Venous thromboembolism in hospitalized adolescents: an approach to risk assessment and prophylaxis.
Pediatric hospital-acquired venous thromboembolism (VTE) is an increasingly prevalent and morbid disease. A multidisciplinary team at a tertiary children's hospital sought to answer the following clinical question: "Among hospitalized adolescents, does risk assessment and stratified VTE prophylaxis compared with no prophylaxis reduce VTE occurrence without an increase in significant adverse effects?" Serial literature searches using key terms were performed in the following databases: Medline, Cochrane Database, CINAHL (Cumulative Index to Nursing and Allied Health), Scopus, EBMR (Evidence Based Medicine Reviews). Pediatric studies were sought preferentially; when pediatric evidence was sparse, adult studies were included. Abstracts and titles were screened, and relevant full articles were reviewed. Studies were rated for quality using a standard rating system. Moderate evidence exists to support VTE risk assessment in adolescents. This evidence comes from pediatric studies that are primarily retrospective in design. The results of the studies are consistent and cite prominent factors such as immobilization and central venous access. There is insufficient evidence to support specific prophylactic strategies in pediatric patients because available pediatric evidence for thromboprophylaxis efficacy and safety is minimal. There is, however, high-quality, consistent evidence demonstrating efficacy and safety of thromboprophylaxis in adults. On the basis of the best available evidence, we propose a strategy for risk assessment and stratified VTE prophylaxis for hospitalized adolescents. This strategy involves assessing risk factors and considering prophylactic measures based on level of risk. We believe this strategy may reduce risk of VTE and appropriately balances the adverse effect profile of mechanical and pharmacologic prophylactic methods.


Idiopathic bladder hyperactivity treated with Ditropan (oxybutynin chloride).
Ditropan (oxybutynin chloride), a tertiary amine with slight anticholinergic and marked "papaverine-like" direct spasmolytic effects has been administered to 25 patients with idiopathic hyperactive bladder function. The drug reduced voiding frequency and abolished urgency. Control cystometry confirmed a significant increase in bladder capacity. Oral dryness was a tolerable side effect.


The sensitivity, specificity and reliability of the GALS (gait, arms, legs and spine) examination when used by physiotherapists and physiotherapy students to detect rheumatoid arthritis.
To evaluate the sensitivity, specificity and reliability of the gait, arms, legs and spine (GALS) examination to detect signs and symptoms of rheumatoid arthritis when used by physiotherapy students and physiotherapists. Two physiotherapy students and two physiotherapists were trained to perform the GALS examination by viewing an instructional DVD and attending a workshop. Two rheumatologists familiar with the GALS examination also participated in the workshop. All healthcare professionals performed the GALS examination on 25 participants with rheumatoid arthritis recruited through a rheumatology practice and 23 participants without any arthritides recruited from a primary care centre. Each participant was assessed by one rheumatologist, one physiotherapist and one physiotherapy student. Abnormalities of gait, arms, legs and spine, including their location and description, were recorded, along with whether or not a diagnosis of rheumatoid arthritis was suspected. Healthcare professionals understood the study's objective to be their agreement on GALS findings and were unaware that half of the participants had rheumatoid arthritis. Sensitivity, specificity and likelihood ratios were calculated to determine the ability of the GALS examination to screen for rheumatoid arthritis. Using rheumatologists' findings on the study day as the standard for comparison, sensitivity and specificity were 71 to 86% and 69 to 93%, respectively. Positive likelihood ratios ranged from 2.74 to 10.18, while negative likelihood ratios ranged from 0.21 to 0.38. The GALS examination may be a useful tool for physiotherapists to rule out rheumatoid arthritis in a direct access setting. Differences in duration and type of experience of each healthcare professional may contribute to the variation in results. The merits of introducing the GALS examination into physiotherapy curricula and practice should be explored.


Comment on: "Energy landscape of a small peptide revealed by dihedral angle principal component analysis".
The dihedral angle principal component analysis method published recently by Mu, Nguyen, and Stock, is shown to produce distortions of the free energy landscape due to the neglect of constraints in the coordinates. It is further shown that these distortions can create artificial minima and energy barriers. The rugged energy landscape that the authors find for a small peptide chain might thus be an artifact of their method.


Role of Vitamin D in Inflammatory Bowel Disease.
Vitamin D is a secosteroid hormone that possesses immunomodulatory properties and has been demonstrated to potentially influence inflammatory bowel disease (IBD) pathogenesis and activity. Epidemiologic data have associated vitamin D deficiency with an increased risk of IBD, hospitalizations, surgery, and loss of response to biologic therapy. Conversely, IBD itself can lead to vitamin D deficiency. This bidirectional relationship between vitamin D and IBD suggests the need for monitoring and repletion of vitamin D, as needed, in the IBD patient. This review discusses the role of vitamin D in IBD and provides practical guidance on vitamin D repletion.


Diffuse sclerosing variant of papillary thyroid carcinoma. Clinicopathologic study of 15 cases.
We report 15 cases of a distinctive variant of thyroid papillary carcinoma designated as "diffuse sclerosing papillary carcinoma" (DSPC). This lesion is characterized by the following morphologic findings: (a) diffuse involvement of one or both lobes, (b) numerous micropapillary formations located within cleftlike spaces consistent with lymph vessels, (c) extensive squamous metaplasia, (d) large number of psammoma bodies, (e) marked lymphocytic infiltration, (f) prominent fibrosis. Of all these features, we believe the widespread intrathyroid lymphatic permeation to be the most important, in the sense of conditioning the other morphologic findings and the behavior of the tumor. When compared with conventional papillary carcinoma, the DSPC variant exhibits the following characteristics: (a) similar predilection for women, (b) younger age at the time of presentation, (c) greater incidence of cervical lymph node involvement, (d) greater incidence of lung metastases, (e) smaller probability of disease-free survival on follow-up. The practical importance of the recognition of this variant of papillary carcinoma lies in its ability to clinically simulate thyroiditis and the more aggressive therapeutic approach that might be needed to eradicate it.


Incidence of mammary intra-arterial calcification: an age-matched control study.
Mammary intra-arterial calcification (MIAC) was seen on the mammograms of 13 of 150 (8.7%) known diabetic patients and 21 of 300 (7.0%) age-matched control patients. Statistical analysis verified no significant difference between the rate of occurrence of MIAC in the diabetic group of patients and the control group. Therefore, contrary to previous reported studies, our study does not support the conclusion of an increased frequency of MIAC in diabetic patients. MIAC is a manifestation of peripheral vascular disease resulting from a variety of causes, one of which may be diabetes.


Dental extractions for preradiation dental clearance and incidence of osteoradionecrosis in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.
The aims of the present retrospective study were to evaluate the outcomes of dental extractions in nasopharyngeal carcinoma patients who had undergone dental clearance pre- and post-radiotherapy (RT) with intensity-modulated RT, and to report on the incidence and timing of osteoradionecrosis (ORN) in these patients. A total of 231 patients were seen pre-, mid-, and postradiation therapy. Information on patient demographics, smoking history, staging, treatment modalities, dental extraction indications, and number and site of dental extractions was gathered. Wilcoxon two-sample tests and Fisher's exact test were used to test the association between groups for patient variables. The mean number of teeth removed was 4.1 teeth per patient. A total of 334 (35.2%) teeth were removed for periodontal reasons, 322 (34.03%) were removed prophylactically, and the remaining teeth were removed because of deep caries, retained roots, partial impaction, endodontic lesions, and prosthodontic reasons. Patients had an average of 19.6 teeth remaining after dental clearance, and only 97 (42%) required prosthetic intervention. The statistical analysis showed that there was no correlation between dental extractions pre- or post-RT and the development of ORN. No specific parameter was directly associated with dental extractions, although smoking and increased number of teeth removed preradiation seemed to be prevalent in patients who developed ORN.


Modulation by cyclic AMP and phorbol myristate acetate of cephaloridine-induced injury in rat renal cortical slices.
Intracellular signaling pathways of cAMP and protein kinase C (PKC) have been suggested to modulate the generation of free radicals. We investigated the effects of cAMP and phorbol myristate acetate (PMA), a PKC activator, on cephaloridine (CER)-induced renal cell injury, which has been reported to be due to the generation of free radicals. Incubation of rat renal cortical slices with CER resulted in increases in lipid peroxidation and lactate dehydrogenase (LDH) release and in decreases in gluconeogenesis and p-aminohippurate (PAH) accumulation in rat renal cortical slices, suggesting free radical-induced injury in slices exposed to CER. A derivative of cAMP ameliorated not only the increase in lipid peroxidation but also the renal cell damage induced by CER. This amelioration by a cAMP derivative of lipid peroxidation and renal cell damage caused by CER was blocked by KT 5720, a protein kinase A (PKA) inhibitor. Lipid peroxidation and the indices of cell injury were increased by PMA. PMA also enhanced CER-induced lipid peroxidation and cell damage in the slices. This enhancement by PMA of CER-induced injury was blocked by H-7, a PKC inhibitor. These results indicated that intracellular signaling pathways of cAMP and PKC modulate free radical-mediated nephrotoxicity induced by CER.


Coercivity of permanent magnetic thin film.
The coercivity of magnetic thin film having a two-dimensional easy-axis distribution is investigated within the framework of a simple micromagnetic model. It is found that the coercivity decreases from 0.14H(K) to a minimum of 0.07H(K) as thickness increases, where H(K) is the anisotropy field. It is substantially lower than that given by the Stoner-Wohlfarth model and is consistent with available experimental data. The calculated hysteresis loop and the initial magnetization curve are also in good agreement with experiments.


[Representation of self-care of health at work among urban bus drivers in Guadalajara, Mexico].
This study aimed to analyze the social representations of health self-care at work among urban bus drivers in Guadalajara, Mexico. The methodology was qualitative, with a multi-method design based on the theory of social representations. The first stage involved active observation sessions with the information recorded in field notes; in the second stage, the associative letter technique and successively hierarchized trees technique were applied to 20 drivers, submitting the data to a classical analysis of the free associations; a third stage involved semi-structured interviews with 4 drivers, submitted to content analysis. The results indicate that structurally, the representation is centered on alimentation, presenting the concepts rest and corrective health care at peripheral levels. Procedurally, the represeentation centers in the psychosocial factors derived from the working conditions, while the rest of the work characteristics are seen as low risk to health. The self-care actions mentioned by the participants only focus on the workinging conditions perceived as risky. The social representation of health self-care at work is a collective mental construction, developed and modified through social interactions, which influences self-care measures used against the risks perceived in the workplace.


Schizophrenic patients who develop postoperative confusion have an increased norepinephrine and cortisol response to surgery.
The purpose of this study was to investigate the relationship between postoperative confusion and the plasma norepinephrine (NE), adrenocorticotropin (ACTH) or cortisol response to surgery in schizophrenic patients. We studied 50 schizophrenic patients and 35 control patients who underwent orthopedic surgery and perioperatively measured plasma NE, ACTH and cortisol levels. Postoperative confusion during 72 h after the end of the operation occurred in 14 of 50 schizophrenic patients (28%) and in 2 of 35 control patients (6%). Plasma NE levels 15 min after skin incision, the next day, the second day and the third day after operation in schizophrenic patients with postoperative confusion (668.0 +/- 59.2, 522.0 +/- 96.5, 463.2 +/- 71.2 and 398.9 +/- 56.2 pg/ml, respectively) were significantly higher than those in schizophrenic patients without confusion (524.1 +/- 62.6, 342.4 +/- 38.6, 311.2 +/- 58.3 and 314.1 +/- 77.1 pg/ml, respectively). Plasma cortisol levels 15 min after the skin incision and the next and second days after operation in schizophrenic patients with postoperative confusion (23.6 +/- 3.2, 21.1 +/- 4.3 and 19.9 +/- 4.4 microg/dl, respectively) were significantly higher than those in schizophrenic patients without confusion (15.2 +/- 4.5, 14.3 +/- 5.1 and 13.8 +/- 3.8 microg/dl, respectively). In conclusion, the occurrence of postoperative confusion in schizophrenic patients is associated with an increase in plasma norepinephrine and cortisol levels during and after surgery.


Clinical factors such as B-type natriuretic peptide link to factor VII, endothelial NO synthase and estrogen receptor alpha polymorphism in elderly women.
This study evaluated the presence of genetic mutations in relation to thrombosis or atherosclerosis in elderly women. This is an observational study of 93 Japanese women with a mean age of 80.9 years recruited from outpatient clinics of Nagoya University and its related hospitals. Ten single nucleotide polymorphisms (SNPs) were studied. Each gene studied acts in or is related to either blood coagulation (factor V Leiden, prothrombin G20210A, factor XIII Val34Leu, factor VII Arg353Gln, MTHFR C677T, beta-fibrinogen G-455A, PAI-1 4G/5G), metabolic syndrome-related pathways (PPARalpha Leu162Val), or endothelium/estrogen system (eNOS Glu298Asp, ERalpha IVS1-401). SNPs were analyzed for their relation to clinical values including lipids, B-type natriuretic peptide (BNP), fasting plasma glucose, tumor necrosis factor-alpha, interleukin-6, cyclic GMP, and nitric oxide metabolites. Comparisons between the distributions of different genotypes and clinical values showed three relationships. First, factor VII Arg353Gln and HDL-cholesterol (HDL-C) were linked to Arg/Arg carriers at higher levels (P=.049). The HDL-C to LDL-cholesterol ratio supported this link (P=.027). Second, eNOS Glu298Asp and triglycerides were linked to Glu/Glu carriers at higher levels (P=.031). Third, ERalpha IVS1-401 and BNP were related to CC genotype at lower levels (P=.031). Additionally, the last two relations showed that genotype does not influence the demarcation line of biomarkers, but the plasma/serum levels of biomarkers instead. Correlations of factor VII Arg353Gln with HDL-C and eNOS Glu298Asp with triglycerides are new findings. Polymorphisms in the endothelium/estrogen system and the heart failure marker BNP are also correlated, with ERalpha IVS1-401 being the first identified marker. SNPs may be helpful for understanding the pathophysiology of atherosclerotic diseases in elderly women.


Nonattendance at a hospital-based otolaryngology clinic: a preliminary analysis within a universal healthcare system.
Missed appointments at specialty clinics generate concerns for physicians and clinic administrators. Appointment nonattendance obstructs the provision of timely medical interventions and the maximization of systemic efficiencies. Yet, empiric study of factors associated with missed appointments at adult specialty clinics has received little attention in North America. We conducted a preliminary study of otolaryngology clinic nonattendance in the context of a universal healthcare system environment in Canada. Our data were based on the schedule of 1,512 new patient appointments at a hospital-based clinic from May 1 through Sept. 30, 2008. Gathered information included the employment status of the attending physician (i.e., full-time vs. part-time), the patient's sex and age, the day of the week and the time of the appointment, and the attendance status. We found that the rate of nonattendance was 24.4% (n = 369). Nonattendance rates varied significantly according to physician employment status (more common for part-time physicians), patient sex (women) and age (younger adults), and the day of the appointment (Wednesdays), but not according to the time of day. Our findings suggest that there are predictable patient and systemic factors that influence nonattendance at medical appointments. Awareness of these factors can have implications for the delivery of healthcare services within a universal healthcare context.


Analysis of polychlorinated n-alkanes in environmental samples.
Polychlorinated n-alkanes (PCAs), also known as chlorinated paraffins (CPs), are highly complex technical mixtures that contain a huge number of structural isomers, theoretically more than 10,000 diastereomers and enantiomers. As a consequence of their persistence, tendency to bioaccumulation, and widespread and unrestricted use, PCAs have been found in aquatic and terrestrial food webs, even in rural and remote areas. Recently, these compounds have been included in regulatory programs of several international organizations, including the US Environmental Protection Agency and the European Union. Consequently, there is a growing demand for reliable methods with which to analyze PCAs in environmental samples. Here, we review current trends and recent developments in the analysis of PCAs in environmental samples such as air, water, sediment, and biota. Practical aspects of sample preparation, chromatographic separation, and detection are covered, with special emphasis placed on analysis of PCAs using gas chromatography-mass spectrometry. The advantages and limitations of these techniques as well as recent improvements in quantification procedures are discussed.


[Effectiveness of iodine prophylaxis and frequency of thyroid enlargement (thyroid goiter) and clinical diagnosis of thyroid diseases in inhabitants of the Szczecin region after the Czernobyl accident].
The study, supported by program MZ-XVII, was carried on 4567 inhabitants of the area of Szczecin (2350 females and 2217 males). The population was chosen randomly, according to a simple drawing scheme. All subjects were clinically examined using standardised questionnaires. In 3468 persons (including 1807 girls and women, 1661 boys and men) apart form clinical examination, the assessment of thyrotropin, thyroxine and triiodothyronine in serum and frequency of antithyroglobulin antibodies and antithyroid membrane antibodies were evaluated. The data indicate that 94% of children in Szczecin's region received the prophylactic dose of iodine, mostly between the 1st and the 5th of May 1986. Only 17% of the adults received iodine. The most common preparation was Lugol solution given in a single dose. Among all persons who received iodine, only in 5% of subjects the side effects were noted (mostly in children), including symptoms of gastrointestinal tract (vomiting, abdomen pain) and occasionally intrathyroid side effects (thyroid pains). In examined population the high frequency of thyroid enlargement, mainly in women (up to 43-44% at the age group 30-50 years) was found. The frequency of clinical diagnosis of thyroid disease was higher in women than in man (most often the diffuse goiter, rarely the nodular goiter). The frequency of thyroid enlargement and clinical diagnosis of thyroid disease was not dependent on prophylactic iodine intake. The iodine prophylaxis did not influence on thyroid hormones and TSH serum levels and on frequency of antithyroid antibodies.


Small airways function of silica-exposed workers.
Small airways obstruction may be present for many years before chronic airway obstruction becomes evident. Several spirometric indices, especially flow rates at low lung volumes, may reflect the status of small airways. Time domain indices, by using moments analysis of the volume time spirogram, have also been shown to be sensitive indicators of small airways obstruction. In this study, we have applied the various spirometric indices as well as time domain indices to a group of granite quarry workers without radiographic evidence of silicosis or physiological evidence of obstruction to the larger airways. The aim was to evaluate small airways function in relation to dust exposure in subjects with normal ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1/FVC) and normal FVC. The volume-time spirograms of 140 quarry workers were digitized using an electronic digitizer connected to a microcomputer where flow and time domain indices were computed. The workers were divided into three exposure groups based on their occupational history. With adjustment for age, height, and smoking status, all the time domain indices showed significant small airways obstruction with increasing dust exposure. Smokers had greater degree of airways obstruction than the non-smokers, with a similar trend of increase in small airways obstruction in relation to higher exposure. Our present study suggests that small airways obstruction is present among silica exposed workers in the absence of radiological evidence of silicosis and large airways obstruction. There was also evidence of increasing small airways obstruction in higher dust exposure group. Our study also suggests that time domain indices are more sensitive to small airways obstruction.


Fidelity and predominant mutations produced by deep vent wild-type and exonuclease-deficient DNA polymerases during in vitro DNA amplification.
Denaturing gradient gel electrophoresis (DGGE) was used to examine error rates and mutations induced by native (wt) and exonuclease-deficient (exo-) Deep Vent DNA polymerases during DNA amplification by polymerase chain reaction (PCR), in the presence or absence of the T4 bacteriophage gene 32 protein (gp32).gp32 was found to decrease the error rate of the wt, but not that of the exo-, Deep Vent. The average errors per base duplication for the native form were 8.0 x 10(-5) and 6.0 x 10(-5) in the absence and presence of gp32, respectively. For the exo- form, the error rates were 2.0 x 10(-4) and 2.2 x 10(-4) errors per base duplication in the absence and presence of gp32, respectively. Examination of mutations produced by native Deep Vent showed that A/T to G/C transition predominated, consistent with the results of our earlier studies with DNA polymerases derived from other thermophilic bacteria. These results indicate that PCR with high fidelity can be achieved by using wt Deep Vent in combination with gp32.


Persistent hyperinsulinemic hypoglycemia of infancy - nesidioblastosis.
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or nesidioblastosis is a rare condition presenting with severe hypoglycemia. Prompt diagnosis and early pancreatectomy can save many of them, in spite of the magnitude of surgery. We present two cases in which near total pancreatectomy was performed with favourable outcome. Both patients are normoglycemic, with one requiring pancreatic enzyme supplements.


Automatic analysis of image of surface structure of cell wall-deficient EVC.
Some computer applications for cell characterization in medicine and biology, such as analysis of surface structure of cell wall-deficient EVC (El Tor Vibrio of Cholera), operate with cell samples taken from very small areas of interest. In order to perform texture characterization in such an application, only a few texture operators can be employed: the operators should be insensitive to noise and image distortion and be reliable in order to estimate texture quality from images. Therefore, we introduce wavelet theory and mathematical morphology to analyse the cellular surface micro-area image obtained by SEM (Scanning Electron Microscope). In order to describe the quality of surface structure of cell wall-deficient EVC, we propose a fully automatic computerized method. The image analysis process is carried out in two steps. In the first, we decompose the given image by dyadic wavelet transform and form an image approximation with higher resolution, by doing so, we perform edge detection of given images efficiently. In the second, we introduce many operations of mathematical morphology to obtain morphological quantitative parameters of surface structure of cell wall-deficient EVC. The obtained results prove that the method can eliminate noise, detect the edge and extract the feature parameters validly. In this work, we have built automatic analytic software named "EVC.CELL".


Squamous cell carcinoma in an African American with discoid lupus erythematosus: a case report and review of the literature.
Discoid lupus is an autoimmune disorder with primarily cutaneous manifestations. Carcinomatous changes in discoid lupus can lead to the development of squamous cell carcinoma. While this most often occurs in Caucasians, the presented patient is an African American. She developed numerous squamous cell carcinomas in areas of scarring from discoid lupus. This case illustrates the need for careful observation of discoid lupus for the development of squamous cell carcinoma in the African American patient.


[Do meniscus injuries affect postural stability?].
Meniscal lesions are known to cause a loss of proprioception, which plays an important role in the regulation of postural stability. It is unclear, however, whether meniscus injuries adversely affect not only the sense of joint position but also postural control. The objective of this study was to investigate the influence of meniscal lesions on postural stability. In this prospective study, postural stability was assessed by posturography in 27 patients with unilateral meniscal lesions. Both the injured and uninjured legs were tested and compared for significant differences using a t-test. Despite the presence of an arthroscopically confirmed meniscal lesion, none of the stability indexes that we calculated revealed significant differences in postural stability between the injured and uninjured sides. It was surprising to note that the loss of proprioception in patients with meniscus injuries did not influence postural stability. Patients with functional knee instability must therefore be examined for the presence of further injuries because a meniscal lesion alone cannot explain instability symptoms.


Upper bounds on noise and model misspecification for robust estimation of real-time brain activity from functional near infrared spectroscopy.
The robust characterization of real-time brain activity carries potential for many applications. However, the contamination of measured signals by various instrumental, environmental, and physiological sources of noise introduces a substantial amount of signal variance and, consequently, challenges real-time estimation of contributions from underlying neuronal sources. Functional near infrared spectroscopy (fNIRS) is an emerging imaging modality whose real-time potential is yet to be fully explored. The objectives of the current study are to (i) validate a time-dependent linear model of hemodynamic responses in fNIRS, and (ii) test the robustness of this approach against measurement noise (instrumental and physiological) and mis-specification of the hemodynamic response basis functions (amplitude, latency, and duration). We propose a linear hemodynamic model with time-varying parameters, which are estimated (adapted and tracked) using a dynamic recursive least square algorithm. Owing to the linear nature of the activation model, the problem of achieving robust convergence to an accurate estimation of the model parameters is recast as a problem of parameter error stability around the origin. We show that robust convergence of the proposed method is guaranteed in the presence of an acceptable degree of model misspecification and we derive an upper bound on noise under which reliable parameters can still be inferred. While here applied to fNIRS, the proposed methodology is applicable to other hemodynamic-based imaging technologies such as functional magnetic resonance imaging.


Recurrences of Pituitary Adenomas or Second De Novo Tumors: Comparisons with First Tumors.
Recurrences of pituitary adenomas are not so rare. In the German Registry of Pituitary Tumors, more than 12,000 surgical specimens were collected between 1967 and 2012, of which 312 patients with altogether 334 recurrences (n = 646 specimens) were included in our study. The histopathology of 162 recurrent adenomas could be compared with the original tumor and 37 second recurrences could be compared with the first recurrence. Comparing the proliferation index (Ki-67) of the original and the first recurrent tumor (n = 162), we found an unchanged index in 43 cases (26%), whereas in 69 cases (43%) the index increased and in 50 cases (31%) it decreased. Comparing the first with the second recurrence (n = 37), we found an unchanged index in 8 cases (22%), an increased index in 15 cases (40%), and a decreased index in 14 cases (38%). The third recurrence showed an unchanged index in 1 case (20%), an increased index in 2 cases (40%), and a decreased index in 2 cases (40%). p53 was unchanged in recurrences in 44% of cases, increased in 33%, and decreased in 22%. In 4 cases, adenomas developed into adenomas with strongly increased proliferation (formerly atypical adenomas, now aggressive adenomas) for the first recurrence, and 9 recurrences became aggressive adenomas. A change of tumor type without change of the common transcription factor occurred in 82 cases. A second independent de novo adenoma was present in 10 cases, probably due to changes of transcription factors.


[Selection of active strains of Actinomadura carminata, the producer of carminomycin].
The method of selecting active strains among a definite group of analogue-resistant mutants was used on the basis of studying the dependence of the carminomycin-producing organism growth and the antibiotic synthesis level on some metabolites. As a result, gamma-ray induced mutants 4 times more active than the parent strains were obtained.


Manifesting pediatric carrier of isolated dystrophinopathy with initial presentation of myalgia and persistent hyperCKemia.
Dystrophinopathy is caused by mutations in the dystrophin gene at Xp21. Although manifesting carriers of dystrophinopathy have been documented in adults, symptomatic dystrophinopathy in female children is rare. We report on a 13-year-old girl with initial presentation of myalgia at age 7 years and an incidental finding of increased transaminases and creatine kinase at regular health check at age 12 years. At age 13 years, manual muscle testing revealed asymmetric bilateral proximal weakness of extremities. Slight calf hypertrophy and winged scapulae were found. Muscle biopsy revealed a mosaic pattern in dystrophin immunostaining. Mutation analysis of the dystrophin gene revealed a novel de novo c.1150-2delA mutation. Accordingly, the patient was found to be an isolated dystrophinopathy carrier, manifesting limb-girdle pattern of muscle weakness in her childhood. This report suggests that dystrophinopathy should always be considered in female patients with sporadic myopathy. Dystrophin immunostaining and mutation analysis for the dystrophin gene are necessary for final diagnosis, subsequent genetic counseling, and long-term care.


Preparation of purified fractions for polysaccharides from Monetaria moneta Linnaeus and comparison their characteristics and antioxidant activities.
The aim of this paper was to prepare purified fractions of polysaccharides from Monetaria moneta Linnaeus and further compare their characteristics and antioxidant activities. Firstly, three novel purified fractions, named MM-P1, MM-P2 and MM-P3, were successfully prepared by a DEAE-Sepharose fast-flow column. Then, their characteristics were compared using chemical testing, FT-IR, GC and HPGPC. The results suggested that MM-P3 had higher molecular weights than MM-P1 and MM-P2. MM-P1 was consisted of glucose, MM-P2 was consisted of glucose and xylose, and MM-P3 was comprised of glucose, xylose and mannose. Differed from MM-P1 and MM-P2, MM-P3 had sulfuric radical and uronic acid groups. Finally, their antioxidant activities were also compared. We found that MM-P3 exhibited better antioxidant bioactivities than MM-P1 and MM-P2. The data demonstrated that three purified fractions derived from different adsorption capacity of DEAE-Sepharose fast-flow column possessed different structural characteristics and antioxidant activity.


[Effects of ossicular reconstruction with partial ossicular replacement prosthesis in patients with tympanosclerosis].
To evaluate the effect of ossicular reconstruction with partial ossicular replacement prosthesis (PORP) in patients with tympanosclerosis. The data of 28 cases of tympanosclerosis treated between 1992 and 2006 were reviewed. Of the 28 patients, 14 (14 ears) underwent ossicular reconstruction with PORP and 14 (14 ears) had ossicular mobilization, and all the patients were followed-up for 3-24 months. Significant improvement was found in postoperative speech frequency (500, 1000, 2000 Hz) pure tone average (PTA) and air-bone gap (ABG) closure after in the operation the two groups. Ossicular reconstruction using PORP resulted in statistically better ABG closure and PTA (P<0.05). In ossicular attic fixation, ossicular reconstruction using PORP can yield better results than mobilization of the major ossicles in patients with tympanosclerosis.


Digitalis-like biological activity in rat cerebellum.
The cytosolic fraction of rat cerebellum possesses a factor(s) which is capable of inhibiting synaptosomal Na,K-ATPase activity, competing with [3H]ouabain binding to rat brain synaptosomes, and inducing positive inotropy in guinea pig atrial strips. These results demonstrate the existence of a ouabain-like principle in rat cerebella. The inhibitory activity of the factor was found to be partially thermolabile and diminished by a proteolytic agent, and the activity could be augmented by increasing concentrations of Mg2+, suggesting a regulatory mechanism for the endogenous digitalis-like principle.


[Tiapride and pain in amputees].
Missing limb pain remains a preoccupying and worrisome problem for amputees. Approximately one-third of amputees experience missing limb pain. Although it often abates with time, this pain disables the patient in the first few months following amputation. We carried out a therapeutic trial of oral tablets of tiapride, which was given to twenty patients in three daily doses of 50 to 100 mg each. Tiapride was the sole medication in most instances. Analgesia appeared after an interval of 24 hours to 15 days. Clinical tolerance was excellent. Efficiency in terms of resolution of pain is observed in most cases.


The melanocortin 1 receptor and the UV response of human melanocytes--a shift in paradigm.
Cutaneous pigmentation is the major photoprotective mechanism against the carcinogenic and aging effects of UV. Epidermal melanocytes synthesize the pigment melanin, in the form of eumelanin or pheomelanin. Synthesis of the photoprotective eumelanin by human melanocytes is regulated mainly by the melanocortins alpha-melanocortin (alpha-MSH) and adrenocorticotropic hormone (ACTH), which bind the melanocortin 1 receptor (MC1R) and activate the cAMP pathway that is required for UV-induced tanning. Melanocortins stimulate proliferation and melanogenesis and inhibit UV-induced apoptosis of human melanocytes. Importantly, melanocortins reduce the generation of hydrogen peroxide and enhance repair of DNA photoproducts, independently of pigmentation. MC1R is a major contributor to the diversity of human pigmentation and a melanoma susceptibility gene. Certain allelic variants of this gene, namely R151C, R160W and D294H, are strongly associated with red hair phenotype and increased melanoma susceptibility. Natural expression of two of these variants sensitizes melanocytes to the cytotoxic effect of UV, and increases the burden of DNA damage and oxidative stress. We are designing potent melanocortin analogs that mimic the effects of alpha-MSH as a strategy to prevent skin cancer, particularly in individuals who express MC1R genotypes that reduce but do not abolish MC1R function, or mutations in other melanoma susceptibility genes, such as p16.


Internet Cognitive-Behavioral Therapy for Depression in Older Adults With Knee Osteoarthritis: A Randomized Controlled Trial.
To determine the efficacy of an internet-based cognitive-behavioral therapy (iCBT) program for depression in older adults with osteoarthritis (OA) of the knee and comorbid major depressive disorder (MDD). We conducted a randomized controlled trial in 69 adults (ages ≥50 years) meeting criteria for MDD and OA of the knee with 1-week postintervention (week 11) and 3-month followup (week 24) end points. Patients were allocated to either a 10-week iCBT program for depression added to treatment as usual (TAU) or to a TAU control group. Primary outcomes were depression symptoms (9-Item Patient Health Questionnaire [PHQ-9]) and psychological distress (Kessler-10 [K-10]). Secondary outcomes included arthritis self-efficacy (Arthritis Self-Efficacy Scale [ASES]), OA pain, stiffness, physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and physical and mental health (Short Form 12-Item health survey physical component and mental component summaries). Depression status was assessed by blinded diagnostic interview (the Mini-International Neuropsychiatric Interview) at intake and followup. Intent-to-treat analyses indicated between-group superiority of iCBT over TAU on the primary outcomes (PHQ-9: Hedges g = 1.01, 95% confidence interval [95% CI] 0.47, 1.54; K-10: Hedges g = 0.75, 95% CI 0.23, 1.28), at postintervention and 3-month followup (PHQ-9: Hedges g = 0.90, 95% CI 0.36, 1.44; K-10: Hedges g = 0.94, 95% CI 0.41, 1.48), and on secondary OA-specific measures (ASES: Hedges g = -0.81, 95% CI -0.29, -1.33; WOMAC: Hedges g = 0.56-0.65, 95% CI 0.04, 1.18) at the 3-month followup. The majority of iCBT participants (84%) no longer met diagnostic criteria at 3-month followup. Results support the efficacy of an iCBT program (requiring no face-to-face contact) for depression in individuals with comorbid depression and OA of the knee. Importantly, the benefits of the program extended beyond reduced depressive symptoms and distress to include increased self-efficacy and improved pain, stiffness, and physical function at followup.


Integrated microRNA and mRNA signatures in peripheral blood lymphocytes of familial epithelial ovarian cancer.
Characterization of the genetic landscapes of familial ovarian cancer through integrated analysis of microRNA and mRNA by partial least squares (PLS) and Monte Carlo technique based on genome-wide association studies (GWAS). The miRNA and mRNA transcriptional data in familial ovarian cancer were characterized from the Gene Expression Omnibus (GEO) database. The miRNA and mRNA expression profiles in peripheral blood lymphocytes (PBLs) of 74 familial ovarian cancer patients and 47 control subjects were analyzed with the integration of partial least squares (PLS) and Monte Carlo techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also performed. Total of 16 miRNA-mRNA pairs were identified with the target gene prediction results of miRNAs and mRNAs. An innovated miRNA-mRNA integrated network was constructed in which 6 downregulated miRNAs and 1 upregulated miRNAs were included. KEGG and GO pathway enrichment analysis revealed over-representation of dysregulated miRNAs in various biological processes especially in cancer pathology. Hsa-miR-34b played a pivotal role in this network and interacted with other miRNAs. Hsa-miR-136 and hsa-miR-335 were associated with p53 and Erk1/2 pathways and tumor suppressors, such as PTEN. The results from this research provide insights on miRNA-mRNA networks and offer new tools for studying transcriptional variants in familial ovarian cancer.


Sensorimotor optimization in higher dimensions.
Most studies of neural control have looked at constrained tasks, with only a few degrees of freedom, but real sensorimotor systems are high dimensional--e.g. gaze-control systems that coordinate the head and two eyes have to work with 12 degrees of freedom in all. These extra degrees of freedom matter, because they bring with them new issues and questions, which make it hard to translate low-dimensional findings into theories of real neural control. Here I show that it is possible to predict high-dimensional behavior if we apply the optimization principles introduced by 19th-century neuroscientists like Helmholtz, Listing, and Wundt. Using three examples--the vestibulo-ocular reflex, saccadic eye movements, and depth vision--I show how simple optimization theories can predict complex, unexpected behaviors and reveal fundamental features of sensorimotor control, e.g. that neural circuits perform noncommutative algebra; that in rapid gaze shifts the eye controllers deliver commands with three degrees of freedom, not two; and that the eyes roll about their lines of sight in a way that may simplify stereopsis.


(K,Na)NbO3 nanofiber-based self-powered sensors for accurate detection of dynamic strain.
A self-powered active strain sensor based on well-aligned (K,Na)NbO3 piezoelectric nanofibers is successfully fabricated through the electrospinning and polymer packaging process. The device exhibits a fast, active response to dynamic strain by generating impulsive voltage signal that is dependent on the amplitude of the dynamic strains and the vibration frequency. When the frequency is fixed at 1 Hz, the peak to peak value of the voltage increases from ∼1 to ∼40 mV, and the strain changes from 1 to 6%. Furthermore, the output voltage is linearly increased by an order of magnitude with the frequency changing from 0.2 to 5 Hz under the same strain amplitude. The influence of frequency on the output voltage can be further enhanced at higher strain amplitude. This phenomenon is attributed to the increased generating rate of piezoelectric charges under higher strain rate of the nanofibers. By counting the pulse separation of the voltage peaks, the vibration frequency is synchronously measured during the sensing process. The accuracy of the sensing results can be improved by calibration according to the frequency-dependent sensing behavior.


Attenuated-total-reflection technique for the determination of optical constants.
In a glass-metal-dielectric system, it is normally impossible to determine simultaneously the complex dielectric constant, the thickness of the metal, and the corresponding parameters of a dielectric overlayer. We propose the use of the pseudo-Brewster or Abelés angle as an additional parameter to characterize simultaneously a dielectric thin-film overcoating and the metal surface parameters. We use a Kretschmann attenuated-total-reflection configuration. An admittance diagram is used to illustrate graphically the role of an absentee layer at this angle. A study of the limitations of the method is also presented.


Automatic junctional tachycardia in an adult.
We report an adult patient with junctional ectopic tachycardia, a condition which was initially described in infants, frequently in association with congenital defects. The patient had a rapid, irregular paroxysmal junctional tachycardia with a rate ranging from 160 to 220 beats/min, distinguishing it from the more common nonparoxysmal junctional tachycardia in which a slower heart rate is seen. The electrophysiological study performed during an episode of tachycardia demonstrated periods of atrioventricular dissociation and narrow QRS complexes as well as a junctional ectopic rhythm, which was suggested by a His deflection preceding each ventricular depolarization with a normal HV interval. Both the response to exercise and the results of atrial and ventricular stimulation suggested enhanced automaticity of a high junctional focus. Therapy combining procainamide, verapamil, and digitalis proved to be effective. Thus, junctional ectopic tachycardia can also occur in adults, probably due to enhancement of automaticity.


Yttrium-90 delivered via a centering catheter and afterloader, given both before and after stent implantation, inhibits neointima formation in porcine coronary arteries.
Background: Intracoronary radiation (IR) studies have shown reduction of neointima formation (NF). Extrapolation of animal studies with beta-radiation to clinical trials have shown variable results, which may be related to dosimetry, centering issues, and/or shielding of beta-rays by the stent metal. We examined the effect of yttrium-90 (90Y), a pure beta-emitter delivered via an automatic afterloader to a centering catheter, on the inhibition of NF in balloon-injured (BI) porcine coronary arteries as well as in arteries receiving 90Y either prior to or following stent implantation (SI).Methods: Twenty-three swine (44 coronary arteries) were studied. In the first study, IR (18 Gy at 1.2 mm from the balloon surface) was administered in 17 arteries following BI, while eight control arteries were subjected to BI only. In the second study, 10 swine (19 coronary arteries) underwent SI. IR (18 Gy) was administered in six arteries before and in eight arteries after SI, while five control arteries received SI only. The animals were sacrificed 2 weeks after BI and 4 weeks after SI. Their coronaries were perfusion fixed and stained, and vessel parameters (intimal area [IA] and medial fracture length [FL]) were analyzed by computer-aided histomorphometry.Results: Arteries subjected to IR following BI had less NF compared to controls (IA/FL=0.14+/-0.2 mm vs. 0.49+/-0.2 mm; P=0.003). IA was reduced significantly in the arteries receiving radiation before and after SI compared to controls (0.92+/-0.98 and 0.00+/-0/00 vs. 2.72+/-1.2 mm(2); P=0.014), despite similar SI in all groups.Conclusions: IR with 90Y delivered via a centering catheter is safe and effective with complete and homogenous inhibition of NF in the context of BI or SI in the porcine coronary model.


Spermine induces cell death in cultured human embryonic cerebral cortical neurons through N-methyl-D-aspartate receptor activation.
The polyamines putrescine, spermidine, and spermine play important roles in cell proliferation, differentiation, and modulation of ion channel receptors. However, the function of increased concentrations of these compounds in brain injury and disease is unclear, in that they have been proposed as being both neuroprotective and neurotoxic. The effects of spermine and putrescine were studied in human primary cerebral cortical cultures containing both neurons and glia. No toxic effects were induced at 8 days in vitro (DIV) by either of the two polyamines at concentrations ranging from 0.3 microM to 2 mM. However, when the oxidative metabolism of spermine that generates toxic byproducts was induced by the presence of fetal calf serum, spermine caused cellular death with an LC(50) of approximately 50 microM. At 14 DIV, the coapplication of spermine 2 mM and glutamate 5 mM induced neuron cell death, but the effect of applying both components separately was null. Both spermine and glutamate were toxic to older neurons (26-42 DIV cultures), and here the coapplication of glutamate was found always to intensify the effect of spermine. Spermine showed greater toxicity than glutamate in neurons. Another effect observed is that glutamate, but not spermine, induced astrocyte swelling. Spermine toxicity was inhibited by both MK801 and ifenprodil, indicating a mechanism involving N-methyl-D-aspartate (NMDA) receptor activation. Moreover, a strong spermine modulation of the NMDA receptor was demonstrated by the inhibition of glutamate toxicity by ifenprodil. Putrescine induced minor effects also as a neurotoxic agent. In conclusion, neuronal death by spermine can be induced by its toxic byproducts as well as through NMDA receptor action. The present results confirm the potentially harmful role of the polyamines in excitotoxicity-related human disorders.


The WW domain containing E3 ubiquitin protein ligase 1 upregulates ErbB2 and EGFR through RING finger protein 11.
The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is a homologous to the E6-associated protein C terminus-type E3 ligase frequently overexpressed in human prostate and breast cancers due to gene amplification. Previous studies suggest that WWP1 promotes cell proliferation and survival; however, the mechanism of WWP1 action is still poorly understood. Here, we showed that WWP1 upregulates and maintains erythroblastic leukemia viral oncogene homolog 2 (ErbB2) and epithelial growth factor receptor (EGFR) in multiple cell lines. WWP1 depletion dramatically attenuates the EGF-induced ERK phosphorylation. WWP1 forms a protein complex with RING finger protein 11 (RNF11), a negative regulator of ErbB2 and EGFR. The protein-protein interaction is through the first and third WW domains of WWP1 and the PY motif of RNF11. Although WWP1 is able to ubiquitinate RNF11 in vitro and in vivo, WWP1 neither targets RNF11 for degradation nor changes RNF11's cellular localization. Importantly, inhibition of RNF11 can rescue WWP1 siRNA-induced ErbB2 and EGFR downregulation and growth arrest. Finally, we demonstrated that RNF11 is overexpressed in a panel of prostate and breast cancer cell lines with WWP1 expression. These findings suggest that WWP1 may promote cell proliferation and survival partially through suppressing RNF11-mediated ErbB2 and EGFR downregulation.


A rapid method for determining the relationship between cDNA clones.
We describe a technique for rapidly screening the inserts of plasmids for homology to each other by using DNA fragments isolated in agarose gels to probe Southern blots of DNA prepared by the "miniprep" alkaline lysis method. The procedure includes a technique for labeling DNA fragments in agarose gel slices without further purification. The protocol results in a significant savings in time and expense and a considerable increase in fragment yield over methods involving fragment purification from polyacrylamide or agarose gels.


Phase separation in a homogeneous shear flow: morphology, growth laws, and dynamic scaling.
We numerically investigate the influence of a homogeneous shear flow on the spinodal decomposition of a binary mixture by solving the Cahn-Hilliard equation in a two-dimensional geometry. Several aspects of this much studied problem are clarified. Our numerical data show unambiguously that, in the shear flow, the domains have on average an elliptic shape. The time evolution of the three parameters describing this ellipse is obtained for a wide range of shear rates. For the lowest shear rates investigated, we find the growth laws for the two principal axis R perpendicular (t) approximately const, R parallel (t) approximately t, while the mean orientation of the domains with respect to the flow is inversely proportional to the strain. This implies that when hydrodynamics is neglected, a shear flow does not stop the domain growth process. We also investigate the possibility of dynamic scaling, and show that only a nontrivial form of scaling holds, as predicted by a recent analytical approach to the case of a nonconserved order parameter. We show that a simple physical argument may account for these results.


Late mortality after partial gastrectomy.
A 10-year prospective study of Hawaii Japanese males with partial gastrectomy shows that the age-adjusted mortality rates in men with partial gastrectomy were slightly higher than in those with an intact stomach, but the difference failed to achieve statistical significance. This excess of mortality is due, in part, to excess smoking by men who had ulcers of the stomach. Although death due to stroke and lung cancer showed the most substantial deviations from the base population, this can be attributed only in part to the tendency of men with these diseases to be smokers. Other factors, possibly related to nutrition, also contribute to the increased risk of mortality from these diseases. Death from coronary heart disease, an illness with a substantial association with smoking in men with an intact stomach was less frequent in men with gastrectomy but the difference was not statistically significant. It would appear that men with partial gastrectomy had other characteristics that weakened the impact of smoking upon coronary disease risk--low blood pressure, low serum cholesterol, low body weight and increased alcohol consumption.


[Surgical outcome after severe craniocerebral trauma in childhood and adulthood. A comparative study].
During a period of 15 years 1123 patients were operated on for severe head injury in our Department of Neurosurgery. We evaluated 936 patients (83%) on the basis of the Glasgow coma scale and the Glasgow outcome scale and allocated them into four groups by diagnosis and also grouped them by age. The 170 patients in the groups of children and adolescents (15%) were compared with the adults, and the features characterizing the causes of the accidents and the prognosis were analysed. Young patients and adults with epidural haematomas or perforating head injuries had a better prognosis than patients with acute subdural haematomas or brain contusions. The postoperative results after severe head injuries in children and adults were the same as in the group with an initial rating of 3-5 points and 9-15 points on the Glasgow coma scale. Only the group of children with 6-8 points on the Glasgow coma scale on admission had better results than the adults. The reason for this might be the greater plasticity of the brain in childhood.


Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study.
Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P < .0001), body mass index (P < .0001), fasting plasma glucose (P < .0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication.


Serratia marcescens bacteremia: clinical features and antimicrobial susceptibilities of the isolates.
From July 1996 to June 1997, 22 adult patients with Serratia marcescens bacteremia were retrospectively studied at China Medical College Hospital. All patients had severe underlying disease, most commonly diabetes mellitus. Eighteen (82%) patients had nosocomial infection. Clinical syndromes included primary bacteremia (68%), pneumonia (14%), urinary tract infection (9%), suppurative thrombophlebitis (5%) and surgical wound infection (5%). Twelve patients had central venous catheters in place at the onset of bacteremia, but only one case met the definition of catheter-related infection. In 14 (64%) patients, portal of entry of S. marcescens infection was unknown. Five (23%) patients had concurrent polymicrobial bacteremia. The overall mortality rate was 50% (11/22). Seven (32%) of the 22 patients died of S. marcescens bacteremia. All isolates were resistant to ampicillin and cephalothin and susceptible to imipenem. Ninety-five percent of strains were susceptible to moxalactam, 68% to amikacin, 55% to ceftazidime, 45% to aztreonam, 32% to ceftriaxone, 27% to gentamicin, 18% to cefoperazone and cefotaxime, and 9% to piperacillin. MICs of various antibiotics demonstrated that ciprofloxacin and imipenem had good activities against S. marcescens, with MIC90 of 0.19 microg/mL and 1.0 microg/mL, respectively. Due to increasing multidrug resistance, choosing appropriate antimicrobial agents such as moxalactam, imipenem, and ciprofloxacin should be highly recommended for the treatment of S. marcescens infections.


Acidification of non-medicated and oxytetracycline-medicated cattle manures during anaerobic digestion.
Possible adverse effects of a commonly used veterinary antibiotic, oxytetracycline (OTC), on acidogenic phase of anaerobic digestion of cattle manure along with optimum operating conditions were investigated. A standard veterinary practice of 50 ml OTC solution (20 mg/kg cattle weight) was injected into the muscles of cattle and then manure samples were collected for 5 days following the injection. The 5-day samples were equally mixed and used throughout digestion experiments. Preliminary batch tests were conducted to obtain the optimum pH range and observe volatile fatty acids (VFAs) production. In this regard, different sets of batch digesters were operated at pH ranging from 5.2 +/- 0.1 to 5.8 +/- 0.1 at mesophilic conditions with total solids content of 6.0 +/- 0.2%. The pH of 5.5 +/- 0.1 was found to be the optimum value for acidification for both non-medicated and OTC-medicated conditions. Under predetermined conditions, maximum total VFA (VFAtot) of 830 +/- 3 mg (as acetic acid)/L was produced and maximum acidification rate was evaluated as 11% for OTC-medicated cattle manure, whereas they were 900 +/- 6 mg (as acetic acid)/L and 12% for non-medicated manure. Digestion studies were further continued in a semi-continuous mode at pH 5.5 +/- 0.1 and SRT/HRT of 5 days. VFAtot concentrations and maximum acidification rate increased up to 2181 +/- 19 mg (as acetic acid)/L and 29% for non-medicated cattle manure. For OTC-medicated cattle manure, lower acidification rate of 18% was observed.


Nanowire coupling to photonic crystal nanocavities for single photon sources.
We demonstrate highly efficient evanescent coupling via a silica loop-nanowire, to ultra-small (0.5 (lambda/n)(3) ), InAs/InP quantum dot photonic crystal cavities, specifically designed for single photon source applications. This coupling technique enables the tuning of both the Q-factor and the wavelength of the cavity mode independently, which is highly relevant for single photon source applications. First, this allows for the optimization of the extraction efficiency while maintaining a high Purcell factor. Second, the cavity mode can be matched with a spectrally misaligned quantum dot without changing the structure or degrading the Q-factor: a 3 nm resonance shift is reported.


Economic burden of irritable bowel syndrome. Proposed strategies to control expenditures.
It has been suggested that the annual direct costs for irritable bowel syndrome (IBS) are now around $US41 billion in the 8 most industrialised countries. This paper reviews the data on calculations of direct costs. The true economic burden is unclear, as there are insufficient data on indirect costs other than absenteeism from work and intangible costs cannot be estimated, particularly since presenters with IBS constitute only a subset of the patients with such symptoms in the community. Strategies to reduce direct costs must include physician and patient education, paramedical-based education and therapy, lay support groups, early consideration of psychosocial issues and psychological treatments, avoidance of unnecessary investigations and optimising the doctor-patient relationship. Indirect and intangible costs could be effectively reduced by novel, effective (not only efficacious) therapies.


Granulocyte macrophage colony-stimulating factor augments ICAM-1 and VCAM-1 activation of eosinophil function.
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily adhesion molecules on vascular endothelium and important in the development of eosinophil (EOS) accumulation in allergic inflammation. To define the role of these adhesion proteins in EOS inflammation, peripheral blood EOS from allergic donors were incubated in either buffer (control)-, recombinant human (rh)-VCAM-1-, or rh-ICAM-1-coated plates, and the effects of these adhesion proteins on EOS effector functions were determined. VCAM-1 induced spontaneous EOS adhesion whereas EOS adhesion to ICAM-1 required a second signal, such as granulocyte macrophage colony-stimulating factor (GM-CSF). Although only VCAM-1 stimulated EOS superoxide anion (O2-) generation, the addition of GM-CSF (100 pM) to the reactions resulted in a greater and equivalent production of O2- with VCAM-1 and ICAM-1. In the presence of GM-CSF, ICAM-1 and VCAM-1 caused significant release of EOS-derived neurotoxin (EDN). Moreover, only ICAM-1 (no GM-CSF) promoted calcium ionophore A23187 (0.2 microM)-induced EOS leukotriene C4 (LTC4). Enhanced O2- generation, EDN release, and LTC4 generation observed with ICAM-1 and VCAM-1 were significantly inhibited by anti-beta2-integrin antibody. These results suggest that ICAM-1 and VCAM-1 are important in determining the eventual function of airway EOS.


[Carbamazepine in paroxysmal choreoathetosis in Sydenham's chorea].
There are presented three different forms of chorea, in which we have observed an spectacular response to the administration of carbamazepine. The two first cases are paroxysmal choreoathetosis. Both are free of episodes of choreoathetosis under the administration or very low dosis of carbamazepine. However when a placebo is been used or in an accidental omit of the drug, the crisis reapears. The third case is a Sydenham chorea. It received three months of treatment on a 20 mg/kg dosis, the symptoms dimished on the first week. After a year he has not suffered any relapse.


Double-blind, parallel, comparative study on quality of life during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicentre study.
To compare tolerance, antihypertensive efficacy and impact on quality of life of amlodipine and enalapril in patients with mild or moderate hypertension. Multicentre, double-blind, double-dummy, comparative trial in general practice. Three phases were conducted: 4 weeks on placebo, 12 weeks of dose adjustment (amlodipine or enalapril) and a 38-week maintenance period. Four hundred and sixty-one patients of both sexes were enrolled; 451 were available for efficacy evaluation at the end of the trial. The patients were allocated to either amlodipine (231) or enalapril (230) treatment. If at the end of dose adjustment (amlodipine 5-10 mg/day, enalapril 10-40 mg/day) diastolic blood pressure was > or = 95 mmHg, hydrochlorothiazide (25-50 mg/day) was added (27 amlodipine patients and 45 enalapril patients). Blood pressure changes after 1 year of treatment; between- and within-group changes in quality of life as assessed by psychological general well-being, social and sexual functioning, health-risk perception, alertness, behaviour, and impact of symptom and side effects. Indices on quality of life were unchanged or increased (2-9%) in both groups. Blood pressure was normalized or reduced by > or = 10 mmHg in 204 (90%) and 190 (85%) patients on amlodipine and enalapril, respectively. Cough was the most frequently reported adverse event in the enalapril group (13%) and oedema in the amlodipine group (22%). Only eight (4%) patients on amlodipine and nine (4%) on enalapril were withdrawn because of drug-related adverse events. At similar blood pressure reduction in mild and moderate hypertension, quality of life is equally well maintained on amlodipine and enalapril therapy.


Polyorchidism: imaging may denote reproductive potential of accessory testicle.
MRI in a 9-year-old boy with left testicular polyorchidism and prior right orchiectomy showed single epididymis-ductus deferens complex. This anatomical arrangement suggests the possibility of reproductive potential and alters the patient's management.


Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney.
Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney. The permanent kidney, or metanephros, develops through a complex series of reciprocal inductive events and involves branching morphogenesis, tubulogenesis, angiogenesis, and tissue remodeling. Fibroblast growth factors (FGFs) are a family of growth and differentiation factors that have been implicated in metanephric development. FGFs exert their actions through tyrosine kinase receptors, FGFRs, which are encoded by four FGFR genes (FGFR1 through FGFR4). Reverse transcriptase-polymerase chain reaction was used to detect the expression of FGFs and FGFRs in rat metanephroi from embryonic day (E) 14 to E21. Nonradioactive in situ hybridization was used to localize FGF1 mRNA in E20 rat metanephroi, and immunohistochemistry was used to localize FGFRs in E15 and E20 rat metanephroi. We detected the expression of mRNAs for FGF1 through FGF5, FGF7 through FGF10, and FGFR1 through FGFR4 (IIIb and IIIc splice variants) in rat metanephroi from E14 to E21. By in situ hybridization, FGF1 mRNA was detected in the nephrogenic zone, ureteric epithelium, and developing nephron elements. FGFR proteins were localized in a distinct pattern that altered with maturation. FGFR1 was widely distributed in developing metanephric epithelia and mesenchyme, but not in developing interstitium. FGFR2 was also widely distributed in nephron epithelia, particularly in proximal convoluted tubules, but was not detected in metanephric mesenchyme, mesenchymal condensates, or developing interstitium. FGFR3 was localized to mesenchymal condensates, nephron elements, and medullary interstitium but not proximal convoluted tubules. FGFR4 was localized mostly to maturing nephron structures and was not detected in nephrogenic mesenchyme, mesenchymal condensates, or developing interstitium. These results indicate that FGFs and FGFRs are expressed in the developing rat metanephros from at least E14 and that they likely play important roles in metanephric development and maturation.


Differential regulation of SERK, LEC1-like and pathogenesis-related genes during indirect secondary somatic embryogenesis in grapevine.
A culture model was developed in Vitis vinifera L., cultivar 'Chardonnay' for studying SE (Somatic Embryogenesis). The auxin 2,4-D (2,4-Dichlorophenoxyacetic acid) was used to induce indirect secondary embryogenesis at a high rate, starting from embryos derived from embryogenic cultures previously obtained. Cotyledonary embryos were shown to be more responsive to SE induction than embryos at the torpedo-stage and were used for molecular analyses. The expression of SERK (Somatic Embryogenesis Receptor Kinase), L1L (Leafy Cotyledon1 Like) and a set of PR (Pathogenesis-Related) genes was monitored during the whole SE process. VvSERK1, VvSERK2 and VvL1L were down-regulated by the 2,4-D treatment but expressed in embryonic tissues. On the contrary, VvPR1, VvPR8, VvPR10.1 and VvPR10.3 were strongly up-regulated by the 2,4-D treatment, and their transcripts were not or only weakly detected in clusters of secondary embryos. VvSERK3, VvPR3 and VvPR10.2 were more stably expressed in all tissues examined. The discussion deals with the putative role of the different genes in grapevine SE.


Proteomics of Tribolium castaneum seminal fluid proteins: identification of an angiotensin-converting enzyme as a key player in regulation of reproduction.
Seminal fluid proteins (SFPs) play important roles in regulation of reproduction and behavior. Proteomics approaches were used to identify 13 SFPs, including 3 new proteins in the red flour beetle, Tribolium castaneum. The 13 SFP genes identified code for Serpin, cysteine-rich protein, odorant binding protein-like (OBPL, G10064 and G10065), Kunitz-like protease inhibitor precursor, and WD 40 family protein and are predominantly expressed in the male accessory glands. The genes coding for 13 putative SFPs were knocked down in males; the RNAi males were mated with virgin females, and the number of eggs produced by the mated females was quantified. Knockdown in the expression of the gene coding for a protein similar to angiotensin-converting enzyme 9 (G15465, TcACE) in the males caused a decrease in egg production by the females when compared to the eggs produced by the females mated with control males. In addition, knockdown in the expression of the gene coding for heat shock cognate 70 led to a reduction in the amount of proteins produced by the male accessory glands by 55%. These data suggest that angiotensin-converting enzyme produced in the male seminal vesicles plays important roles in sperm protection during and after transfer to females.


Competition between weak OH⋯π and CH⋯O hydrogen bonds: THz spectroscopy of the C2H2-H2O and C2H4-H2O complexes.
THz absorption spectra have been recorded for the weakly bound molecular complexes of H2O with C2H4 and C2H2 embedded in cryogenic neon matrices at 2.8 K. The observation and assignment of a large-amplitude acceptor OH librational mode of the C2H2-H2O complex at 145.5 cm-1 confirms an intermolecular CH⋯O hydrogen-bonded configuration of C2v symmetry with the H2O subunit acting as the hydrogen bond acceptor. The observation and assignment of two large-amplitude donor OH librational modes of the C2H4-H2O complex at 255.0 and 187.5 cm-1, respectively, confirms an intermolecular OH⋯π hydrogen-bonded configuration with the H2O subunit acting as the hydrogen bond donor to the π-cloud of C2H4. A (semi)-empirical value for the change of vibrational zero-point energy of 4.0-4.1 kJ mol-1 is proposed and the combination with quantum chemical calculations at the CCSD(T)-F12b/aug-cc-pVQZ level provides a reliable estimate of 7.1 ± 0.3 kJ mol-1 for the dissociation energy D0 of the C2H4-H2O complex. In addition, tentative assignments for the two strongly infrared active OH librational modes of the ternary C2H4-HOH-C2H4 complex having H2O as a doubly OH⋯π hydrogen bond donor are proposed at 213.6 and 222.3 cm-1. The present findings demonstrate that the relative stability of the weak hydrogen bond motifs is not entirely rooted in differences of electronic energy but also to a large extent by differences in the vibrational zero-point energy contributions arising from the class of large-amplitude intermolecular modes.


Mussel (Mytilus coruscus) Water Extract Containing Taurine Prevents LPS-Induced Inflammatory Responses in Zebrafish Model.
Mussel (Mytilus coruscus) water extract had strong anti-inflammatory activities, but the effects and its mechanisms of mussel on anti-inflammatory properties in vivo remain to be determined. This study, therefore, was designed to investigate anti-inflammatory activities of mussel water extract containing a large amounts of taurine (151.96 nmol/mg) using the lipopolysaccharide (LPS)-induced inflammatory zebrafish model. In this study, mussel water extract containing taurine shows potent protective effects against the cell death stimulated by LPS exposure in zebrafish embryos. In addition, zebrafish subjected to LPS treatment exhibited significantly increased reactive oxygen species (ROS) and nitric oxide (NO) levels. However, mussel water extract markedly suppressed LPS-induced ROS and NO production. Our results indicate that mussel water extract attenuated inflammation by inhibiting the LPS-induced intracellular ROS and NO production in zebrafish embryos. These findings could demonstrate the anti-inflammatory activity of mussel water extract containing taurine, which might have a protective effects on inflammatory diseases.


Microfilariae of Wuchereria bancrofti in cytologic smears.
Microfilariae of Wuchereria bancrofti were observed in cytologic material in 35 cases. The material included cervicovaginal smears (17 cases), effusions (14), urine (2), bronchial washings (1) and ovarian cyst fluid (1). The initial diagnosis was made from the cytologic smear in all cases; none had clinical filariasis. Symptomatic vaginal bleeding in 9 of the 17 cases with microfilaria-positive cervicovaginal smears was reflected in the large numbers of red blood cells found in the smear. Blood eosinophilia was present in 11 of 19 cases investigated. Eosinophils were seen in the smears in 20 cases. In the majority of the cases of effusions with microfilariae the effusions were malignant. Significant adherence of inflammatory cells and macrophages to microfilariae was present in 7 of the 35 cases. The significance of these findings is discussed.


Analysis of CDK Inhibitor Action on Mitochondria-Mediated Apoptosis.
The role of cyclin-dependent kinase inhibitors (CDKIs) is to negatively regulate cyclin-dependent kinases as a mechanism of control of cell proliferation. As such, CDKIs are being used to induce apoptosis in cancer cells to prevent their excessive reproduction. This chapter describes procedures to study apoptosis induction upon treatment with any CDKI through the evaluation of morphological and functional mitochondrial alterations, in particular, how to measure the mitochondrial membrane potential (ΔΨm) using TMRE dye, determine the content of intracellular ATP, observe mitochondrial network morphology using HeLa cells stably expressing fluorescent reporter DsRed targeting mitochondrial matrix, observe ultrastructure of the organelle using transmission electron microscopy, and, finally, assure that mitochondrial outer membrane permeabilization takes place by assessing the subcellular localization of cyt C in HeLa cells stably expressing fluorescent cyt C-GFP.


Ischemic preconditioning by selective occlusion of the pulmonary artery in rats.
To evaluate the effect of lung ischemic preconditioning (IPC) on normothermic ischemia/reperfusion (I/R) injury in a rat model, quantifying the production of reactive oxygen species. Forty-seven male Wistar rats were randomized into four groups: control, sham, I/R and IPC. Control group animals were anesthetized and killed by decapitation, after which pneumonectomy was performed and the left lungs were stored in liquid nitrogen. Sham, IPC and I/R group rats were anesthetized, tracheostomized, ventilated, anticoagulated and submitted to left thoracotomy with dissection of the left pulmonary artery for clamping. Sham group rats underwent dissection of the left pulmonary artery, I/R group rats underwent 30 min of total hilar clamping, and IPC group rats underwent 5-min clamping of the left pulmonary artery followed by 30 min of total hilar clamping. Lungs were reperfused for 90 min and ventilated with the same parameters, with additional positive end-expiratory pressure of 1 cmH2O. Hemodynamic and blood gas values were obtained prior to thoracotomy, prior to total hilar clamping, after 30 min of reperfusion and after 90 min of reperfusion. Lipid peroxidation was determined by measuring levels of thiobarbituric acid reactive substances. There were no significant differences among the groups in terms of the levels of thiobarbituric acid reactive substances. Nor were there any significant differences among the sham, I/R and IPC groups in terms of arterial oxygen tension, arterial carbon dioxide tension or hemodynamic values. In an in situ I/R rat model, 5-min IPC of the left pulmonary artery does not attenuate I/R injury.


Effects of weight and energy content of preloads on subsequent appetite and food intake.
This study was done to determine the relative effects of energy content and weight of ingested food on subsequent satiety and food intake. The weight/volume and the energy content of nine preloads were manipulated, in a 3 x 3 factorial design, to give three weight levels, 250, 500 and 750 g, and three energy levels 0, 1.26 and 2.51 MJ (0, 300 and 600 kcal). The weights were varied by the addition of water, while the energy levels were varied by using yogurt and cream. Each of the 1.26 and 2.51 MJ preloads contained 27 g of protein and 31 g of carbohydrates. The 1.26 MJ preloads contained 8 g of fat and the 2.51 MJ preloads had 41 g of fat. Each of the nine preloads was presented as a lunch to 21 female and 16 male subjects. Two hours after the preloads, subjects consumed sweet and savory snacks and various drinks ad libitum from a buffet. The weight of the preload had a small but statistically significant effect on feelings of hunger and satiety between preload and buffet, and on energy intake during the buffet (5.34, 5.05 and 5.04 MJ after 250, 500 and 750 g preloads). There was a large difference between 0 and 1.26 MJ, but little difference in effect between 1.26 and 2.51 MJ preloads. Mean energy intakes in the buffet after the 0, 1.26 and 2.51 MJ preloads were 6.17, 4.83 and 4.42 MJ. These results suggest that the weight or amount of food affects subsequent appetite and food intake, but the effect of energy is stronger.


Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer's disease?
Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.


Clinical evaluation of plasma des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes.
We measured des-gamma-carboxyprothrombin (DCP) (prothrombin induced by vitamin K absence or antagonist-II, abbreviated as PIVKA-II) by a newly developed enzyme immunoassay using an anti-DCP monoclonal antibody in 665 human subjects, of which 112 were patients with hepatocellular carcinoma (HCC). PIVKA-II was elevated to more than 0.1 AU/ml in 54 of the 112 patients (48.2%) with HCC, while it was positive only in 7.1% of those with liver cirrhosis and 3.1% of those with chronic hepatitis. Three patients with elevated PIVKA-II greater than 0.1 AU/ml who had been diagnosed as having liver cirrhosis by ultrasonography and computed tomography at the start of this study developed a diffuse type of HCC three or six months later, which was detected by angiography. No obvious correlation was observed between plasma PIVKA-II concentration and serum alpha-fetoprotein (AFP) level in HCC patients. Of the 112 HCC patients, 40.2% showed an increase in AFP to above 200 ng/ml. In the remaining patients, 32.8% had a PIVKA-II concentration greater than 0.1 AU/ml. In these patients with a negative or low serum AFP concentration, PIVKA-II proved to be a valuable tumor marker for laboratory diagnosis of HCC. Among them, 59.8% tested positive for PIVKA-II and/or AFP. Thus, combination assay with PIVKA-II and AFP seems useful for increasing the accuracy of laboratory diagnosis of HCC. None of patients with a solitary tumor smaller than 2 cm had elevated PIVKA-II. In patients with larger-sized and multiple HCC, positive results of elevated PIVKA-II were more frequent than those of increased AFP.(ABSTRACT TRUNCATED AT 250 WORDS)


[Mechanisms of resistance in Enterobacteriaceae towards beta-lactamase antibiotics].
Except for Salmonella spp., all Enterobacteriaceae produce intrinsic chromosomal encoded beta-lactamases which, beside their physiologic role in cell-wall synthesis and natural beta-lactam protection, are responsible for intrinsic resistance of individual species among Enterobacteriaceae. E. coli and Shigella spp. produce a small amount of AmpC beta-lactamases and are susceptible to ampicillin and other beta-lactam antibiotic agents. Enterobacter spp, C. freundii, Serratia spp., M. morganii, P. stuarti and P. rettgeri produce small amounts of inducible AmpC beta-lactamases which are not inhibited by beta-lactamases inhibitor, causing intrinsic resistance to ampicillin, co-amoxiclav and first-generation cephalosporins. K. pneumoniae produces small amounts of SHV-1 beta-lactamases, and K. oxytoca chromosomal K1 beta-lactamase, causing resistance to ampicillin, carbencillin, ticarcillin and attenuated zone of inhibition to piperacillin, compared to piperacillin with tazobactam. They are susceptible to beta-lactamase inhibitors. Whereas P. mirabilis shows a minor chromosomal expression of beta-lactamases, P. vulgaris produces chromosomal beta-lactamases of class A (cefuroximases), causing resistance to ampicillin, ticarcillin, and first- and second-generation cephalosporins. Antibiotics have caused the appearance of acquired or secondary beta-lactamases, with the sole function of protecting bacteria from antibiotics. The production of broad-spectrum beta-lactamases (TEM-1, TEM-2, SHV-1, OXA-1) results in resistance to ampicillin, ticarcillin, first-generation cephalosporins and piperacillin. A high level of beta-lactamases leads to resistance to their inhibitors. The plasmid-mediated extended-spectrum beta-lactamases (ESBLs) are of increasing concern. Most are mutants of classic TEM- and SHV-beta-lactamases types. Unlike these parent enzymes, ESBLs hydrolyze oxymino-cephalosporins such as cefuroxime, cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefpirome and cefepime, aztreonam, as well as penicillins and other cephalosporins, except for cephamycin (cefoxitin and cefotetan). They are inhibited by beta-lactamase inhibitors. AmpC beta-lactamases are chromosomal and inducible in most Enterobacter spp., C. freundii, Serratia spp., M. morganii and Providentia spp. They are resistant to almost all penicillins and cephalosporins, to beta-lactamase inhibitors and aztreonam, and are susceptible to cefepime and carbapenems as well. Plasmid-mediated AmpC beta-lactamases have arisen through the transfer of chromosomal genes for the inducible AmpC beta-lactamase onto plasmids. All plasmid-mediated AmpC beta-lactamases have similar substrate profiles to the parental enzymes from which they appear to be derived. With one exception, plasmid-mediated AmpCs differ from chromosomal AmpCs in being uninducible. The National Committee for Clinical Laboratory Standards (NCCLS) has issued recommendations for ESBL screening and confirmation for isolates of E. coli, K. pneumoniae and K. oxytoca. No NCCLS recommendations exist for ESBLs detection and reporting for other organisms or for detecting plasmid-mediated AmpC beta-lactamases. High-level expression of AmpC may prevent recognition of an ESBL in species that produce a chromosomally encoded inducible AmpC beta-lactamase. AmpC-inducible species (e. g. Enterobacter spp. and C. freundii) can be recognized by cefoxitin/cefotaxime disk antagonism tests. Since clinical laboratories are first to encounter bacteria with new forms of antibiotic resistance, they need appropriate tools to recognize these bacteria, including trained staff with sufficient time and equipment to follow up important observations. Because bacterial pathogenes are constantly changing, training must be an ongoing process.


Cerebral malaria in non-paediatric subjects resident in southwestern Nigeria.
Seven previously healthy, non-immuno compromised adolescents and adults with cerebral malaria were seen over a nine-month period in an endemic area where the disease was previously thought to be rare in persons above the age of 11 years. Six of these, treated with quinine responded promptly to therapy with mean parasite and fever clearance times of 58.0 +/- 4.9 hrs and 30.0 +/- 16.5. hrs respectively and regained consciousness in 20.0 +/- 14.5 hrs. One patient treated with chloroquine regained consciousness in 28 hrs, with parasite and fever clearance times of 120 hrs and 48 hrs respectively. No neurological deficit was observed on discharge in any of the subjects.


Coenzyme A, more than 'just' a metabolic cofactor.
In all organisms biomolecules play a vital role to enable proper cellular metabolism. Alteration of metabolite homoeostasis disrupts the physiology of cells, leading to various diseases [DeBerardinis and Thompson (2012) Cell, 148, 1132-1144]. Recent studies advances our understanding that some metabolites are not only involved in cellular metabolism, but also have other molecular functions. It has become evident that similar to multifunctional 'moonlighting proteins', 'moonlighting metabolites' also exists. One clear example is nicotinamide adenine dinucleotide (NAD). NAD is a ubiquitous molecule with a well-known function in many metabolic reactions, but it also has become clear that NAD is involved in the regulation of sirtuins. Sirtuins play a role in cancer, diabetes, and cardiovascular, neurodegenerative and other diseases [Donmez and Outeiro (2013) EMBO Mol. Med. 5, 344-352] and the deacetylation capacity of sirtuin proteins is NAD-dependent. This direct role of NAD in age-related diseases could not be anticipated when NAD was initially discovered as a metabolic cofactor [Donmez and Outeiro (2013) EMBO Mol. Med. 5, 344-352; Mouchiroud et al. (2013) Crit. Rev. Biochem. Mol. Biol. 48, 397-408]. Recent findings now also indicate that CoA (coenzyme A), another metabolic cofactor, can be considered as being more than 'just' a metabolic cofactor, and altered CoA levels lead to severe and complex effects.


Genetic variability of begomoviruses associated with cotton leaf curl disease originating from India.
Cotton leaf curl disease (CLCuD) causing viruses belong to the Begomovirus genus of the family Geminiviridae. Most begomoviruses are bipartite with two molecules of circular single stranded DNA (A and B) encapsidated in icosahedral geminate particles. However, the begomoviruses associated with CLCuD have DNA-beta instead of DNA-B. In this communication we report the complete genomic sequence of DNA-A component of two CLCuD-causing begomoviruses, cotton leaf curl Kokhran virus-Dabawali (CLCuKV-Dab), tomato leaf curl Bangalore virus-Cotton [Fatehabad] (ToLCBV-Cotton [Fat]) and partial sequences of two other isolates cotton leaf curl Rajasthan virus-Bangalore (CLCuRV-Ban) and cotton leaf curl Kokhran virus-Ganganagar (CLCuKV-Gang). A phylogenetic analysis of these isolates along with other related begomoviruses showed that ToLCBV-Cotton [Fat] isolate was closest to the tomato leaf curl Bangalore virus-5 (ToLCBV-Ban5) where as CLCuKV-Dab isolate was close to the cotton leaf curl Kokhran virus-Faisalabad1 (CLCuKV-Fai1), cotton leaf curl Kokhran virus-72b (CLCuKV-72b) and cotton leaf curl Kokhran virus-806b (CLCuKV-806b) isolates from Pakistan. The phylogenetic analysis further showed that the ToLCBV-Cotton [Fat] and CLCuKV-Dab isolates along with CLCuKV-Fai1, CLCuKV-72b and CLCuKV-806b are closer to the ToLCBV, tomato leaf curl Gujarat virus (ToLCGV), tomato leaf curl Gujarat virus-Varanasi (ToLCGV-Var) and tomato leaf curl Sri Lanka virus (ToLCSLV) isolates, where as cotton leaf curl Alabad virus-804a (CLCuAV-804a), cotton leaf curl Multhan virus (CLCuMV) cluster with the isolates from cotton leaf curl Rajasthan virus (CLCuRV) and okra yellow vein mosaic virus (OYVMV). These results demonstrate the extensive variability observed in this group of viruses. The AC4 ORF is the least conserved among these viruses. In order to further asses the variability in the CLCuD-causing begomoviruses, the region showing minimum similarity in the DNA-A sequence was first determined by a comparison of segments of different lengths of the aligned sequences. The results indicated that region 2411-424 (771 nt) was the least conserved. A phylogenetic tree constructed using the sequences of all the CLCuD causing begomoviruses, corresponding to the least conserved region showed that they form two distinct clusters.


[Functional childhood gastrointestinal disorders. I. Chronic abdominal pain].
Chronic abdominal pain occurs in 17% of children aged 0-14 years with a peak of 33% at the age of 7 years. According to the Rome II criteria abdominal pain disorders can be classified as functional dyspepsia, irritable bowel syndrome, functional abdominal pain, abdominal migraine, and aerophagia. This new classification will hopefully lead to a more careful diagnosis of functional abdominal pain syndromes and to better treatment strategies. A thorough history taking and physical examination are the cornerstone of diagnostic workup in children with chronic abdominal pain. An extensive explanation and reassurance are the basis of an adequate treatment and in the majority of cases this is successful.


Optical clearing of small intestine for three-dimensional visualization of cellular proliferation within crypts.
New methods on optical clearing provide a valuable alternative to traditional physical section histology. Optical clearing allows investigation of relatively large tissue samples at histological resolution while maintaining the three-dimensional architecture of the intact system. There is significant potential for applying optical clearing to gastrointestinal tissues. In particular, intestinal crypts contain high concentrations of stem cells, making these structures especially important for research on cellular proliferation in the intestinal epithelium. The objective of our study is to demonstrate an optical clearing method that is easy to implement and is compatible with mitotic fluorescent labeling. The optical clearing method we present utilizes a Triton/DMSO delipidization step followed by refractive index matching, rendering the tissue nearly transparent. We use EdU click chemistry to fluorescently label mitotic cell nuclei. Our results demonstrate successful clearing of jejunal samples with readily visible EdU staining by means of confocal microscopy. Three-dimensional reconstruction of labeled samples reveals preservation of intestinal cytoarchitecture including muscular, submucosal, and mucosal layers. Additionally, the morphology of intestinal crypts and individual EdU-positive mitotic nuclei are visible in sharp detail within their intact three-dimensional organization. In summary, we present an optical clearing method that is easy to implement and has the potential to provide more accurate assessment of cellular proliferation within the gastrointestinal tract in both healthy and disease states.


[Group housing for two to eight week old fattening calves].
The effect of three different feeding techniques (electronic automated feeder, teat bucket and bucket with floating teat) on oral activities, skin condition, health and performance of 144 German Holstein group housed veal calves was investigated. About 21% of the observed time over 24 hours was spent on oral activities and only about 1% with the particularly health-relevant activities at prepuce, navel or scrotum. As a consequence of sucking activities at pen mates in most cases reddening of the skin and, with low incidence (about 7%), additional loss of hair could be found. Altogether about 74% of the calves were affected with the highest incidence in the electronic automated feeder groups. Calves of these groups had, moreover, higher disease incidences and a lower weight gain and feed conversion rate than those fed by teat bucket or by bucket with floating teat. Altogether results show that in terms of behaviour and health it is possible to keep calves at the age of two weeks in groups, even in conventional veal calf production, when satisfactory management is applied. The electronic automated feeder still needs further technical development for use with veal calves.


Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.
Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.


Enhancing the Effect of Lorentz Invariance and Einstein's Equivalence Principle Violation in Nuclei and Atoms.
Local Lorentz invariance violating (LLIV) and Einstein equivalence principle violating (EEPV) effects in atomic experiments are discussed. The EEPV effects are strongly enhanced in the narrow 7.8 eV transition in the _{90}^{229}Th nucleus. The nuclear LLIV tensors describing the anisotropy in the maximal attainable speed for massive particles (analog of the Michelson-Morley experiment for light) are expressed in terms of the experimental values of the nuclear quadrupole moments. Calculations for nuclei of experimental interest _{55}^{133}Cs, _{37}^{85}Rb, _{37}^{87}Rb, _{80}^{201}Hg, _{54}^{131}Xe, and _{10}^{21}Ne are performed. The results for _{10}^{21}Ne are used to improve the limits on the proton LLIV interaction constants by 4 orders of magnitude.


Training volunteer caregivers of persons with AIDS.
Volunteers have played an important role in the care and support of PWAs. This paper discusses the issues that will face professionals who are involved in recruitment, training and support of volunteer caregivers in the coming years, utilizing a review of the literature and case examples. The hospice volunteer model is discussed and serves as the basis for a proposed model of training and support specifically designed for volunteer caregivers of PWAs.


Cognitive egocentrism in institutionalized adult males.
Spatial egocentrism and its relationships to discrimination ability and communicative egocentrism were investigated in a sample of 80 adult males from a single institutional setting. The participants ranged in age from 33 to 83 years. As predicted, no significant age differences were obtained on any of the three dependent measures. However, significant effects of order of task presentation indicated that the experimental procedure influenced performance on the spatial and communicative egocentrism and discrimination tasks. The findings, which provide support for the Piagetian position of maintenance of operational level through the life-span, were discussed in terms of social and affective factors which may influence adult performance on cognitive tasks.