An attentional learning account of the shape bias: reply to Cimpian and Markman (2005) and Booth, Waxman, and Huang (2005).
Recently, Developmental Psychology published 2 articles on the shape bias; both rejected the authors' previous proposals about the role of attentional learning in the development of a shape bias in object name learning. A. Cimpian and E. Markman (2005) did so by arguing that the shape bias does not exist but is an experimental artifact. A. E. Booth, S. R. Waxman, and Y. T. Huang (2005), in contrast, concluded that the shape bias (and its contextual link to artifact categories) does exist but that the mechanisms that underlie it are conceptual knowledge and not attentional learning. In response, in this article the authors clarify the claims of the Attentional Learning Account (ALA) and interpretations of the data under question. The authors also seek to make explicit the deeper theoretical divide: cognition as sequestered from processes of perceiving and acting versus as embedded in, and inseparable from, those very processes.


Bayesian methods in bioinformatics and computational systems biology.
Bayesian methods are valuable, inter alia, whenever there is a need to extract information from data that are uncertain or subject to any kind of error or noise (including measurement error and experimental error, as well as noise or random variation intrinsic to the process of interest). Bayesian methods offer a number of advantages over more conventional statistical techniques that make them particularly appropriate for complex data. It is therefore no surprise that Bayesian methods are becoming more widely used in the fields of genetics, genomics, bioinformatics and computational systems biology, where making sense of complex noisy data is the norm. This review provides an introduction to the growing literature in this area, with particular emphasis on recent developments in Bayesian bioinformatics relevant to computational systems biology.


Exploring the Role of Insulin Signaling in Relative Growth: A Case Study on Wing-Body Scaling in Lepidoptera.
Adult forms emerge from the relative growth of the body and its parts. Each appendage and organ has a unique pattern of growth that influences the size and shape it attains. This produces adult size relationships referred to as static allometries, which have received a great amount of attention in evolutionary and developmental biology. However, many questions remain unanswered, for example: What sorts of developmental processes coordinate growth? And how do these processes change given variation in body size? It has become increasingly clear that nutrition is one of the strongest influences on size relationships. In insects, nutrition acts via insulin/TOR signaling to facilitate inter- and intra-specific variation in body size and appendage size. Yet, the mechanism by which insulin signaling influences the scaling of growth remains unclear. Here we will discuss the potential roles of insulin signaling in wing-body scaling in Lepidoptera. We analyzed the growth of wings in animals reared on different diet qualities that induce a range of body sizes not normally present in our laboratory populations. By growing wings in tissue culture, we survey how perturbation and stimulation of insulin/TOR signaling influences wing growth. To conclude, we will discuss the implications of our findings for the development and evolution of organismal form.


Chronic exposure to beta-hydroxybutyrate impairs insulin action in primary cultures of adult cardiomyocytes.
Type 1 and type 2 diabetic patients often show elevated plasma ketone body concentrations. Because ketone bodies compete with other energetic substrates and reduce their utilization, they could participate in the development of insulin resistance in the heart. We have examined the effect of elevated levels of ketone bodies on insulin action in primary cultures of adult cardiomyocytes. Cardiomyocytes were cultured with the ketone body beta-hydroxybutyrate (beta-OHB) for 4 or 16 h, and insulin-stimulated glucose uptake was evaluated. Although short-term exposure to ketone bodies was not associated with any change in insulin action, our data demonstrated that preincubation with beta-OHB for 16 h markedly reduced insulin-stimulated glucose uptake in cardiomyocytes. This effect is concentration dependent and persists for at least 6 h after the removal of beta-OHB from the media. Ketone bodies also decreased the stimulatory effect of phorbol 12-myristate 13-acetate and pervanadate on glucose uptake. This diminution could not be explained by a change in either GLUT-1 or GLUT-4 protein content in cardiomyocytes. Chronic exposure to beta-OHB was associated with impaired protein kinase B activation in response to insulin and pervanadate. These results indicate that prolonged exposure to ketone bodies altered insulin action in cardiomyocytes and suggest that this substrate could play a role in the development of insulin resistance in the heart.


Molecular cloning and functional characterization of Cynomolgus monkey (Macaca fascicularis) CC chemokine receptor, CCR3.
We have cloned and performed the first functional characterization of the chemokine receptor, CCR3, of Cynomolgus monkey (Macaca fascicularis). The deduced amino acid sequence of the cloned Cynomolgus CCR3 was found to be more similar to that of a previously-reported Rhesus (Macaca mulatta) CCR3 (99.4%) than that of a reported Cynomolgus CCR3 (98.0%). Stably-transfected Cynomolgus CCR3 bound human eotaxin (CCL11) with similar kinetics (Kd 240 pM) and was responsive to human CCR3 ligands (eotaxin [CCL11], eotaxin-2 [CCL24], and MCP4 [CCL13]) in Ca(2+) mobilization and chemotaxis assays, thus provides a useful alternative species model system for the analysis of modulators of eotaxin--CCR3 induced signaling and activation.


Effect of surrounded shade and specimen`s thickness on color adjustment potential of a single-shade composite.
This study evaluated the effect of surrounded shade and specimens` thickness on the color adjustment potential (CAP) of a single-shade composite. The composite Vittra APS Unique was surrounded (dual specimens) or not (simple specimens) by a control composite (shade A1, A2, or A3). Simple specimens of the control composite were also confectioned. Opacity and whiteness index for dentistry (WID) were calculated for simple specimens. Color differences between the simple (ΔE*SIMPLE)/ dual specimens (ΔE*DUAL) and the controls were calculated. CAP was calculated based on the ratio between ΔE* SIMPLE and ΔE* DUAL. The tested composite presented lower opacity (53 to 62% vs. 80 to 93%) and higher WID (≈ 42 vs. 18 to 32) than controls. Irrespective of the specimens' thickness (1.0/ 1.5 mm), the lowest values of ΔE* SIMPLE (11.1/ 10.8) and ΔE*DUAL (7.2/ 6.1) were observed using the surrounding shade A1. The shade A3 yielded higher ΔE*SIMPLE (16.4/ 17.1) and ΔE* DUAL (11.3/ 12.3) than the A2 (ΔE*SIMPLE = 13.4/ 14.6; and ΔE* DUAL = 9.7/ 10.3). The specimen`s thickness significantly affected the CAP (0.35 and 0.44 for 1.0 and 1.5 mm, respectively) only for shade A1, which had the highest CAP values. The shade A3 resulted in higher CAP values (0.31) than A2 (0.27) when 1.0-mm thick specimens were used, but similar values were observed for 1.5 thick specimens (≈ 0.29). In conclusion, both surrounding shade and specimen thickness can affect the CAP of a single-shade resin composite.


1,4-Benzenedithiol-Bridged Nanogap-Based Individual Particle Surface-Enhanced Raman Spectroscopy Mechanical Probe for Revealing the Endocytic Force.
1,4-Benzenedithiol (BDT)-bridged core-satellite assemblies, as surface-enhanced Raman spectroscopy (SERS) mechanical probes, can be employed for real-time monitoring of the dynamics of endocytic forces and the accompanying trajectory of nanoparticles during the endocytosis process. These mechanical probes exhibit good responses in terms of SERS intensity ratios while undergoing mechanical pressure. Force tracing and the accompanying trajectory of nanoparticles are resolved accurately to render the endocytosis process in live cells. Density functional theory simulation results further proved the sensing scheme due to the electrons transforming between BDT and gold nanoparticles. Furthermore, this SERS mechanical probe is a valid method to visualize endocytic forces at multiple locations and establish a direct criterion to discriminate between cancer cells and normal cells.


Adiposity and biological maturity in girls 6-16 years of age.
The aim of this study was to investigate the relationships between adiposity and skeletal maturity, relative skeletal maturity and percentage of predicted adult stature. A representative sample of 6,029 Flemish girls aged 6-16 years of age was investigated. Age specific correlations between adiposity and biological maturity indicators were calculated and in each age group the fattest 5% were compared with the leanest 5%. Adiposity was estimated from the sum of five skinfolds (biceps, triceps, subscapular, suprailiac and medial calf). Skeletal age was assessed according to the Tanner-Whitehouse technique. Relative skeletal age was calculated as the difference between skeletal age and chronological age and percentage of predicted adult stature was calculated according to the Tanner-Whitehouse Mark II regression technique. Correlations between adiposity and maturity indicators are positive, but vary between r = 0.00 and r = 0.39. When stature is statistically controlled, correlations are reduced slightly. The 5% fattest girls are equally advanced (0.2 to 1.2 years) as the 5% leanest girls are delayed (0.0 to 0.9 years) in skeletal maturation. Attained statures are consistent with the maturity data and indicate that size differences between fat and lean girls are primarily due to maturity differences. It was concluded that during childhood and adolescence, fatness is associated with advanced and leanness with delayed biological maturity status. This association seems to have long term effects that merit further study.


Accuracy of three dimensional-planned patient-specific instrumentation in femoral and tibial rotational osteotomy for patellofemoral instability.
Patellofemoral instability can be caused by tibial or femoral torsional deformity. Established surgical treatment options are rotational osteotomies, but the transfer from pre-operative planning to surgical execution can be challenging. Patient-specific instruments (PSI) are proofed to be helpful tools in realignment surgery. However, accuracy of PSI in femoral and tibial rotational osteotomies remains still unknown. Goal of the present study was to evaluate the accuracy of PSI in femoral and tibial rotational osteotomies in a patient population suffering from patellofemoral instability. All patients that underwent femoral or tibial rotational osteotomy using PSI in case of patellofemoral instability from October 2015 until April 2019 in our clinic were included. Twelve knees with twelve supracondylar femoral and seven supratuberositary tibial rotational osteotomies could be included. Accuracy of the correction was assessed using pre- and post-operative CT scans based on conventional measurements and, in 3D, based on 3D bone models of the respective patients. CT measurements revealed an absolute difference between planned and achieved rotation of 4.8° ± 3.1° for femoral and 7.9° ± 3.7° for tibial rotational osteotomies without significant difference (p = 0.069). Regarding 3D assessment, a significant difference could be observed for the residual error between femoral and tibial rotational osteotomies in the 3D angle (p = 0.014) with a higher accuracy for the femoral side. The application of PSI for femoral and tibial rotational osteotomy is a safe surgical treatment option. Accuracy for femoral rotational osteotomies is higher compared with tibial rotational osteotomies using PSI.


Renal Cell Carcinoma with Supradiaphragmatic Tumor Thrombus: Avoiding Sternotomy and Cardiopulmonary Bypass.
Renal cell carcinoma (RCC) accounts for 2-3% of all malignant disease in adults and has a propensity to infiltrate the surrounding adjacent structures with a biologic predisposition for vascular invasion. This tropism for the venous system facilitates propagation into the renal vein and inferior vena cava (IVC) in up to 25% of patients with RCC. Surgical resection remains the mainstay treatment for RCC with venous tumor thrombus (TT) extension and the only hope for a potential cure. Higher thrombus levels correlate with more advanced stages of disease and thus poorer survival rates. Although CPB with circulatory arrest has been successfully performed during resection of these tumors, its use remains controversial due to the risk of coagulopathy, platelet dysfunction, and central nervous system complications. Complete intraabdominal surgical excision of level III thrombi can be achieved without sternotomy and CPB by utilizing hepatic mobilization maneuvers. The purpose of this review is to provide an update on the surgical management of these difficult cases of RCC with supradiaphragmatic tumor thrombi, including a description of transplant-based techniques that avoid sternotomy and cardiopulmonary bypass (CPB), minimizing intra- and post-operative complications.


Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study.
In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 microm column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine, Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption.


The new techniques of gynaecologic laparoscopy. Gasless, open Hasson, optic trocar.
New techniques of laparoscopy: gasless, open Hasson, optic trocars allow to avoid the risks of vessel and bowel injuries. The objective of this study was to evaluate the capability of a retractor system as an alternative to conventional technique without pneumoperitoneum and to assess if the system facilitates the use of conventional surgical instruments during gynaecological surgery. Prospective evaluation. University-affiliated county hospital. Gasless laparoscopy surgery was performed on 49 patients between December 1995 and July 1996 with a retractor system without pneumoperitoneum consisting of an intrabdominal retractor using conventional surgical and laparoscopic instruments and to enable a simultaneous vaginal approach. Gasless laparoscopy was successful in 44 (90%) of cases. A simultaneous vaginal approach was used in one third of indications including vaginal myomectomy and laparoscopic assisted hysterectomy. Conversion to laparotomy was required in 5% of cases. Mean procedure duration was 90 minutes and mean hospitalisation time was 5.7 days. The introduction of new techniques of laparoscopy: gasless, open Hasson, optic trocars has broadened the application of operative laparoscopy. Gasless technique in lieu of conventional laparoscopy can be performed reliably and safely for most gynaecological indications. The most outstanding benefit of this method is that it can be combined with a vaginal approach which is not possible using a pneumoperitoneum due to gas leakage. The place of gasless laparoscopy will depend on continuing development by instrument manufacturers, in order to achieve an instrument providing vision as good as that seen with the pneumoperitoneum.


Genetically modified and organic crops in developing countries: a review of options for food security.
Since two decades ago, when the first GM crops were introduced, there have increasingly been hot debates on the applications of gene manipulation. Currently, the development of GM crop varieties has raised a wide range of new legal, ethical and economic questions in agriculture. There is a growing body of literature reflecting the socio-economic and environmental impacts of GM crops which aims to criticize their value for farming systems. While organic crops are promoted as environmentally-friendly products in developed countries, they have provoked great controversy in developing countries facing food security and a low agricultural productivity. Discussion has been especially vigorous when organic farming was introduced as an alternative method. There are in fact, a few tradeoffs in developing countries. On the one hand, farmers are encouraged to accept and implement GM crops because of their higher productivity, while on the other hand, organic farming is encouraged because of socio-economic and environmental considerations. A crucial question facing such countries is therefore, whether GM crops can co-exist with organic farming. This paper aims to review the main considerations and tradeoffs.


Cross-cultural differences in driver risk-taking.
This study investigated differences in simulated driver risk-taking behavior among U.S., Spanish, and West German subjects. The task consisted of performing a simulated intersection crossing on a video display. Subjects were shown an intersection with moving traffic on a horizontal road, and they were asked to attempt (under time pressure) a fixed number of crossings with a car moving vertically. The subjects in all three countries included younger, middle-aged, and older persons of both sexes. The following are the main findings: (1) The performance of West German subjects tended to differ from those of U.S. and Spanish subjects. Specifically, West German subjects attempted fewer crossings, had a higher probability of success, and had greater safety margins. (2) Target risk-level of performance, measured by probability of successful crossings, was not affected by age or sex. (3) Probability of attempted crossings was greater for males and younger subjects than for females and older subjects. (4) Similarly, safety margins during attempted crossings were smaller for males and younger subjects than for females and older subjects. These results suggest that there are differences among countries in the target risk-level of performance. However, the present findings imply that within each country all subjects (regardless of age and sex) tended to have the same target risk-level. To attain this risk-level of performance, males and younger subjects (because of their presumed superior psychomotor skills and/or greater experience with video tasks) attempted to cross more gaps (and, consequently, smaller gaps), with resulting smaller safety margins.


[Treatment of NASH: nutritional counseling and physical exercise].
Nonalcoholic fatty liver disease(NAFLD) is recognized as a cause of potentially progressive liver damage. NAFLD is often associated with metabolic syndrome that comprises central obesity, insulin resistance, and hyperlipidemia. Among these, severer forms with histopathological features of increasing ballooned hepatocytes and fibrosis are defined as nonalcoholic steatohepatitis (NASH). The natural history of NASH is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. Since central obesity and insulin resistance are most likely involved in the pathogenesis, justification of life style including physical exercise and nutritional counseling is essential for the treatment of NASH.


Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial.
In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label, three-way crossover, controlled multicenter study comparing GLU with ASP and insulin lispro (LIS). Subjects with type 1 diabetes were allocated to one of three treatment orders-GLU-ASP-LIS, ASP-LIS-GLU, or LIS-GLU-ASP-with each insulin used for 13 weeks. The study was designed to demonstrate the superiority of GLU over ASP and LIS on unexplained hyperglycemia and/or perceived infusion set occlusion. A prespecified P value of 0.025 was considered significant to correct for multiple testing. Percentages of subjects with at least one unexplained hyperglycemia and/or infusion set occlusion were not significantly different between GLU and ASP (68.4% [62.7-74.1%] vs. 62.1% [56.2-68.1%], P = 0.04) and GLU and LIS (68.4% [62.7-74.1%] vs. 61.3% [55.4-67.3%], P = 0.03). No differences were seen in hemoglobin A1c at end point, most points of the seven-point glucose curves, severe hypoglycemia, and symptomatic ketoacidosis. The overall rate of hypoglycemia with a plasma glucose level below 70 mg/dL per patient-year was significantly different between GLU and ASP (73.84 vs. 65.01, P = 0.008) and GLU and LIS (73.84 vs. 62.69, P < 0.001). Insulin doses remained unchanged during the trial. GLU was not superior to ASP and LIS with no significant difference seen among GLU, ASP, and LIS in CSII use with respect to unexplained hyperglycemia and/or perceived catheter set occlusion. GLU was associated with a higher frequency of symptomatic hypoglycemia, possibly because of slight overdosing, as previous trials suggested lower insulin requirements when GLU is initiated in type 1 diabetes.


[Design and assessment of a outpatient living with PICC-line support program: A pilot study].
The peripheral insertion central catheter (PICC-Line) is indicated for long term intravenous medication administration. Some adverse events (AE) might occur, especially for patients after hospital discharge. Therefore, patient empowerment about the side effects and precaution for use is essential to prevent potential patient harm. A multidisciplinary working group met and designed support program for outpatient living with PICC-line. Pharmacy consultations (PC) were proposed to patient before and after PICC-line insertion. A strip cartoon and card game were created to facilitate patient education. The aim of the study was to assess the comprehension of patient then secondarily to follow up AE awareness. During 10 months, 30 patients of mean age 65.9±14 years were included. Thirty-sixPICC-Line were installed and followed on 1659days of catheterization. 4, 9 and 13patients received respectively no, at least one and two PCs before discharge from the hospital. Although the differences were not statistically significant, comprehension tends to improve when patients benefit from both PCs especially when it concerns complications. Twenty-fiveambulatory AEs were recorded including 9infections or suspicion of infection, 2 thrombosis and 2 displacements of PICC-line. Among the patients who had no PC, four experienced delayed care. In comparison, it occurred in only one patient in the group who received at least one PC after PICC-line insertion. Further studies are warranted to confirm this trend.


Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite.
The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function.


Caval syndrome in a Dirofilaria immitis-infected dog treated with dichlorvos.
In the dog of this report, lesions found were compatible with death attributable to acute circulatory collapse induced by caval syndrome and compounded by microfilarial death. Hepatic centrilobular hemorrhage and necrosis were suggestive of circulatory collapse, renal hemosiderosis was suggestive of disseminated intravascular coagulopathy, and multifocal subacute hepatic inflammation associated with microfilariae was similar to lesions attributed to microfilarial death. Treatment with dichlorvos may have precipitated these events. Previous descriptions of dichlorvos toxicity in microfilaremic dogs have suggested that death is attributable to shock, but pathogenic mechanisms have not been established. Although generalizations from a single case must be made with caution, lesions in this dog suggest that toxic effects may be mediated through effects on adult and larval heartworms.


Traumatic intrusion of permanent teeth. Part 3. A clinical study of the effect of treatment variables such as treatment delay, method of repositioning, type of splint, length of splinting and antibiotics on 140 teeth.
A prospective study of 140 intruded permanent teeth was examined for the following healing complications: pulp necrosis (PN), root resorption (RR; surface, inflammatory and replacement resorption), and defects in marginal periodontal bone healing (MA). The occurrence of these healing complications was related to various treatment factors such as treatment delay, method of repositioning (i.e. expecting re-eruption, orthodontic reposition and surgical reposition), type of splint (rigid, semirigid and flexible), length of splinting (days) and the use of antibiotics. Treatment delay, i.e. before and after 24 h, had no effect upon healing. Active repositioning in individuals with incomplete root formation (surgical or orthodontic) had a negative effect upon the three healing parameters compared with spontaneous eruption. In teeth with complete root formation and an age of 12-17 no repositioning was still the best treatment in regard to MA. In individuals older than 17 years of age, cases were not anticipated to spontaneously erupt and in these cases, the general choice of treatment was either active orthodontic or surgical repositioning. The former procedure appeared in this treatment scenario to slightly reduce the risk of MA complications. However, this treatment procedure was also found to be more time demanding (an average of 22 consultations for orthodontic repositioning compared with 17 consultations for surgical repositioning). If a surgical repositioning was performed, the type of splint (i.e. flexible, semirigid or rigid) appeared to have no significant effect on the type of healing. The same applied to the length of splinting time (shorter or longer than 6 weeks). No effect of dentin covering procedures for associated crown fractures (enamel-dentin fractures) could be demonstrated. Likewise, antibiotics had no apparent effect upon healing. In conclusion, in patients with intruded teeth with incomplete root formation, spontaneous eruption should be expected. In patients with completed root formation and with an age of 12-17 spontaneous eruption can still occur, but must be monitored very carefully. In older patients (i.e. >17 years) with completed root formation, either surgical or orthodontic extrusion should be attempted. The latter procedure appeared to lead to a slight reduction (not significant) in the risk of MA complications. The extent and direction of the intrusion may however favour surgical repositioning.


Endobronchial ultrasound-guided intranodal forceps biopsy (EBUS-IFB) using 19G needle tract: First case series from India.
EBUS-TBNA is a well-established procedure for diagnosis of mediastinal lymphadenopathy replacing the need for mediastinoscopy. In certain diseases like lymphomas, the yield is reportedly 50%, sarcoidosis lymph nodes also give a yield of 80% with EBUS and at times, more material is needed for better characterization of malignancies. EBUS-intranodal forceps biopsy may be useful in these situations. In our series of seven cases, we describe a unique and safe technique of obtaining forceps biopsy from mediastinal lymph nodes under real-time endobronchial ultrasound guidance using a 19G EBUS-TBNA needle tract and thin biopsy forceps. Lymph node biopsy was able to give a conclusive diagnosis in 42% patients negative with TBNA, and was able to suggest a diagnosis in one case. No complications were seen. Thus, surgical biopsy can be avoided in nearly 50% of failed EBUS-FNAC cases.


Textured hydroxyapatite interface onto biomedical titanium-based coatings.
Hydroxyapatite (HAP) bioceramic coatings grown onto titanium-nitride (TiN) buffer layers by the aerosol-gel procedure present interfaces with a preferred growth orientation. These coatings were crystallized at 800 degrees C and subsequently etched to ease the study of the interface by Auger electron spectroscopy depth profiling. Ion beam milling was applied to cross-section samples to analyze the interface structures using transmission electron microscopy. At the interface, the HAP crystals showed a <002> orientation. It was shown by Auger electron spectroscopy depth profiling that O atoms diffuse into the nitride interlayer, indicating that the formation of O channels in the HAP structure is the driving force inducing the textured film. The outstanding biocompatible properties of both the materials and properties of their interface suggest that HAP/TiN structures are particularly well suited for endoprosthetic applications.


Two-stage clinical trial stopping rules.
Two-stage stopping rules for clinical trials are considered. The nominal significance level needed for the second-stage test, for any choice of first-stage significance level, is derived for rules with overall significance levels of .01 and .05 and for studies with either half or two-thirds of the patients analyzed in the first stage. A graphical demonstration is given of the inherent tradeoff between power and expected sample size (or probability of early termination). A specific rule, intermediate to those advocated by Pocock (1977, Biometrika 64, 191-199) and O'Brien and Fleming (1979, Biometrics 5, 549-556), is recommended.


Highly Conductive, Transparent, Adhesive, and Self-Healable Ionogel Based on a Deep Eutectic Solvent with Widely Adjustable Mechanical Strength.
Ionogels have attracted intensive attentions as promising flexible conductive materials. However, simultaneous integration of excellent mechanical properties, high conductivity, outstanding self-healing ability, and strong adhesiveness is still challenging. Here, an ingenious composition design is proposed to address this long-standing challenge of ionogels. High-performance PEI/PAA/CMC ionogels, consist of a loosely cross-linked poly(acrylic acid) (PAA) network, dynamically cross-linked network based on polycationic polyethyleneimine (PEI) and polyanionic PAA, and carboxymethyl cellulose (CMC) reinforcing filler, are formed in a deep eutectic solvent (DES) composed of choline chloride and urea. Benefiting from the loose PAA network and dynamic noncovalent interactions, ionogels with both highly enhanced mechanical robustness and excellent conductivity are obtained at high loading of DES, overcoming the strength-ductility/conductivity trade-off dilemma. By adjusting PEI/PAA mass ratio, the tensile strength and strain of PEI/PAA/CMC ionogels are effectively controlled in a wide range of 0.15-7.9 MPa and 232-1161%, respectively, while maintaining the desirable conductivity of ≈10-4 S cm-1 . Besides, healed tensile strength over 2.1 MPa and adhesion strength up to 0.2 MPa are achieved for the PEI0.06 /PAA0.25 /CMC0.01 ionogel. The delicate design strategy provides a feasible approach to prepare ionogels with outstanding comprehensive performance, which have potential for applications in flexible electronics.


Primary extracorporeal shockwave lithotripsy in management of large bladder calculi.
Large bladder calculi are often outside the range of treatment with conventional endoscopic lithotrites because of either anatomic factors or the mechanical limits of available instruments. Alternative methods of cystolithotripsy: ultrasonic, electrohydraulic, or laser, can prove time-consuming or even hazardous, so that open surgery is often the most expeditious option. We report our experience using Dornier HM3 extracorporeal shockwave lithotripsy (SWL) for initial bladder stone reduction preparatory to transurethral litholapaxy and definitive treatment of any underlying obstructive pathology. Primary cystolitholapaxy was judged impractical in these 24 patients (21 adults and 3 children) presenting 31 large bladder stones (mean size 35.6 mm). In all patients, primary transpelvic SWL was followed immediately by endoscopic evacuation of stone debris or cystolitholapaxy. In addition, 10 of the 24 patients (42%) underwent a definitive endoscopic operation for treatment of an underlying obstructive lesion at either the same or a follow-on session. Morbidity was minimal, and the mean hospital stay after the initial SWL treatment was 3.5 days. In our experience, Dornier SWL has proved invaluable in enabling cystolitholapaxy of very large bladder calculi that would otherwise require protracted and difficult endoscopic manipulation or open surgery.


Transcriptomic Changes in Mouse Bone Marrow-Derived Macrophages Exposed to Neuropeptide FF.
Neuropeptide FF (NPFF) is a neuropeptide that regulates various biological activities. Currently, the regulation of NPFF on the immune system is an emerging field. However, the influence of NPFF on the transcriptome of primary macrophages has not been fully elucidated. In this study, the effect of NPFF on the transcriptome of mouse bone marrow-derived macrophages (BMDMs) was explored by RNA sequencing, bioinformatics, and molecular simulation. BMDMs were treated with 1 nM NPFF for 18 h, followed by RNA sequencing. Differentially expressed genes (DEGs) were obtained, followed by GO, KEGG, and PPI analysis. A total of eight qPCR-validated DEGs were selected as hub genes. Subsequently, the three-dimensional (3-D) structures of the eight hub proteins were constructed by Modeller and Rosetta. Next, the molecular dynamics (MD)-optimized 3-D structure of hub protein was acquired with Gromacs. Finally, the binding modes between NPFF and hub proteins were studied by Rosetta. A total of 2655 DEGs were obtained (up-regulated 1442 vs. down-regulated 1213), and enrichment analysis showed that NPFF extensively regulates multiple functional pathways mediated by BMDMs. Moreover, the 3-D structure of the hub protein was obtained after MD-optimization. Finally, the docking modes of NPFF-hub proteins were predicted. Besides, NPFFR2 was expressed on the cell membrane of BMDMs, and NPFF 1 nM significantly activated NPFFR2 protein expression. In summary, instead of significantly inhibiting the expression of the immune-related gene transcriptome of RAW 264.7 cells, NPFF simultaneously up-regulated and down-regulated the gene expression profile of a large number of BMDMs, hinting that NPFF may profoundly affect a variety of cellular processes dominated by BMDMs. Our work provides transcriptomics clues for exploring the influence of NPFF on the physiological functions of BMDMs.


[Sepsis as a cause of intrahepatic cholestasis].
The causes of intrahepatic cholestasis include cholestatic viral hepatitis, primary biliary cirrhosis, benign recurrent cholestasis, primary sclerosing cholangitis and sepsis. During sepsis, proinflammatory cytokines and nitric oxide cause cholestasis by impairing hepatocellular and ductal bile formation. We report a 48-year-old woman who was admitted to hospital due to malaise, jaundice, fever and pain in the neck. Physical examination revealed jaundice, tachycardia (pulse rate was 120/min), hypotension 90/60 mm Hg. Laboratory findings showed normocytic normochromic anaemia, inflammatory syndrome and abnormal liver function tests indicating cholestasis and hepatocellular necrosis. Abdominal ultrasonography detected hepatosplenomegaly. Chest computed tomography showed bronchopneumonic infiltrates. Percutaneous liver biopsy was performed using a Menghini needle of 1.4 mm. Pathohystological analysis of the liver tissue confirmed reactive, intrahepatic cholestasis. Blood cultures isolated Staphylococcus aureus. After the diagnosis was established the treatment with broad-spectrum antibiotics was carried out, resulting in the improvement of general condition of the patient, regression of inflammatory syndrome, disappearance of cholestasis and regression of pulmonary infiltrates. Abdominal ultrasonography after antibiotic treatment did not show hepatosplenomegaly. Concerning patients with cholestasis of uncertain origin, we should always think of sepsis as a possible cause in order to start antibiotic treatment in time.


Language use in an internet support group for smoking cessation: development of sense of community.
The use of the internet for health purposes is increasing, as is the number of sites and online communities aimed at helping people to stop smoking. Some of the effects of online communities may be mediated through a sense of community. By using the computer-program Linguistic Inquiry and Word Count with a Norwegian dictionary, we investigated whether there was a development of sense of community in a forum related to a Norwegian smoking cessation intervention, by examining the use of self-referencing vs. collective referencing words. Data from a 4-year period, including in total 5242 web pages, were included. There was a significant increase in the use of collective words over time and a significant decrease in the use of self-referencing words. The increase in the use of collective words suggests that there appears to be a development of a sense of community in the forum over time. More research is needed to study the importance of an online sense of community.


Development of Two Innovative Performance-Based Objective Measures in Feline Osteoarthritis: Their Reliability and Responsiveness to Firocoxib Analgesic Treatment.
The metrological properties of two performance-based outcome measures of feline osteoarthritis (OA), namely Effort Path (Path) and Stairs Assay Compliance (Stairs), were tested. Cats naturally affected by OA (n = 32) were randomly distributed into four groups (A: 0.40, B: 0.25, C: 0.15, or D: 0.00 mg firocoxib/kg bodyweight) and assessed during baseline, treatment, and recovery periods. For Path, from an elevated walking platform, the cats landed on a pressure-sensitive mattress and jumped up onto a second elevated platform. Analysis included velocity, time to completion, peak vertical force (PVF), and vertical impulse. For Stairs, the number of steps and time to completion were recorded for 16 steps up and down in a 4 min period. Reliability was moderate to very good for Path and poor to good for Stairs. Different normalization methods are described in the manuscript. The placebo group remained stable within-time in Path, whereas treated cats trotted faster on the ramp (p < 0.0001), improved their PVF (p < 0.018) and completed the task quicker (p = 0.003). The percentage of cats completing the Stairs finish line was higher under treatment (p < 0.036), with huge effect size, the placebo group results being stable within-time. Both are promising performance-based outcome measures to better diagnose and manage feline OA pain.


Personality and coping traits: A joint factor analysis.
OBJECTIVES: The main objective of this paper is to explore the structural similarities between Eysenck's model of personality and the dimensions of the dispositional COPE. Costa et al. {Costa P., Somerfield, M., & McCrae, R. (1996). Personality and coping: A reconceptualisation. In (pp. 44-61) Handbook of coping: Theory, research and applications. New York: Wiley} suggest that personality and coping behaviour are part of a continuum based on adaptation. If this is the case, there should be structural similarities between measures of personality and coping behaviour. This is tested using a joint factor analysis of personality and coping measures. DESIGN: Cross-sectional survey. METHODS: The EPQ-R and the dispositional COPE were administered to 154 participants, and the data were analysed using joint factor analysis and bivariate associations. RESULTS: The joint factor analysis indicated that these data were best explained by a four-factor model. One factor was primarily unrelated to personality. There was a COPE-neurotic-introvert factor (NI-COPE) containing coping behaviours such as denial, a COPE-extroversion (E-COPE) factor containing behaviours such as seeking social support and a COPE-psychoticism factor (P-COPE) containing behaviours such as alcohol use. This factor pattern, especially for NI- and E-COPE, was interpreted in terms of Gray's model of personality {Gray, J. A. (1987) The psychology of fear and stress. Cambridge: Cambridge University Press}. NI-, E-, and P-COPE were shown to be related, in a theoretically consistent manner, to perceived coping success and perceived coping functions. CONCLUSIONS: The results indicate that there are indeed conceptual links between models of personality and coping. It is argued that future research should focus on identifying coping 'trait complexes'. Implications for practice are discussed.


Localization of genes affecting alcohol drinking in mice.
The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.


[Clinical study of nanometer calcium phosphate ceramic artificial bone].
To study the clinical effects and security of nanometer ceramics artificial bone transplantation to treat the bone defect. From March 2005 to November 2007, 32 patients (artificial bone group) with extremity bone defects applied nanometer ceramics artificial bone transplantations, included 19 males and 13 females, aged from 17 to 63 years old (averaged 31.4 years). The other 36 patients (internal fixation group) with extremity bone defects were treated by the internal fixation in the same period, included 21 males and 15 females, aged from 16 to 65 years old (averaged 32.6 years). Ca, P, B-ALP, IgG, IgA, IgM, CIC, C3, SL-2R and CD4+/CD8+ in the peripheral venous blood were measured in the 1st and 2th week and 1st, 3rd, 6th month after operation. All patients were followed up and the limb function was evaluated according to Enneking standard. The wounds of all patients smoothly healed after operation. Every immunological indicators had no significant difference between two groups. Serum calcium and phosphorus content did not significantly increased. Serum B-ALP of all patients were increased after operation, fell to normal levels in the internal fixation group, but remained at a relatively high level in the artificial bone group. All patients were followed-up for from 9 to 24 months (averaged 15 months). All patients get the excellent physical function. The artificial bone has no immunogenicity, no rejection,does not affect the blood calcium and phosphorus content, and has higher osteogenic activity. It is affirmed that nanometer ceramics artificial bone is used to treat the smaller bone defect on clinical.


Nursing performance in COVID-19 and non-COVID-19 units: Implications for occupational health.
to analyze the implications of the pandemic on the Nursing team's occupational health according to its performance in COVID-19 and non-COVID-19 units. a multicenter and mixed-methods study, with a sequential explanatory strategy. A total of 845 professionals took part in the first stage, answering an electronic form which contained sociodemographic and work-related variables, as well as about the pandemic and their health, in addition to the Self-Reporting Questionnaire. 19 professionals were interviewed in the second stage. The quantitative data were submitted to statistical analysis and the qualitative ones to thematic content analysis, with integration by connection. the pandemic exerted impacts on the professionals' health, both in the COVID-19 and non-COVID-19 areas. However, composition of the teams presented different characteristics between the areas, as well as the risk perceptions and the work demands. the professionals working in areas COVID-19 and non-COVID-19 areas are equally affected, although with different work exposure regarding the requirements at work in the COVID-19 units and the fear of contamination in non-COVID-19 units.


Expanding Our Methodological Toolbox to Improve Quality: The Role of Mixed-Methods Evaluations.
The care delivered to patients with cardiovascular disease involves coordination among a multitude of clinical team members spanning diverse inpatient and outpatient settings. The majority of quality improvement interventions in cardiovascular care have been developed based on quantitative evidence, which neither fully accounts for multilevel determinants (eg, patient, clinician, and institution) nor contextualization from key informants. The rigor and effectiveness of these interventions would be enhanced by mixed-methods studies whose strengths include (1) the use of qualitative research methodologies (eg, eliciting patient or clinician perspectives on barriers and facilitators of best practices) and (2) integrating qualitative and quantitative data and analyses to understand more fully effective strategies for achieving optimal care and outcomes for these patients across diverse settings. This article illustrates the application of a complex mixed-methods design to advance an evidence-based, customizable infection prevention toolkit for durable left ventricular assist device therapy. The study (1) uses quantitative clinical data merged with Medicare claims to evaluate interhospital variability in the incidence of infection; (2) uses qualitative methods to understand local practice patterns across low- and high-performing centers; and (3) integrates both data sources to gain a comprehensive understanding of the overall findings.


Marijuana: a time-honored but untested treatment for epilepsy.
The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures. However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done. Proper dosage and means of administration remain unknown. Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy. This is a review of this topic from a Canadian perspective.


Acute effects of resisted and assisted locomotor activation on sprint performance.
Sprinting speed is one of the most significant motor abilities in team sport games and all sprint, hurdling and jumping events in athletics. Over the years numerous methods and devices have been developed to improve sprinting performance. One of the most effective methods of developing sprinting speed includes resisted sprinting with the use of different towing devices, parachutes, uphill running, and now intelligent drag technology. Resisted sprinting can be used for chronic changes in performance or for acute enhancement of running speed through locomotor post-activation. The other method of enhancing sprinting speed includes assisted sprinting in which the objective is to achieve supramaximal speed through high speed treadmill running, downhill sprinting, the use of elastic tubing or different towing mechanisms. The main objectives of this research were to determine the acute effects of resisted and assisted sprint activation on sprinting performance in male and female sprinters. Eleven, international and national level 200-400 m sprinters, 6 female and 5 male, participated in the study. The study protocol had a crossover design, with the activation protocol for both days consisting of either 3 × 30 m resisted sprints or 3 × 40 m assisted sprints. At baseline, and following the activation protocol, all athletes performed a 50 m maximum sprint, measured electronically with photocells from a crouched start. During particular trials, the SPRINT 1080 engine assisted measuring system was used with the load set individually to 10% BM. During the resisted and assisted PAP intervention the results of intragroup ANOVA revealed significant differences between resisted baseline results and resisted post activation results in the 10 m and 50 m test trials in men (respectively p = 0.002, η2 = 0.25; p = 0.001, η2 = 0.45), as well as in the group of female sprinters at these distances (10 m and 50 m) (respectively p = 0.002, η2 = 0.20; p = 0.001, η2 = 0.29). There were no statistically significant improvements in the 10 and 50 m test trials following assisted activation for both female and male sprinters. It was concluded that resisted sprint activation with a load of 10% BM enhances sprinting speed over 50 m in elite male and female sprinters.


Injuries to the azygous venous system.
Azygous venous system injuries are rare. Although not commonly classified as a thoracic great vessel, the azygous system manifests morbidity and mortality that is similar to that of other great vessel injuries. Over a 40 year period, data were retrospectively collected and charts reviewed from a vascular injury database. A total of 22 injuries to the azygous venous system were identified with 21 to the azygous vein and 1 to the hemiazygous vein. All were secondary to penetrating trauma, with 19 from gunshot wounds and 3 from stab wounds. Eight of 22 patients died for an overall mortality of 36%. All patients had associated injuries, with concomitant injury to the lung noted in all cases. Injuries to the azygous venous system have a significant associated lethality. As an azygous venous injury is not typically the indication for operation, anterior incisions are often employed, making exposure difficult. In the majority of injured patients, the azygous system injury was found after excluding injuries to the heart, lung, and great vessels. A key finding in detecting these injuries through an anterior incision is continued hemorrhage of dark blood from a posterior location in the thoracic cavity. The azygous venous system should be considered early as a source of significant hemorrhage from the posterior mediastinum.


Dose linearity and steady state pharmacokinetics of the new antiparkinson agent budipine after oral administration.
The dose-dependency of budipine pharmacokinetic characteristics was studied. Eighteen healthy male subjects were given 10, 20 and 30 mg oral single doses according to a randomized, open, 3-period crossover design. Additionally, the steady state conditions were investigated after repeated intake of 10 mg t.i.d for 10 days and compared to the 10 mg single dose. The area under the concentration vs time curve (AUC) and the maximum serum concentration (Cmax) showed a linear increase in line with ascending doses of orally given budipine. Time to maximum serum concentration (tmax) and terminal half-life (t1/2) were independent of the administered dose. As compared to the 10 mg single dose pharmacokinetics, the repeated oral administration of budipine 10 mg t.i.d. resulted in an increase in AUC of 11% and 93% for budipine and its metabolite p-OH-budipine, respectively. In clinical practice, a predictable response in proportion to the dose is to be expected.


[Surgical treatment of urinary stress incontinence in women].
Long-term results obtained in 54 surgical procedures to correct effort urinary incontinence performed in 49 patients with this pathology are reviewed. One group was treated with suprapubic urethrovesical suspension with the Marshall-Marchetti-Krantz technique; the other group with endoscopic suspension of the neck of the bladder, with the Stamey technique and the third group with sling techniques. The authors conclude that any of the surgical techniques achieving a correct reposition of urethrovesical anatomy, rising the posterior urethra to its primitive anatomical bed, obtain a similar success rate.


A customized light sheet microscope to measure spatio-temporal protein dynamics in small model organisms.
We describe a customizable and cost-effective light sheet microscopy (LSM) platform for rapid three-dimensional imaging of protein dynamics in small model organisms. The system is designed for high acquisition speeds and enables extended time-lapse in vivo experiments when using fluorescently labeled specimens. We demonstrate the capability of the setup to monitor gene expression and protein localization during ageing and upon starvation stress in longitudinal studies in individual or small groups of adult Caenorhabditis elegans nematodes. The system is equipped to readily perform fluorescence recovery after photobleaching (FRAP), which allows monitoring protein recovery and distribution under low photobleaching conditions. Our imaging platform is designed to easily switch between light sheet microscopy and optical projection tomography (OPT) modalities. The setup permits monitoring of spatio-temporal expression and localization of ageing biomarkers of subcellular size and can be conveniently adapted to image a wide range of small model organisms and tissue samples.


Legal harm reduction among intravenous drug users.
HIV/AIDS infection in injecting drug users occurs with explosive rapidity and, having occurred, they can form a core group for further sexual and vertical transmission. As HIV transmission among injecting drug users can be extremely rapid, various approaches to intervention and obstructing the spread of HIV infection have been explored. Overall, these have been relatively ineffective so what has emerged, both in the developed and developing world, is harm reduction. In the light of these general considerations, the authors reviewed the law of Thailand in relation to drug abuse and dependence according to the harm reduction for the prevention of HIV/AIDS infection in injecting drug users. With the review, the authors recommend some changes in the law: 1. Introducing a law that allows IDUs to possess sterile syringes and needles while under supervision of a physician. 2. Introducing a law that allows for testing for HIV in people in custody in whom there are grounds for suspecting drug abuses. 3. Establishing and financing a Multi-disciplinary Coordinating Committee on the Prevention of HIV/AIDS (MCCPH/A). It should be emphasized that, as in other countries, drug abuse and dependence should, where appropriate, be decriminalized. A large proportion of people with drug-related problems are ill and in need of treatment rather than criminals requiring harsh penalties handed down by the courts.


Rib Fracture Map in High-Energy Injuries.
To use a novel rib unfurling technology to investigate the locations of multiple rib fractures occurring from high-energy trauma to discern if there are reproducible rib fracture patterns. Patients between the ages of 18 and 48 years presenting to a Level 1 academic trauma center with ≥2 rib fractures after a high-energy mechanism of injury between 2017 and 2019 were identified. Curved planar reformatting of CT scans was used to create two-dimensional unfurled rib images by flattening out the view of the ribs from a CT scan. Rib fractures were placed on a template map using a standardized measurement method, and subsequent frequency and heat maps were created. Among 100 consecutive patients, 534 fractures on 454 ribs were identified. The most common high-energy mechanism of injury was motor vehicle accidents (41%). Flail chest occurred in 8% of patients. The mean number of ribs fractured per patient was 4.54 ± 3.14 and included a mean of 5.34 ± 4.38 total fractures. Among all fractures, 50.9% were located on ribs 4 through 7. The most common fracture location was located in the lateral or anterolateral zone of the rib cage. Patients with multiple rib fractures from high-energy trauma have rib fractures with locations of common occurrence. An understanding of location and frequency of rib fractures can help inform surgical approaches, prognosis, indications, classifications, and implant design in the management of a complex population of patients with chest wall injury after trauma. Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


[In vitro and in vivo studies of the "VITA" device].
Many in vitro and in vivo experiments using contemporary methods supported safety and efficiency of "VITA" device protecting humans and living beings from electromagnetic fields. Therefore, bioenergetic safety device "VITA" is advisable for use.


Initial Cell Concentration and Selective Media Effects on the Isolation of Listeria monocytogenes from Enrichment Cultures of Inoculated Foods.
To facilitate rapid quantitation of Listeria monocytogenes in artificially inoculated dairy products, seafoods, and other foods, the recently revised U.S. Food and Drug Administration methodology for Listeria in foods was further abbreviated. The ability to isolate L. monocytogenes was measured in terms of the number of inoculated colony forming units (cfu)/g of food. Isolation values for the foods tested, using modified McBride's agar (MMA), were <1, 1-10, and >11 inoculated cfu/g in 30, 44, and 26% of test samples, respectively. The corresponding percentages with lithium chloride-phenylethanol-moxalactam (LPM) agar were 41, 51, and 8%, respectively. In eight (21%) instances, isolation values on LPM agar were significantly superior to those on MMA. The superiority of LPM was most dramatic when MMA isolation values were >10 initial cfu/g. However, LPM was not an infallible remedy for MMA deficiencies even at >10 cfu/g. Ease of isolation was apparently not related to food type. For 10 different test portions of Brie cheese, isolation values ranged from 0.3 to > 10,000 of inoculated cfu/g with MMA and 0.3 to 2500 of inoculated cfu/g with LPM agar.


Mechanism of radiosensitization by halogenated pyrimidines: effect of BrdU on radiation induction of DNA and chromosome damage and its correlation with cell killing.
The effect of BrdU incorporation on cell radiosensitivity as well as on the induction of DNA double-strand breaks (DSB) and chromosome damage by radiation was studied in CHO cells. Induction of DNA DSB was measured by the nonunwinding filter elution technique and damage at the chromosome level was visualized and scored in G1 cells using the technique of premature chromosome condensation. The results indicated an increase in the radiosensitivity of cells grown in the presence of BrdU. Although sensitization was observed both in cells irradiated in the exponential phase and in cells irradiated in the plateau phase of growth, the degree of sensitization was greater in exponentially growing cells for the same degree of thymidine replacement by BrdU in the DNA. It is hypothesized that this indicates the possible importance of chromatin structure at the time of irradiation and/or the importance of chromatin conformation changes after irradiation in the expression of radiation-induced potentially lethal damage in cells containing BrdU. Incorporation of BrdU affected both the slope and the width of the shoulder of the survival curve and increased the induction of DNA and chromosome damage per unit absorbed dose. The increase observed in the slope of the survival curve was quantitatively similar to the increase observed in damage induction at the DNA and the chromosome level, suggesting a cause-effect relationship between these phenomena. Reduction in the width of the shoulder did not correlate with the increase in the induction of DNA and chromosome damage, suggesting that different phenomena, probably related to enhanced fixation of radiation-induced potentially lethal damage in cells containing BrdU, underlie its modulation.


[Effects of grazing, cutting and decapitating on grass populations on the artificial grassland in subtropical zone of China].
Studies on the effects of grazing, cutting and decapitating on grass populations on the artificial grassland in the subtropical zone of China showed that moderate grazing and cutting could increase the adaptability of Dactylis glomerata and Lolium prenn due to decapitating. Decapitating could rescind the apical dominance and reproduction growth of grass, and hence, the ecological effects of grazing and cutting on grass could be realized by decapitating, and the population density, caloric value and energy accumulation of Dactylis glomerata and Lolium prenn increased obviously. Apical dominance of grasses could lower the population density, energy accumulation and intra-population competitive ability.


Controlling the Energy-Level Alignment of Silicon Carbide Nanocrystals by Combining Surface Chemistry with Quantum Confinement.
The knowledge of band edges in nanocrystals (NCs) and quantum-confined systems is important for band alignment in technologically significant applications such as water purification, decomposition of organic compounds, water splitting, and solar cells. While the band energy diagram of bulk silicon carbides (SiCs) has been studied extensively for decades, very little is known about its evolution in SiC NCs. Moreover, the interplay between quantum confinement and surface chemistry gives rise to unusual electronic properties and remains barely understood. Here, we report for the first time the complete band energy diagram of SiC NCs synthesized such that they span the regime from strong to intermediate to weak quantum confinement. The absolute positions of the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular orbitals show clear size dependence. While the HOMO level follows the expected behavior for quantum-confined electronic states, the LUMO energy shifts below the bulk conduction band minimum, which cannot be explained by a simple quantum confinement caused by the size effect. We show that this effect is a result of the interplay between quantum confinement and the formation of surface states due to partial and site-selective oxygen passivation.


Mediastinal seroma post laparoscopic repair of type IV paraesophageal hernia.
Laparoscopic repair of paraesophageal hernia is safe and feasible and can provide comparable results for patients with type IV paraesophageal hernia. We report a rare case of mediastinal seroma in an 80-year-old gentleman who had a giant type IV paraesophageal hernia and was eventually admitted to our hospital for elective laparoscopic repair and recovered very well after surgery with resolution of the atelectatic lungs and air-fluid collection in his chest.


Chronic exposure to rotenone models sporadic Parkinson's disease in Drosophila melanogaster.
Parkinson's disease (PD) is a movement disorder characterized by the selective degeneration of nigrostriatal dopaminergic neurons. Both familial and sporadic cases present tremor, rigidity, slowness of movement, and postural instability. Although major insights into the genes responsible for some rare hereditary cases have arisen, the etiology of sporadic cases remains unknown. Epidemiological studies have suggested an association with environmental toxins, mainly mitochondrial complex I inhibitors such as the widely used pesticide rotenone. In recent years, Drosophila melanogaster has been used as a model of several neurodegenerative diseases, including a genetic model of PD. Here, we studied the neurodegenerative and behavioral effects of a sublethal chronic exposure to rotenone in Drosophila. After several days, the treated flies presented characteristic locomotor impairments that increased with the dose of rotenone. Immunocytochemistry analysis demonstrated a dramatic and selective loss of dopaminergic neurons in all of the brain clusters. The addition of l-dopa (3,4-dihydroxy-L-phenylalanine) into the feeding medium rescued the behavioral deficits but not neuronal death, as is the case in human PD patients. In contrast, the antioxidant melatonin (N-acetyl-5-methoxytryptamine) alleviated both symptomatic impairment and neuronal loss, supporting the idea that this agent may be beneficial in the treatment of PD. Therefore, chronic exposure to pesticides recapitulates key aspects of PD in Drosophila and provides a new in vivo model for studying the mechanisms of dopaminergic neurodegeneration.


A simple objective evaluation and grading for facial paralysis outcomes.
A simple measuring box to determine lip-shift angle and eye-width narrowing offered simultaneous and objective data on outcome dysfunction. The method is as easy as visual approaches. The method is objective and as easy as visual access. It is practical for routine clinical use in any clinic. The outcome dysfunction after facial paralysis is commonly evaluated by subjective visual access. This paper introduces a new method for simple objective evaluation and grading with documentation of lip-shift and eye-width changes. Thirty adult controls were used to determine standard deviations (SDs) for angular shift of the lip at rest and eye-width narrowing at maximum lip protrusion. Thirty patients with facial paralysis more than 6 months after onset were studied for outcomes in terms of synkinesis, contracture, and lip deviation to the healthy side. Abnormalities were read with a simple measuring box. Among the controls, mean lip shift at rest and its SD were 0° and 1.2. Mean eye narrowing at maximum lip protrusion effort and its SD were -0.6 mm and 1.6. This paper proposes a new grading system that relies simply on the sum of evaluating items exceeding 2 SDs, or residual lip deviation to the healthy side.


Generating the evidence base for the National Service Framework for Long Term Conditions: a new research typology.
The UK National Service Framework (NSF) for Long Term Conditions was published in May 2005. This article describes the challenges and some proffered solutions towards development of the evidence base to support best practice in the management of life-long neurological conditions, which are the principal focus of the NSF. The inherent limits in current systems for appraisal of evidence and their lack of applicability to these conditions are discussed. A new typology of evidence is proposed, which acknowledges the importance of expert opinion from users, carers and professionals as well as encompassing a broad range of research designs. To apply the typology, a brief evaluation tool is presented, which provides simple assessment of both qualitative and quantitative research evidence in terms of design, quality and applicability, and is practical for use by clinicians. Preliminary testing and application in development of the evidence base for the NSF are described.


Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis: How valid is the GABAergic hypothesis?
Acquired nystagmus occurs frequently in patients with multiple sclerosis and is often the cause of illusory motion of the environment (oscillopsia), and blurring of vision. Based primarily on the beneficial effect of gabapentin on acquired pendular nystagmus (APN), a GABAergic mechanism in controlling nystagmus has been hypothesised. If increasing GABA concentrations in the CNS are critical for the treatment of nystagmus, then a selective GABAergic drug should be highly successful. However, as gabapentin is not a selective GABAergic agent, vigabatrin, a "pure" GABAergic medication, and gabapentin, were compared in a single blind cross over trial in eight patients with definite multiple sclerosis. Patients were randomly assigned to begin with gabapentin (1200 mg daily) or vigabatrin (2000 mg daily). Neuro-ophthalmological and electro-oculographic (EOG) evaluations were performed four and three times, respectively. Treatment efficacy was based on improving visual acuity and EOG indices (amplitude or frequency of nystagmus, or both) by at least 50% of pretreatment values. Three out of eight patients dropped out due to adverse effects. In the remaining five patients gabapentin improved symptomatic pendular or gaze evoked jerk nystagmus in four. Three patients decided to continue gabapentin therapy. Importantly, vigabatrin proved useful in only one out of five patients, suggesting that gabapentin effectiveness may be related to additional non-GABAergic mechanisms of action. Interaction with cerebral glutamate transmission by inhibition of NMDA receptor might be an alternative hypothesis for the therapeutic action of gabapentin.


Flame retardants in placenta and breast milk and cryptorchidism in newborn boys.
Polybrominated diphenyl ethers (PBDEs) are widely used in Western countries. Because the prevalence of cryptorchidism appears to be increasing, we investigated whether exposure to PBDEs was associated with testicular maldescent. In a prospective Danish-Finnish study, 1997-2001, all boys were examined for cryptorchidism. We analyzed whole placentas (for 95 cryptorchid/185 healthy boys) and individual breast milk samples (62/68) for 14 PBDEs and infant serum samples for gonadotropins, sex-hormone binding globulin, testosterone, and inhibin B. In 86 placenta-milk pairs, placenta PBDE concentrations in fat were lower than in breast milk, and a larger number of congeners were nondetectable. There was no significant difference between boys with and without cryptorchidism for individual congeners, the sum of 5 most prevalent, or all 14 congeners. The concentration of PBDEs in breast milk was significantly higher in boys with cryptorchidism than in controls (sum of BDEs 47, 153, 99, 100, 28, 66, and 154: median, 4.16 vs. 3.16 ng/g fat; p < 0.007). There was a positive correlation between the sum of PBDEs and serum luteinizing hormone (p < 0.033). The sum of PBDEs in breast milk did not differ between Denmark and Finland (median, 3.52 vs. 3.44 ng/g fat), but significant differences in some individual congeners were found. Two different proxies were used for prenatal PBDE exposure, and levels in breast milk, but not in placenta, showed an association with congenital cryptorchidism. Other environmental factors may contribute to cryptorchidism. Our observations are of concern because human exposure to PBDEs is high in some geographic areas.


Race Is Associated With Risk of Salvage Procedures and Postoperative Complications After Hip Procedures in Children With Cerebral Palsy.
Despite the many surgical interventions available for spastic hip dysplasia in children with cerebral palsy, a radical salvage hip procedure may still ultimately be required. The purpose of this study was to assess whether race is an independent risk factor for patients with cerebral palsy to undergo a salvage hip procedure or experience postoperative complications for hip dysplasia treatment. This is a retrospective cohort analysis utilizing the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Pediatric database from 2012 to 2019. International Classification of Diseases, 9th and 10th Revisions, Clinical Modifications (ICD-9-CM, ICD-10-CM), and current procedural terminology (CPT) codes were used to identify patients with cerebral palsy undergoing hip procedures for hip dysplasia and to stratify patients into salvage or reconstructive surgeries. There was a total of 3906 patients with cerebral palsy between the ages of 2 and 18 years undergoing a procedure for hip dysplasia, including 1995 (51.1%) White patients, 768 (19.7%) Black patients, and 1143 (29.3%) patients from other races. Both Black ( P =0.044) and White ( P =0.046) races were significantly associated with undergoing a salvage versus a reconstructive hip procedure, with Black patients having an increased risk compared to White patients [adjusted odds ratio (OR) 1.77, confidence interval (CI) 1.02-3.07]. Only Black patients were found to have an increased risk of any postoperative complication compared to White patients, with an adjusted OR of 1.26 (CI 1.02-1.56; P =0.033). Both White ( P =0.017) and black ( P =0.004) races were found to be significantly associated with medical complications, with Black patients having an increased risk (adjusted OR 1.43, CI 1.12-1.84) compared to White patients. There were no significant findings between the race and risk of surgical site complications, unplanned readmissions, or reoperations. This study demonstrates that patient race is an independent association for the risk of pediatric patients with cerebral palsy to both undergo a salvage hip procedure and to experience postoperative medical complications, with Black patients having an increased risk compared to White. Level III Retrospective Cohort Study.


An evaluation of brachytherapy and external beam radiation used with wide-margin surgical resection in the treatment of extra-abdominal desmoid tumors.
Surgical resection has had control rates of 53% to 77% in the treatment of extra-abdominal desmoid tumors. Surgical excision combined with external beam radiation therapy (EBRT) has had local control rates of up to 83% in some series. The purpose of this study was to evaluate the effectiveness of resection combined with radiotherapy (brachytherapy, EBRT, or both) in the treatment of extra-abdominal desmoid tumors. We retrospectively reviewed the charts of 24 consecutive patients (27 histologically confirmed extra-abdominal desmoid tumors). Patients were included in the study if they had a lesion that was potentially resectable with a wide margin, allowing for limb salvage, and if they did not have a contraindication to radiotherapy. Limb functioning was assessed with the Musculoskeletal Tumor Society (MSTS) scoring system. Seventeen patients (7 men, 10 women) with 19 tumors met the inclusion criteria. Mean age at diagnosis was 23.4 years. Follow-up (mean, 4.28 years) involved serial clinical examinations and magnetic resonance imaging of tumor sites. After surgery, the tumors were treated with brachytherapy (n = 6), EBRT (n = 10), or both (n = 3). Two of the 17 tumors in patients with negative margins of resection recurred locally (local control rate, 88.2%). Mean MSTS score was 29/30 (96.7%). The role of surgery, radiotherapy, chemotherapy, hormone therapy, and other treatments for extra-abdominal desmoid tumors is not well defined. When wide-margin resection and radiotherapy can be performed with limb preservation surgery, local control and complication rates compare favorably with those of other reported methods of treatment. Given the results and limitations of our study, we cannot make a definitive recommendation as to which modality--brachytherapy or EBRT--should be used in the treatment of extra-abdominal desmoid tumors.


Short-Term Intake of a Fructose-, Fat- and Cholesterol-Rich Diet Causes Hepatic Steatosis in Mice: Effect of Antibiotic Treatment.
Intestinal microbiota and barrier functions seem to play an important role in the development of non-alcoholic fatty liver disease (NAFLD). However, whether these changes are an early event in the development of NAFLD or are primarily associated with later stages of the disease, has not yet been clarified. Using a pair-feeding model, we determined the effects of a short-term intake of a fat-, fructose- and cholesterol-rich diet (FFC) on the development of early hepatic steatosis and markers of intestinal barrier function in mice treated with and without non-resorbable antibiotics (AB). For four days, C57BL/6J mice were either pair-fed a control diet or a FFC diet ± AB (92 mg/kg body weight (BW) polymyxin B and 216 mg/kg BW neomycin). Hepatic steatosis and markers of inflammation, lipidperoxidation and intestinal barrier function were assessed. Lipid accumulation and early signs of inflammation found in the livers of FFC-fed mice were markedly attenuated in FFC + AB-fed animals. In FFC-fed mice the development of NAFLD was associated with a significant loss of tight junction proteins and an induction of matrix metalloproteinase-13 in the upper parts of the small intestine as well as significantly higher portal endotoxin levels and an induction of dependent signaling cascades in the liver. As expected, portal endotoxin levels and the expression of dependent signaling cascades in liver tissue were almost at the level of controls in FFC + AB-fed mice. However, FFC + AB-fed mice were also protected from the loss of zonula occludens-1 and partially of occludin protein in small intestine. Our data suggest that the development of early diet-induced hepatic steatosis in mice at least in part results from alterations of intestinal barrier function.


Modifiable Maternal Factors and Their Relationship to Postpartum Depression.
The purpose of the study was to examine how modifiable maternal factors (body mass index (BMI), household income, fatigue, sleep, breastfeeding status, diet, and physical activity) relate to postpartum depression (PPD) at 6 and 12 months postpartum. Participants (n = 26) participated in two study visits (6 and 12 months postpartum) where vitals, weight, body composition (skinfold anthropometrics), and physical activity levels (Actigraph GTX9 accelerometer) were assessed. Validated instruments (BRUMS-32, Subjective Exercise Experience Scale, Pittsburg Sleep Quality index, NIH breastfeeding survey, NIH Dietary History Questionnaire, and Edinburg Postnatal Depression Scale) assessed lifestyle and demographic factors of interest. PPD at six months was correlated to PPD at 12 months (r = 0.926, p < 0.001). At six months postpartum, PPD was positively correlated to BMI (r = 0.473, p = 0.020) and fatigue (r = 0.701, p < 0.001), and negatively correlated to household income (r = -0.442, p = 0.035). Mothers who were breastfeeding had lower PPD scores (breastfeeding 3.9 ± 3.5 vs. not breastfeeding 7.6 ± 4.8, p = 0.048). At 12 months, PPD was positively correlated to sleep scores (where a higher score indicates poorer sleep quality) (r = 0.752, p < 0.001) and fatigue (r = 0.680, p = 0.004). When analyzed collectively via regression analyses, household income and fatigue appeared to be the strongest predictors of PPD at six months postpartum.


Multilevel spinal injuries. Incidence, distribution and neurological patterns.
Spinal injury at more than one level is not uncommon. Awareness of multilevel injury of the spine and associated neurological patterns is important for the proper initial management of the patient. This study presents the incidence, pattern of signs and the neurological consequences of multilevel spinal injury. A review of 935 patients with spinal injuries revealed that lesions occurred in multiple levels in 9.7%; in over half of the cases, neurological lesions were incomplete. Multiple level non-contiguous lesions at more than two levels had the worst prognosis with 70% of patients suffering complete paraplegia.


The effect of ethanol on oral cocaine pharmacokinetics reveals an unrecognized class of ethanol-mediated drug interactions.
Ethanol decreases the clearance of cocaine by inhibiting the hydrolysis of cocaine to benzoylecgonine and ecgonine methyl ester by carboxylesterases, and there is a large body of literature describing this interaction as it relates to the abuse of cocaine. In this study, we describe the effect of intravenous ethanol on the pharmacokinetics of cocaine after intravenous and oral administration in the dog. The intent is to determine the effect ethanol has on metabolic hydrolysis using cocaine metabolism as a surrogate marker of carboxylesterase activity. Five dogs were administered intravenous cocaine alone, intravenous cocaine after ethanol, oral cocaine alone, and oral cocaine after ethanol on separate study days. Cocaine, benzoylecgonine, and cocaethylene concentrations were determined by high-performance liquid chromatography. Cocaine had poor systemic bioavailability with an area under the plasma concentration-time curve that was approximately 4-fold higher after intravenous than after oral administration. The coadministration of ethanol and cocaine resulted in a 23% decrease in the clearance of intravenous cocaine and a 300% increase in the bioavailability of oral cocaine. Cocaine behaves as a high extraction drug, which undergoes first-pass metabolism in the intestines and liver that is profoundly inhibited by ethanol. We infer from these results that ethanol could inhibit the hydrolysis of other drug compounds subject to hydrolysis by carboxylesterases. Indeed, there are numerous commonly prescribed drugs with significant carboxylesterase-mediated metabolism such as enalapril, lovastatin, irinotecan, clopidogrel, prasugrel, methylphenidate, meperidine, and oseltamivir that may interact with ethanol. The clinical significance of the interaction of ethanol with specific drugs subject to carboxylesterase hydrolysis is not well recognized and has not been adequately studied.


Structure and correlates of self-reported empathy in schizophrenia.
Research on empathy in schizophrenia has relied on dated self-report scales that do not conform to contemporary social neuroscience models of empathy. The current study evaluated the structure and correlates of the recently-developed Questionnaire of Cognitive and Affective Empathy (QCAE) in schizophrenia. This measure, whose structure and validity was established in healthy individuals, includes separate scales to assess the two main components of empathy: Cognitive Empathy (assessed by two subscales) and Affective Empathy (assessed by three subscales). Stable outpatients with schizophrenia (n = 145) and healthy individuals (n = 45) completed the QCAE, alternative measures of empathy, and assessments of clinical symptoms, neurocognition, and functional outcome. Exploratory and confirmatory factor analyses provided consistent support for a two-factor solution in the schizophrenia group, justifying the use of separate cognitive and affective empathy scales in this population. However, one of the three Affective Empathy subscales was not psychometrically sound and was excluded from further analyses. Patients reported significantly lower Cognitive Empathy but higher Affective Empathy than controls. Among patients, the QCAE scales showed significant correlations with an alternative self-report empathy scale, but not with performance on an empathic accuracy task. The QCAE Cognitive Empathy subscales also showed significant, though modest, correlations with negative symptoms and functional outcome. These findings indicate that structure of self-reported empathy is similar in people with schizophrenia and healthy subjects, and can be meaningfully compared between groups. They also contribute to emerging evidence that some aspects of empathy may be intact or hyper-responsive in schizophrenia.


Contractures in the post-stroke wrist: a pilot study of its time course of development and its association with upper limb recovery.
Contractures are common in a stroke population, yet there is little information on the time course of development. Investigate quantitatively changes associated with contracture formation in an acute stroke population. Longitudinal study on 22 subjects who were 2-4 weeks post stroke. Contractures were assessed by quantifying the resting posture, resistance to passive movement and passive range of movement. Upper limb function was measured using the Action Research Arm Test and the Nine-Hole Peg Test. Active range of extension, wrist extension strength (isometric), grip strength and neglect were also measured. REPEATED MEASURES: Following an initial assessment, repeated measurements were taken at 4, 8, 20 and 32 weeks after recruitment. Two distinct subgroups, one capable of some functional movement (F group; 8 subjects) and another which was not (NF group; 14 subjects), were identified at the start of the study. The NF group showed changes associated with contracture formation at the wrist, i.e., reduction in the passive range of movement, an increase in resistance to passive movement and a worsening of the flexion posture. Changes were observed from the time of recruitment even though neglect improved. The F group showed improvements in upper limb function and there was no evidence to support contracture formation. Subjects most prone to contracture formation were those who showed no signs of early functional recovery (2-4 weeks after the stroke). Changes consistent with adaptive shortening were seen from week 4 of the study period.


Exercise-induced changes to in vitro T-lymphocyte mitogen responses using CFSE.
Carboxyfluorescein diacetate succinamidyl ester (CFSE) labeling of lymphocyte populations can provide unique insights into cell function at rest and with exercise, due to its ability to quantify cell division on an individual cell basis. This study aimed to characterize the effect of acute, intense exercise on T-lymphocyte function. Well-trained endurance runners completed 60 min of treadmill running at 95% of individual anaerobic threshold. Blood samples were collected before exercise; after 30 and 60 min of exercise; and after 30, 60, and 90 min of recovery. Isolated peripheral blood mononuclear cells were labeled with CFSE and cultured with or without mitogen (phytohemagglutinin). After culture, cell suspensions were labeled with CD3 (allophycocyanin) and CD8 (phycoerythrin), and expansion rates and cell death rates were calculated for each sample, as well as mitosis rates for each cell generation. Exercise was associated with a 60% decrease in cell expansion in both CD4 and CD8 cell types from before exercise to midexercise (P < 0.05). The significant decrease in expansion rate in the midexercise samples for both cell types was mirrored by a 65% increase in cell death (P < 0.05) in both cell types at that sample point. Exercise had no effect on the mitosis rate of either CD4 or CD8 cells in any cell generation (generations 0-3). This study indicates that 1 h of intense exercise affects in vitro T-lymphocyte function. These data suggest, for the first time, that exercise decreases cell expansion rate via an increase in cell death of both CD4 and CD8 T lymphocytes, rather than a decrease in mitosis.


Help for the hurting elderly. Safe use of drugs to relieve pain.
Pharmacologic management of pain in elderly patients is a common and difficult clinical problem. Because of altered drug metabolism and pharmacodynamics in the elderly, the drugs of choice are different than in younger patients and side effects occur more often. However, with judicious use and monitoring for toxicity, oral medications given as part of a multimodality approach can achieve adequate analgesia in most elderly patients.


A frequent ala 4 to val superoxide dismutase-1 mutation is associated with a rapidly progressive familial amyotrophic lateral sclerosis.
Familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons, is associated with mutations in the Cu/Zn superoxide dismutase gene SOD1 in some affected families. We confirm a recently reported ala4-->val mutation in exon 1 of the SOD1 gene and report that this mutation is both the most commonly detected of all SOD1 mutations and among the most clinically severe. By comparison with our other FALS families, the exon 1 mutation is associated with reduced survival time after onset: 1.2 years, as compared to 2.5 years for all other FALS patients. We also demonstrate that SOD1 is prominently expressed in normal motor neurons and that neural expression of SOD1 is not prevented by this exon 1 mutation. Assays of SOD1 enzymatic activity in extracts from red blood cells, lymphoblastoid cells, and brain tissues revealed an approximately 50% reduction in activity of cytosolic SOD1 in patients with this mutation compared to normal individuals. By contrast, patients with sporadic ALS had normal levels of SOD1 enzymatic activity. Why this SOD1 mutation causes motor neuron death in FALS remains to be established. While it may be that FALS is a consequence of loss of SOD1 function, it is also possible that motor neuron death in this dominantly inherited disease occurs because the mutations confer an additional, cytotoxic function on the SOD1 protein.


[The role of spiral CT in the preoperative evaluation of malignant gastric neoplasms].
The purpose of this study was to evaluate the performance of spiral CT in preoperative staging in patients with gastric cancer. A total of 28 patients with an established diagnosis of 24 gastric adenocarcinoma, 2 gastric lymphoma, 1 carcinoid tumor, 1 leiomyosarcoma were evaluated with spiral CT for serosal invasion, pancreatic invasion, metastasis and peritoneal involvement. Results were compared with surgical and pathological staging. The accuracy of spiral CT in determining the depth of tumor invasion, pancreatic invasion, lymph node metastasis, peritoneal metastasis, liver metastasis and splenic metastasis were 82% (23/28), 96% (27/28), 82% (23/28), 96% (27/28), 100% (28/28) and 100% (28/28) respectively. The differentiation between T2-T3, T3-T4, N0-N1, N1-N2, N2-N3 were possible in 83% (15/18), 92% (23/25), 79% (15/19), 73% (8/11), and 89% (8/9). The accuracy of spiral CT in overall TNM staging of gastric adenocarcinomas was 67% (16/24). Spiral CT is an effective tool in the preoperative staging of gastric malignancies.


Nonparkinsonism movement disorders in the elderly.
The primary objective of this article is to review the clinical presentation and pharmacologic management of essential tremor and tardive dyskinesia. The MEDLINE (1966-August 2005), Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-August 2005) databases were searched for original research and review articles published in English. The search terms were essential tremor and tardive dyskinesia. Reference lists from articles were also consulted. Essential tremor is most commonly manifested as a postural or action tremor of the upper extremities. Midline regions such as the head and voice are also commonly affected. Based on review of the literature, propranolol and primidone are the current pharmacologic mainstays for treating essential tremor of the upper extremities. The choice of agent depends on patient-specific factors such as underlying medical conditions. Other agents with demonstrated efficacy include gabapentin and topiramate. Benzodiazepines are effective adjunctive agents, but should be utilized judiciously in the elderly. Botulinum toxin is effective for essential tremor of the voice and head. Surgery is very effective, but may not be appropriate in the frail elderly and should be avoided in the presence of cognitive impairment. Tardive dyskinesia is characterized by involuntary choreoathetoid movements of the orofacial region. For the management of tardive dyskinesia, emphasis is placed on primary prevention and early recognition of signs and symptoms. In some cases, discontinuation of the offending agent can result in reversal of symptoms. If a conventional neuroleptic is the causative agent, switching to an atypical antipsychotic may be helpful. Overall, few treatments have proven to be consistently useful. Other agents that may be helpful include acetylcholinesterase inhibitors, amantadine, baclofen, benzodiazepines, branched chain amino acids, gabapentin, levetiracetam, pyridoxine, verapamil, and vitamin E. Current pharmacologic agents for essential tremor can be expected to provide partial benefit. However, agents for the symptomatic management of tardive dyskinesia are limited, and additional research is warranted in this area.


[A case of serous cystadenoma of the pancreas communicating with the pancreatic duct].
Serous cystadenoma of the pancreas is a rare disease and is usually benign. Mucinous cystadenoma, another cystic neoplasm of the pancreas, has a malignant potential. Serous cystadenoma is usually composed of many small cysts lined by small, cuboidal or flattened cells containing abundant glycogen. With the finding of endoscopic retrograde pancreatography, a communication between the cyst and pancreatic duct is observed occasionally in the mucinous cystadenoma, but rarely in the case of serous cystadenoma of the pancreas. We experienced a case of serous cystadenoma of the pancreas that had a communication between a cyst and the pancreatic duct.


Behavioural thermal regulation explains pedestrian path choices in hot urban environments.
Due to phenomena such as urban heat islands, outdoor thermal comfort of the cities' residents emerges as a growing concern. A major challenge for mega-cities in changing climate is the design of urban spaces that ensure and promote pedestrian thermal comfort. Understanding pedestrian behavioural adaptation to urban thermal environments is critically important to attain this goal. Current research in pedestrian behaviour lacks controlled experimentation, which limits the quantitative modelling of such complex behaviour. Combining well-controlled experiments with human participants and computational methods inspired by behavioural ecology and decision theory, we examine the effect of sun exposure on route choice in a tropical city. We find that the distance walked in the shade is discounted by a factor of 0.86 compared to the distance walked in the sun, and that shadows cast by buildings have a stronger effect than trees. The discounting effect is mathematically formalised and thus allows quantification of the behaviour that can be used in understanding pedestrian behaviour in changing urban climates. The results highlight the importance of assessment of climate through human responses to it and point the way forward to explore scenarios to mitigate pedestrian heat stress.


Differential Reinforcement of Low Rate Schedules Reduce Severe Problem Behavior.
Differential-reinforcement-of-low-rate (DRL) schedules are reinforcement contingencies designed to reduce response rates. A common variation of the DRL arrangement is known as full-session DRL ( f-DRL), in which a reinforcer is presented at the end of an interval if the response rate during that interval is below a predetermined criterion. Prior human operant research involving arbitrary mouse clicks has shown that the f-DRL is likely to reduce target responding to near zero rates. Similarly, applied research has shown that the f-DRL is likely to reduce minimally disruptive classroom behavior. There are, however, relatively few successful applications of the f-DRL to severe forms of problem behavior (e.g., self-injurious behavior). Thus, the purpose of this study was to examine the effects of f-DRL on the severe problem behavior of individuals with intellectual and developmental disabilities. For four participants, the f-DRL reduced severe problem behavior by clinically significant levels. Furthermore, results of a contingency strength analysis showed a strong negative contingency strength between target responding and reinforcer delivery for all participants.


Prolonged bedtime bottle feeding and respiratory symptoms in infants.
Infants with chronic respiratory symptoms should be evaluated thoroughly because there are various causes which are different from those of children and adolescents. This study was designed to investigate the relationship between chronic respiratory symptoms and bedtime bottle feeding in infants after the age of 6 months. We conducted a prospective study that included 44 infants who presented with respiratory symptoms for more than 8 weeks and also had been bottle-fed during bedtime even after 6 months of age. The infants were divided into 2 groups; infants who discontinued bedtime bottle feeding and those who did not. Respiratory symptom scores were graded with a four-point scale at 0, 1, 2 and 3 months, and were compared between the 2 groups. Twenty eight infants (63.6%) stopped being bottle-fed during bedtime and 16 infants (36.4%) were still bottle-fed. The respiratory symptom scores were significantly decreased in infants who stopped bedtime bottle feeding (p = 0.0003). It is suggested that prolonged bedtime bottle feeding might be one of the causes of chronic respiratory symptoms in infants.