Plasmonic Nanospectroscopy of Platinum Catalyst Nanoparticle Sintering in a Mesoporous Alumina Support.
In situ plasmonic nanospectroscopy has proven useful to bridge the pressure gap in heterogeneous catalysis. The method has, however, so far been used only for idealized two-dimensional systems without the structural complexity of realistic three-dimensional porous oxides, which generally are used as supports for the catalytically active metal nanoparticles. Here, we report a generic method that addresses this structural gap by demonstrating the possibility to use nanoplasmonic sensing to monitor surface processes in a traditional three-dimensional mesoporous alumina matrix, wet-impregnated with Pt nanoparticles. The capability of the experimental platform is illustrated by measuring sintering kinetics of the Pt nanoparticles inside the mesoporous matrix under oxidizing conditions at atmospheric pressure and at temperatures up to 625 °C. The study thus demonstrates in operando plasmonic nanospectroscopy of realistic, commercial catalyst systems.


Proficiency Testing to Assess Technical Performance for CTC-Processing and Detection Methods in CANCER-ID.
Multiple technologies are available for detection of circulating tumor cells (CTCs), but standards to evaluate their technical performance are still lacking. This limits the applicability of CTC analysis in clinic routine. Therefore, in the context of the CANCER-ID consortium, we established a platform to assess technical validity of CTC detection methods in a European multi-center setting using non-small cell lung cancer (NSCLC) as a model. We characterized multiple NSCLC cell lines to define cellular models distinct in their phenotype and molecular characteristics. Standardized tumor-cell-bearing blood samples were prepared at a central laboratory and sent to multiple European laboratories for processing according to standard operating procedures. The data were submitted via an online tool and centrally evaluated. Five CTC-enrichment technologies were tested. We could identify 2 cytokeratin expressing cell lines with distinct levels of EpCAM expression: NCI-H441 (EpCAMhigh, CKpos) and NCI-H1563 (EpCAMlow, CKpos). Both spiked tumor cell lines were detected by all technologies except for the CellSearch system that failed to enrich EpCAMlow NCI-H1563 cells. Mean recovery rates ranged between 49% and 75% for NCI-H411 and 32% and 76% for NCI-H1563 and significant differences were observed between the tested methods. This multi-national proficiency testing of CTC-enrichment technologies has importance in the establishment of guidelines for clinically applicable (pre)analytical workflows and the definition of minimal performance qualification requirements prior to clinical validation of technologies. It will remain in operation beyond the funding period of CANCER-ID in the context of the European Liquid Biopsy Society (ELBS).


Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis.
We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-section histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally nephrectomized Munich-Wistar rats and (b) adriamycin (ADM) treatment in nonnephrectomized Munich-Wistar rats. Single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) were measured repeatedly for 8 (PAN rats) or 31 wk (ADM rats). In all animals studied, values for PGC remained at, or slightly below, levels measured before PAN or ADM administration. SNGFR values declined progressively in all glomeruli in PAN rats. Although some glomeruli in ADM rats had an increase in SNGFR above levels observed in nonnephrectomized control rats, these hyperfiltering glomeruli did not have abnormally high PGC nor did they exhibit glomerular sclerosis at the completion of the study. Histological analysis revealed the existence of a significant inverse correlation between the degree of sclerosis and SNGFR assessed at the time of sacrifice in both PAN and ADM groups. Chronic administration of captopril, an angiotensin I converting enzyme inhibitor, in PAN rats substantially attenuated development of glomerular sclerosis without affecting PGC in earlier stages. The observations in these models indicate that glomerular hyperfiltration and hypertension are not required for the development of glomerular sclerosis in renal diseases, and angiotensin I converting enzyme inhibitor can exert its protective effect independently of its effect on glomerular capillary pressure.


Surgical anatomy of the superior hypophyseal artery and its relevance for endoscopic endonasal surgery.
The endoscopic endonasal approach has become a routine corridor to the suprasellar region. The superior hypophyseal arteries (SHAs) are intimately related to lesions in the suprasellar space, such as craniopharyngiomas and meningiomas. Here the authors investigate the surgical anatomy and variations of the SHA from the endoscopic endonasal perspective. Thirty anatomical specimens with vascular injection were used for endoscopic endonasal dissection. The number of SHAs and their origin, course, branching, anastomoses, and areas of supply were collected and analyzed. A total of 110 SHAs arising from 60 internal carotid arteries (ICAs), or 1.83 SHAs per ICA (range 0-3), were found. The most proximal SHA always ran in the preinfundibular space and provided the major blood supply to the infundibulum, optic chiasm, and proximal optic nerve; it was defined as the primary SHA (pSHA). The more distal SHA(s), present in 78.3% of sides, ran in the retroinfundibular space and supplied the stalk and may also supply the tuber cinereum and optic tracts. In the two sides (3.3%) in which no SHA was present, the territory was covered by a pair of infundibular arteries originating from the posterior communicating artery. Two-thirds of the pSHAs originated proximal to the distal dural ring; half of these arose from the carotid cave portion of the ICA, whereas the other half originated proximal to the cave. Four branching patterns of the pSHA were recognized, with the most common pattern (41.7%) consisting of three or more branches with a tree-like pattern. Descending branches were absent in 25% of cases. Preinfundibular anastomoses between pSHAs were found in all specimens. Anastomoses between the pSHA and the secondary SHA (sSHA) or the infundibular arteries were found in 75% cases. The first SHA almost always supplies the infundibulum, optic chiasm, and proximal optic nerve and represents the pSHA. Compromising this artery can cause a visual deficit. Unilateral injury to the pSHA is less likely to cause an endocrine deficit given the artery's abundant anastomoses. A detailed understanding of the surgical anatomy of the SHA and its many variations may help surgeons when approaching challenging lesions in the suprasellar region.


Posterior reversible encephalopathy syndrome associated with left horizontal gaze palsy.
Posterior reversible encephalopathy syndrome (PRES) is characterized by rapid onset of symptoms including headache, seizures, altered consciousness, and visual disturbance, as well as radiologic findings of focal reversible vasogenic edema. Multiple visual disturbances have been described in PRES, such as hemianopia, visual neglect, auras, visual hallucinations, and cortical blindness. However, horizontal gaze palsy has not been previously reported. We report a 72-year-old female who presented with blurred vision, severe headache, lethargy, and later developed seizures. She was found to have left horizontal gaze palsy with intact vestibulo-ocular reflex. Brain magnetic resonance imaging (MRI) showed severe edema throughout the subcortical white matter, and signal in the posterior parietal and occipital lobes. She was diagnosed with PRES associated with supranuclear gaze palsy.


Semi-allogeneic dendritic cells can induce antigen-specific T-cell activation, which is not enhanced by concurrent alloreactivity.
Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses. To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC. Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo. In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival. Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.


Seasonal prevalence of MS disease activity.
This observational cohort study investigated the seasonal prevalence of multiple sclerosis (MS) disease activity (likelihood and intensity), as reflected by new lesions from serial T2-weighted MRI, a sensitive marker of subclinical disease activity. Disease activity was assessed from the appearance of new T2 lesions on 939 separate brain MRI examinations in 44 untreated patients with MS. Likelihood functions for MS disease activity were derived, accounting for the temporal uncertainty of new lesion occurrence, individual levels of disease activity, and uneven examination intervals. Both likelihood and intensity of disease activity were compared with the time of year (season) and regional climate data (temperature, solar radiation, precipitation) and among relapsing and progressive disease phenotypes. Contrast-enhancing lesions and attack counts were also compared for seasonal effects. Unlike contrast enhancement or attacks, new T2 activity revealed a likelihood 2-3 times higher in March-August than during the rest of the year, and correlated strongly with regional climate data, in particular solar radiation. In addition to the likelihood or prevalence, disease intensity was also elevated during the summer season. The elevated risk season appears to lessen for progressive MS and occur about 2 months earlier. This study documents evidence of a strong seasonal pattern in subclinical MS activity based on noncontrast brain MRI. The observed seasonality in MS disease activity has implications for trial design and therapy assessment. The observed activity pattern is suggestive of a modulating role of seasonally changing environmental factors or season-dependent metabolic activity.


Characterization of Heterorhabditis Isolates by PCR Amplification of Segments of mtDNA and rDNA Genes.
Restriction digests of amplified DNA from the mitochondrial genome and the nuclear ribosomal internally transcribed spacer region have been evaluated as genetic markers for species groups in Heterorhabditis. Six RFLP profiles have been identified. These profiles supported groupings determined by cross-breeding studies and were in agreement with less definitive groupings based on other biochemical and molecular methods. Digestion patterns of both amplification products provided strong evidence for the recognition of species groups, which include Irish, NW European, tropical, and a H. bacteriophora complex. The H. bacteriophora complex could be further resolved into three genotypes represented by H. zealandica, the H. bacteriophora, Brecon (Australian) type isolate for H. bacteriophora, and a grouping composed of isolates NC1, V16, HI82, and HP88. All cultures obtained of the H. megidis isolate were identical to the NW European group. These results could be used to aid monitoring of field release of Heterorhabditis as well as allowing a rapid initial assessment of taxonomic grouping.


Cutaneous lymphadenoma.
Thirteen cases of a unique cutaneous tumor are presented. The lesions presented as single, nondescript, skin-color nodules. Eleven were located on the head and two were on the legs. The male/female ratio was 8:5. The age at diagnosis ranged between 21 and 55 years (mean: 39). The duration of the lesions was from several months to more than 20 years. All tumors were excised and did not recur. The tumors typically presented as well-circumscribed nodules with scant or no epidermal connections. (One example, however, had a plate-like configuration amply connected with the basal layers of the epidermis.) The proliferation consisted of multiple, rounded lobules of basaloid cells with some degree of peripheral palisading, immersed in a dense, fibrous stroma. There was an intense infiltrate of small lymphocytes within the lobules, with some spillage into the stroma. No clear adnexal differentiation was noted except for rare isolated cells showing apparent sebaceous differentiation within the tumor lobules. Areas of central keratinization were also present. Numerous cells with ample amphophilic cytoplasm, large vesicular nuclei, and prominent nucleoli were also seen. Immunohistochemistry confirmed the presence of keratin within tumor cells. Common leukocytic antigen highlighted the intense intralobular lymphocytic component. Vimentin not only highlighted the stromal fibroblastic component, but also stained scattered intralobular cells. Epithelial membrane antigen was positive within some of the large intraepithelial cells. S-100 protein was extensively positive within dendritic intralobular and stromal cells. Lymphocytic markers demonstrated a polyclonal B and T population. This unique tumor appears to represent a form of adnexal neoplasm with basaloid features, possibly immature pilosebaceous differentiation.


Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants.
Non-vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. This study's objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R(2) = 0.92 to 0.99) and ecarin-based assays (R(2) = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R(2) = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed.


Development of Human Posture Simulation Method for Assessing Posture Angles and Spinal Loads.
Video-based posture analysis employing a biomechanical model is gaining a growing popularity for ergonomic assessments. A human posture simulation method of estimating multiple body postural angles and spinal loads from a video record was developed to expedite ergonomic assessments. The method was evaluated by a repeated measures study design with three trunk flexion levels, two lift asymmetry levels, three viewing angles and three trial repetitions as experimental factors. The study comprised two phases evaluating the accuracy of simulating self and other people's lifting posture via a proxy of a computer-generated humanoid. The mean values of the accuracy of simulating self and humanoid postures were 12° and 15°, respectively. The repeatability of the method for the same lifting condition was excellent (~2°). The least simulation error was associated with side viewing angle. The estimated back compressive force and moment, calculated by a three dimensional biomechanical model, exhibited a range of 5% underestimation. The posture simulation method enables researchers to simultaneously quantify body posture angles and spinal loading variables with accuracy and precision comparable to on-screen posture matching methods.


The role of heat shock proteins in gastrointestinal diseases.
Heat shock proteins (HSPs) are a highly conserved family of proteins which inhabit almost all subcellular locations and cellular membranes. Depending on their location, these proteins perform a variety of chaperoning functions including folding of newly synthesised polypeptides. HSPs also play a major role in the protection of cells against stressful and injury-inciting stimuli. By virtue of this protective function, HSPs have been shown to prevent acinar cell injury in acute pancreatitis. Also, the levels of HSPs have been shown to be markedly elevated in various forms of cancers when compared with non-transformed cells. Further, inhibition of HSPs has been shown to induce apoptotic cell death in cancer cells suggesting that inhibition of HSPs has a potential to emerge as novel anti-cancer therapy, either as monotherapy or in combination with other chemotherapeutic agents. Several studies have suggested that HSPs can interact with and inhibit both intrinsic and extrinsic pathways of apoptosis at multiple sites. Besides the anti-apoptotic role of HSPs, recent studies suggest that they play a role in the generation of anti-cancer immunity, and attempts have been made to utilise this property of HSPs in the generation of anti-cancer vaccines. The anti-apoptotic function and mechanism of various subtypes of HSPs as well as the current status of anti-HSP therapy are discussed in this review.


Experimental perspective on fallback foods and dietary adaptations in early hominins.
The robust jaws and large, thick-enameled molars of the Plio-Pleistocene hominins Australopithecus and Paranthropus have long been interpreted as adaptations for hard-object feeding. Recent studies of dental microwear indicate that only Paranthropus robustus regularly ate hard items, suggesting that the dentognathic anatomy of other australopiths reflects rare, seasonal exploitation of hard fallback foods. Here, we show that hard-object feeding cannot explain the extreme morphology of Paranthropus boisei. Rather, analysis of long-term dietary plasticity in an animal model suggests year-round reliance on tough foods requiring prolonged postcanine processing in P. boisei. Increased consumption of such items may have marked the earlier transition from Ardipithecus to Australopithecus, with routine hard-object feeding in P. robustus representing a novel behaviour.


A systematic review and meta-analysis of the efficacy of medical treatments for the management of solitary rectal ulcer syndrome.
Solitary rectal ulcer syndrome (SRUS) is a benign, poorly understood disorder that is difficult to manage. Medical interventions such as sucralfate, sulfasalzine, human fibrin, and a high fibre diet are reported as the first line of treatment. The aim of this study is to perform a systematic review and meta-analysis of the efficacy of medical treatments for SRUS. Databases including PubMed, Cochrane, and Embase were searched for randomised clinical trials (RCT) and observational studies that evaluated medical treatments for SRUS. Two authors independently performed selection of eligible studies based on eligiblity criteria. Data extraction from potentially eligible studies was carried out according to predefined data collection methods. Medical treatments, including sucralfate, sulfasalzine, human fibrin, a high fibre diet, and psyllium powder as a single or combination therapy were compared to placebo alone or combined with other treatments. The primary outcome was the proportion of patients with ulcer remission; this was presented as pooled prevalence (PP) with a 95% confidence interval (CI). The I2 value and Q statistic test were used to test for heterogeneity. In the presence of heterogeneity, a random-effects model was applied. A total of 9 studies with 216 patients (males = 118, females = 98) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimate of treatment efficacy revealed that, of the patients receiving medical treatment, 57% had resolution of their ulcers (PP 0.57; 95% CI; 0.41 to 0.73). Statistically significant heterogeneity was observed (I2 = 63%; τ2 = 0.64, P= <0.01). The scarcity of RCTs comparing medical treatments with other interventions was a major limitation. The majority of patients receiving medical treatment for the management of SRUS experience resolution of their ulcers.


Adherence to Telemonitoring Therapy for Medicaid Patients With Hypertension: Case Study.
Almost 50% of the adults in the United States have hypertension. Although clinical trials indicate that home blood pressure monitoring can be effective in managing hypertension, the reported results might not materialize in practice because of patient adherence problems. The aims of this study are to characterize the adherence of Medicaid patients with hypertension to daily telemonitoring, identify the impacts of adherence reminder calls, and investigate associations with blood pressure control. This study targeted Medicaid patients with hypertension from the state of Texas. A total of 180 days of blood pressure and pulse data in 2016-2018 from a telemonitoring company were analyzed for mean transmission rate and mean blood pressure change. The first 30 days of data were excluded because of startup effects. The protocols required the patients to transmit readings by a specified time daily. Patients not transmitting their readings received an adherence reminder call to troubleshoot problems and encourage transmission. The patients were classified into adherent and nonadherent cohorts; adherent patients were those who transmitted data on at least 80% of the days. The mean patient age was 73.2 (SD 11.7) years. Of the 823 patients, 536 (65.1%) were women, and 660 (80.2%) were urban residents. The adherent cohort (475/823, 57.7%) had mean transmission rates of 74.9% before the adherence reminder call and 91.3% after the call, whereas the nonadherent cohort (348/823, 42.3%) had mean transmission rates of 39% and 58% before and after the call, respectively. From month 1 to month 5, the transmission rates dropped by 1.9% and 10.2% for the adherent and nonadherent cohorts, respectively. The systolic and diastolic blood pressure values improved by an average of 2.2 and 0.7 mm Hg (P<.001 and P=.004), respectively, for the adherent cohort during the study period, whereas only the systolic blood pressure value improved by an average of 1.6 mm Hg (P=.02) for the nonadherent cohort. Although we found that patients can achieve high levels of adherence, many experience adherence problems. Although adherence reminder calls help, they may not be sufficient. Telemonitoring lowered blood pressure, as has been observed in clinical trials. Furthermore, blood pressure control was positively associated with adherence.


The tales of two geckos: does dispersal prevent extinction in recently fragmented populations?
Although habitat loss and fragmentation threaten species throughout the world and are a major threat to biodiversity, it is apparent that some species are at greater risk of extinction in fragmented landscapes than others. Identification of these species and the characteristics that make them sensitive to habitat fragmentation has important implications for conservation management. Here, we present a comparative study of the population genetic structure of two arboreal gecko species (Oedura reticulata and Gehyra variegata) in fragmented and continuous woodlands. The species differ in their level of persistence in remnant vegetation patches (the former exhibiting a higher extinction rate than the latter). Previous demographic and modelling studies of these two species have suggested that their difference in persistence levels may be due, in part, to differences in dispersal abilities with G. variegata expected to have higher dispersal rates than O. reticulata. We tested this hypothesis and genotyped a total of 345 O. reticulata from 12 sites and 353 G. variegata from 13 sites at nine microsatellite loci. We showed that O. reticulata exhibits elevated levels of structure (FST=0.102 vs. 0.044), lower levels of genetic diversity (HE=0.79 vs. 0.88), and fewer misassignments (20% vs. 30%) than similarly fragmented populations of G. variegata, while all these parameters were fairly similar for the two species in the continuous forest populations (FST=0.003 vs. 0.004, HE=0.89 vs. 0.89, misassignments: 58% vs. 53%, respectively). For both species, genetic structure was higher and genetic diversity was lower among fragmented populations than among those in the nature reserves. In addition, assignment tests and spatial autocorrelation revealed that small distances of about 500 m through fragmented landscapes are a barrier to O. reticulata but not for G. variegata. These data support our hypothesis that G. variegata disperse more readily and more frequently than O. reticulata and that dispersal and habitat specialization are critical factors in the persistence of species in habitat remnants.


Molecular epidemiology of enterococcal bacteremia in Australia.
Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.


Combination treatment with chondroitinase ABC in spinal cord injury--breaking the barrier.
After spinal cord injury (SCI), re-establishing functional circuitry in the damaged central nervous system (CNS) faces multiple challenges including lost tissue volume, insufficient intrinsic growth capacity of adult neurons, and the inhibitory environment in the damaged CNS. Several treatment strategies have been developed over the past three decades, but successful restoration of sensory and motor functions will probably require a combination of approaches to address different aspects of the problem. Degradation of the chondroitin sulfate proteoglycans with the chondroitinase ABC (ChABC) enzyme removes a regeneration barrier from the glial scar and increases plasticity in the CNS by removing perineuronal nets. its mechanism of action does not clash or overlap with most of the other treatment strategies, making ChABC an attractive candidate as a combinational partner with other methods. in this article, we review studies in rat SCI models using ChABC combined with other treatments including cell implantation, growth factors, myelin-inhibitory molecule blockers, and ion channel expression. We discuss possible ways to optimize treatment protocols for future combinational studies. To date, combinational therapies with ChABC have shown synergistic effects with several other strategies in enhancing functional recovery after SCI. These combinatorial approaches can now be developed for clinical application.


Baseline patient characteristics associated with response to biologic therapy in patients with psoriatic arthritis enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.
To compare baseline characteristics between patients with psoriatic arthritis (PsA) who achieved and did not achieve minimal disease activity (MDA) with biologic therapy in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis Registry. Patients with PsA aged ≥18 years enrolled between March 2013 and March 2016 who were receiving biologics at enrolment (baseline), not in MDA and had ≥2 follow-up visits were included. Patients were classified as those who remained on their index biologic and achieved MDA at the second follow-up visit (MDA achievers (MDA-A)) and those who did not (MDA non-achievers (MDA-NA)). Demographics, clinical characteristics, patient-reported outcomes and medication history were compared between groups. Of 148 patients with PsA who met the inclusion criteria, 34 (23.0%) and 114 (77.0%) were classified as MDA-A and MDA-NA, respectively. At baseline, most patients (96.6%) were receiving tumour necrosis factor inhibitors, and both groups were similar in age, sex, race, medication history, enthesitis and dactylitis counts, disease duration and comorbidities. Compared with MDA-A, MDA-NA had significantly worse mean tender joint count (7.2 vs 3.4), patient-reported pain (51.2 vs 35.7), patient-reported fatigue (54.1 vs 42.4), physical function (Health Assessment Questionnaire, 1.0 vs 0.6), Bath Ankylosing Disease Activity Index (5.0 vs 3.4) and Bath Ankylosing Spondylitis Functional Index (4.0 vs 2.0) scores (all p<0.05). Approximately one in four patients achieved MDA with their index biologic at the time of the second follow-up visit. Both groups were similar in several baseline demographic and clinical features; however, patients who did not achieve MDA generally had worse tender joint counts and patient-reported outcomes.


Flying-foxes in the Australian urban environment-community attitudes and opinions.
The urban presence of flying-foxes (pteropid bats) in eastern Australia has increased in the last 20 years, putatively reflecting broader landscape change. The influx of large numbers often precipitates community angst, typically stemming from concerns about loss of social amenity, economic loss or negative health impacts from recently emerged bat-mediated zoonotic diseases such as Hendra virus and Australian bat lyssavirus. Local authorities and state wildlife authorities are increasingly asked to approve the dispersal or modification of flying-fox roosts to address expressed concerns, yet the scale of this concern within the community, and the veracity of the basis for concern are often unclear. We conducted an on-line survey to capture community attitudes and opinions on flying-foxes in the urban environment to inform management policy and decision-making. Analysis focused on awareness, concerns, and management options, and primarily compared responses from communities where flying-fox management was and was not topical at the time of the survey. While a majority of respondents indicated a moderate to high level of knowledge of both flying-foxes and Hendra virus, a substantial minority mistakenly believed that flying-foxes pose a direct infection risk to humans, suggesting miscommunication or misinformation, and the need for additional risk communication strategies. Secondly, a minority of community members indicated they were directly impacted by urban roosts, most plausibly those living in close proximity to the roost, suggesting that targeted management options are warranted. Thirdly, neither dispersal nor culling was seen as an appropriate management strategy by the majority of respondents, including those from postcodes where flying-fox management was topical. These findings usefully inform community debate and policy development and demonstrate the value of social analysis in defining the issues and options in this complex human-wildlife interaction. The mobile nature of flying-foxes underlines the need for a management strategy at a regional or larger scale, and independent of state borders.


Withdrawal from gamma-hydroxybutyrate, 1,4-butanediol and gamma-butyrolactone: a case report and systematic review.
1,4-butanediol (1,4-BD) is an industrial solvent that is metabolized to gamma-hydroxybutyrate (GHB), a gamma-aminobutyric acid agonist and central nervous system depressant. GHB and its analogues are popular drugs of abuse. Withdrawal from these agents is characterized by autonomic instability and altered mental status. We report a case of withdrawal from 1,4-BD lasting 6 days and complicated by new onset of seizures and rhabdomyolysis. In addition, we conducted a systematic review of the English literature pertaining to withdrawal from GHB, 1,4-BD and gamma-butyrolactone (GBL). Data collected from source articles included last use prior to symptom onset, clinical features on presentation, duration of symptoms and outcome. Twenty-seven studies with 57 episodes of withdrawal were included. Thirty-six cases (63%) involved GHB, 3 cases (5%) involved 1,4-BD and 18 (32%) involved GBL. The most common patient symptoms were tremor (67%), hallucinations (63%), tachycardia (63%) and insomnia (58%). Seizures and rhabdomyolysis each occurred in 7% of cases, but only 1 death occurred. Emergency physicians must consider withdrawal from these agents when patients present with clinical features suggestive of a sedative-hypnotic withdrawal syndrome.


Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial.
This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy.Pre-trial:144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment,the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks,according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks' treatment 41.0% and 27.5% of patients from ta-VNS and tn-VNS groups, respectively, experienced reduction in seizure frequency that reached I, II and III levels according to the standards of the Modified Engel Scale compared with the baselines, indicating significant difference in seizure reduction between the two groups. After 24 weeks of treatment, ta-VNS patients had a 47.7% reduction, and tn-VNS, with an additional 16 weeks of treatment, reached 47.5% in reduction. After 8 weeks' treatment, the percentages of average seizure frequency in ta-VNS and tn-VNS were reduced by 42.6% and 11.5% respectively, providing a statistically significant difference in the results between the two groups (P<0.05). In addition, there were significant improvements in electroencephalograph (EEG) and the quality of daily life of the patients after treatment.The results show that this ta-VNS treatment can effectively reduce the frequency of seizures and improve the patient's quality of life. This may be an effective treatment for refractory epilepsy. At the same time,it is also safe,economic, and widely applicable.


Assisted reproductive technology surveillance -- United States, 2010.
Since the first U.S. infant conceived with Assisted Reproductive Technology (ART) was born in 1981, both the use of advanced technologies to overcome infertility and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely to deliver multiple-birth infants than those who conceive naturally because more than one embryo might be transferred during a procedure. Multiple births pose substantial risks to both mothers and infants, including pregnancy complications, preterm delivery, and low birthweight infants. This report provides state-specific information on U.S. ART procedures performed in 2010 and compares infant outcomes that occurred in 2010 (resulting from procedures performed in 2009 and 2010) with outcomes for all infants born in the United States in 2010. 2010. In 1996, CDC began collecting data on all ART procedures performed in fertility clinics in the United States and U.S. territories, as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collecting system developed by CDC. In 2010, a total of 147,260 ART procedures performed in 443 U.S. fertility clinics were reported to CDC. These procedures resulted in 47,090 live-birth deliveries and 61,564 infants. The largest numbers of ART procedures were performed among residents of six states: California (18,524), New York (excluding New York City) (14,212), Illinois (10,110), Massachusetts (9,854), New Jersey (8,783), and Texas (8,754). These six states also had the highest number of live-birth deliveries as a result of ART procedures and together accounted for 48.0% of all ART procedures performed, 45.0% of all infants born from ART, and 45.0% of all multiple live-birth deliveries but only 34.0% of all infants born in the United States and U.S. territories. Nationally, the average number of ART procedures performed per 1 million women of reproductive age (15-44 years), which is a proxy indicator of ART use, was 2,331. In 13 states (California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia), this proxy measure was higher than the national rate, and in four states (Connecticut, Massachusetts, New Jersey, and New York) and the District of Columbia, it exceeded twice the national rate. Nationally, among cycles in which at least one embryo was transferred, the average number of embryos transferred increased with increasing age (2.0 among women aged <35 years, 2.4 among women aged 35-40 years, and 3.0 among women aged >40 years). Elective single-embryo transfer (eSET) rates decreased with increasing age (10.0% among women aged <35 years, 3.8% among women aged 35-40 years, and 0.6% among women aged >40 years). ESET rates also varied substantially between states (range: 0 to 45.0% among women aged <35 years). The number of ART births as a percentage of total infants born in the state or territory is considered as another measure of ART use. Overall, ART contributed to 1.5% of U.S. births (range: 0.1% in Guam to 4.8% in Massachusetts) with the highest rates (>3.5% of all infants born) observed in four states (Connecticut, Massachusetts, New Jersey, and New York), and the District of Columbia. The proportion of ART births was ≤2.5% in the remaining states and territories. Infants conceived with ART comprised 20.0% of all multiple-birth infants (range: 0 in Guam to 40.5% in Massachusetts), 19.0% of all twin infants (range: 0 in Guam to 40.0% in Massachusetts), and 33.0% of triplet or higher order infants (range: 0 in several states to 60.0% in Arizona). Among infants conceived with ART, 46.0% were born in multiple deliveries (range: 0 in Guam to 55.4% in Utah), compared with only 3.0% of infants among all births in the general population (range: 1.3% in Guam to 4.7% in Connecticut). A substantial proportion (43.4%) of ART-conceived infants were twin infants, and a smaller proportion (3.0%) were triplets and higher order infants. Nationally, infants conceived with ART comprised 5.6% of all low birthweight (<2,500 grams) infants (range: 0 in Guam to 16.0% in Massachusetts) and 5.6% of all very low birthweight (<1,500 grams) infants (range: 0 in Guam to 15.8% in Massachusetts). Overall, among ART-conceived infants, 31.6% were low birthweight (range: 22.6% in New Hampshire to 48.2% in Puerto Rico), compared with 8.0% among all infants (range: 5.7% in Alaska to 12.6% in Puerto Rico); 5.6% of ART infants were very low birthweight (range: 1.9% in Maine to 14.3% in Montana), compared with 1.4% among all infants (range: 0.9% in Alaska to 2.3% in the District of Columbia). Finally, ART-conceived infants comprised 4.4% of all infants born preterm (<37 weeks; range: 0 in Guam to 13.3% in Massachusetts) and 4.9% of all infants born very preterm (<32 weeks; range: 0 in Guam to 16.2% in Massachusetts). Overall, among infants conceived with ART, 36.6% were born preterm (range: 23.6% in New Hampshire to 56.8% in Wyoming), compared with 12.0% among all infants born in the general population (range: 8.4% in Vermont to 17.9% in Guam); 6.6% of ART infants were born very preterm (range: 0 in Maine to 14.5% in Puerto Rico), compared with 2.0% among all infants born in the general population (range: 1.3% in Alaska to 3.0% in the District of Columbia). The percentage of infants conceived with ART varied considerably by state and territory (range: 0.1% to 4.8%). In most states, multiples from ART comprised a substantial proportion of all twin, triplet, and higher-order infants born in the state, and the rates of low birthweight and preterm infants were disproportionately higher among ART infants than in the birth population overall. Even among women aged <35 years, for whom single embryo transfers should be considered (particularly in patients with a favorable prognosis) according to American Society of Reproductive Medicine (ASRM) guidelines, on average, two embryos were transferred per cycle in ART procedures, influencing the overall multiple infant rates in the United States. ART use per population unit was distributed disproportionately in the United States, with only 13 states showing ART use above the national rate, which might suggest barriers to ART services in the remaining states. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive statewide-mandated health insurance coverage for ART procedures (e.g., coverage for at least four cycles of IVF), three states (Illinois, Massachusetts, and New Jersey) also had rates of ART use >1.5 times the national level. This type of mandated insurance has been associated with greater use of ART and might account for the differences observed in other states. Reducing the number of embryos transferred per ART procedure among all age groups and promotion of eSET procedures, when clinically appropriate, is needed to reduce multiple births, including twin births, and related adverse consequences of ART. Improved patient education and counseling on the risks of twins might be useful in reducing twin births because twins account for the majority of multiples. Although ART contributes to increasing rates of multiple births, it does not explain all of the increases, and therefore the possible role of non-ART fertility treatments warrants further study.


Alterations of the intestinal transport and processing of gliadin peptides in celiac disease.
The hypothesis of a defect in the intestinal transport and processing of toxic (31-49) or immunostimulant (57-68 and the 33-mer 56-89) gliadin peptides was tested in patients with active celiac disease (ACD), patients with treated celiac disease (TCD), and controls. Using duodenal biopsy specimens mounted in Ussing chambers, we measured electrical resistance, mucosal-to-serosal radiolabeled-peptide fluxes, and peptide processing during transport using radio-reverse-phase high-performance liquid chromatography. Peptide 31-49 fluxes (24.7 microg x 3 h(-1). cm(-2)) were increased in patients with ACD compared with controls and patients with TCD (12.7 and 12.3 microg x 3 h(-1). cm(-2); P < 0.01). In contrast, no increase was observed for peptide 57-68 or 56-89 (33-mer). Electrical resistance was decreased in patients with ACD versus controls (15.3 vs. 23.9 ohms. cm(2); P < 0.001). Peptide 57-68 was partially degraded by brush-border peptidases in controls but not in patients with celiac disease. However, it was totally degraded after intestinal transport both in controls and patients with celiac disease. Peptides 31-49 and 56-89 were resistant to brush-border peptidases in all groups of patients but were totally degraded during intestinal transport in controls and patients with TCD. In patients with ACD, however, 50% of peptide 31-49 was delivered intact into the serosal compartment and only partial degradation of the 33-mer was observed. These abnormalities were not related to a nonspecific paracellular leakage. Our data indicate that gliadin peptides, although poorly or not digested by intraluminal enzymes, can be fully digested by enterocytes in controls and patients with TCD. In patients with ACD, incomplete degradation of the 33-mer and protected transport of the peptide 31-49 might favor their respective immunostimulatory and toxic effects.


Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial.
To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop "treatable" biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D3, alone and in combination on markers of apoptosis, in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2.0 g/d calcium or 800 IU/d vitamin D3, alone or in combination, versus placebo over 6 months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter) in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, Bax expression along the full lengths of crypts increased 56% (P = 0.02) in the vitamin D group and 33% in both the calcium (P = 0.31) and calcium plus vitamin D (P = 0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; P = 0.01). There were no statistically significant treatment effects on Bcl-2 expression. Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.


Climate change and the microbiology of the Antarctic Peninsula region.
Antarctic terrestrial ecosystems are cold, dry, low nutrient environments, with large temperature fluctuations and paradoxically low levels of water availability. These extreme environments are dominated by microorganisms (viruses, archaea, eubacteria, fungi and microsporidia, alveolata, stmramenopila, rhodophyta, green algae and protists), which can either tolerate or are adapted to exploit unfavourable growth conditions. However, climate change is altering the growth environment in Antarctica, and so selection pressures on these microorganisms are changing which, in turn, might affect microbial activity in key processes such as biogeochemical cycling. Although the direct effect of a change in, for example, temperature, is known for very few Antarctic microorganisms, molecular techniques (to monitor population structure) and genomic techniques (to identify specific gene function) are starting to give us an insight into what the potential effects of climate change might be at the cellular level. The key to how microorganisms respond to such change depends upon the rate and magnitude of the change along with the physiological capability of microorganisms to adapt or tolerate those changes. Here we will examine a number of case studies in which the effects of factors such as temperature, nutrient availability, grazing, salinity, seasonal cycle and carbon dioxide concentration have each been demonstrated to affect bacterial community structure in polar and alpine ecosystems. The results suggest that the spatial distribution of genetic variation and, hence, comparative rates of evolution, colonization and extinction are particularly important when considering the response of microbial communities to climate change.


Neither here nor there: localizing conflicting visual attributes.
Natural visual scenes are a rich source of information. Objects often carry luminance, colour, motion, depth and textural cues, each of which can serve to aid detection and localization of the object within a scene. Contemporary neuroscience presumes a modular approach to visual analysis in which each of these attributes are processed within ostensibly independent visual streams and are transmitted to geographically distinct and functionally dedicated centres in visual cortex (van Essen & Maunsell, 1983; Zihl, von Cramon & Mai, 1983; Maunsell & Newsome, 1987; Tootell, Hadjikhani, Mendola, Marrett & Dale, 1998). In the present study we ask how the visual system localizes objects within this framework. Specifically, we investigate how the visual system assigns a unitary location to objects defined by multiple stimulus attributes, where such attributes provide conflicting positional cues. The results show that conflicting sources of visual information can be effortlessly combined to form a global estimate of spatial position, yet, this conflation of visual attributes is achieved at a cost to localization accuracy. Furthermore, our results suggest that the visual system assigns more perceptual weight (Landy, 1993; Landy & Kojima, 2001) to visual attributes which are reliably related to object contours.


Mifamurtide for high-grade, resectable, nonmetastatic osteosarcoma following surgical resection: a cost-effectiveness analysis.
Mifamurtide is an immune macrophage stimulant that when added to standard chemotherapy has demonstrated survival benefit for newly diagnosed osteosarcoma. The objectives of this study were to investigate the cost-effectiveness of adding mifamurtide to standard three- or four-agent chemotherapy for high-grade, resectable, nonmetastatic osteosarcoma following surgical resection and the issues of obtaining robust cost-effectiveness estimates for ultra-orphan drugs, given the shortage of data. An economic evaluation was conducted from the perspective of the UK's National Health Service as part of the manufacturer's submission to the National Institute for Health and Care Excellence. The disease process was simplified to a transition through a series of health states, modeled by using a Markov approach. Data to inform the model were derived from patient-level data of Study INT-0133, published literature, and expert opinion. The final efficacy measure was life-years gained (LYG), and utilities were used to obtain quality-adjusted life-years (QALYs). For a 60-year time frame and a discount rate of 3.5% for outcomes, patients receiving mifamurtide benefited from an average additional 1.57 years of life and 1.34 QALYs, compared with patients receiving chemotherapy alone, giving an incremental cost-effectiveness ratio (ICER) of £58,737 per LYG and £68,734 per QALY. Because treatment effects were both substantial in restoring health and sustained over a very long period, the National Institute for Health and Care Excellence changed its guidance to allow a discount of 1.5% for outcomes to be applied in these special circumstances. By using this discount factor, it was found that patients receiving mifamurtide had an average additional 2.58 years of life and 2.20 QALYs compared with patients receiving chemotherapy alone, resulting in an ICER of £35,765 per LYG and £41,933 per QALY. Mifamurtide's ICER is cost-effective compared with that of other orphan and ultra-orphan drugs, for which prices and corresponding cost-effectiveness estimates are high.


Topical treatment of psoriasis: questionnaire results on topical therapy accessibility and influence of body surface area on usage.
Topical treatment of mild to moderate psoriasis is first-line treatment and exhibits varying degrees of success across patient groups. Key factors influencing treatment success are physician topical treatment choice (high efficacy, low adverse events) and strict patient adherence. Currently, no formalized, international consensus guidelines exist to direct optimal topical treatment, although many countries have national guidelines. To describe and analyse cross-regional variations in the use and access of psoriasis topical therapies. The study was conducted as an observational cross-sectional study. A survey was distributed to dermatologists from the International Psoriasis Council (IPC) to assess topical therapy accessibility in 26 countries and to understand how body surface area (BSA) categories guide clinical decisions on topical use. Variation in the availability of tars, topical retinoids, dithranol and balneotherapy was reported. The vast majority of respondents (100% and 88.4%) used topical therapy as first-line monotherapy in situations with BSA < 3% and BSA between 3% and 10%, respectively. However, with disease severity increasing to BSA > 10%, the number of respondents who prescribe topical therapy decreased considerably. In addition, combination therapy of a topical drug and a systemic drug was frequently reported when BSA measured >10%. This physician survey provides new evidence on topical access and the influence of disease severity on topical usage in an effort to improve treatment strategies on a global level.


Dysphagia in stroke: a new solution.
Dysphagia is extremely common following stroke, affecting 13%-94% of acute stroke sufferers. It is associated with respiratory complications, increased risk of aspiration pneumonia, nutritional compromise and dehydration, and detracts from quality of life. While many stroke survivors experience a rapid return to normal swallowing function, this does not always happen. Current dysphagia treatment in Australia focuses upon prevention of aspiration via diet and fluid modifications, compensatory manoeuvres and positional changes, and exercises to rehabilitate paretic muscles. This article discusses a newer adjunctive treatment modality, neuromuscular electrical stimulation (NMES), and reviews the available literature on its efficacy as a therapy for dysphagia with particular emphasis on its use as a treatment for dysphagia in stroke. There is a good theoretical basis to support the use of NMES as an adjunctive therapy in dysphagia and there would appear to be a great need for further well-designed studies to accurately determine the safety and efficacy of this technique.


Transcranial magnetic stimulation entrains alpha oscillatory activity in occipital cortex.
Parieto-occipital alpha rhythms (8-12 Hz) underlie cortical excitability and influence visual performance. Whether the synchrony of intrinsic alpha rhythms in the occipital cortex can be entrained by transcranial magnetic stimulation (TMS) is an open question. We applied 4-pulse, 10-Hz rhythmic TMS to entrain intrinsic alpha oscillators targeting right V1/V2, and tested four predictions with concurrent electroencephalogram (EEG): (1) progressive enhancement of entrainment across time windows, (2) output frequency specificity, (3) dependence on the intrinsic oscillation phase, and (4) input frequency specificity to individual alpha frequency (IAF) in the neural signatures. Two control conditions with an equal number of pulses and duration were arrhythmic-active and rhythmic-sham stimulation. The results confirmed the first three predictions. Rhythmic TMS bursts significantly entrained local neural activity. Near the stimulation site, evoked oscillation amplitude and inter-trial phase coherence (ITPC) were increased for 2 and 3 cycles, respectively, after the last TMS pulse. Critically, ITPC following entrainment positively correlated with IAF rather than with the degree of similarity between IAF and the input frequency (10 Hz). Thus, we entrained alpha-band activity in occipital cortex for ~ 3 cycles (~ 300 ms), and IAF predicts the strength of entrained occipital alpha phase synchrony indexed by ITPC.


Encephalocraniocutaneous lipomatosis (Haberland syndrome): A rare case report.
Haberland syndrome or Fishman syndrome also known as encephalocraniocutaneous lipomatosis (ECCL) is a rare, congenital neurocutaneous disorder. It is characterized by unilateral involvement of skin, eyes and central nervous system. We report the case of a 28-year-old woman who presented with soft lipomatous swelling over right temporal area with nonscarring alopecia of part of frontal and parietal region. The patient had a history of seizures and ipsilateral scleral dermoid. Computed tomography scan findings were suggestive of lipomas and calcification of falx. Magnetic resonance imaging showed right-sided hemi atrophy and two intracranial cysts. We report this case because of its rarity.


Protective factor screening for prevention practice: Sensitivity and specificity of the DESSA-Mini.
The Devereux Student Strengths Assessment Mini (DESSA-Mini; Naglieri, LeBuffe, & Shapiro, 2011/2014) was designed to overcome practical obstacles to universal prevention screening. This article seeks to determine whether an entirely strength-based, 8-item screening instrument achieves technical accuracy in routine practice. Data come from a district-wide implementation of a new social emotional learning (SEL) initiative designed to promote students' social-emotional competence. All students, kindergarten through Grade 8, were screened using the DESSA-Mini. A random 5 students per classroom received additional assessment. Concurrent and predictive criterion studies were conducted using the full DESSA as well as administrative records of serious disciplinary infraction. The DESSA-Mini showed excellent internal reliability, exceeding .90. Negligible to small differences were found between scores on the DESSA-Mini screen and the DESSA full assessment. Classification consistency between the DESSA-Mini and the DESSA was high (87%-94%) in routine practice, with sensitivity and specificity estimates exceeding Glascoe's (2005) standards. Finally, predictive validity of the DESSA-Mini was reliable; students screened as having a Need for SEL Instruction at the beginning of the year were 4.5 times more likely to have a record of serious disciplinary infraction at the end of the school year compared with those who were not identified (p < .001). These findings compare quite favorably with other instruments used in schools to screen entire student populations, in cases where such analyses have been conducted, and is consistent with a practice preference of identifying, but not overidentifying, students for accelerated preventative interventions for mental, emotional, and behavioral problems. (PsycINFO Database Record


Walking the tightrope: using power and authority in child welfare supervision.
Recognizing the importance of understanding the way in which supervisors in child welfare perceive their administrative responsibilities and use power and authority, an exploratory study was conducted. Supervisors in child welfare agencies in urban and rural settings participated in focus groups and discussed the impact of macro and micro factors on their performance. Policy changes, including using new approaches to child welfare and organizational culture had a major affect on the way they offered supervision. At the micro level, their use of power was related to elements in their relationships with frontline workers and their own professional development. Implications for child welfare practice and for new and experienced supervisors are presented.


A conceptual framework for understanding and reducing overuse by primary care providers.
Primary care providers frequently recommend, administer, or prescribe health care services that are unlikely to benefit their patients. Yet little is known about how to reduce provider overuse behavior. In the absence of a theoretically grounded causal framework, it is difficult to predict the contexts under which different types of interventions to reduce provider overuse will succeed and under which they will fail. In this article, we present a framework based on the theory of planned behavior that is designed to guide overuse research and intervention development. We describe categories of primary care provider beliefs that lead to the formation of intentions to assess the appropriateness of services, and propose factors that may affect whether the presence of assessment intentions results in an appropriate recommendation. Interventions that have been commonly used to address provider overuse behavior are reviewed within the context of the framework.


The role of the multidisciplinary team in antifungal stewardship.
There are a variety of challenges faced in the management of invasive fungal diseases (IFD), including high case-fatality rates, high cost of antifungal drugs and development of antifungal resistance. The diagnostic challenges and poor outcomes associated with IFD have resulted in excessive empirical use of antifungals in various hospital settings, exposing many patients without IFD to potential drug toxicities as well as causing spiralling antifungal drug costs. Further complexity arises as different patient groups show marked variation in their risk for IFD, fungal epidemiology, sensitivity and specificity of diagnostic tests and the pharmacokinetics and pharmacodynamics of antifungal drugs. To address these issues and to ensure optimal management of IFD, specialist knowledge and experience from a range of backgrounds is required, which extends beyond the remit of most antibiotic stewardship programmes. The first step in the development of any antifungal stewardship (AFS) programme is to build a multidisciplinary team encompassing the necessary expertise in the management of IFD to develop and implement the AFS programme. The specific roles of the key individuals within the AFS team and the importance of collaboration are discussed in this article.


Biomechanical comparison of unilateral and bilateral pedicle screws fixation for transforaminal lumbar interbody fusion after decompressive surgery--a finite element analysis.
Little is known about the biomechanical effectiveness of transforaminal lumbar interbody fusion (TLIF) cages in different positioning and various posterior implants used after decompressive surgery. The use of the various implants will induce the kinematic and mechanical changes in range of motion (ROM) and stresses at the surgical and adjacent segments. Unilateral pedicle screw with or without supplementary facet screw fixation in the minimally invasive TLIF procedure has not been ascertained to provide adequate stability without the need to expose on the contralateral side. This study used finite element (FE) models to investigate biomechanical differences in ROM and stress on the neighboring structures after TLIF cages insertion in conjunction with posterior fixation. A validated finite-element (FE) model of L1-S1 was established to implant three types of cages (TLIF with a single moon-shaped cage in the anterior or middle portion of vertebral bodies, and TLIF with a left diagonally placed ogival-shaped cage) from the left L4-5 level after unilateral decompressive surgery. Further, the effects of unilateral versus bilateral pedicle screw fixation (UPSF vs. BPSF) in each TLIF cage model was compared to analyze parameters, including stresses and ROM on the neighboring annulus, cage-vertebral interface and pedicle screws. All the TLIF cages positioned with BPSF showed similar ROM (<5%) at surgical and adjacent levels, except TLIF with an anterior cage in flexion (61% lower) and TLIF with a left diagonal cage in left lateral bending (33% lower) at surgical level. On the other hand, the TLIF cage models with left UPSF showed varying changes of ROM and annulus stress in extension, right lateral bending and right axial rotation at surgical level. In particular, the TLIF model with a diagonal cage, UPSF, and contralateral facet screw fixation stabilize segmental motion of the surgical level mostly in extension and contralaterally axial rotation. Prominent stress shielded to the contralateral annulus, cage-vertebral interface, and pedicle screw at surgical level. A supplementary facet screw fixation shared stresses around the neighboring tissues and revealed similar ROM and stress patterns to those models with BPSF. TLIF surgery is not favored for asymmetrical positioning of a diagonal cage and UPSF used in contralateral axial rotation or lateral bending. Supplementation of a contralateral facet screw is recommended for the TLIF construct.


Identification of phenolics in litchi and evaluation of anticancer cell proliferation activity and intracellular antioxidant activity.
Litchi leaf is a good resource for phenolics, which are good candidates for medicines. In this work, three phenolics were isolated from litchi leaf by column chromatography. Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy as secoisolariciresinol 9'-O-β-D-xyloside (1), 4,7,7',8',9,9'-hexahydroxy-3,3'-dimethoxy-8,4'-oxyneolignan (2), and cinnamtannin B1 (3). Cinnamtannin B1 showed better extra- and intracellular antioxidant activities than Compounds 1 and 2. The intracellular antioxidant activity of cinnamtannin B1 was related to the upregulation of endogenous antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), and inhibition of ROS generation. Furthermore, cinnamtannin B1 exhibited strong antiproliferative effects against HepG2 and Siha cell lines with no significant cytotoxicities. In the case of the HepG2 cell line, cell cycle arrest and apoptosis induction were the underlying anticancer mechanisms of cinnamtannin B1. The results indicated that cinnamtannin B1 was a potent cancer cell proliferation inhibitor and a good intracellular antioxidant.


Differences in the volume of pharmaceutical advertisements between print general medical journals.
Pharmaceutical advertisements have been argued to provide revenue that medical journals require but they are intended to alter prescribing behaviour and they are known to include low quality information. We determined whether a difference exists in the current level of pharmaceutical advertising in print general medical journals, and we estimated the revenue generated from print pharmaceutical advertising. Six print general medical journals in Canada, the United States, and the United Kingdom were sampled between 2007 and 2012. The number of advertisements and other journal content in selected issues of the Canadian Medical Association Journal (CMAJ), Canadian Family Physician (CFP), Journal of the American Medical Association (JAMA), New England Journal of Medicine (NEJM), British Medical Journal (BMJ), and Lancet were determined. Revenue gained from pharmaceutical advertising was estimated using each journal's 2013 advertising price list. The two Canadian journals sampled (CMAJ, CFP) contained five times more advertisements than the two American journals (JAMA, NEJM), and two British journals (BMJ, Lancet) (p<0.0001). The estimated annual revenue from pharmaceutical advertisements ranged from £0.025 million (for Lancet) to £3.8 million (for JAMA). The cost savings due to revenue from pharmaceutical advertising to each individual subscriber ranged from £0.02 (for Lancet) to £3.56 (for CFP) per issue. The volume of pharmaceutical advertisements differs between general medical journals, with the two Canadian journals sampled containing the most advertisements. International and temporal variations suggest that there is an opportunity for all general medical journals to reduce the number of pharmaceutical advertisements, explore other sources of revenue, and increase transparency regarding sources of revenue.


A long-term follow-up study of men born with very low birth weight and their reproductive hormone profile.
Environmental factors during the fetal period may adversely affect reproductive functions in men being born with very low birth weight (VLBW, <1500 g). The objective of this prospective, controlled cohort study was to investigate if VLBW men have an altered reproductive hormone profile compared with men born at term. The study group initially consisted of all VLBW boys live-born between 1 February 1987 and 30 April 1988 in the south-east region of Sweden (n = 47). A control child was chosen born at term, at the same hospital, with the same parity, without malformations, and next in order after each VLBW child who survived the first four weeks (n = 45). The present follow-up was performed when the men were 26-28 years of age and included measurements of serum hormone levels, hair testosterone concentration, and anthropometric data. Also life-style questionnaires were collected from 26 VLBW men and 19 controls. The VLBW group (n = 26) had higher median levels of serum estradiol, 84.5 pmol/L than controls (n = 19), 57.5 pmol/L (p = 0.008). There was no significant correlation between serum estradiol and BMI (r = 0.06, p = 0.74). There were no differences in other hormone levels or the reproductive pattern between the groups. In conclusion, even though there was a statistically significant difference in estradiol levels between the groups, both groups had low normal mean levels of questionable clinical significance. The reproductive pattern was similar in the two groups and in this study being born VLBW does not seem to affect these measured aspects of reproduction. ADHD: attention deficit hyperactive disorder; AGA: average for gestational age; BMI: body mass index; CP: cerebral palsy; DHT: dihydrotestosterone; FSH: follicle stimulating hormone; LBW: low birth weight; LH: luteinizing hormone; SAD: sagittal abdominal diameter; SGA: small for gestational age; SHBG: sex hormone binding globulin; TSH: thyroid stimulating hormone; T3: triiodothyronine; T4: thyroxin; VLBW: very low birth weight.


Carbon dioxide wedged arterial splenoportography: a new technique--a case report and an experimental study.
Patients with splenic vein occlusion may present a diagnostic problem when the location, morphology, and cause of the obstructive lesion and the associated collateral veins cannot be clearly defined by standard diagnostic imaging modalities such as computed tomography, magnetic resonance venography, or indirect splenoportography (arterial portography). To evaluate the safety and effectiveness of carbon dioxide (CO(2)) wedged arterial splenoportography for definitive investigation of splenic vein occlusion. Following unsuccessful diagnosis with computed tomography and standard contrast arterial portography in a patient with recurrent gastric variceal bleeding, CO(2) was injected into a wedged splenic arterial catheter and successfully outlined splenic vein occlusion and gastric varices. Our experience with this patient prompted us to perform an experimental study in swine to evaluate the safety and effectiveness of CO(2) wedged arterial splenoportography for visualization of the splenic and portal veins. A microcatheter was advanced coaxially and wedged into the splenic arteries of three pigs. After checking the wedged positioning with contrast medium injection, CO(2) was injected manually and the splenic region imaged. The spleens were then removed for gross and microscopic examinations. In the patient, CO(2) wedged arterial splenoportography demonstrated gastric varices associated with splenic vein occlusion. In all animals, CO(2) wedged arterial splenoportography visualized the splenic and portal veins. No CO(2) extravasations occurred in the spleen. Gross and microscopic examinations revealed no evidence of splenic rupture or intrasplenic hematoma. CO(2) wedged arterial splenoportography may be a useful method for visualizing gastric varices associated with splenic vein occlusion. This new technique has the potential to replace the standard splenic arterial portography for visualization of splenic and portal veins, thus eliminating the need for injection of a large volume of iodinated contrast material. Further clinical studies are justified to evaluate this technique.


Toward a more comprehensive greenhouse gas emissions assessment of biofuels: the case of forest-based fischer-tropsch diesel production in Finland.
Increasing the use of biofuels influences atmospheric greenhouse gas concentrations. Although widely recognized, uncertainties related to the particular impacts are typically ignored or only partly considered. In this paper, various sources of uncertainty related to the GHG emission savings of biofuels are considered comprehensively and transparently through scenario analysis and stochastic simulation. Technology and feedstock production chain-specific factors, market-mediated factors and climate policy time frame issues are reflected using as a case study Fischer-Tropsch diesel derived from boreal forest biomass in Finland. This case study shows that the GHG emission savings may be positive or negative in many of the cases studied, and are subject to significant uncertainties, which are mainly determined by market-mediated factors related to fossil diesel substitution. Regardless of the considerable uncertainties, some robust conclusions could be drawn; it was likely of achieving some sort of but unlikely of achieving significant savings in the GHG emissions within the 100 year time frame in many cases. Logging residues (branches) performed better than stumps and living stem wood in terms of the GHG emission savings, which could be increased mainly by blocking carbon leakage. Forest carbon stock changes also significantly contributed to the GHG emission savings.


Multifocal central serous chorioretinopathy with photoreceptor-retinal pigment epithelium diastasis in heritable pulmonary arterial hypertension.
To report atypical central serous chorioretinopathy and choroidal thickening in a patient with heritable pulmonary arterial hypertension. A 40-year-old man with heritable pulmonary arterial hypertension presented with blurred vision in his left eye and was followed up for 1 year with clinical examination, enhanced depth optical coherence tomography, fluorescein and indocyanine green angiography, and fundus photography. At presentation, atypical central serous chorioretinopathy with multiple retinal pigment epithelial detachments, a thick subfoveal choroid, and dilated choroidal vessels were seen in the patient's symptomatic left eye. After treatment for pulmonary hypertension, the serous detachments disappeared and choroidal thickness gradually decreased over a period of 4 weeks and remained unchanged at 13 months of follow-up. Central serous chorioretinopathy and choroidal thickening that responded to treatment of pulmonary arterial hypertension suggest a pathophysiological link between pulmonary arterial hypertension and central serous chorioretinopathy, perhaps mediated by choroidal venous stasis.


Unusually severe case of dermatosis neglecta.
An 18-year-old black woman with cerebral palsy was admitted for evaluation of an intrathecal baclofen pump site infection. The dermatology service was consulted for treatment suggestions of a presumed diagnosis of chronic tinea capitis. Three courses of oral griseofulvin during the past 2 years failed to resolve the patient's chronic scalp dermatosis. Scalp lesions first began about 2 years earlier after hospitalization for placement of an intrathecal baclofen pump. The patient was unable to care for her scalp due to her cerebral palsy, and her mother interpreted the scalp condition as infectious. No routine shampoo care, scalp care, or topical treatment was performed for more than 1 1/2 years. The mother felt that touching the patient's scalp might cause pain and noted that the majority of her time was spent concentrating on more critical medical issues. Physical examination revealed coalescing hyperkeratotic plaques extending dorsally from the anterior hairline to the occipital scalp with small flecks of keratinous debris throughout the remaining hair (Figure 1). The plate-like plaques were devoid of hair, except at a few fissures where a few tufts of hair emerged. No cervical lymph nodes were appreciated on palpation. Treatment was initiated with compresses consisting of large warm water-soaked towels 4 times daily. Three times a day, a nursing staff applied 5% salicylic acid in olive oil to the scalp under a shower cap for approximately 1 hour. Over the following 2 days, a significant reduction in keratinous debris was appreciated. Within 2 weeks, the bulk of the plaques had been removed (Figure 2). At 6-week follow-up, the underlying scalp showed areas of fibrosis and possible scarring with a few emerging tufts of hair. On the basis of history and response to treatment with salicylic acid and routine scalp care, the patient was diagnosed with an unusually severe case of dermatosis neglecta.


Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Tromsø Study.
Though the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population. Measurements and DNA were obtained from the participants in the Tromsø Study in 1994-1995, registered with the outcomes of interest and a randomly selected control group. The impact of the rs7968585 genotypes was evaluated with Cox proportional hazards. A total of 8,461 subjects were included among whom 1,054 subjects were registered with T2D, 2,287 with MI, 3,166 with cancer, and 4,336 with death. Mean follow-up time from birth was 60.8 years for T2D and MI, 61.2 years for cancer, while mean follow-up time from examination date was 16.5 years for survival. Mean serum 25(OH)D levels did not differ across the rs7968585 genotypes. With the major homozygote genotype as reference, the minor homozygote subjects had hazard ratios of 1.25 (95% CI 1.05-1.49) for T2D and 1.14 (1.02-1.28) for MI (P = 0.011 and 0.023, respectively, without the Bonferroni correction). No significant interaction between serum 25(OH)D status and the rs7968585 genotype was found for any of the endpoints. The VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.


Emotion-attention network interactions during a visual oddball task.
Emotional and attentional functions are known to be distributed along ventral and dorsal networks in the brain, respectively. However, the interactions between these systems remain to be specified. The present study used event-related functional magnetic resonance imaging (fMRI) to investigate how attentional focus can modulate the neural activity elicited by scenes that vary in emotional content. In a visual oddball task, aversive and neutral scenes were presented intermittently among circles and squares. The squares were frequent standard events, whereas the other novel stimulus categories occurred rarely. One experimental group [N=10] was instructed to count the circles, whereas another group [N=12] counted the emotional scenes. A main effect of emotion was found in the amygdala (AMG) and ventral frontotemporal cortices. In these regions, activation was significantly greater for emotional than neutral stimuli but was invariant to attentional focus. A main effect of attentional focus was found in dorsal frontoparietal cortices, whose activity signaled task-relevant target events irrespective of emotional content. The only brain region that was sensitive to both emotion and attentional focus was the anterior cingulate gyrus (ACG). When circles were task-relevant, the ACG responded equally to circle targets and distracting emotional scenes. The ACG response to emotional scenes increased when they were task-relevant, and the response to circles concomitantly decreased. These findings support and extend prominent network theories of emotion-attention interactions that highlight the integrative role played by the anterior cingulate.


Network Mapping of Connectivity Alterations in Disorder of Consciousness: Towards Targeted Neuromodulation.
Disorder of consciousness (DoC) refers to a group of clinical conditions that may emerge after brain injury, characterized by a varying decrease in the level of consciousness that can last from days to years. An understanding of its neural correlates is crucial for the conceptualization and application of effective therapeutic interventions. Here we propose a quantitative meta-analysis of the neural substrate of DoC emerging from functional magnetic resonance (fMRI) and positron emission tomography (PET) studies. We also map the relevant networks of resulting areas to highlight similarities with Resting State Networks (RSNs) and hypothesize potential therapeutic solutions leveraging network-targeted noninvasive brain stimulation. Available literature was reviewed and analyzed through the activation likelihood estimate (ALE) statistical framework to describe resting-state or task-dependent brain activation patterns in DoC patients. Results show that task-related activity is limited to temporal regions resembling the auditory cortex, whereas resting-state fMRI data reveal a diffuse decreased activation affecting two subgroups of cortical (angular gyrus, middle frontal gyrus) and subcortical (thalamus, cingulate cortex, caudate nucleus) regions. Clustering of their cortical functional connectivity projections identify two main altered functional networks, related to decreased activity of (i) the default mode and frontoparietal networks, as well as (ii) the anterior salience and visual/auditory networks. Based on the strength and topography of their connectivity profile, biophysical modeling of potential brain stimulation solutions suggests the first network as the most feasible target for tES, tDCS neuromodulation in DoC patients.


Culture medium for enterobacteria.
A new minimal medium for enterobacteria has been developed. It supports growth of Escherichia coli and Salmonella typhimurium at rates comparable to those of any of the traditional media that have high phosphate concentrations, but each of the macronutrients (phosphate, sulfate, and nitrogen) is present at a sufficiently low level to permit isotopic labeling. Buffering capacity is provided by an organic dipolar ion, morpholinopropane sulfonate, which has a desirable pK (7.2) and no apparent inhibitory effect on growth. The medium has been developed with the objectives of (i) providing reproducibility of chemical composition, (ii) meeting the experimentally determined nutritional needs of the cell, (iii) avoiding an unnecessary excess of the major ionic species, (iv) facilitating the adjustment of the levels of individual ionic species, both for isotopic labeling and for nutritional studies, (v) supplying a complete array of micronutrients, (vi) setting a particular ion as the crop-limiting factor when the carbon and energy source is in excess, and (vii) providing maximal convenience in the manufacture and storage of the medium.


Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions.
In 2017, the World Health Organization (WHO) designated clarithromycin-resistant Helicobacter pylori a high priority for antibiotic research and development. However, there are no clear data on the global distribution of resistance or its clinical effects. We performed a systematic review and meta-analysis to assess the distribution of H pylori resistance to commonly used antibiotics and to measure the association between antibiotic resistance and treatment failure. We searched publication databases for studies that assessed rates of H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline. Pooled estimates of primary and secondary resistance and 95% confidence intervals (CIs) were grouped by WHO region. The association between antibiotic resistance and treatment failure was measured by extracting data on treatment efficacy in patients with resistant and susceptible isolates and pooling odds ratios with 95% CIs. We identified 178 studies, comprising 66,142 isolates from 65 countries. Primary and secondary resistance rates to clarithromycin, metronidazole, and levofloxacin were ≥15% in all WHO regions, except primary clarithromycin resistance in the Americas (10%; 95% CI, 4%-16%) and South-East Asia region (10%; 95% CI, 5%-16%) and primary levofloxacin resistance in the European region (11%; 95% CI, 9%-13%). There was considerable heterogeneity (I2 > 75%) among all analyses-this might have resulted from the grouping of resistance rates by country. Increasing antibiotic resistance was observed in most WHO regions. Resistance to clarithromycin was significantly associated with failure of clarithromycin-containing regimens (odds ratio, 6.97; 95% CI, 5.23-9.28; P < .001). Resistance of H pylori to antibiotics has reached alarming levels worldwide, which has a great effect on efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.


Lumbar disc degeneration and sagittal flexibility.
It is uncertain whether intervertebral disc degeneration is associated with reduced or increased flexibility, although lumbar flexibility is known to reduce with advancing age. This cross-sectional study of 214 middle-aged men attempted to determine the influence on lumbar sagittal flexibility from intervertebral disc degeneration parameters measured from magnetic resonance images (disc height, signal intensity, bulging, osteophytes). Multivariate analyses showed that a reduced extent of lumbar flexibility could be accounted for by the combined effect of decreasing disc height together with increasing age, weight, and back pain frequency. Although it remains possible that single degenerate discs will display increased mobility, the presence of discs at various stages of degeneration results in a net reduction of flexibility. The factors studied here explained only 31% of the variance in flexibility; the major determinants remain to be identified and quantified.


Distant metastases from prostatic carcinoma express androgen receptor protein.
Nearly all primary prostatic carcinomas have been found to express the androgen receptor (AR) protein, which is the intracellular mediator of androgen action. To gain a better insight into the mechanisms of androgen independence of advanced prostatic carcinoma, it is important to know whether the AR is also present in metastases of androgen-independent tumors. We have assessed the status of the AR and the prostate-specific antigen in 22 metastases of 18 patients with progressive prostate cancer. In 18 cases, the metastases were localized in bone, in 3 cases in the epidural space, and in 1 case in the periosteum. All but one patient had received some kind of endocrine treatment for prostatic carcinoma. Paraffin-embedded tissue sections were stained for the AR following a streptavidinbiotin-peroxidase protocol with the polyclonal antibody PG-21, which is directed against amino acids 1 through 21 of the rat and the human AR. The percentage of AR-positive cells was evaluated on the basis of an arbitrary 4-point scale. All 22 tumor metastases displayed AR positivity. One AR-positive metastatic lesion did not stain for prostate-specific antigen, but in all other metastases, this protein was detected by means of immunohistochemistry. The present study provides evidence that, unlike androgen-independent prostatic carcinoma cell lines, distant prostatic carcinoma metastases do express the AR. These findings indicate that the AR may be involved in the progression of prostate cancer.


25-hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus.
Low serum levels of 25-hydroxyvitamin D (25[OH]D; vitamin D) are associated with a higher frequency of cardiovascular disease and risk factors in the general population. Vitamin D deficiency has also been noted in systemic lupus erythematosus (SLE). The objective of this study was to evaluate the associations of serum 25(OH)D levels with cardiovascular risk factors in women with SLE. Data collected in 181 women with SLE included demographics, SLE activity and damage assessments, cardiovascular risk factors, medications, and laboratory assessments of inflammatory markers and 25(OH)D levels. Multiple linear and logistic regressions were used to estimate the association of 25(OH)D levels with cardiovascular risk factors. The mean age and disease duration were 43.2 and 11.9 years, respectively. The mean 25(OH)D level was 27.1 ng/ml and 62.2% had 25(OH)D levels <30 ng/ml. In unadjusted analyses, lower 25(OH)D levels were significantly associated with higher diastolic blood pressure, low-density lipoprotein cholesterol, lipoprotein(a), body mass index (BMI), and fibrinogen levels, as well as self-reported hypertension and diabetes mellitus. Lower 25(OH)D levels were also significantly associated with higher SLE disease activity and damage scores. After adjustment for age, seasonal variation, and race/ethnicity, lower 25(OH)D levels were also significantly related to higher fasting serum glucose. With further adjustment for BMI, associations between 25(OH)D and cardiovascular risk factors were no longer significant. This study demonstrates that vitamin D levels are low in women with SLE and significant associations exist with selected cardiovascular risk factors, although most of these associations can be explained by BMI.


On a new acanthocephalan family and a new order, from birds in Vietnam.
During November 2000, a collection of acanthocephalans from birds in Quang Ninh Province, Vietnam, included a new genus and species in a new family and order. Pyrirhynchus heterospinus n. gen., n. sp. (Pyrirhynchidae n. fam.: Heteramorphida: new order) is described from Actitis hypoleucos (Linnaeus, 1758) (common sandpiper). The new family combines characters from Polymorphidae and Heteracanthocephalidae, and it includes new features. Specimens of the new species are distinguished from those of Heteracanthocephalidae and/or Polymorphidae by their long cylindrical trunk with anterior swelling, pyriform proboscis with hooks much larger ventrally, brain at the anterior end of the receptacle, specialized tubular cement glands, and elliptoid eggs with concentric shells. A detailed analysis of proboscis and trunk armature is included, and specimens of several species of Arhythmorhynchus Lühe, 1911 (Polymorphidae) were studied for comparative purposes. The proboscis of P. heterospinus is armed with 17 to 20 rows of 17 to 19 hooks each, with anterior 9-11 hooks rooted and posterior 6-10 spines rootless.


Pharmacokinetic Analysis of Propofol Target-Controlled Infusion Models in Chinese Patients with Hepatic Insufficiency.
BACKGROUND Effects of liver dysfunction on target-controlled infusion (TCI) with Marsh parameters of propofol remain poorly documented. The purpose of this study was to evaluate the performance of propofol TCI in a cohort of Chinese patients with severe hepatic insufficiency. MATERIAL AND METHODS We assigned 32 patients who underwent liver transplantation to 3 groups according to Child-Turcotte-Pugh (CTP) score. Anesthesia, preceding liver transplantation, was induced and maintained with TCI of 3 µg/mL propofol. Plasma propofol concentration was assessed. Propofol TCI system performance was analyzed in terms of error size, bias, and divergence. Data on plasma propofol concentrations were analyzed, and population pharmacokinetic parameters of propofol were fitted by NONMEM software. RESULTS In the CTP C group, measured concentrations of propofol were much higher than those of predictive concentrations, with significantly higher overshoots compared to CTP A patients. Overall, TCI system performance was significantly lower in CTP C patients. Linear regression equations of Cm vs. Cp and a regression model of pharmacokinetics were obtained. CONCLUSIONS Propofol TCI device performance with Marsh parameters was clinically acceptable in CTP A patients but may not be suitable for patients with severe hepatic impairment.


The salivary testosterone response to a chance-determined contest is associated with face-gazing behaviours in athletic women.
Human gaze is an important indicator of dominant and submissive behaviours related to positioning in a social hierarchy. This study investigated face gazing after a chance-determined contest and its linkage to salivary testosterone (sal-T) reactivity in athletic women. Twenty-six women athletes completed a coin-toss game on days 7 (D7), 14 (D14) and 21 (D21) of a single menstrual cycle. The game was played against an unknown opponent of similar age with the winner congratulated and rewarded with all coins. Gazing towards an opponent's head or face was timed after each contest (over 2 min) from video footage. Salivary T (sal-T) was assessed before and 15 min after these contests. The sal-T residuals increased after winning and decreased after losing on D7, D14 and D21 (p < 0.05). Gaze times were longer after a loss (M = 7.8 s) than a win (M = 3.1 s) across all days. Regression analyses revealed that the sal-T residuals and contest outcome interacted to predict gaze time. Upon deconstruction we found that, when losing a contest, a larger sal-T response (i.e., smaller decline) predicted a longer gaze (β = 1.71, p = 0.004), but no association was evident when winning (β = -0.06, p = 0.821), and these slope patterns differed (p = 0.011). In conclusion, winning a contest by chance increased sal-T responsivity and decreased opponent gaze across the menstrual cycle. A positive relationship between individual sal-T reactivity and gaze duration was observed, but only when losing. These preliminary results support suggestions that women's T may help modulate post-competition behaviours (e.g., face gazing) possibly to achieve social cohesion and cooperation.


Loquat (Eriobotrya japonica) extracts suppress the adhesion, migration and invasion of human breast cancer cell line.
We examined the inhibitory effects of loquat methanol extract on the adhesion, migration, invasion and matrix metalloproteinase (MMP) activities of MDA-MB-231 human breast cancer cell line. Cells were cultured with DMSO or with 10, 25, or 50 microg/ml of loquat methanol extract. Both leaf and seed extracts significantly inhibited growth of MDA-MB-231 cells in a dose-dependent manner, although leaf extract was more effective. Adhesion and migration were significantly inhibited by loquat extracts in a dose-dependent manner. Loquat extract also inhibited the invasion of breast cancer cells in a dose-dependent manner and leaf extract was more effective than seed extract. MMP-2 and MMP-9 activities were also inhibited by loquat extract. Our results indicate that methanol extracts of loquat inhibit the adhesion, migration and invasion of human breast cancer cells partially through the inhibition of MMP activity and leaf extract has more anti-metastatic effects in cell based assay than seed extract. Clinical application of loquat extract as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.