Hypermanganesemia with Dystonia, Polycythemia and Cirrhosis (HMDPC) due to mutation in the SLC30A10 gene.
Manganese (Mn) is an essential element for metabolic pathways but it can be toxic when present in excessive amounts in the body. Hypermanganesemia along with dystonia, polycythemia, characteristic MRI brain findings in the basal ganglia, and chronic liver disease are the hallmarks of an inherited Mn transporter defect due to mutations in the SLC30A10 gene. We are reporting three siblings who presented with features of dystonia, polycythemia, MRI brain showing basal ganglia hyperintensity on T1 weighted images and chronic liver disease. Blood Mn levels were markedly elevated in the affected patients. Mutation analysis of DNA samples of the affected children confirmed a homozygous missense mutation in SLC30A10. Chelation therapy with intravenous disodium calcium edetate was started in two siblings and led to a marked decrease in whole blood Mn. Oral Penicillamine was later added to the therapy which further improved blood Mn levels. This is a rare disorder and is one of the potentially treatable inherited metal storage disorders. It can be fatal if left untreated. Penicillamine may be an effective alternative to disodium calcium edetate.


Effect of surfactants on the solubility and intrinsic dissolution rate of sparfloxacin.
The effect of surfactants on the solubility and intrinsic dissolution rate of sparfloxacin was investigated at room temperature. The surfactants used in the study were anionic sodium lauryl sulfate (SLS) and nonionic polysorbate 80 (Tween 80). Sodium lauryl sulfate showed very significant increase in solubility Tween 80 at the highest concentration studied. The intrinsic dissolution rates were determined compared to at the same surfactant concentrations used in the solubility study by rotating disk method. Diffusion coefficient (D) of sparfloxacin was evaluated to be 7.19 x 10(-6) cm2S(-1) and the apparent mean diffusion coefficient for sparfloxacin-loaded micelle was estimated to 3.98 x 10(-6) and 2.21 x 10(-6) cm2S(-1) in Tween 80 and SLS respectively.


Insulin-specific receptor-mediated slowing of beat rate in embryonic heart cells.
Spheroidal aggregates of embryonic heart cells showed their spontaneous beat rate when exposed to insulin. The concentration that produced a half-maximal response (1.7 nM) corresponded to the dissociation constant of binding to a specific high-affinity insulin receptor. The pace-maker phase of action potentials recorded during insulin perfusion was preceded by a prolonged or flattened after hyperpolarization, and its slope was less steep than controls. The action potential duration was also prolonged. These results indicate that physiological concentrations of insulin can regulate the embryonic heart rate.


Does a focal neurologic deficit contraindicate operation in a patient with endocarditis?
As many as 40% of patients with left-sided bacterial endocarditis will sustain a neurologic insult. The importance of a neurologic change as an indication or a contraindication for valve replacement remains controversial. We performed a retrospective analysis of the records of 33 patients admitted to the University of Virginia Health Sciences Center between January 1, 1978, and June 30, 1996, with a diagnosis of endocarditis and a neurologic change. All 33 patients had echocardiographic or pathologic evidence of left-sided endocarditis; 23 were seen with focal neurologic findings and had a mortality rate of 22% (5 of 23), and 10 patients were seen with nonfocal, diffuse encephalopathy and had a mortality rate of 60% (6 of 10) (p<0.05). Of the 33 patients, 14 underwent operation and 19 were treated medically. The mortality rate was 21.4% (3 of 14) in the surgical group and 42.1% (8 of 19) in the medical group (p = not significant). In 71% (10 of 14) of the surgical patients, the operation was done within 1 week of the neurologic event. Additional neurologic deterioration occurred in 18.2% (2 of 11) of survivors in the surgical group and 9.1% (1 of 11) in the medical group (p = not significant). Choosing therapy for a patient with endocarditis and a neurologic change remains a difficult challenge. Initial findings of nonfocal, global dysfunction on examination are a predictor of a poor outcome. By comparing surgical and medical groups derived from the same series of patients, it is clear that patients with bacterial endocarditis and central nervous system changes face substantial mortality regardless of intervention. However, these data demonstrate that when compared with a similar group of medical patients, surgical patients who require and receive operation early in the course of their illness do comparatively well. Improving outcomes by delaying surgical intervention may serve to "select out" hardier patients but will lead to the death of patients who might benefit from such intervention.


A Readability Analysis of Online Cardiovascular Disease-Related Health Education Materials.
Online cardiovascular health materials are easily accessible with an Internet connection, but the readability of its content may limit practical use by patients. The goal of our study was to assess the readability of the most commonly searched Internet health education materials for cardiovascular diseases accessed via Google. We selected 20 commonly searched cardiovascular disease terms: aneurysm, angina, atherosclerosis, cardiomyopathy, congenital heart disease, coronary artery disease, deep vein thrombosis, heart attack, heart failure, high blood pressure, pericardial disease, peripheral arterial disease, rheumatic heart disease, stroke, sudden death, valvular heart disease, mini-stroke, lower extremity edema, pulmonary embolism, and exertional dyspnea. Terms were selected on Google and selected up to 10 results in order of presentation in the search results by reviewing a maximum of 15 pages of Google search results specifically providing education toward patients to yield 196 total patient education articles. All readability measures assessing grade level measures found the 196 articles were written at a mean 10.9 (SD = 1.8) grade reading level. Moreover, 99.5% of the articles were written beyond the 5th- to 6th-grade level recommended by the American Medical Association. Given the prominent use of online patient education material, we consider readability as a quality metric that should be evaluated prior to online publication of any health education materials. Further study of how to improve the readability of online materials may enhance patient education, engagement, and health outcomes.


Sesamoid bones also show functional adaptation in their microanatomy-The example of the patella in Perissodactyla.
The patella is the largest sesamoid bone of the skeleton. It is strongly involved in the knee, improving output force and velocity of the knee extensors, and thus plays a major role in locomotion and limb stability. However, the relationships between its structure and functional constraints, that would enable a better understanding of limb bone functional adaptations, are poorly known. This contribution proposes a comparative analysis, both qualitative and quantitative, of the microanatomy of the whole patella in perissodactyls, which show a wide range of morphologies, masses, and locomotor abilities, in order to investigate how the microanatomy of the patella adapts to evolutionary constraints. The inner structure of the patella consists of a spongiosa surrounded by a compact cortex. Contrary to our expectations, there is no increase in compactness with bone size, and thus body size and weight, but only an increase in the tightness of the spongiosa. No particular thickening of the cortex associated with muscle insertions is noticed but a strong thickening is observed anteriorly at about mid-length, where the strong intermediate patellar ligament inserts. The trabeculae are mainly oriented perpendicularly to the posterior articular surface, which highlights that the main stress is anteroposteriorly directed, maintaining the patella against the femoral trochlea. Conversely, anteriorly, trabeculae are rather circumferentially oriented, following the insertion of the patellar ligament and, possibly also, of the quadriceps tendon. A strong variation is observed among perissodactyl families but also intraspecifically, which is in accordance with previous studies suggesting a higher variability in sesamoid bones. Clear trends are nevertheless observed between the three families. Equids have a much thinner cortex than ceratomorphs. Rhinos and equids, both characterized by a development of the medial border, show an increase in trabecular density laterally suggesting stronger stresses laterally. The inner structure in tapirs is more homogeneous despite the absence of medial development of the medial border with no "compensation" of the inner structure, which suggests different stresses on their knees associated with a different morphology of their patellofemoral joint.


Berberine enhances the function of db/db mice islet β cell through GLP-1/GLP-1R/PKA signaling pathway in intestinal L cell and islet α cell.
Background: The evidence on berberine stimulating the secretion of GLP-1 in intestinal L cell has been studied. However, few research has explored its role on generating GLP-1 of islet α cell. Our experiment aims to clarify the mechanism of berberine promoting the secretion of GLP-1 in intestinal L cell and islet α cell, activating GLP-1R and its downstream molecules through endocrine and paracrine ways, thus improving the function of islet β cell and treating T2DM. Methods: After confirming that berberine can lower blood glucose and improve insulin resistance in db/db mice, the identity maintenance, proliferation and apoptosis of islet cells were detected by immunohistochemistry and immunofluorescence. Then, the activation of berberine on GLP-1/GLP-1R/PKA signaling pathway was evaluated by Elisa, Western blot and PCR. Finally, this mechanism was verified by in vitro experiments on Min6 cells, STC-1 cells and aTC1/6 cells. Results: Berberine ameliorates glucose metabolism in db/db mice. Additionally, it also increases the number and enhances the function of islet β cell. This process is closely related to improve the secretion of intestinal L cell and islet α cell, activate GLP-1R/PKA signaling pathway through autocrine and paracrine, and increase the expression of its related molecule such as GLP-1, GLP-1R, PC1/3, PC2, PKA, Pdx1. In vitro, the phenomenon that berberine enhanced the GLP-1/GLP-1R/PKA signal pathway had also been observed, which confirmed the results of animal experiments. Conclusion: Berberine can maintain the identity and normal function of islet β cell, and its mechanism is related to the activation of GLP-1/GLP-1R/PKA signal pathway in intestinal L cell and islet α cell.


An inquiry into how parents of children with autism spectrum disorder interact with their children in a motor skill-based play setting.
Most studies examining parental behaviors of parents of young children with autism spectrum disorder (ASD) and typically developing (TD) children have taken place in free play settings and have primarily focused on examining social behaviors. Motor skill-based play settings, which are distinctly different from free play settings, have not been explicitly studied as it relates to parental behaviors in these environments. The purpose of this study was to examine parental behaviors of parents of children with and without ASD in two distinctly different play settings. Parental behaviors of eighteen parents of children with (n = 9) and without ASD (n = 9) were examined by observation in different play settings (free play [a social-play/traditional play based setting] and a motor skill-based play setting). The examined parental behaviors included parental encouragement, negativity, sensitivity, detachment, and intrusiveness. A 2 × 2 (group × play setting) repeated measures of ANOVA was conducted to examine the main effect of group (TD vs ASD) and play setting (a social-play based setting and a motor skill-based setting) and the interaction effect between group and play setting on parental behaviors. Post-hoc independent t-tests between groups in each setting were conducted to follow-up on significant interactions indicated in the repeated measures of ANOVA RESULTS: The repeated measures ANOVA revealed that parental encouragement showed a significant interaction effect, suggesting that the effect of group on parental encouragement depended on play setting. A post-hoc analysis revealed that parents of children with ASD showed statistically significant lower parental encouragement in a motor skill-based play setting but not in a social-play based setting compared to parents of TD children. Moreover, there was a main effect of group (parents of children with ASD vs. parents of TD children) on parental intrusiveness indicating that the mean parental intrusiveness on children with ASD was significantly higher than parents of TD children across both play settings. There were no statistically significant main or interaction effects on the other parental behaviors (parental negativity, sensitivity, and detachment) between groups. The current study indicated parental encouragement differences between parents of children with ASD and parents of TD children varied based on the play setting. These results identify a need to examine parental behaviors, especially parental encouragement and parental intrusiveness across various types of play settings. Furthermore, as parents of children with ASD displayed lower parental encouragement in a motor skill-based play setting compared to parents of TD children, future studies are warranted to improve parental encouragement of parents of children with ASD in a motor skill-based play setting.


Seasonal dimorphism in the horny bills of sparrows.
Bill size is often viewed as a species-specific adaptation for feeding, but it sometimes varies between sexes, suggesting that sexual selection or intersexual competition may also be important. Hypotheses to explain sexual dimorphism in avian bill size include divergence in feeding niche or thermoregulatory demands, intrasexual selection based on increased competition among males, or female preference. Birds also show seasonal changes in bill size due to shifts in the balance between growth rate and wear, which may be due to diet or endogenous rhythms in growth. Insight into the function of dimorphism can be gained using the novel approach of digital x-ray imaging of museum skins to examine the degree to which the skeletal core or the rhamphotheca contribute to overall dimorphism. The rhamphotheca is ever-growing and ever-wearing, varying in size throughout life; whereas the skeletal core shows determinant growth. Because tidal marsh sparrows are more dimorphic in bill size than related taxa, we selected two marsh taxa to investigate dimorphism and seasonality in the size of the overall bill, the skeletal core, and the rhamphotheca. Bill size varied by sex and season, with males having larger bills than females, and bill size increasing from nonbreeding to breeding season more in males. Skeletal bill size varied with season, but not sex. The rhamphotheca varied primarily with sex; males had a larger rhamphotheca (corrected for skeletal bill size), which showed a greater seasonal increase than females. The rhamphotheca, rather than the skeletal bill, was responsible for sexual dimorphism in overall bill size, which was particularly well developed in the breeding season. The size of the rhamphotheca may be a condition-based character that is shaped by sexual selection. These results are consistent with the evidence that bill size is influenced by sexual selection as well as trophic ecology.


[Combined operations for cholelithiasis].
The experience of 1560 combined operations performed in N.N.Burdenko clinic from 1974 to March 1999 for cholelithiasis is analysed. The results of 7461 cholecystectomies are analysed depending on patients' age (17.8% of patients aged 65 years and older), urgency of the operations (there were 35.6% of patients of this age group who underwent surgery under strictly urgent conditions), and complicacy of the operation (combined operations were carried out in 837 patients with cholecystitis). Last years in the clinic each 10th cholecystectomy is carried out as an additional procedure in more complicated surgery, or it is combined with less complicated one. Thus, in 389 patients with more complicated diseases than cholelithiasis (approximately in a half of them tumors of various locations were observed), cholecystectomy was performed as a combined procedure (1st group), and in 448 patients (2nd group) it was the main procedure. In the 1st group 27% of patients were aged 65 years and older, the overwhelming majority of the operations were carried out by the same approach, mortality rate being 3.3%. In the 2nd group elderly patients made up 20.7%; 68.3% of patients were operated by two approaches, lethality rate being 0.2%. Thus, lethality after 837 combined operations made up 1.7%, total mortality rate after 7461 cholecystectomies made up 0.29%.


The effect of completing a surrogacy information and decision-making tool upon admission to an intensive care unit on length of stay and charges.
Many critically ill patients in intensive care units (ICUs) are unable to communicate their wishes about goals of care, particularly about the use of life-sustaining treatments. Surrogates and clinicians struggle with medical decisions because of a lack of clarity regarding patients' preferences, leading to prolonged hospitalizations and increased costs. This project focused on the development and implementation of a tool to facilitate a better communication process by (1) assuring the early identification of a surrogate if indicated on admission and (2) clarifying the decision-making standards that the surrogate was to use when participating in decision making. Before introducing the tool into the admissions routine, the staff were educated about its use and value to the decision-making process. PROJECT AND METHODS: The study was to determine if early use of a simple method of identifying a patient's surrogate and treatment preferences might impact length of stay (LOS) and total hospital charges. A pre- and post-intervention study design was used. Nurses completed the surrogacy information tool for all patients upon admission to the neuroscience ICU. Subjects (total N = 203) were critically ill patients who had been on a mechanical ventilator for 96 hours or longer, or in the ICU for seven days or longer.The project included staff education on biomedical ethics, critical communication skills, early identification of families and staff in crisis, and use of a simple tool to document patients' surrogates and previously expressed care wishes. Data on hospital LOS and hospital charges were collected through a retrospective review of medical records for similar four-month time frames pre- and post-implementation of the assessment tool. Significant differences were found between pre- and post-groups in terms of hospital LOS (F = 6.39, p = .01) and total hospital charges (F = 7.03, p = .009). Project findings indicate that the use of a simple admission assessment tool, supported by staff education about its completion, use, and available resources, can decrease LOS and lower total hospital charges. The reasons for the difference between the pre- and post-intervention groups remain unclear. Further research is needed to evaluate if the quality of communications between patients, their legally authorized representatives, and clinicians--as suggested in the literature--may have played a role in decreasing LOS and total hospital charges.


A deterministic mechanism producing the loose coupling phenomenon observed in an actomyosin system.
Myosins are molecular motors that convert the chemical energy of ATP into mechanical work called a power stroke. Class II myosin engaged in muscle contraction is reported to show a "loose coupling phenomenon", in which the number of power strokes is greater than the number of ATP hydrolyses. This phenomenon cannot be explained by the lever-arm hypothesis, which is currently accepted as a standard theory for myosin motility. In this paper, a model is proposed to reproduce the loose coupling phenomenon. The model is based on a mechanochemical process called "Driven by Detachment (DbD)" mechanism, which assumes that the energy of the power strokes originates from the potential energy generated by the attractive force between myosin and actin. During the docking process, the potential energy is converted into an intramolecular strain in a myosin molecule, which drives the power stroke after the myosin is firmly attached to an actin filament. The energy of ATP is used to temporarily reduce the attractive force and to increase the potential energy. Therefore, it is not directly linked to the power strokes. When myosin molecules work as an aggregate, the sliding movement of a myosin filament driven by the power strokes of some myosin heads makes other myosin heads that have completed their power strokes detach from the actin without consuming ATP. Under the DbD mechanism, these passively detached myosins can be again engaged in power strokes after the next attachment to actin. As a result, the number of power strokes becomes greater than the number of ATP hydrolyses, and the loose coupling phenomenon will be observed. A theoretical analysis indicates that the efficiency of converting the potential energy into intramolecular elastic energy determines the number of power strokes per each ATP hydrolysis. Computer simulations showed that the DbD mechanism actually produced the loose coupling phenomenon. A critical requirement for this mechanism is that ATP must preferentially facilitate the detachment of myosins that have completed their power strokes, but are still strongly attached to the actin. This requirement may be fulfilled by ATP hydrolysis tightly depending on the conformation of a myosin molecule.


Medications for panic disorder and generalized anxiety disorder during pregnancy.
Approximately 30% of women experience some type of anxiety disorder during their lifetime. In addition, some evidence exists that anxiety disorders can affect pregnancy outcomes. This article reviews the literature on the course of generalized anxiety disorder (GAD) and panic disorder during pregnancy and the postpartum period and presents guidelines for management. An English language electronic search of relevant studies using PubMed (January 1, 1985-January 2004) was performed using the search terms anxiety and pregnancy, maternal mental illness, panic and pregnancy, psychotropic medications in pregnancy, and treatment options in pregnancy. Review articles and primary pharmacologic treatment articles were selected for discussion. Despite the extensive use of psychotropic drugs such as antidepressants during pregnancy, there is a scarcity of information regarding the effect of such exposure on the developing fetus. Review articles and primary pharmacologic treatment trials were analyzed and incorporated into the review based on adequate methodology, completeness of data, and information on pregnancy outcome. It is important that physicians understand the course of these disorders during pregnancy and available treatments so they appropriately counsel women who are or intend to become pregnant. The goal of treatment during pregnancy and lactation is sufficient treatment for syndrome remission. To minimize the potential for neonatal withdrawal and maternal toxicity after delivery, vigilant monitoring of side effects is indicated. Also, if possible, nonpharmacologic treatment, such as cognitive-behavioral therapy, should be first-line treatment in pregnant women with GAD or panic disorder.


Swept-source OCT angiography of macular telangiectasia type 2.
To evaluate the central macular microvascular network in patients with macular telangiectasia type 2 (MacTel2) using optical coherence tomography (OCT)-based microangiography (OMAG). Prospective, observational study of patients with MacTel2 evaluated using a swept-source OCT (SS-OCT) prototype. OMAG was performed using a 3 mm × 3 mm central foveal raster scan. The algorithm segmented the retina into three layers. Microvascular distribution was depicted as en face images, and qualitative information was compared to fluorescein angiography (FA) images. OMAG detected abnormal microvasculature in all MacTel2 eyes, predominantly in the middle retinal layers with neovascularization in the outer retina. These vessels correlated well with the FA alterations. The abnormal temporal, juxtafoveal microvasculature in MacTel2 became apparent as the disease progressed and in later stages tended to extend circumferentially, with anastomotic vessels temporally. OMAG provided detailed, depth- resolved information about the perifoveal macular microvasculature in MacTel2. In most cases, images were better using OMAG than FA. The OMAG images demonstrated that most of the leakage seen on FA appeared to arise from the abnormal perifoveal microvasculature in the middle retinal layer.


Binding affinity and biological activity of gonadotropin releasing hormone agonists in isolated pituitary cells.
The relationships between binding affinity and the biological potency of eight GnRH agonist analogs were evaluated in isolated rat pituitary cells. For this purpose, binding affinity and biological activity were assayed under similar physiological conditions in medium 199, pH 7.4, and binding affinity was also measured under the standard conditions in hypotonic buffer at low temperature. Under physiological conditions, receptor binding affinity was consistently lower than when measured in the hypotonic Tris buffer usually employed for GnRH receptor studies. In the low temperature binding assay at 0 C, which provided a measure of the affinity constant without degradation, a difference of 20- to 30-fold was observed between native GnRH and its most potent analog, [D-Ser(t-Bu)6]des-Gly10-GnRH N-ethylamide. Modifications of the amino acid residues at both positions 6 and 10 of the decapeptide increased the binding affinity of GnRH analogs. When the receptor binding assay was performed at 37 C, the range of the apparent affinity constants was extended up to 60-fold. The affinity constants derived at 37 C were closely correlated with the biological potencies of the individual analogs measured in the same cell system. The effect of temperature on binding affinity was not significantly influenced by peptide metabolism, which was minor in the absence of horse serum from the incubation medium. At the pituitary level, the biological potency of the GnRH agonist analogs is predominantly determined by their higher receptor affinity, and reduced degradation is a less important aspect of the high biological activity of the superagonist analogs.


Risk factors for development of acute kidney injury in critically ill patients: a systematic review and meta-analysis of observational studies.
Background. Acute kidney injury (AKI) is a frequent complication of critically ill patients. The impact of different risk factors associated with this entity in the ICU setting is unknown. Objectives. The purpose of this research was to assess the risk factors associated with the development of AKI in critically ill patients by meta-analyses of observational studies. Data Extraction. Two reviewers independently and in duplicate used a standardized form to collect data from published reports. Authors were contacted for missing data. The Newcastle-Ottawa scale assessed study quality. Data Synthesis. Data from 31 diverse studies that enrolled 504,535 critically ill individuals from a wide variety of ICUs were included. Separate random-effects meta-analyses demonstrated a significantly increased risk of AKI with older age, diabetes, hypertension, higher baseline creatinine, heart failure, sepsis/systemic inflammatory response syndrome, use of nephrotoxic drugs, higher severity of disease scores, use of vasopressors/inotropes, high risk surgery, emergency surgery, use of intra-aortic balloon pump, and longer time in cardiopulmonary bypass pump. Conclusion. The best available evidence suggests an association of AKI with 13 different risk factors in subjects admitted to the ICU. Predictive models for identification of high risk individuals for developing AKI in all types of ICU are required.


Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats.
Human bone marrow stromal cells (hMSCs) constitute a potential source of pluripotent stem cells. In the present study, hMSCs were transplanted into an area of spinal cord contusion in nude rats to determine their survival, differentiation, potential for neuroprotection, and influence on axonal growth and functional recovery. Twenty-nine animals received 6 x 10(5) hMSCs in 6 microl medium 1 week after a contusion, while 14 control animals received an injection of 6 microl medium alone. Basso-Beattie-Bresnahan (BBB) tests were performed weekly. The spinal cords were collected at 6 weeks posttransplantation for histological analysis and assessment of tissue injury. Immunostaining with anti-human mitochondria antibody and pretransplantation labeling with green fluorescent protein demonstrated that the grafted hMSCs survived and were capable of achieving a flattened appearance in the grafted area; however, none of the transplanted cells stained positively for human-specific neuronal, anti-neurofilament H or glial fibrillary acidic protein within the sites of engraftment. While neuronal or astrocytic differentiation was not seen, cells lining blood vessels in the vicinity of the transplant stained positively for anti-human endothelium CD105 antibody. Staining for anti-neurofilament H antibody demonstrated abundant axonlike structures around the transplanted area in the hMSC group. Tissue sparing analysis showed that animals with grafted hMSCs had a smaller area of contusion cyst compared with controls, but there was no significant difference between the two groups in BBB scores. The grafted hMSCs survived for > or = 6 weeks posttransplantation, although they did not differentiate into neural or glial cells. Cells with human endothelial characteristics were observed. Spinal cord-injured rats grafted with hMSCs had smaller contusion cavities, which did not have a significant influence on functional recovery.


Inhibition of herpes simplex virus types 1 and 2 in vitro infection by sulfated derivatives of Escherichia coli K5 polysaccharide.
Herpes simplex virus type 1 (HSV-1) and HSV-2 are neurotropic viruses and common human pathogens causing major public health problems such as genital herpes, a sexually transmitted disease also correlated with increased transmission and replication of human immunodeficiency virus type 1 (HIV-1). Therefore, compounds capable of blocking HIV-1, HSV-1, and HSV-2 transmission represent candidate microbicides with a potential added value over that of molecules acting selectively against either infection. We report here that sulfated derivatives of the Escherichia coli K5 polysaccharide, structurally highly similar to heparin and previously shown to inhibit HIV-1 entry and replication in vitro, also exert suppressive activities against both HSV-1 and HSV-2 infections. In particular, the N,O-sulfated [K5-N,OS(H)] and O-sulfated epimerized [Epi-K5-OS(H)] forms inhibited the infection of Vero cells by HSV-1 and -2, with 50% inhibitory concentrations (IC(50)) between 3 +/- 0.05 and 48 +/- 27 nM, and were not toxic to the cells at concentrations as high as 5 muM. These compounds impaired the early steps of HSV-1 and HSV-2 virion attachment and entry into host cells and reduced the cell-to-cell spread of HSV-2. Since K5-N,OS(H) and Epi-K5-OS(H) also inhibit HIV-1 infection, they may represent valid candidates for development as topical microbicides preventing sexual transmission of HIV-1, HSV-1, and HSV-2.


[Effect of nitroammofoska on the aldolase activity of the normal hemolymph in the mollusk Planorbarius banaticus and in trematode invasion].
The infection of Planorbarius banaticus with sporocysts of Cotylurus cornutus is accompanied by an increase in aldolase activity of molluscs' haemolymph of 1.2 fold. In solutions of nitroammofoska (0.1, 1 and 10 mg/1) the activity of this ferment in infected individuals increases much higher than in non-infected ones. This results in fast carbohydrate expenditures by molluscs, intermediate hosts of trematodes, and their death from exhaustion.


Comparison of automated measurements of electrocardiographic intervals and durations by computer-based algorithms of digital electrocardiographs.
Automated measurements of electrocardiographic (ECG) intervals are widely used by clinicians for individual patient diagnosis and by investigators in population studies. We examined whether clinically significant systematic differences exist in ECG intervals measured by current generation digital electrocardiographs from different manufacturers and whether differences, if present, are dependent on the degree of abnormality of the selected ECGs. Measurements of RR interval, PR interval, QRS duration, and QT interval were made blindly by 4 major manufacturers of digital electrocardiographs used in the United States from 600 XML files of ECG tracings stored in the US FDA ECG warehouse and released for the purpose of this study by the Cardiac Safety Research Consortium. Included were 3 groups based on expected QT interval and degree of repolarization abnormality, comprising 200 ECGs each from (1) placebo or baseline study period in normal subjects during thorough QT studies, (2) peak moxifloxacin effect in otherwise normal subjects during thorough QT studies, and (3) patients with genotyped variants of congenital long QT syndrome (LQTS). Differences of means between manufacturers were generally small in the normal and moxifloxacin subjects, but in the LQTS patients, differences of means ranged from 2.0 to 14.0 ms for QRS duration and from 0.8 to 18.1 ms for the QT interval. Mean absolute differences between algorithms were similar for QRS duration and QT intervals in the normal and in the moxifloxacin subjects (mean ≤6 ms) but were significantly larger in patients with LQTS. Small but statistically significant group differences in mean interval and duration measurements and means of individual absolute differences exist among automated algorithms of widely used, current generation digital electrocardiographs. Measurement differences, including QRS duration and the QT interval, are greatest for the most abnormal ECGs.


Faecal ammonia and pH during lactulose administration in man: comparison with other cathartics.
The effect of lactulose on faecal pH and ammonia has been studied in three normal subjects with the aid of dialysis of faeces in vivo. Observations were also made with sodium sulphate and the two hexahydric alcohols, mannitol and sorbitol, given in doses sufficient to cause a similar increase in stool weight. All four cathartics rendered the stool more acid, but there was no increase in the concentration of faecal ammonia. Lactulose, despite increasing faecal volume, did not cause an increase in the absolute amount of ammonia lost in the faeces, but the other purgatives did show a modest rise. The results are inconsistent with the theory that lactulose benefits the clinical picture of portosystemic encephalopathy by trapping ammonia in an acid stool. An alternative suggestion is advanced, namely, that any cathartic (including lactulose) reduces ammonia absorption from the colon by decreasing colonic transit time, and so reducing the amount of ammonia generated by autolysis of colonic bacteria.


Cardiac involvement in patients with hematologic malignancies.
Authors have reviewed literature about the management of patients with cardiologic disease occurring secondary to hematologic pathology itself or its therapy, with a focus on infiltration of myocardium in acute and chronic leukemia, lymphoma, multiple myeloma, and hypereosinophilic syndrome. Moreover, they evaluated chemotherapy-associated toxicity, particularly for new drugs such as monoclonal antibody therapy, tyrosine kinase inhibitors, arsenic trioxide, bortezomib, and epigenetic therapy. In fact, cardiac toxicity may range from asymptomatic subclinical abnormalities, such as electrocardiographic changes and left ventricular ejection decline, to life-threatening events and lead to chemotherapy dose reduction and delay and, in some cases, for patients with severe side effects, discontinuation of treatment. Finally, they discussed on the identification of early markers of cardiac injury and on cardiac stem cell therapy as a promising approach to facilitate myocardial regeneration.


Effects of hypervaccination with bovine herpesvirus type 1 gE-deleted marker vaccines on the serological response and virological status of calves challenged with wild-type virus.
Twenty-four calves were immunised four times with gE-deleted infectious bovine rhinotracheitis marker vaccines before being challenged with small doses of wild-type bovine herpesvirus type 1 (BHV-1). The repeated vaccinations induced strong immunity that prevented detectable virus replication and gE-seroconversion after the challenge infection in most of the calves. The hypervaccinated calves that shed virus after the challenge infection showed no delay in gE-seroconversion compared with unvaccinated control calves. Using a sensitive nested PCR, BHV-1 gE sequences could be detected in the trigeminal ganglia of several of the gE-seronegative, challenge-infected calves, possibly indicating the presence of wild-type BHV-1 DNA.


[Activity of Ca(2+)-dependent neutral proteinases in rat organs under cobalt and mercury chloride injection].
The activity of Ca(2+)-dependent neutral proteinases in rats under cobalt and mercury chloride injection was investigated. The calpains activity increase in the lungs, heart, liver and kidneys was revealed after 2 h cobalt chloride action. The mercury chloride gives a reliable increase of calcium-dependent neutral proteinases only in the kidneys.


Crystal structures of Escherichia coli gamma-glutamyltranspeptidase in complex with azaserine and acivicin: novel mechanistic implication for inhibition by glutamine antagonists.
gamma-Glutamyltranspeptidase (GGT) catalyzes the cleavage of such gamma-glutamyl compounds as glutathione, and the transfer of their gamma-glutamyl group to water or to other amino acids and peptides. GGT is involved in a number of biological phenomena such as drug resistance and metastasis of cancer cells by detoxification of xenobiotics. Azaserine and acivicin are classical and irreversible inhibitors of GGT, but their binding sites and the inhibition mechanisms remain to be defined. We have determined the crystal structures of GGT from Escherichia coli in complex with azaserine and acivicin at 1.65 A resolution. Both inhibitors are bound to GGT at its substrate-binding pocket in a manner similar to that observed previously with the gamma-glutamyl-enzyme intermediate. They form a covalent bond with the O(gamma) atom of Thr391, the catalytic residue of GGT. Their alpha-carboxy and alpha-amino groups are recognized by extensive hydrogen bonding and charge interactions with the residues that are conserved among GGT orthologs. The two amido nitrogen atoms of Gly483 and Gly484, which form the oxyanion hole, interact with the inhibitors directly or via a water molecule. Notably, in the azaserine complex the carbon atom that forms a covalent bond with Thr391 is sp(3)-hybridized, suggesting that the carbonyl of azaserine is attacked by Thr391 to form a tetrahedral intermediate, which is stabilized by the oxyanion hole. Furthermore, when acivicin is bound to GGT, a migration of the single and double bonds occurs in its dihydroisoxazole ring. The structural characteristics presented here imply that the unprecedented binding modes of azaserine and acivicin are conserved in all GGTs from bacteria to mammals and give a new insight into the inhibition mechanism of glutamine amidotransferases by these glutamine antagonists.


An association analysis for 14 candidate genes mapping to meat quality quantitative trait loci in a Duroc pig population reveals that the ATP1A2 genotype is highly associated with muscle electric conductivity.
In previous GWAS carried out in a Duroc commercial line (Lipgen population), we detected on pig chromosomes 3, 4 and 14 several QTL for gluteus medius muscle redness (GM a*), electric conductivity in the longissimus dorsi muscle (LD CE) and vaccenic acid content in the LD muscle (LD C18:1 n - 7), respectively. We have genotyped, in the Lipgen population, 19 SNPs mapping to 14 genes located within these QTL. Subsequently, association analyses have been performed. After correction for multiple testing, two SNPs in the TGFBRAP1 (rs321173745) and SELENOI (rs330820437) genes were associated with GM a*, whereas ACADSB (rs81449951) and GPR26 (rs343087568) genotypes displayed significant associations with LD vaccenic content. Moreover, the polymorphisms located at the ATP1A2 (rs344748241), ATP8B2 (rs81382410) and CREB3L4 (rs321278469 and rs330133789) genes showed significant associations with LD CE. We made a second round of association analyses including the SNPs mentioned above as well as other SNPs located in the chromosomes to which they map. After performing a correction for multiple testing, the only association that remained significant at the chromosome-wide level was that between the ATP1A2 genotype and LD CE. From a functional point of view, this association is meaningful because this locus encodes a subunit of the Na+ /K+ -ATPase responsible for maintaining an electrochemical gradient across the plasma membrane.


[Percutaneous stimulation of sensitive peripheral nerves in acute crises of essential trigeminal neuralgia].
The electric stimulation of sensitive peripheric fibres has been used with good results in the control of pain. It is belived that the modern theory of pain phisiology offers scientific basis to explain its action mechanism. This method was applied to twenty-one patients suffering from trigeminalgia, being continually stimulated during thirty minutes with variable voltages, according to the affected region. As a result, it was obtained the immediate relief of pain for periods of time varying from six and forty-eight hours.


Impact of wearing a helmet on the risk of hospitalization and intracranial haemorrhage after a sports injury.
Despite their reported protective effect against the occurrence of head injuries, helmets are still used inconsistently in sports in which they are optional. We aimed to assess the impact of helmet use on the risk of hospitalization and intracranial haemorrhage for trauma occurring during sport activities. Retrospective cohort of all patients who presented themselves, over an 18-month period, at the emergency department of a tertiary trauma centre for an injury sustained in a sport or leisure activity where the use of a helmet is optional. Impact of helmet use was assessed using multivariable regression analyses (relative risks, RR). Among the 1,022 patients included in the study, half were cyclists and 40% were skiers or snowboarders. A total of 40 % of patients wore a helmet at the time of injury, 18% had a head injury, 16% were hospitalized and 13% of patients with a head injury had an intracranial haemorrhage. Among all patients, no association was observed between hospital admission and helmet use. However, helmet use in patients with a head injury was associated with significant reductions in the risks of hospitalization (RR 0.41 [95% CI: 0.22-0.76]) and intracranial haemorrhage (RR 0.28 [95% CI: 0.11-0.71]). Results suggest that, in recreational athletes who sustain a head injury, helmet use is associated with a reduced risk of hospitalization (all sports) and intracranial haemorrhage (cyclists).


Motif affinity and mass spectrometry proteomic approach for the discovery of cellular AMPK targets: identification of mitochondrial fission factor as a new AMPK substrate.
AMP-activated protein kinase (AMPK) is a key cellular energy sensor and regulator of metabolic homeostasis. Although it is best known for its effects on carbohydrate and lipid metabolism, AMPK is implicated in diverse cellular processes, including mitochondrial biogenesis, autophagy, and cell growth and proliferation. To further our understanding of energy homeostasis through AMPK-dependent processes, the design and application of approaches to identify and characterise novel AMPK substrates are invaluable. Here, we report an affinity proteomicstrategy for the discovery and validation of AMPK targets using an antibody to isolate proteins containing the phospho-AMPK substrate recognition motif from hepatocytes that had been treated with pharmacological AMPK activators. We identified 57 proteins that were uniquely enriched in the activator-treated hepatocytes, but were absent in hepatocytes lacking AMPK. We focused on two candidates, cingulin and mitochondrial fission factor (MFF), and further characterised/validated them as AMPK-dependent targets by immunoblotting with phosphorylation site-specific antibodies. A small-molecule AMPK activator caused transient phosphorylation of endogenous cingulin at S137 in intestinal Caco2 cells. Multiple splice-variants of MFF appear to express in hepatocytes and we identified a common AMPK-dependent phospho-site (S129) in all the 3 predominant variants spanning the mass range and a short variant-specific site (S146). Collectively, our proteomic-based approach using a phospho-AMPK substrate antibody in combination with genetic models and selective AMPK activators will provide a powerful and reliable platform for identifying novel AMPK-dependent cellular targets.


The effect of cola consumption on oral mucosa in rats.
Drinks that contain phosphoric acid have been shown to have erosive effects and cola drinks are strongly acidic (pH 2.5). Gingivitis may be caused by dietary acids. Therefore, this study analyses the interaction of Coca Cola consumption and oral mucosal damage. Thirty rats were divided into three groups of 10. The animals received saline (pH 7.0) or HCl acid buffered to pH 2.6 or Coca Cola (pH 2.6) per os with 24-h free access to these solutions. A biopsy was taken from the front of the gingiva and the tongue. Histopathological analysis showed no specific lesion and there were no differences among saline, Coca Cola and HCl groups. Flow cytometric analysis was used to assess proliferative activity. In the HCl acid and Coca Cola groups, cell cycle analysis showed that the effects of Coca Cola and HCl acid in inducing oral mucosal damage are similar. In both Coca Cola [G0/G1, 70.38+/-7.9; S, 28.06+/-10.13; G2/M, 1.62+/-2.80; proliferative index (PI), 28.68+/-7.981 and HCI (G0/G1, 67.7+/-18.9; S, 27.8+/-17.5; G2/M, 4.4+/-3.8; PI, 30.9+/-20.98), the rat cell population G0/G1 and G2/M phases were found to be low (p < 0.05) and the cell population S and PI phases were found to be significantly elevated compared with the control group (p < 0.05) (G0/G1, 86.92+/-8.69; S, 9.8+/-1.21; G2/M, 3.25+/-2.87; P1, 13.2+/-8.7). This result was reflected in the proliferative index, which is used as a measure of the regeneration index. The data show that Coca Cola and HCl acid have similar proliferative and regenerative effects on oral mucosa, and it is possible that their regenerative effects are caused as a result of an irritant effect.


Systematic determination of telomerase activity and telomerase length during the progression of human breast cancer in cell culture models.
The purpose of the study was to determine systematically the expression of telomerase activity and the length of telomere repeat arrays by utilizing two different cell culture models that derive from normal individual donors, and probably represent various stages of human breast oncogenesis in cell culture. The models consist of mortal, non-tumorigenic immortal and tumorigenic immortal human mammary epithelial cell (MEC) lines. Using a recently developed polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay, telomerase activity was undetectable in mortal MEC cells. In contrast, the immortal MEC that were nontumorigenic or tumorigenic in immunosuppressed athymic mice, showed telomerase activity. The absence of telomerase activity in mortal and its presence in both non-tumorigenic and tumorigenic immortal cell lines did not reflect their proliferative rate, as demonstrated by the similar pattern and intensity of reactivity of these cell lines with anti-Ki 67 antibody which recognizes a human nuclear cell proliferation--associated antigen. Southern blot analyses of Hinf I-digested genomic DNA hybridized with a (TTAGGG)4 probe revealed arrays of telomeric repeat lengths ranging from 3 to 5, 3.5 to 9, 3.2 to 9 or 3 to 15 kilobase pair (kbp) for mortal, nontumorigenic immortal, and tumorigenic immortal or established MEC lines respectively. These results suggest that telomerase activity and stable telomeric repeat lengths may be a molecular phenotype of the early stages in the progression of breast cancer.


[Special attention intensive care in the Netherlands once again].
The organizational structure of intensive care departments is still under debate. 'Open' (without) or 'closed format' (with intensivists), that is the question. However, various studies establish that the presence of full-time intensivists reduces mortality rates in intensive care units substantially. Currently, only a minority of Dutch hospitals have properly staffed intensive care units, despite clear guidelines. It is estimated that yearly 250 to 600 lives could be saved. While the capacity of training intensivists in the Netherlands has recently been increased enormously, only a faction of young intensivists will under the circumstances be able to find jobs. More jobs should be created, for the sake of patients and young doctors as well.


Implementing reduced-risk integrated pest management in fresh-market cabbage: improved net returns via scouting and timing of effective control.
During 1998-2001, field studies were done to assess the efficacy of an integrated pest management (IPM) program using an action threshold and "reduced-risk" insecticides. The IPM program was compared with a conventional grower-based program. Program performance was evaluated based on management of Trichoplusia ni (Hiibner), Pieris (=Artogeia) rapae (L.), and Plutella xylostella (L.), as well as the economic impact of each program on net returns. The action threshold used in the IPM program consisted of 10% plants infested with T. ni larvae, based on previous small-plot experiment station trials. In all years of the study, the IPM program resulted in significantly lower percentages of plants infested than the conventional program or untreated check. The mean reduction in insecticide applications for the IPM program compared with the conventional program was 23.5%, whereas, on average, the costs of the IPM program were 46.0% higher than the conventional program. Pest reduction in the IPM program resulted in an average of 10.5% higher marketable yields than the conventional program. Percentages of marketable heads in the IPM program ranged from 82 to 99% and from 63 to 96% in the conventional program. Mean net returns for the IPM program exceeded the conventional program by $984.20/ha. These results indicated that the IPM program reduced insecticide use overall, even though costs of the IPM program, with either spinosad or indoxacarb, were sometimes higher. Overall, net returns of the IPM program were higher due to active pest scouting, improved application timing, and increases in marketable yield. Given the potential decrease in insecticide applications and increases in net profit resulting from this IPM program, additional analyses should be conducted to quantify the economic risk, or consistency of the results, to fully evaluate the benefits of the IPM program compared with a conventional program.


Acaricidal efficacy of cypermethrine (a new synthetic pyrethroid) against Boophilus annulatus ticks in cattle.
Resistance of ticks to acaricides had spread dramatically in recent years, so changing of acaricides periodically is needed to avoid resistant strains. Cypermethrine is a new pyrethroid acaricide recently introduced in the skin parasites control programs in Egypt. Fourteen crossbred cows (Friesian X Egyptian native) were used to assess the acaricidal efficacy of cypermethrine against Boophilus annulatus ticks. Cows were allocated into treated and control groups, each consists of 7 animals. At day 0 before treatment, ticks of more than 4.5 mm in length attached to both treated and control animals were counted and every week thereafter. The average tick number on vaccinated and control animals were counted and the efficacy percentage of cypermethrine was then determined. The number of ticks which laid eggs were counted in treated and control animals and hatching percentage of eggs were then calculated. Spraying of animals with cypermethrine showed that complete elimination of ticks occurred early on the 7th day post-treatment. The average number of ticks was 1673 and that of controls was 1578 at day 0 before treatment. The maximum efficacy (100%) was sustained for up to 7 weeks post-treatment after which the efficacy was slightly dropped and reached 98%. The results of cypermethrine on oviposition and egg hatchability of the ticks which survived treatment were surprising. The percentage of ticks collected from treated cows that succeeded to lay eggs was 22%, the average number of eggs laid per tick was 259 and hatching rate was 8.6%.


Characterization of Brucella abortus strain 19 isolated from human and bovine tissues and fluids.
One hundred isolates of Brucella abortus, which were recovered from bovine and human tissues or fluids, were identified as strain 19 by conventional bacteriologic methods. Each isolate was examined using a Warburg respirometer to determine oxidative rates on substrates of D- and L-alanine, L-glutamic acid, d(+)-galactose, D-ribose, and i-erythritol. These results were compared with those of repository (seed) cultures of strain 19 used for making antigens and vaccines. Except on the substrate of i-erythritol, each of the 100 isolates oxidized these substrates with rates different from the repository cultures and indistinguishable from those of field strains of B abortus. Thus, oxidatively, i-erythritol was the only substrate useful to help distinguish between strain 19 and virulent strains of B abortus biotype 1.


Predictors of Functional Changes in Italian Nursing Home Residents: The U.L.I.S.S.E. Study.
To identify independent predictors of the risk of functional decline in older nursing home (NH) residents. A longitudinal observational study. Thirty-one NHs participating in the U.L.I.S.S.E. project, distributed throughout Italy. All older (≥65 years) long-term NH residents without complete disability and with at least one follow-up evaluation during the 12-month study period (n = 1263). All participants underwent a standardized comprehensive evaluation using the Italian version of the Minimum Data Set for NHs. The activities of daily living (ADLs) Long-Form scale was used to evaluate functional status. Facility characteristics were collected using an ad hoc designed questionnaire. Of the NH residents, 40.4% experienced a decline in the ADL during the follow-up. The mixed effect logistic regression model showed that depression (odds ratio [OR] 1.45, confidence interval [CI] 1.16-1.81, P = .005) and the use of antipsychotics (OR 1.30, CI 1.06-1.60, P = .016) were associated with a higher probability of ADL decline, whereas the presence of a geriatrician (OR 0.60, CI 0.41-0.88, P = .015) and a higher than median hour per resident per week of nursing care (OR 0.55, CI 0.37-0.80, P = .006) were associated with a lower risk. Our findings suggest that preventing functional decline in NH residents might be possible by optimizing the management of depression and by reducing the current high prescription rate of antipsychotics. Moreover, the presence of a geriatrician, associated with an adequate amount of nursing care, seem to be important facilities characteristics to achieve this goal. These findings should be tested in large-scale pragmatic clinical trials.


Sexually transmitted diseases in adolescents: what's new?
Sexually transmitted diseases (STDs) are an important cause of morbidity and, potentially, mortality for adolescents in the United States. Each year, 2.5 million teenagers in this country will contract an STD. An understanding of recent advances in risk factors, epidemiology, diagnosis, and treatment of these important infections is vital for clinicians providing care for adolescents. To identify topics for review, a MEDLINE search for the years 1993 to 1997 was conducted, using the general term sexually transmitted diseases. Separate searches were performed for individual infections, including chlamydia, gonorrhea, herpes simplex virus (HSV), human papillomavirus (HPV), human immunodeficiency virus (HIV), and Trichomonas vaginalis. Relevant publications addressing risk factors for STD acquisition, as well as the epidemiology, diagnosis, and treatment of these infections were reviewed. Information derived from the search that was considered relevant and important for the care of adolescents is presented. Risk factors for STD acquisition, including sexual activity, condom use, and substance use are discussed. Recent information about the epidemiology of bacterial (eg, chlamydia, gonorrhea), viral (eg, HSV, HPV, HIV), and protozoal (T vaginalis) infections is presented. Novel diagnostic techniques and advances in treatment of specific infections are reviewed. Sexually transmitted diseases represent a significant health problem for adolescents in the United States. Recent advances in the area of diagnosis likely will lead to enhanced recognition of infected individuals, particularly those who lack symptoms. In addition, new drugs and novel approaches to therapy have simplified treatment and may lead to enhanced compliance.


The changing dielectric properties of CHO cells can be used to determine early apoptotic events in a bioprocess.
To ensure maximum productivity of recombinant proteins it is desirable to prolong cell viability during a mammalian cell bioprocess, and therefore important to carefully monitor cell density and viability. In this study, five different and independent methods of monitoring were applied to Chinese hamster ovary (CHO) cells grown in a batch culture in a controlled bioreactor to determine cell density and/or cell viability. They included: a particle counter, trypan blue exclusion (Cedex), an in situ bulk capacitance probe, an off-line fluorescent flow cytometer, and a prototype dielectrophoretic (DEP) cytometer. These various techniques gave similar values during the exponential growth phase. However, beyond the exponential growth phase the viability measurements diverged. Fluorescent flow cytometry with a range of fluorescent markers was used to investigate this divergence and to establish the progress of cell apoptosis: the cell density estimates by the intermediate stage apoptosis assay agreed with those obtained by the bulk capacitance probe and the early stage apoptosis assay viability measurements correlated well with the DEP cytometer. The trypan blue assay showed higher estimates of viable cell density and viability compared to the capacitance probe or the DEP cytometer. The DEP cytometer measures the dielectric properties of individual cells and identified at least two populations of cells, each with a distinct polarizability. As verified by comparison with the Nexin assay, one population was associated with viable (non-apoptotic) cells and the other with apoptotic cells. From the end of the exponential through the stationary and decline stages there was a gradual shift of cell count from the viable into the apoptotic population. However, the two populations maintained their individual dielectric properties throughout this shift. This leads to the conclusion that changes in bulk dielectric properties of cultures might be better modeled as shifts in cells between different dielectric sub-populations, rather than assuming a homogeneous dielectric population. This shows that bulk dielectric probes are sensitive to the early apoptotic changes in cells. DEP cytometry offers a novel and unique technology for analyzing and characterizing mammalian cells based on their dielectric properties, and suggests a potential application of the device as a low-cost, label-free, electronic monitor of physiological changes in cells.


Management of detrusor external sphincter dyssynergia in neurogenic bladder.
Spinal cord injury (SCI) affects 11.5 to 53.4 individuals per million of the population in developed countries each year. SCI is caused by trauma, although it can also result from myelopathy, myelitis, vascular disease or arteriovenous malformations and multiple sclerosis. Patients with complete lesions of the spinal cord between spinal cord level T6 and S2, after they recover from spinal shock, generally exhibit involuntary bladder contractions without sensation, smooth sphincter synergy, but with detrusor striated sphincter dyssynergia (DESD). Those with lesions above spinal cord level T6 may experience, in addition, smooth sphincter dyssynergia and autonomic hyperreflexia. DESD is a debilitating problem in patients with SCI. It carries a high risk of complications, and even life expectancy can be affected. Nearly half of the patients with untreated DESD will develop deleterious urologic complications, due to high intravesical pressures, resulting in urolithiasis, urinary tract infection (UTI), vesicoureteral reflux (VUR), hydronephrosis, obstructive uropathy, and renal failure. The mainstay of treatment is the use of antimuscarinics and catheterization, but in those for whom this is not possible external sphincterotomy has been a last resort option. External sphincterotomy is associated with significant risks, including haemorrhage; erectile dysfunction and the possibility of redo procedures. Over the last decade alternatives have been investigated, such as urethral stents and intrasphincteric botulinum toxin injection. In this review, we will cover neurogenic DESD, with emphasis on definition, classifications, diagnosis and different therapeutic options available.


Extracellular vs Intracellular Delivery of CO: Does It Matter for a Stable, Diffusible Gasotransmitter?
Carbon monoxide (CO) is a gasotransmitter produced in humans. An essential unanswered question in the design of carbon monoxide releasing molecules (CORMs) is whether the delivery molecule should be localized extra- or intracellularly to produce desired biological effects. Herein we show that extracellular CO release is less toxic and is sufficient to produce an anti-inflammatory effect similar to that of intracellular CO release at nanomolar concentrations. This information is valuable for the design of CORMs.


BALB/c mice produce blister-causing antibodies upon immunization with a recombinant human desmoglein 3.
Pemphigus vulgaris (PV) is an Ab-mediated autoimmune blistering disease of mucotaneous surfaces. Over 95% of the patients with PV express DR4 or DRw6, and the disease is characterized by the presence of autoantibodies directed against desmoglein 3 (Dsg 3), a protein expressed on keratinocytes. An appropriate animal model is required to understand immunoregulation and to address the role of immunogenetic components in the production of pathogenic Abs that are characteristic of PV. Therefore, we turned to the development of a mouse model. Four strains of female mice (BALB/c, DBA/1, SJL/J, and HRS/J) were screened for their ability to produce pathogenic anti-Dsg 3 Abs. We demonstrated that only BALB/c mice immunized with a full-length Dsg 3 can produce pathogenic Abs capable of causing acantholysis of human foreskin in culture and blistering in neonatal mice. This observation suggested that either H-2d or the BALB background contains the immunogenetic makeup necessary for the production of pathogenic anti-Dsg 3 Abs. No correlation was noted between a given isotype and the pathogenic potential of autoantibodies from different strains of mice. Similarly, the pattern of reactivity of Abs with a panel of 46 synthetic peptides that span the entire Dsg 3 failed to reveal any association between binding specificity and the pathogenic potential, and suggested that pathogenic Abs might recognize conformational epitopes. Moreover, our studies showed that the epitopes recognized by pathogenic Abs are contained within the extracellular Dsg 3.


The sites of synthesis and transport of extracellular polysaccharides in the root tissues of maize.
1. Subcellular fractionation of maize roots resulted in the isolation of the following enriched fractions: cell wall, dictyosome, smooth-membrane and rough-microsomal fractions. In addition, extracellular polysaccharide of the root slime was isolated. 2. Maizeseedling roots were incubated in vivo with d-[U-(14)C]glucose, and the pattern of incorporation of radioactivity into the polysaccharides of each fraction was investigated. 3. The differentiation of maize-root cells with respect to the synthesis of specific extracellular polysaccharide directly relates to the polysaccharide synthesized and transported within the membrane system of the cell. A fucose-containing polysaccharide, characteristic only of root slime, was present only in the membrane system of the root-tip region of the root. Regions of typical secondary wall development within the root were characterized by an increased incorporation of radioactivity into xylose of polysaccharide within the membrane system. 4. The incorporation of radioactivity into glucan polymers in the membrane fractions was very low in all regions of the root. Since in regions of secondary wall development greater than 60% of all radioactive incorporation was into a glucan polymer, it can be inferred that this polymer, most probably cellulose, is not synthesized or transported within the compartments of the membrane system. It is suggested that synthesis of cellulose occurs at the surface of the plasmalemma. 5. Maize-root cells contained 40 times more rough endoplasmic reticulum than dictyosome membrane. The relative specific radioactivities of each fraction indicated that polysaccharide was concentrated in the region of the Golgi apparatus, which showed a 100% increase in specific radioactivity compared with the rough endoplasmic reticulum. The Golgi apparatus can thus be regarded as a localized focal point on the synthetic and transport system of polysaccharide by the intracellular membrane compartments.


Genetic life history effects on juvenile survival in bluegill.
Foraging behaviour under the risk of predation has important consequences on an individual's survivorship and fitness. In bluegill (Lepomis macrochirus), we have recently shown that offspring sired by males of alternative life histories differ in their foraging behaviour. Specifically, offspring sired by 'cuckolder' males take fewer risks during foraging than do offspring sired by 'parental' males. This behavioural difference can have important consequences on the fitness of the two life histories and thus the underlying evolutionary mechanism. Here, we examine the consequences of this behavioural variation on growth rate, condition and survivorship during early development of juveniles. We used split in vitro fertilization to generate maternal half-sibs that differed in sire life history. The resulting 18 455 larvae from 50 families were released into a microcosm with safe and risky foraging areas for approximately 2 months. A total of 262 juveniles (1.4%) survived of which parentage was unambiguously determined using microsatellite genetic markers for 254 (97%). Although we found significant dam effects, there was no difference in apparent growth rate or condition of juveniles sired by males of the two life histories. Of the 25 paired half-sib families, 15 had higher survivorship when sired by a cuckolder male, seven had higher survivorship when sired by a parental male and three had no surviving offspring from either sire. Thus, although growth was similar between the two offspring types, survivorship was not. Combining the differential survivorship estimate with paternity data from natural nests and the frequency of males adopting each life history, we calculated that the cuckolder life history has 1.87 times higher fitness than the parental life history. As such, the life histories likely are not governed by a genetic polymorphism.


A patch-clamp study of acetylcholine-activated ion channels in Ascaris suum muscle.
Acetylcholine-activated single-channel currents were recorded from cell-attached and inside-out patches of isolated muscle vesicles from Ascaris suum. Acetylcholine (1-10 mumols l-1) activated cation-selective channels of two amplitudes: 40-50 pS and 25-35 pS. Both channels had linear I/V relationships and mean open durations independent of voltage. The larger conductance was analysed in detail to determine its open-, closed- and burst-time kinetics; the open and burst durations were composed of two components (short and long), while closed durations had at least three components (short, intermediate and long). The data were then corrected to allow for missing short events in order to estimate various parameters including corrected mean open time (1.26 + 0.11 ms, mean +/- S.E.). Values were also derived for the efficacy (beta/alpha = 4.9) and affinity [1/KD = 147 x 10(3) (mol l-1) -1] of acetylcholine at this receptor. Larger concentrations of acetylcholine (25-100 mumols l-1) were shown to produce desensitization and caused single-channel currents to occur in clusters with long closed times (mean 171 s) between clusters. It was concluded that the extrasynaptic muscle of Ascaris suum contains two types of acetylcholine-activated ion channel and these are possible sites of action of various anthelmintic drugs. This paper is the first to describe acetylcholine-activated single-channel currents in invertebrate muscle.


Survival and neurological outcome in the elderly after in-hospital cardiac arrest.
There have been few studies of the outcome in elderly patients who have suffered in-hospital cardiac arrest (IHCA) and the association between cardiac arrest characteristics and survival. The aim of this large observational study was to investigate the survival and neurological outcome in the elderly after IHCA, and to identify which factors were associated with survival. We investigated elderly IHCA patients (≥70years of age) who were registered in the Swedish Cardiopulmonary Resuscitation Registry 2007-2015. For descriptive purposes, the patients were grouped according to age (70-79, 80-89, and ≥90years). Predictors of 30-day survival were identified using multivariable analysis. Altogether, 11,396 patients were included in the study. Thirty-day survival was 28% for patients aged 70-79 years, 20% for patients aged 80-89 years, and 14% for patients aged ≥90years. Factors associated with higher survival were: patients with an initially shockable rhythm, IHCA at an ECG-monitored location, IHCA was witnessed, IHCA during daytime (8 a.m.-8 p.m.), and an etiology of arrhythmia. A lower survival was associated with a history of heart failure, respiratory insufficiency, renal dysfunction and with an etiology of acute pulmonary oedema. Patients over 90 years of age with VF/VT as initial rhythm had a 41% survival rate. We found a trend indicating a less aggressive care with increasing age during cardiac arrest (fewer intubations, and less use of adrenalin and anti-arrhythmic drugs) but there was no association between age and delay in starting cardiopulmonary resuscitation (CPR). In survivors, there was no significant association between age and a favourable neurological outcome (CPC score: 1-2) (92%, 93%, and 88% in the three age groups, respectively). Increasing age among the elderly is associated with a lower 30-day survival after IHCA. Less aggressive treatment and a worse risk profile might contribute to these findings. Relatively high survival rates among certain subgroups suggest that discussions about advanced directives should be individualized. Most survivors have good neurological outcome, even patients over 90 years of age.


AVP-sensitive cAMP production is dependent on calmodulin in both MTAL and MCT.
Vasopressin (AVP) plays a key role in maximal urine concentration by stimulating NaCl reabsorption in the medullary thick ascending limbs of Henle (MTAL) and by increasing water permeability in the medullary collecting tubules (MCT). These effects of AVP in MTAL and MCT are mediated by activation of adenylate cyclase. Because effects of high ambient Ca2+ on AVP-sensitive adenosine 3',5'-cyclic monophosphate (cAMP) production are quite different in MTAL and MCT, we examined whether the Ca2+-calmodulin system is involved differently in AVP-sensitive cAMP production in MTAL and MCT of mouse kidney using two dissimilar calmodulin inhibitors, trifluoperazine (TFP) and W-7. TFP and W-7 inhibited AVP-sensitive cAMP production in both nephron segments in a dose-dependent manner with maximal inhibition of both agents being greater than 90%. A half-maximal inhibition by TFP and W-7 was about 45, 100 microM in MTAL and about 40, 40 microM in MCT, respectively. The inhibitory effect of W-5, a chemically similar to W-7 but less potent calmodulin inhibitor, was significantly less than that of W-7 in both nephron segments. TFP and W-7 but not W-5 also inhibited glucagon-sensitive cAMP production in MTAL. W-7 inhibited forskolin-sensitive cAMP production but the inhibition by W-5 was significantly less than that by W-7 in MTAL and MCT. Results suggest that AVP-sensitive cAMP production is MCT.(ABSTRACT TRUNCATED AT 250 WORDS)


Energy turnover during 24 hours and 6 days of adventure racing.
Energy turnover was assessed in two conditions of mixed ultra-endurance exercise. In Study 1, energy expenditure and intake were measured in nine males in a laboratory over 24 h. In Study 2, energy expenditure was assessed in six males during an 800-km Adventure race (mean race time 152.5 h). Individual correlations between heart rate and oxygen uptake (VO(2)) were established during pre-tests when kayaking, cycling, and running. During exercise, energy expenditure was estimated from continuous heart rate recordings. Heart rate and VO(2) were measured regularly during fixed cycling work rates to correct energy expenditure for drift in oxygen pulse. Mean energy expenditure was 18,050 +/- 2,390 kcal (750 +/- 100 kcal h(-1)) and 80,000 +/- 18,000 kcal (500 +/- 100 kcal h(-1)) in Study 1 and Study 2 respectively, which is higher than previously reported. Energy intake in Study 1 was 8,450 +/- 1,160 kcal, resulting in an energy deficit of 9,590 +/- 770 kcal. Body mass decreased in Study 1 (-2.3 +/- 0.8 kg) but was unchanged in Study 2. Fat mass decreased in Study 2 (-2.3 +/- 1.5 kg). In Study 1, muscle glycogen content decreased by only 60%. Adventure racing requires a high energy expenditure, with large inter-individual variation. A large energy deficit is caused by inadequate energy intake, possibly due to suppressed appetite and gastrointestinal problems. The oxygen pulse, comparing start to 12 h of exercise and beyond, increased by 10% and 5% in Study 1 and Study 2 respectively. Hence, estimations of energy expenditure from heart rate recordings should be corrected according to this drift.


A comparison of the effect of soybeans roasted at different temperatures versus calcium salts of fatty acids on performance and milk fatty acid composition of mid-lactation Holstein cows.
To evaluate the effect of soybeans roasted at different temperatures on milk yield and milk fatty acid composition, 8 (4 multiparous and 4 primiparous) mid-lactation Holstein cows (42.9±3 kg/d of milk) were assigned to a replicated 4×4 Latin square design. The control diet (CON) contained lignosulfonate-treated soybean meal (as a source of rumen-undegradable protein) and calcium salts of fatty acids (Ca-FA, as a source of energy). Diets 2, 3, and 4 contained ground soybeans roasted at 115, 130, or 145°C, respectively (as the source of protein and energy). Dry matter intake (DMI) tended to be greater for CON compared with the roasted soybean diets (24.6 vs. 23.3 kg/d). Apparent total-tract digestibilities of dry matter, organic matter, and crude protein were not different among the treatments. Actual and 3.5% fat-corrected milk yield were greater for CON than for the roasted soybean diets. Milk fat was higher for soybeans roasted at 130°C than for those roasted at either 115 or 145°C. No differences were observed between the CON and the roasted soybean diets, or among roasting temperatures, on feed efficiency and nitrogen concentrations in rumen, milk, and plasma. Milk from cows fed roasted soybeans had more long-chain fatty acids and fewer medium-chain fatty acids than milk from cows fed Ca-FA. Compared with milk from cows fed the CON diet, total milk fat contents of conjugated linoleic acid, cis-9,trans-11 conjugated linoleic acid, cis-C18:2, cis-C18:3, and C22:0 were higher for cows fed the roasted soybean diets. Polyunsaturated fatty acids and total unsaturated fatty acids were greater in milk from cows fed roasted soybean diets than in milk from cows fed CON. Concentrations of C16:0 and saturated fatty acids in milk fat were greater for CON than for the roasted soybean diets. Cows fed roasted soybean diets had lower atherogenic and thrombogenic indices than cows fed CON. Milk fatty acid composition did not differ among different roasting temperatures. In summary, results showed that cows fed CON had higher DMI and milk yield than cows fed roasted soybean diets. Among different roasting temperatures (115, 130, and 145°C), soybeans roasted at 115°C led to higher milk production and lower DMI. Cows fed roasted soybeans, regardless of the roasting temperature, had more unsaturated fatty acids in milk. Using roasted soybeans in dairy cow rations could, therefore, improve the health indices of milk for human nutrition.


Brief communication: the human humerus from the Broken Hill Mine, Kabwe, Zambia.
The distal half of a right human humerus (E.898), recovered ex situ in 1925 by Hrdlička at the Broken Hill Mine, Kabwe, Zambia, has figured prominently in assessments of Middle Pleistocene Homo postcranial variation and of the phylogenetic polarity and functional anatomy of Pleistocene Homo upper limb morphology. Reassessment of distal humeral features that distinguish modern human and some archaic Homo humeri, especially relative olecranon breadth and medial and lateral pillar thicknesses, confirm previous studies placing it morphologically close to recent humans, as well as possibly to Early Pleistocene Homo. However, it completely lacks stratigraphic context, and there is faunal and archeological evidence for human activity at Broken Hill from the Middle Pleistocene to the Holocene. Given its uncertain geological age and modern human morphology, the Broken Hill E.898 humerus should not be used in analyses of Pleistocene humans until it is securely dated.


[Morphological changes in gametes of tiger barb Puntius tetrazona (Cypriniformes: Cyprinidae) and the implementation of in vitro fertilization].
The production of ornamental fishes represents an economic activity of a growing number of Mexican families. Nevertheless, the reproduction of fish in captivity is one of the complications faced by farmers. This study was set up to: (i) evaluate the morphological and functional changes induced by hydration in the gametes of fish tiger barb (Puntius tetrazona; 240 samples) at tree times after hydration (10, 20 and 30s) with classic spermograms (volume, sperm concentration, viability, motility, and normal morphology); and (ii) evaluate the implementation of in vitro fertilization based on the ovulation rate, the percentage of fertilization and hatching; and the larval numbers obtained after 72 hours. The average volume of milt was 3.0 ± 0.7 μL, and the minimum, maximum and average concentration of sperm was 44.4 x 10(6) spz/mL, 52.3 x 10(6) spz/mL, and 48.1 ± 5.9 x 10(6) spz/mL, respectively. The viability and motility of the sperm was 84.6 ± 3.2% and 81.5 ± 2.2%, respectively. The diameter of the sperm with/without water contact was 2.10 ± 6 μm and 3.8 ± 1.0 μm (p < 0.05); the largest diameter was recorded 30 seconds after the contact with water. For oocytes, the smaller and larger diameters were recorded at 10 and 30s, respectively (both with/without water contact); the oocytes diameters after 10 and 30 seconds of contact with water were 1.11 and 1.55 mm, respectively. A higher ovulation rate was recorded using the in vitro fertilization: 250 ± 50 oocytes versus 28 ± 09 oocytes (during natural fertilization; p < 0.05). Nevertheless, fertilization and hatching rates were higher for the natural fertilization (80 and 60%, respectively). Considering the number of larvae obtained after 72 hours, our results showed a higher value for the in vitro fertilization (75 ± 18 compared to 13.4 ± 12 of the natural fertilization; p < 0.05). We propose this fish as a model for other ornamental fishes of commercial interest. Our results demonstrate that the in vitro fertilization is a very high viable option to optimize and maximize resources; besides, the reproduction management optimization under controlled conditions may enhance wild fish stocks preservation.


Amygdala activation to masked happy facial expressions.
The amygdala has a key role in automatic non-conscious processing of emotions. Highly salient emotional stimuli elicit amygdala activity, and happy faces are among the most rapidly perceived facial expressions. In backward masking paradigms, an image is presented briefly and then masked by another stimulus. However, reports of amygdala responses to masked happy faces have been mixed. In the present study, we used functional magnetic resonance imaging (fMRI) to examine amygdala activation to masked happy, sad, and neutral facial expressions. Masked happy faces elicited greater amygdala activation bilaterally as compared to masked sad faces. Our findings indicate that the amygdala is highly responsive to non-consciously perceived happy facial expressions.


The ERR-1 orphan receptor is a transcriptional activator expressed during bone development.
We studied the expression of estrogen-related receptor ERR-1 during mouse embryonic development. ERR-1 mRNA is present in bones formed by both the endochondral and intramembranous routes, and the onset of its expression coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone. By gel shift analysis we found that ERR-1 binds as a monomer specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are required for efficient ERR-1 binding. In transient transfection assays, ERR-1 acts as a potent transactivator through the SFRE sequence. This effect is cell-specific since ERR-1 activates transcription in the rat osteosarcoma cell line ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2 cells. Notably, the osteopontin (a protein expressed by osteoblasts and released in the bone matrix) gene promoter is a target for ERR-1 transcriptional regulation. Our findings suggest a role for ERR-1 in bone development and metabolism.


The unique region of the human herpesvirus 6 genome is essentially collinear with the UL segment of human cytomegalovirus.
The entire genome of human herpesvirus 6 (HHV-6) strain U1102 was cloned as overlapping fragments in cosmid and plasmid vectors. Cleavage maps were constructed for the restriction endonucleases BamHI, EcoRI, NotI and SmaI. The genome of HHV-6 U1102 is a linear dsDNA of 163 kbp, consisting of a long unique 142 kbp region flanked by direct terminal repeats of 10.5 kbp. Short stretches (290 to 470 nucleotides) of DNA, four from the terminal repeats and 55 from the UL region, were sequenced and compared by computer with the known herpesvirus amino acid sequences. Homologies were found for 10 open reading frames that are scattered over the UL region of HHV-6. Their relative positions and orientations indicate that the unique region of HHV-6 is essentially collinear with the UL region of human cytomegalovirus (HCMV), but is not collinear with the other human herpesviruses. It confirms and extends earlier observations that HHV-6 is more closely related to the beta-herpesvirus HCMV, suggesting that HHV-6 may be considered as the prototype of a new beta 2-herpesvirus subgroup.


An interprofessional team approach to fall prevention for older home care clients 'at risk' of falling: health care providers share their experiences.
Providing care for older home care clients 'at risk' of falling requires the services of many health care providers due to predisposing chronic, complex conditions. One strategy to ensure that quality care is delivered is described in the integrated care literature; interprofessional collaboration. Engaging in an interprofessional team approach to fall prevention for this group of clients seems to make sense. However, whether or not this approach is feasible and realistic is not well described in the literature. As well, little is known about how teams function in the community when an interprofessional approach is engaged in. The barriers and facilitators of such an approach are also not known. The purpose of this qualitative study was to describe the experiences of five different health care professionals as they participated in an interprofessional team approach to care for the frail older adult living at home and at risk of falling. This study took place in Hamilton, ON, Canada and was part of a randomized controlled trial, the aim of which was to determine the effects and costs of a multifactorial and interdisciplinary team approach to fall prevention for older home care clients 'at risk' of falling. The current study utilized an exploratory descriptive design to answer the following research questions: how do interprofessional teams describe their experiences when involved in a research intervention requiring collaboration for a 9-month period of time? What are the barriers and facilitators to teamwork? Four focus groups were conducted with the care-provider teams (n=9) 6 and 9 months following group formation. This study revealed several themes which included, team capacity, practitioner competencies, perceived outcomes, support and time. Overall, care providers were positive about their experiences and felt that through an interprofessional approach benefits could be experienced by both the provider and the patient and his/her family. Findings from this study suggest that research needs to be conducted to further explore the issues faced by this group of care providers and potential client outcomes.


A case of chordoma invading multiple neuroaxial bones: report of ten years follow up.
Chordoma is a rare, slow-growing primary malignant tumor of the axial skeleton, arising from the embryonic cells of primitive notochord. Chordomas may arise at different sites of the vertebral column simultaneously or more probably they may metastasise along the neural axis insidiously. Recurrence despite radical surgery and following adjuvant therapy is possible. A 46-year-old female patient presented weakness and numbness of the lower extremities. She was operated for clivus chordoma five years ago at another institute. First the patient underwent surgery for resection of the tumor at the cervical region. a second surgery was performed to resect tumor on the foramen magnum and at the C1 level. Histologic examination of the removed vertebra confirmed the diagnosis of chordoma involving the vertebral body. Radiotherapy was administered after the second surgery. Follow-up neurological and radiological examinations revealed no abnormal neurological symptoms 2,5 years after second surgery. There were no distant organ metastases. A patient with diagnosed chordoma of the spine must be investigated with MRI of other regions of the neuraxis to exclude second or even third source of chordoma metastases. In metastatic chordoma cases, radical or gross total resection should be performed for each lesion but if complete surgical resections are impossible, preoperative or postoperative radiation therapy should be planned to improve life expectancy.


Helping carers to care--the 10/66 dementia research group's randomized control trial of a caregiver intervention in Russia.
Dementia is a rapidly growing public health problem in low and middle income countries. There is an urgent need, in the absence of formal services, to develop interventions designed to improve the lives of people with dementia, and their families. This study tests the effectiveness of the 10/66 caregiver intervention among people with dementia, and their carers. A single blind parallel group randomized controlled trial (ISRCTN41039907). Moscow. Sixty family caregivers of people aged 65 and over with dementia were randomized to receive the intervention and medical care as usual (n = 30) or medical care as usual only (n = 30). Caregiver and person with dementia outcomes were assessed at baseline and after 6 months. The caregiver education and training intervention was delivered over five, weekly, half-hour sessions and was made up of three modules: (i) assessment (one session); (ii) basic education about dementia (two sessions); and (iii) training regarding specific problem behaviors (two sessions). Dementia was diagnosed using DSM-IV criteria. Caregiver: Zarit Carer Burden Interview; carer psychological distress (SRQ 20); and carer Quality of Life (WHOQOL-BREF). Person with dementia: Behavioural and Psychological symptoms (NPI-Q); quality of life (DEMQOL). Caregivers in the intervention group reported large and statistically significant net improvements at 6-month follow-up in burden compared to controls. No group differences were found on caregiver psychological distress and patient and caregiver quality of life. The low-level intervention seems to be as, if not more, effective than similar interventions applied in high income countries.


Chemical composition of Corallina mediterranea Areschoug and Corallina granifera Ell. et Soland.
The composition of sterols, volatiles and some polar compounds from three Corallina samples (C. granifera and C. mediterranea from the Black Sea and C. mediterranea from the Mediterranean Sea) was established. The sterol composition of the Black Sea samples was similar but it differs from that of the Mediterranean sample. The composition of the volatiles was very complex. The main groups of constituent were hydrocarbons, alcohols, carbonyl compounds, acids and their esters, terpenes. The composition of the polar components, soluble in n-butanol, was also established. There were some differences in the chemical composition of the two Black Sea species, which may be due to the biodiversity between them, while the differences in the composition of the two C. mediterranea samples could be due to the differences in the environment (salinity, temperature, pollution, etc.).


Solid mature ovarian teratoma with intrarectal protusion: case report.
Primary rectal teratoma is a very rare entity. It has been suggested that these tumors grow from aberrant germinal cells of the embryonic digestive tract. Ovarian tumor can also erode the rectal wall, allowing the formation of a fistula localized inside the rectum, becoming an extremely rare complication. We report the first case of a 54-year old woman with transanal bleeding whose endoscopic investigation showed a hairy-covered tumor in its surface localized 15 cm from the anal margin. Scanning detected its exact location and the presence of bony tissue within. By means of a laparotomy, we identified the left ovary fusioned to the anterior face of the rectum where a 5 x 4 cm tumor was originally protruding towards its lumen. Left oophorectomy was performed and through a peri-tumoral section of the intestinal wall we extracted the tumor from the inner rectum and closed the defect with simple sutures. Histological report demonstrated a conglomerate of tissues that corresponded to the three germinal layers. Although rare, diagnosis of intrarectal ovarian teratoma must be considered as a differential diagnosis in patients with rectal tumors. Diagnosis is relatively easy in the presence of a tumor with a hairy surface that is evaluated endoscopically. For treatment we suggest a simple procedure with adequate results.


Is Neuromuscular Blocker Necessary in Pediatric Patients Undergoing Laparoscopic Inguinal Hernia Repair with Percutaneous Internal Ring Suturing?
Purpose The aim of this study is to evaluate operating conditions during general anesthesia with or without neuromuscular blocker (NMB) in patients undergoing percutaneous internal ring suturing (PIRS). Materials and Methods In this study, 40 patients, with American Society of Anesthesiologists I and II between the ages of 1 and 12 years, were randomly assigned to two groups to receive muscle relaxant with endotracheal tube (ETT) (ETT group) or without muscle relaxant with supreme laryngeal mask airway (sLMA) (LMA group). Anesthesia was maintained with sevoflurane in oxygen (Fio 2 0.3-0.5), thiopental sodium, fentanyl, and rocuronium in ETT group. In LMA group, same protocol was used without rocuronium. Heart rate, blood pressure, peak airway pressure, end-tidal carbon dioxide (EtCO2), and Spo 2 were recorded before and during pneumoperitoneum maintained at a pressure of 8 to 10 mm Hg. Duration of surgery, recovery time, anesthetic time, and grade of quality view were also recorded. Airway problems (cough, hoarseness, laryngospasm, and aspiration) were recorded. Results In LMA group, there was a statistically significant reduction in recovery time versus ETT group (11.6 ± 4.08 vs. 17.15 ± 5.32 minutes; p = 0,001). There were no statistically significant differences grade of quality view between the two groups (p = 0.548). There were no statistically significant differences in oxygen saturation (Spo 2), peak airway pressure, and EtCO2 between the two groups before or during insufflation (p > 0.05). Postoperative airway complications were significantly more prevalent in the ETT group. There was no case of inadequate ventilation, regurgitation, or aspiration recorded. Conclusion sLMA is safe and suitable alternative to ETT and NMB is not necessary in general anesthesia with sLMA, pediatric patients undergoing laparoscopic hernia repair with PIRS.


Wearable Performance Devices in Sports Medicine.
Wearable performance devices and sensors are becoming more readily available to the general population and athletic teams. Advances in technology have allowed individual endurance athletes, sports teams, and physicians to monitor functional movements, workloads, and biometric markers to maximize performance and minimize injury. Movement sensors include pedometers, accelerometers/gyroscopes, and global positioning satellite (GPS) devices. Physiologic sensors include heart rate monitors, sleep monitors, temperature sensors, and integrated sensors. The purpose of this review is to familiarize health care professionals and team physicians with the various available types of wearable sensors, discuss their current utilization, and present future applications in sports medicine. Data were obtained from peer-reviewed literature through a search of the PubMed database. Included studies searched development, outcomes, and validation of wearable performance devices such as GPS, accelerometers, and physiologic monitors in sports. Clinical review. Level 4. Wearable sensors provide a method of monitoring real-time physiologic and movement parameters during training and competitive sports. These parameters can be used to detect position-specific patterns in movement, design more efficient sports-specific training programs for performance optimization, and screen for potential causes of injury. More recent advances in movement sensors have improved accuracy in detecting high-acceleration movements during competitive sports. Wearable devices are valuable instruments for the improvement of sports performance. Evidence for use of these devices in professional sports is still limited. Future developments are needed to establish training protocols using data from wearable devices.


Functional Roles of Mesenchymal Stem Cell-derived Exosomes in Ischemic Stroke Treatment.
Stroke is a life-threatening disease and one of the leading causes of death and physical disability worldwide. Currently, no drugs on the market promote neural recovery after stroke insult, and spontaneous remodeling processes are limited to induce recovery in the ischemic regions. Therefore, promoting a cell-based therapy has been needed to elevate the endogenous recovery process. Mesenchymal stem cells (MSCs) have been regarded as candidate cell sources for therapeutic purposes of ischemic stroke, and their therapeutic effects are mediated by exosomes. The microRNA cargo in these extracellular vesicles is mostly responsible for the positive effects. When it comes to the therapeutic viewpoint, MSCsderived exosomes could be a promising therapeutic strategy against ischemic stroke. The aim of this review is to discuss the current knowledge around the potential of MSCs-derived exosomes in the treatment of ischemic stroke.