The coding of odour-intensity in the honeybee antennal lobe: local computation optimizes odour representation.
We investigated strategies involved in odour intensity coding by the primary olfactory centre of insects, the antennal lobe (AL), the structural and functional analogue of the olfactory bulb. Using calcium imaging in the honeybee, we simultaneously measured the projection neuron output responses and a compound signal dominated by receptor neuron input in identified olfactory glomeruli to odours spanning seven log units of concentration. A comparison of the two processing levels indicates that the intercellular computation within the AL modulates and contrast-enhances the primary olfactory signals. As a result the AL network optimizes the olfactory code: odour representation is improved at lower concentrations, the relative activity of olfactory glomeruli allows encoding odour quality over up to four log-unit concentrations, and odour-intensity is reliably represented in the overall excitation across AL.


Improvement in health-related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study.
Little is known about the health-related quality of life (HRQoL) burden of haemophilia B. The aim of this study was to assess HRQoL burden of haemophilia B, the benefit of recombinant factor IX (rFIX) prophylaxis and the HRQoL benefit of achieving a zero annual bleed rate. Subjects receiving rFIX (BAX326) prophylaxis or on-demand completed the SF-36 survey. Baseline SF-36 scores were compared to the general US population scores to understand the HRQoL burden. Changes in SF-36 scores between baseline and follow-up were tested using t-tests. Subgroup analysis was conducted to examine SF-36 change among subjects who switched to BAX326 prophylaxis. SF-36 scores were also compared between those with zero bleeds and those who bled during the study. Compared to the US norms, subjects reported lower average scores in all physical and several mental HRQoL domains. At follow-up, prophylaxis subjects reported statistically significant and clinically meaningful improvements in overall physical HRQoL, as measured by the Physical Component Score (PCS) (mean change 2.60, P = 0.019), Bodily Pain (BP) (3.45, P = 0.015) and Role Physical (RP) domains (3.47, P = 0.016). Subjects who switched to prophylaxis from intermittent prophylaxis or on-demand experienced more pronounced improvements not only in the PCS (3.21, P = 0.014), BP (3.71, P = 0.026), RP (4.43, P = 0.008) but also in Vitality (3.71, P = 0.04), Social Functioning (5.06, P = 0.002) and General Health domains (3.40, P = 0.009). Subjects achieving zero bleeds reported lower BP (P = 0.038). Prophylaxis with BAX326 significantly improved HRQoL in patients with moderately severe or severe haemophilia B by reducing bleeds.


[Progress on recessive blood loss after total knee arthroplasty].
After total knee arthroplasty, the hemoglobin descending level is not in accord with blood loss volume because of recessive blood loss. Recessive blood loss will delay wound healing, increase infected opportunity, prolong rehabilitation exercise time, effect clinical outcome, so prevention of recessive blood loss is very important. This review is about the effect of gender, age, height and weight, tourniquet, operative time and operative trauma, postoperative anticoagulation, unilateral or bilateral total knee arthroplasty, autoblood reinfusion on the recessive blood loss, which maybe is helpful for the prevention of recessive blood in total knee arthroplasty.


An alternate pathway for the processing of the prolipoprotein signal peptide in Escherichia coli.
Previous studies showed that when the signal sequence plus 9 amino acid residues from the amino terminus of the major lipoprotein of Escherichia coli was fused to beta-lactamase, the resulting hybrid protein was modified, proteolytically processed, and assembled into the outer membrane as was the wild-type lipoprotein (Ghrayeb, J., and Inouye, M. (1983) J. Biol. Chem. 259, 463-467). We have constructed several hybrid proteins with mutations at the cleavage site of the prolipoprotein signal peptide. These mutations are known to block the lipid modification of the lipoprotein at the cysteine residue, resulting in the accumulation of unprocessed, unmodified prolipoprotein in the outer membrane. The mutations blocked the lipid modification of the hybrid protein. However, in contrast to the mutant lipoproteins, the cleavage of the signal peptides for the mutant hybrid proteins did occur, although less efficiently than the unaltered prolipo-beta-lactamase. The mutant prolipo-beta-lactamase proteins were cleaved at a site 5 amino acid residues downstream of the prolipoprotein signal peptide cleavage site. This new cleavage between alanine and lysine residues was resistant to globomycin, a specific inhibitor for signal peptidase II. This indicates that signal peptidase II, the signal peptidase which cleaves the unaltered prolipo-beta-lactamase, is not responsible for the new cleavage. The results demonstrate that the cleavage of the signal peptide is a flexible process that can occur by an alternative pathway when the normal processing pathway is blocked.


Anomaly of the supraclavicular nerve: case report and review of the literature.
We report a male cadaver found to have his right intermediate branch of the supraclavicular nerve piercing the clavicle. No other anomalies were found in this specimen. Following a review of the literature, it appears that symptoms related to this finding are rare but do occur most commonly involving the intermediate branch of the supraclavicular nerve. Symptoms may be alleviated with surgical decompression of the entrapped nerve. Although rare, the clinician should include entrapment of the supraclavicular nerve within the clavicle in their differential diagnosis of shoulder pain.


Primary hyperoxaluria type 1 in The Netherlands: prevalence and outcome.
Primary hyperoxaluria type 1 (PH1) is a phenotypically heterogeneous disease. To date the relationship between biochemical parameters and outcome is unclear. We therefore undertook a national cohort study on biochemical and clinical parameters and outcome in PH1. Review of medical charts of all Dutch PH1 patients, who were identified by sending questionnaires to all Dutch nephrologists for children and adults. Fifty-seven patients were identified. The prevalence and incidence rates were 2.9/10(6) and 0.15/10(6)/year, respectively. Median age at diagnosis was 7.3 years (range 0-57). Seventeen (30%) patients were older than 18 years at time of diagnosis, of whom 10 (59%) presented with end-stage renal disease (ESRD), in contrast to only nine (23%) of those aged under 18 years. Median age at initial symptoms was 6.0 years (range 0-50). In four of nine patients with infantile PH1, normal renal function was preserved after a median follow-up of 7.7 years (range 0.1-16). Progression to renal insufficiency was associated with the presence of nephrocalcinosis, as assessed by ultrasound (relative risk=1.8; 95% CI, 1.0-3.4) and with pyridoxine-unresponsiveness (relative risk=2.2; 95% CI, 1.1-4.2) but not with age at presentation, the extent of hyperoxaluria, or AGT activity. No apparent nephrocalcinosis was found in five of the 19 patients who presented with ESRD. Although more than one-half of the PH1 patients have symptoms under the age of 10 years, PH1 can present at any age. In adults, PH1 presents predominantly with ESRD, which may be due to misinterpretation of early symptoms. Although nephrocalcinosis is correlated with development of renal insufficiency, the latter can occur even in the absence of nephrocalcinosis. Pyridoxine sensitivity is associated with better outcome in PH1.


Novel molecular hybrids of cinnamic acids and guanylhydrazones as potential antitubercular agents.
In an attempt to identify potential new agents active against tuberculosis, 20 novel phenylacrylamide derivatives incorporating cinnamic acids and guanylhydrazones were synthesized using microwave assisted synthesis. Activity of the synthesized compounds was evaluated using resazurin microtitre plate assay (REMA) against Mycobacterium tuberculosis H37Rv. Based on empirical structure-activity relationship data it was observed that both steric and electronic parameters play major role in the activity of this series of compounds. Compound 7s (2E)-N-((-2-(3,4-dimethoxybenzylidene) hydrazinyl) (imino) methyl)-3-(4-methoxyphenyl) acrylamide showed MIC of 6.49microM along with good safety profile of >50-fold in VERO cell line. Thus, this compound could act as a potential lead for further antitubercular studies.


Chromosome numbers of Tritrichomonas foetus and Tritrichomonas suis.
Tritrichomonas foetus and Tritrichomonas suis isolates were cultivated axenically in Diamond's medium. Studies on the chromosome numbers of these two species with a light microscope were done by adding different concentrations of colchicine into the medium, incubating at 37 degrees C for 6-8 h and using a hypotonic swelling technique. The diploid chromosome numbers of both T. foetus and T. suis were 2n=10.


A metronidazole-resistant strain of Trichomonas vaginalis and its sensitivity to Go 10213.
In the present study the comparative in-vitro and in-vivo efficacy of Go 10213 was compared with those of metronidazole, secnidazole, tinidazole, ornidazole and nimorazole against a metronidazole-resistant strain of T. vaginalis. Go 10213 was found to be superior in activity. It appears more promising than the drugs mentioned above on the basis of the evidence presented.


Comparative analysis of the reproductive ecology of Monotropa and Monotropsis: Two mycoheterotrophic genera in the Monotropoideae (Ericaceae).
Studies of mycoheterotrophs, defined as plants that obtain carbon resources from associated mycorrhizal fungi, have fundamentally contributed to our understanding of the importance and complexity of symbiotic ecological interactions. However, to date, the reproductive ecology of these organisms remains empirically understudied, with existing literature presenting hypotheses about traits including a generalist pollination syndrome and autogamous self-pollination. To address this gap in our knowledge of the reproductive ecology of mycoheterotrophic plants, we comparatively analyzed three species of two monotropoid genera, Monotropa and Monotropsis. During three consecutive years of field observations and manipulations of four populations of Monotropa uniflora, seven of M. hypopitys (both red and yellow color forms), and two of Monotropsis odorata, we investigated flowering phenology, pollination ecology, breeding system, floral herbivory, and reproductive effort and output. Contrary to previous predictions, our results revealed that taxa are largely outcross-pollinated and specialized toward Bombus pollinators. Additionally, species differ in breeding system, timing and duration of reproductive development, fluctuations in reproductive effort and output, and fitness impacts of herbivory. This study is the first thorough investigation of the reproductive ecology of mycoheterotrophic species and provides insight into possible limitations in reproductive traits imposed by a mycoheterotrophic life history.


In vitro recognition of an orf virus early promoter in a vaccinia virus extract.
DNA fragments containing varying lengths of the 5' end of an orf virus early gene (ORF3) and its associated promoter were introduced into sodium deoxycholate-solubilized vaccinia virus extracts capable of initiating transcription in vitro from vaccinia virus early promoters. After separation of the radiolabelled products of the reactions on a 5% polyacrylamide/7 M urea gel, discrete transcripts were detected the sizes of which were consistent with initiation of transcription from the orf virus early promoter. This is the first demonstration in a functional assay of the conservation of early transcriptional promoters between an orthopoxvirus and a parapoxvirus.


Crypt cells of the zebrafish Danio rerio mainly project to the dorsomedial glomerular field of the olfactory bulb.
The olfactory mucosa of the zebrafish consists of 3 morphological types of olfactory receptor neurons (ORNs): ciliated, microvillous, and crypt cells. Previous studies in the zebrafish have revealed differential projections of ciliated and microvillous ORNs, which project to different glomerular fields. However, the bulbar targets of zebrafish crypt cells were not identified. Here, we analyze the relationship between crypt cells of the olfactory epithelium and dorsal glomerular fields of the zebrafish olfactory bulbs, as wells as the connections between these bulbar regions and forebrain regions. For this purpose, a lipophilic carbocyanine tracer (DiI) was used in fixed tissue. Application of DiI to the dorsomedial glomerular field mainly labeled crypt cells in the zebrafish olfactory epithelium. By contrast, application of DiI to the dorsolateral glomerular fields mainly labeled bipolar ORNs and only occasionally crypt cells. Bulbar efferent cells (mitral cells) contacting these dorsal glomerular fields project to different telencephalic areas, with the posterior zone of the dorsal telencephalic area (Dp) as the common target. However, dorsomedial and dorsolateral glomerular fields projected differentially to the ventral telencephalon, the former projecting to the ventrolateral supracommissural region. Retrograde labeling from the ventrolateral supracommissural region revealed mitral cells associated with 2 large glomeruli in the bulbar dorsomedial region, which putatively receives inputs from the crypt cells, indicating the existence of a crypt cell olfactory subsystem with separate projections, in the zebrafish. The comparative significance of the secondary olfactory pathways of zebrafish that convey information from crypt cells is discussed.


Pain as an evolutionary necessity.
The proposed title "Pain as an evolutionary necessity" could lead to a broad debate with implications covering many chapters of the medicine and particularly of clinical neurology. In the present perspective, the discussion will focus on migraine and cluster headache chosen as elective examples of biological and not only clinical conditions, that unveil the bond between pain and necessity. Migraine, cluster headache, and perhaps other primary headaches begin to be depicted in terms of recurrent activation of innate bio-behavioral specific patterns, with a crucial and highly conserved evolutionarily adaptive significance. The pan-mammalian sickness behavior and the fight or flight response, selectively activated by different kinds of pain, are here proposed as paradigmatic of migraine and cluster headache attacks associated behaviors, allowing to reformulate these forms as the inappropriate recurrent presentation of coordinated allostatic processes, modeled along million of years of natural evolution. In this light, all the multifaceted characteristics of migraine and cluster headache attacks can be reinterpreted as complex and integrated allostatic defensive reactions to an inescapable or to an escapable pain, respectively aimed to the restoration of biologic homeostasis through a temporary disengagement from active interaction with environment (migraine associated sickness behavior) or, on the contrary, to promote the coordinated biological changes preparatory to emergency and defensive behaviors (cluster headache-related fight or flight response).


Chemotherapy for advanced cervical cancer with methotrexate, bleomycin, and cis-dichlorodiammineplatinum(II).
Nine patients with advanced cancer of the uterine cervix, having failed radiotherapy, were treated with a combination regimen of parenteral methotrexate, bleomycin, and cis-dichlorodiammineplatinum(II). Eight of the patients had objective partial remissions lasting a median of 4 months. All patients improved subjectively. Five of the patients, however, had sudden unpredictable onset of severe myelosuppression accompanied by stomatitis. Such frequent severe toxicity was not observed in patients with other malignancies treated with this combination. It is likely that impaired excretion of methotrexate resulting from ureteral dysfunction led to increased toxicity. In future protocols for advanced cervical cancer, methotrexate will be replaced by other effective agents. The very high response rate (89%) suggests that similar but less toxic combinations may contribute substantially to the future effective treatment of advanced cervical cancer.


Temporal and Spatial Patterns in Utilization of Mental Health Services During and After Hurricane Sandy: Emergency Department and Inpatient Hospitalizations in New York City.
Hurricane Sandy made landfall on October 29, 2012, causing a coastal storm surge and extensive flooding, which led to the closure of several health care facilities in New York City (NYC) and prolonged interruptions in service delivery. The impact on mental health-related emergency department (ED) and inpatient hospital service utilization was studied. Data came from the New York Statewide Planning and Research Cooperative System. We obtained mental health-related data among NYC residents from 2010 to 2013. Patients were grouped into 5 geographic areas, including service areas of closed hospitals, the Hurricane Sandy evaluation zone, and all of NYC. The Farrington method was used to detect increases in ED visits and hospitalizations for the post-Sandy period. Open hospitals experienced a substantial increase in psychiatric ED visits from patients living in the service areas of closed hospitals. This surge in psychiatric ED visits persisted for 4 to 6 months after Hurricane Sandy. However, the increase in psychiatric hospitalizations was observed for 1 to 3 months. Several NYC hospitals received a substantially larger number of ED patients from service areas of closed hospitals after Hurricane Sandy, unlike other hospitals that experienced a decrease. Because of potential surges in the number of psychiatric ED visits, resource allocation to hospitals should be considered. (Disaster Med Public Health Preparedness. 2016;10:512-517).


Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts.
Abnormal alterations in cardiac expression of vascular endothelial growth factor (VEGF) as well as its receptors and impairment in the development of coronary collaterals have recently been reported in diabetic subjects. However, the presence of pharmacological intervention on these defects in diabetes remains unsettled. Here, we studied the effect of endothelin (ET) receptor blockade on cardiac VEGF signaling pathways and cardiac function in Sprague-Dawley rats 5 wk after induction of type I diabetes with streptozotocin (65 mg/kg ip) in comparison with age-matched control rats. After streptozotocin (1 wk), some diabetic rats were treated with the ET receptor antagonist SB-209670 (1 mg/day) for 4 wk. VEGF, its receptors, and its angiogenic signaling molecules [phosphorylated Akt and endothelial nitric-oxide synthase (eNOS)] were analyzed by Western blot, ELISA, real-time PCR, and immunohistochemistry, and cardiac function was evaluated by echocardiography. Coronary capillary morphology was assessed by lectin and enzymatic double staining. We found significant decreases in cardiac expression of VEGF, its receptors, phosphorylation of Akt and eNOS, and coronary capillary density in diabetic rats compared with controls. Treatment of diabetic rats with SB-209670 reversed these alterations to the control levels and ameliorated impairment of cardiac function. From a molecular point of view, the present study is the first to indicate the potential usefulness of an ET receptor antagonist in the treatment of cardiac dysfunction in type I diabetes.


Molecular cloning, genomic structure and expression analysis of major histocompatibility complex class Iα gene of half-smooth tongue sole (Cynoglossus semilaevis).
Major histocompatibility complex (MHC) has a central role in the adaptive immune system by presenting foreign peptide to the T-cell receptor. The full length of MHC class Iα cDNA was cloned from half-smooth tongue sole by homology cloning and rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR), genomic organization and expression of MHC Iα were examined to study the function of MHC gene in fish. The domain structure feature and antigen-binding motifs of other teleost and mammals MHC are conserved in the half-smooth tongue sole MHC Iα gene. The deduced amino acid sequence of half-smooth tongue sole MHC Iα (GenBank accession no. FJ372720) had 12.1-61.8% identity with those of human and other fish. Eight exons and seven introns were identified in MHC Iα gene. Real-time quantitative PCR demonstrated that MHC Iα gene was ubiquitously expressed in normal tissues, while that in Vibrio anguillarum infected fish was significantly increased in intestines and decreased in spleen and liver from 24 to 72 h after infection, followed by a recovery to normal level after 96 h.


Combined effects of proinflammatory cytokines and intermittent cyclic mechanical strain in inhibiting osteogenicity in human periodontal ligament cells.
Mechanical strain plays an important role in bone formation and resorption during orthodontic tooth movement. The mechanism has not been fully studied, and the process becomes complex with increased amounts of periodontal patients seeking orthodontic care. Our aims were to elucidate the combined effects of proinflammatory cytokines and intermittent cyclic strain (ICS) on the osteogenic capacity of human periodontal ligament cells. Cultured human periodontal ligament cells were exposed to proinflammatory cytokines (interleukin-1β 5 ng/mL and tumor necrosis factor-α 10 ng/mL) for 1 and 5 days, and ICS (0.5 Hz, 12% elongation) was applied for 4 h per day. The autocrine of inflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of osteoblast markers runt-related transcription factor 2 and rabbit collagen type I was determined using real-time polymerase chain reaction and Western blot. The osteogenic capacity was also detected by alkaline phosphatase (ALP) staining, ALP activity, and alizarin red staining. We demonstrated that ICS impaired the osteogenic capacity of human periodontal ligament cells when incubated with proinflammatory cytokines, as evidenced by the low expression of ALP staining, low ALP activity, reduced alizarin red staining, and reduced osteoblast markers. These data, for the first time, suggest that ICS has a negative effect on the inductive inhibition of osteogenicity in human PDL cells mediated by proinflammatory cytokines.


The development of a patient-specific method for physiotherapy goal setting: a user-centered design.
To deliver client-centered care, physiotherapists need to identify the patients' individual treatment goals. However, practical tools for involving patients in goal setting are lacking. The purpose of this study was to improve the frequently used Patient-Specific Complaints instrument in Dutch physiotherapy, and to develop it into a feasible method to improve physiotherapy goal setting. An iterative user-centered design was conducted in co-creation with the physiotherapists and patients, in three phases. Their needs and preferences were identified by means of group meetings and questionnaires. The new method was tested in several field tests in physiotherapy practices. Four main objectives for improvement were formulated: clear instructions for the administration procedure, targeted use across the physiotherapy process, client-activating communication skills, and a client-centered attitude of the physiotherapist. A theoretical goal-setting framework and elements of shared decision making were integrated into the new-called, Patient-Specific Goal-setting method, together with a practical training course. The user-centered approach resulted in a goal-setting method that is fully integrated in the physiotherapy process. The new goal-setting method contributes to a more structured approach to goal setting and enables patient participation and goal-oriented physiotherapy. Before large-scale implementation, its feasibility in physiotherapy practice needs to be investigated. Implications for rehabilitation Involving patients and physiotherapists in the development and testing of a goal-setting method, increases the likelihood of its feasibility in practice. The integration of a goal-setting method into the physiotherapy process offers the opportunity to focus more fully on the patient's goals. Patients should be informed about the aim of every step of the goal-setting process in order to increase their awareness and involvement. Training physiotherapists to use a patient-specific method for goal setting is crucial for a correct application.


Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults.
Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to 'schizophrenia-like' cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter:total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.


[What is the role of surgery in low back pain associated with Modic changes?]
Benign low back pain is frequent in the lucratively active population. Degenerative changes are considered the most frequent causes. The identification of pain generators remain challenging. Bone marrow lesions, Modic changes, are frequently associated with benign low back pain, mostly type 1. The etiology of Modic changes is unknown, both infectious and autoimmune mechanisms have been suggested. Despite the strong association of Modic changes with low back pain it is not clear whether lumbar surgery (lumbar fusion, total disc replacement) has any role in the management of these patients. We conclude that all available evidence in literature is inconclusive and future studies are needed addressing more precisely the question of minimal clinically important difference (MCID) while considering of all confounding factors influencing outcome.


Magnetic resonance imaging and histopathology in dementia, clinically of frontotemporal type.
The magnetic resonance imaging (MRI) and computed tomography findings in 28 patients with the clinical diagnosis of frontotemporal dementia (FTD) were compared with the findings in a control group of 76 individuals without dementia or stroke. A pattern of frontal and temporal atrophy with predominantly frontal white matter changes was found in the FTD patients, and this was significantly different from the radiological findings in the control group. Six of the FTD patients have undergone autopsy. Histopathological evaluation showed a primary cortical degenerative disease (frontal lobe degeneration of non-Alzheimer type) in 3 of them, and primary white matter disorder, mainly frontal, of basically ischemic type (selective incomplete white matter infarction) in 3 of them. MRI could be a helpful tool to support the clinical diagnosis FTD, especially in young patients. MRI may also be helpful for the differentiation of a primary neurodegenerative from a mainly ischemic-vascular type of dementia.


[Molecular genetic findings in patients with congenital cone dysfunction. Mutations in the CNGA3, CNGB3, or GNAT2 genes].
This study compares clinical and molecular genetic findings in patients with congenital cone dysfunction. In this study 28 patients underwent a basic ophthalmologic examination. Except for a 1-year-old boy, color vision, perimetry, and full-field ERG (ISCEV standard) were evaluated in all patients. Blood samples were taken for molecular genetic analysis of the CNGA3, CNGB3, or GNAT2 genes. Two patient groups could be distinguished: patients without and with residual cone function in the ERG. In 14 of 17 patients without cone function, mutations in one of the three genes were detected, and except for one patient mutations in both alleles could be determined. In these patients, visual acuity was reduced to 20/400 and color discrimination was absent. In 2 of 11 patients with residual cone function, mutations in one allele of the CNGB3 gene were detected. It is of interest that 6 of 16 patients with mutations perceived their disease as progressive; in three of them we could determine a progression. Only in 4 of 16 patients was the ocular fundus normal. The other patients with mutations presented with central pigment irregularities, attenuated vessels, or pale optic disk. In patients with congenital cone dysfunction without cone function in the ERG, an analysis of the CNGA3, CNGB3, or GNAT2 gene is advisable. In contrast, patients with residual cone function did not show clear association with mutations in one of the three genes. In patients with mutations, retinal alterations and nystagmus are frequent. In contrast to the designation of these disorders as stationary, in some patients with mutations in the CNGA3 and CNGB3 gene slow progression was observed.


Lowering the Size Detection Limits of Ag and TiO2 Nanoparticles by Single Particle ICP-MS.
As the production and use of engineered nanomaterials increase, there is an urgent need to develop analytical techniques that are sufficiently sensitive to be able to measure the very small nanoparticles (NP) at very low concentrations. Although single particle ICP-MS (SP-ICP-MS) is emerging as one of the best techniques for detecting NP, it is limited by relatively high size detection limits for several NP, including many of the oxides. The use of a high sensitivity sector field ICP-MS (ICP-SF-MS), microsecond dwell times, and dry aerosol sample introduction systems were examined with the goal of lowering the size detection limits of the technique. For samples injected as a wet aerosol, size detection limits as low as 4.9 nm for Ag NP and 19.2 nm for TiO2 NP were determined. By using a dry aerosol, a significant gain in ion extraction from the plasma was obtained, which resulted in a noticeable decrease of the size detection limits to 3.5 nm for the Ag NP and 12.1 nm for the TiO2 NP. These substantial improvements were applied to the detection of TiO2 NP in sunscreen lotions, rainwaters, and swimming pool waters. Concentrations of Ti-containing NP between 27 and 193 μL-1 were found in rain samples. Similar NP concentrations were detected in public swimming pools, although much higher particle number concentrations (6046 ± 290 μL-1) were measured in a paddling pool, which was attributed to a high concentration of sunscreen lotions in a small recirculated water volume. High losses of TiO2 NP through adsorption or agglomeration resulted in recoveries ranging from 14-34%.


[Age structure of methanol-assimilating Candida boidinii cells].
A population of Candida boidinii was grown under the chemostat conditions at a dilution rate of 0.14-0.20 h-1 in a mineral medium with methanol as a sole source of carbon and energy. Its age structure was analysed taking account of the reproductive age (the number of cycles) and the cyclic age of the cells (the phase of a cell cycle). Four morphological phases of the cycle, namely, one phase of preparation for budding and three successive budding phases, were compared with the phases G1, S, G2 and M. In terms of their reproductive age, the cells can be arranged as follows: (1) cells that formed no buds at all, 43 +/- 5%; (2) cells after one cycle of budding, 28 +/- 4%; (3) cells from which two and more daughter cells have separated, 29 +/- 4%. The age structure of an yeast population must be analysed when it is necessary to estimate its physiological heterogeneity or to elaborate the cultivation of microorganisms involving the control over the age structure of the population.


Ventilator Liberation for High-Risk-for-Failure Patients: Improving Value of the Spontaneous Breathing Trial.
Several patient populations have been identified as high risk for extubation failure despite successful completion of a spontaneous breathing trial (SBT). Extubation failure and subsequent need for emergent re-intubation have been associated with increased morbidity and mortality. In this review, we discuss ways to optimize the value and performance of the SBT in a subgroup of high-risk patients (elderly, cardiac, and/or respiratory failure) to reduce the rate of extubation failure. We recommend the use of T-piece mode, longer duration SBT, and measurement of the rapid shallow breathing index (breathing frequency/tidal volume in L) off ventilatory support to increase the predictive value of the SBT. In addition, measurement of changes in central venous oxygen saturation and serum brain natriuretic peptide, and measurements of mitral inflow and annular velocity using bedside transthoracic echocardiography with tissue Doppler imaging may help guide the clinician in determining who and when to extubate and thus minimize the rate of extubation failure. Arterial blood gas analysis performed at the end of the SBT may help determine who will benefit from prophylactic use of noninvasive ventilatory support postextubation.


Carbon-concentrating mechanism in a green alga, Chlamydomonas reinhardtii, revealed by transcriptome analyses.
Aquatic photosynthetic organisms can acclimate to the variable and limiting availability of CO(2) by operation of carbon-concentrating mechanism (CCM) that allows them to optimize carbon acquisition for photosynthesis. The CCMs of both eukaryotic alga and cyanobacteria function to facilitate CO(2) assimilation, when inorganic carbon (Ci; CO(2) and/or HCO(3)(-)) is limited. By active Ci uptake systems, internal Ci levels are increased and then carbonic anhydrase supplies sufficient CO(2) to ribulose 1,5-bisphosphate carboxylase/oxygenase by the dehydration of accumulated bicarbonate. Although the molecular components of CCM have been intensively studied in cyanobacteria, significant advances in understanding of the eukaryotic CCM have been achieved especially in a model green alga, Chlamydomonas reinhardtii. Recent accumulation of genomic sequence data of algae leads to start comparative genomic analyses of functional components of eukaryotic CCM. This review focuses on the recent advances in identifying and characterizing the components of the CCM by transcriptome analyses of the Chlamydomonas cells that are transferred to CO(2)-limiting stress conditions in light.


Ligament and tendon substitution with composite carbon fiber strands.
Carbon fiber strands were used experimentally to substitute for tendons in dogs and clinically to reconstruct tendons and ligaments in human. The investigation was carried out to determine the histologic appearance of the new composite structure and its tensile strength in comparison to the natural structure. The histologic picture disclosed a remarkable structure evolved by continuous irritation of the carbon fibers and consisting of two interrelated components: synthetic carbon fibers and biologic collagenous tissue. This carbon fiber composite structure was composed of long cylindrical units containing concentric layers of collagenous fibers and cells enveloping the core of each carbon fiber. After one year of physiologic use in dogs, the average ultimate tensile strength of the composite structure which replaced the quadriceps and triceps was 372 N, or 88% the strength of the natural tendons. One year after implantation the histologic picture of the composite structure in human showed a relatively dense collagenous architecture. However, a significant proportion of the structure was taken up by histiofibroblasts produced by the irritation of the carbon fibers. Thus, the density of the collagen in the composite structure remained relatively deficient in comparison to the nature tendon, and the structural tensile strength continued to depend entirely on the integrity of the carbon fibers.


[Introduction on the schools of the scalp acupuncture for treatment of the stroke hemiplegia].
Three representative schools of scalp acupuncture for the stroke hemiplegia such as Jiao's scalp acupuncture, Yu's scalp acupuncture and temporal three-needle are introduced and analyzed. Since the schools of scalp acupuncture are numerous and the bases of selection acupoints are complicated, it demands to determine the optimal needling acupoints by means of scientific research. Therefore, the selection acupoints would be adhering to scientific principles. The theoretical basis needs to be explored and studied further.


[Right pneumonectomy for typical bronchial carcinoid in a 19-year-old man].
A 19-year-old man visited our hospital with a diagnosis of carcinoid arising from the right intermediate bronchus. Clinical examination revealed T3N1M0 lung cancer, so right pneumonectomy with mediastinal lymph node dissection was performed after obtaining informed consent from the patient and his parents. Final pathological diagnosis was T2N2M0 typical carcinoid. Typical bronchial carcinoid with lymph node metastasis is very rare in patients under 20 years old.


In vitro detection of small molecule metabolites excreted from cancer cells using a Tenax TA thin-film microextraction device.
We developed a new device for the in vitro extraction of small molecule metabolites excreted from cancer cells. The extraction device, which was biocompatible and incubated with cancer cells, consists of a thin Tenax TA film deposited on the surface of a cylindrical aluminum rod. The Tenax TA solid phase was utilized for the direct extraction and preconcentration of the small molecule metabolites from a cell culture sample. The device fabrication and the metabolite extraction were optimized, tested, and validated using HeLa cell cultures. Comparison of metabolic profiles with the control measurement from the culture medium enabled detection of metabolites that were consumed or produced by the cell culture. Tentative identification and semi-quantitative investigation of the excreted metabolites were performed by GC-MS analysis. The proposed approach can be a valuable tool for the characterization of low-volatile cancer cell metabolites that are not covered by use of conventional methods based on headspace solid phase microextraction.


Developmental biology of the pancreas.
The pancreas is an organ containing two distinct populations of cells, the exocrine cells that secrete enzymes into the digestive tract, and the endocrine cells that secrete hormones into the bloodstream. It arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. Mammals, birds, reptiles and amphibians have a pancreas with similar histology and mode of development, while in some fish, the islet cells are segregated as Brockmann bodies. Invertebrates do not have a pancreas, but comparable endocrine cells may be found in the gut or the brain. The early pancreatic bud shows uniform expression of the homeobox gene IPF-1 (also known as IDX-1, STF-1 or PDX), which when mutated to inactivity leads to total absence of the organ. The occurrence of heterotopic pancreas in the embryo, and also the metaplasias that can be displayed by a regenerating pancreas in the adult, both suggest that only a few gene products distinguish the pancreatic cell state from that of the surrounding tissues of duodenum, gall bladder and liver. In the developing pancreatic buds, the endocrine cells start to differentiate before the exocrine cells, and co-expression of different hormones by the same cell is often observed at early stages. Although pancreatic endocrine cells produce many gene products also characteristic of neurons, evidence from in vitro cultures and from quailchick grafts shows that they are of endogenous and not of neural crest origin. Observational studies suggest strongly that both endocrine and exocrine cells arise from the same endodermal rudiment. Development of the pancreas in embryonic life requires a trophic stimulus from the associated mesenchyme. In postnatal life, all cell types in the pancreas continue to grow. Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration. Surgical removal of parts of the pancreas is followed by moderate but incomplete regeneration of both acini and islets. Poisoning with alloxan or streptozotocin can lead to permanent depletion of beta cells. Although the cell kinetics of the pancreas are not understood, it seems likely that there is a continuous slow turnover of cells, fed from a stem cells population in the ducts, and that the controls on the production rate of each cell type are local rather than systemic.


Monoamine metabolites in cerebrospinal fluid of depressive subgroups.
Lumbar punctures were performed on 69 patients who met Research Diagnostic Criteria (RDC) for major affective disorder, while they were drug-free and depressed. None of the patients met RDC for alcoholism. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured by fluorometry and 3-methoxy-4-hydroxyphenylglycol (MHPG) by gas chromatography. Family histories were ascertained by systematic interviews of patients and their relatives, and diagnoses were made by family history diagnostic criteria (Andreasen et al., 1977). Depressed patients with alcoholism in a first degree relative had significantly lower levels of 5-HIAA and MHPG than patients without a family history of alcoholism (p < 0.05). No difference in HVA levels was found. The metabolite differences remained significant when the influence of sex ratio was considered. These results are in agreement with previous work linking alcoholism to abnormal serotonin metabolism. They provide further biochemical evidence of distinct genetic subtypes of affective disorder along lines suggested by Winokur (1979a, 1979b), and illustrate the usefulness of the family history method in defining patient subgroups.


Combined MR imaging and numerical simulation of flow in realistic arterial bypass graft models.
We report methods for (a) transforming a three-dimensional geometry acquired by magnetic resonance angiography (MRA) in vivo, or by imaging a model cast, into a computational surface representation, (b) use of this to construct a three dimensional numerical grid for computational fluid dynamic (CFD) studies, and (c) use of the surface representation to produce a stereo-lithographic replica of the real detailed geometry, at a scale convenient for detailed magnetic resonance imaging (MRI) flow studies. This is applied to assess the local flow field in realistic geometry arterial bypass grafts. Results from a parallel numerical simulation and MRI measurement of flow in an aorto-coronary bypass graft with various inlet flow conditions demonstrate the strong influence of the graft inlet waveform on the perianastomotic flow field. A sinusoidal and a multi harmonic coronary flow waveform both with a mean Reynolds number (Re) of 100 and a Womersley parameter of 2.7 were applied at the graft inlet. A weak axial flow separation region just distal to the toe was found in sinusoidal flow near end deceleration (Re = 25). At the same location and approximately the same point in the cycle (Re = 30) but in coronary flow, the axial flow separation was stronger and more spatially pronounced. No axial flow separation occurred in steady flow for Re = 100. Numerical predictions indicate a region in the vicinity of the suture line (where there is a local narrowing of the graft) with a wall shear magnitude in excess of five times that associated with fully developed flow at the graft inlet.


Mutations affecting the structural genes and the genes coding for modifying enzymes for ribosomal proteins in Escherichia coli.
Temperature-sensitive mutants of an Escherichia coli K-12 strain PA3092 have been isolated following mutagenesis with nitrosoguanidine, and their ribosomal proteins analyzed by two-dimensional gel electrophoresis. This method was found to be very efficient in obtaining mutants with various structural alterations in ribosomal proteins. Thus a total of some 160 mutants with alterations in 41 different ribosomal proteins have so far been isolated. By characterizing these mutants, we could isolate not only those mutants with alterations in the structural genes for various ribosomal proteins, but also those with impairments in the modification of proteins S5, S18 and L12. Furthermore, a mutant has been obtained which apparently lacks the protein S20 (L26) with a concomitant reduction to a great extent of the polypeptide synthetic activity of the small subunit. The usefulness of these mutants in establishing the genetic architecture of the genes coding for the ribosomal proteins and their modifiers is discussed.


Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis.
Wnts are secreted signaling molecules implicated in a large number of developmental processes. Frizzled proteins have been identified as likely receptors for Wnt ligands in vertebrates and invertebrates, but a functional role for vertebrate frizzleds has not yet been defined. To assess the endogenous role of frizzled proteins during vertebrate development, we have identified and characterized a Xenopus frizzled gene (xfz8). It is highly expressed in the deep cells of the Spemann organizer prior to dorsal lip formation and in the early involuting marginal zone. Ectopic expression of xfz8 in ventral cells leads to complete secondary axis formation and can synergize with Xwnt-8 while an inhibitory form of xfz8 (Nxfz8) blocks axis duplication by Xwnt-8, consistent with a role for xfz8 in Wnt signal transduction. Expression of Nxfz8 in dorsal cells has profound effects on morphogenesis during gastrulation and neurulation that result in dramatic shortening of the anterior-posterior axis. Our results suggest a role for xfz8 in morphogenesis during the gastrula stage of embryogenesis.


The prevalence and predictors of solar protection use among adolescents.
Adolescence has been identified as a critical period in the etiology of subsequent melanoma and nonmelanocytic skin cancer. This study examines the prevalence and predictors of solar protection use among adolescents. A total of 3,642 adolescents between the ages of 11 and 16 years were recruited from a random sample of 27 schools in an Australian state. The participants completed a validated survey that provided information on a range of demographic, knowledge, attitudinal, and behavioral factors. Sun protection practices adopted during the preceding weekend were assessed using a validated self-report diary. A formula that quantifies protection status was then employed to categorize adolescents into those who were using adequate versus low levels of solar protection. Overall 54% of males and 44% of females were classified as adequately protected during the preceding weekend. Logistic regression analyses identified the following as significant predictors of having an adequate level of sun protection--gender (males more likely to be protected), age (11 to 13 year olds more likely to be protected than 14 to 16 years olds), ownership of a broad-brimmed hat or cap, attitudes relating to the discomfort associated with wearing a hat, image to peers, "hassle" associated with the use of sun protective measures, school attended, and sun protective policies of the school. Implications of these findings for future preventive strategies are discussed and include improved targeting of sun protection programs to non-adopters, modification of attitudes relating to suntans and image to peers, reducing the level of perceived difficulty associated with utilizing sunscreen, and the potential role that schools may play in fostering sun protection.


Non-locally coded Fourier-transform ghost imaging.
A non-locally coded Fourier-transform ghost imaging (FGI) scheme and relevant coded phase retrieval method have been proposed to improve the image quality in ghost imaging. By inserting masks in the reference beam, the sample in the test beam is non-locally modulated, and coded Fourier-transform diffraction patterns of the sample are obtained via intensity correlation calculations between the two beams. Encoding and decoding procedures are incorporated in the phase retrieval process based on traditional hybrid input-output algorithm. Simulation and experiment results show that the spatial information of samples is successfully recovered from the coded diffraction patterns obtained using three masks, and the image quality is improved remarkably. If promoting this approach to x-ray FGI systems, it may realize high-resolution x-ray microscopy without increasing the sample's radiation damage.


[Comparable efficacy between twice and three times daily for treatment of balance system disturbances].
In spite of detailed examinations it is impossible to find reasons for balance system disturbances in more than 25 per cent of patients. Therefore doctors have to treat symptoms but not the reasons for balance system disturbances. One of the most frequently administered medicine in treatment of both central and peripheral balance system disturbances is betahistine dihydrochloride (Betaserc). The aim of the study was to evaluate the influence of Betaserc an balance system disturbances with reference to dosage. Patients were divided into two groups. The first group (Group I) was treated with Betaserc three times a day: 16 mg for minimum 4 weeks and 8 mg for minimum 8 weeks. The second group (Group II) was treated with Betaserc twice a day: 24 mg for maximum 4 weeks and next 12 mg for minimum 8 weeks. The data from interviews and additional examinations (videonystagmography and posturography) were considered. The latter group more often showed smaller balance system disturbances and vertigo than the first group both after 4 and 12 weeks. After 12 weeks of treatment more patients from the second group reported "a complete disappearance" of the symptoms. A substantial improvement of results was observed in videonystagmography and posturography examinations. The treatment with 24 mg for 4 weeks and 12 mg for 8 weeks twice daily was better tolerated and gave higher positive effects than the treatment three times a day with 16 mg for 4 weeks and 8 mg for 8 weeks.


A low molecular weight heparin alters the fetal coagulation system in the pregnant sheep.
Standard heparin and a LMWH, CY222 do not cross the placenta nor alter fetal coagulation when injected into the pregnant ewe. We found that another LMWH, Pharmuka-10169 (PK-10169) alters fetal coagulation without crossing the placenta in the pregnant sheep. To characterize this anticoagulant we measured the in vitro and in vivo effects of 125I-PK-10169 in maternal and fetal plasmas following administration of PK-10169 to the mother or fetus. The fetal anticoagulant activity was not neutralizable by protamine sulphate and was attributable to the inhibition of thrombin but not factor Xa. In vitro, the fetal anticoagulant activity had properties similar to dermatan sulphate; both catalyzed the inhibition of thrombin but not factor Xa by sheep plasma; and neither was neutralizable by protamine sulphate. These effects were due to the enhanced neutralization of thrombin by heparin cofactor II. We conclude that PK-10169 does not cross the placenta, but does induce the release of an endogenous dermatan sulphate-like substance which alters fetal coagulation.


Mechanistic Details of Early Steps in Coenzyme Q Biosynthesis Pathway in Yeast.
Coenzyme Q (Q) is a redox lipid that is central for the energetic metabolism of eukaryotes. The biosynthesis of Q from the aromatic precursor 4-hydroxybenzoic acid (4-HB) is understood fairly well. However, biosynthetic details of how 4-HB is produced from tyrosine remain elusive. Here, we provide key insights into this long-standing biosynthetic problem by uncovering molecular details of the first and last reactions of the pathway in the yeast Saccharomyces cerevisiae, namely the deamination of tyrosine to 4-hydroxyphenylpyruvate by Aro8 and Aro9, and the oxidation of 4-hydroxybenzaldehyde to 4-HB by Hfd1. Inactivation of the HFD1 gene in yeast resulted in Q deficiency, which was rescued by the human enzyme ALDH3A1. This suggests that a similar pathway operates in animals, including humans, and led us to propose that patients with genetically unassigned Q deficiency should be screened for mutations in aldehyde dehydrogenase genes, especially ALDH3A1.


Transverse electric field modulated tunneling magnetoresistance in a DNA molecular device.
Quantum spin-dependent transport in a ferromagnetic(FM)/DNA/ferromagnetic(FM) device is theoretically investigated based on the lattice Green function method and the Landauer-Büttiker theory. The effect of a transverse electric field on magnetoresistance (MR) of the device is investigated. It is predicted that either the direction or strength of the transverse electric field can change the MR of the device. We suggest a possible application of modulating MR of the FM/DNA/FM device by a transverse electric field.


Epidemiological survey of Neospora caninum infection in dogs from Romania.
The aim of this study was to evaluate the seroprevalence of Neospora caninum infection in dogs from Romania at a national level and to detect possible correlations between the value of seroprevalence and a series of factors like sex, age, breed category and area. The prevalence of anti-N. caninum antibodies was determined in sera samples from 1114 dogs located in different regions of Romania using the IFAT method. Antibodies to N. caninum were found in 364 dogs (32.7%). The titers of anti-N. caninum antibodies varied from 1:50 to 1:800.


Transnasal Prelacrimal Recess Approach for Recurrent Antrachoanal Polyp.
To assess the effectiveness and usefulness of transnasal prelacrimal recess approach (TPRA) in patients with recurrent antrochoanal polyps. Twelve patients with antrochoanal polyp recurrence underwent surgery with a transnasal endoscopic prelacrimal recess approach. Success for visualization of the origin of the polyps, surgical complications, and recurrence was evaluated. Transnasal prelacrimal recess approach was successful in 83% of the patients (10/12); polyps that originated from a posterior location (2 patients) were excised using the middle meatal approach. Nasolacrimal duct injury occurred in 2 patients but neither had epiphora postoperatively. Three patients (3/12; 25%) had synechia formation between the lateral nasal wall and septum just superior to the inferior turbinate. One of the 3 patients (1/12; 8.3%) with synechia was symptomatic and required surgical treatment under local anesthesia. During a mean follow-up period of 14.2 months (range, 8-21 months) no recurrence had developed. In experienced hands, TPRA is a novel, reliable, and useful method for the treatment of recurrent antrochoanal polyps. It ensures good exploration of the maxillary antrum and easy access to the polyp origin on the maxillary wall without the need of additional approaches.


Ultra-sensitive tandem colloidal quantum-dot photodetectors.
The solution-processed PbSe colloidal quantum-dot (CQD) infrared photodetector with tandem architecture is proposed to address the high dark current issue. The electrical transport mechanism in tandem has been fundamentally changed in which the recombination of carriers at an intermediate layer becomes dominant rather than carriers hopping between nearest neighbors in CQD materials. As a result, the tandem photodetector exhibits ultra-high detectivities of 4.7 × 10(13) Jones and 8.1 × 10(13) Jones under 34 μW cm(-2) illumination at 1100 nm, at 275 K and 100 K, respectively.


The power of language in a bilingual community.
Recent language policy in Wales has helped ensure that issues such as nurse-patients interactions, particularly at a cross-cultural level, are examined from a new perspective. This paper focuses on the significance of promoting cultural and linguistic sensitivity in health care to promote effective clinical practice and the implications that this has for developing nursing education programmes in Wales.


Cranial nerve defects in congenital facial palsy.
Cranial nerve defects were enumerated in 29 children with congenital facial palsy presenting for reanimation via chart review with a view to determining unaffected donor nerves. The literature was searched via Medline to reveal 186 additional case reports that were complete enough in their description to allow assessment of cranial nerve defects. The group presenting for reanimation comprised 24 females and 5 males. All of the males had unilateral isolated facial nerve paralysis. Of the females, 9 had isolated unilateral palsy and 14 had bilateral palsy, and half of these were isolated. Six had bilateral abducens nerve palsy, fulfilling the original definition of Möbius syndrome. Of these, 3 had a right-sided hypoglossal weakness, one had a bilateral oculomotor palsy, and one had a bilateral trochlear palsy. One girl had bilateral facial and auditory involvement. The literature review revealed a group that was 60% male, with 85% having bilateral facial palsy. Abducens palsy was present in 68%, glossopharyngeal in 28%, hypoglossal in 26%, and oculomotor in 20%. The group was very heterogeneous in many ways. There are many theories of pathogenesis of this syndrome. Isolated facial palsy is in concordance with previous findings of nerve lesions within the temporal bone. Multiple cranial nerve defects are more likely to have brainstem lesions, related to prenatal ischemic events. The cranial nerve least likely to be involved was the accessory nerve, suggesting that this may be a reliable donor for reanimation procedures.


Relationship between symptom clusters and quality of life in patients at stages 2 to 4 chronic kidney disease in Korea.
This study was conducted to identify the relationship between symptom clusters and quality of life (QOL) in patients with stages 2 to 4 chronic kidney disease (CKD) in Korea. Using self-reported questionnaires, data were collected from 143 patients who underwent treatment for CKD at one hospital in Korea. The 17-item Patient Outcome Scale was used to measure symptoms, and the 36-item Short Form Health Survey Instrument Version 2 (SF-36v2) was used to measure the QOL. Data were analyzed using factor analysis to draw symptom clusters. Among five symptom clusters, the energy insufficiency and pain cluster was found to have the highest prevalence and greatest severity. The severity of symptom clusters showed negative correlations with both physical and mental component summary (PCS and MCS) scores. Elderly patients scored low on PCS, whereas younger patients in their 30s and 40s scored low on MCS. Negative correlations were found between symptom clusters and PCS as well as MCS. The severity of symptoms and QOL had stronger relationships with subjective perception of symptoms and psychological factors than with objective clinical indicators. As the effects of physical and psychological symptoms on the QOL in patients with stages 2 to 4 CKD were identified in this study, nurses should develop strategic nursing plans focused on symptom clusters and patients' subjective perception of symptoms rather than objective clinical indicators in order to improve the QOL in patients with CKD.


The RecBCD and SbcCD DNases suppress homology-facilitated illegitimate recombination during natural transformation of Acinetobacter baylyi.
During natural transformation of Acinetobacter baylyi, the genomic integration of foreign (non-homologous) DNA is possible when the DNA contains a single segment homologous to the recipient genome (anchor) through homologous recombination in the anchor facilitating illegitimate recombination in the neighbouring foreign DNA (homology-facilitated illegitimate recombination; HFIR). DNA integration by HFIR occurs about 10 000 times less frequently than fully homologous recombination, but at least 100 000-fold more frequently than integration in the absence of any homology. We investigated the influence of the RecBCD enzyme (DNase/helicase) and SbcCD DNase (DNA-structure-specific single-strand endonuclease and exonuclease) on HFIR. In a recBCD null mutant the acquisition of foreign DNA was elevated 11-fold relative to wild-type cells by a 6.9-fold increased HFIR frequency and by the integration of longer stretches of foreign DNA in each event. In an sbcCD null mutant, the foreign DNA acquisition was 4.5-fold higher than in the wild-type, while homologous transformation with large DNA molecules was unaffected and increased 3.2-fold with small DNA fragments. The sbcCD mutation partially suppressed the high UV sensitivity and low viability of the recBCD mutant and also decreased its foreign DNA acquisition by HFIR to the lower level of the sbcCD mutant. We propose that suppression of HFIR results from the elimination of double-stranded intermediates of the HFIR process during transformation by RecBCD, and by SbcCD interfering with branched molecules. Our results provide evidence that the homologous recombination enzymes RecBCD and SbcCD control the level of foreign DNA acquisition by HFIR.


Early macular retinal ganglion cell loss in dominant optic atrophy: genotype-phenotype correlation.
To assess the peripapillary retinal nerve fiber and macular retinal ganglion cell (RGC) loss in patients with dominant optic atrophy (DOA) stratified by OPA1 mutation type. Cross-sectional study. We studied 39 patients from 28 pedigrees with DOA harboring heterozygous mutations in the OPA1 gene along with 45 age-matched healthy subjects. The retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) of patients with DOA were evaluated by optical coherence tomography (OCT) and compared to those of controls. Patients' eyes were divided into 4 groups based on increasing severity of visual loss (DOA1 to DOA4) and were stratified by OPA1 mutation type. The average thicknesses of the RNFL and GC-IPL were smaller in patients with DOA than in healthy controls (P < 0.0001). RNFL analysis showed a significant reduction of the average, superior and inferior quadrants thicknesses in the DOA4 group compared to the DOA1 group (P = 0.001, P = 0.002 and P = 0.001, respectively). GC-IPL analysis showed a significant thinning in the superotemporal and superior sectors in the patients with DOA2 compared to those with DOA1 (P = 0.046 and P = 0.04, respectively). Stratifying by mutation type, average, superior and nasal RNFL thinning was significantly more severe in missense mutations and had a presumed dominant-negative effect compared to mutations causing haploinsufficiency. The present study demonstrates that in DOA, loss of macular RGCs is the earliest pathologic event, better reflected by GC-IPL measurements, whereas RNFL thickness is a measure of spared axons in late stages of the disease. Thus, mild cases (DOA2) show significant macular RGC loss as opposed to substantial maintenance of RNFL thickness, which is significantly decreased only in severe cases (DOA4). A clear genotype/phenotype correlation emerged, stratifying OCT measures by OPA1 mutation type, missense mutations being the most severe.


Natural DNA-modified graphene/Pd nanoparticles as highly active catalyst for formic acid electro-oxidation and for the Suzuki reaction.
Natural DNA has been considered as a building block for developing novel functional materials. It is abundant, renewable, and biodegradable and has a well-defined structure and conformation with many unique features, which are difficult to find in other polymers. Herein, calf thymus DNA modified graphene/Pd nanoparticle (DNA-G-Pd) hybrid materials are constructed for the first time using DNA as a mediator, and the prepared DNA-G-Pd hybrid shows high catalytic activity for fuel cell formic acid electro-oxidation and for organic Suzuki reaction. The main advantages of using DNA are not only because the aromatic nucleobases in DNA can interact through π-π stacking with graphene basal surface but also because they can chelate Pd via dative bonding in such defined sites along the DNA lattice. Our results indicate that isolated, homogeneous, and ultrafine spherical Pd nanoparticles are densely in situ decorated on DNA-modified graphene surfaces with high stability and dispersibility. The prepared DNA-G-Pd hybrid has much greater activity and durability for formic acid electro-oxidation than the commercial Pd/C catalyst and polyvinylpyrrolidone-mediated graphene/Pd nanoparticle (PVP-G-Pd) hybrid used for direct formic acid fuel cells (DFAFCs). Besides, the DNA-G-Pd hybrid can also be an efficient and recyclable catalyst for the organic Suzuki reaction in aqueous solution under aerobic conditions without any preactivation. Since DNA can chelate various transition metal cations, this proof-of-concept protocol provides the possibility for the tailored design of other novel catalytic materials based on graphene with full exploitation of their properties.


Linking payment to health outcomes: a taxonomy and examination of performance-based reimbursement schemes between healthcare payers and manufacturers.
To identify, categorize and examine performance-based health outcomes reimbursement schemes for medical technology. We performed a review of performance-based health outcomes reimbursement schemes over the past 10 years (7/98-010/09) using publicly available databases, web and grey literature searches, and input from healthcare reimbursement experts. We developed a taxonomy of scheme types by inductively organizing the schemes identified according to the timing, execution, and health outcomes measured in the schemes. Our search yielded 34 coverage with evidence development schemes, 10 conditional treatment continuation schemes, and 14 performance-linked reimbursement schemes. The majority of schemes are in Europe and Australia, with an increasing number in Canada and the U.S. These schemes have the potential to alter the reimbursement and pricing landscape for medical technology, but significant challenges, including high transaction costs and insufficient information systems, may limit their long-term impact. Future studies regarding experiences and outcomes of implemented schemes are necessary.


Molecular simulation study of feruloyl esterase adsorption on charged surfaces: effects of surface charge density and ionic strength.
The surrounding conditions, such as surface charge density and ionic strength, play an important role in enzyme adsorption. The adsorption of a nonmodular type-A feruloyl esterase from Aspergillus niger (AnFaeA) on charged surfaces was investigated by parallel tempering Monte Carlo (PTMC) and all-atom molecular dynamics (AAMD) simulations at different surface charge densities (±0.05 and ±0.16 C·m(-2)) and ionic strengths (0.007 and 0.154 M). The adsorption energy, orientation, and conformational changes were analyzed. Simulation results show that whether AnFaeA can adsorb onto a charged surface is mainly controlled by electrostatic interactions between AnFaeA and the charged surface. The electrostatic interactions between AnFaeA and charged surfaces are weakened when the ionic strength increases. The positively charged surface at low surface charge density and high ionic strength conditions can maximize the utilization of the immobilized AnFaeA. The counterion layer plays a key role in the adsorption of AnFaeA on the negatively charged COOH-SAM. The native conformation of AnFaeA is well preserved under all of these conditions. The results of this work can be used for the controlled immobilization of AnFaeA.


Methods for analysis of incorporation and annealing methods for analysis of tRNA(Lys) in HIV-1.
In HIV-1, tRNA(Lys3) serves as the primer for reverse transcription of minus strand strong stop cDNA. During viral assembly, the tRNA(Lys) isoacceptors, tRNA(Lys1,2) and tRNA(Lys3), are selectively packaged into the virion. The selectively packaging of tRNA(Lys3) facilitates the annealing of tRNA(Lys3) to the viral genome and the initiation of reverse transcription. We describe herein a set of experimental approaches for studying the mechanism by which tRNA(Lys) is selectively incorporated into HIV-1 and investigate how primer tRNA(Lys3) is annealed to viral genome. The methods described will also help in the analysis of cellular RNAs packaged in the virus particles.


Mechanism for bone invasion of oral cancer cells mediated by interleukin-6 in vitro and in vivo.
Osteoclastic bone resorption is an important step in bone invasion in several malignancies. Although interleukin (IL)-6 accelerates osteoclastic bone resorption, it remains unclear whether IL-6 may be involved in bone invasion of oral cancer. The pit formation assay with calf femur-derived bone slices was performed to examine the bone-resorbing activity of osteoclasts and cancer cells. The chemotaxis activity of the culture media was analyzed by the use of Boyden chamber technique. Nude mice, which were inoculated with IL-6-producing oral cancer cells into masseter, were treated with anti-IL-6 neutralizing antibody, and mandibular-bone invasion of the cells was assessed. BHY, a bone-invasive oral cancer cell line, but not HNT, a noninvasive cell line, produced large amounts of IL-6. In a pit formation assay, addition of conditioned medium (CM) derived from BHY but not HNT increased osteoclastic bone resorption, and the effects were inhibited by anti-IL-6 antibody. BHY-secreted IL-6 showed significant chemotaxis activity for osteoclasts. Of note, CM from the cocultivation of osteoclasts and BHY markedly enhanced the cancer cell migration, and the chemotaxis activity was significantly reduced when anti-IL-6 antibody was added into the coculture and then CM were collected, but not when the antibody was added into the CM after they were collected. Furthermore, treatment with anti-IL-6 antibody almost completely inhibited mandibular bone invasion of BHY in nude mice. These results strongly suggest that IL-6 secreted by oral cancer cells plays a significant role in bone invasion.


The role of excretory urography in the evaluation of girls with urinary tract infection.
Excretory urography and cystography were done in 200 girls from less than 1 year to 14 years old with a history of urinary tract infections. In 147 girls (73.5 per cent) the excretory urogram and cystogram were normal. Reflux was demonstrated on voiding cystourethrography in 19.5 per cent of the patients. Only 3 patients were found to have a normal voiding cystourethrogram and a significant abnormal excretory urogram. In only 1 patient (0.5 per cent) was an abnormality (an ectopic obstructed ureter) identified, which was amenable to intervention. We conclude that in the evaluation of girls with urinary tract infection an excretory urogram is indicated only in the presence of vesicoureteral reflux.


Robotic surgery.
This article discusses the developments that led up to robotic surgical systems as well as what is on the horizon for new robotic technology. Topics include how robotics is enabling new types of procedures, including natural orifice endoscopic translumenal surgery in which one cannot reach by hand under any circumstances, and how these developments will drive the next generation of robots.


Insulin resistance and β-cell function influence postprandial blood glucose levels in Japanese patients with gestational diabetes mellitus.
The aim of this study in patients with gestational diabetes mellitus (GDM) was to evaluate the relationship of insulin resistance and secretion to area-under-the-sensor glucose concentration-time curve from before to 120 min postmeal (CGM-AUC(0-120 min)) as determined with continuous glucose monitoring (CGM). Immunoreactive insulin and HbA1c were determined in 22 Japanese patients with GDM undergoing a 75 g oral glucose tolerance test. Patients underwent CGM within 3 weeks of receiving a diagnosis of GDM. HbA1c (NGSP) was 5.5 ± 0.4%, BMI was 24.8 ± 5.3 kg/m(2), mean sensor glucose by CGM was 94.2 ± 10.3 mg/dL, standard deviation was 17.5 ± 4.4 mg/dL, and CGM-AUC(0-120 min) was 204.2 ± 23.8 h mg/dL. The insulin resistance indices the homeostasis model assessment ratio (HOMA-R), quantitative insulin sensitivity check index (QUICKI), and the Matsuda Index were correlated with CGM-AUC(0-120 min). The disposition index (DI), which was used to evaluate insulin secretion, was negatively correlated with CGM-AUC(0-120 min). Not only insulin resistance but also beta cell dysfunction contributes to postprandial hyperglycemia in Japanese patients with GDM.


Professional theatre actors: environmental and socio-occupational use of voice.
To investigate the occurrence of vocal complaints and symptoms among professional theatre actors, and its relationship with environmental aspects of this professional activity and with the history of specialized intervention. Cross-sectional study with 48 professional actors who answered a questionnaire regarding vocal and extra-vocal complaints, as well as environmental aspects, habits and demands related to their professional activity in the theatre. A specific previously structured protocol (PROTEA) was used for this purpose. Previous history of acting vocal training was reported by 40 (83.3%) subjects. The most used resources were vocal warming, hydrating therapy, and alternative methods. Vocal difficulties in day-to-day demands were reported by 14 (35.0%) subjects, and eight (16.7%) of them noticed these difficulties since the beginning of their career. During performances, 14 (29.2%) reported difficulties coordinating breathing and speaking. All actors interviewed consider vocal health important for theatre acting. Most actors denied difficulties regarding vocal projection, breathing and/or articulation of words in scene. However, the Italian stage seems to be more related to difficulties coordinating breathing and speaking than the arena theater (p=0.00). In spite of professional actors who have a history of training and orientation regarding the use of professional voice, a significant portion of them have complaints related to professional voice use, especially associated to the environment conditions at work.


A statistical appraisal of disproportional versus proportional microbial source tracking libraries.
Library-based microbial source tracking (MST) can assist in reducing or eliminating fecal pollution in waters by predicting sources of fecal-associated bacteria. Library-based MST relies on an assembly of genetic or phenotypic "fingerprints" from pollution-indicative bacteria cultivated from known sources to compare with and identify fingerprints of unknown origin. The success of the library-based approach depends on how well each source candidate is represented in the library and which statistical algorithm or matching criterion is used to match unknowns. Because known source libraries are often built based on convenience or cost, some library sources may contain more representation than others. Depending on the statistical algorithm or matching criteria, predictions may become severely biased toward classifying unknowns into the library's dominant source category. We examined prediction bias for four of the most commonly used statistical matching algorithms in library-based MST when applied to disproportionately-represented known source libraries; maximum similarity (MS), average similarity (AS), discriminant analyses (DA), and k-means nearest neighbor (k-NN). MS was particularly sensitive to disproportionate source representation. AS and DA were more robust. k-NN provided a compromise between correct prediction and sensitivity to disproportional libraries including increased matching success and stability that should be considered when matching to disproportionally-represented libraries.


Paediatric idiopathic limbal stem cell deficiency.
Acquired limbal stem cell deficiency (LSCD) describes a condition in which the corneal limbal stem cells are altered or destroyed, typically due to ocular trauma, chronic allergy or inflammation. Idiopathic LSCD is a term used to describe limbal stem cell failure in the absence of any identifiable causative factor. While several cases of adult-onset LSCD have been identified previously, this case report describes a rare presentation of bilateral asymmetric idiopathic paediatric limbal stem cell deficiency in a sixteen-year-old male with an otherwise unremarkable ocular history.


Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xanthine oxidase-derived radicals.
Ethanol-induced gastric mucosal injury closely resembles an inflammatory response. Thus, in vivo and in vitro experimental models were used to assess whether ethanol is proinflammatory in concentrations likely to be encountered by the gastric mucosa during acute intoxication. Perfusing the rat gastric lumen with progressively increasing concentrations of ethanol (10%, 20%, and 30%) resulted in a dose-dependent increase in 51Cr-ethylenediaminetetraacetic acid clearance from blood-to-gastric lumen. Rendering the animals neutropenic (with antineutrophil serum) ameliorated the ethanol-induced mucosal injury; the degree of protection was directly related to the severity of neutropenia. Neither superoxide dismutase, catalase, nor sodium benzoate offered any protection against ethanol-induced injury, indicating that neither superoxide anion, hydrogen peroxide, nor the hydroxyl radical is involved. To assess further whether ethanol could exert proinflammatory effects an in vitro model consisting of cultured bovine microvascular endothelial cells and isolated human neutrophils was used. Ethanol at concentrations of 1.0%-4.0% (but not at 0.1%-0.5%) increased neutrophil adherence to endothelial cells and enhanced neutrophil-mediated endothelial cell injury. We conclude that ethanol is proinflammatory at concentrations that may be achieved in the gastric mucosa during acute intoxication. The ethanol-induced, neutrophil-mediated cell injury does not appear to involve oxy radicals.


Dietary supplements and medications in elite sport--polypharmacy or real need?
The aim of this study was to describe qualitatively and quantitatively dietary supplements (DS) and medication use in elite athletes. Athletes (n=912; age 23.9 ± 6 years; 72% male) reported medications and DSs taken within 3 days before doping control. We analyzed data collected from 2006 to 2008, identified and classified substances. Total of 74.6% athletes reported use of at least one substance, 61.2% took DS (3.17 per user) and 40.6% took medications. Among users, 21.2% reported the use of six and more different products, and one took 17 different products at the same time. Majority of medication users took non-steroidal anti-inflammatory drugs (NSAID) (24.7%), and 22.2% used more than one NSAID. We found no gender differences in DS use (P=0.83). Individual sport athletes used more DS (P<0.01). Our study showed widespread use of DS and drugs by elite athletes. Consumption of DS with no evident performance or health benefits, demonstrated the need for specific educational programs focused on DS use. Amount, quantity and combination of the reported products raised concern about the risk of potential side effects.


Sexual function in women with urinary incontinence and pelvic organ prolapse.
To compare sexual function in women with urinary incontinence and pelvic organ prolapse and to determine the effects of therapy on sexual function. 343 community-dwelling women older than 45 years with urinary incontinence or advanced prolapse were recruited into a multi-armed clinical trial. Women with incontinence were stratified to receive estrogen therapy, behavioral therapy, or surgical therapy. Women with prolapse were enrolled in a randomized surgical trial. All women completed a standardized urogynecologic evaluation and a sexual function questionnaire at baseline and after therapy. Women with prolapse or detrusor instability were more likely to cite pelvic floor symptoms as a reason for sexual inactivity than were women with other conditions. One third of patients with prolapse reported that their pelvic floor condition affected their ability to have sexual relations "moderately" or "greatly" significantly more than did other groups. Patients with genuine stress incontinence who underwent surgical or behavioral therapy were less likely to report being worried about urine leakage during intercourse after therapy than at baseline. After surgery, women with prolapse were less likely to report that their symptoms affected their ability to have sexual relations compared with baseline. Overall sexual satisfaction was the same at baseline and remained unchanged in all therapeutic groups at 6 months. Prolapse is more likely than urinary incontinence to result in sexual inactivity and to be perceived as affecting sexual relations. However, overall sexual satisfaction appears to be independent of diagnosis of or therapy for urinary incontinence or prolapse.


Different transition-state structures for the reactions of beta-lactams and analogous beta-sultams with serine beta-lactamases.
Beta-sultams are the sulfonyl analogues of beta-lactams, and N-acyl beta-sultams are novel inactivators of the class C beta-lactamase of Enterobacter cloacae P99. They sulfonylate the active site serine residue to form a sulfonate ester which subsequently undergoes C-O bond fission and formation of a dehydroalanine residue by elimination of the sulfonate anion as shown by electrospray ionization mass spectroscopy. The analogous N-acyl beta-lactams are substrates for beta-lactamase and undergo enzyme-catalyzed hydrolysis presumably by the normal acylation-deacylation process. The rates of acylation of the enzyme by the beta-lactams, measured by the second-order rate constant for hydrolysis, kcat/K(m), and those of sulfonylation by the beta-sultams, measured by the second-order rate constant for inactivation, k(i), both show a similar pH dependence to that exhibited by the beta-lactamase-catalyzed hydrolysis of beta-lactam antibiotics. Electron-withdrawing groups in the aryl residue of the leaving group of N-aroyl beta-lactams increase the rate of alkaline hydrolysis and give a Bronsted beta(lg) of -0.55, indicative of a late transition state for rate-limiting formation of the tetrahedral intermediate. Interestingly, the corresponding Bronsted beta(lg) for the beta-lactamase-catalyzed hydrolysis of the same substrates is -0.06, indicative of an earlier transition state for the enzyme-catalyzed reaction. By contrast, although the Bronsted beta(lg) for the alkaline hydrolysis of N-aroyl beta-sultams is -0.73, similar to that for the beta-lactams, that for the sulfonylation of beta-lactamase by these compounds is -1.46, compatible with significant amide anion expulsion/S-N fission in the transition state. In this case, the enzyme reaction displays a later transition state compared with hydroxide-ion-catalyzed hydrolysis of the beta-sultam.


Increasing HIV diagnoses in Australia among men who have sex with men correlated with the growing number not taking antiretroviral therapy.
Australia has experienced rising notifications of HIV diagnoses despite widely available combination antiretroviral therapy (CART). New HIV diagnoses have also been younger than the average age of those living with HIV. We investigated the degree to which several risk factors could explain this rise in notifications and the younger age profile. Numbers and ages of men who have sex with men (MSM) living with HIV in Australia from 1983 to 2007 were calculated from notifications of HIV diagnoses and deaths. We compared the trend over time as well as the average ages of MSM newly diagnosed with HIV infection from 1998 to 2007 with those for: notifications of gonorrhoea and syphilis, total MSM living with HIV infection, and the component not on CART. The percentage of younger MSM not taking CART has increased since 1998 (aged <30 years P<0.001; 30-39 years P=0.004). The trend of new HIV diagnoses was most significantly correlated with the total number of MSM living with HIV infection and the sector not taking CART (P<0.0001). Based on similarity of average ages, MSM living with HIV infection and not taking CART was the best predictor of the increasing trend in new HIV diagnoses (99.9999% probability, Akaike information criterion). Our analyses suggest MSM living with HIV infection and not taking CART could be the source of the increase in HIV infections. Consequently, greater CART enrolment should decrease HIV incidence, especially in younger MSM.


Identification of two keratinocyte stem cell regulatory loci implicated in skin carcinogenesis.
Several converging lines of evidence suggest that keratinocyte stem cells including those clonogenic in vitro, are the target cells in skin carcinogenesis. However, the mechanism of their involvement in carcinogenesis continues to be unknown. Recently, we have demonstrated that the number of keratinocyte clonogenic stem cells from mice is a genetically defined and quantitative complex trait. In this study, we analyzed the size of the colonies in BALB/c, C57BL/6, and their (BALB/cxC57BL/6)F1 hybrid mice. We found that the size of the colonies is also genetically regulated and that there are at least two types of clonogenic keratinocytes that form either small or large colonies. Small and large colony numbers were significantly different in BALB/c and C57BL/6 mice. We performed a genome-wide scan of small and large colony number in the two backcrosses [BALB/cx (BALB/cxC57BL/6)F1]; [C57BL/6x (BALB/cxC57BL/6) F1]; and [(BALB/cxC57BL/6)F1x (BALB/cxC57BL/6)F1] intercross mice. We report here that the loci on chromosomes 4 and 9 play a role in the regulation of large and small colony number respectively. We conclude that mouse epidermis has two major types of stem cells generating small and large colonies, and regulated by different genes. Our results suggest that the loci, including one major and several minor loci linked to the subpopulation of keratinocytes forming small colonies were related, if not identical to, the loci linked to susceptibility or resistance to skin tumor promotion and skin tumor development.


International cooperation in support of homeopathy and complementary medicine in developing countries: the Tuscan experience.
Health is a fundamental human right which contributes to reducing poverty, and encourages social development, human safety, and economic growth. International initiatives have fallen far short of their goals. This paper describes collaboration between the region of Tuscany and Cuba, Western Sahara, Senegal and Serbia. These have introduced various forms of Complementary and Alternative Medicine, including homeopathy and Traditional Chinese Medicine into primary healthcare particularly obstetrics, and into veterinary medicine. Complementary and traditional medicine can represent a useful and sustainable resource in various fields of health care. Inclusion in the public health system must go hand in hand with scientific evaluation.


Delayed diagnosis in a sight-threatening lesion.
Acute chiasmal compression has several aetiologies including pituitary apoplexy, a medical emergency caused by acute haemorrhagic or ischemic infarction in pituitary macroadenomas. Clinical diagnosis can often be difficult as the patient is frequently unaware of an existing adenoma. Delayed diagnosis may lead to increased morbidity and mortality. We describe a rarely presenting case report of acute chiasmal compression with unusual visual symptoms of hemifield slide, with initial delayed diagnosis. Knowledge of this infrequently presenting visual phenomenon may aid in rapid diagnosis, appropriate imaging and intervention leading to improved visual and systemic outcomes.


Phylogeny of Sphingomonas species that degrade pentachlorophenol.
Four pentachlorophenol (PCP)-degrading bacteria isolated from geographically diverse areas have been examined in detail as regards their physiology and phylogeny. According to traditional biochemical methods, these strains had been classified as members of the genera Arthrobacter, Flavobacterium, Pseudomonas, and Sphingomonas. The PCP degradation pathway has been studied extensively in Sphingomonas (Flavobacterium) sp strain ATCC 39723 and the first three degradation steps catalyzed by a PCP-4-monooxygenase (PcpB) and a reductive dehalogenase (PcpC) that functions twice are well established. A fourth step appears to involve ring-fission of the aromatic nucleus (PcpA). Molecular analyses revealed that the PCP degradation pathway in these four strains was rather conserved, leading to a phylogenetic analysis using 16S rDNA. The results revealed a much closer phylogenetic relationship between these organisms than traditional classification indicated, placing them into the more recently established genus Sphingomonas where they may even represent a single species. With 16S rDNA analysis, many bacterial isolates involved in degradation of xenobiotic compounds that were previously classified into diverse genera have been reclassified into the genus Sphingomonas.


Activity analyses of staphylococcal isolates from pediatric, adult, and elderly patients: AWARE Ceftaroline Surveillance Program.
Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and common Gram-negative organisms. We evaluated the activity of ceftaroline and various antimicrobial agents against S. aureus isolates according to patient age. A total of 2143 consecutive unique patient strains of clinical significance were collected between January and December 2010 from 65 US medical centers as part of the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Program. Ceftaroline and various comparator agents were tested by reference Clinical and Laboratory Standards Institute broth microdilution methods. Ceftaroline was consistently active against methicillin-susceptible S. aureus (MSSA) (MIC(50), 0.25 μg/mL; MIC(90), 0.25 μg/mL; 100.0% susceptible) and MRSA (MIC(50), 0.50 μg/mL, MIC(90), 1 μg/mL; 98.4% susceptible) from all age groups. In general, resistance rates to erythromycin, clindamycin, and levofloxacin were higher in the population aged ≥ 65 years, whereas resistance rates to clindamycin and levofloxacin were lowest among isolates from patients aged 6-17 years. When tested against MSSA, levofloxacin resistance was higher among isolates from patients aged ≥ 65 years (16.1%) than among isolates from the other age groups (6.1%-10.5%), and ceftaroline was generally 16-fold more active than ceftriaxone (MIC(50), 4 μg/mL; MIC(90), 4 μg/mL; 97.9% susceptible overall). Ceftaroline (MIC(50), 0.50 μg/mL; MIC(/90), 1 μg/mL), daptomycin (MIC(50), 0.25 μg/mL; MIC(90), 0.5 μg/mL), linezolid (MIC(50), 1 μg/mL; MIC(90), 1 μg/mL), and vancomycin (MIC(50), 1 μg/mL(;) MIC(90), 1 μg/mL) were the most active compounds tested against MRSA strains, and the activity of these compounds did not vary significantly among the age groups. In contrast, susceptibility rates to clindamycin and levofloxacin varied from 94.0% and 60.7% (aged 6-17 years), respectively, to only 57.6% and 15.1% (aged ≥ 65 years), respectively, among MRSA strains. The results of this study showed major differences in the susceptibility rates to clindamycin and levofloxacin according to patient age group. The results also indicate that ceftaroline is highly active against MSSA and MRSA isolated from US medical centers, independent of patient age group.


Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle: First Experience.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established first-line invasive modality for mediastinal lymph node staging in lung cancer patients and in the diagnostic workup of patients with mediastinal adenopathy. With the current 21- and 22-gauge (G) EBUS-TBNA needles, the procedure can be limited by the degree of flexibility in the needle and the size of the lumen in tissue acquisition. We report our initial experience with a first-generation flexible 19-G EBUS-TBNA (Flex 19G; Olympus Respiratory America, Redmond, WA, USA) needle with regards to efficacy and safety. The Flex 19G EBUS-TBNA needle was used in 47 selected patients with enlarged hilar and/or mediastinal lymphadenopathy at 3 centers. The standard Olympus EBUS scope with a 2.2-mm working channel was used in all cases. The diagnostic yield of the Flex 19G needle according to clinical cytopathology reports was 89% (42/47). The diagnosis and their respective diagnostic yield with the Flex 19G EBUS-TBNA needle were malignancy 24/27 (89%), sarcoidosis 13/14 (93%), and reactive lymph node hyperplasia 5/6 (83%). The mean short axis of the sampled lymph nodes was 19 ± 9 mm. No complications occurred except for 1 instance of moderate bleeding, which did not require intervention beyond suctioning and subsequently resolved. All 13 patients diagnosed with adenocarcinoma by the 19-G needle had sufficient tissue for genetic testing. EBUS-TBNA using the first-generation Flex 19G needle is feasible and safe with promising diagnostic yield while providing a greater degree of flexion with the Olympus EBUS scope. Additional clinical evaluations are warranted.


Sensitivity of virally-driven luciferase reporter plasmids to members of the steroid/thyroid/retinoid family of nuclear receptors.
During a series of transfection experiments, the pRSV-luc plasmid used as an internal control was found to be sensitive to cotransfection with expression vectors for several members of the steroid/thyroid/retinoid superfamily of nuclear receptors. Therefore, a survey of the effect of these expression vectors on the activity of four reporter plasmids was conducted. In CV-1 cells, the activity of pRSV-luc, which contains the P. pyralis luciferase gene, was repressed by co-transfection of PPARalpha and ARP-1 and was activated by COUP-TFI. Expression of pSV40-luc, containing the same luciferase gene, was repressed by PPARalpha and HNF-4 and activated by both COUP-TFI and ARP-1. All four of these expression vectors reduced the expression of the pRL-TK plasmid, which contains the luciferase gene from Renilla reniformis. RXR expression vectors had no effect on luciferase activity in CV-1 cells but induced luciferase activity in H4IIEC3 hepatoma cells. This activation was blocked by the addition of ligand, 9-cis retinoic acid. pSV2-CAT, which contains the chloramphenicol acetyltransferase gene, was insensitive to all receptor expression vectors tested. Both the P. pyralis and R. reniformis luciferase genes appear to contain sequences that render them responsive to steroid/thyroid/retinoid nuclear receptors.


Acute back pain: a psychological analysis.
A cross-sectional evaluation of 117 people who sustained acute back injuries was undertaken within 15 days of the first report of the pain. The subjects showed no discal or neural signs and had not experienced previous episodes of back or neck pain. All subjects were given a structured interview and filled in a series of psychological evaluation instruments. Results show acute pain reactions to be comparable to those seen in chronic pain groups. The predominant emotion is one of frustration rather than anxiety or depression and considerable behavioural disruption is evident from this early point. The extent to which these data undermine the model of gradual evolution of chronic back pain problems is discussed.


Apoptosis in sea bream Sparus aurata eggs.
In the present study, the sea-bream Sparus aurata, a pelagic egg spawner, was used as experimental model, in order to establish the occurrence of apoptosis in vertebrates with external reproduction. The same female ovulates floating and nonfloating eggs, but only the former, after fertilization, proceed to embryo development. The eggs were divided into floating and nonfloating and both were analyzed for the presence of several apoptosis markers. The results here reported provide evidence that the nonfloating cells present severe shrinkage and highly express both FAS receptor and FAS ligand on their surface. Furthermore, DNA fragmentation and mitochondria swelling were found, suggesting that the nonfloating eggs were cells programmed to die.