of NF protein in sporadic and familial forms of amyotrophic lateral sclerosis, but that aggregates of NFL may also promote aggregation of wildly expressed proteins that are destabilized by missense mutations, such as by mutations in superoxide dismutase-1 protein. This review examines the potential role of NFs in determining and promoting the preferential degeneration of motor neurons in motor neuron disease. The underlying premise is that motor neurons are selectively susceptible to alterations in NF expression, that alterations in NF expression lead to NF aggregates in motor neurons, and that elevated levels of NF aggregates provide a favorable microenvironment for the formation of neurotoxic aggregation and degeneration of motor neurons.


Creatine kinase reference intervals determined from a multi-centre data pool.
Reference intervals for creatine kinase assayed at 37 degrees C using N-acetyl cysteine-activated methods have been determined on data obtained from 10 laboratories throughout Australia. The pooled distributions for males and females are skewed towards higher values and cannot be transformed to Gaussian distributions. The reference interval for females was calculated to be 34 to 180 U/l and for males it was 46 to 300 U/l. However, if creatine kinase is to be used in the diagnosis of myocardial infarction, the upper limit of the reference interval for males is considered to be too high. It is concluded that for males, the upper limit may need to be determined on specific populations such as hospital inpatients.


Mechanistic constraints on the trade-off between photosynthesis and respiration in response to warming.
Phytoplankton are responsible for half of all oxygen production and drive the ocean carbon cycle. Metabolic theory predicts that increasing global temperatures will cause phytoplankton to become more heterotrophic and smaller. Here, we uncover the metabolic trade-offs between cellular space, energy, and stress management driving phytoplankton thermal acclimation and how these might be overcome through evolutionary adaptation. We show that the observed relationships between traits such as chlorophyll, lipid content, C:N, and size can be predicted on the basis of the metabolic demands of the cell, the thermal dependency of transporters, and changes in membrane lipids. We suggest that many of the observed relationships are not fixed physiological constraints but rather can be altered through adaptation. For example, the evolution of lipid metabolism can favor larger cells with higher lipid content to mitigate oxidative stress. These results have implications for rates of carbon sequestration and export in a warmer ocean.


Identification, prevalence and pathogenicity of Colletotrichum species causing anthracnose of Capsicum annuum in Asia.
Anthracnose of chili (Capsicum spp.) causes major production losses throughout Asia where chili plants are grown. A total of 260 Colletotrichum isolates, associated with necrotic lesions of chili leaves and fruit were collected from chili producing areas of Indonesia, Malaysia, Sri Lanka, Thailand and Taiwan. Colletotrichum truncatum was the most commonly isolated species from infected chili fruit and was readily identified by its falcate spores and abundant setae in the necrotic lesions. The other isolates consisted of straight conidia (cylindrical and fusiform) which were difficult to differentiate to species based on morphological characters. Taxonomic analysis of these straight conidia isolates based on multi-gene phylogenetic analyses (ITS, gapdh, chs-1, act, tub2, his3, ApMat, gs) revealed a further seven known Colletotrichum species, C. endophyticum, C. fructicola, C. karsti, C. plurivorum, C. scovillei, C. siamense and C. tropicale. In addition, three novel species are also described as C. javanense, C. makassarense and C. tainanense, associated with anthracnose of chili fruit in West Java (Indonesia); Makassar, South Sulawesi (Indonesia); and Tainan (Taiwan), respectively. Colletotrichum siamense is reported for the first time causing anthracnose of Capsicum annuum in Indonesia and Sri Lanka. This is also the first report of C. fructicola causing anthracnose of chili in Taiwan and Thailand and C. plurivorum in Malaysia and Thailand. Of the species with straight conidia, C. scovillei (acutatum complex), was the most prevalent throughout the surveyed countries, except for Sri Lanka from where this species was not isolated. Colletotrichum siamense (gloeosporioides complex) was also common in Indonesia, Sri Lanka and Thailand. Pathogenicity tests on chili fruit showed that C. javanense and C. scovillei were highly aggressive, especially when inoculated on non-wounded fruit, compared to all other species. The existence of new, highly aggressive exotic species, such as C. javanense, poses a biosecurity risk to production in countries which do not have adequate quarantine regulations to restrict the entry of exotic pathogens.


Effects of Hexane in Supercritical Fluid Chromatography for the Separation of Enantiomers.
Supercritical fluid chromatography (SFC), operated in conventional mode, is normally recognized as normal phase chromatography, and uses a solvent combination of supercritical CO2 and alcohols to separate compounds. Hexane, a commonly used solvent in normal phase liquid chromatography (NP-LC), is rarely used in SFC and, in some cases, is added to the organic modifiers to increase liquid content in order to achieve better efficiency in preparative SFC for poorly retained compounds. Although hexane is believed to have similar solvent strength to that of supercritical CO2, its effects on the enantioseparation in SFC is largely unknown. To understand the chromatographic effects of an apolar solvent, such as hexane in SFC, we compared the chromatographic behaviors of 35 chiral compounds using a parallel SFC method under traditional SFC mode of only "pure" alcohol-CO2 to that of hexane-assisted SFC (HA-SFC), which uses mixtures of alcohol and hexane (as cosolvents) and CO2. We observed that, in some cases, hexane behaves just like supercritical CO2, where replacement of a portion of CO2 with hexane does not significantly change retention times or resolution of the peaks. In many cases, however, addition of hexane in mobile phases does affect chromatographic behavior of one or both enantiomers. Such effects might provide opportunities for separation of some enantiomers.


A review of leptospirosis in Malaysia.
This paper reviews the literature on leptospirosis in Malaysia from its first description in 1928 until the present day. Most of the early reports were on investigations of leptospirosis in wildlife and man and up-to-date, thirty-seven leptospiral serovars from thirteen serogroups have been bacteriologically identified. The thirteen serogroups are: Australis, Autumnalis Bataviae, Canicola, Celledoni, Grippotyphosa, Hebdomadis, Icterohaemorrhagiae, Javanica, Pomona, Pyrogenes, Sejroe and Tarassovi. Rats have been ascribed as the principal maintenance host of leptospires in Malaysia. However, serovars from the Pomona, Pyrogenes and Sejroe serogroups have yet to be isolated from rats. It is considered that the majority of leptospirosis cases in man were due to association of man with an environment where rats were plentiful. Recent investigations on domestic animals disclosed a high prevalence of infection in cattle and pigs and they were suspected as being the maintenance host for serovar hardjo and pomona respectively. There is ample scope for research in leptospirosis, particularly in the epidemiology and control of the disease in domestic animals. The strategy to control the infection in domestic animals and man in Malaysia is bound to be different from that of the temperate countries, basically due to the presence of a large number of leptospiral serovars in wildlife, further confounded by geographical and financial constraints.


Posttraumatic Stress Trajectories in World Trade Center Tower Survivors: Hyperarousal and Emotional Numbing Predict Symptom Change.
There is a paucity of knowledge concerning the underlying symptomatology of heterogeneous posttraumatic stress symptom (PTSS) trajectories following mass trauma, such as a terrorist attack. This study examined longitudinal PTSS trajectories using latent growth mixture modeling in 2,355 World Trade Center (WTC) tower survivors surveyed by the WTC Health Registry an average of 2.5, 5.5, and 10.5 years after the September 11, 2001 terrorist attacks. Covariates included sociodemographic characteristics, WTC-related exposure, and other traumas/stressors. Four curvilinear PTSS trajectories were identified: low symptom (74.9%), recovering (8.0%), worsening (6.7%), and chronic (10.4%). The majority of WTC survivors (85.3%) maintained stable symptom trajectories over time, with PTSS changes occurring less often. Although WTC-related exposure was associated with initial PTSS severity, exposure was not associated with chronicity or change of PTSS over time. Male gender and a higher number of post-WTC disaster life-stressors were associated with worsening symptom severity over time. Individuals with more severe hyperarousal symptoms at Wave 1, particularly of anxious arousal, were more likely to have PTSS that worsened over time, adjusted odds ratio (aOR) = 1.55. Less severe emotional numbing symptoms, particularly of dysphoria, at Wave 1, were marginally significantly associated with subsequent PTSS recovery, aOR = 0.75. Interventions that target hyperarousal and emotional numbing symptoms may mitigate a worsening of symptoms and facilitate posttraumatic recovery following future mass traumas, such as terrorist attacks. Further clinical implications are discussed.


Conditional survival of uveal melanoma using The Cancer Genome Atlas (TCGA) classification (Simplified Version) in 1001 cases.
To understand conditional prognostic value of the Cancer Genome Atlas (TCGA) for uveal melanoma metastasis based on event-free survival at 1, 2, 3, 4, and 5 years. A retrospective study of eyes with uveal melanoma categorized according to TCGA and studied for nonconditional and conditional risks for metastasis at 5 and 10 years. Of 1001 eyes with uveal melanoma, the nonconditional (standard, at presentation) 5-year/10-year metastatic rate was 18%/25%. The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed 10%/18% and the conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed 9%. The TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). The non-conditional 5-year/10-year metastatic rate revealed Group A (4%/6%), Group B (12%/20%), Group C (23%/49%), and Group D (60%/68%). The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed Group A (2%/5%), Group B (8%/18%), Group C (21%/40%), and Group D (38%/50%). The conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed Group A (2%), Group B (10%), Group C (33%), and Group D (20%). The peak incidence of metastasis for Groups A and B occurred during years 5-6, C during years 4-6, and D during years 1-2. Survival outcomes for uveal melanoma as non-conditional (at presentation) and conditional (event-free survival during follow-up) reveal reduction in metastatic rate over time. For those with 5-year metastasis-free survival, the 10-year conditional risk for metastasis was 9%.


Desert on the menu? What children are served in German full-service restaurants.
Prevalence of obesity and overweight among children is rising worldwide. Thus, the importance of restaurants as food environments is also growing. Considering these developments, the present study describes and evaluates menus and meals offered to children in German full-service restaurants. Using quota sampling procedure, a representative sample of German full-service restaurants was identified. The individual meals were then assessed, using the Children's Menu Assessment tool (CMA). A total of 500 restaurants and 1,877 individual meals were analyzed. On average, every menu included 3.76 ± 1.31 meals for children. The arithmetic mean of the CMA score was 0.73 ± 0.85. Around 80% of all offered meals were limited to eight typical dishes and over 50% included French fries or another form of fried potatoes. Not one of the meals included any nutritional information. Healthy entrees were never marked (e.g. by an optional qualitative information such as healthy food symbol or a healthier choice tag). Eighty-one percent of all the main components in the meals were rated as unhealthy and none of the meals used wholegrain products. The automatic inclusion of a drink and free refill options are both rather unusual in Germany, as well as the use of cartoon characters and product logos or giving away promotional toys. A positive correlation was found between the price of the food and its quality. The majority of dishes feature a high energy density while simultaneously having a low nutrient density. Overall, the range of food on offer for children in German restaurants is unhealthy and lacking in variety. There is an urgent need for improvement of both the menus themselves as well as the offered meals. Our study is not only by far the most comprehensive study, but also the study with the worst CMA score values worldwide.


Betatron coupling measurement and optimization in Indus-2 storage ring.
Brightness is an important parameter for any synchrotron radiation source. Correcting the emittance coupling is one of the ways to increase photon beam brightness in the operational storage ring. The main source of this effect is betatron coupling, resulting from the skew quadrupolar errors. Tune split and Linear Optics from Closed Orbit (LOCO) techniques are used to measure the betatron coupling. We discuss the measurement result of betatron coupling and its correction in the Indus-2 storage ring using available four power supplies, as the knobs, driving the skew quadrupole windings located on sextupoles. The measured coupling ratio of ∼0.8% closely matches with the coupling ratio obtained from the LOCO fit model. Based on LOCO correction, the coupling ratio can be reduced to ∼0.4%, which is limited by the degrees of freedom and not by the field strengths. To achieve a smaller and controlled value of coupling, simulation studies based on the LOCO fit model and using the multi-objective differential evolution algorithm with more skew quadrupole power supplies are performed in Indus-2. With sixteen independent power supplies, the emittance ratio can be reduced to <0.04% and the brightness enhances by an order of magnitude. Besides, the optimization method used provides quantitative trade-offs between coupling related parameters such as beam tilt angle, emittance ratio, vertical emittance, and vertical beam size, and desired values can be chosen from the Pareto optimal front.


Cochlear implantation in Donnai-Barrow syndrome.
Donnai-Barrow syndrome is a rare autosomal recessive disorder associated with severe sensorineural hearing loss (SNHL). Several ocular abnormalities have also been described in this syndrome, including hypertelorism, down-slanting palpebral fissures, myopia and retinal detachment. The condition is also associated with diaphragmatic hernia, exomphalos, absent corpus callosum and developmental delay. We describe the first recorded case of cochlear implantation in this rare disorder. This case of Donnai-Barrow syndrome was identified from our paediatric cochlear implant database. A case-note review was performed identifying patient demographics, operative findings and surgical outcome. In addition, pre- and post-operative auditory and communication performance was analysed. The child initially received a right cochlear implant at 39 months of age, but unfortunately the device failed 4 years post-operatively. Subsequently, bilateral simultaneous cochlear implantation was performed. BKB scores were 98% for bilateral implant use when tested 2 years post-operatively. Individual testing revealed a score of 94% for the right ear alone, and 80% for the left. The child achieved a 100% score on sound localisation testing using 3 speakers. Donnai-Barrow syndrome is a rare cause of SNHL compounded by the potential for visual impairment. To our knowledge this is the first report of cochlear implantation to rehabilitate hearing loss in this condition.


[The extension of the Leipzig questionnaire of motives to have a child (LKM) for use in oncology--test construction and psychometric review].
Many young cancer patients had not completed family planning at the time of diagnosis. A cancer disease may change procreative attitudes and the development of specific motivations of having a child (for and against) is possible. This paper addresses the extension of the Leipzig questionnaire on motives for wanting children (LKM) in the context of cancer. Specific motivations of cancer patients are presented and test-statistically verified. Based on previous findings and a qualitative questioning (patients, professionals) items for specific motivations were developed and pre-tested. The revised version (20 items) was tested on a sample of 175 young cancer patients. Good to adequate item discrimination parameter and reliability (α=0.86) were shown. The factor analysis revealed the 2 scales "PRO - motivations for having children after cancer" and "CON - motivations against having children after cancer". These additional scales of specific motivations allow for a reliable and economical measure of motivations to have a child in young cancer patients. In the future the scales can be also used for other serious physical disease in young adulthood.


Effects of fludioxonil and pyrimethanil, two fungicides used against Botrytis cinerea, on carbohydrate physiology in Vitis vinifera L.
In Vitis vinifera L, photosynthesis and photosynthate partitioning are affected in the presence of fludioxonil and pyrimethanil, two fungicides commonly used in vineyards against Botrytis cinerea Pers. However, the effects were found to be different according to the model studied: plantlets (cv Chardonnay) grown in vitro, fruiting cuttings (cv Chardonnay) and plants grown in vineyards (cvs Chardonnay, Pinot noir and Pinot Meunier). In the plantlets grown in vitro, both fungicides decreased gas exchanges, photosynthetic pigment and starch concentrations in the leaves, whereas soluble carbohydrates transiently accumulated, suggesting that plantlets mobilised starch in response to photosynthesis inhibition caused by fungicides. In the fruiting cuttings, the fungicides did not affect photosynthesis, although fludioxonil caused starch decrease in parallel with sucrose accumulation, suggesting that the fungicide effects were of lower intensity than in vitro. Conversely, in vineyard, the two fungicides stimulated photosynthesis and increased pigment concentrations in the three vine cultivars tested. In the meantime, glucose, fructose and starch levels of the leaves declined after fungicide exposure, whereas sucrose accumulated, indicating that sucrose synthesis increased in the leaves following the fungicide treatment. Among the three varieties, Chardonnay was the most sensitive to the fungicides as revealed by the intensity of the responses and the longer period for recovery. In vineyard, the results suggested that the two fungicides, in addition to inhibiting B cinerea development, had a beneficial effect on vine physiology through the stimulation of leaf carbon nutrition, which may further enable the plant to rapidly make use of its defence reactions.


Speed and accuracy of visual image discrimination by rats.
The trade-off between speed and accuracy of sensory discrimination has most often been studied using sensory stimuli that evolve over time, such as random dot motion discrimination tasks. We previously reported that when rats perform motion discrimination, correct trials have longer reaction times than errors, accuracy increases with reaction time, and reaction time increases with stimulus ambiguity. In such experiments, new sensory information is continually presented, which could partly explain interactions between reaction time and accuracy. The present study shows that a changing physical stimulus is not essential to those findings. Freely behaving rats were trained to discriminate between two static visual images in a self-paced, two-alternative forced-choice reaction time task. Each trial was initiated by the rat, and the two images were presented simultaneously and persisted until the rat responded, with no time limit. Reaction times were longer in correct trials than in error trials, and accuracy increased with reaction time, comparable to results previously reported for rats performing motion discrimination. In the motion task, coherence has been used to vary discrimination difficulty. Here morphs between the previously learned images were used to parametrically vary the image similarity. In randomly interleaved trials, rats took more time on average to respond in trials in which they had to discriminate more similar stimuli. For both the motion and image tasks, the dependence of reaction time on ambiguity is weak, as if rats prioritized speed over accuracy. Therefore we asked whether rats can change the priority of speed and accuracy adaptively in response to a change in reward contingencies. For two rats, the penalty delay was increased from 2 to 6 s. When the penalty was longer, reaction times increased, and accuracy improved. This demonstrates that rats can flexibly adjust their behavioral strategy in response to the cost of errors.


Products of aqueous chlorination of bisphenol A and their estrogenic activity.
To assess the estrogenic activity potentially stemming from bisphenol A (BPA) in drinking water, APCI/LC/MS and NMR were used to identify the products of its aqueous chlorination under the following conditions: 500 microg/L bisphenol A and 1.46 mg/L sodium hypochlorite (pH 7.5) at 25 degrees C. The 13 products (4-chloro-BPA; 2,6'-dichloro-BPA; 2,6-dichloro-BPA; 2,2',6'-trichloro-BPA; 2,2',6,6'-tetrachloro-BPA; trichlorophenol; 4-isopropyl-2'-hydroxylphenol; and six kinds of polychlorinated phenoxyphenols (PCPPs)) were found in the chlorinated BPA solution. Three main pathways are proposed: (1) chlorine-substitution reactions on the aromatic ring, followed by dehydration to form the chlorine-substituted BPA, (2) chlorine substitution reactions followed by cleavage of the alpha-C on the isopropyl moiety with positive partial charge and beta'-C on the benzene moiety with a negative partial charge to form trichlorophenol and 4-isopropyl-2'-hydroxylphenol, and (3) the formation of PCPPs. Especially for pathway 2, the reaction mechanism was clarified based on semiempirical quantum mechanical calculations. The reaction proceeded by attack of the OH and Cl (from HOCl) on the alpha-C on the isopropyl moiety with a positive partial charge and on the beta'-C with a negative partial charge on the benzene moiety. The activation energies forthe HOCl/4-chloro-BPA and 2,2',6,6'-tetrachloro-BPA reactions were 0.14 and 0.15 kcal/mol, respectively. Finally, the estrogenic activity of the aqueous chlorinated BPA solution was assessed by an estrogen receptor binding assay and a yeast two-hybrid system. It was found that the binding affinity of the chlorinated aqueous BPA at 60 min was 24 times that before chlorination. The transcriptional activation-induced by products were detected by a yeast two-hybrid system based on the ligand-dependent interaction of two proteins, a human ER and a coactivator, suggesting that the chlorinated BPA solution elicits an ability to mimic the effect of the estrogen hormone.


Thalidomide in the treatment of Kaposi's sarcoma.
Kaposi's sarcoma (KS) is a lymphangioproliferative tumour. Therapy of KS depends on the characteristics of the disease, especially area and growth rate of lesions, and patient condition. Currently symptomatic resectable lesions are excised, whereas more advanced disease and unresectable lesions are treated with radiotherapy. If a large area or internal organs are affected or other treatments fail, chemotherapy is used. Recently some authors have reported their encouraging experience in the use of thalidomide in patients with AIDS-related KS. To evaluate the efficacy of thalidomide in 3 patients with non-AIDS-related KS. Two patients with classic widespread cutaneous and 1 with iatrogenic cutaneous and visceral KS were treated with thalidomide (100 mg/day) for 12 months. In all 3 patients partial remission was evident after 4 months of thalidomide therapy; in 2 out of 3 complete remission was achieved after 12 months of treatment. Our results seem to confirm the utility of thalidomide in the treatment of non-AIDS-related KS.


Angioplasty and stenting in carotid dissection with or without associated pseudoaneurysm.
Carotid angioplasty and stent placement may be the preferred treatment in patients with carotid dissection who have failed medical management. The goal of this study was to determine the procedural feasibility and safety as well as long-term complication rates of carotid angioplasty and stent placement in a consecutive cohort of relatively young, high-surgical-risk patients. A series of 26 consecutive patients (mean age, 49 years; 15 men and 11 women) who underwent angioplasty and stent placement for carotid dissection with or without pseudoaneurysm from April 1997 to April 2005 at our institution (9 traumatic, 8 spontaneous, and 9 iatrogenic) was retrospectively reviewed. Twenty-eight stents were used in 29 procedures performed on 27 vessels (20 internal carotid arteries and 7 common carotid arteries). Patients were followed with cerebral angiography, CT, sonography, or clinically for a mean of 14.6 months (range, 5 days to 48.2 months) with 17 of 26 patients having at least 6 months of follow-up. Procedural and long-term complication rates were calculated. Dissection-induced stenosis was reduced from 71 +/- 18% to no significant stenosis in 20 of the 21 patients with measurable stenosis. The procedural transient ischemic attack (TIA) rate was 3 of 29 procedures (10.3%). There were no procedural strokes. One patient required angioplasty of a common femoral artery. One procedure was terminated when an asymptomatic new intimal flap was created before intervention. Two patients had occlusions of the treated vessel noted at 22 days (presented with contralateral stroke) and 3.4 months (asymptomatic). There were 2 unrelated deaths from myocardial infarction at 8 days and 15.2 months. Two patients had recurrent ipsilateral TIA at 2.7 months and 12 months. The 30-day occlusion and death rate was 2 of 29 procedures (6.9%). In this series, angioplasty and stent placement were effective in relieving stenosis secondary to carotid dissection with or without pseudoaneurysm and have low rates of ischemic complications.


Receptor-mediated endocytosis across human placenta: emphasis on megalin.
Receptor-mediated endocytosis plays an important role in the maternal-fetal transport of various nutrients and drugs across human placenta. Megalin, a 600 kDa endocytic receptor, is expressed in placental syncytiotrophoblasts and is thought to contribute to the transport functions of the placenta. However, the molecular mechanisms involved in megalin-mediated transplacental transport of most substrates have not yet been characterized. Megalin is most extensively expressed on the apical surface of renal proximal tubular epithelial cells, where it is involved in the reabsorption of proteins, vitamins, and polybasic drugs including aminoglycoside (AG) antibiotics. It has been suggested that megalin-mediated endocytosis is primarily responsible for accumulation of aminoglycosides (AGs) in the renal proximal tubule, which results in direct cellular injury and death. The role of megalin in the renal uptake and accumulation of aminoglycosides has therefore received much attention. It is not known, however, whether megalin is involved in the maternal-fetal transport of AGs and other commonly used polybasic drugs. Studies designed to characterize the role of megalin in transplacental transport and to understand the molecular mechanisms involved in megalin-mediated endocytosis across human placenta are therefore needed.


Long-term functional outcomes after 10 years of bilateral cochlear implantat use.
The aims were to determine the benefit of bilateral cochlear implantation in a 20 years old patient implanted in Croatia on hearing and speech development. The male patient, after 10 years of deafness, got cochlear implants Med-EL Combi 40+ on both sides in one-stage surgery. The etiology of his deafness was posttraumatic meningitis. Auditory capacity and speech recognition tests were performed for both ears separately and together Average hearing level on the right ear with right cochlear implant switched on started at 62 dB 1 month after the cochlear implantation and was on 55 dB after 10 years. Average hearing level on the left ear with left cochlear implant switched on started at 55 dB 1 month after the cochlear implantation and was on 32 dB after 10 years. Average hearing level on the both ears with 2 cochlear implants switched on started at 35 dB 1 month after the cochlear implantation and was on 27 dB after 10 years. Long-term functional outcomes with bilateral cochlear implantation provides advantages over unilateral implantation including improved hearing level, speech perception in noise and improved sound localization.


Improving compliance with guidelines may lead to favorable clinical outcomes for patients with non-muscle-invasive bladder cancer: A retrospective multicenter study.
Clinical guidelines recommend that patients with non-muscle-invasive bladder cancer (NMIBC) should be treated with appropriate adjuvant therapy. However, compliance with guideline recommendations is insufficient, and this may lead to unfavorable outcomes. We aimed to investigate the level of adherence to guideline recommendations in patients with NMIBC and evaluate the outcomes of those who did and did not receive guideline-recommended therapies. We performed a retrospective analysis of patients with histologically diagnosed NMIBC. The percentage of patients with intermediate- and high-risk tumors who received adjuvant intravesical therapy or second transurethral resection (TUR) was calculated. Recurrence-free survival was assessed in patients who did and did not receive the therapies. We conducted a propensity score-matched analysis to compare outcomes between patients with intermediate-risk and T1 NMIBC who did and did not undergo guideline-recommended therapies. Overall, 1204 patients from the Tohoku Urological Evidence-Based Medicine Study Group and Kyoto University Hospital were included. Of patients with intermediate- and high-risk tumors, 91.0% and 74.0% did not receive maintenance bacillus Calmette-Guérin (BCG), respectively. In both groups, significantly better recurrence-free survival was found for patients treated with maintenance BCG. Among patients with T1 NMIBC, only 16.7% underwent guideline-recommended therapies, that is, a second TUR and maintenance BCG. Significantly greater recurrence-free survival was observed in patients who received guideline-recommended therapies compared with propensity-matched patients who did not. Guideline-recommended therapies may contribute to improvements in outcomes for patients with NMIBC, suggesting that improvements in adherence to clinical guidelines may lead to favorable outcomes.


Application of ELISA with antigenic glycolipids in early diagnosis of pulmonary tuberculosis.
Antibodies against M. tuberculosis antigenic glycolipids were determined by enzyme-linked immunosorbent assay (ELISA) in 80 sera from patients suspected of pulmonary tuberculosis, with suggestive clinical signs and radiological abnormalities, but smears negative. The test was also performed on 68 control sera from patients with bacteriologically confirmed pulmonary tuberculosis, in different stages of disease. We obtained the test sensitivity of 89.5% for the confirmed tuberculosis patient sera. Low levels of specific antibodies and the sensitivity of 75% were found when using ELISA in smears negative patients at the onset of clinical tuberculosis. The experimental results showed that ELISA could be used as a supporting test in early diagnosis of pulmonary tuberculosis.


[Fast-track multimodal rehabilitation programs in laparoscopic colorectal surgery].
For the last two decades, general and digestive surgeons have attempted to improve the postoperative course of surgical patients. Classical perioperative treatment can be described as a period of preoperative dehydration caused by fasting and intensive colon preparation followed by fluid overload generally due to excessively prolonged serum therapy. There is also perioperative surgical stress, the trauma of surgery itself, and a long period of drainage and nasogastric tubes. The patient is thus literally confined to bed and mobilization is, at the very least, difficult. Moreover, the use of opiates delays intestinal peristalsis and consequently oral nutrition. All together, these factors prolong the length of hospital stay and hamper recovery. All these perioperative treatment modalities have been questioned by Kehlet, resulting in a set of new, more realistic and evidence-based modalities, currently known as the fast-track program. The aim of this program is to decrease perioperative stress, reduce organ involvement produced by surgical trauma and hasten the patient's general recovery. Major advantages of this program consist not only of shorter length of hospital stay but also of a concurrent improvement in patients' quality of life and a reduction in mortality. The present review article analyzes all these modalities, with special emphasis on laparoscopic colorectal surgery. This approach is presented as one of the elements of the fast-track program.


Parry Romberg syndrome presenting with a giant intracranial aneurysm: a case report.
A giant intracranial aneurysm was diagnosed in a 10-year-old girl when she developed a right abducens nerve palsy. The aneurysm was treated successfully. Six years later, however, she presented with a progressive en coup de sabre deformity, leading to the diagnosis Parry Romberg Syndrome (PRS), a rare diagnosis characterized by hemifacial atrophy of skin, subcutaneous tissue, skeletal muscle and bones and often associated with various non-specific intracerebral abnormalities. In this patient retrospective analysis of computed tomography and magnetic resonance imaging imaging indeed revealed intracerebral calcifications and aspecific white matter lesions. Remarkably, in this patient the giant intracranial aneurysm turned out to be the presenting symptom of PRS years before the characteristic facial deformities became apparent.


Effects of Forsythia suspensa extract on growth performance, nutrient digestibility, and antioxidant activities in broiler chickens under high ambient temperature.
A 42-d trial was conducted with 252 broiler chickens (d 1 of age, 38.8 +/- 1.3 g of BW) to determine the effects of Forsythia suspensa extract on growth performance, nutrient digestibility, and antioxidant activities under high ambient temperature (32 +/- 1 degrees C). The feeding program consisted of a starter diet from d 1 to 21 of age and a finisher diet from d 22 to 42 of age. Dietary treatments included a negative control group (NC) fed a cornsoybean meal based diet without vitamin C or Forsythia suspensa extract, a positive control group fed a diet with 200 mg of vitamin C/kg, and a test group (FS) fed with 100 mg of Forsythia suspensa extract/kg. There were 14 cages per treatment and 6 birds per cage during the study. Birds had free access to diets and water during the entire period. Body weight and feed intake were measured at d 21 and 42. Blood and tissue samples were collected at d 21 and 42 for assay of antioxidant indices. Growth performance did not differ among treatment groups during the starter period. In the finisher phase, birds in FS had greater (P < 0.05) average daily gain, feed conversion, and apparent digestibility of energy, CP, calcium, and phosphorus than birds in NC. Furthermore, birds in FS had greater (P < 0.05) total antioxidant capacity and superoxide dismutase activity and lower (P < 0.05) malondialdehyde activity in the serum than birds in NC. The FS birds had greater (P < 0.05) muscle superoxide dismutase activity and lower (P < 0.05) malondialdehyde than NC birds. During the entire period, hepatic superoxide dismutase activity of FS birds was greater (P < 0.05) than that of NC birds. Dietary supplementation with Forsythia suspensa extract can enhance nutrient digestibility and growth performance possibly by reducing oxidative stress of broiler chickens under high ambient temperatures.


Electrophoretic mobility of human red blood cells coated with poly(ethylene glycol).
Poly(ethylene glycol), abbreviated as PEG, was covalently attached to the surface of human red blood cells (RBC) and the effects of such coating on the regions near the cell's glycocalyx were explored by means of cell electrophoresis. RBC electrophoretic mobilities were measured, in polymer-free buffers of various ionic strengths, as functions of PEG molecular mass (3.35, 18.5, 35.0, 35.9 kDa), geometry, (linear or 8-arm branched) and polymer/RBC ratio during attachment. The results indicate marked decreases of the mobility (up to 85%) which were affected by polymer molecular mass and geometry. Since PEG is neutral and its covalent attachment only removes positively-charged amino groups on the cell membrane, such decreases of mobility likely reflect structural changes near and within the RBC glycocalyx. Experimental results were analyzed using an extended "hairy sphere" model to consider friction and thickness of the polymer layer. Calculated polymer layer thickness increased with molecular mass for linear PEGs and was less extended for a branched PEG of similar molecular mass. Friction within the polymer layer increased with polymer/RBC ratio and for the linear PEGs was inversely related to molecular mass; friction was greatest for the branched PEG. Our results are consistent with the effects of attached PEGs on RBC aggregation and surface antigenic site masking, and suggest the usefulness of electrophoretic mobility techniques for studies of bound neutral polymers.


Immunogenicity of self-associated aggregates and chemically cross-linked conjugates of the 42 kDa Plasmodium falciparum merozoite surface protein-1.
Self-associated protein aggregates or cross-linked protein conjugates are, in general, more immunogenic than oligomeric or monomeric forms. In particular, the immunogenicity in mice of a recombinant malaria transmission blocking vaccine candidate, the ookinete specific Plasmodium falciparum 25 kDa protein (Pfs25), was increased more than 1000-fold when evaluated as a chemical cross-linked protein-protein conjugate as compared to a formulated monomer. Whether alternative approaches using protein complexes improve the immunogenicity of other recombinant malaria vaccine candidates is worth assessing. In this work, the immunogenicity of the recombinant 42 kDa processed form of the P. falciparum merozoite surface protein 1 (MSP1(42)) was evaluated as a self-associated, non-covalent aggregate and as a chemical cross-linked protein-protein conjugate to ExoProtein A, which is a recombinant detoxified form of Pseudomonas aeruginosa exotoxin A. MSP1(42) conjugates were prepared and characterized biochemically and biophysically to determine their molar mass in solution and stoichiometry, when relevant. The immunogenicity of the MSP1(42) self-associated aggregates, cross-linked chemical conjugates and monomers were compared in BALB/c mice after adsorption to aluminum hydroxide adjuvant, and in one instance in association with the TLR9 agonist CPG7909 with an aluminum hydroxide formulation. Antibody titers were assessed by ELISA. Unlike observations made for Pfs25, no significant enhancement in MSP1(42) specific antibody titers was observed for any conjugate as compared to the formulated monomer or dimer, except for the addition of the TLR9 agonist CPG7909. Clearly, enhancing the immunogenicity of a recombinant protein vaccine candidate by the formation of protein complexes must be established on an empirical basis.


Effect of culture conditions on the isocitrate dehydrogenase and isocitrate lyase activities in Chlamydomonas reinhardtii.
In the green alga Chlamydomonas reinhardtii, nitrogen staravation induced a reversible increase (2-fold) in NAD-isocitrate dehydrogenase (NAD-IDH; EC 18.104.22.168) and NADP-isocitrate dehydrogenase (NADP-IDH; EC 188.8.131.52) activities. Both enzymes were not affected by the concentration of CO2 , the dark or the nature of the nitrogen source (nitrate, nitrite, or ammonium). When cells growing autotrophically were transferred to heterotrophic conditions, a 40% reduction of the NAD-IDH activity was detected, a 2-fold increase of NADP-IDH was observed and isocitrate lyase (ICL; EC 220.127.116.11) activity was induced. The replacement of autotrophic conditions led to the initial activity levels. NAD- and NADP-IDH activities showed markedly different patterns of increase in synchronous cultures of this alga obtained by 12 h light/12 h dark transitions. While NAD-IDH increased in the last 4 h of the dark period, NADP-IDH increased during the last 4 h of the light period, remaining constant for the rest of the cycle.


[Rupture of the rotator cuff. Quantification of indirect signs in standard radiology and the Leclercq maneuver].
The roentgenograms and the "Leclercq's manoeuvre" of 105 patients who had a shoulder arthrography were reviewed. We differentiated two groups: One with a rotator cuff tear. The other without a rotator cuff tear. The space between the acromion and the head of the humerus was measured on rotation zero degree and external rotational roentgenograms. When the acromio-humeral space was less than 8 mm, it was always correlated with a rotator cuff tear (specificity = 1). If at least tow of the following signs were present, there was in most cases a rotator cuff tear (specificity = 0.96): Sclerosed acromion. Spur of the acromion. Cystic changes around the greater tuberosity. Rounded tuberosities. Inferior gleno-humeral spur. The "Leclercq's manoeuvre" was considered positive either when there was an acromio-humeral space narrowing compared with the other side, or when there was an upward subluxation of the head of the humerus. When positive there was always a rotator cuff tear (sensibility = 0.7; specificity = 1).


Essential fatty acids and malignant disease.
EFAs have shown promising anti-tumour effects in cell culture studies and in animal models. However, it is also clear that in man EFAs can have marked immunomodulatory effects, in particular, inhibiting certain aspects of host anti-tumour defence mechanisms (natural cytotoxicity and cytokine production). Further careful studies are required to evaluate more precisely the role of EFAs in the treatment of malignant disease in man.


Unknown biological effects of L-glucose, ALA, and PUFA.
Key substrates including glucose, amino acids, and fatty acids play core roles in nutrient metabolism. In this review, we describe phenomena observed when key substrates are applied to cells. We focused on three promising substrates: L-glucose derivatives, 5-aminolevulinic acid, and polyunsaturated fatty acid. Since they are assumed to give a specific reaction when they are transported into cells or metabolized in cells, they are expected to be applied in a clinical setting. We provide the latest knowledge regarding their behaviors and effects on cells.


Production of corticotrophin releasing hormone by the sheep placenta in vivo.
Corticotrophin-releasing hormone (CRH)-like activity has been reported in placental tissue and to rise sharply in maternal and fetal plasma during the third trimester of human pregnancy. It is unclear whether this applies to other species, if the placental secretes CRH, and if so what factors regulate its production. The present experiments were conducted on sheep 123-144 days pregnant. CRH-like activity was detected in the plasma of the uterine and umbilical vein at modest concentrations. These concentrations rose in the final days before delivery. Reduction of uterine blood flow, particularly caused by an elevation of maternal adrenaline, had the capacity to sharply increase placental output. The CRH-like activity on separation by hplc had the characteristics of 41CRH. The results are discussed in relation to the potential role of placentally-derived CRH.


Non-arteritic anterior ischemic optic neuropathy after uneventful delivery in a healthy woman.
Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of optic nerve swelling and optic neuropathy in adults over 50 years of age. It has been rarely reported during pregnancy, mostly related to systemic and ocular predisposing conditions. We report the case of a 44 years-old healthy female with no previous remarkable clinical history. She had in vitro fertilisation treatment to get pregnant. 18 days after uneventful cesarean section she referred sudden painless vision loss in her right eye (RE), denser inferiorly, with concurrent optic disc edema and relative afferent pupillary defect. Steroid intravenous treatment during the acute episode showed no improvement. Our patient showed normal magnetic resonance imaging (MRI), blood test, autoimmune disease biomarkers, infectious serology and inflammatory markers. She was diagnosed of RE NAION. After one year follow-up visual field defect remains stable. As far as we know this is the first report of NAION after in vitro fertilisation, uneventful pregnancy and cesarean section showing no systemic or ocular risk factors other than a small cup to disc ratio. Hemodynamic and hormonal changes during late pregnancy and uneventful cesarean section can trigger an episode of NAION in a healthy young woman.


[Articular fractures of the distal femur. Comparative analysis of three surgical treatments].
The distal articular femur fracture is a serious injury that for years has been a problem in traumatology. It is often believed that produced varying degrees of permanent disability in the knee and that the fate of the joint was determined by the injury rather than treatment. Present the results of surgical treatment of articular distal femur fractures type C2 with three treatment modalities: dynamic condylar screw (TDC), condylar buttress plate (PSC) and periarticular plate (PPA). We conducted a comparative study of three therapeutic series designed to compare the effectiveness of dynamic condylar screw, the condylar buttress plate and periarticular plate in treating complete articular fractures of distal femur type C2. Patients of both genders, aged between 16 and 60 years, treated in the IAHULA, with a minimum follow up of 24 months. We included 42 patients divided into three groups. Males predominated with 73.8%, the most affected age group was 21-30 years with 28.57%. The most common type of fracture was the 33C2.3 with 42.86%. The 71.43% of patients experienced complications, highlighting joint stiffness, angular deviation in recurvatum, chronic pain and post traumatic osteoarthritis. TDC and the PPA are valid options for the treatment of distal femur fractures AO 33C2, as offered better functional results than PSC.


Effective Reparation for the Guatemala S.T.D. Experiments: A Victim-Centered Approach.
Discussion of reparations for U.S.-Guatemala STD experiments of the 1940s and 50s should be informed by a range of international and U.S. reparation experiences, so that features that impair the effectiveness of repair are avoided, and features that enhance effectiveness of repair are emulated. Two features have contributed to the effectiveness or ineffectiveness of repair elsewhere but have not been critically examined in relation to the Guatemalan experiments: Whether experimental subjects or their families have the opportunity to participate in reparations processes, and whether any group of experimental subjects is intentionally denied recognition. Three advantages of victim participation are explored, and a critique provided of one narrow delimitation of victims. Even if political and moral failings ultimately prevent reparations for Guatemalan experimental subjects, an emphasis on effectiveness and victim-centeredness should nonetheless shape reparations for other, future victims of human rights abuses in experimentation.


Differential anesthetic depression of chronotropic baroreflexes in rats.
To assess anesthetic alteration of chronotropic baroreflexes, arterial pressure and heart rate (HR) were monitored continuously during intravenous (i.v.) infusions of phenylephrine or sodium nitroprusside in rats that were either awake or anesthetized (with pentobarbital, urethane, or chloralose). Ensuing reflex HR responses during each drug infusion were determined in two ways: (a) at 10-s intervals (time analysis), and (b) with every 5-mm Hg change in pressure (pressure analysis). Results were less variable with pressure than with time analysis. With responses from awake rats as a basis for comparison, pressure analysis showed that pentobarbital greatly attenuated both reflex tachycardia and bradycardia, whereas urethane and chloralose reduced only reflex tachycardia. Depression by pentobarbital of both reflex tachycardia and bradycardia suggests severe attenuation of both sympathetic and parasympathetic tone. In contrast, preferential alteration of reflex tachycardia by chloralose and urethane implies a greater attenuation of sympathetic than parasympathetic tone.


The Clouclip, a wearable device for measuring near-work and outdoor time: validation and comparison of objective measures with questionnaire estimates.
To validate a novel wearable device that can measure both viewing distance and light exposure, Clouclip, and compare questionnaire estimates regarding near-work and outdoor time with the objective measures obtained using Clouclip. Fifteen Clouclips were selected to measure different distances and levels of illuminance. With each Clouclip, five measurements at different distances and light intensities were measured and recorded. Eighty participants wore Clouclips for a week and completed an activity questionnaire afterwards. The intra- and inter-Clouclip coefficients were 1.00 and 0.99 for measuring distance and 1.00 and 1.00 for illuminance, respectively. Within the measurement limit, the maximum relative error was 2.07% for distance and 2.23% for illuminance. Assuming that <30 cm was the typical distance for near-work activities and >1000 Lux was the typical cut-off for outdoor environments, the questionnaire showed a trend of overestimation for both. The greatest overestimation of near-work occurred during the school period [Questionnaire: 4.73 hr (4.73, 5.07) versus Clouclip: 2.16 hr (1.74, 2.78); p < 0.01]. The greatest overestimation of outdoor activity also occurred during the school period [Questionnaire: 1.60 hr (1.33, 1.85) versus Clouclip: 1.21 hr (0.96, 1.50); p < 0.01]. Based on Clouclip, the total time spent outdoors was estimated to be 1.55 hr on school days, of which 0.34 hr occurred after school. For weekend days, however, the duration was only 0.17 hr. Clouclip had excellent precision and accuracy. Although the agreement between the questionnaire and Clouclip was relatively poor, they were able to complement each other to provide a more logical and feasible assessment of exposure to near-work and outdoor activity. Indoor-oriented lifestyles were found to predominate in Chinese children.


Understanding User Requirements for a Senior-Friendly Mobile Health Application.
The advancement of mobile technologies has motivated countries around the world to aim for smarter health management to support senior citizens. However, the use of mobile health applications (mHealth apps) among senior citizens appears to be low. Thus, drawing upon user expectations, the present study examined user requirements for a senior-friendly mHealth application. A total of 74 senior citizens were interviewed to explore the difficulties they encounter when using existing mobile apps. This study followed Nielsen's usability model to identify user requirements from five aspects, namely learnability, efficiency, memorability, error, and satisfaction. Based on the results, a guideline was proposed pertaining to usability and health management features. This guideline offers suggestions for mHealth app issues related to phrasing, menus, simplicity, error messages, icons and buttons, navigation, and layout, among others. The study also found that speech recognition technology can help seniors access information quickly. The proposed guideline and findings offer valuable input for software and app developers in building more engaging and senior-friendly mHealth apps.


Prolonged paralysis after treatment with neuromuscular junction blocking agents.
Previous reports have described prolonged paralysis after treatment with neuromuscular junction blocking agents in critically ill patients. The purpose of this study was to further describe a group of patients who developed prolonged weakness after treatment with these agents. Clinical information, electrodiagnostic and muscle pathology results are described in this group of patients. Clinical information includes diagnoses, dosage of neuromuscular junction blocker, other medications affecting the neuromuscular system, and neuromuscular examination and clinical course. All patients were seen in the ICUs of three local hospitals. Included were critically ill patients with a variety of diagnoses, all of whom developed severe weakness after discontinuation of neuromuscular junction blocking agents. Electrodiagnostic studies and muscle biopsies were performed on several of the patients. All patients had pronounced weakness without sensory loss. Electrodiagnostic and muscle pathology findings were consistent with failed neuromuscular transmission. Although many patients had disorders or were taking medications that can injure the neuromuscular system, no disorder or medication was common to all. Recovery of strength often took several months and most patients were slow to wean from mechanical ventilator support. Although alternative explanations cannot be excluded with certainty, the use of neuromuscular junction blocking agents may lead to neurogenic atrophy and care must be taken when using them.


Methicillin-resistant Staphylococcus aureus: a controversial food-borne pathogen.
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of severe healthcare-associated (HA) infections. Although during the last decade the incidence of HA invasive infections has dropped, the incidence of community-associated MRSA (CA-MRSA) infections has risen among the general population. Moreover, CA-MRSA, livestock-associated MRSA (LA-MRSA) and HA-MRSA (HA-MRSA) can be found in foods intended for human consumption. Several studies from different geographical areas have reported the presence of enterotoxin genes in several MRSA food isolates. Molecular typing studies have revealed genetic relatedness of these enterotoxigenic isolates with isolates incriminated in human infections. The contamination sources for foods, especially animal-origin foods, may be livestock as well as humans involved in animal husbandry and food-processing. Under favourable environmental conditions for growth and enterotoxin production, enterotoxigenic S. aureus isolates present in foods can cause staphylococcal food poisoning (SFP), irrespective of the contamination origin. Owing to the typically moderate clinical manifestations of SFP, the S. aureus strains responsible for SFP (cases or outbreaks) are frequently either not identified or not further characterized. Antimicrobial susceptibility testing is rarely performed, because administration of antimicrobial therapy is not required in the vast majority of cases. Staphylococcal food poisoning is the result of consumption of foods with preformed enterotoxins. Hence, similar to methicillin-sensitive enterotoxigenic S. aureus, enterotoxigenic MRSA can also act as food-borne pathogens upon favourable conditions for growth and enterotoxin production. The severity of the intoxication is not related to the antimicrobial resistance profile of the causative S. aureus strain and therefore MRSA food-borne outbreaks are not expected to be more severe. This review evaluates the potential of methicillin-resistant Staphylococcus aureus (MRSA) as food-borne pathogens based on the current knowledge about the epidemiology of MRSA, their prevalence in livestock, foods of animal origin and humans, and their ability to produce enterotoxins.


Formalinized bacterial "antigens" as a potential infection hazard.
It is widely thought that after enteric bacteric have been "formalinized" (treated with an equal volume of 0.6% formalin) for 1 h, the bacteria become "antigens" and are no longer viable. None of the 27 cultures of Salmonella and other Enterobacteriaceae were entirely killed within 1 h after formalin was added, but all 27 were reduced from 10(9) viable cells per ml to less than 10(2) per ml within 7 h. Thus, mouth pipetting of cultures formalinized for only 1 h is a possible infection hazard.


Inflammatory infiltrate in prostatic hyperplasia--evidence of a host response to intraprostatic spermatozoa?
The inflammatory infiltrate was characterised in 20 samples of prostatic hyperplasia using cell surface specific monoclonal antibodies. The infiltrate was composed predominantly of CD-3+ T-lymphocytes. The distribution of the T-lymphocyte subsets (CD-4 and CD-8) between the epithelial and stromal components of the gland was significantly different, with most of the intra-epithelial infiltrate being CD8+, T cytotoxic/suppressor cells. This may be a necessary immunological barrier, as in the epididymis, to prevent the development of autoimmunisation to sperm antigens. Large numbers of CD4+ T helper/inducer cells and significant numbers of CD-11c+ macrophages were demonstrated in the extra-glandular stromal tissues, suggesting a delayed type hypersensitivity reaction. Intraprostatic spermatozoa have been demonstrated recently and we have confirmed this finding on post mortem specimens. It is postulated that the presence of an intra-epithelial cytotoxic barrier and the marked stromal infiltrate may be due, in part, to the intermittent presence of spermatozoa within the prostate.


[Present status of psychosurgery in Spain].
In order to know the present activity of psychosurgery in Spain, and the opinion of neurosurgeons relative to it, a survey was designed and applied to all active neurosurgeons in our country. We obtained data from at least one neurosurgeon from the 74 neurosurgical centers in Spain (response rate= 100%). Only 6 neurosurgeons performed psychosurgical interventions. In total, 121 psychosurgeries were performed between 1999 and 2003, 75.7% of them in private centers. The most frequent indication is obsessive-compulsive disorder and the most frequent technique is anterior capsulotomy, although techniques and indications differ among the practising neurosurgeons. Those not performing them cite lack of patient referral (54.4%) or unexperience (36.8%) as the causes. A suspected lack of efficacy or the possible adverse effects are seldom expressed. The possibility of using deep brain stimulation for psychiatric indications, as well as the experience of some neurosurgeons and the favorable opinion of the rest, might increase the number of operations in our country.


Acute mountain sickness: increased severity in eucapnic hypoxia.
This study examined the hypothesis that prevention of hypocapnia and alkalosis would ameliorate the symptoms of acute mountain sickness (AMS). Five subjects were exposed to simulated high altitude for 4 d with 3.8% CO2 added to the chamber to maintain normocapnia. Four other subjects were exposed for 4 d to hypobaric hypoxia without CO2 supplementation, and became hypocapnic. Barometric pressure was lower in the group with added CO2 so that alveolar oxygen tensions (55-60 mm Hg) would not be different. The severity of symptoms was clearly greater in normocapnic than in hypocapnic subjects. Thus, prevention of hypocapnia did not alleviate AMS symptoms. The efficacy of CO2 addition in reducing symptoms, as reported by earlier workers, was probably the result of induced hyperventilation and partial relief of hypoxia. Indeed, in the present study with two comparably hypoxic groups, CO2 addition augmented the sysptoms, possibly by causing increased cerebral vasodiladation and spinal fluid pressure.


Undermining and Hemostasis.
Undermining and hemostasis are basic surgical techniques that can have a significant impact on surgical outcomes. To review the mechanisms and techniques of undermining and hemostasis, with an emphasis on the advantages and limitations of each modality. The PubMed database was searched for articles with the keywords "undermining," "hemostasis," and "electrosurgery." Whether performing blunt, sharp, or electrosurgical techniques, undermining at the appropriate depth and width is necessary for tissue movement during closures. Both excessive and inadequate undermining can compromise surgical healing. Surgical hemostasis techniques include pressure, suture ligation, topical hemostatic agents, and electrosurgery. Dermatologic surgeons should select the appropriate amount and type of hemostasis for each procedure. Particular care should be taken in performing electrosurgery, given the potential for complications. Understanding and optimizing hemostasis and undermining will allow dermatologic surgeons to execute complex closures with minimal complications.


Dynamics of lymphocytes and inflammatory cells recruited in liver during murine listeriosis. A cytofluorimetric study.
During primary infection of mice by Listeria monocytogenes, bacterial elimination is dependent on the recruitment of myelomonocytic cells in the infectious foci and the activation of their bactericidal mechanisms through cytokines secreted by Listeria-specific T lymphocytes. The immune events occurring in the liver, one of the main infected organs, have not yet been studied in detail. In the present quantitative study, we describe the dynamics of recruitment of cells belonging to the lymphoid or myelomonocytic lineages in the liver. The different cell populations mobilized into the liver were isolated each day during the course of a sublethal L. monocytogenes infection and their phenotype was characterized by flow cytometry. Three distinct phases of recruitment were observed. 1) During the first day of infection, 17 x 10(6) lymphomyeloid cells were recruited in the liver with a predominance of myelomonocytic cells; 51% of the incoming cells were M1/70+; the NK cell population (detected by the 4D11 antibody) also increased transiently at this period. 2) From day 3 to 5, a high number of myelomonocytic cells infiltrated the liver (13 x 10(6) M1/70+ cells); most of these cells were macrophages (as detected with the macrophage-restricted antibody FA/11 or observed after May-Grünwald Giemsa staining); the antigranulocytic antibodies 7/4 and RB6.8C5 were found to label these mononuclear phagocytes at this period of infection. A subpopulation of Thy-1+ cells (16%) was found to be labeled by the RB6.8C5 antibody in normal liver and, at day 5 and 6, all Thy-1+ cells also bound the RB6.8C5 mAb.3) From day 5 onward, two waves of phenotypically distinct T lymphocytes were observed; the number of CD8+ T lymphocytes (15 x 10(6) cells) increased first at day 5 and peaked on day 7; CD4+ T lymphocytes (6.2 x 10(6) cells) were then recruited with a 2-day delay (on day 7) in the liver.


Genetic, Epigenetic and Pharmacogenetic Aspects of Psoriasis and Psoriatic Arthritis.
There is a strong familial component to psoriatic disease as well as a complex array of genetic, immunologic, and environmental factors. The dominant genetic effect is located on chromosome 6p21.3 within the major histocompatibility complex region, accounting for one-third of genetic contribution. Genome-wide association studies (GWAS) identified additional genes, including skin barrier function, innate immune response, and adaptive immune response genes. To better understand disease susceptibility and progression requires replication in larger cohorts, fine-mapping efforts, new technologies, and functional studies of genetic variants, gene-gene interactions and gene-environmental interactions. New technologies available include next-generation sequencing, copy number variation analysis, and epigenetics.


High-resolution nonlinear fluorescence microscopy using repetitive stimulated transition based on the saturation of stimulated emission implemented with two-color continuous-wave lasers.
High-resolution nonlinear fluorescence (NF) microscopy that utilizes repetitive stimulated transition due to the saturation of stimulated emission caused by two-color continuous-wave lasers was developed. The resulting NF signal, detected via the lock-in technique, is produced by the multiplicative combination of incident beams, which results in an improvement of the optical resolution. The proposed method is demonstrated to have a three-dimensional optical resolution superior to that of conventional NF microscopy. The results of biological imaging reveal the feasibility and superiority of the proposed method.