Whiplash injury and oculomotor dysfunctions: clinical-posturographic correlations.
Oculomotor dysfunctions are hidden causes of invalidity following whiplash injury. Many patients with whiplash injury grade II present oculomotor dysfunctions related to input disturbances of cervical or vestibular afferents. We used static posturography to investigate 40 consecutive patients with whiplash injury grade II and oculomotor dysfunctions. We demonstrated a relation between length and surface of body sway: the surface value (A) was higher than the length value (L) and this led to an open graph of body sway in the statokinesigram. Oculomotor rehabilitation can resolve the impairment of vestibular function but if therapy is delayed or the patient has been wearing an orthopaedic neck collar, more therapeutic sessions are required. In conclusion, without rehabilitation of the oculomotor muscles other therapies are not sufficient to recover the impairment caused by whiplash injury.


Length of stay and impact on readmission rates after laparoscopic gastric bypass.
A decreased length of stay (LOS) is one of the many advantages of laparoscopic over open Roux-en-Y gastric bypass for the treatment of morbid obesity. However, the mean LOS after laparoscopic gastric bypass (LGB) ranges from 1.8 to 4.5 days. In addition, the LOS has tended to improve as bariatric programs have matured. With the use of a standardized perioperative care plan, we studied the effects of LOS on readmission rates in patients undergoing LGB in a new minimally invasive bariatric surgery program. All patients undergoing LGB between September 20, 2001 and April 5, 2004 were entered into a standardized perioperative care plan. All patient outcomes were entered into a prospective database. The discharge criteria included adequate oral intake and adequate pain control on oral medication. The reasons for patients staying >2 days were analyzed and documented. A total 250 patients underwent LGB. Of these, 212 patients (84.8%) were discharged on postoperative day 2. The most common reason for a LOS >2 days was bleeding (42.1%), followed by nausea (26.3%), inadequate pain control on oral medication (15.8%), and various other reasons (15.8%). The mean LOS did not change with time (P = .19). Readmission within 30 days was significantly less in patients discharged by day 2 (1.9% versus 13.1%, P = .005). The LOS remained constant as our program matured. The vast majority of patients undergoing LGB who have an uncomplicated postoperative course were safely discharged home on postoperative day 2. Patients staying >2 days were more likely to be readmitted within 30 days of discharge.


Intrathecal baclofen for multiple sclerosis related spasticity: A twenty year experience.
Evaluate long-term efficacy and safety of ITB in treating MS-related spasticity over ∼ 20 years of service provision in a single centre. A single centre prospective observational cohort study was performed. Eligible subjects underwent ITB trial by bolus dose via lumbar puncture and responders proceeded to pump implantation. Demographics, spasticity scores (Ashworth), spasm score (Penn), stiffness, pain and discomfort (Visual Analogue Scale), mobility (10 M walk), spasticity treatment, and ITB doses were analysed longitudinally. 106 people were included with 568 patient years of data. Ashworth, Penn and VAS/NRS mean scores improved post-trial compared with baseline (p < 0.001). Sustained efficacy was reported on Ashworth, Penn and VAS scores over time. After 1 year, 73 (69%) discontinued all oral antispasticity medications. Complication rates were low at 0.05 complications per pump year and mostly mechanical (usually catheter) related. In 8 ambulatory subjects, 7 (87%) continued to walk one year after pump insertion, 5 (62%) were still walking at time of analysis (mean follow up 3.4 years). ITB is an effective and safe long term treatment for refractory MS related spasticity. Efficacy was sustained over time and the majority of subjects subsequently discontinued systemic medications. In a small cohort, ability to walk was preserved, indicating ITB should be considered earlier in this cohort.


[Association psychology versus learning psychology theory of schizophrenia (author's transl)].
This study has been stimulated by the parallel process of knowledge gained by association psychology and learning psychology approaches to the theory of schizophrenia. It is based on the hypothesis that this parallel must entail structural agreement for the symptomatologies influenced in each case. In order to examine whether this hypothesis is correct, the basic disturbance concept by G. Huber and L. Súllwold, which has been developed on the lines of learning psychology, is compared and contrasted with the theory of symptoms according to E. Bleuler, which has been developed by association psychology. This comparison shows an indeed far-reaching agreement in all structure-determining categories, besides differences in specificity problems and in the psychoreactive derivation model. The original concept of schizophrenia, therefore, emerges after half a century of phenomenological and holistic-psychological schizophrenia research, as a highly topical precursor of the modern concept of this disease.


Expression of NADPH oxidase is induced by all-trans retinoic acid but not by phorbol myristate acetate and 1,25 dihydroxyvitamin D3 in the human promyelocytic cell line NB4.
Human promyelocytic cells, NB4, differentiate into neutrophils in response to all-trans retinoic acid (ATRA). It has recently been proposed that NB4 cells have bilineage potential because these cells are also able to differentiate into monocyte/macrophages when exposed to a combination of 1,25-dihydroxyvitamin D3 (VD3) and phorbol myristate acetate (PMA). Differentiation of myeloid cells into neutrophils or monocytes is associated with the acquisition of the O2- producing enzyme, NADPH oxidase, which plays a critical role in microbial killing. In this study, the expression of the components of the NADPH oxidase complex during the differentiation of NB4 cells into neutrophils or macrophages has been investigated. Whereas cells exposed to ATRA were able to produce O2- after 2 days of differentiation, they remain unable to generate O2- when exposed to PMA or PMA + VD3. With the exception of p21rac, none of the other oxidase components was expressed in non-differentiated cells. Addition of ATRA induced the progressive expression and accumulation of p22phox, p91phox, p47phox and p67phox. Compared to the other components, p67phox was expressed late and its expression appeared to correlate most closely with the generation of O2- in the differentiation process. In PMA or PMA + VD3-differentiated NB4 cells, expression of the NADPH oxidase components was incomplete. Therefore, ATRA induced the expression of a functional NADPH oxidase complex in neutrophil-like NB4 cells. In contrast, when NB4 cells are exposed to monocytic differentiating agents, they acquire only part of the phenotypic characteristics of monocytes and lack one of the major phagocytic functionalities, the respiratory burst oxidase.


Synaptosomal protein kinase C subspecies: B. Down-regulation promoted by phorbol ester and its effect on evoked norepinephrine release.
The effect of phorbol esters was investigated on the down-regulation of protein kinase C (PKC) and on the release of [3H]norepinephrine (NE) in synaptosomes from the rat cerebrum. Treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) promoted the translocation of PKC activity in a P2 fraction from the cytosol to the membrane fraction and then its down-regulation, in a dose-dependent manner. TPA induced a rapid down-regulation of the type II(beta) and type III(alpha) subspecies, but did not change the activity of the type I(gamma) subspecies in the cytosolic fraction for at least 15 min. The gamma-subspecies was subsequently decreased at a slower rate. In the synaptosomes thus having only the gamma-subspecies, a subsequent dose of TPA could not enhance K(+)-evoked NE release, although, in the original synaptosomes, TPA was able to enhance K(+)-evoked NE release. Pretreatment with TPA did not alter the K(+)-evoked NE release itself. TPA was also found to enhance the K(+)-evoked NE release from synaptosomes prepared from both hippocampus, which express the gamma-subspecies of PKC at a negligible level, and cerebral cortex, which have a significant level of the gamma-subspecies, to the same degree. These results suggest that the gamma-subspecies of PKC does not participate in the TPA-enhanced K(+)-evoked NE release from synaptosomes.


Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary.
Increases in plasma FFA levels inhibit GH responses to a variety of pharmacological and physiological stimuli. To gain further insight into the mechanism by which FFA exert their effect, we studied the plasma GH responses to GHRH-(1-44) (1 microgram/kg, iv) in normal subjects in whom plasma FFA levels were raised by a lipid-heparin infusion (250 mL 10% Intralipid plus 2500 U heparin). Paired tests were performed in 10 normal subjects, with and without lipid-heparin pretreatment. Lipid-heparin infusion from -30 to 120 min increased mean FFA levels from 0.41 +/- 0.03 (+/- SEM) to 3.12 +/- 0.40 mmol/L at 120 min. The mean plasma GH levels after GHRH administration were lower at all times; however, the values were significantly different (P less than 0.05) only at the later times (45, 60, and 90 min). When considered individually, an all or none pattern was observed; 5 subjects had no plasma GH response to GHRH, and 5 had no reduction. To investigate the time relationships between the FFA peak and subsequent GH blockade, a different protocol of paired tests was performed with GHRH with or without a different lipid-heparin infusion protocol. Lipid-heparin was infused from -90 to 0 min, with an additional heparin pulse at -15 min, to obtain a higher and earlier (0 min) FFA increase. FFA increased from 1.06 +/- 0.19 to 11.61 +/- 0.83 mmol/L at zero time. The GHRH-induced GH secretory peak (15.8 +/- 3.5 ng/ml) at 15 min was completely blocked (0.9 +/- 0.2 ng/ml), and the mean plasma GH levels were also lower at 30, 45, and 60 min. To determine whether the FFA-induced blockade of GH secretion was exerted in the pituitary, a series of in vitro studies was conducted using monolayer cultures of rat anterior pituitary glands, with GHRH concentrations of both 10(-10) and 10(-8) M and 10(-5) M forskolin to stimulate GH release. Both caprylic and oleic acid inhibited basal GH release and GHRH- or forskolin-induced GH release. PRL release was not altered, nor were toxic actions noted on the cells. In conclusion, FFA are able to block GH secretion directly at the pituitary level.


Phenotypes and genotypes in epilepsy with febrile seizures plus.
In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes.


Yeast and lactic acid flora of tej, an indigenous Ethiopian honey wine: variations within and between production units.
A total of 200 samples of tej, an indigenous Ethiopian honey wine, were collected from ten production units at different production times. The samples were analysed for their microbial flora. Mean counts of aerobic mesophilic bacteria and aerobic spores for the different production units were <3 log cfu/ml. Coliforms and other members of Enterobacteriaceae were below detectable levels basically due to the low pH of the samples (<4.0). Yeasts were among the dominant micro-organisms in all samples with mean counts of 6 log cfu/ml for all production units. Over 25% of the yeast isolates belonged to Saccharomyces cerevisiae followed by Kluyvermyces bulgaricus (16%), Debaromyces phaffi (14%) and K. veronae (10%). Yeast counts showed significant variation within samples of a production unit (CV>10%) and difference in counts among all samples was also significant (P<0.01). The lactic acid bacteria had counts of 6 log cfu/ml with a significant variation within samples of a production unit (CV>10%) or among all samples (P<0.01). In most production units, the heterolactics had higher counts than the homolactics. The lactic flora consisted of Lactobacillus, Streptococcus, Leuconostoc and Pediococcus species. The lactobacilli were, however, the most frequently encountered groups. In most of the samples, the lactic flora was dominated by two (49.5%) or three (46%) groups of lactic acid bacteria.


[Quantitative stereologic analysis of metabolize dynamic of protein and DNA during somatic embryogensis in Lycium barbarum L].
The protein and DNA content in somatic embryos of Lycium barbarum L were analysed using quantitative stereologicai procedure formed from Cell Morphometry. The photos were transformed into digital images by the Sharp JX-610 scanner. Then the quantity of protein and DNA was count applying digital images processing software. By the result we discuss the relationship between changes in protein and DNA metabolize dynamic and somatic embryogensis.


Are children's early emotions antecedents to risk taking?
To explore the processes by which early emotional experiences affect behavior and to investigate the use of basic development characteristics to guide primary care. A randomized cohort of 74 children from a wide range of socio-economic classes were followed from infancy until 54 months of age. Children were assessed at 2 days, 12, 18 and 54 months by laboratory tests and maternal report. The personality characteristic of inhibition/shyness appeared to be an enduring trait from infancy through the preschool years. However, findings did not support the view that early personality variables (e.g., avidity, shyness, security) alone predict risk taking during later years. Nurses offering safety counseling about risk taking in order to minimize injuries during early childhood should consider personality concepts to be multi-dimensional. Infant and toddler profiles should not be considered solely predictive of later behavior.


Hearing aids. I. Conventional hearing devices.
State-of-the-art hearing aids incorporate advances in signal processing, miniaturization, and programmability. This technological progress has been accompanied by parallel enhancements in evaluating and fitting strategies. In addition, in the past several years, knowledge has increased about the influences of amplification on hearing ability and about the influences of hearing ability on benefit from amplification.


Chylous reflux pathologies: diagnosis and microsurgical treatment.
This article aims to make a contribution to the present knowledge of the diagnosis and therapy of chylous reflux pathologies, based largely on the authors' clinical experience in the microsurgical treatment of these disorders. In 47 patients affected by chylostatic disorders the diagnosis was based on the clinical history, physical examination, lymphoscintigraphy, lymphography, ultrasound, CT scanning and lymphangio-MR. In cases of chylous reflux towards the external genitalia or the lower limbs, the puncture of one of the lymphostatic verrucae which may be part of the symptomatology, can be sufficient for the clinical diagnosis. If patients suffer from hypoproteinaemia and/or an intestinal malabsorption syndrome, this should be dealt with to ensure them at least temporary metabolic compensation before surgical treatment, if any. In patients affected by chylous ascites, antigravitational ligatures of incompetent collectors, sometimes associated with lymphovenous shunts, can be a therapeutic solution. We have found that CO2 laser irradiation at very low power achieved full section closure of lymphatic and chylous vessels as complete as if they had been tied. In the case of chyloedema of the external genitalia and of/or the lower limbs, reductive plastic treatment completes the result after antigravitational ligatures and derivative microsurgery. A laser-microsurgical technique used to manage chylous reflux pathologies achieved positive and permanent results, especially after an accurate preoperative diagnostic study to determine the site and nature of the lymphatic and chylous leakage and associated disorders.


Efficacy and safety of direct oral anticoagulants in patients undergoing cardioversion for atrial fibrillation: A systematic review and meta-analysis of the literature.
DOACs are increasingly used in patients with NVAF. Information on efficacy and safety of these compounds in patients undergoing electrical or pharmacological cardioversion is limited. Thus, we performed a systematic review and a meta-analysis of the literature to address this issue. Randomized controlled trials comparing the efficacy and safety of DOACs and VKAs in patients with NVAF were systematically searched in Medline, Web of Science, Scopus, Cochrane, and EMBASE databases (up to September 2014). Pooled relative risk (RR) and the corresponding 95% confidence interval (CI) were calculated for each outcome. Four randomized controlled trials (3635 patients), for a total of 4517 cardioversions (2869 with DOACs and 1648 with VKAs), were included in the analysis. DOACs and VKAs appeared equally effective in the prevention of stroke/systemic embolism (0.41% vs 0.61%; RR: 0.73, 95% CI: 0.31, 1.72; P=0.48) and of post-cardiovascular death (0.52% vs 0.81%; RR: 0.73, 95% CI: 0.27, 2.03; P=0.55), with a similar risk of major bleeding complications (0.81% vs 0.60%; RR: 1.23, 95% CI: 0.55, 2.71). Heterogeneity among studies was generally absent. Furthermore, the Weighted Mean Incidence (WMI) of complications appeared very low in patients randomized to DOACs (WMI: 0.6% and 0.9% for stroke/systemic embolism and major bleeding, respectively). Our results suggest that DOACs are at least as effective and safe as VKAs in patients with NVAF undergoing to an electrical or pharmacological cardioversion. Thus, DOACs may be considered a valid and practical alternative to VKAs.


Surgical outcomes for diverticulitis in young patients: results from the NSQIP database.
The incidence of diverticulitis is increasing among young patients (≤ 50 years), as are rates of recurrent disease. There is ongoing controversy regarding the best management strategy for this patient group. Guidelines have changed from elective colectomy after a single episode to a more individualized approach no longer based on patient age. This study investigated the clinical presentation and surgical outcomes of young patients undergoing surgery for diverticulitis over two time periods. The American College of Surgeons National Surgical Quality Improvement Program database was searched from 2005 to 2014 to identify all patients ≤ 50 with a diagnosis of diverticulitis. Data were obtained on patient demographics, comorbidity, perioperative details, and 30-day post-operative outcomes. Data were compared between two time periods, being 2005-2010 (Group 1) and 2011-2014 (Group 2). 10,844 patients were included in the analysis. The mean patient age was 43 years (range 18-50), and 35% were female. Significantly more patients were obese (BMI > 30) in Group 2 (52%) versus Group 1 (47%). Laparoscopic surgery and emergency surgery and perforation rates were significantly higher in Group 2. Wound infection was significantly less in Group 2. Post-operative organ/space infection and medical morbidity were significantly higher in Group 2. In recent years, there has been a change to a more conservative approach for elective colonic resection in young patients with a history of diverticulitis. Increasingly young patients presenting for surgery for diverticulitis are male and obese, and increased rates of post-operative medical morbidity have been observed. The laparoscopic approach is more common, with resultant increased operative times, and decreased wound infection rates. The observed increased in emergency surgery and perforation rates may be explained by the change in management approach with less elective resections.


Activation and inhibition of 3H-strychnine binding to the glycine receptor by Eccles' anions: modulatory effects of cations.
The ammonium salts of Eccles' anions are inhibitors of 3H-strychnine binding. By contrast, the binding is activated by the sodium salts of these anions. This activation is due to an increase in the affinity for 3H-strychnine. Pretreatment of the membranes with acetic anhydride abolishes the effect of sodium salt, whereas ammonium salts remain unaffected. In the presence of chloride the inhibitory effect of ammonium predominates over the effect of sodium. These results suggest that the effect of Eccles' anions is profoundly modified by their counter-ions and that Na+ and ammonium are acting through distinct sites on the glycine receptor.


Predictors of a sustained response to exercise training in patients with chronic heart failure: a telemonitoring study.
Exercise training (ExT) improves exercise capacity in chronic heart failure, but the results of home-based training have been variable. We sought the predictors of favorable outcome using a telemonitoring approach. Exercise capacity and quality of life (QOL) were assessed in 30 patients (28 men, age 64 +/- 8 years) with symptomatic chronic heart failure and left ventricular ejection fraction < or = 35% (28% +/- 9%) undergoing 8 months of home ExT. Patients were provided with heart rate monitors and exercise diaries after undergoing 4 months of hospital-based ExT. Weekly telephone contact was established and heart rate data were downloaded bimonthly. Changes in peak oxygen consumption per unit time (V*O2) and QOL were compared between the 15 most and 15 least adherent patients defined by the number of hours per week at > 60% maximum heart rate, observed during heart-rate monitoring. Peak V*O2 increased by 26% (P < .001) after 4 months of hospital ExT, but this increase had fallen to 8% (P = .07) at 12 months; only adherent patients (n = 15) showed persistent improvement of peak V*O2 at 12 months (P = .02). Improvement in peak V*O2 at 12 months was associated with baseline peak V*O2 (r = -0.61, P < .001) and hours logged on the heart rate monitor (r = 0.47, P = .01). Quality of life improvements were sustained at 12 months for the Minnesota Living with Heart Failure Questionnaire and Hare-Davis Depression Questionnaire. Nevertheless, QOL improvements achieved during the outpatient program were lost or attenuated at 12 months in nonadherent patients but were maintained in adherent patients. Telemonitoring is feasible for following adherence to home ExT. Ongoing adherence is critical in obtaining sustained benefit from ExT in heart failure.


Do we need any more new antiepileptic drugs?
The last decade has seen the licensing of nine new antiepileptic drugs (AEDs) with more to come. Despite this, only 58 and 63% of patients with localisation-related and newly diagnosed epilepsy, respectively, had been seizure-free for more than a year in separate prospective outcome studies undertaken at the Epilepsy Unit in Glasgow. Data will be presented to support the hypothesis that adolescent and adult epileptic patients comprise two distinct populations. Around 60% will be controlled on monotherapy with the first or second choice AED, while the majority of the remainder is difficult-to-control. It is for this latter group and the many pharmacoresistant paediatric patients with encephalopathic syndromes that we need new AEDs. For a successful clinical outcome, patients must be able to tolerate the treatment. Neurotoxic, sedative, cognitive and psychiatric symptoms, dysmorphic and other long-term side effects, and teratogenesis plague the current crop of AEDs. Pharmacokinetic and pharmacodynamic interactions complicate the situation still further. These problems may, in part, be a consequence of combining drugs with similar mechanisms of action. Unravelling the genetics of the epilepsies will provide a range of tempting targets for pharmacological intervention. We need, also, models of refractory epilepsy to help identify promising therapies. An efficient regulatory trial programme will ensure rapid availability of new AEDs for the many children and adults whose lives continue to be blighted by seizures.


Role of osteoblast suppression in multiple myeloma.
Multiple myeloma is the most common form of plasma cell dyscrasia and virtually all cases of myeloma exhibit osteolytic lesions, which result in bone pain, pathological fractures, spinal cord compression, and hypercalcaemia. Malignant plasma cells disrupt the delicate balance between bone formation and bone resorption, which ultimately leads to the debilitating osteolytic lesions. This review focuses principally on mechanisms of osteoblast inhibition by malignant plasma cells with emphasis placed on our experimental findings, which support a model for abnormal Wnt signaling in osteoblast suppression. We describe how excessive amounts of soluble Wnt inhibitors secreted by malignant plasma cells in multiple myeloma could promote osteolytic lesions, tumor growth, suppress hematopoiesis, prevent proper engraftment, and expansion of transplanted stem cells. Finally, we detail current therapies shown to disrupt the interaction between the myeloma cell and the microenvironment, leading to activation of osteoblasts.


Absorption and Fluorescence Features of an Amphiphilic meso-Pyrimidinylcorrole: Experimental Study and Quantum Chemical Calculations.
Corroles are emerging as an important class of macrocycles with numerous applications because of their peculiar photophysical and metal chelating properties. meso-Pyrimidinylcorroles are easily deprotonated in certain solvents, which changes their absorption and emission spectra as well as their accessible supramolecular structures. To enable control over the formation of supramolecular structures, the dominant corrole species, i.e., the deprotonated form or one of the two NH-tautomers, needs to be identified. Therefore, we focus in the present article on the determination of the UV-vis spectroscopic properties of the free-base NH-tautomers and the deprotonated form of a new amphiphilic meso-pyrimidinylcorrole that can assemble to supramolecular structures at heterointerfaces as utilized in the Langmuir-Blodgett and liquid-liquid interface precipitation techniques. After quantification of the polarities of the free-base NH-tautomers and the deprotonated form by means of quantum chemically derived electrostatic potential distributions at the corroles' van der Waals surfaces, the preferential stabilization of (some of) the considered species in solvents of different polarity is identified by means of absorption spectroscopy. For the solutions with complex mixtures of species, we applied fluorescence excitation spectroscopy to estimate the relative weights of the individual corrole species. This technique might also be applied to identify dominating species in molecularly thin films directly on the subphase' surface of Langmuir-Blodgett troughs. Supported by quantum chemical calculations we were able to differentiate between the spectral signatures of the individual NH-tautomers by means of fluorescence excitation spectroscopy.


Manganese-Catalyzed Sustainable Synthesis of Pyrroles from Alcohols and Amino Alcohols.
The development of reactions that convert alcohols into important chemical compounds saves our fossil carbon resources as alcohols can be obtained from indigestible biomass such as lignocellulose. The conservation of our rare noble metals is of similar importance, and their replacement by abundantly available transition metals, such as Mn, Fe, or Co (base or nonprecious metals), in key technologies such as catalysis is a promising option. Herein, we report on the first base-metal-catalyzed synthesis of pyrroles from alcohols and amino alcohols. The most efficient catalysts are Mn complexes stabilized by PN5 P ligands whereas related Fe and Co complexes are inactive. The reaction proceeds under mild conditions at catalyst loadings as low as 0.5 mol %, and has a broad scope and attractive functional-group tolerance. These findings may inspire others to use Mn catalysts to replace Ir or Ru complexes in challenging dehydrogenation reactions.


Interferon-beta1b treatment modulates cytokines in patients with primary progressive multiple sclerosis.
It is unknown whether the immunological effects of beta-interferon (IFN-beta) differ in primary progressive multiple sclerosis (PPMS) when compared with relapsing-remitting multiple sclerosis (RRMS). Therefore, we investigated the effects of IFN-beta1b treatment in PPMS on proliferation and cytokine pattern of peripheral blood mononuclear cells (PBMC) and interleukin-10 (IL-10) serum level. Eighteen patients were treated with IFN-beta1b for 12 months in an open-label trial. Serum and PBMC were collected longitudinally. Interleukin-10 serum levels increased (P = 0.02) during treatment. Tumor necrosis factor-alpha was increased in anti CD3 (OKT3) antibody stimulated PBMC during treatment (P = 0.04), whereas secretion of IL-10 was decreased in OKT3 (P = 0.04), but increased in concavalin A stimulated PBMC (P = 0.02). Interleukin-10 serum levels rose in IFN-beta1b-treated patients as has been observed in RRMS. The changes in cytokine patterns secreted by T-lymphocytes of PPMS patients, however, differ from effects observed in RRMS supporting the hypothesis that PPMS differs in some immunological aspects from RRMS.


Ferritin Light Chain (FTL) competes with long noncoding RNA Linc00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer.
Although the colorectal cancer (CRC) mortality rates are decreasing in virtue of CRC screening and improved therapeutic methods, CRC is still a leading cause of cancer deaths. One of the main causes is chemoresistance occurrence in CRC. Understanding of the molecular mechanisms of chemoresistance benefits to CRC diagnosis and treatment. In this study, gene expression was determined by Western blot and qRT-PCR. The biological functions of genes in CRC cells were studied by knocking down or overexpressing the gene in CRC cells and then analyzing cell sensitivity to 5-Fu by the MTT assay and the flow cytometry, and analyzing cell migration and invasion by transwell assays. The luciferase reporter assay was used to examine microRNA regulation of target gene expression, and biotin pulldown assay was performed to detect interaction between RNA molecules. This study found that Ferritin Light Chain (FTL) and long intergenic non-coding RNA Linc00467 were both upregulated in CRC tissues and cell lines, and inversely correlated to CRC patient survival. FTL and Linc00467 promoted CRC cells abilities to resistance against 5-fluor-ouracil (5-Fu), migration and invasion. These effects were compromised by miR-133b which targeted both FTL and Linc00467. miR-133b interacted with Linc00467 and miR-133b inhibitor prevented Linc00467 knockdown-induced alternations of FTL expression and biological functions. Both FTL and Linc00467 are oncogenes in CRC. FTL expression upregulated in CRC via Linc00467/ miR-133b axis, and leads to CRC cell resistance against 5-FU treatment and promotes CRC metastasis.


Extended linear response for bioanalytical applications using multiple enzymes.
We develop a framework for optimizing a novel approach to extending the linear range of bioanalytical systems and biosensors by utilizing two enzymes with different kinetic responses to the input chemical as their substrate. Data for the flow injection amperometric system devised for detection of lysine based on the function of L-lysine-alpha-oxidase and lysine-2-monooxygenase are analyzed. Lysine is a homotropic substrate for the latter enzyme. We elucidate the mechanism for extending the linear response range and develop optimization techniques for future applications of such systems.


Beneficial effects of catechin-rich green tea and inulin on the body composition of overweight adults.
Green tea catechin has been proposed to have an anti-obesity effect. The aim of the present study was to investigate whether the effect of catechin-rich green tea in combination with inulin affects body weight and fat mass in obese and overweight adults. A total of thirty subjects were divided into a control group and an experimental group who received 650 ml tea or catechin-rich green tea plus inulin. A reduction of body weight ( - 1·29 (sem 0·35) kg) and fat mass (0·82 (sem 0·27) kg) in the experimental group was found after 6 weeks, and no adverse effects were observed. After refraining from consumption for 2 weeks, sustained effects on body weight and fat mass were observed. We conclude that continuous intake of catechin-rich green tea in combination with inulin for at least 3 weeks may be beneficial for weight management.


Immunohistochemical evaluation of hematologic malignancies.
This article summarizes the most recent developments and current practice of immunohistochemistry in the diagnosis of hematologic malignancy. Increased availability of monoclonal antibodies applicable in formaldehyde-fixed and paraffin-embedded tissue is discussed as are immunohistochemical definitions for many small cell lymphoma entities. Evaluation is made of the biologic potential of lymphomas and leukemias by the use of antibodies to proliferation antigens, such as Ki-67 and products of tumor suppressor genes (p53).


Morphine tolerance in male and female rats.
Several studies indicate greater sensitivity to morphine (MOR) analgesia in male compared to female rats under the acute dosing condition. The present study investigated whether the same sex difference in sensitivity persists in MOR-tolerant rats. MOR was administered chronically (7 mg/kg twice daily) until tolerance developed in each rat. Tolerant rats were treated randomly with higher graded doses of MOR (10-25 mg/kg). Analgesia (tail-flick test) and spontaneous motor activity (total locomotion) were measured. The present data confirmed previous studies showing a greater sensitivity to acute MOR in male than in female rats. However, the sex differences seen in MOR sensitivity were abolished in tolerant rats. The rate of acquisition of tolerance was similar in male and female rats. The analgesic response was not affected by motor depression.


Ascites and right pleural effusion: demonstration of a peritoneo-pleural communication.
A 54-yr-old female with known liver cirrhosis presented with a right transudative pleural effusion and ascites. To find the source of pleural fluid, [99mTc]sulfur colloid was injected intraperitoneally and a serial imaging study revealed its passage to the right pleural space on 2-hr and 24-hr images. Mechanisms proposed in the formation of pleural effusion in liver cirrhosis are (a) lymphatic drainage and (b) diaphragmatic defect. Radioisotope migration speed may be a clue for differentiating these two mechanisms, being more rapid in the presence of a diaphragmatic defect.


Treatment of herniated lumbar disk syndrome with chymopapain.
One hundred twenty-four patients with herniated lumbar disks received intradiskal injections of chymopapain before the Food and Drug Administration's withdrawal of the drug. One year after injection, 90 patients (72.6%) experienced major improvement, 21 (16.9%) had slight improvement, and 13 (10.5%) had no improvement. Of those patients who had no previous back surgery and who were not compensation cases, 77 patients (81%) had marked improvement, 13 (13.7%) had slight improvement, and five (5.3%) had no improvement. Three- to six-year follow-ups were obtained by questionnaire. Of the 114 patients responding, overall 83 patients (72.8%) had marked improvement, and 75 (83.3%) of those with no previous surgery and who were not workmen's compensation cases had major improvement. Since all patients met objective criteria for diskectomy, favorable results from chemonucleolysis spared most the trauma of surgery and its attendant convalescence. These results indicate that chemonucleolysis can and should be considered an advantageous alternative to surgery in appropriately selected patients.


Primary anaplastic glio-neuronal tumor of the pineal gland: a new type of pineal neoplasm?
Tumors of the pineal gland are relatively rare. Most are solid, infiltrative lesions characterized by either germ cell, glial, or pineal parenchymal origin. To our knowledge, none have been described that contain an admixture of both anaplastic glial and neuronal elements. The authors present a case of a primary anaplastic glio-neuronal tumor of the pineal gland in a 78-year-old gentleman who presented with hydrocephalus. The patient underwent an endoscopic third ventriculostomy for treatment of his hydrocephalus as well as tumor biopsy under endoscopic visualization. Sections of the tumor displayed a modestly to moderately cellular neoplasm infiltrating the residual pineal gland. The majority of the nuclei appeared hyperchromatic, spindle-shaped, and pleomorphic, with fibrillary cytoplasmic processes. Rare nuclei were round with vesicular chromatin and red nucleoli. Mitotic figures were easily identified, despite small sample size. GFAP immunostaining highlighted the fibrillar background and cytoplasmic processes while synaptophysin immunostains revealed intense, dot-like positivity in the rounder nuclei with vesicular chromatin. Although the different nuclear morphologies seen on the hematoxylin-eosin stained slides suggested both glial and neuronal origin, immunostains were required to confirm the presence of dual differentiation. We present the first case of a primary anaplastic glio-neuronal neoplasm of the pineal gland. Increased use of immunostaining may unveil additional cases in the future. Furthermore, additional research will be required to determine whether the dual differentiation has prognostic significance.


Beyond integrated care.
Integrated care tops the health care agenda. But more integration alone will not remedy the crisis in health care, and there is a danger in the increasingly prevalent conceptualization of care integration as a goal in itself rather than as an instrument for improving performance. Operating integrated care systems, staffed by an overly specialized medical workforce, is unsustainable in terms of human and financial resources and is likely to produce little benefit for patients with multi-morbidity. An alternative approach involves health care leaders going beyond integrated care and nurturing transformative change from within the medical workforce instead. To be fit for purpose, the doctors must be encouraged and facilitated to customize their expertise to current and expected future burdens of disease. This would lead to more adaptive doctors who could actively support people in healing and managing their own health. Integrated care should be conceptualized as one possible lever for transformative change rather than its endpoint.


Spatial heterogeneity of caffeine- and inositol 1,4,5-trisphosphate-induced Ca2+ transients in isolated snail neurons.
Inositol 1,4,5-trisphosphate- and caffeine-induced Ca2+ release was examined in neurons isolated from the mollusc Helix pomatia using Ca2+ indicator fura-2 and fluorescent digital-imaging microscopy technique. Extracellular application of caffeine caused a fast and pronounced augmentation of [Ca2+]i whose amplitude and kinetics differ in the centre of the cell and near its membrane. Mean values of caffeine-induced increase of [Ca2+]i were 0.97 +/- 0.11 microM at the periphery and 0.53 +/- 0.13 microM in the centre. The rates of rise and relaxation of caffeine-evoked [Ca2+]i transients were faster near the membrane. Pressure injection of inositol, 1,4,5-trisphosphate into the same neurons produced an abrupt and significant increase of [Ca2+]i in the centre (mean value of inositol 1,4,5-trisphosphate-induced elevation = 0.55 +/- 0.11 microM) while the response was smaller or even absent near the cellular membrane. Inositol 1,4,5-trisphosphate- and caffeine-induced Ca2+ transients did not affect each other. The data obtained indicate that in snail neurons these two calcium pools are not overlapping and at least some part of the caffeine-sensitive store is located close to the cellular membrane and that the inositol 1,4,5-trisphosphate-sensitive one is located in the centre of the cell.


Characteristics of six small heat shock protein genes from Bactrocera dorsalis: Diverse expression under conditions of thermal stress and normal growth.
To explore the functions of small heat shock proteins (sHsps) in relation to thermal stress and development in Bactrocera dorsalis (Hendel), one of the most economically important pest species attacking a wide range of fruits and vegetables, six full-length cDNAs of sHsp genes (BdHsp17.7, 18.4, 20.4, 20.6, 21.6 and 23.8) were cloned, and the expression patterns in different developmental stages and tissues, as well as in response to both thermal and 20-hydroxyecdysone (20E) exposures, were examined using real time quantitative PCR. The open reading frames (ORFs) of six sHsps are 453, 489, 537, 543, 567 and 630bp in length, encoding proteins with molecular weights of 17.7, 18.4, 20.4, 20.6, 21.6 and 23.8kDa, respectively. BdHsp18.4 and BdHsp20.4 maintained lower expression levels in both eggs and larvae, whereas remarkably up-regulated after the larval-pupal transformation, suggesting that these two sHsps may be involved in metamorphosis. Significant tissue specificity exists among sHsps: the highest expression of BdHsp20.6 and BdHsp23.8 in the Malpighian tubules and ovary, respectively, versus a peak in the fat body for others. BdHsp20.4 and BdHsp20.6 were significantly up-regulated by thermal stress. In contrast, BdHsp18.4 and BdHsp23.8 reacted only to heat stress. BdHsp17.7 and BdHsp21.6 were insensitive to both heat and cold stresses. The degree of sHsps response depends on intensity of 20E treatment, i.e., dose and time. These results strongly suggest functional differentiation within the sHsp subfamily in B. dorsalis. The physiological function of sHsp members under thermal stress and normal growth remains the subjects of further investigation.


Invasive aspergillosis: epidemiology and environmental study in haematology patients (Sfax, Tunisia).
Invasive aspergillosis (IA) is a major opportunistic infection in haematology patients. Preventive measures are important to control IA because diagnosis is difficult and the outcome of treatment is poor. We prospectively examined the environmental contamination by Aspergillus and other fungal species and evaluated the prevalence of invasive aspergillosis in the protect unit of haematology. A three-year prospective study (December 2004-September 2007) was carried out in the department of haematology of Hedi Chaker Hospital. Suspected invasive aspergillosis cases were reviewed and classified as proven, probable and possible invasive aspergillosis using the EORTC criteria. During the study period, we collected weekly environmental samples (patient's rooms, tables and acclimatisers) and clinical samples from each patient (nasal, expectoration and auricular). Among 105 neutropenic patients, 16 had probable and 13 had possible IA. A total of 1680 clinical samples were collected and A. flavus was most frequently isolated (79.2%). Analysis of 690 environmental samples revealed that Penicillium (44%) was the most frequent followed by Cladosporium (20%), Aspergillus spp. (18%) and Alternaria (13%). The PCR-sequencing of 30 A. flavus isolates detected from clinical and environmental samples confirmed the mycological identification. Our findings underline the importance of environmental surveillance and strict application of preventive measures.


Predictors of cancer screening among low-income primary care patients.
Although population-based studies report lower rates of cancer screening among racial/ethnic minorities than among Whites in the U.S., few studies have examined predictors of screening among low-income Hispanic, Black, and Chinese primary care patients. We examined utilization of mammography, Pap smear, digital rectal examination, fecal occult blood testing, sigmoidoscopy/colonoscopy, and prostate-specific antigen testing in 833 patients from 2 community health centers in New York City, ascertaining relationships between use of screening and race/ethnicity, income, education, years in the U.S., insurance, cancer risk perception, family disease history, and physician recommendation. Despite similar access to primary care, Hispanics and Blacks reported higher utilization rates of all screening tests than Chinese (p<.01). Physician recommendation and more years in the U.S. were associated with greater use of all screening services (p<.001), with physician recommendation most strongly associated with screening. Interventions to enhance screening by at-risk groups should emphasize both physician recommendation and culturally-sensitive patient education.


Geographical origin and breed discrimination of Apulian lamb meat samples by means of analytical and spectroscopic determinations.
With the aim of finding parameters capable of characterizing meat according to geographical origin, twenty-five lamb meat samples from three areas located in Apulia (Southern Italy) were analysed for moisture, ash, fat and protein content, stable isotope ratios ((15)N/(14)N and (13)C/(12)C), major elements (Ca, Mg, Na, K) and trace metals (Zn, Cu, Fe, Cr). (1)H high resolution magic angle spinning (HR-MAS) NMR spectra were also obtained for all the samples. The advantages of the (1)H HR-MAS NMR technique are that sample preparation is easy, since the spectrum is obtained directly on the minced solid sample, and that information is acquired for a large number of metabolites (amino acids, fatty acids, sugars, etc.). The application of multivariate statistical analysis to two data sets containing tissue composition results together with the metals contents and (1)H HR-MAS NMR spectral data together with isotope ratios, respectively, provided in both cases a satisfactory origin differentiation of lamb meat samples.


Sex differences in principal farm operators' tractor driving safety beliefs and behaviors.
To examine the widely accepted hypothesis that farm women are more concerned with safety issues and behaviors than their male counterparts are. A telephone survey was administered to a random sample of Kentucky principal farm operators, 90 of whom were women. Participants were questioned about their tractor safety beliefs and practices. No significant sex differences in tractor safety perceptions and behavior were observed. Socialization of women to the role of principal farm operator may override their typically greater sensitivity to safety issues, an important consideration when designing safety campaigns for this population.


Lasers for the treatment of dentin hypersensitivity: a meta-analysis.
This systematic review and meta-analysis assessed the efficacy of lasers in reducing dentin hypersensitivity (DH) as compared with placebo or no treatment. Seven electronic databases and a manual search resulted in 2,538 unique publications. After selection, 13 studies were included in the meta-analysis. A CONSORT-based quality assessment revealed that 3 and 10 studies were at low and high risk of bias, respectively. A random-effects model with the generic inverse variance standardized mean difference (SMD) was used because of expected heterogeneity. Meta-analyses of the baseline-end of follow-up changes in pain revealed no differences for Er,Cr:YSSG vs. placebo (SMD = 2.49; 95% CI, -0.25 to 5.22; p = .07) but did reveal differences in favor of lasers for Er:YAG vs. placebo (SMD, 2.65; 95% CI, 1.25 to 4.05; p = .0002), Nd:YAG vs. placebo (SMD, 3.59; 95% CI, 0.49 to 6.69; p = .02), and GaAlAs vs. placebo (SMD, 3.40; 95% CI, 1.93 to 4.87; p < .00001). High and significant heterogeneity was found for all comparisons. In conclusion, Er:YAG, Nd:YAG, and GaAlAs lasers appear to be efficacious in reducing DH. However, given the high heterogeneity of the included studies, future randomized controlled clinical trials are needed to confirm these results.


Expression of the gene encoding glycogen phosphorylase is elevated in diabetic rat skeletal muscle and is regulated by insulin and cyclic AMP.
Glycogen phosphorylase regulates the breakdown of glycogen into glucose, but as previous studies have demonstrated, the control of glycogen metabolism becomes deregulated in diabetes mellitus. Messenger RNA levels encoding several different proteins are altered in skeletal muscle biopsies of patients with insulin-dependent and non-insulin-dependent diabetes. The possible alteration of expression of the gene encoding the skeletal muscle isoform of glycogen phosphorylase during diabetes has not previously been investigated. We examined the effect of streptozotocin-induced diabetes and insulin treatment on glycogen phosphorylase mRNA in rat skeletal muscle; glycogen phosphorylase mRNA levels were elevated in diabetic rat muscle tissue, but were partially suppressed in diabetic rat muscle following insulin treatment. To distinguish between the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA levels, we employed differentiating rat L6 myoblasts in culture. Insulin stimulated the accumulation of glycogen phosphorylase mRNA as determined by Northern blot analysis. Moreover, insulin and dibutyryl cAMP stimulated expression of a transiently transfected chloramphenicol acetyl transferase reporter gene under the control of the muscle glycogen phosphorylase promoter in differentiating myotubes in culture, suggesting that the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA are at the level of transcription. These results suggest that insulin and epinephrine may participate in the induction of the glycogen phosphorylase gene during myogenesis; moreover, activation of this gene in muscle tissue may be a contributing factor in impaired glycogen storage during uncontrolled diabetes.


Nonsurgical treatment of posterior fossa epidural hematoma.
The recommended treatment for posterior fossa epidural hematoma has been prompt surgical evacuation. We report 2 patients who were treated conservatively. Both patients were younger than 10 years of age and developed subacute symptoms and signs. Serial computed tomography demonstrated complete resolution of the hematomas and no development of hydrocephalus during nonsurgical treatment. They recovered well without any neurologic deficits. In order to evaluate an indicative factor for nonsurgical treatment in young children with posterior fossa epidural hematoma, we review both of our patients and 36 well-documented patients from the literature, all of whom were younger than 10 years of age. The results demonstrate that the development of hydrocephalus is a critical factor in clinical progression. Nonsurgical management can be applied in these circumstances until spontaneous resolution of the hematoma unless early signs of medullary compression appear acutely after head trauma or serial computed tomography demonstrates the development of hydrocephalus followed by medullary compression.


Morphological changes and nuclear translocation of DLC1 tumor suppressor protein precede apoptosis in human non-small cell lung carcinoma cells.
We have previously shown that reactivation of DLC1, a RhoGAP containing tumor suppressor gene, inhibits tumorigenicity of human non-small cell lung carcinoma cells (NSCLC). After transfection of NSCLC cells with wild type (WT) DLC1, changes in cell morphology were observed. To determine whether such changes have functional implications, we generated several DLC1 mutants and examined their effects on cell morphology, proliferation, migration and apoptosis in a DLC1 deficient NSCLC cell line. We show that WT DLC1 caused actin cytoskeleton-based morphological alterations manifested as cytoplasmic extensions and membrane blebbings in most cells. Subsequently, a fraction of cells exhibiting DLC1 protein nuclear translocation (PNT) underwent caspase 3-dependent apoptosis. We also show that the RhoGAP domain is essential for the occurrence of morphological alterations, PNT and apoptosis, and the inhibition of cell migration. DLC1 PNT is dependent on a bipartite nuclear localizing sequence and most likely is regulated by a serine-rich domain at N-terminal part of the DLC1 protein. Also, we found that DLC1 functions in the cytoplasm as an inhibitor of tumor cell proliferation and migration, but in the nucleus as an inducer of apoptosis. Our analyses provide evidence for a possible link between morphological alterations, PNT and proapoptotic and anti-oncogenic activities of DLC1 in lung cancer.


Plasma IGFBP-3 and its relationship with quantitative growth hormone secretion in short children.
We assessed the relationship between serum IGFBP-3 levels with IGF-I and quantitative GH secretory status in poorly growing children. We studied the relationship between 24-hour integrated concentration of GH, peak GH to paired sequential stimulation tests, IGF-I and the IGFBP-3 serum levels. One hundred and two children (82 males, 20 females, age 11.7 +/- 2.7 years) with short stature (height -2.6 +/- 0.7 SDS) were studied. Quantitative GH secretory status was assessed by the 24-hour integrated GH and by response to arginine and insulin stimulation. GH, IGFBP-3 and IGF-I were measured by radioimmunoassay. To adjust for age and gender, IGFBP-3 levels were converted to SD score. IGFBP-3 SDS was strongly correlated with IGF-I SDS (r = 0.64, P < 0.0001), and weakly with peak GH (r = 0.28, P < 0.0004), but not with the integrated GH concentration (r = 0.07, P < 0.46). IGFBP-3 SDS increased with pubertal maturation (P < 0.0001). There was no difference in mean IGFBP-3 SDS in subgroupings of the patients based on the results of their quantitative GH tests. In short children, IGFBP-3 levels increase with puberty, are strongly correlated with IGF-I levels, weakly correlated with peak response to GH stimulation tests, but not correlated with integrated GH. Consequently, diagnostic classifications of patients based on quantitative measurements of GH secretion and IGFBP-3 differ.


A review of patient safety measures based on routinely collected hospital data.
The literature on patient safety measures derived from routinely collected hospital data was reviewed to inform indicator development. MEDLINE and Embase databases and Web sites were searched. Of 1738 citations, 124 studies describing the application, evaluation, or validation of hospital-based medical error or complication of care measures were reviewed. Studies were frequently conducted in the United States (n = 88) between 2005 and 2009 (n = 77) using Agency for Healthcare Research and Quality patient safety indicators (PSIs; n = 79). The most frequently cited indicators included "postoperative hemorrhage or hematoma" and "accidental puncture and laceration." Indicator refinement is supported by international coding algorithm translations but is hampered by data issues, including coding inconsistencies. The validity of PSIs and similar adverse event screens beyond internal measurement and the effects of organizational factors on patient harm remain uncertain. Development of PSIs in ambulatory care settings, including general practice and psychiatric care, needs consideration.


What is dialogical research, and why should we do it?
Social scientists have explored the writing of Russian literary philosopher Bakhtin from a variety of perspectives, but little attempt has been made to apply Bakhtin's conception of dialogue to the conduct of research and the production of research reports. The author's questions relate to what dialogical research would look like and the ethical imperative of dialogical research.


[Pneumonia in cyclosporin A-treated chronic polyarthritis (a case report)].
A 71 year old patient with seropositive rheumatoid arthritis developed rapidly progressive pneumonitis with bilateral pulmonary infiltrations and severe hypoxemia. At this time the patient was treated with cyclosporin A, indomethacin, chlorthalidone, amitriptyline and chlordiazepoxide. After these medicaments were discontinued and prednisone therapy was initiated a rapid remission of the pneumopathy was observed. It is probable that the reversible pneumopathy was induced by the treatment with cyclosporin A. Among the other medicaments which were stopped at the same time as cyclosporin A no comparable side effects are known.


Critical issues with clinical research in children: the example of premature infants.
Research in pediatrics has led to marked improvements in survival in pediatric patients. In no other age group have these improvements been more dramatic than in neonatology, where antenatal steroid administration to mothers and postnatal utilization of surfactant have led to marked improvements in survival so that infants born at 24 weeks gestation now have a greater than 50% chance of survival. Unfortunately, more than 50% of these patients develop significant complications of prematurity with potential long-term impact on the health of these infants. Therefore, additional research must be done in these patients to prevent these complications or reduce the impact of these complications. There are many practical and some ethical issues that could impede research in the area. Interventional studies have succeeded because literally decades of research defined unequivocally the pathophysiology of diseases such as surfactant deficiency in RDS. Unfortunately, the pathophysiology leading to the complications of prematurity has been extrapolated from old concepts without verification as the population has become smaller and more premature than the previous era. Thus, an extremely important practical issue in pediatric research is whether to design interventions to address the extrapolated pathophysiology risking misinterpretations of the results of such studies. Or should our efforts be focused on defining endpoints associated with the development of diseases and complications which may define pathophysiology more completely but delay the design of interventions to improve the outcomes of patients. Another crucial practical issue in pediatric research is how to power studies so that interventions can be studied adequately. In the US, large neonatal networks have been formed so that large databases can be created and large multi-center trials can be performed. The practical issues associated with these network studies is the center to center variability in patient care may dwarf the beneficial effect of the intervention on the disease process, so that a "negative" study of an intervention may not represent the true effect of the intervention in the disease process. These practical issues among others will be the focus of this review.


Self-assessed and functional health of older women.
This study examines the contributions made by functional health, age self-concept, and attitudes, and demographic variables toward explaining health self-assessments in a sample of older women. The participants in the study were a simple random sample of white females (114) over age sixty years and who were residents in five apartment complexes for the aged in a large Midwestern city. Significant correlations to self-assessment of health were found among measures of functional health, self-concept and attitudes, and demographic variables. Multiple regression analysis using five variables (self-assessment of speed, emotional behavior, age self-concept, body care and movement, and occupation) explained almost 40 percent of variance in self-assessment of health data.


Disturbances of purinergic system in affective disorders and schizophrenia.
Purinergic system plays a role in the regulation of many psychological processes, including mood and activity. It consists of P1 receptors, with adenosine as the agonist, and P2 receptors, activated by nucleotides (e.g., adenosine 5'-triphosphate - ATP). Propounded disturbances of uric acid in affective disorders were related to the introduction of lithium for the treatment of these disorders in the 19th and 20th century. At the beginning of the 21st century, new evidence was accumulated concerning a role of uric acid in the pathogenesis and treatment of bipolar disorder (BD). In patients with BD, higher prevalence of gout and increased concentration of uric acid have been found as well as the therapeutic activity of allopurinol, used as an adjunct to mood stabilizers, has been demonstrated in mania. In recent years, the research on the role of the purinergic system in the pathogenesis and treatment of affective disorders and schizophrenia focuses on the role of adenosine (P1) receptors and nucleotide (P2) receptors. Activation of adenosine receptors is related to an antidepressant activity. Alterations of P2 receptors are also significant for the pathogenesis of affective disorders. The role of purinergic system in schizophrenia is related to the effect of adenosine and nucleotide receptors on dopaminergic and glutamatergic neurotransmission. A lot of data indicate that schizophrenia is related to a deficit of adenosine system. Changes in the purinergic system are also significant for psychopathological symptoms of schizophrenia and for the action of antipsychotic drugs.


Clinical effectiveness of a cognitive behavioral group treatment program for anxiety disorders: a benchmarking study.
Previous research has established efficacy of cognitive behavioral therapy (CBT) for anxiety disorders, yet it has not been widely assessed in routine community clinic practices. Efficacy research sacrifices external validity to achieve maximum internal validity. Recently, effectiveness research has been advocated as more ecologically valid for assessing routine clinical work in community clinics. Furthermore, there is a lack of effectiveness research in group CBT. This study aims to extend existing research on the effectiveness of CBT from individual therapy into group therapy delivery. It aimed also to examine outcome using not only symptom measures, but also measures of related symptoms, cognitions, and life quality and satisfaction. Results from a cohort of patients with various anxiety disorders demonstrated that treatment was effective in reducing anxiety symptoms to an extent comparable with other effectiveness studies. Despite this, only 43% of individuals showed reliable change, and 17% were 'recovered' from their anxiety symptoms, and the post-treatment measures were still significantly different from the level of anxiety symptoms observed in the general population.


Terahertz multistatic reflection imaging.
We describe a new imaging method using single-cycle pulses of terahertz (THz) radiation. This technique emulates the data collection and image processing procedures developed for geophysical prospecting and is made possible by the availability of fiber-coupled THz receiver antennas. We use a migration procedure to solve the inverse problem; this permits us to reconstruct the location, the shape, and the refractive index of targets. We show examples for both metallic and dielectric model targets, and we perform velocity analysis on dielectric targets to estimate the refractive indices of imaged components. These results broaden the capabilities of THz imaging systems and also demonstrate the viability of the THz system as a test bed for the exploration of new seismic processing methods.


Epidemiology of illicit drug use disorders in Iran: prevalence, correlates, comorbidity and service utilization results from the Iranian Mental Health Survey.
Drug abuse is a significant social and public health problem in Iran. The present study aimed to provide prevalence estimates and information on correlates of illicit drug use disorder and opioid dependence, as well as service use for these disorders in Iran. This report is based on the Iranian household Mental Health Survey (IranMHS) conducted in 2011. A three-stage probability sampling was employed. Face-to-face interviews by trained psychologists were carried out with a nationally representative sample of 7841 individuals (3366 men and 4475 women) aged 15-64 years. The Composite International Diagnostic Interview and questionnaires for socio-demographic correlates and service use. The prevalence of 12-month use disorders for any illicit drug according to DSM-IV and DSM-5 criteria were 2.09% [95% confidence interval (CI) = 1.70-2.47%] and 2.44% (95% CI = 2.03-2.85%), respectively. Opioid use disorders, and opium in particular, were the most common use disorder. The odds of drug use disorders were greater in men than in women, in previously married participants than in currently or never married participants, and in participants with lower socio-economic status than in those with higher socio-economic status (all P-values <0.05). Approximately half of those with drug use disorders and 40% with opioid dependence had a 12-month unmet need for treatment. Self-help groups were the most common type of service used, followed by obtaining medication from pharmacies directly and outpatient treatment services. Opioid use disorders are the most common type of drug use disorders in Iran, setting Iran apart from many other countries. Patterns of service use suggest a large unmet need for drug use disorder treatment in Iran.


Thrombocytosis in liver transplant recipients: prevalence, natural history, and impact.
The prevalence, natural history, and implications of reactive thrombocytosis after liver transplantation (LT) are unknown. Prospectively collected data from July 2000 to February 2006 were analyzed. Post-LT thrombocytosis was defined as a platelet count of > 450 x 10(3)/microL lasting for >7 days and starting within 8 weeks of transplantation. In patients who survived >8 weeks, graft and patient outcomes were compared with liver transplant recipients who survived >8 weeks and did not develop any thrombocytosis. Post-LT thrombocytosis was seen in 92 (14.7%) of 627 patients. The median onset was on day 13 (range, days 1-44) and the peak platelet count was seen on day 17 (range, days 3-110). The median duration of thrombocytosis was 25 days (range, 7-1,253 days), with a median peak platelet count of 625 x 10/microL (range, 472-1,381 x 10/microL). Seronegative fulminant hepatic failure was the indication for transplantation in 18% of patients with post-LT thrombocytosis compared with 3% of controls (P < 0.001). There was a lower proportion of patients transplanted for hepatitis C-related cirrhosis in the thrombocytosis group (10% vs. 18%, P = 0.04). The occurrence of hepatic arterial thrombosis was similar in the 2 groups (5% vs. 4%, P = NS). None of the 4 patients with platelet count higher than 1,000 x 10/microL developed thrombotic complications. Post-LT thrombocytosis is more often associated with seronegative fulminant hepatic failure, and there is a negative association with hepatitis C-related cirrhosis. Post-LT thrombocytosis does not increase the risk of hepatic artery thrombosis, and patients without thrombotic complications should not be treated.


Molecular analysis of human T-cell lymphotropic virus type II from Wayuu Indians of Colombia demonstrates two subtypes of HTLV-IIb.
Studies of the genetic heterogeneity of human T-cell lymphotropic virus type II (HTLV-II) have revealed the presence of two genetic subtypes, termed HTLV-IIa and HTLV-IIb. The HTLV-IIb subtype encodes an immunodominant epitope present at the C-terminus of the extended Tax protein and, by using an LTR-based, restriction fragment-length polymorphism (RFLP) assay, can be further classified into IIb60-IIb5, with HTLV-IIb1 (Central Amerindian-like) and HTLV-IIb5 (North Amerindian-like) being characteristic subtypes for Native American Indians. To determine the antigenic and genetic heterogeneity among HTLV-II-infected South Amerindians, we used a Tax synthetic peptide immunoassay on serum, and RFLP and phylogenetic analysis on LTR sequences amplified from genomic DNA from four Wayuu Indians of Colombia. The Wayuu specimens displayed seroreactivity to the immunodominant epitope located in the extended Tax region, as predicted, and demonstrated genetic heterogeneity by the presence of both the IIB1 (Wyu1, Zuc31) and IIb5 (Wyu2, Zuc42) subtypes sequences within separate phylogroups represented by the Guaymi Indian (IIb1) and North Amerindian (IIb5) sequences, respectively. Sequence analysis showed that major LTR regulatory motifs and the cis-acting repressive elements in the LTR RNA secondary structure were relatively conserved in both Wayuu subtypes, but the predicted secondary structure of the rex response stem loop in the Wyu2 (IIb5) LTR sequence was 45 nucleotides (nt) and 95 nt longer than that observed in the Wyu1 (IIb1) and G12.1 (IIb1) LTR sequences, respectively. These results extend our knowledge of the genetic heterogeneity of HTLV-II in South Amerindians.


Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial.
Treatment of ankylosing spondylitis (AS) with infliximab, an anti-tumor necrosis factor alpha monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31-63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36-67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.


Expression, site-directed mutagenesis, and steady state kinetic analysis of the terminal thioesterase domain of the methymycin/picromycin polyketide synthase.
The thioesterase (TE) domain of the methymycin/picromycin synthase (PICS) was functionally expressed in Escherichia coli, and the optimal N-terminal boundary of the recombinant TE was determined. A series of diketide-N-acetylcysteamine (SNAC) thioesters were tested as substrates. PICS TE showed a strong preference for the 2-methyl-3-ketopentanoyl-SNAC substrate 5 over the stereoisomers of the reduced diketides 1-4, with an approximately 1.6:1 preference for the (2R,3S)-2-methyl-3-hydroxy diastereomer 2 over the (2S,3R)-diketide 1. The closely related DEBS TE, the thioesterase from the 6-deoxyerythronolide B synthase, showed a more marked 4.4:1 preference for 2 over 1, with only a slightly greater preference for the 3-ketoacyl-SNAC substrate 5. The roles of several active site residues in PICS TE were examined by site-directed mutagenesis. Serine 148, which is part of the apparent catalytic triad consisting of S148, H268, and D176, was found to be essential for thioesterase activity, while replacement of D176 with asparagine (D176N) gave a mutant thioesterase that retained substantial, albeit reduced, hydrolytic activity toward diketide-SNAC substrates. Mutation of E187 and R191, each of which is thought to play a role in substrate binding, had only minor effects on the relative specificity for diketide substrates 1, 2, and 5. Finally, when PICS TE was fused to the C-terminus of DEBS module 3, the resultant chimeric protein converted diketide 1 with methylmalonyl-CoA to triketide ketolactone 6 with improved catalytic efficiency compared to that of the previously developed DEBS module 3-(DEBS)TE construct.


Racemization of amino acids in marine sediments.
Isoleucine, one of several amino acids isolated from a suite of welldated deep-sea cores, shows a progressive increase in the degree of racemization with the age of the sediment. Amino acids in sediments show an initial rate of racemization almost an order of magnitude faster than the rate observed for free amino acids at a comparable pH and temperature. The observed kinetics depend on a variety of diagenetic processes, but it appears that the ratio of alloisoleucine to isoleucine is a reliable indicator of age for samples less than 400,000 years old; for older samples the results are more ambiguous. Isoleucine is racemic in samples older than about 15 x 10(6) years.


Human and ovine amniotic fluid composition differences: implications for fluid dynamics.
The ovine model is frequently utilized to extrapolate data regarding fetal and amniotic fluid dynamics to human pregnancy. The ovine amnion is highly vascularized, facilitating intramembranous exchange of water and solutes between the amniotic fluid and fetal plasma. In comparison, the relatively avascular human amniotic membrane may have a reduced potential for intramembranous absorption. In view of these anatomical differences, we hypothesized that comparison of human and ovine amniotic fluid composition would provide insight into differences in the mechanisms of amniotic fluid exchange. Amniotic fluid was sampled from 43 patients upon hospital admission, and from 27 ovine ewes at five days following amniotic fluid catheter placement. Both human (32 to 39 weeks' gestation) and ovine pregnancies (125 to 136 days' gestation) were sampled during the last 20% of gestation. Samples were analyzed for osmolality and sodium, potassium and chloride concentrations. The contribution of electrolytes to amniotic fluid osmolality and changes in osmolality and electrolyte composition versus gestational age were assessed by regression and covariance analysis. Mean (+/-SEM) amniotic fluid sodium concentration (134.6+/-1.9 vs. 127.1+/-2.0 mEq/1) was greater and potassium (4.6+/-0.1 vs. 6.1+/-0.6 mEq/l) and osmolality (263.9+/-3.7 vs. 285.1+/-1.6 mOsm/kg) less in human than sheep. The range of amniotic fluid osmolality was greater in human (223 to 336 mOsm/kg) than in sheep (274 to 298 mOsm/kg). Human amniotic fluid osmolality was highly correlated with amniotic fluid sodium (r = 0.97) and chloride (r = 0.96) while ovine amniotic fluid osmolality was only weakly correlated with amniotic fluid sodium (r = 0.75) and chloride (r = 0.51). The slope of the regression line of amniotic fluid sodium and osmolality was greater for human than for sheep amniotic fluid (P < 0.0001). The percent of amniotic fluid osmolality accounted for by sodium, chloride and potassium concentrations was greater for human (97%) than for sheep (86%; P < 0.0001). The results suggest that human amniotic fluid osmolality is comprised almost entirely of the major electrolytes while alternative solutes (e.g., fructose) contribute to ovine amniotic fluid osmolality. Extrapolation of fetal and amniotic fluid dynamics from ovine models to humans should incorporate differences in amniotic fluid osmolality and electrolyte composition.


Immunogenicity of recombinant vaccinia virus vaccines co-expressing GP3/GP5 of European PRRSV and Cap protein of PCV2 in pigs.
Porcine reproductive and respiratory syndrome (PRRS) is almost always caused by the North American strain of PRRS virus (PRRSV) in China; the European genotype of PRRSV has emerged in China. The mixed infection of PRRSV and Porcine circovirus type 2 virus (PCV2) are always found in pigs and PRRSV-augmented PCV2 replication and serious clinical symptoms. Current vaccines cannot protect mixed European PRRSV and PCV2 infections. Therefore, the development of a safe and effective new vaccine to prevent and control the mixed infection of European PRRSV and PCV2 is both urgent and necessary. In this study, we developed a recombinant vaccinia vaccine co-expressing the GP3 and GP5 proteins of European PRRSV and the ORF2 protein of PCV2 and evaluated the immunogenicity and its protective effects and its inactivated vaccine in pigs. The recombinant vaccinia vaccine and its inactivated vaccine both elicited significant humoral and cellular immune responses with a higher level of specific antibody responses and T-lymphocyte proliferation than the control group. Furthermore, the pigs inoculated with the recombinant vaccinia vaccine were completely protected against challenge with 105 TCID50 of European PRRSV strain LV. These data suggest that the recombinant vaccinia vaccine is a potential candidate vaccine against European PRRSV and PCV2.


The development and validation of a predictive index for postpartum depression.
A sample of over 6000 women was recruited in the last trimester of pregnancy and administered a 40-item self-report questionnaire designed to detect the presence of factors that were likely to increase the risk of postpartum depression. The mental state of almost 5000 of these women was determined at around 6 to 8 weeks postpartum. By conducting a series of logistic regressions on two-thirds of this sample the original set of variables was reduced to a predictive index of 17 items with weighted scores calculated for each. This index was then applied to the remaining one-third of the sample as a validating procedure and specificity and sensitivity calculated. The index offers a system for the prediction of postpartum depression that could be of use in both research and clinical practice.


Cytokine promoter polymorphisms in severe sepsis.
The need to develop individualized risk profiles and drug therapy regimens motivates interest in genetic studies of critically ill patients. Gene promoter variants may predict interindividual variability in response to inflammatory stimuli, such as infection and trauma. Genomic variations also may affect gene expression profiles, as well as the structure and production of proteins. The genes involved in inflammation are numerous, as are genomic variations within most of those genes. Cytokine genes involved in inflammatory cascades are important candidate genes that may determine the extent of a person's response to injury. Understanding the genetic determination of the inflammatory process includes the possibility of developing valuable diagnostic tools and new therapeutic approaches in severe sepsis. To date, specific patterns of markers of genomic variation reliably indicating at-risk populations do not exist. Evaluation of possible genomic markers for risk stratification of patients with sepsis and persons at high risk of developing organ failure has begun at a level of well-powered genetic epidemiological research. Cytokine promoter variants may contribute substantially to studies of genetic predisposition of sepsis because they operate in a gene region of high regulatory activity.


Liposome-modified titanium surface: A strategy to locally deliver bioactive molecules.
Titanium and its alloys are widely employed materials for implants in orthopedic or dental surgery due to their mechanical properties, resistance to corrosion and osseointegration capability. However adverse reactions at the tissue/implant interface may occur, which limit the success of the osseointegration process. Therefore, different strategies have to be used to overcome these drawbacks. In this work, we developed two different liposome-based coatings on titanium surfaces as drug or bioactive molecule deposits for dental/orthopedic implant applications. The first one is a supported vesicular layer (SVL), obtained by liposome adhesion on passivated Ti surface, the second one is a covalently bonded vesicular layer (CBVL) grafted on properly functionalized Ti. Photoluminescence spectroscopy and atomic force microscopy investigations demonstrated the effective anchoring of intact liposomes in both systems. Cytotoxicity assays, performed after 48h, showed a MG63 cell viability higher than 75% and 70% on SVLs and CBVLs, respectively. Scanning electron microscopy investigation revealed numerous and spread MG63 cells after 48h on SVL modified Ti surface and a lower cell adhesion on samples coated with CBVL. The cellular uptake capability of liposome content was proved by fluorescence microscopy using carboxyfluorescein loaded SVLs and CBVLs. Finally, we demonstrated that these liposome-modified Ti surfaces were able to deliver a model bioactive molecule (phosphatidylserine) to adherent cells, confirming the potentiality of developed systems in bone related prosthetic applications.


Fashioning of aortic isthmoplasty patch. A mathematical model.
Patch enlargement of the aortic isthmus in congenital coarctation of the aorta (aortic isthmoplasty) has been extensively performed since its introduction in 1957. Even after forty years, the size and shape of the prosthetic patch used as an on a graft is still determined, most of the time, empirically through eyeballing. Not infrequently, it has resulted in an ugly looking repaired aortic segment or with a significant residual systolic gradient across it. These twin problems have called for a mathematical model for designing the patch more precisely. The model envisages a patch of the shape of an asymmetric octagon whose cranio-caudal length equals the distance from a point 8 mm on the proximal aorta to a point 8 mm on the distal dilated aorta on either side of the coarcted segment. The side to side length of the patch is determined by first subtracting the circumference of the narrowest part of the coarcted segment from the circumference of the distal dilated portion of the aorta and then adding 4 mm more. The larger slant sides of the octagon are obtained by joining the four smaller sides, of 8 mm in length each. Since July 1993 this mathematical model has been employed in 7 patients to prepare the exact size and the shape of the tightly woven low porosity Dacron patch. In each instance a neat cylindrical aorta was obtained without any measurable post-repair systolic pressure gradient across the repaired site. In view of these very satisfying results, we believe that this mathematical model of tailoring the patch has succeeded in converting the patch-aortoplasty procedure for coarctation of the aorta into a precise and hemodynamically fully corrective operation.


Selection criteria for outpatient group psychotherapy.
A tentative set of selection criteria for referral to outpatient group psychotherapy is outlined. The criteria do not distinguish between different schools of therapy but are organized around indications for referral to heterogeneous and homogeneous groups. Noting that the most common and difficult differential therapeutic decision is choosing between heterogeneous group treatment an individual therapy, or selecting some combination of both, the authors also discuss factors to be considered in making that determination.


Research for leveraging food policy in universal eating disorder prevention.
Policy and legislation have emerged as important levers for universal prevention efforts in the context of eating disorders. However, to date, little attention has been paid to generating research that will inform opportunities to regulate the food environment, specifically the way that food is produced and marketed. The present paper aims to lay out a framework for research that will examine (1) the ways in which food industry may influence risk for eating disorders and (2) the impact of legislative efforts on eating disorder cognitions and behaviors. For these two pathways, specific examples of research that would serve to inform policy efforts aiming to decrease the risk for eating disorders by targeting the food environment are proposed. Overall, the present paper aims to issue a call for the eating disorder field to become involved in food policy and regulation.


Dental pulp cells produce neurotrophic factors, interact with trigeminal neurons in vitro, and rescue motoneurons after spinal cord injury.
Interactions between ingrowing nerve fibers and their target tissues form the basis for functional connectivity with the central nervous system. Studies of the developing dental pulp innervation by nerve fibers from the trigeminal ganglion is an excellent example of nerve-target tissue interactions and will allow specific questions regarding development of the dental pulp nerve system to be addressed. Dental pulp cells (DPC) produce an array of neurotrophic factors during development, suggesting that these proteins might be involved in supporting trigeminal nerve fibers that innervate the dental pulp. We have established an in vitro culture system to study the interactions between the dental pulp cells and trigeminal neurons. We show that dental pulp cells produce several neurotrophic factors in culture. When DPC are cocultured with trigeminal neurons, they promote survival and a specific and elaborate neurite outgrowth pattern from trigeminal neurons, whereas skin fibroblasts do not provide a similar support. In addition, we show that dental pulp tissue becomes innervated when transplanted ectopically into the anterior chamber of the eye in rats, and upregulates the catecholaminergic nerve fiber density of the irises. Interestingly, grafting the dental pulp tissue into hemisected spinal cord increases the number of surviving motoneurons, indicating a functional bioactivity of the dental pulp-derived neurotrophic factors in vivo by rescuing motoneurons. Based on these findings, we propose that dental pulp-derived neurotrophic factors play an important role in orchestrating the dental pulp innervation.


The effects of "cell age" upon the lethal effects of physical and chemical mutagens in the yeast, Saccharomyces cerevisiae.
Yeast cultures progressing from the exponential to the stationary phase of growth showed changes in cell sensitivity to physical agents such as UV light, heat shock at 52 degrees C and the chemical mutagens ethyl methane sulphonate, nitrous acid and mitomycin C. Exponential phree chemicals. The increased resistance of exponential phase cells to UV light was shown to be dependent upon the functional integrity of the RAD50 gene. Treatment of growing yeast cultures with radioactively labelled ethyl methane sulphonate indicated the preferential uptake of radioactivity during the sensitive exponential stage of growth. The results indicated that the differential uptake of the chemical mutagens was responsible for at least a fraction of the variations in cell sensitivity observed in yeast cultures at different phases of growth.


Photic regulation of c-fos gene expression in the suprachiasmatic nucleus and the circadian rhythm of photosensitivity in the mink.
The relationship between the photic stimulation of the c-fos gene product in cells of the suprachiasmatic nuclei and the photoperiodic control of testicular activity were examined in mink. Mink were kept in a short photoperiod (control, LD4:20), or in 'asymmetric skeleton photoperiods' (groups A and B). The light period for groups A and B was divided into two fractions (3 h 30 min and 30 min); the shorter fraction occurred in the night, 4 h (group A) or 8 h (group B) after the end of the main light period. There was no photic activation of the proto-oncogene c-fos on the control or group A, and 4 weeks on this photoperiodic treatment produced marked testicular development. In contrast, in group B, c-fos mRNA was induced 30 min after the end of the secondary photofraction, was maximal 30 min later and then decreased. Fos-like immunoreactivity was detected 2 h after the end of the secondary photofraction, with activity peaking 1 h later. The animals of this group remained sexually quiescent. These results suggest that photo-induction of the proto-oncogene c-fos is implicated in the gonadal inhibition induced in this species when the light period, extends into the photosensitive phase of the circadian rhythm of photosensitivity.


Microwave selective effect: a new approach towards oxygen inhibition removal for highly-effective NO decomposition by microwave catalysis over BaMn(x)Mg(1-x)O3 mixed oxides at low temperature under excess oxygen.
A significant microwave selective effect on oxygen inhibition removal was found for NO decomposition through microwave catalysis over BaMn(x)Mg(1-x)O3 catalysts. Especially, the NO conversion and N2 selectivity were up to 99.8% and 99.9%, respectively for the BaMn(0.9)Mg(0.1)O3 catalyst even with the coexistence of 10% oxygen and low temperature of 250 °C.


Fractionated epibulbar I-125 plaque radiotherapy for recurrent mucoepidermoid carcinoma of the bulbar conjunctiva.
A patient with recurrent conjunctival mucoepidermoid carcinoma was treated successfully with surgical excision of the tumor and fractionated epibulbar I-125 plaque radiotherapy. Local excision with fractionated epibulbar plaque radiotherapy is an effective means of eradication in select cases of recurrent mucoepidermoid carcinomas of the conjunctiva. This treatment may avoid more aggressive surgical treatment and preserve vision.


[Automated Cell Counting Using "Deep Learning" in Donor Corneas from Organ Culture Achieves High Precision and Accuracy].
Human corneal grafts from organ culture need to have more than 2000 endothelial cells/mm2 to be suitable for transplantation. Measurement of the endothelial cell density is complicated by invisible cell borders in phase contrast microscopy, as well as by limited areas for counting due to folds in the Descemet membrane of the swollen corneal grafts. To date, no automated counting method for measuring the endothelial cell density exists. The neuronal network U-Net has already proven itself in automated segmentation of specular microscopy images of human corneal endothelium. The aim of this study was the application of the U-Net in the quality control of human corneal grafts. Training of the U-Net was performed using 100 manually tagged endothelial cell images of corneal grafts from the Lions eye bank in Baden-Württemberg. Another 100 images were obtained for testing the precision of measurements of the U-Net. These were adjudged manually by a) an experienced investigator and b) a less experienced ophthalmologist. The endothelial cells in identical images were then counted automatically by the trained U-Net. Comparison with the manually counted results was drawn by Pearson correlation. The correlation coefficient between the U-Net and the experienced investigator as gold standard was 0.9. The correlation coefficient between the less experienced ophthalmologist and the gold standard was only 0.81. Both correlations were statistically highly significant (p < 0.0001). The strong correlation between the U-Net and the gold standard points out that, given medical approval, effective assistance for eye banks is possible in quality control by automated counting. This could improve objectivity and efficiency of work flow.


Structured diagnostic and treatment approach versus the usual primary care approach in patients with gastroesophageal reflux disease: a cluster-randomized multicenter study.
To compare the clinical outcomes of gastroesophageal reflux disease (GERD) patients treated with an implemented new structured pathway (NSP) or according to existing local clinical practices [old clinical pathway (OCP)]. GERD is a major challenge at the primary care level. Primary care centers (n=24) were cluster randomized to handle patients suffering from symptoms suggestive of GERD according to the NSP (n=97) or the OCP (n=134). In the NSP, the GerdQ questionnaire score was used both for diagnosis and management including treatment. We used validated questionnaires to evaluate disease symptoms, quality of life, and costs at inclusion and at follow-up 2 to 6 months later. On the basis of the Reflux Disease Questionnaire, 56% of the patients treated with the NSP reported total symptom relief at the follow-up compared with 33% in the OCP group (P=0.0013). The reflux symptoms after treatment affected daily activities to a lesser extent in the patients in the NSP group compared with the OCP group (10% vs. 13%, respectively, P=0.01). The utility score of the EuroQoL-5D questionnaire improved more in the NSP group than in the OCP group (0.05 vs. 0.02, respectively, P<0.001). The patients in the NSP group had an approximately 50% lower average total cost for GERD-related health care resources compared with the OCP group [301 Swedish Kronor (SEK) vs. 588 SEK, respectively, NS]. The management of GERD patients in primary care centers using a structured clinical pathway and the results of the GerdQ improves the clinical outcome compared with prevailing local routines (NCT00842387).


Updating reactivated memories in infancy: II. Time passage and repetition effects.
Previous attempts to modify a reactivated memory by passively exposing infants to a novel cue immediately after reactivation were unsuccessful. Presently, we examined other conditions in which passive exposure to a novel cue immediately after reactivation might modify the memory. In three experiments, sixty-two 3-month-olds learned to move a distinctive mobile by kicking, forgot the training memory, and then received a reminder that reactivated it. Immediately afterward, they were passively exposed to a novel mobile. We found that passive exposure to novel information could modify reactivated memories that were older or had been reactivated before. Although exposure to a novel mobile occasionally produced only retroactive interference, memory modification never occurred alone, suggesting that response suppression to the original cue is prerequisite for the modification of reactivated memories. We propose that memory distortion (modification) is not an anomaly but is an adaptive, updating mechanism that ensures that behavior will be guided by memories containing contemporaneous information.


Rapid identification of 2009 H1N1 influenza A virus using fluorescent antibody methods.
Identification of the 2009 H1N1 influenza A virus requires emergency use authorized (EUA) molecular reverse transcriptase-polymerase chain reaction. Laboratories lacking molecular capabilities outsource testing, which is costly and may delay result reporting. A fluorescent antibody (FA; D(3) Ultra 2009 H1N1 influenza A virus ID Kit, Diagnostic Hybrids, Athens, OH) recently received Food and Drug Administration EUA status for 2009 H1N1 virus identification. The performance of this FA reagent was evaluated in this study. Influenza A-positive nasopharyngeal specimens (seasonal H1, H3, and 2009 H1N1) were prepared for culture and FA testing and were stained using influenza A antibodies and the 2009 H1N1 reagent. Other respiratory viruses were also evaluated. The FA reagent demonstrated 100% sensitivity and specificity. Bright, apple-green fluorescence was effortlessly identified in culture-positive cells, particularly around cell membrane perimeters. Laboratory-prepared slides were preferred over bedside-prepared specimens because background fluorescence obscured identification in the latter. The new FA reagent provides an accurate, rapid, and inexpensive assay for identifying the 2009 H1N1 virus in nonmolecular diagnostic laboratories.


Evidence for a direct hepatotrophic role for insulin in the fetal rat: implications for the impaired hepatic growth seen in fetal growth retardation.
Perturbations of fetal growth produce parallel but disproportionate changes in fetal liver growth that correlate with circulating fetal insulin concentration. We have studied the effects of insulin and two hepatotrophic factors, transforming growth factor-alpha (TGF alpha) and hepatocyte growth factor (HGF), on DNA synthesis by fetal and adult rat hepatocytes in primary culture. Using serum-free Minimum Essential Medium, fetal hepatocytes synthesized DNA without growth factors, unlike adult hepatocytes. Insulin augmented fetal hepatocyte DNA synthesis after 16-24 h in culture. In contrast, TGF alpha or HGF maximally stimulated fetal hepatocyte DNA synthesis after 40 h in culture. Insulin and TGF alpha were not synergistic in stimulating fetal hepatocyte DNA synthesis, but were synergistic in their action on adult hepatocytes. Brief (10-min) exposure of fetal hepatocytes to TGF alpha or HGF, but not insulin, activated mitogen-activated protein kinases 4-fold. Prolonged (24-h) exposure to TGF alpha or HGF abolished the ability of either to activate mitogen-activated protein kinases, whereas insulin had no effect. Maternal fasting for 48 h before isolation and culturing of fetal hepatocytes abolished the in vitro stimulation of DNA synthesis by insulin without affecting TGF alpha action. We conclude that insulin has growth-promoting actions on fetal hepatocytes that are distinct and independent from those of TGF alpha of HGF.