The experiences and needs of persons with spinal cord injury who can walk.
The purpose was to explore the experiences and needs of persons with spinal cord injury (SCI) who can walk. Thematic analysis was undertaken on the transcripts of semistructured interviews with 12 individuals who could walk following SCI. Experiences shared across the group were related to walking in hospital and community settings, fatigue, frustration and invisible impairments. A need was identified for psychological support whilst in hospital and beyond. Professional and peer support following discharge from hospital were needed to assist with adjusting to their injury. Differences were noted between the experiences and needs of persons who had sustained their injury through a traumatic cause and persons who had sustained their injury through nontraumatic cause and the rehabilitation environment in which participants were hospitalized. The lived experiences of the general cohort in this small-scale study suggest that innovative strategies/programs be developed to address the needs of walkers within inpatient settings and following their discharge into the community. Programs should include self-help mental health strategies. Programs are required to better inform health professionals of the needs of this subset of the spinal cord injured population. Attention should be drawn particularly towards the needs of persons who had sustained their injury through nontraumatic cause.


Assessment and Clinical Decision-Making During Imminent Death in Hospice Music Therapy.
Assessment is a critical aspect of treatment planning, and while there exist standards for facilitating music therapy assessments in a variety of clinical settings, no such standards exist for music therapists in hospice and palliative care. This gap in knowledge, which limits music therapists' ability to provide patients and caregivers best practices promoting supported movement through the dying process, becomes particularly problematic when assessing patients who are imminently dying with a 24-72 hour prognosis. To further develop and define assessment and clinical decision-making processes used by music therapists in hospice and palliative care, the authors used a constructivist grounded theory and situational analysis methodology to analyze interviews of 15 hospice music therapists. The resulting theoretical model describes an ongoing process of assessment and clinical decision-making shaped by participants' individual epistemologies. Epistemologies were comprised of 5 ways of knowing, which were termed experiential, personal, musical, ethical, and integral, and provided participants critical foundations for their practice. The results support a development of a model for reflective practice as well as continued research on epistemological foundations of clinical practice.


Frequency-domain measurement of neuronal activity using dynamic optical coherence tomography.
We report preliminary results on high-resolution in vivo imaging of fast intrinsic optical signals of neuronal activity in the frequency domain. An optical coherence tomography (OCT) system was used for dynamic imaging of the cross section of rodent somatosensory cortex at 250 frame/s. Neurons in the cortex were excited by contralateral forepaw stimulation, and the ipsilateral forepaw was stimulated as a control. Hemodynamic responses at the cortical surface, which were simultaneously measured using a CCD, confirmed that forepaw stimulation properly evoked neuronal activation. Analysis of the OCT signal in the frequency domain resulted in that the spectrum significantly increased at the stimulation frequency during activation. This spectrum change was only observed during contralateral stimulation and highly localized at the stimulation frequency in the frequency space. Therefore, the spectrum change we observed is likely associated with neuronal activation.


Circular dichroism of oligosaccharides containing neuraminic acid.
In order to test the usefulness of circular dichroism in stereochemical and structural studies of oligosaccharides of glycoproteins, we measured the circular dichroism (CD) for N-acetylneuraminic acid (NAcNA) and several derivates. By acidic mathanolysis, we have prepared the deacetylated methyl ester, methyl glycoside of NAcNA, as well as a saponified product. Circular dichroism of these compounds allows us to assign the transition due to the amide chromophore. There is a carboxyl n-pi transition at about 220 nm which has a negative CD band associated with it for the beta-methocyneuraminic acid, but changes sign for the methyl ester (methyl (methyl beta-D-neuraminid)ate). We isolated the trisaccharides N-acetylneuraminyl-(2 leads to 3)-beta-D-galactopyranosyl-(1 leads to 4)-D-glucopyranose [(2leads to 3)NAcN-Lac] as well as (2 leads to 6)NAcN-Lac by paper chromatography and compared the CD for each. The two isomers show similar but distinguishable CD patterns, with a weak negative band due to the carboxyl group centered at 225 nm and a stronger positive band at 200 nm containing contributions from both the amide and carboxyl groups.


[Fatty acids in confectionery products].
The content of fat and fatty acids in 144 different confectionery products purchased on the market in Warsaw region during 1997-1999 have been investigated. In examined confectionery products considerable variability of both fat and fatty acids content have been found. The content of fat varied from 6.6% (coconut cookies) up to 40% (chocolate wafers). Saturated fatty acids were present in both cis and trans form. Especially trans fatty acids reach (above 50%) were fats extracted from nut wafers, coconuts wafers.


Patterns and prognostic value of total and differential leukocyte count in chronic kidney disease.
The purpose of this study was to evaluate the levels and patterns of total and differential leukocyte counts and their prognostic importance in a cohort of people with and without chronic kidney disease (CKD). Among 153 veterans without CKD and 267 with, blood leukocyte count was measured at baseline and then repeatedly over a decade. The patterns of change in leukocyte count between the two groups were compared. In the CKD cohort, the spikes in leukocyte counts were compared to the combined endpoint of ESRD and death. Patients with CKD had more granulocytes and eosinophils and fewer lymphocytes. Over time, granulocytes increased and lymphocytes decreased in those with and without CKD. In addition, in those with CKD, over time eosinophils fell and monocytes increased. Compared with their non-CKD counterparts, patients with CKD had between 1.5- and 3.0-fold more spikes in leukocyte counts. Independent risk factors for the combined endpoint were associated with spikes in the leukocyte counts of absolute and percent eosinophil count, percent granulocyte, and percent monocyte counts. In a multivariate adjusted joint model, both granulocyte and monocyte spikes were independently associated with ESRD and death (hazard ratio 1.67 and 1.52 respectively, P < 0.05). Compared with those without CKD, patients with CKD have more eosinophils and granulocytes and fewer lymphocytes. Greater variation in leukocytes is seen. Spikes in granulocyte and monocyte percentages among patients with CKD are of independent prognostic importance.


Use of a nasal bridle prevents accidental nasoenteral feeding tube removal.
Reinserting feeding tubes that are accidentally removed exposes patients to risk and consumes hospital resources. We were interested to know if using a bridle to secure tubes would be more effective than tape at preventing accidental tube removal. This was a quality improvement project with a before-and-after design. Between May 2007 and August 2007, we prospectively followed 90 tubes (50 tape, 40 bridle). Tubes were followed up daily until accidental tube removal, ICU discharge, or planned tube removal. Our primary endpoint was accidental tube removal. We compared the 2 groups on the following: (1) proportion of tubes accidentally removed; (2) rate of accidental tube removal (per 100 tube-days); and (3) Kaplan-Meier survival analysis. Survival analysis data were right-censored at ICU discharge or planned tube removal. There were no significant differences between groups in any demographics. The proportion of tubes accidentally removed was 36% (18 of 50) in the tape group and 10% (4 of 40) in the bridle group; P<.05. The rate of accidental tube removal (per 100 tube-days) was 6.4 (18 in 281 tube-days) in the tape group and 1.6 (4 in 248 tube-days) in the bridle group; P<.05. Survival analysis showed a significant difference between the groups with a log-rank test for equality of survivor function of P<.05. Using a bridle to secure feeding tubes significantly reduces the proportion and rate of accidental tube removal and results in increased tube survival by Kaplan-Meier analysis.


[Preliminary screening for antiviral AIDS drugs. VII. Report for fiscal year 1994].
Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 246 samples of different origin tested, six were shown to inhibit the growth of HIV in vitro. Two of the positive samples have hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.


Predominance of gluconate formation from glucose during germination of Bacillus megaterium QM B1551 spores.
Metabolic pathways of glucose during germination of Bacillus megaterium QM B1551 spores were studied by using specifically labeled glucose and gluconate. The Embden-Meyerhof pathway, the pentose cycle, and the direct oxidation route of glucose to gluconate (the gluconate pathway) were all operative at this stage; among those, gluconate accumulation was most predominant, especially in the early stage. Potassium fluoride, an enolase inhibitor, abolished the catabolism by the Embden-Meyerhof pathway totally without affecting gluconate accumulation. Under these conditions glucose was exclusively oxidized to gluconate. Gluconate thus accumulated could be metabolized further via phosphorylation by gluconate kinase. Remarkable gluconate accumulation was also demonstrated in several other spores requiring alanine as an effective germinant. NADH formed by the direct glucose oxidation may serve as a initial ATP source to phosphorylate glucose in germinating spores.


FosB expression in the central nervous system following isotonic volume expansion in unanesthetized rats.
We examined c-Fos and FosB staining in the central nervous system 8 and 24 h following acute volume expansion in unanesthetized rats. Male rats were instrumented with a femoral artery catheter for measurement of blood pressure and heart rate (HR), a jugular venous catheter for measurement of central venous pressure (CVP), and a femoral vein catheter for i.v. infusion. After 48 h, rats were volume expanded with isotonic saline (10% of body weight for 10 min i.v.) or given a control infusion (0.01 ml/min for 10 min i.v.). After a period of 8 or 24 h, the rats were deeply anesthetized and perfused transcardially with 4% paraformaldehyde. Separate sets of serial sections of the hypothalamus were processed for either FosB (Santa Cruz) or c-Fos (Oncogene AB-5) immunocytochemistry. The volume expansion protocol significantly increased central venous pressure but did not affect blood pressure or heart rate. Volume expansion produced a significant increase in FosB-positive cells in the paraventricular nucleus (PVN) of the hypothalamus, the supraoptic nucleus (SON), the perinuclear zone (PNZ) of the supraoptic nucleus, the nucleus of the solitary tract (NST), and the caudal ventrolateral medulla (CVL) in both the 8- and 24-h groups. In the area postrema (AP), the number of FosB-positive cells was significantly increased only at 8 h post-infusion. However, c-Fos was not significantly increased above control levels at either time point. The results demonstrate that FosB activation is maintained for at least 24 h following an acute increase in central venous pressure.


Solitary vortices supported by localized parametric gain.
We demonstrate the existence and stability of bright vortex solitons sustained by a ring-shaped parametric gain, for both focusing and defocusing Kerr nonlinearities in lossy optical media. With the defocusing nonlinearity, the vortices are stable at all values of the detuning parameter, while under the focusing nonlinearity their stability region is limited to some positive values of the detuning. Unstable vortices in the focusing medium transform into stable rotating azimuthons.


Functional similarity between the haemolysins of Escherichia coli and Morganella morganii.
Haemolysin produced by a clinical isolate of Morganella morganii was examined for antigenic relatedness to the haemolysin of Escherichia coli and for similarities in mode of action. The M. morganii haemolysin migrated in SDS-PAGE as a single protein band with a slightly higher molecular weight than that of E. coli haemolysin. Several murine monoclonal antibodies against E. coli haemolysin cross-reacted with the M. morganii haemolysin in Western blots. Diminished haemolysis in the presence of osmotically-stabilising solutes indicated the formation of a pore by M. morganii haemolysin with an effective diameter of 1.5-3 nm. Results from dose-response experiments indicated that a single "hit" was sufficient for lysis of an erythrocyte. Detergent solubilisation of toxin-treated membranes led to recovery of bound toxin exclusively in monomeric form. M. morganii haemolysin was a potent leucocidin, that caused rapid leakage of ATP and death of human polymorphonuclear leucocytes. Under in-vitro conditions M. morganii haemolysin displayed similar leucocidal and haemolytic efficiency. The data demonstrate that M. morganii haemolysin shows functional properties virtually identical with those of E. coli haemolysin.


Microdissection and Immunofluorescence Staining of Myocardial Sleeves in Murine Pulmonary Veins.
Pulmonary veins (PVs) are the major source of ectopic beats in atrial arrhythmias and play a crucial role in the development and progression of atrial fibrillation (AF). PVs contain myocardial sleeves (MS) composed of cardiomyocytes. MS are implicated in the initiation and maintenance of AF, as they preserve similarities to the cardiac working myocardium, including the ability to generate ectopic electrical impulses. Rodents are widely used and may represent excellent animal models to study the pulmonary vein myocardium since cardiomyocytes are widely present all over the vessel wall. However, precise microdissection and preparation of murine PVs is challenging due to the small organ size and intricate anatomy. We demonstrate a microscopy-guided microdissection protocol for isolating the murine left atrium (LA) together with the PVs. Immunofluorescence staining using cardiac Troponin-T (cTNT) and connexin 43 (Cx43) antibodies is performed to visualize the LA and PVs in full length. Imaging at 10x and 40x magnification provides a comprehensive view of the PV structure as well as detailed insights into the myocardial architecture, particularly highlighting the presence of connexin 43 within the MS.


Dijet imbalance measurements in Au+Au and pp collisions at sqrt[s_{NN}]=200 GeV at STAR.
We report the first dijet transverse momentum asymmetry measurements from Au+Au and pp collisions at RHIC. The two highest-energy back-to-back jets reconstructed from fragments with transverse momenta above 2 GeV/c display a significantly higher momentum imbalance in heavy-ion collisions than in the pp reference. When reexamined with correlated soft particles included, we observe that these dijets then exhibit a unique new feature-momentum balance is restored to that observed in pp for a jet resolution parameter of R=0.4, while rebalancing is not attained with a smaller value of R=0.2.


Determination of trace Para Red residues in foods through on-line molecularly imprinted solid phase extraction coupled with high-performance liquid chromatography.
In this article, we prepared a novel imprinted polymer by a room temperature ionic liquid-mediated surface molecular imprinting technique in combination with a sol-gel process. This polymer was characterized by static and kinetic adsorption experiments and exhibited good recognition ability and offered fast kinetics for the adsorption of Para Red. A simple and sensitive analytical method, based on the coupling of molecularly imprinted solid phase extraction with high-performance liquid chromatography (HPLC), had been developed for determination of trace Para Red. With a loading flow rate of 0.42 mL min(-1) for 25 mL, an enrichment factor of 1061 was achieved. Under the selected experimental condition, the detection limit (S/N = 3) of Para Red was 6.6 ng L(-1), and the peak area precision (RSD) for 5 replicate detections of 0.15 microg L(-1) Para Red was 4.1%. The applicability of this method for determination of the blank chili sauce sample, spiked with Para Red at 5 to 25 ng g(-1) levels, was demonstrated, with recoveries ranging from 86% to 95%. In this paper, a simple and sensitive analytical method, based on the coupling of molecularly imprinted solid phase extraction with high performance liquid chromatography, had been developed for determination of trace Para Red. It was applied to the analysis of spiking Para Red in chili sauce sample with satisfactory recovery and repeatability. This proposed method has the potential to be used for monitoring the illegal addition of Para Red in foods in the future due to its simple, reliable, rapid, and excellent precision.


Factors associated with functional recovery in bipolar disorder patients.
Among bipolar disorder (BPD) patients, functional recovery, defined as regaining individual premorbid residential and vocational status, is far less common than symptomatic recovery. As several factors have tentatively been implicated in outcomes in BPD, we investigated predictors of functional recovery among BPD patients, including demographic, clinical, and neurocognitive factors. We assessed functional recovery status with standardized residential and occupational indices, assessed neurocognitive functioning with performance-based neuropsychological tests, and collected demographic and clinical information for 65 euthymic or residually depressed Structured Clinical Interview for DSM-IV-defined type I or II BPD patients. We examined predictors of functional recovery with multiple logistic regression modeling. More education (p = 0.006), fewer years of illness (p = 0.037), and being married (p = 0.045) were associated independently with functional recovery, even after controlling for residual depressive symptoms, diagnostic type (I versus II), and psychiatric comorbidity. Functionally unrecovered BPD patients performed less well than recovered patients on verbal fluency (effect size = 0.54, p = 0.03), a measure of executive functioning, but this difference was not significant when adjusted for residual mood symptoms and education. Among euthymic or mildly depressed BPD patients, functional recovery was associated with more education, being married, and fewer years of illness.


CD49f (alpha 6 integrin) and CD66a (BGP) are specifically induced by retinoids during human monocytic differentiation.
Retinoic acid (RA) and 1,25(OH)2-cholecalciferol (VitD3) are potent regulators of normal and malignant myeloid cells. In the human monoblast cell line U-937 they induce terminal differentiation, and the resulting phenotypes display both common and distinct, inducer-specific, properties. This paper shows that in U-937 cells the two retinoids, all-trans and 9-cis RA, induced the expression of CD49f (alpha 6 integrin subunit) and CD66a (biliary glycoprotein, BGP) mRNA and protein. In contrast, expression of CD49f and CD66a was not found in untreated or VitD3-induced cells. Cytokine-induced modulation of CD49f and CD66a expression was restricted to the retinoid-induced U-937 cells. The retinoid specific induction of CD49f and CD66a was confirmed in the related monoblastic cell line THP-1. Human blood monocytes and the monocytic cell line Mono Mac 6 responded poorly to RA, with respect to the regulation of CD49f and CD66a expression, indicating that early monocytic precursors were targets for the retinoid-specific regulation. Thus, the expression of CD49f and CD66a is developmentally regulated and specifically induced by all-trans and 9-cis Ra in human monocytic cells.


Population pharmacokinetic modeling and dosing simulations of nitrogen-scavenging compounds: disposition of glycerol phenylbutyrate and sodium phenylbutyrate in adult and pediatric patients with urea cycle disorders.
Sodium phenylbutyrate and glycerol phenylbutyrate mediate waste nitrogen excretion in the form of urinary phenylacetylglutamine (PAGN) in patients with urea cycle disorders (UCDs); rare genetic disorders characterized by impaired urea synthesis and hyperammonemia. Sodium phenylbutyrate is approved for UCD treatment; the development of glycerol phenylbutyrate afforded the opportunity to characterize the pharmacokinetics (PK) of both compounds. A population PK model was developed using data from four Phase II/III trials that collectively enrolled patients ages 2 months to 72 years. Dose simulations were performed with particular attention to phenylacetic acid (PAA), which has been associated with adverse events in non-UCD populations. The final model described metabolite levels in plasma and urine for both drugs and was characterized by (a) partial presystemic metabolism of phenylbutyric acid (PBA) to PAA and/or PAGN, (b) slower PBA absorption and greater presystemic conversion with glycerol phenylbutyrate, (c) similar systemic disposition with saturable conversion of PAA to PAGN for both drugs, and (d) body surface area (BSA) as a significant covariate accounting for age-related PK differences. Dose simulations demonstrated similar PAA exposure following mole-equivalent PBA dosing of both drugs and greater PAA exposure in younger patients based on BSA.


Trans-diagnostic comparison of response inhibition in Tourette's disorder and obsessive-compulsive disorder.
Impaired response inhibition is related to neurodevelopmental disorders, such as Tourette's disorder (TD) and obsessive-compulsive disorder (OCD). Unlike OCD, in which neural correlates of response inhibition have been extensively studied, TD literature is limited. By using a Stop-Signal task, we investigated the neural mechanisms underlying response inhibition deficits in TD compared to OCD and healthy controls (HCs). Twenty-three TD patients, 20 OCD patients and 22 HCs were scanned (3T MRI). Region-of-interest analyses were performed between TD, OCD and HCs. Performance was similar across all subject groups. During inhibition TD compared with HCs showed higher right inferior parietal cortex (IPC) activation. During error processing TD compared with HCs showed hyperactivity in the left cerebellum, right mesencephalon, and right insula. Three-group comparison showed an effect of group for error-related activation in the supplementary motor area (SMA). Post-hoc analyses showed higher error-related SMA activity in TD compared with OCD and HCs. Error-related left cerebellar activity correlated positively with tic severity. Hyperactivation of IPC during inhibition and a widespread hyperactivated network during error processing in TD suggest compensatory inhibition- and error-related circuit recruitment to boost task performance. The lack of overlap with activation pattern in OCD suggests such compensatory mechanism is TD-specific.


Exercise and nutrition interventions in advanced lung cancer: a systematic review.
In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc). A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools. Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions. Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias. More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population.


Stromal extracellular matrix is a microenvironmental cue promoting resistance to EGFR tyrosine kinase inhibitors in lung cancer cells.
The acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a critical problem in lung cancer clinic, but the underlying mechanisms have remained incompletely understood. Although the TKI-induced or -selected genetic changes are known to drive resistance, resistance also occurs in tumor cells without genetic changes through poorly-characterized processes. Here, we show that the extracellular matrix (ECM) from various components of the tumor microenvironment, including neighboring tumor cells and fibroblasts, may be the driver of resistance in the absence of genetic changes. Unlike genetic changes, which may evolve during relatively long time of chronic EGFR TKI treatment to drive resistance, briefly culturing on de-cellularized ECM, or co-culturing with the ECM donor cells, immediately confers resistance to tumor cells that are otherwise sensitive to EGFR TKIs. We show evidence that collagen in the ECM may be its primary constituent driving resistance, at least partly through the collagen receptor Integrin-β1. Intriguingly, such effect of ECM and collagen is dose-dependent and reversible, suggesting a potential clinic-relevant application for targeting this effect. Collectively, our results reveal that the stromal ECM acts as a microenvironmental cue promoting EGFR TKI resistance in lung cancer cells, and targeting collagen and Integrin-β1 may be useful for treating resistance, especially the resistance without clearly-defined genetic changes, for which effective therapeutics are lacking.


[Characterization of dynamic behavior of side groups of globular proteins by spin-label, NMR and luminescence polarization methods].
In this work we suggest a quantitative estimation of a complicated motion of side groups of globular proteins. In the general case, three basic parameters determine the motion: (a) rotational correlation time of a side unit under study, or covalently bound spin label, or dye, (b) parameter S that reflects sterical restrictions for re-orientation of the given unit (these two parameters depending on the side-chain structure and its conformational change within the immediate dynamic protein surrounding whereas correlation times of side units on microviscosity in addition), (c) rotational correlation time of protein globule. These parameters can be measured by spin-label, NMR and fluorescence polarization techniques. An attempt to describe a complicated dynamic behaviour of side units of protein macromolecules with a single dynamics parameter--rotational correlation time--not only leads to a loss of part of information about the local structural dynamics of macromolecules but also can diminish the tau value.


Unexplained and underpowered: the relationship between psychosomatic disorders and interpersonal abuse -- a critical review.
Although it is commonly accepted that interpersonal violence (IntPV) leads to adverse health consequences, the available data are far from decisive. To test the hypothesized link, the authors devised an evidence-based strategy to determine the data quality in studies purporting to link IntPV and some medically unexplained disorders in women (irritable bowel syndrome, chronic pelvic pain, fibromyalgia/chronic fatigue, and other chronic pain syndromes). English language studies with control groups of unaffected women were assessed for the quality of their methodologies. The number of studies, together with the consistency of their findings in each domain, was collated to determine the overall weight of evidence regarding the link for each condition. The quantity and quality of research in each clinical area proved to be sparse. In general, most research was limited to small, convenience samples, with insufficient attention to the design of control groups and to sample size. The evidence currently available regarding irritable bowel syndrome, fibromyalgia/chronic fatigue, chronic pelvic pain, and other chronic pain syndromes does not allow for any firm conclusion regarding their link to IntPV. More research - paying particular regard to the methodological concerns identified here - is required in order to generate any definitive conclusions.


Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones.
A series of 2,5-bis(alkyl/arylamino)-1,4-benzoquinones (1-12) were investigated in vitro for their potential to inhibit the activity of jack bean urease. Compounds 1-6, 8, 9, 11 and 12 effectively inhibited the jack bean urease activity by 90.8 % when tested at 5 μm, whereas 7 and 10 had relatively little effect. The IC50 for most compounds was in the nanomolar range (31.4 nm and 36.0 nm for 2 and 8, respectively). The mechanism of enzyme inhibition shown by 2 and 8 is typical of mixed-type inhibitors, whose affinity for the active site is over 6- and 2-fold higher (Ki =30.0 and 22.8 nm, for 2 and 8, respectively) than that of an allosteric site. Molecular docking studies revealed that both 2 and 8 establish hydrogen bonds with the amino acids residues Asp494, Met588, His593 and Ala636 in the active site of jack bean urease. These results indicate that such aminoquinones are useful leads for the development of more efficient urease inhibitors of wider utility.


Role of ner protein in bacteriophage Mu transposition.
The Ner protein of bacteriophage Mu negatively regulates transcription initiated at the early promoter and at the major repressor promoter. The construction and isolation of a Ner- mutant of Mu is described. Ner is an essential function for Mu, because the mutant phage only forms plaques when complemented for Ner. Mutations in the repressor protein did not abolish the need for Ner. However, when transcription of the repressor gene c was blocked by deleting the major repressor promoter, Ner was no longer essential for normal Mu development.


Metabolic oxidation of carcinogenic arylamines by rat, dog, and human hepatic microsomes and by purified flavin-containing and cytochrome P-450 monooxygenases.
Hepatic N-oxidation and aryl ring oxidation are generally regarded as critical activation and detoxification pathways for arylamine carcinogenesis. In this study, we examined the in vitro hepatic metabolism of the carcinogens, 2-aminofluorene (2-AF) and 2-naphthylamine (2-NA), and the suspected carcinogen, 1-naphthylamine (1-NA), using high-pressure liquid chromatography. Hepatic microsomes from rats, dogs, and humans were shown to catalyze the N-oxidation of 2-AF and of 2-NA, but not of 1-NA; and the rates of 2-AF N-oxidation were 2- to 3-fold greater than the rates of 2-NA N-oxidation. In each species, rates of 1-hydroxylation of 2-NA and 2-hydroxylation of 1-NA were comparable and were 2- to 5-fold greater than 6-hydroxylation of 2-NA or 5- and 7-hydroxylation of 2-AF. Purified rat hepatic monooxygenases, cytochromes P-450UT-A, P-450UT-H, P-450PB-B, P-450PB-D, P-450BNF-B, and P-450ISF/BNF-G but not P-450PB-C or P-450PB/PCN-E, catalyzed several ring oxidations as well as the N-oxidation of 2-AF. Cytochromes P-450PB-B, P-450BNF-B, and P-450ISF/BNF-G were most active; however, only cytochrome P-450ISF/BNF-G, the isosafrole-induced isozyme, catalyzed the N-oxidation of 2-NA. The purified porcine hepatic flavin-containing monooxygenase, which was known to carry out the N-oxidation of 2-AF, was found to catalyze only ring oxidation of 1-NA and 2-NA. No activity for 1-NA N-oxidation was found with any of the purified enzymes. These data support the hypothesis that 1-NA is probably not carcinogenic. Furthermore, carcinogenic arylamines appear to be metabolized similarly in humans and experimental animals and perhaps selectively by a specific form of hepatic cytochrome P-450. Enzyme mechanisms accounting for the observed product distributions were evaluated by Hückel molecular orbital calculations on neutral, free radical, and cation intermediates. A reaction pathway is proposed that involves two consecutive one-electron oxidations to form a paired substrate cation-enzyme hydroxyl anion intermediate that collapses to ring and N-hydroxy products.


Microangiography and correlated histology: a research technique for examining renal microcirculation.
A technique for radiographic delineation of the microvasculature of the canine kidney is described. The renal vasculature was perfused (at a physiologic pressure) with a finely divided barium sulfate. Microangiograms of sagittal renal slices were produced, using a special radiography machine that allows low kilovolt peak, low milliamperage, and exposure times up to 5 minutes. A special high resolution film (800 lines/mm) was used. With this technique, it was possible to delineate interlobar, arcuate, and interlobular arteries, afferent arterioles, glomerular capillaries, and peritubular vessels. The kidney slices prepared for microangiography were undamaged and available for histochemical processing. Thus, the microvascularity was correlated with the histologic appearance of the renal tissues.


Spatial and temporal asymmetries in gait predict split-belt adaptation behavior in stroke.
Step asymmetries during gait in persons after stroke can occur in temporal or spatial domains. Prior studies have shown that split-belt locomotor adaptation can temporarily mitigate these asymmetries. . We investigated whether baseline gait asymmetries affected how patients adapt and store new walking patterns. Subjects with stroke and age-matched controls were studied walking at a 2:1 speed ratio on the split-belt during adaptation and assessed for retention of the learned pattern (the after-effect) with both belts at the same speed. Those with stroke adapted more slowly (P < .0001), though just as much as healthy older adults. During split-belt walking, the participants with stroke adapted toward their baseline asymmetry (eg, F = 14.02, P < .01 for step symmetry), regardless of whether the subsequent after-effects improved or worsened their baseline step asymmetries. No correlation was found between baseline spatial and temporal measures of asymmetry (P = .38). Last, the initial spatial and temporal asymmetries predicted after-effects independently of one another. The after-effects in the spatial domain (ie, center of oscillation difference) are only predicted by center of oscillation difference baseline (F = 15.3, P = .001), while all other parameters were nonsignificant (all Ps > .17). Temporal coordination (ie, phasing) after-effects showed a significant effect only from phasing baseline (F = 26.92, P < .001, all others P > .33). This work demonstrates that stroke patients adapt toward their baseline temporal and spatial asymmetries of walking independently of one another. We define how a given split-belt training session would affect asymmetries in these domains, which must be considered when developing rehabilitation interventions for stroke patients.


Loss of p16 and high Ki67 labeling index is associated with poor outcome in esophageal carcinoma.
The p16 tumor suppressor is coded by CDKN2A (9p21) and plays an important role during carcinogenesis and tumor progression in numerous tumor entities. The aim of our study was to evaluate the prognostic role of p16 expression and CDKN2A deletion in esophageal cancer (EC). Therefore, we analyzed p16 and KI67 expression by immunohistochemistry and 9p21 deletion by fluorescence in-situ hybridization on a tissue microarray including 398 adenocarcinomas (AC) and 293 squamous cell carcinomas (SCC) with clinical follow up-data. p16 positivity was found in 30.2% of AC and 13.9% of SCC and CDKN2A deletion in 32.1% of AC and 33.5% of SCC. In SCC p16 immunostaining correlated with low tumor stage (P = 0.014). In AC Ki67 positivity was associated with high tumor stage (P = 0.001), presence of lymph node metastasis (P = 0.009), high UICC stage (P = 0.001) and poor grading (P = 0.005). Overall survival (OS) was shorter for patients with high Ki67 labeling index (Ki67LI; P = 0.009) and negative p16 immunostaining (P = 0.026). In both histological tumor types, CDKN2A deletion showed no association with phenotype or outcome. Proportional cox-regression modeling revealed patients' age, tumor stage, lymph node metastasis and Ki67 labeling index as independent prognostic markers in AC. In SCC, only patients' age and tumor stage proved to be independent prognosticators. In summary, our study shows that loss of p16 expression and high Ki67LI is linked to shortened OS in AC. CDKN2A deletion shows no relevant association with tumor phenotype and patient outcome.


Advanced treatment of coking wastewater: Recent advances and prospects.
Advanced treatment of refractory industrial wastewater is still a challenge. Coking wastewater is one of coal chemical wastewater, which contains various refractory organic pollutants. To meet the more and more rigorous discharge standard and increase the reuse ratio of coking wastewater, advanced treatment process must be set for treating the biologically treated coking wastewater. To date, several advanced oxidation processes (AOPs), including Fenton, ozone, persulfate-based oxidation, and iron-carbon micro-electrolysis, have been applied for the advanced treatment of coking wastewater. However, the performance of different advanced treatment processes changed greatly, depending on the components of coking wastewater and the unique characteristics of advanced treatment processes. In this review article, the state-of-the-art advanced treatment process of coking wastewater was systematically summarized and analyzed. Firstly, the major organic pollutants in the secondary effluents of coking wastewater was briefly introduced, to better understand the characteristics of the biologically treated coking wastewater. Then, the performance of various advanced treatment processes, including physiochemical methods, biological methods, advanced oxidation methods and combined methods were discussed for the advanced treatment of coking wastewater in detail. Finally, the conclusions and remarks were provided. This review will be helpful for the proper selection of advanced treatment processes and promote the development of advanced treatment processes for coking wastewater.


Medical management of paraquat ingestion.
Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-κB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-κB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.


Long-term follow-up evaluation of magnetic resonance imaging in the prognosis of permanent GH deficiency.
In patients with GH deficiency (GHD), magnetic resonance imaging (MRI) has revealed morphological abnormalities such as pituitary hypoplasia, pituitary stalk agenesis (PSA) and ectopia of the posterior pituitary (PPE). The MRI anomalies have been more frequently reported in patients with multiple pituitary hormone deficiency (MPHD) than in subjects with isolated GH deficiency (IGHD). The aim of this work was to define which MRI anatomical abnormalities of the hypothalamo-pituitary area can be considered as a prognostic marker of permanent GHD. To investigate the relationship between the neuroradiological images and endocrine findings, we clinically re-evaluated 93 out of the 121 GHD patients with IGHD and MPHD previously studied. No additional hormone deficiencies were observed in 55 out of 60 patients initially classified as having IGHD with a normal (15 cases) or reduced (40 cases) pituitary gland size, without other MRI abnormalities. The remaining five children, who had initially shown an apparently IGHD in spite of PSA and PPE, developed a MPHD over time. In 33 MPHD patients with (25 cases) or without (8 cases) MRI abnormalities, the associated hormone deficiencies were confirmed during follow-up. The IGHD patients showing PSA and PPE inevitably develop additional hormone deficiencies, while IGHD subjects having no MRI abnormalities maintain IGHD. Moreover, the anatomical abnormalities of the hypothalamo-pituitary area can be considered as a prognostic marker of permanent GHD.


Case studies on forecasting for innovative technologies: frequent revisions improve accuracy.
Health technology forecasting is designed to provide reliable predictions about costs, utilization, diffusion, and other market realities before the technologies enter routine clinical use. In this article we address three questions central to forecasting's usefulness: Are early forecasts sufficiently accurate to help providers acquire the most promising technology and payers to set effective coverage policies? What variables contribute to inaccurate forecasts? How can forecasters manage the variables to improve accuracy? We analyzed forecasts published between 2007 and 2010 by the ECRI Institute on four technologies: single-room proton beam radiation therapy for various cancers; digital breast tomosynthesis imaging technology for breast cancer screening; transcatheter aortic valve replacement for serious heart valve disease; and minimally invasive robot-assisted surgery for various cancers. We then examined revised ECRI forecasts published in 2013 (digital breast tomosynthesis) and 2014 (the other three topics) to identify inaccuracies in the earlier forecasts and explore why they occurred. We found that five of twenty early predictions were inaccurate when compared with the updated forecasts. The inaccuracies pertained to two technologies that had more time-sensitive variables to consider. The case studies suggest that frequent revision of forecasts could improve accuracy, especially for complex technologies whose eventual use is governed by multiple interactive factors.


Exploring indicators of genetic selection using the sniffer method to reduce methane emissions from Holstein cows.
This study aimed to evaluate whether the methane (CH4) to carbon dioxide (CO2) ratio (CH4/CO2) and methane-related traits obtained by the sniffer method can be used as indicators for genetic selection of Holstein cows with lower CH4 emissions. The sniffer method was used to simultaneously measure the concentrations of CH4 and CO2 during milking in each milking box of the automatic milking system to obtain CH4/CO2. Methane-related traits, which included CH4 emissions, CH4 per energy-corrected milk, methane conversion factor (MCF), and residual CH4, were calculated. First, we investigated the impact of the model with and without body weight (BW) on the lactation stage and parity for predicting methane-related traits using a first on-farm dataset (Farm 1; 400 records for 74 Holstein cows). Second, we estimated the genetic parameters for CH4/CO2 and methane-related traits using a second on-farm dataset (Farm 2; 520 records for 182 Holstein cows). Third, we compared the repeatability and environmental effects on these traits in both farm datasets. The data from Farm 1 revealed that MCF can be reliably evaluated during the lactation stage and parity, even when BW is excluded from the model. Farm 2 data revealed low heritability and moderate repeatability for CH4/CO2 (0.12 and 0.46, respectively) and MCF (0.13 and 0.38, respectively). In addition, the estimated genetic correlation of milk yield with CH4/CO2 was low (0.07) and that with MCF was moderate (-0.53). The on-farm data indicated that CH4/CO2 and MCF could be evaluated consistently during the lactation stage and parity with moderate repeatability on both farms. This study demonstrated the on-farm applicability of the sniffer method for selecting cows with low CH4 emissions.


A model of magnesium metabolism in young sheep. Magnesium absorption and excretion.
A model of Mg metabolism in sheep is proposed. It is based on standard Michaelis-Menten enzyme kinetics to describe the transport of Mg across the rumen wall and passive diffusion to describe the absorption of Mg in the hindgut. Factors known to have an effect on Mg metabolism in farm animals, namely the concentrations of K and Mg in the diet, and the physico-chemical conditions within the rumen as determined by the type of diet, are incorporated into the model. Consideration of the rumen as the only site of Mg absorption provided an inadequate mechanistic description of Mg metabolism in sheep. To ensure compatibility between predicted Mg absorption and recent independent data sets for Mg balances, it was necessary to include in the model aspects of Mg absorption that operate in the hindgut. The results from this model suggest that there is a need for a series of experiments to determine the important aspects of Mg transport in the hindgut of sheep. Mechanisms of homeostasis are discussed.


Dosimetric considerations of 99mTc-MDP uptake within the epiphyseal plates of the long bones of pediatric patients.
Skeletal scintigraphy is most performed in pediatric patients using the radiopharmaceutical 99mTc labelled methylene diphosphonate (99mTc-MDP). Reference biokinetic models for 99mTc-MDP indicate 50% of the administered activity is uniformly localized to the interior bone surfaces (trabecular and cortical regions), yet imaging data clearly show some preferential uptake to the epiphyseal growth plates of the long bones. To explore the dosimetric consequences of these regional activity concentrations, we have modified mesh-type computational phantoms of the International Commission on Radiological Protection (ICRP) reference pediatric series to explicitly include geometric models of the epiphyseal growth plates (2 mm in thickness) within the left/right, distal/proximal ends of the humeri, radii, ulnae, femora, tibia, and fibulae. Bone mineral activity from the ICRP Publication 128 biokinetic model for 99mTc-MDP (ICRP 2015) was then partitioned to the growth plates at values of 0.5%, 4.4%, 8.3%, 12.2%, 16.1%, and 20%. Radiation transport simulations were performed to compute 99mTc S-values and organ dose coefficients to the soft tissues and to bone site-specific regions of spongiosa. As the percentage of bone activity assigned to the growth plates was increased (from 0.5% to 20%), absorbed doses to the soft tissue organs, active bone marrow, bone endosteum (BE), as well as the detriment-weighted dose, were shown to decrease from their nominal values (no substantial growth plate activity), while epiphyseal plate self-doses increased. In the 15 year old male phantom, moving from 0.5% to 20% relative bone activity within the epiphyseal plates resulted in a 15% reduction in active marrow (AM) and BE dose, a 10% reduction in mean soft tissue and detriment-weighted dose, and a 6.3-fold increase in epiphyseal plate self-dose. In the newborn female phantom, we observed a 18% decrease in AM and BE dose, a 10% decrease in mean soft tissue dose, a 15% decrease in detriment-weighted dose, and 12.8-fold increase in epiphyseal plate self-dose. Increases (to 3 mm) and decreases (to 1 mm) in the assumed growth plate thickness of our models were shown to impact only the growth plate self-dose. Future work in differential quantification of 99mTc-MDP activity-growth plates versus other bone surfaces-is required to provide clinically realistic data on activity partitioning as a function of patient age, and perhaps skeletal site. The phantom series presented here may be used to develop more optimized age-related guidance on 99mTc-MDP administered activities to children.


Extract from the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery - Patient Blood Management.
The 2022 Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology are an update on the previous guidelines reported in 2014. The revised guidelines provide standardized perioperative cardiovascular management of surgical patients and emphasis on risk assessment of the patient combined with the inherent risk of the surgical procedure. One of the novelties in these guidelines is the Patient Blood Management programme, which is based on a three pillar concept: preoperative hemoglobin optimization, minimize iatrogenic blood loss and bleeding, and harness tolerance to anemia in an effort to improve patient outcome. In this review, we highlight the three pillars of Patient Blood Management and recommendations made by the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.


[Magnetic resonance arthrography of the hip joint in patients with suspected rupture of labrum acetabulare].
MR arthrography by direct joint puncture and instillation of contrast medium is a minimally-invasive diagnostic technique in patients with suspected acetabular labral tear. The joint is distended, and the intraarticular structures are well separated. 31 patients with chronic hip joint pain underwent MR arthrography by direct joint puncture and instillation of diluted gadolinium to evaluate the glenoid labrum. The glenoid labrum was seen in all patients. Labral tear was found in ten patients. Two of these underwent arthroscopy, and the tears were verified. We also found other causes of hip pain. One patient with villonodular synovitis at MR arthrography was verified at arthroscopy. MR arthrography is a promising diagnostic technique for evaluating the acetabular labrum.


[Characteristics related to STD/HIV in men working in Mexico City bars where female prostitution takes place].
This research work intended to describe the characteristics and the seroprevalence of some sexually transmitted diseases (STD), in men working in bars where female commercial sex takes place. The study included an evaluation of 171 males during 1993, who were employed in bars and who were potentially at risk of contact with female commercial sex workers (FCSW). A structured survey was conducted in order to collect information about social, demographic and sexual behavior characteristics. Blood samples were also obtained to test for antibodies against Treponema pallidum (RPR/FTA-ABS), human immunodeficiency virus (VIH) (ELISA, Western blot), Herpes simplex virus type-2 (HSV-2) (Western blot) and the core antigen of hepatitis B virus (HBV) (ELISA). Test results showed low infection rates of HIV, T: pallidum and HBV: 0%, 2.4% and 1.8%, respectively. However, their HSV-2 infection proportion (32.4%) was considered intermediate in comparison to the prevalence of FCSW from bars (55.5%), to that found in heterosexual men (14.6%), and to proportions found in women general population (29.3% and 17.9%). The men's age and a history of sexual intercourse with FCSW were strong predictors of HSV-2 infection. These findings evidence a relationship between men working in bars and FCSW in terms of STD transmission and show the need for preventive care directed to this group.


Glutamine synthetase activity in patients with Parkinson's disease.
According to current concepts, the excitatory amino acid glutamate is involved in the pathogenesis of Parkinson's disease (PD). Overactivity of glutamatergic projection neurons and beneficial effect of antiglutamatergic substances in animal experiments suggest that excess supply of glutamate might contribute to the pathophysiology of PD. Reduced activity of the glutamate metabolizing enzyme glutamine synthetase (GS) leads to decreased uptake of glutamate and thus abundant glutamate. Here we report that PD patients and age-matched controls are comparable with respect to GS activity in peripheral blood mononuclear cells (PBMC). These results imply no systemic dysregulation of the enzyme GS in patients with PD.


Toward Electronic Health Recording: Evaluation of Electronic Patient-reported Outcome Measures System for Remote Monitoring of Early Rheumatoid Arthritis.
To assess the use of electronic patient-reported outcome measures (ePROM) in standard clinical practice for early rheumatoid arthritis (RA) management, the ePROM ability to enhance clinical care, and how computing technology can improve the patients' adherence to therapy. In a double-blinded randomized-controlled study, 211 patients with early RA diagnosed according to American College of Rheumatology/European League Against Rheumatism criteria completed a PROM in paper format at their first clinic visit. Patients were then randomized to Group 1, which completed an ePROM questionnaire monthly, or Group 2, which continued the standard paper PROM format. Over a 12-month period, Group 1 patients were assessed every 3 months in the clinic, whereas Group 2 patients were assessed in the clinic initially monthly for 6 months, then every 3 months. The primary endpoint was the equivalence of outcomes [Routine Assessment of Patient Index Data 3 (RAPID-3) and 28-joint Disease Activity Score (DAS28)] in both groups. The secondary endpoint was the patients' adherence to their medications. There was no significant difference between disease activity measures as well as DAS28 and RAPID-3 scores at 3, 6, and 12 months of management, although there was a trend toward lower patient-reported tender joint count and functional disability score in the active group versus the control group. The patients' adherence to antirheumatic therapy was significantly higher (p < 0.01) in the ePROM group, whereas stopping disease-modifying antirheumatic drugs for intolerability was significantly higher (p < 0.01) in the control group at 12 months of treatment. We found ePROM equivalent to standard paper PROM format. Further, it enabled the patients to personally monitor how they are doing regarding their disease activity and helped to optimize their adherence to their treatment.


Demographic profile of the veterinary profession in New Zealand, 1985.
The demographic characteristics of the veterinary profession in New Zealand are examined using information supplied by registered veterinarians to the Veterinary Surgeons Board in their applications for annual practising certificates in 1985. Comparisons are made with the veterinary professions in other similar countries, and with the medical and paramedical professions in New Zealand. In 1985 1308 registered veterinarians were working in New Zealand and 304 were overseas, whereas in 1976 the equivalent figures were 748 and 182. This represents an increase of 73% in the number of registered veterinarians in the last 10 years. Eighteen percent of veterinarians were female. The mean age of veterinarians was 38 years, but females in the profession were on average much younger (32 years) than males (42 years). Clinical practice provides employment for 70% of veterinarians: of these 59% work principally with farm animals and 41% with non-farm animals. The remaining veterinarians are employed by Government (22%), University (5%) and Industry (3%). The current demographic structure of the profession has been markedly influenced by the opening of New Zealand's only veterinary school at Massey University in 1963. Differences from other medical professional populations in New Zealand and overseas principally reflect the marked change in the number and sex ratio of graduates entering the veterinary profession since that time. It will take about another twenty years before the population reaches a stable age and sex structure, assuming that current graduation patterns persist throughout that period. Because the structure of the population is changing, considerable caution is needed in predicting future employment trends from data for a single year.


The "Facebook-self": characteristics and psychological predictors of false self-presentation on Facebook.
In this study we present and empirically examine a new phenomenon related to social networking sites, such as Facebook, the "false Facebook-self." Arguably false self-presentation on Facebook is a growing phenomenon, and in extreme cases; i.e., when ones Facebook image substantially deviates from their true image, it may serve as a gateway behavior to more problematic behaviors which may lead to psychological problems and even pathologies. In this study we show that certain users are more vulnerable to such false self-presentation than others. The study involved 258 Facebook users. Applying ANOVA and SEM analyses we show that users with low self-esteem and low trait authenticity are more likely than others to present a Facebook-self which deviates from their true selves. These social-interaction-related traits are influenced by one's upbringing and the anxious and avoidant attachment styles he or she has developed. Several cases (7.5%) with large gaps between the true and false Facebook-self were detected, which implies that future research should consider the adverse consequences and treatments of high levels of false Facebook-self.


House dust mites and their allergens in Danish mattresses -- results from a population based study.
The purpose of this study was to identify the level of house dust mites (HDMs) and their allergens in mattresses, not selected on their owners atopic status, and to find associated factors. Dust was collected from 68 mattresses. The recruitment was population-based and conducted during the screening phase of a HDM intervention study. The visited persons declared to have had a "cold" bedroom the previous winter. HDMs were counted and dust was analysed by ELISA for Der 1 (= Der f 1+ Der p 1+ Der m 1). Multiple regression analysis was carried out to find housing conditions associated with high HDM levels. Type of housing, mattress age and self-assessed winter bedroom-temperature explained 47% of Der 1. Median concentrations were 3.77 microg Der 1/g and 1 HDM/0.1 g dust. Both immunochemically and microscopically Dermatophagoides farinae was dominant; D. pteronyssinus less frequent but important; and D. microceras insignificant. In 62% of these suburban homes the mattress dust exceeded 2 microg Der 1/g; and measurement of both Der f 1 and Der p 1 was necessary and sufficient to evaluate HDM allergen exposure. The association with a high HDM level was highest and most consistent for one-family houses.


In vivo and ex vivo measurement of polyethylene wear in total hip arthroplasty: comparison of measurements using a CT algorithm, a coordinate-measuring machine, and a micrometer.
Determination of the amount of wear in a polyethylene liner following total hip arthroplasty (THA) is important for both the clinical care of individual patients and the development of new types of liners. We measured in vivo wear of the polyethylene liner using computed tomography (CT) (obtained in the course of regular clinical care) and compared it to coordinate-measuring machine (CMM) readings. Also, changes in liner thickness of the same retrieved polyethylene liner were measured using a micrometer, and were compared to CT and CMM measurements. The distance between the centers of the acetabular cup and femoral head component was measured in 3D CT, using a semi-automatic analysis method. CMM readings were performed on each acetabular liner and data were analyzed using 3D computer-aided design software. Micrometer readings compared the thickest and thinnest regions of the liner. We analyzed 10 THA CTs and retrievals that met minimal requirements for CT slice thickness and explanted cup condition. RESULTS - For the 10 cups, the mean difference between the CT readings and the CMM readings was -0.09 (-0.38 to 0.20) mm. This difference was not statistically significant (p = 0.6). Between CT and micrometer, the mean difference was 0.11 (-0.33 to 0.55) mm. This difference was not statistically significant (p = 0.6). INTERPRETATION - Our results show that CT imaging is ready to be used as a tool in clinical wear measurement of polyethylene liners used in THA.


Valence-to-core-detected X-ray absorption spectroscopy: targeting ligand selectivity.
X-ray absorption spectroscopy (XAS) can provide detailed insight into the electronic and geometric structures of transition-metal active sites in metalloproteins and chemical catalysts. However, standard XAS spectra inherently represent an average contribution from the entire coordination environment with limited ligand selectivity. To address this limitation, we have investigated the enhancement of XAS features using valence-to-core (VtC)-detected XAS, whereby XAS spectra are measured by monitoring fluorescence from valence-to-core X-ray emission (VtC XES) events. VtC emission corresponds to transitions from filled ligand orbitals to the metal 1s core hole, with distinct energetic shifts for ligands of differing ionization potentials. VtC-detected XAS data were obtained from multiple valence emission features for a series of well-characterized Mn model compounds; taken together, these data correspond to a VtC resonant XES (VtC RXES) plane. For comparison, standard total fluorescence yield (TFY) XAS and nonresonant XES data were obtained. Dramatic intensity variations and the appearance of new features were observed in the pre-edge region by detecting at different VtC emission energies. The TFY XAS, nonresonant XES, and VtC RXES data were all modeled within a density functional theory approach. While the TFY XAS and nonresonant XES data are readily interpreted by theory, the VtC RXES cannot be reproduced within such a simplified model. Nonetheless, dramatic changes in the experimental spectra are observed that have the potential to further the information content and selectivity of XAS. Potential applications and required theoretical developments are discussed.


Are thyroid cancer patients sensitive to ionising radiation?
To determine the ionising radiation sensitivity of peripheral blood lymphocytes in a group of differentiated thyroid cancer (DTC) patients. A total of 53 thyroid cancer patients (26 women and 27 men) and 50 donors (23 women and 27 men) were included in the study. The cytokinesis-block micronucleus assay (CBMN) in G0 peripheral blood lymphocytes was carried out using the cytochalasin B technique. Four cultures were established per each donor, two were irradiated with 0.5 Gy 137Cs g-rays, while the other two remained untreated. No significant differences were observed in the frequency of binucleated cells with micronuclei (BNMN) between patients and controls, for both spontaneous and after the irradiation frequencies. Nevertheless, a positive and significant correlation was found between the frequencies of both spontaneous and after irradiation DNA damage, for control and patient groups. We have found that DTC patients do not present particular sensitivity to ionising radiation when an in vitro treatment is performed in G0 stage of the cell cycle, but this result does not discard the hypothesis about an increased sensitivity in other stages of the cell cycle in DTC patients.


Live donor nephrectomy in patients with fibromuscular dysplasia of the renal arteries.
We determine the suitability of patients with fibromuscular dysplasia of the renal arteries as renal donors. We evaluated 37 patients with fibromuscular dysplasia who were potential renal donors. Renal artery lesions were graded I (mild) to IV (severe). Of the patients 19 underwent donor nephrectomy and 18 were rejected as donors. Reasons for rejection included severity of disease or availability of a better donor. Nephrectomy was performed on the side with fibromuscular dysplasia when disease was unilateral or on the side with more advanced disease when the lesions were bilateral. Patients were followed at 1 month, 1 year and then yearly. Of the 19 patients undergoing donor nephrectomy serum creatinine increased by a mean of 0.4 mg./dl. (range 0.1 to 1.1) on postoperative day 1. Effective renal plasma flow of the remaining kidney increased by 25% on postoperative day 5 and by 29% after 1 year. After a mean followup of 4.5 years no patient had hypertension, proteinuria or any significant change in serum creatinine compared to baseline values. Of the 18 patients not undergoing nephrectomy 11 were contacted at a mean followup of 4 years, and none had hypertension, proteinuria or abnormal serum creatinine. Patients with fibromuscular dysplasia may be acceptable renal donors. The decision to use a patient with fibromuscular dysplasia as a donor is based on patient age, the availability of other suitable donors, and the extent and severity of disease.


Acute respiratory failure among lung transplant adults requiring intensive care: Changing spectrum of causative organisms and impact of procalcitonin test in the diagnostic workup.
The aim was to identify the causing organisms and assess the association of procalcitonin (PCT) with bacterial pneumonia within 24 hours of intensive care unit admission (ICU-A) among lung transplant (LT) adult recipients. Secondary analysis from a prospective cohort study. All LT adults admitted to ICU for acute respiratory failure (ARF) over 5 years were included. Patients were followed until hospital discharge or death. Fifty-eight consecutive LT patients were enrolled. The most important cause of ICU-A due to ARF was pneumonia 29 (50%) followed by acute rejection 3 (5.2%) and bronchiolitis obliterans syndrome exacerbation 3 (5.2%). Microorganisms were isolated from 22/29 cases with pneumonia (75.9%): 17 (77.2%) bacterial, 4 (18.2%) viral, 1 (4.5%) Aspergillus fumigates, with Pseudomonas aeruginosa being the most common cause (45.5%) of pneumonia, with 10 patients presenting chronic colonization by P aeruginosa. Median [Interquartile range (IQR)] PCT levels within 24 hours after admission were higher in pneumonia (1.5 µg/L; IQR:0.3-22.0), than in non-pneumonia cases (0.2 µg/L; IQR:0.1-0.7) (P = .019) and PCT levels within 24 hours helped to discriminate bacterial pneumonia (8.2 µg/L; IQR:0.2-43.0) from viral pneumonia and non-pneumonia cases (0.2 µg/L; IQR:0.1-0.7). The overall negative predictive value for bacterial pneumonia was 85.1%, increasing to 91.6% among episodes after 6 months of LT. Causes of severe pneumonia in LT are changing, with predominant role of P aeruginosa and respiratory viruses. PCT ≤ 0.5 μg/L within 24 hours helps to exclude bacterial pneumonia diagnosis in LT adults requiring ICU-A. A negative PCT test allows antimicrobial de-escalation and requires an alternative diagnostic to bacterial pneumonia.


Living Close to Natural Outdoor Environments in Four European Cities: Adults' Contact with the Environments and Physical Activity.
This study investigated whether residential availability of natural outdoor environments (NOE) was associated with contact with NOE, overall physical activity and physical activity in NOE, in four different European cities using objective measures. A nested cross-sectional study was conducted in Barcelona (Spain); Stoke-on-Trent (United Kingdom); Doetinchem (The Netherlands); and Kaunas (Lithuania). Smartphones were used to collect information on the location and physical activity (overall and NOE) of around 100 residents of each city over seven days. We used Geographic Information Systems (GIS) to determine residential NOE availability (presence/absence of NOE within 300 m buffer from residence), contact with NOE (time spent in NOE), overall PA (total physical activity), NOE PA (total physical activity in NOE). Potential effect modifiers were investigated. Participants spent around 40 min in NOE and 80 min doing overall PA daily, of which 11% was in NOE. Having residential NOE availability was consistently linked with higher NOE contact during weekdays, but not to overall PA. Having residential NOE availability was related to NOE PA, especially for our Barcelona participants, people that lived in a city with low NOE availability.


Parent Perspectives on Pediatric Inpatient OpenNotes.
169 U.S. health systems now engage in OpenNotes: a movement to share clinical notes with patients. Few studies have focused on releasing notes during hospitalization, pediatrics, or parents/caregiver perspectives. A focus group was conducted with eight parents with experience caring for a hospitalized child at a Midwest children's hospital. In the 2-hour session, parents were asked about their perspectives of the idea of sharing inpatient doctors' daily notes with parents during their child's hospitalization. Qualitative analysis was conducted to elicit themes related to the potential benefits and challenges of sharing inpatient notes. The most mentioned benefits included notes providing information as a reference for improved family education/understanding, communication/continuity, and advocacy/empowerment. Challenges were primarily related to note content, impaired communication and negative impact on families. Participants identified multiple potential benefits of and challenges to sharing notes with parents during their child's hospitalization but also acknowledged the impact on healthcare professionals who work alongside them.


Nuclear factor-κB/Bcl-XL pathway is involved in the protective effect of hydrogen-rich saline on the brain following experimental subarachnoid hemorrhage in rabbits.
Early brain injury (EBI), a significant contributor to poor outcome after subarachnoid hemorrhage (SAH), is intimately associated with neuronal apoptosis. Recently, the protective role of hydrogen (H2 ) in the brain has been widely studied, but the underlying mechanism remains elusive. Numerous studies have shown nuclear factor-κB (NF-κB) as a crucial survival pathway in neurons. Here we investigated the role of H2 in EBI following SAH, focusing on the NF-κB pathway. A double blood injection model was used to produce experimental SAH, and H2 -rich saline was injected intraperitoneally. NF-κB activity within the occipital cortex was measured. Immunofluorescence was performed to demonstrate the activation of NF-κB; Bcl-xL and cleaved caspase-3 were determined via Western blot. Gene expression of Bcl-xL was detected by real-time PCR, and TUNEL and Nissl staining were performed to illustrate brain injury in the occipital cortex. SAH induced a significant increase of cleaved caspase-3. Correspondingly, TUNEL staining demonstrated obvious neuronal apoptosis following SAH. In contrast, H2 treatment markedly increased NF-κB activity and the expression of Bcl-xL and decreased the level of cleaved caspase-3. Additionally, H2 treatment significantly reduced post-SAH neuronal apoptosis. The current study shows that H2 treatment alleviates EBI in the rabbits following SAH and that NF-κB/Bcl-xL pathway is involved in the protective role of H2 .


Three-dimensional kinematics of capuchin monkey bipedalism.
Capuchin monkeys are known to use bipedalism when transporting food items and tools. The bipedal gait of two capuchin monkeys in the laboratory was studied with three-dimensional kinematics. Capuchins progress bipedally with a bent-hip, bent-knee gait. The knee collapses into flexion during stance and the hip drops in height. The knee is also highly flexed during swing to allow the foot which is plantarflexed to clear the ground. The forefoot makes first contact at touchdown. Stride frequency is high, and stride length and limb excursion low. Hind limb retraction is limited, presumably to reduce the pitch moment of the forward-leaning trunk. Unlike human bipedalism, the bipedal gait of capuchins is not a vaulting gait, and energy recovery from pendulum-like exchanges is unlikely. It extends into speeds at which humans and other animals run, but without a human-like gait transition. In this respect it resembles avian bipedal gaits. It remains to be tested whether energy is recovered through cyclic elastic storage and release as in bipedal birds at higher speeds. Capuchin bipedalism has many features in common with the facultative bipedalism of other primates which is further evidence for restrictions on a fully upright striding gait in primates that transition to bipedalism. It differs from the facultative bipedalism of other primates in the lack of an extended double-support phase and short aerial phases at higher speeds that make it a run by kinematic definition. This demonstrates that facultative bipedalism of quadrupedal primates need not necessarily be a walking gait.


Proteolytic processing of foot-and-mouth disease virus polyproteins expressed in a cell-free system from clone-derived transcripts.
All picornaviral genes are expressed as a single, large polyprotein, which is proteolytically processed into the system produces functional proteins, including viral protease 3C, which plays a major role in processing the precursor proteins. To study the function of the two putative proteases 3C and leader (L) in processing, we constructed several cDNA plasmids encoding various regions of the FMDV type A12 genome. These plasmids, containing FMDV cDNA segments under the control of the T7 promoter, were transcribed in vitro by using T7 RNA polymerase and then translated in rabbit reticulocyte lysates. The expressed FMDV gene products were identified by immunoprecipitation with specific antisera and analyzed by gel electrophoresis. The results demonstrate the following: (i) the leader protein, L, is processed from the structural protein precursor, P1, in the absence of any P2 or P3 region proteins; (ii) protein 2A remains associated with the structural protein precursor, P1, rather than the precursor, P2; (iii) the processing of the P1-2A/P2 junction is not catalyzed by 3C or L; (iv) the proteolytic processing of polyproteins from the structural P1 region (except VP4/VP2) and the nonstructural P2 and P3 region is catalyzed by 3C.


Effects of Light Quality on Colonization of Tomato Roots by AMF and Implications for Growth and Defense.
Beneficial soil microbes can enhance plant growth and defense, but the extent to which this occurs depends on the availability of resources, such as water and nutrients. However, relatively little is known about the role of light quality, which is altered during shading, resulting a low red: far-red ratio (R:FR) of light. We examined how low R:FR light influences arbuscular mycorrhizal fungus (AMF)-mediated changes in plant growth and defense using Solanum lycopersicum (tomato) and the insect herbivore Chrysodeixis chalcites. We also examined effects on third trophic level interactions with the parasitoid Cotesia marginiventris. Under low R:FR light, non-mycorrhizal plants activated the shade avoidance syndrome (SAS), resulting in enhanced biomass production. However, mycorrhizal inoculation decreased stem elongation in shaded plants, thus counteracting the plant's SAS response to shading. Unexpectedly, activation of SAS under low R:FR light did not increase plant susceptibility to the herbivore in either non-mycorrhizal or mycorrhizal plants. AMF did not significantly affect survival or growth of caterpillars and parasitoids but suppressed herbivore-induced expression of jasmonic acid-signaled defenses genes under low R:FR light. These results highlight the context-dependency of AMF effects on plant growth and defense and the potentially adverse effects of AMF under shading.


Poverty effects of public health reforms in Turkey: A focus on out-of-pocket payments.
Expanded financial coverage is critical to fight against poverty through public health reforms in developing countries. This study explores inequity in public health financing reforms in Turkey between 2003 and 2015. This paper has two parts. The first part examines inequity in health care financing in Turkey between 2003 and 2015. Gini, entropy (Theil and mean logarithmic deviation), and Atkinson indexes were calculated. In the second part of the paper, we investigated the degree of progressivity by using Kakwani index and Lorenz and concentration curves. We found a decreasing trend in terms of inequity. After major public health reforms and unification of the health financing system, it is seen that the distribution of out-of-pocket expenditure on health stands on the shoulders of vulnerable groups. Study results provide a deep understanding of the effects of poverty on public health financing reforms on households in Turkey. To reduce out-of-pocket health spending inequities and to protect vulnerable groups from increasing the level of health expenditures, we suggest that the government enlarges health insurance coverage for the poor.


Autism in children and correlates in Lebanon: a pilot case-control study.
Autism spectrum disorder (ASD) is a neurological disorder typically appearing before the age of three. The exact cause of autism remains uncertain, and several factors may be involved in its onset: genetic factors and possible environmental factors. The aim of this study was to assess the correlates of autism in the Lebanese population. We investigated the association of autism with several factors in 86 autism cases from specialized schools for children with developmental disabilities and 172 control children from regular public schools in the same regions. Several risk factors for autism were investigated after comparison with a cohort control on parental age, sex, maternal unhappy feeling during pregnancy, consanguineous marriage, and province of residence. The Chi-square test was used to compare nominal variables, and Fisher exact test was used in case expected values within cells were inferior to five. For quantitative variables, we used t-test to compare means between two groups, after checking their distribution normality. For multivariate analysis, we used a forward stepwise likelihood ratio logistic regression. We observed male predominance (79.1%) among autistic infants. There was a significant association between autism and older parents age (OR=1.27), male sex (OR=3.38), unhappy maternal feeling during pregnancy (OR=5.77), living close to industry (OR=6.58), previous childhood infection (OR=8.85), but none concerning maternal age, paternal age and consanguinity. In this pilot epidemiological study of autism in Lebanon, we found several prenatal and perinatal risk factors for autism that could be modified.


The impact of concomitant viral pathogens on the course of Pneumocystis carinii pneumonia.
A large retrospective study was conducted to evaluate the impact of culturing cytomegalovirus from the respiratory secretions of AIDS patients with Pneumocystis carinii pneumonia. Pneumocystis carinii was found in 220 (67%) of 327 episodes and cytomegalovirus was found in 106 (48%) of the P. carinii-positive patients. Cytomegalovirus-positive and -negative patients were similar at baseline and had a similar number of hospital days, but had a lower incidence of early deterioration in oxygenation, fewer intensive-care days, were less frequently intubated, and had a higher 30-day survival. The better short-term outcome of cytomegalovirus positive patients observed in this study may relate to the immunosuppressive effects of cytomegalovirus.


Treadmill-based system for postural studies: Design and validation.
Computer-controlled treadmills are common in many gait labs and offer great potential for conducting perturbation-based postural studies. However, the time-course of these disturbances can be too brief to be controlled manually through product software. Here we present a system that combines a Bertec® split-belt treadmill with custom hardware and software to deliver postural disturbances during standing and record data from multiple sources simultaneously. We used this system to administer to 15 healthy participants an 8-session perturbation-based training protocol in which they learned to respond without stepping to progressively larger perturbations. Kinematic, electromyographic, and force data were collected throughout. Motion capture was used to characterize the accuracy and repeatability of the treadmill-delivered perturbations with respect to duration, displacement, and peak velocity. These (observed) data were compared to that expected based on software commands and the known constraints of the treadmill (i.e., 10 Hz operating speed). We found perturbation durations to be as expected. Peak velocities and displacements were slightly higher than expected (average increases were 0.59 cm/s and 1.76 cm, respectively). Because this increase in magnitude was consistent, it did not impede training or affect data analysis. Treadmill behavior was repeatable across 95 % of trials.


Physical activity correlates with arterial stiffness in community-dwelling individuals with stroke.
Physical inactivity contributes to atherosclerotic processes, which manifest as increased arterial stiffness. Arterial stiffness is associated with myocardial demand and coronary perfusion and is a risk factor for stroke and other adverse cardiac outcomes. Poststroke mobility limitations often lead to physical inactivity and sedentary behaviors. This exploratory study aimed to identify functional correlates, reflective of daily physical activity levels, with arterial stiffness in community-dwelling individuals >1 year poststroke. Carotid-femoral pulse wave velocity (cfPWV) was measured in 35 participants (65% men; mean ± SD age 66.9 ± 6.9 years; median time poststroke 3.7 years). Multivariable regression analyses examined the relationships between cfPWV and factors associated with daily physical activity: aerobic capacity (VO2 peak), gait speed, and balance ability (Berg Balance Scale). Age and the use of antihypertensive medications, known to be associated with pulse wave velocity, were also included in the model. Mean cfPWV was 11.2 ± 2.4 m/s. VO2 peak and age were correlated with cfPWV (r = -0.45 [P = .006] and r = 0.46 [P = .004], respectively). In the multivariable regression analyses, age and the use of antihypertensive medication accounted for 20.4% of the variance of cfPWV, and the addition of VO2 peak explained an additional 4.5% of the variance (R2 = 0.249). We found that arterial stiffness is elevated in community-dwelling, ambulatory individuals with stroke relative to healthy people. Multivariable regression analysis suggests that aerobic capacity (VO2 peak) may contribute to the variance of cfPWV after accounting for the effects of age and medication use. Whether intense risk modification and augmented physical activity will improve arterial stiffness in this population remains to be determined.


[How to improve continuing education and quality improvement in general practice?].
Research has shown that many activities routinely used for continuing education and quality improvement in general practice, such as written information and lectures, have little or no effect on practice. The Norwegian Institute of Public Health initiated a consensus-building process on how to improve continuing education and quality improvement in Norwegian general practice. The work of the consensus panel led to a report in which nine initiatives were proposed: development of a national plan, strengthening of the support available for group-based learning, academic outreach visits, practice based activities, personal learning plans, a national centre for quality improvement in general practice, improved use of referral and discharge information, multidisciplinary collaboration, and patient involvement.


Status of the feline retina 5 years after subretinal implantation.
Retinal prosthetics are designed to restore functional vision to patients with photoreceptor degeneration by detecting light and stimulating the retina. Since devices are surgically implanted into the eye, long-term biocompatibility and durability are critical for viable treatment of retinal disease. To extend our previous work, which demonstrated the biocompatibility of a microphotodiode array (MPA) for 10 to 27 months in the normal feline retina, we implanted normal cats with an MPA implant backed with either an iridium oxide or platinum electrode and examined retinal function and biocompatibility for 3 to 5 years. All implants functioned throughout the study period. Retinal function remained steady and normal with a less than 15 percent decrease in electroretinogram response. The retinas had normal laminar structure with no signs of inflammation or rejection in areas adjacent to or distant from the implants. Directly over the implants, a loss of photoreceptor nuclei and remodeling of inner retinal layers existed. These results indicate that the subretinal MPA device is durable and well tolerated by the retina 5 years postimplantation.


Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL).
The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective. This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6-8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients. The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits. ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019.


The transsphenoidal approach. A historical perspective.
Over the last century, the transsphenoidal approach has evolved into the first-line method of treatment for sellar as well as select groups of parasellar and suprasellar lesions. The journey to its current popularity has been marked by controversy and near abandonment in the late 1920s, followed by its renaissance in the late 1960s. Despite the profound skepticism with which this procedure was viewed, several visionary neurosurgeons persevered through its nadir in popularity, preserving this surgical corridor to the skull base. Advances in medical and surgical techniques, paralleling an improved understanding of pituitary pathophysiology, contributed to its resurgence. The transsphenoidal procedures now performed stem from an array of modifications and refinements accumulated through nearly 100 years of medical and surgical evolution. This era's critical innovations and neurosurgical personalities are the topic of this historical overview.


Pattern electroretinogram progression in glaucoma suspects.
To prospectively monitor progressive changes of retinal ganglion cell function in early glaucoma using the pattern electroretinogram (PERG). Fifty-nine patients enrolled as glaucoma suspects were observed untreated over an average of 5.7±1.4 years, during which they were tested with PERG (PERGLA paradigm) and standard automated perimetry (SAP) 2 times per year. PERG amplitude and phase were normalized for physiological age-related changes, and linear regressions fitted to the data to calculate progression slopes (signal), slope SE (noise), and corresponding signal-to-noise ratios (SNR=slope÷SE). Linear regressions were also used to fit SAP global indices mean deviation (MD) and pattern standard deviation (PSD). On average, progression slopes of PERG amplitude/phase were skewed toward negative values, their mean being significantly (P<0.01) different from zero. In contrast, mean slopes of SAP-MD and PSD were not significantly different from zero. SNRs were higher for PERG than SAP (P<0.01). A substantial number of eyes displayed significant (P<0.05) progression of PERG amplitude (15% to 20%) or PERG phase (16% to 25%). Fewer eyes displayed significant progression of SAP-MD (0% to 2%) or SAP-PSD (4% to 8%). The PERG displayed clear longitudinal loss of signal (diminished amplitude, phase delay, or both) in a substantial number of eyes of patients, indicating progressive deterioration of retinal ganglion cell function. Progression of SAP global indices MD and PSD was found in a relatively smaller number of eyes. It remains to be established whether PERG progression has predictive value for developing visual dysfunction.


Harnessing bacteriocin biology as targeted therapy in the GI tract.
Recently, our laboratory demonstrated that bacteriocins produced by commensal enterococci provide an advantage in niche maintenance in the highly competitive environment of the gastrointestinal (GI) tract. Bacterial production of bacteriocins is a conserved defense strategy to help establish an ecological niche. Bacteriocin-encoding genes in enterococci are often carried on mobile genetic elements, including conjugative plasmids, enabling the transfer of such traits to other community members in a shared niche. Use of a novel mouse model for enterococcal colonization of the GI tract allowed us to investigate enterococcal dynamics and the role of enterococcal bacteriocins in the mouse GI tract. We examined the role of bacteriocin-21, carried on the pPD1 plasmid, in enterococcal colonization of the gut. We discovered that Enterococcus faecalis (EF) harboring pPD1 effectively colonizes the GI tract by using Bac-21 to eliminate its competition. In our study, we also present evidence for active conjugation in the GI tract, a strategy EF uses to enhance the number of bacteriocin producers in a given niche and eliminate bacteriocin-susceptible populations. Using an engineered strain of EF that is capable of producing Bac-21 but impaired in its conjugation ability, we were able to reduce pre-existing colonization by vancomycin-resistant enterococci in the mouse gut. Thus, our results suggest a novel therapeutic strategy to de-colonize antibiotic-resistant enterococci from the GI tract of patients and thereby prevent the emergence of resistant enterococcal infections that are otherwise difficult, or impossible, to treat.


Optical characterization of two-dimensional array of 2,048 tilting micromirrors for astronomical spectroscopy.
A micromirror array composed of 2048 silicon micromirrors measuring 200 × 100 μm² and tilting by 25° was developed as a reconfigurable slit mask for multi-object spectroscopy (MOS) in astronomy. The fill factor, contrast, and mirror deformation at both room and cryogenic temperatures were investigated. Contrast was measured using an optical setup that mimics a MOS instrument, and mirror deformation was characterized using a Twyman-Green interferometer. The results indicate that the array exhibited a fill factor of 82%, a contrast ratio of 1000:1, and surface mirror deformations of 8 nm and 27 nm for mirrors tilted at 298 K and 162 K, respectively.


Detection of latent bloodstains beneath painted surfaces using reflected infrared photography.
Bloodstain evidence is a highly valued form of physical evidence commonly found at scenes involving violent crimes. However, painting over bloodstains will often conceal this type of evidence. There is limited research in the scientific literature that describes methods of detecting painted-over bloodstains. This project employed a modified digital single-lens reflex camera to investigate the effectiveness of infrared (IR) photography in detecting latent bloodstain evidence beneath a layer or multiple layers of paint. A qualitative evaluation was completed by comparing images taken of a series of samples using both IR and standard (visible light) photography. Further quantitative image analysis was used to verify the findings. Results from this project indicate that bloodstain evidence can be detected beneath up to six layers of paint using reflected IR; however, the results vary depending on the characteristics of the paint. This technique provides crime scene specialists with a new field method to assist in locating, visualizing, and documenting painted-over bloodstain evidence.


No-scalpel vasectomy outside China.
Since 1985, the no-scalpel vasectomy technique has been widely used outside China. The prevalence of this technique has helped to increase the acceptability of male sterilization in many parts of the world. More than 5000 physicians in twenty-five developing countries have been trained in the no-scalpel vasectomy technique. In the United States in 1995, nearly one third of vasectomies employed the no-scalpel technique, and in the whole Northern American region, a total of 1100 doctors have been made familiar with the technique. Doctors believe that there are several advantages of the no-scalpel technique, including no incision, no stitches, faster procedure, faster recovery, less chance of bleeding, less discomfort and high efficacy. The key steps of the technique include fixation of the vas and infiltration anaesthesia of the spermatic cord, as well as grasping, delivering and isolating the vas. No-scalpel technique provides a good approach to expose the vas, in conjunction with which, different vas-end occlusion methods may be used.


[Famotidine versus placebo in prevention of the recurrence of duodenal ulcer disease. A multicenter study in Germany, Austria and Italy].
The aim of this study was to gain experience concerning efficacy and safety of famotidine, the new H2-receptor antagonist, for the maintenance of duodenal ulcer disease. 344 patients whose acute duodenal ulceration had recently been healed under famotidine or ranitidine were recruited for a year maintenance treatment with 20 mg bedtime dose of famotidine or placebo. 167 patients were treated with famotidine over 6 and 52 over 12 months. The corresponding numbers in the placebo control were 177 and 21. A life table method of analyses showed that the ulcer relapse rate was consistently and significantly (p less than 0.01) lower on famotidine than on placebo after 6 months (26% [43/167] versus 55% [98/177]). Of the 52 patients treated with 20 mg famotidine at night for further 6 months 7 (14%) developed an ulcer relapse. Of the 21 patients treated for further 6 months with placebo 5 (24%) showed an acute ulcer crater at endoscopy. Famotidine was well tolerated in the longterm therapy. The results confirm the efficacy and safety of famotidine in the prevention of duodenal ulcer relapse for at least 6 months.