Understanding who benefits most from cognitive rehabilitation for multiple sclerosis: A secondary data analysis.

BACKGROUND: Up to 70% of people with multiple sclerosis (MS) experience cognitive difficulties. Cognitive rehabilitation is a type of therapy that helps manage cognitive problems. OBJECTIVE: The Cognitive Rehabilitation for Attention and Memory in MS (CRAMMS) trial showed some evidence of effectiveness of cognitive rehabilitation in improving cognitive function, with some participants benefitting more than others. We therefore conducted a secondary analysis of the CRAMMS data to understand who benefits most. METHODS: We grouped baseline data into four categories of possible predictors. We used regression models to identify specific factors/characteristics that could predict the likelihood that an individual will benefit from cognitive rehabilitation. RESULTS: The models predicted whether a participant improved or did not improve in neuropsychological function following cognitive rehabilitation in up to 86% of participants. Results suggest that younger participants with medium to high education, diagnosed with relapsing-remitting multiple sclerosis (RRMS) and primary-progressive multiple sclerosis (PPMS) who have not experienced any recent relapses, with mild to moderate cognitive difficulties were most likely to benefit from cognitive rehabilitation. CONCLUSION: We can predict which participants are most likely to demonstrate significant improvements in neuropsychological function following group-based cognitive rehabilitation. Clinically, this allows us to optimise limited neuropsychology resources by offering such cognitive rehabilitation to those most likely to benefit.

The need for accredited training in gynaecological oncology: a report from the European Network of Young Gynaecological Oncologists (ENYGO).

BACKGROUND: Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbach's-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.

A High-Pressure Polymorph of Troilite, FeS.

A new polymorph of FeS was produced in a diamond-anvil cell and observed at high pressure both optically and by x-ray diffraction. Fourteen x-ray reflections of the high-pressure FeS were recorded; however, the crystal structure is unknown. This form of FeS is stable at 25 degrees C only at pressures above approximately 55 kilobars. The transition to the lower pressure polymorph, troilite, is rapid and reversible.

Allan hills 77005: a new meteorite type found in antarctica.

The unique achondrite ALHA 77005 appears to be related to shergottite meteorites through igneous differentiation and may have affinities with mafic rocks on the earth.

Oxygen isotopes and the moon-forming giant impact.

We have determined the abundances of 16O, 17O, and 18O in 31 lunar samples from Apollo missions 11, 12, 15, 16, and 17 using a high-precision laser fluorination technique. All oxygen isotope compositions plot within +/-0.016 per mil (2 standard deviations) on a single mass-dependent fractionation line that is identical to the terrestrial fractionation line within uncertainties. This observation is consistent with the Giant Impact model, provided that the proto-Earth and the smaller impactor planet (named Theia) formed from an identical mix of components. The similarity between the proto-Earth and Theia is consistent with formation at about the same heliocentric distance. The three oxygen isotopes (delta17O) provide no evidence that isotopic heterogeneity on the Moon was created by lunar impacts.

American health care paradox-high spending on health care and poor health.

BACKGROUND: For decades, US taxpayers have been lamenting the high cost of health care. Since the mid-1980s, Americans have had double-digit spending on health care. Despite this investment, Americans are less healthy than their European and Scandinavian counterparts across an array of health measures. AIM: We sought to explore how inadequate attention to the social, behavioral and environmental determinants of health may contribute to the American health care paradox of high health care spending and poor health outcomes. DESIGN: Mixed methods. METHODS: We report previous findings related from a 10-year analysis of national-level health and social service spending and health outcome data from the Organization of Economic and Cooperation and Development (OECD). We also put forth case studies representing different socioeconomic strata to illustrate the relationship between health care and social service spending and health. RESULTS: Although the US spending more of its GDP on health care than any other country, it is not a high spender when one sums spending on both health care and social services. The U.S. however has the lowest ratio of our social service spending to health care spending in the OECD, and countries with lower ratios on average have worse health outcomes. Cases from diverse socioeconomic strata demonstrate how limited attention to the social determinants of health can result in extremely high health care costs and poor health outcomes. CONCLUSIONS: Greater investment in addressing the social, behavioral and environmental determinants of health may foster better health without accelerating health care costs in America.

Comparative analyses of tooth wear in free-ranging and captive wild equids.

REASONS FOR PERFORMING STUDY: Captive breeding has played a crucial role in the conservation of threatened equid species. Grazing ruminants and rhinoceros in captivity have less abrasion-dominated tooth wear than their free-ranging conspecifics, with potential negative consequences for their health. However, a similar study on wild equids in captivity is missing. OBJECTIVES: The aim was to establish if different tooth wear patterns are exhibited by free-ranging and captive equids. STUDY DESIGN: Cross-sectional study of museum specimens comparing free-ranging and captive equids. METHODS: Dental casts of maxillary cheek teeth of 228 museum specimens (122 from free-ranging and 106 from captive individuals) of 7 wild equid species were analysed using the extended mesowear method. Although teeth showing specific abnormalities were not scored, the presence of focal overgrowths (hooks) of the rostral premolars (106, 206) was recorded. RESULTS: Captive Equus ferus przewalskii, E. grevyi, E. hemionus, E. quagga boehmi and E. zebra hartmannae have less abrasion-dominated tooth wear on their premolars than their free-ranging conspecifics (P<0.001). Fewer differences were exhibited between populations in the molars. No differences were exhibited in the distal cusp of the molars (110, 210) between populations, except in a small sample of E. kiang. Captive equids exhibited more homogeneous wear along the tooth row whereas free-ranging equids exhibited a tooth wear gradient, with more abrasion on premolars than molars. There were more rostral hooks on the premolars (106, 206) in the captive than the free-ranging population (P = 0.02). CONCLUSIONS: Captive equids did experience less abrasion-dominated tooth wear than their free-ranging conspecifics, but the differences in tooth wear were less pronounced than those between captive and free-ranging wild ruminant and rhinoceros species. This indicates that feeding regimes for captive equids deviate less from natural diets than those for captive ruminants and rhinoceros but that factors leading to hook formation, in particular feeding height, should receive special attention. The Summary is available in Chinese - see Supporting information.

Differential inhibition of indirect immunofluorescence in rat liver sections incubated with antibodies against microsomal cytochromes P-450a, b, and c and epoxide hydrolase.

Rat liver sections were incubated with antibodies (100-1000 micrograms IgG/ml) against microsomal cytochromes P-450a, P-450b, and P-450c, and epoxide hydrolase. Inhibition of indirect immunofluorescence, which progressed with higher concentrations of primary antibody, corresponded with antigen-enriched tissue in frozen liver sections from male and female rats. It was found in liver sections from phenobarbital-treated rats incubated with anti-P-450b and anti-epoxide hydrolase and from 3-methylcholanthrene-treated rats incubated with anti-P-450c. No inhibition was found in sections from untreated rats or rats receiving treatments that did not induce the specific antigen. No inhibition was found in sections incubated with anti-P-450a. Inhibition of immunofluorescence was abolished in frozen sections subjected to dehydration-rehydration protocols known to extract antigens, and was prevented by certain solvents and detergent-wash. Inhibition of immunofluorescence provides a unique method for confirming the antigen-rich regions of the liver lobules specific for microsomal expoxide hydrolase and the cytochrome P-450s.

The expression of the proteins of equine herpesvirus 1 which share homology with herpes simplex virus 1 glycoproteins H and L.

Several expression systems were used in studies aimed at characterizing the equine herpesvirus 1 (EHV-1) glycoprotein H and L homologues of HSV-1 (EHV-1 gH and gL) and the products were compared to the authentic proteins synthesized in virus infected cells. Using an in vitro transcription/translation system two gH species were detected (an unprocessed 89 kDa and a processed 116 kDa product). Three low molecular weight proteins were found in the case of gL (21.8 kDa, 22.9 kDa and 26.9 kDa) and these showed a slight reduction in mobility on the addition of microsomal membranes to the reactions. A gL fusion protein was produced in pGEX-2T, expression being confirmed by Western blotting using a gL-specific antiserum raised against a peptide incorporating the 13 carboxyl terminal amino acids of the protein. A gH specific peptide antiserum precipitated both gH and two smaller proteins from EHV-1 infected cells thought to be two forms of gL. Insect cells infected with gH or gL baculovirus recombinants were used to vaccinate C3H (H-2k) mice. Some protection against EHV-1 infection was conferred to the gH inoculated mice. The results will enable further studies on the importance of the gH and gL interaction in the pathogenesis of EHV-1 to be evaluated and their potential in contributing to a subunit vaccine to be assessed.

Sodium cholate extraction of rat liver nuclear xenobiotic-metabolizing enzymes.

DNA is the purported target of several carcinogenic and mutagenic agents. Nuclear enzymes which could generate or detoxify reactive metabolites are of major concern. Several such enzymes have been identified within nuclei, but obtaining samples with enriched content or activity is difficult, time-consuming, and uses harsh isolation techniques. Extraction of rat liver nuclear suspensions with cholate-containing buffer results in solubilization of 25-30% of the protein. Linear extraction was obtained for total protein and cytochromes P-450 and b5, NADPH-cytochrome P-450 reductase, NADH-cytochrome b5 reductase, DT-diaphorase, and microsomal-like epoxide hydrolase with specific activities comparable to values reported for isolated nuclear membrane, while the yield was five to ten times greater. Detergent extracts of rat liver nuclei were employed to study the comparative response of microsomal and nuclear enzymes to chemical treatment. While the responses to acute inductive (phenobarbital and 3-methylcholanthrene) and toxic (carbon tetrachloride and dibromochloropropane) treatments were qualitatively similar, an initiation-promotion protocol (diethylnitrosamine with phenobarbital promotion) resulted in divergent responses between the enzymes in the two subcellular fractions. Detergent extracts of nuclei offer an efficient means of recovering xenobiotic-metabolizing enzymes from rat liver nuclei, and have been utilized to demonstrate a differential response of nuclear enzymes during preneoplastic development.

Haloperidol inhibits maternal retrieval and licking, but enhances nursing behavior and litter weight gains in lactating rats.

Abstract To determine whether the motorically-active and -inactive components of maternal behavior in rats are differentially affected by dopamine, we administered haloperidol, a dopamine receptor antagonist, to lactating rats on day 7 (+/-1) post-partum, 3 h after dam-litter separation and 1 h before their reunion. Compared to treatment with saline or domperidone, a peripherally-active dopamine antagonist, haloperidol treatment inhibited retrieval and licking of pups in a dose-dependent manner and hastened the onset of nursing behavior, but impaired the high crouch posture at the highest doses (8 and 10 mg/kg). Also, litters of dams treated with 0.2, 0.4, or 1.0 mg/kg haloperidol gained almost twice as much weight as litters of controls or of dams treated with 5 to 10 mg/ kg haloperidol. To determine whether the milk ejection pattern accounts for differential litter weight gain after moderate and high doses of haloperidol, milk ejections were assessed by pup stretch and nipple-switching responses for 30 min after the onset of crouching following a 4 h dam-litter separation on day 12 or 13 post-partum. The litters of dams treated with 1 or 3 mg/kg haloperidol had substantially greater litter weight gains than litters of control dams or of dams treated with 5 mg/kg haloperidol. The smaller litter weight gain of 5 mg/kg haloperidol litters was due to a retardation of milk ejections in their dams, while the smaller gain of control litters was due, at least in part, to greater behavioral activation by their dams. Non-dopaminergic effects of large doses of haloperidol (>/=5 mg/kg) may have reduced the display of the high crouching posture during nursing and contributed to the retardation of milk ejections. Thus, dopamine is necessary for the motorically-active components of maternal behavior, but its inhibition may be necessary for the assumption of the immobile nursing postures and for maximal litter weight gains. We hypothesize that extra-hypothalamic as well as tuberoinfundibular dopaminergic systems are inactivated by the suckling stimulus.

Felbamate, a novel antiepileptic drug, reverses N-methyl-D-aspartate/glycine-stimulated increases in intracellular Ca2+ concentration.

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel, orally active anticonvulsant that has recently been approved for the treatment of Lennox-Gastaut syndrome and partial onset seizures in the United States. Felbamate is active in a broad range of animal anticonvulsant tests. Although its mechanism of action has yet to be fully elucidated, felbamate appears to act by inhibiting the spread of seizures and elevating seizure threshold. One proposed mechanism of action for felbamate is via the NMDA receptor complex. Previous studies have demonstrated the ability of felbamate to inhibit glycine binding at the NMDA receptor complex. The present study examined the effects of felbamate on NMDA/glycine-stimulated increases in intracellular calcium (Ca2+) using cultured rat hippocampal neurons. The results of these experiments demonstrate that felbamate inhibits NMDA/glycine-stimulated increases in intracellular Ca2+ with a minimal effective concentration of 100 microM.

Distribution of muscarinic receptor subtypes in rat brain from postnatal to old age.

In an effort to understand the developmental changes in the distribution of muscarinic receptor subtypes (m1-m5), specific brain regions from juvenile (16-day-old), young (21-day-old) and adult (90-day-old) rats were analyzed using subtype-selective antibodies. These studies revealed significant age-dependent changes in the four brain regions examined. In cortex, an area associated with higher cognitive functions, significant increases of m2 and m4 receptors occurred between juvenile and adult rats. In the striatum, the level of m4 receptor increased with age whereas the m1, m2 and m3 receptors had reached mature levels within the first 16 days. Small but significant changes occurred in the cerebellum with a decrease in m1, m3 and m4 receptor subtypes. In contrast to other brain regions, the hippocampus displayed consistent expression levels of muscarinic receptor subtypes. Suggesting that this brain region, which is involved in the foundation of numerous neural networks, requires a full complement of muscarinic receptors at a very early age. Muscarinic receptors have been shown to be important in a number of behavioral activities, including learning and memory. The changes observed in the age-dependent expression of these receptors most likely play an important role in how acetylcholine produces its effects in vivo.

Intraseptal injection of GABA and benzodiazepine receptor ligands alters high-affinity choline transport in the hippocampus.

Injection of GABA and benzodiazepine (BDZ) agonists and antagonists into the medial septum produced bidirectional alterations in hippocampal high-affinity choline transport (HAChT). Male Sprague-Dawley rats were injected in the medial septum with either drug vehicle, a BDZ agonist, antagonist, or inverse agonist, or with a GABA-A or GABA-B agonist or antagonist and sacrificed 1 h later for assessment of HAChT in hippocampal synaptosomes. The GABA-A agonist muscimol, the GABA-B agonist baclofen, and the BDZ agonist chlordiazepoxide (CDP) produced dose-related decreases in HAChT 1 h following injection into the septum. The muscimol-induced decrease in HAChT was prevented by prior intraseptal injection of the GABA-A antagonist, bicuculline. Intraseptal injection of GABA-A (bicuculline) or GABA-B (2-hydroxysaclofen) antagonists did not alter HAChT, whereas the BDZ antagonist flumazenil (RO15,1788) and the BDZ inverse agonist methyl-beta-carboline-3-carboxylate (beta-CCM) increased this measure up to 30% in a dose-dependent manner. These results demonstrate that cholinergic neurons in the medial septum can be modulated in a bidirectional way through the pharmacological manipulation of GABA-A, GABA-B, and BDZ receptors. The potential functional and therapeutic consequences of these interactions are discussed.

The binding of SCH 39166 and SCH 23390 to 5-HT1C receptors in porcine choroid plexus.

SCH 39166 is a novel benzonaphthazepine, which has been characterized as a potent and selective D1 antagonist. Recently, its D1 selective benzazepine predecessor, SCH 23390, has been shown to bind to 5-HT1C binding sites in the choroid plexus. Therefore, the present studies were undertaken to determine if SCH 39166 has any measurable affinity for 5-HT1C binding sites. Our results indicate that SCH 39166 exhibited poor affinity for the 5-HT1C receptor, with a Ki of 1327 nM. In contrast, SCH 23390 inhibited [3H]-mesulergine binding to 5-HT1C receptors with a Ki of 30 nM. The non-selective 5-HT antagonist, methysergide, inhibited binding with a Ki of 2.4 nM. Finally, studies with the stereoisomers of SCH 39166 and SCH 23390 demonstrated that stereoselectivity at the 5-HT1C site is significantly less than for the D1 site.

SCH 57790: a novel M2 receptor selective antagonist.

As a decrease in cholinergic neurons has been observed in Alzheimer's Disease (AD), therapeutic approaches to AD include inhibition of acetylcholinesterase to increase acetylcholine levels. Evidence suggests that acetylcholine release in the CNS is modulated by negative feedback via presynaptic M2 receptors, blockade of which should provide another means of increasing acetylcholine release. Structure-activity studies of [4-(phenylsulfonyl)phenyl]methylpiperazines led to the synthesis of 4-cyclohexyl-alpha-[4-[[4-methoxyphenyl]sulfinyl]-phenyl]-1-piperazin eacetonitrile. This compound, SCH 57790, binds to cloned human M2 receptors expressed in CHO cells with an affinity of 2.78 nM; the affinity at M1 receptors is 40-fold lower. SCH 57790 is an antagonist at M2 receptors expressed in CHO cells, as the compound blocks the inhibition of adenylyl cyclase activity mediated by the muscarinic agonist oxotremorine. This compound should be useful in assessing the potential of M2 receptor blockade for enhancement of cognition.

Characterization of the binding of SCH 39166 to the five cloned dopamine receptor subtypes.

Characterization studies were conducted on the five cloned dopamine receptor subtypes (D1-D5) using the novel D1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D1 and D5 receptors, but binds with low affinity to the D2, D3, and D4 receptors. In contrast, the D2 antagonist haloperidol showed low affinity for the "D1-like" receptors and high affinity for the "D2-like" receptors. A series of agonists was also evaluated and the D5 receptor subtype displayed a two-site fit for the endogenous agonist dopamine, as well as for the agonist apomorphine. Differences in agonist binding among the D1-like receptors reflect the importance of the nonconserved amino acid substitutions.

Chronic lung disease is the leading risk factor correlating with the failure (wrap disruption) of antireflux procedures in children.

Recurrent gastroesophageal reflux (GER) after antireflux procedures (ARP) has been correlated with significant neurological impairment (NI). Other major risk factors for recurrent GER have not been extensively characterized. The authors reviewed their experience with ARPs in children to better characterize the risk factors for recurrent GER and identify successful management strategies for these patients. The charts of 281 consecutively treated children who had an ARP at our institution (1985 to 1992) were reviewed. The neurological status of each child was assessed as normal or impaired (cerebral palsy, seizures, mental retardation, spasticity), and other medical diagnoses such as chronic pulmonary disorders (eg, interstitial disease, cystic fibrosis, bronchopulmonary dysplasia, asthma, etc), and congenital malformations and syndromes were identified. The average follow-up period was 3 years (range, 1 to 7.5 years). Patients with symptoms of recurrent GER were evaluated with an upper gastrointestinal study. Patients with a radiologically intact fundoplication and suspected GER were further evaluated with a 24-hour pH probe. Statistical analyses were performed using the Fisher's Exact Test. Of the 281 patients who underwent ARP, 39 had documented recurrent GER (average, 16 months after surgery). Twenty-five (64%) of these children had chronic pulmonary disease (CPD). Thirty-two percent of all children with CPD had recurrent GER after ARP, versus 7% of those without CPD (P < .0001). For children with NI and CPD there was an increased risk (P < .0001) of failure when compared with the risk in the normal subgroup (children without CPD or NI) who underwent ARP.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous translumbar and transhepatic inferior vena caval catheters for prolonged vascular access in children.

Central venous access for children with caval occlusion remains a major challenge to pediatric surgeons. Traditionally, children with superior and inferior vena cava (SVC, IVC) thrombosis have often required a thoracotomy to directly cannulate the azygos system or right atrium (RA). Recently, the possibility of placing tunneled RA catheters (RACs) by a percutaneous translumbar or transhepatic approach has become available. We report our experience of seven children with SVC and IVC obstruction who have received 11 transhepatic and 4 translumbar RACs from 1987 to 1991. All but one child was less than 2.5 years old and all were chronically dependent on parenteral nutrition. All catheters were placed in the angiography suite under general anesthesia using ultrasound guidance and Seldinger technique. This technique was successful in all seven children. Perioperative complications included accidental extubation in one patient and aspiration pneumonia in another. Mechanical complications requiring RAC replacement occurred 5 times in three infants (greater than 2,650 catheter days) and included catheter dislodgement (2) and thrombosis (3). In the patients with catheter thrombosis, the existing tract was successfully wired and the catheter exchanged on three occasions. Thrombolytic therapy was effective in restoring catheter patency on three other occassions. Nine episodes of catheter sepsis occurred in five children. Two late deaths occurred from infection. Of the five remaining children, four are dependent on total parenteral nutrition and have a translumbar or transhepatic catheter in situ and one child has adapted successfully to enteral feedings. Percutaneous translumbar or transhepatic IVC catheters provide excellent alternative routes for prolonged central venous access in those patients whose traditional vascular access sites are no longer available. Complications of the technique itself were minimal and although late catheter complications were not infrequent, they appear to be comparable to the standard approaches reported.

Haematuria and abdominal aortic aneurysm.

Haematuria and left loin pain in a patient with abdominal aortic aneurysm and associated with the radiological finding of a poorly or non-functioning left kidney are the pathognomonic features of aorto-left renal vein fistula, a condition in which the aneurysm leaks into an anomalous retro-aortic left renal vein.